question,question_id,question_type,answer,focus,id,source,url,cui,semanticType,semanticGroup
What is (are) Aarskog-Scott syndrome ?,0000001-1,information,"Aarskog-Scott syndrome is a genetic disorder that affects the development of many parts of the body. This condition mainly affects males, although females may have mild features of the syndrome.  People with Aarskog-Scott syndrome often have distinctive facial features, such as widely spaced eyes (hypertelorism), a small nose, a long area between the nose and mouth (philtrum), and a widow's peak hairline. They frequently have mild to moderate short stature during childhood, but their growth usually catches up during puberty. Hand abnormalities are common in this syndrome and include short fingers (brachydactyly), curved pinky fingers (fifth finger clinodactyly), webbing of the skin between some fingers (syndactyly), and a single crease across the palm. Some people with Aarskog-Scott syndrome are born with more serious abnormalities, such as heart defects or a cleft lip with or without an opening in the roof of the mouth (cleft palate).  Most males with Aarskog-Scott syndrome have a shawl scrotum, in which the scrotum surrounds the penis. Less often, they have undescended testes (cryptorchidism) or a soft out-pouching around the belly-button (umbilical hernia) or in the lower abdomen (inguinal hernia).  The intellectual development of people with Aarskog-Scott syndrome varies widely among affected individuals. Some may have mild learning and behavior problems, while others have normal intelligence. In rare cases, severe intellectual disability has been reported.",Aarskog-Scott syndrome,0000001,GHR,https://ghr.nlm.nih.gov/condition/aarskog-scott-syndrome,C0175701,T019,Disorders
How many people are affected by Aarskog-Scott syndrome ?,0000001-2,frequency,"Aarskog-Scott syndrome is believed to be a rare disorder; however, its prevalence is unknown because mildly affected people are often not diagnosed.",Aarskog-Scott syndrome,0000001,GHR,https://ghr.nlm.nih.gov/condition/aarskog-scott-syndrome,C0175701,T019,Disorders
What are the genetic changes related to Aarskog-Scott syndrome ?,0000001-3,genetic changes,"Mutations in the FGD1 gene cause some cases of Aarskog-Scott syndrome. The FGD1 gene provides instructions for making a protein that turns on (activates) another protein called Cdc42, which transmits signals that are important for various aspects of embryonic development.  Mutations in the FGD1 gene lead to the production of an abnormally functioning protein. These mutations disrupt Cdc42 signaling, which causes the wide variety of developmental abnormalities seen in Aarskog-Scott syndrome.  Only about 20 percent of people with this disorder have identifiable mutations in the FGD1 gene. The cause of Aarskog-Scott syndrome in other affected individuals is unknown.",Aarskog-Scott syndrome,0000001,GHR,https://ghr.nlm.nih.gov/condition/aarskog-scott-syndrome,C0175701,T019,Disorders
Is Aarskog-Scott syndrome inherited ?,0000001-4,inheritance,"Aarskog-Scott syndrome is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause Aarskog-Scott syndrome. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. Females who carry one altered copy of the FGD1 gene may show mild signs of the condition, such as hypertelorism, short stature, or a widow's peak hairline. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",Aarskog-Scott syndrome,0000001,GHR,https://ghr.nlm.nih.gov/condition/aarskog-scott-syndrome,C0175701,T019,Disorders
What are the treatments for Aarskog-Scott syndrome ?,0000001-5,treatment,These resources address the diagnosis or management of Aarskog-Scott syndrome:  - Genetic Testing Registry: Aarskog syndrome  - MedlinePlus Encyclopedia: Aarskog syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Aarskog-Scott syndrome,0000001,GHR,https://ghr.nlm.nih.gov/condition/aarskog-scott-syndrome,C0175701,T019,Disorders
What is (are) abdominal wall defect ?,0000002-1,information,"An abdominal wall defect is an opening in the abdomen through which various abdominal organs can protrude. This opening varies in size and can usually be diagnosed early in fetal development, typically between the tenth and fourteenth weeks of pregnancy. There are two main types of abdominal wall defects: omphalocele and gastroschisis. Omphalocele is an opening in the center of the abdominal wall where the umbilical cord meets the abdomen. Organs (typically the intestines, stomach, and liver) protrude through the opening into the umbilical cord and are covered by the same protective membrane that covers the umbilical cord. Gastroschisis is a defect in the abdominal wall, usually to the right of the umbilical cord, through which the large and small intestines protrude (although other organs may sometimes bulge out). There is no membrane covering the exposed organs in gastroschisis.  Fetuses with omphalocele may grow slowly before birth (intrauterine growth retardation) and they may be born prematurely. Individuals with omphalocele frequently have multiple birth defects, such as a congenital heart defect. Additionally, underdevelopment of the lungs is often associated with omphalocele because the abdominal organs normally provide a framework for chest wall growth. When those organs are misplaced, the chest wall does not form properly, providing a smaller than normal space for the lungs to develop. As a result, many infants with omphalocele have respiratory insufficiency and may need to be supported with a machine to help them breathe (mechanical ventilation). Rarely, affected individuals who have breathing problems in infancy experience recurrent lung infections or asthma later in life. Affected infants often have gastrointestinal problems including a backflow of stomach acids into the esophagus (gastroesophageal reflux) and feeding difficulty; these problems can persist even after treatment of omphalocele. Large omphaloceles or those associated with multiple additional health problems are more often associated with fetal death than cases in which omphalocele occurs alone (isolated).  Omphalocele is a feature of many genetic syndromes. Nearly half of individuals with omphalocele have a condition caused by an extra copy of one of the chromosomes in each of their cells (trisomy). Up to one-third of people born with omphalocele have a genetic condition called Beckwith-Wiedemann syndrome. Affected individuals may have additional signs and symptoms associated with these genetic conditions.  Individuals who have gastroschisis rarely have other birth defects and seldom have chromosome abnormalities or a genetic condition. Most affected individuals experience intrauterine growth retardation and are small at birth; many affected infants are born prematurely.  With gastroschisis, the protruding organs are not covered by a protective membrane and are susceptible to damage due to direct contact with amniotic fluid in the womb. Components of the amniotic fluid may trigger immune responses and inflammatory reactions against the intestines that can damage the tissue. Constriction around exposed organs at the abdominal wall opening late in fetal development may also contribute to organ injury. Intestinal damage causes impairment of the muscle contractions that move food through the digestive tract (peristalsis) in most children with gastroschisis. In these individuals, peristalsis usually improves in a few months and intestinal muscle contractions normalize. Rarely, children with gastroschisis have a narrowing or absence of a portion of intestine (intestinal atresia) or twisting of the intestine. After birth, these intestinal malformations can lead to problems with digestive function, further loss of intestinal tissue, and a condition called short bowel syndrome that occurs when areas of the small intestine are missing, causing dehydration and poor absorption of nutrients. Depending on the severity of the condition, intravenous feedings (parenteral nutrition) may be required.  The health of an individual with gastroschisis depends largely on how damaged his or her intestine was before birth. When the abdominal wall defect is repaired and normal intestinal function is recovered, the vast majority of affected individuals have no health problems related to the repaired defect later in life.",abdominal wall defect,0000002,GHR,https://ghr.nlm.nih.gov/condition/abdominal-wall-defect,C0238577,T033,Disorders
How many people are affected by abdominal wall defect ?,0000002-2,frequency,"Abdominal wall defects are uncommon. Omphalocele affects an estimated 2 to 2.5 in 10,000 newborns. Approximately 2 to 6 in 10,000 newborns are affected by gastroschisis, although researchers have observed that this malformation is becoming more common. Abdominal wall defects are more common among pregnancies that do not survive to term (miscarriages and stillbirths).",abdominal wall defect,0000002,GHR,https://ghr.nlm.nih.gov/condition/abdominal-wall-defect,C0238577,T033,Disorders
What are the genetic changes related to abdominal wall defect ?,0000002-3,genetic changes,"No genetic mutations are known to cause an abdominal wall defect. Multiple genetic and environmental factors likely influence the development of this disorder. Omphalocele and gastroschisis are caused by different errors in fetal development.  Omphalocele occurs during an error in digestive tract development. During the formation of the abdominal cavity in the sixth to tenth weeks of fetal development, the intestines normally protrude into the umbilical cord but recede back into the abdomen as development continues. Omphalocele occurs when the intestines do not recede back into the abdomen, but remain in the umbilical cord. Other abdominal organs can also protrude through this opening, resulting in the varied organ involvement that occurs in omphalocele.  The error that leads to gastroschisis formation is unknown. It is thought to be either a disruption in the blood flow to the digestive tract or a lack of development or injury to gastrointestinal tissue early in fetal development. For reasons that are unknown, women under the age of 20 are at the greatest risk of having a baby with gastroschisis. Other risk factors in pregnancy may include taking medications that constrict the blood vessels (called vasoconstrictive drugs) or smoking, although these risk factors have not been confirmed.",abdominal wall defect,0000002,GHR,https://ghr.nlm.nih.gov/condition/abdominal-wall-defect,C0238577,T033,Disorders
Is abdominal wall defect inherited ?,0000002-4,inheritance,"Most cases of abdominal wall defect are sporadic, which means they occur in people with no history of the disorder in their family. Multiple genetic and environmental factors likely play a part in determining the risk of developing this disorder.  When an abdominal wall defect, most often omphalocele, is a feature of a genetic condition, it is inherited in the pattern of that condition.",abdominal wall defect,0000002,GHR,https://ghr.nlm.nih.gov/condition/abdominal-wall-defect,C0238577,T033,Disorders
What are the treatments for abdominal wall defect ?,0000002-5,treatment,"These resources address the diagnosis or management of abdominal wall defect:  - Cincinnati Children's Hospital: Gastroschisis  - Cincinnati Children's Hospital: Omphalocele  - Cleveland Clinic: Omphalocele  - Genetic Testing Registry: Congenital omphalocele  - Great Ormond Street Hospital for Children (UK): Gastroschisis  - MedlinePlus Encyclopedia: Gastroschisis Repair  - MedlinePlus Encyclopedia: Gastroschisis Repair--Series (images)  - MedlinePlus Encyclopedia: Omphalocele Repair  - MedlinePlus Encyclopedia: Omphalocele Repair--Series (images)  - Seattle Children's Hospital: Gastroschisis Treatment Options  - Seattle Children's Hospital: Omphalocele Treatment Options  - The Children's Hospital of Philadelphia: Diagnosis and Treatment of Gastroschisis  - The Children's Hospital of Philadelphia: Overview and Treatment of Omphalocele  - University of California, San Francisco Fetal Treatment Center: Gastroschisis  - University of California, San Francisco Fetal Treatment Center: Omphalocele   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",abdominal wall defect,0000002,GHR,https://ghr.nlm.nih.gov/condition/abdominal-wall-defect,C0238577,T033,Disorders
What is (are) abetalipoproteinemia ?,0000003-1,information,"Abetalipoproteinemia is an inherited disorder that affects the absorption of dietary fats, cholesterol, and fat-soluble vitamins. People affected by this disorder are not able to make certain lipoproteins, which are particles that carry fats and fat-like substances (such as cholesterol) in the blood. Specifically, people with abetalipoproteinemia are missing a group of lipoproteins called beta-lipoproteins. An inability to make beta-lipoproteins causes severely reduced absorption (malabsorption) of dietary fats and fat-soluble vitamins (vitamins A, D, E, and K) from the digestive tract into the bloodstream. Sufficient levels of fats, cholesterol, and vitamins are necessary for normal growth, development, and maintenance of the body's cells and tissues, particularly nerve cells and tissues in the eye.  The signs and symptoms of abetalipoproteinemia appear in the first few months of life. They can include failure to gain weight and grow at the expected rate (failure to thrive); diarrhea; abnormal star-shaped red blood cells (acanthocytosis); and fatty, foul-smelling stools (steatorrhea). Other features of this disorder may develop later in childhood and often impair the function of the nervous system. Disturbances in nerve function may cause affected people to eventually develop poor muscle coordination and difficulty with balance and movement (ataxia). Individuals with this condition may also develop an eye disorder called retinitis pigmentosa, in which progressive degeneration of the light-sensitive layer (retina) at the back of the eye can cause vision loss. Adults in their thirties or forties may have increasing difficulty with balance and walking. Many of the signs and symptoms of abetalipoproteinemia result from a severe vitamin deficiency, especially a deficiency of vitamin E.",abetalipoproteinemia,0000003,GHR,https://ghr.nlm.nih.gov/condition/abetalipoproteinemia,C0000744,T047,Disorders
How many people are affected by abetalipoproteinemia ?,0000003-2,frequency,Abetalipoproteinemia is a rare disorder with approximately 100 cases described worldwide.,abetalipoproteinemia,0000003,GHR,https://ghr.nlm.nih.gov/condition/abetalipoproteinemia,C0000744,T047,Disorders
What are the genetic changes related to abetalipoproteinemia ?,0000003-3,genetic changes,"Mutations in the MTTP gene cause abetalipoproteinemia. The MTTP gene provides instructions for making a protein called microsomal triglyceride transfer protein, which is essential for creating beta-lipoproteins. These lipoproteins are necessary for the absorption of fats, cholesterol, and fat-soluble vitamins from the diet and the efficient transport of these substances in the bloodstream. Most of the mutations in the MTTP gene lead to the production of an abnormally short microsomal triglyceride transfer protein, which prevents the normal creation of beta-lipoproteins in the body. A lack of beta-lipoproteins causes the nutritional and neurological problems seen in people with abetalipoproteinemia.",abetalipoproteinemia,0000003,GHR,https://ghr.nlm.nih.gov/condition/abetalipoproteinemia,C0000744,T047,Disorders
Is abetalipoproteinemia inherited ?,0000003-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",abetalipoproteinemia,0000003,GHR,https://ghr.nlm.nih.gov/condition/abetalipoproteinemia,C0000744,T047,Disorders
What are the treatments for abetalipoproteinemia ?,0000003-5,treatment,These resources address the diagnosis or management of abetalipoproteinemia:  - Genetic Testing Registry: Abetalipoproteinaemia  - MedlinePlus Encyclopedia: Bassen-Kornzweig syndrome  - MedlinePlus Encyclopedia: Malabsorption  - MedlinePlus Encyclopedia: Retinitis pigmentosa  - MedlinePlus Encyclopedia: Stools - floating   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,abetalipoproteinemia,0000003,GHR,https://ghr.nlm.nih.gov/condition/abetalipoproteinemia,C0000744,T047,Disorders
What is (are) acatalasemia ?,0000004-1,information,"Acatalasemia is a condition characterized by very low levels of an enzyme called catalase. Many people with acatalasemia never have any health problems related to the condition and are diagnosed because they have affected family members.  Some of the first reported individuals with acatalasemia developed open sores (ulcers) inside the mouth that led to the death of soft tissue (gangrene). When mouth ulcers and gangrene occur with acatalasemia, the condition is known as Takahara disease. These complications are rarely seen in more recent cases of acatalasemia, probably because of improvements in oral hygiene.  Studies suggest that people with acatalasemia have an increased risk of developing type 2 diabetes mellitus, which is the most common form of diabetes. A higher percentage of people with acatalasemia have type 2 diabetes mellitus than in the general population, and the disease tends to develop at an earlier age (in a person's thirties or forties, on average). Researchers speculate that acatalasemia could also be a risk factor for other common, complex diseases; however, only a small number of cases have been studied.",acatalasemia,0000004,GHR,https://ghr.nlm.nih.gov/condition/acatalasemia,C0268419,T047,Disorders
How many people are affected by acatalasemia ?,0000004-2,frequency,"More than 100 cases of acatalasemia have been reported in the medical literature. Researchers estimate that the condition occurs in about 1 in 12,500 people in Japan, 1 in 20,000 people in Hungary, and 1 in 25,000 people in Switzerland. The prevalence of acatalasemia in other populations is unknown.",acatalasemia,0000004,GHR,https://ghr.nlm.nih.gov/condition/acatalasemia,C0268419,T047,Disorders
What are the genetic changes related to acatalasemia ?,0000004-3,genetic changes,"Mutations in the CAT gene can cause acatalasemia. This gene provides instructions for making the enzyme catalase, which breaks down hydrogen peroxide molecules into oxygen and water. Hydrogen peroxide is produced through chemical reactions within cells. At low levels, it is involved in several chemical signaling pathways, but at high levels it is toxic to cells. If hydrogen peroxide is not broken down by catalase, additional reactions convert it into compounds called reactive oxygen species that can damage DNA, proteins, and cell membranes.  Mutations in the CAT gene greatly reduce the activity of catalase. A shortage of this enzyme can allow hydrogen peroxide to build up to toxic levels in certain cells. For example, hydrogen peroxide produced by bacteria in the mouth may accumulate in and damage soft tissues, leading to mouth ulcers and gangrene. A buildup of hydrogen peroxide may also damage beta cells of the pancreas, which release a hormone called insulin that helps control blood sugar. Malfunctioning beta cells are thought to underlie the increased risk of type 2 diabetes mellitus in people with acatalasemia. It is unclear why some people have no health problems associated with a loss of catalase activity.  Many people with reduced catalase activity do not have an identified mutation in the CAT gene; in these cases, the cause of the condition is unknown. Researchers believe that other genetic and environmental factors can also influence the activity of catalase.",acatalasemia,0000004,GHR,https://ghr.nlm.nih.gov/condition/acatalasemia,C0268419,T047,Disorders
Is acatalasemia inherited ?,0000004-4,inheritance,"Acatalasemia has an autosomal recessive pattern of inheritance, which means both copies of the CAT gene in each cell have mutations. When both copies of the gene are altered, the activity of catalase is reduced to less than 10 percent of normal.  When only one of the two copies of the CAT gene has a mutation, the activity of catalase is reduced by approximately half. This reduction in catalase activity is often called hypocatalasemia. Like acatalasemia, hypocatalasemia usually does not cause any health problems.",acatalasemia,0000004,GHR,https://ghr.nlm.nih.gov/condition/acatalasemia,C0268419,T047,Disorders
What are the treatments for acatalasemia ?,0000004-5,treatment,"These resources address the diagnosis or management of acatalasemia:  - Genetic Testing Registry: Acatalasemia  - Genetic Testing Registry: Acatalasemia, japanese type   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",acatalasemia,0000004,GHR,https://ghr.nlm.nih.gov/condition/acatalasemia,C0268419,T047,Disorders
What is (are) aceruloplasminemia ?,0000005-1,information,"Aceruloplasminemia is a disorder in which iron gradually accumulates in the brain and other organs. Iron accumulation in the brain results in neurological problems that generally appear in adulthood and worsen over time.  People with aceruloplasminemia develop a variety of movement problems. They may experience involuntary muscle contractions (dystonia) of the head and neck, resulting in repetitive movements and contortions. Other involuntary movements may also occur, such as rhythmic shaking (tremors), jerking movements (chorea), eyelid twitching (blepharospasm), and grimacing. Affected individuals may also have difficulty with coordination (ataxia). Some develop psychiatric problems and a decline of intellectual function (dementia) in their forties or fifties.  In addition to neurological problems, affected individuals may have diabetes mellitus caused by iron damage to cells in the pancreas that make insulin, a hormone that helps control blood sugar levels. Iron accumulation in the pancreas reduces the cells' ability to make insulin, which impairs blood sugar regulation and leads to the signs and symptoms of diabetes.  Iron accumulation in the tissues and organs results in a corresponding shortage (deficiency) of iron in the blood, leading to a shortage of red blood cells (anemia). Anemia and diabetes usually occur by the time an affected person is in his or her twenties.  Affected individuals also have changes in the light-sensitive tissue at the back of the eye (retina) caused by excess iron. The changes result in small opaque spots and areas of tissue degeneration (atrophy) around the edges of the retina. These abnormalities usually do not affect vision but can be observed during an eye examination.  The specific features of aceruloplasminemia and their severity may vary, even within the same family.",aceruloplasminemia,0000005,GHR,https://ghr.nlm.nih.gov/condition/aceruloplasminemia,C0878682,T047,Disorders
How many people are affected by aceruloplasminemia ?,0000005-2,frequency,"Aceruloplasminemia has been seen worldwide, but its overall prevalence is unknown. Studies in Japan have estimated that approximately 1 in 2 million adults in this population are affected.",aceruloplasminemia,0000005,GHR,https://ghr.nlm.nih.gov/condition/aceruloplasminemia,C0878682,T047,Disorders
What are the genetic changes related to aceruloplasminemia ?,0000005-3,genetic changes,"Mutations in the CP gene cause aceruloplasminemia. The CP gene provides instructions for making a protein called ceruloplasmin, which is involved in iron transport and processing. Ceruloplasmin helps move iron from the organs and tissues of the body and prepares it for incorporation into a molecule called transferrin, which transports it to red blood cells to help carry oxygen.  CP gene mutations result in the production of ceruloplasmin protein that is unstable or nonfunctional, or they prevent the protein from being released (secreted) by the cells in which it is made. When ceruloplasmin is unavailable, transport of iron out of the body's tissues is impaired. The resulting iron accumulation damages cells in those tissues, leading to neurological dysfunction, and the other health problems seen in aceruloplasminemia.",aceruloplasminemia,0000005,GHR,https://ghr.nlm.nih.gov/condition/aceruloplasminemia,C0878682,T047,Disorders
Is aceruloplasminemia inherited ?,0000005-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",aceruloplasminemia,0000005,GHR,https://ghr.nlm.nih.gov/condition/aceruloplasminemia,C0878682,T047,Disorders
What are the treatments for aceruloplasminemia ?,0000005-5,treatment,These resources address the diagnosis or management of aceruloplasminemia:  - Gene Review: Gene Review: Aceruloplasminemia  - Genetic Testing Registry: Deficiency of ferroxidase   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,aceruloplasminemia,0000005,GHR,https://ghr.nlm.nih.gov/condition/aceruloplasminemia,C0878682,T047,Disorders
What is (are) achondrogenesis ?,0000006-1,information,"Achondrogenesis is a group of severe disorders that affect cartilage and bone development. These conditions are characterized by a small body, short limbs, and other skeletal abnormalities. As a result of serious health problems, infants with achondrogenesis usually die before birth, are stillborn, or die soon after birth from respiratory failure. However, some infants have lived for a short time with intensive medical support.  Researchers have described at least three forms of achondrogenesis, designated as type 1A, type 1B, and type 2. The types are distinguished by their signs and symptoms, inheritance pattern, and genetic cause. However, types 1A and 1B are often hard to tell apart without genetic testing.  Achondrogenesis type 1A, which is also called the Houston-Harris type, is the least well understood of the three forms. Affected infants have extremely short limbs, a narrow chest, short ribs that fracture easily, and a lack of normal bone formation (ossification) in the skull, spine, and pelvis.  Achondrogenesis type 1B, also known as the Parenti-Fraccaro type, is characterized by extremely short limbs, a narrow chest, and a prominent, rounded abdomen. The fingers and toes are short and the feet may turn inward and upward (clubfeet). Affected infants frequently have a soft out-pouching around the belly-button (an umbilical hernia) or near the groin (an inguinal hernia).  Infants with achondrogenesis type 2, which is sometimes called the Langer-Saldino type, have short arms and legs, a narrow chest with short ribs, and underdeveloped lungs. This condition is also associated with a lack of ossification in the spine and pelvis. Distinctive facial features include a prominent forehead, a small chin, and, in some cases, an opening in the roof of the mouth (a cleft palate). The abdomen is enlarged, and affected infants often have a condition called hydrops fetalis, in which excess fluid builds up in the body before birth.",achondrogenesis,0000006,GHR,https://ghr.nlm.nih.gov/condition/achondrogenesis,C0001079,T019,Disorders
How many people are affected by achondrogenesis ?,0000006-2,frequency,"Achondrogenesis types 1A and 1B are rare genetic disorders; their incidence is unknown. Combined, achondrogenesis type 2 and hypochondrogenesis (a similar skeletal disorder) occur in 1 in 40,000 to 60,000 newborns.",achondrogenesis,0000006,GHR,https://ghr.nlm.nih.gov/condition/achondrogenesis,C0001079,T019,Disorders
What are the genetic changes related to achondrogenesis ?,0000006-3,genetic changes,"Mutations in the TRIP11, SLC26A2, and COL2A1 genes cause achondrogenesis type 1A, type 1B, and type 2, respectively.  The genetic cause of achondrogenesis type 1A was unknown until recently, when researchers discovered that the condition can result from mutations in the TRIP11 gene. This gene provides instructions for making a protein called GMAP-210. This protein plays a critical role in the Golgi apparatus, a cell structure in which newly produced proteins are modified so they can carry out their functions. Mutations in the TRIP11 gene prevent the production of functional GMAP-210, which alters the structure and function of the Golgi apparatus. Researchers suspect that cells called chondrocytes in the developing skeleton may be most sensitive to these changes. Chondrocytes give rise to cartilage, a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Malfunction of the Golgi apparatus in chondrocytes likely underlies the problems with bone formation in achondrogenesis type 1A.  Achondrogenesis type 1B is the most severe of a spectrum of skeletal disorders caused by mutations in the SLC26A2 gene. This gene provides instructions for making a protein that is essential for the normal development of cartilage and for its conversion to bone. Mutations in the SLC26A2 gene cause the skeletal problems characteristic of achondrogenesis type 1B by disrupting the structure of developing cartilage, which prevents bones from forming properly.  Achondrogenesis type 2 is one of several skeletal disorders that result from mutations in the COL2A1 gene. This gene provides instructions for making a protein that forms type II collagen. This type of collagen is found mostly in cartilage and in the clear gel that fills the eyeball (the vitreous). It is essential for the normal development of bones and other connective tissues that form the body's supportive framework. Mutations in the COL2A1 gene interfere with the assembly of type II collagen molecules, which prevents bones and other connective tissues from developing properly.",achondrogenesis,0000006,GHR,https://ghr.nlm.nih.gov/condition/achondrogenesis,C0001079,T019,Disorders
Is achondrogenesis inherited ?,0000006-4,inheritance,"Achondrogenesis type 1A and type 1B both have an autosomal recessive pattern of inheritance, which means both copies of the TRIP11 or SLC26A2 gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene but do not show signs and symptoms of the condition.  Achondrogenesis type 2 is considered an autosomal dominant disorder because one copy of the altered gene in each cell is sufficient to cause the condition. It is almost always caused by new mutations in the COL2A1 gene and typically occurs in people with no history of the disorder in their family.",achondrogenesis,0000006,GHR,https://ghr.nlm.nih.gov/condition/achondrogenesis,C0001079,T019,Disorders
What are the treatments for achondrogenesis ?,0000006-5,treatment,"These resources address the diagnosis or management of achondrogenesis:  - Gene Review: Gene Review: Achondrogenesis Type 1B  - Genetic Testing Registry: Achondrogenesis type 2  - Genetic Testing Registry: Achondrogenesis, type IA  - Genetic Testing Registry: Achondrogenesis, type IB  - MedlinePlus Encyclopedia: Achondrogenesis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",achondrogenesis,0000006,GHR,https://ghr.nlm.nih.gov/condition/achondrogenesis,C0001079,T019,Disorders
What is (are) achondroplasia ?,0000007-1,information,"Achondroplasia is a form of short-limbed dwarfism. The word achondroplasia literally means ""without cartilage formation."" Cartilage is a tough but flexible tissue that makes up much of the skeleton during early development. However, in achondroplasia the problem is not in forming cartilage but in converting it to bone (a process called ossification), particularly in the long bones of the arms and legs. Achondroplasia is similar to another skeletal disorder called hypochondroplasia, but the features of achondroplasia tend to be more severe.  All people with achondroplasia have short stature. The average height of an adult male with achondroplasia is 131 centimeters (4 feet, 4 inches), and the average height for adult females is 124 centimeters (4 feet, 1 inch). Characteristic features of achondroplasia include an average-size trunk, short arms and legs with particularly short upper arms and thighs, limited range of motion at the elbows, and an enlarged head (macrocephaly) with a prominent forehead. Fingers are typically short and the ring finger and middle finger may diverge, giving the hand a three-pronged (trident) appearance. People with achondroplasia are generally of normal intelligence.  Health problems commonly associated with achondroplasia include episodes in which breathing slows or stops for short periods (apnea), obesity, and recurrent ear infections. In childhood, individuals with the condition usually develop a pronounced and permanent sway of the lower back (lordosis) and bowed legs. Some affected people also develop abnormal front-to-back curvature of the spine (kyphosis) and back pain. A potentially serious complication of achondroplasia is spinal stenosis, which is a narrowing of the spinal canal that can pinch (compress) the upper part of the spinal cord. Spinal stenosis is associated with pain, tingling, and weakness in the legs that can cause difficulty with walking. Another uncommon but serious complication of achondroplasia is hydrocephalus, which is a buildup of fluid in the brain in affected children that can lead to increased head size and related brain abnormalities.",achondroplasia,0000007,GHR,https://ghr.nlm.nih.gov/condition/achondroplasia,C0001080,T019,Disorders
How many people are affected by achondroplasia ?,0000007-2,frequency,"Achondroplasia is the most common type of short-limbed dwarfism. The condition occurs in 1 in 15,000 to 40,000 newborns.",achondroplasia,0000007,GHR,https://ghr.nlm.nih.gov/condition/achondroplasia,C0001080,T019,Disorders
What are the genetic changes related to achondroplasia ?,0000007-3,genetic changes,"Mutations in the FGFR3 gene cause achondroplasia. The FGFR3 gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. Two specific mutations in the FGFR3 gene are responsible for almost all cases of achondroplasia. Researchers believe that these mutations cause the FGFR3 protein to be overly active, which interferes with skeletal development and leads to the disturbances in bone growth seen with this disorder.",achondroplasia,0000007,GHR,https://ghr.nlm.nih.gov/condition/achondroplasia,C0001080,T019,Disorders
Is achondroplasia inherited ?,0000007-4,inheritance,"Achondroplasia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. About 80 percent of people with achondroplasia have average-size parents; these cases result from new mutations in the FGFR3 gene. In the remaining cases, people with achondroplasia have inherited an altered FGFR3 gene from one or two affected parents. Individuals who inherit two altered copies of this gene typically have a severe form of achondroplasia that causes extreme shortening of the bones and an underdeveloped rib cage. These individuals are usually stillborn or die shortly after birth from respiratory failure.",achondroplasia,0000007,GHR,https://ghr.nlm.nih.gov/condition/achondroplasia,C0001080,T019,Disorders
What are the treatments for achondroplasia ?,0000007-5,treatment,These resources address the diagnosis or management of achondroplasia:  - Gene Review: Gene Review: Achondroplasia  - GeneFacts: Achondroplasia: Diagnosis  - GeneFacts: Achondroplasia: Management  - Genetic Testing Registry: Achondroplasia  - MedlinePlus Encyclopedia: Achondroplasia  - MedlinePlus Encyclopedia: Hydrocephalus  - MedlinePlus Encyclopedia: Lordosis  - MedlinePlus Encyclopedia: Spinal Stenosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,achondroplasia,0000007,GHR,https://ghr.nlm.nih.gov/condition/achondroplasia,C0001080,T019,Disorders
What is (are) achromatopsia ?,0000008-1,information,"Achromatopsia is a condition characterized by a partial or total absence of color vision. People with complete achromatopsia cannot perceive any colors; they see only black, white, and shades of gray. Incomplete achromatopsia is a milder form of the condition that allows some color discrimination.  Achromatopsia also involves other problems with vision, including an increased sensitivity to light and glare (photophobia), involuntary back-and-forth eye movements (nystagmus), and significantly reduced sharpness of vision (low visual acuity). Affected individuals can also have farsightedness (hyperopia) or, less commonly, nearsightedness (myopia). These vision problems develop in the first few months of life.  Achromatopsia is different from the more common forms of color vision deficiency (also called color blindness), in which people can perceive color but have difficulty distinguishing between certain colors, such as red and green.",achromatopsia,0000008,GHR,https://ghr.nlm.nih.gov/condition/achromatopsia,C0152200,T047,Disorders
How many people are affected by achromatopsia ?,0000008-2,frequency,"Achromatopsia affects an estimated 1 in 30,000 people worldwide. Complete achromatopsia is more common than incomplete achromatopsia.  Complete achromatopsia occurs frequently among Pingelapese islanders, who live on one of the Eastern Caroline Islands of Micronesia. Between 4 and 10 percent of people in this population have a total absence of color vision.",achromatopsia,0000008,GHR,https://ghr.nlm.nih.gov/condition/achromatopsia,C0152200,T047,Disorders
What are the genetic changes related to achromatopsia ?,0000008-3,genetic changes,"Achromatopsia results from changes in one of several genes: CNGA3, CNGB3, GNAT2, PDE6C, or PDE6H. A particular CNGB3 gene mutation underlies the condition in Pingelapese islanders.  Achromatopsia is a disorder of the retina, which is the light-sensitive tissue at the back of the eye. The retina contains two types of light receptor cells, called rods and cones. These cells transmit visual signals from the eye to the brain through a process called phototransduction. Rods provide vision in low light (night vision). Cones provide vision in bright light (daylight vision), including color vision.  Mutations in any of the genes listed above prevent cones from reacting appropriately to light, which interferes with phototransduction. In people with complete achromatopsia, cones are nonfunctional, and vision depends entirely on the activity of rods. The loss of cone function leads to a total lack of color vision and causes the other vision problems. People with incomplete achromatopsia retain some cone function. These individuals have limited color vision, and their other vision problems tend to be less severe.  Some people with achromatopsia do not have identified mutations in any of the known genes. In these individuals, the cause of the disorder is unknown. Other genetic factors that have not been identified likely contribute to this condition.",achromatopsia,0000008,GHR,https://ghr.nlm.nih.gov/condition/achromatopsia,C0152200,T047,Disorders
Is achromatopsia inherited ?,0000008-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",achromatopsia,0000008,GHR,https://ghr.nlm.nih.gov/condition/achromatopsia,C0152200,T047,Disorders
What are the treatments for achromatopsia ?,0000008-5,treatment,These resources address the diagnosis or management of achromatopsia:  - Gene Review: Gene Review: Achromatopsia  - Genetic Testing Registry: Achromatopsia  - MedlinePlus Encyclopedia: Color Vision Test   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,achromatopsia,0000008,GHR,https://ghr.nlm.nih.gov/condition/achromatopsia,C0152200,T047,Disorders
What is (are) acral peeling skin syndrome ?,0000009-1,information,"Acral peeling skin syndrome is a skin disorder characterized by painless peeling of the top layer of skin. The term ""acral"" refers to the fact that the skin peeling in this condition is most apparent on the hands and feet. Occasionally, peeling also occurs on the arms and legs. The peeling is usually evident from birth, although the condition can also begin in childhood or later in life. Skin peeling is made worse by exposure to heat, humidity and other forms of moisture, and friction. The underlying skin may be temporarily red and itchy, but it typically heals without scarring. Acral peeling skin syndrome is not associated with any other health problems.",acral peeling skin syndrome,0000009,GHR,https://ghr.nlm.nih.gov/condition/acral-peeling-skin-syndrome,C1853354,T047,Disorders
How many people are affected by acral peeling skin syndrome ?,0000009-2,frequency,"Acral peeling skin syndrome is a rare condition, with several dozen cases reported in the medical literature. However, because its signs and symptoms tend to be mild and similar to those of other skin disorders, the condition is likely underdiagnosed.",acral peeling skin syndrome,0000009,GHR,https://ghr.nlm.nih.gov/condition/acral-peeling-skin-syndrome,C1853354,T047,Disorders
What are the genetic changes related to acral peeling skin syndrome ?,0000009-3,genetic changes,"Acral peeling skin syndrome is caused by mutations in the TGM5 gene. This gene provides instructions for making an enzyme called transglutaminase 5, which is a component of the outer layer of skin (the epidermis). Transglutaminase 5 plays a critical role in the formation of a structure called the cornified cell envelope, which surrounds epidermal cells and helps the skin form a protective barrier between the body and its environment.  TGM5 gene mutations reduce the production of transglutaminase 5 or prevent cells from making any of this protein. A shortage of transglutaminase 5 weakens the cornified cell envelope, which allows the outermost cells of the epidermis to separate easily from the underlying skin and peel off. This peeling is most noticeable on the hands and feet probably because those areas tend to be heavily exposed to moisture and friction.",acral peeling skin syndrome,0000009,GHR,https://ghr.nlm.nih.gov/condition/acral-peeling-skin-syndrome,C1853354,T047,Disorders
Is acral peeling skin syndrome inherited ?,0000009-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",acral peeling skin syndrome,0000009,GHR,https://ghr.nlm.nih.gov/condition/acral-peeling-skin-syndrome,C1853354,T047,Disorders
What are the treatments for acral peeling skin syndrome ?,0000009-5,treatment,"These resources address the diagnosis or management of acral peeling skin syndrome:  - Birmingham Children's Hospital, National Health Service (UK)  - Genetic Testing Registry: Peeling skin syndrome, acral type   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",acral peeling skin syndrome,0000009,GHR,https://ghr.nlm.nih.gov/condition/acral-peeling-skin-syndrome,C1853354,T047,Disorders
What is (are) acromicric dysplasia ?,0000010-1,information,"Acromicric dysplasia is a condition characterized by severely short stature, short limbs, stiff joints, and distinctive facial features.  Newborns with acromicric dysplasia are of normal size, but slow growth over time results in short stature. The average height of adults with this disorder is about 4 feet, 2 inches for women and 4 feet, 5 inches for men. The long bones of the arms and legs, and the bones in the hands and feet, are shorter than would be expected for the individual's height. Other skeletal features that occur in this disorder include slowed mineralization of bone (delayed bone age), abnormally shaped bones of the spine (vertebrae), and constrained movement of joints. Affected individuals often develop carpal tunnel syndrome, which is characterized by numbness, tingling, and weakness in the hands and fingers. A misalignment of the hip joints (hip dysplasia) can also occur in this disorder. These skeletal and joint problems may require treatment, but most affected individuals have few limitations in their activities.  Children with acromicric dysplasia may have a round face, sharply defined eyebrows, long eyelashes, a bulbous nose with upturned nostrils, a long space between the nose and upper lip (philtrum), and a small mouth with thick lips. These facial differences become less apparent in adulthood. Intelligence is unaffected in this disorder, and life expectancy is generally normal.",acromicric dysplasia,0000010,GHR,https://ghr.nlm.nih.gov/condition/acromicric-dysplasia,C0265287,T019,Disorders
How many people are affected by acromicric dysplasia ?,0000010-2,frequency,Acromicric dysplasia is a rare disorder; its prevalence is unknown.,acromicric dysplasia,0000010,GHR,https://ghr.nlm.nih.gov/condition/acromicric-dysplasia,C0265287,T019,Disorders
What are the genetic changes related to acromicric dysplasia ?,0000010-3,genetic changes,"Acromicric dysplasia is caused by mutations in the FBN1 gene, which provides instructions for making a large protein called fibrillin-1. This protein is transported out of cells into the extracellular matrix, which is an intricate lattice of proteins and other molecules that forms in the spaces between cells. In this matrix, molecules of fibrillin-1 attach (bind) to each other and to other proteins to form threadlike filaments called microfibrils. The microfibrils become part of the fibers that provide strength and flexibility to connective tissues, which support the bones, skin, and other tissues and organs. Additionally, microfibrils store molecules called growth factors, including transforming growth factor beta (TGF-), and release them at various times to control the growth and repair of tissues and organs throughout the body.  Most of the FBN1 gene mutations that cause acromicric dysplasia change single protein building blocks in the fibrillin-1 protein. The mutations result in a reduction and disorganization of the microfibrils. Without enough normal microfibrils to store TGF-, the growth factor is abnormally active. These effects likely contribute to the physical abnormalities that occur in acromicric dysplasia, but the mechanisms are unclear.",acromicric dysplasia,0000010,GHR,https://ghr.nlm.nih.gov/condition/acromicric-dysplasia,C0265287,T019,Disorders
Is acromicric dysplasia inherited ?,0000010-4,inheritance,"Acromicric dysplasia is an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family. In other cases, an affected person inherits the mutation from one affected parent.",acromicric dysplasia,0000010,GHR,https://ghr.nlm.nih.gov/condition/acromicric-dysplasia,C0265287,T019,Disorders
What are the treatments for acromicric dysplasia ?,0000010-5,treatment,These resources address the diagnosis or management of acromicric dysplasia:  - Genetic Testing Registry: Acromicric dysplasia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,acromicric dysplasia,0000010,GHR,https://ghr.nlm.nih.gov/condition/acromicric-dysplasia,C0265287,T019,Disorders
What is (are) actin-accumulation myopathy ?,0000011-1,information,"Actin-accumulation myopathy is a disorder that primarily affects skeletal muscles, which are muscles that the body uses for movement. People with actin-accumulation myopathy have severe muscle weakness (myopathy) and poor muscle tone (hypotonia) throughout the body. Signs and symptoms of this condition are apparent in infancy and include feeding and swallowing difficulties, a weak cry, and difficulty with controlling head movements. Affected babies are sometimes described as ""floppy"" and may be unable to move on their own.  The severe muscle weakness that occurs in actin-accumulation myopathy also affects the muscles used for breathing. Individuals with this disorder may take shallow breaths (hypoventilate), especially during sleep, resulting in a shortage of oxygen and a buildup of carbon dioxide in the blood. Frequent respiratory infections and life-threatening breathing difficulties can occur. Because of the respiratory problems, most affected individuals do not survive past infancy. Those who do survive have delayed development of motor skills such as sitting, crawling, standing, and walking.  The name actin-accumulation myopathy derives from characteristic accumulations in muscle cells of filaments composed of a protein called actin. These filaments can be seen when muscle tissue is viewed under a microscope.",actin-accumulation myopathy,0000011,GHR,https://ghr.nlm.nih.gov/condition/actin-accumulation-myopathy,C3711389,T047,Disorders
How many people are affected by actin-accumulation myopathy ?,0000011-2,frequency,Actin-accumulation myopathy is a rare disorder that has been identified in only a small number of individuals. Its exact prevalence is unknown.,actin-accumulation myopathy,0000011,GHR,https://ghr.nlm.nih.gov/condition/actin-accumulation-myopathy,C3711389,T047,Disorders
What are the genetic changes related to actin-accumulation myopathy ?,0000011-3,genetic changes,"Actin-accumulation myopathy is caused by a mutation in the ACTA1 gene. This gene provides instructions for making a protein called skeletal alpha ()-actin, which is a member of the actin protein family found in skeletal muscles. Actin proteins are important for cell movement and the tensing of muscle fibers (muscle contraction). Thin filaments made up of actin molecules and thick filaments made up of another protein called myosin are the primary components of muscle fibers and are important for muscle contraction. Attachment (binding) and release of the overlapping thick and thin filaments allows them to move relative to each other so that the muscles can contract.  ACTA1 gene mutations that cause actin-accumulation myopathy may affect the way the skeletal -actin protein binds to ATP. ATP is a molecule that supplies energy for cells' activities, and is important in the formation of thin filaments from individual actin molecules. Dysfunctional actin-ATP binding may result in abnormal thin filament formation and impair muscle contraction, leading to muscle weakness and the other signs and symptoms of actin-accumulation myopathy.  In some people with actin-accumulation myopathy, no ACTA1 gene mutations have been identified. The cause of the disorder in these individuals is unknown.",actin-accumulation myopathy,0000011,GHR,https://ghr.nlm.nih.gov/condition/actin-accumulation-myopathy,C3711389,T047,Disorders
Is actin-accumulation myopathy inherited ?,0000011-4,inheritance,"Actin-accumulation myopathy is an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases are not inherited; they result from new mutations in the gene and occur in people with no history of the disorder in their family.",actin-accumulation myopathy,0000011,GHR,https://ghr.nlm.nih.gov/condition/actin-accumulation-myopathy,C3711389,T047,Disorders
What are the treatments for actin-accumulation myopathy ?,0000011-5,treatment,These resources address the diagnosis or management of actin-accumulation myopathy:  - Genetic Testing Registry: Nemaline myopathy 3   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,actin-accumulation myopathy,0000011,GHR,https://ghr.nlm.nih.gov/condition/actin-accumulation-myopathy,C3711389,T047,Disorders
What is (are) activated PI3K-delta syndrome ?,0000012-1,information,"Activated PI3K-delta syndrome is a disorder that impairs the immune system. Individuals with this condition often have low numbers of white blood cells (lymphopenia), particularly B cells and T cells. Normally, these cells recognize and attack foreign invaders, such as viruses and bacteria, to prevent infection. Beginning in childhood, people with activated PI3K-delta syndrome develop recurrent infections, particularly in the lungs, sinuses, and ears. Over time, recurrent respiratory tract infections can lead to a condition called bronchiectasis, which damages the passages leading from the windpipe to the lungs (bronchi) and can cause breathing problems. People with activated PI3K-delta syndrome may also have chronic active viral infections, commonly Epstein-Barr virus or cytomegalovirus infections.  Another possible feature of activated PI3K-delta syndrome is abnormal clumping of white blood cells. These clumps can lead to enlarged lymph nodes (lymphadenopathy), or the white blood cells can build up to form solid masses (nodular lymphoid hyperplasia), usually in the moist lining of the airways or intestines. While lymphadenopathy and nodular lymphoid hyperplasia are noncancerous (benign), activated PI3K-delta syndrome also increases the risk of developing a form of cancer called B-cell lymphoma.",activated PI3K-delta syndrome,0000012,GHR,https://ghr.nlm.nih.gov/condition/activated-pi3k-delta-syndrome,C0039082,T047,Disorders
How many people are affected by activated PI3K-delta syndrome ?,0000012-2,frequency,The prevalence of activated PI3K-delta syndrome is unknown.,activated PI3K-delta syndrome,0000012,GHR,https://ghr.nlm.nih.gov/condition/activated-pi3k-delta-syndrome,C0039082,T047,Disorders
What are the genetic changes related to activated PI3K-delta syndrome ?,0000012-3,genetic changes,"Activated PI3K-delta syndrome is caused by mutations in the PIK3CD gene, which provides instructions for making a protein called p110 delta (p110). This protein is one piece (subunit) of an enzyme called phosphatidylinositol 3-kinase (PI3K), which turns on signaling pathways within cells. The version of PI3K containing the p110 subunit, called PI3K-delta, is specifically found in white blood cells, including B cells and T cells. PI3K-delta signaling is involved in the growth and division (proliferation) of white blood cells, and it helps direct B cells and T cells to mature (differentiate) into different types, each of which has a distinct function in the immune system.  PIK3CD gene mutations involved in activated PI3K-delta syndrome lead to production of an altered p110 protein. A PI3K-delta enzyme containing the altered subunit is abnormally turned on (activated). Studies indicate that overactive PI3K-delta signaling alters the differentiation of B cells and T cells, leading to production of cells that cannot respond to infections and that die earlier than usual. Lack of functioning B cells and T cells makes it difficult for people with this disorder to fight off bacterial and viral infections. Overactivation of PI3K-delta signaling can also stimulate abnormal proliferation of white blood cells, leading to lymphadenopathy and nodular lymphoid hyperplasia in some affected individuals. An increase in B cell proliferation in combination with reduced immune system function may contribute to development of B-cell lymphoma.",activated PI3K-delta syndrome,0000012,GHR,https://ghr.nlm.nih.gov/condition/activated-pi3k-delta-syndrome,C0039082,T047,Disorders
Is activated PI3K-delta syndrome inherited ?,0000012-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",activated PI3K-delta syndrome,0000012,GHR,https://ghr.nlm.nih.gov/condition/activated-pi3k-delta-syndrome,C0039082,T047,Disorders
What are the treatments for activated PI3K-delta syndrome ?,0000012-5,treatment,These resources address the diagnosis or management of activated PI3K-delta syndrome:  - Genetic Testing Registry: Activated PI3K-delta syndrome  - National Institute of Allergy and Infectious Diseases: Primary Immune Deficiency Diseases: Talking To Your Doctor   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,activated PI3K-delta syndrome,0000012,GHR,https://ghr.nlm.nih.gov/condition/activated-pi3k-delta-syndrome,C0039082,T047,Disorders
What is (are) acute promyelocytic leukemia ?,0000013-1,information,"Acute promyelocytic leukemia is a form of acute myeloid leukemia, a cancer of the blood-forming tissue (bone marrow). In normal bone marrow, hematopoietic stem cells produce red blood cells (erythrocytes) that carry oxygen, white blood cells (leukocytes) that protect the body from infection, and platelets (thrombocytes) that are involved in blood clotting. In acute promyelocytic leukemia, immature white blood cells called promyelocytes accumulate in the bone marrow. The overgrowth of promyelocytes leads to a shortage of normal white and red blood cells and platelets in the body, which causes many of the signs and symptoms of the condition.  People with acute promyelocytic leukemia are especially susceptible to developing bruises, small red dots under the skin (petechiae), nosebleeds, bleeding from the gums, blood in the urine (hematuria), or excessive menstrual bleeding. The abnormal bleeding and bruising occur in part because of the low number of platelets in the blood (thrombocytopenia) and also because the cancerous cells release substances that cause excessive bleeding.  The low number of red blood cells (anemia) can cause people with acute promyelocytic leukemia to have pale skin (pallor) or excessive tiredness (fatigue). In addition, affected individuals may heal slowly from injuries or have frequent infections due to the loss of normal white blood cells that fight infection. Furthermore, the leukemic cells can spread to the bones and joints, which may cause pain in those areas. Other general signs and symptoms may occur as well, such as fever, loss of appetite, and weight loss.  Acute promyelocytic leukemia is most often diagnosed around age 40, although it can be diagnosed at any age.",acute promyelocytic leukemia,0000013,GHR,https://ghr.nlm.nih.gov/condition/acute-promyelocytic-leukemia,C0023487,T191,Disorders
How many people are affected by acute promyelocytic leukemia ?,0000013-2,frequency,"Acute promyelocytic leukemia accounts for about 10 percent of acute myeloid leukemia cases. Acute promyelocytic leukemia occurs in approximately 1 in 250,000 people in the United States.",acute promyelocytic leukemia,0000013,GHR,https://ghr.nlm.nih.gov/condition/acute-promyelocytic-leukemia,C0023487,T191,Disorders
What are the genetic changes related to acute promyelocytic leukemia ?,0000013-3,genetic changes,"The mutation that causes acute promyelocytic leukemia involves two genes, the PML gene on chromosome 15 and the RARA gene on chromosome 17. A rearrangement of genetic material (translocation) between chromosomes 15 and 17, written as t(15;17), fuses part of the PML gene with part of the RARA gene. The protein produced from this fused gene is known as PML-RAR. This mutation is acquired during a person's lifetime and is present only in certain cells. This type of genetic change, called a somatic mutation, is not inherited.  The PML-RAR protein functions differently than the protein products of the normal PML and RARA genes. The protein produced from the RARA gene, RAR, is involved in the regulation of gene transcription, which is the first step in protein production. Specifically, this protein helps control the transcription of certain genes important in the maturation (differentiation) of white blood cells beyond the promyelocyte stage. The protein produced from the PML gene acts as a tumor suppressor, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way. The PML-RAR protein interferes with the normal function of both the PML and the RAR proteins. As a result, blood cells are stuck at the promyelocyte stage, and they proliferate abnormally. Excess promyelocytes accumulate in the bone marrow and normal white blood cells cannot form, leading to acute promyelocytic leukemia.  The PML-RARA gene fusion accounts for up to 98 percent of cases of acute promyelocytic leukemia. Translocations involving the RARA gene and other genes have been identified in a few cases of acute promyelocytic leukemia.",acute promyelocytic leukemia,0000013,GHR,https://ghr.nlm.nih.gov/condition/acute-promyelocytic-leukemia,C0023487,T191,Disorders
Is acute promyelocytic leukemia inherited ?,0000013-4,inheritance,Acute promyelocytic leukemia is not inherited but arises from a translocation in the body's cells that occurs after conception.,acute promyelocytic leukemia,0000013,GHR,https://ghr.nlm.nih.gov/condition/acute-promyelocytic-leukemia,C0023487,T191,Disorders
What are the treatments for acute promyelocytic leukemia ?,0000013-5,treatment,These resources address the diagnosis or management of acute promyelocytic leukemia:  - American Cancer Society: Diagnosis of Acute Myeloid Leukemia  - American Cancer Society: Treatment of Acute Promyelocytic (M3) Leukemia  - Genetic Testing Registry: Acute promyelocytic leukemia  - MedlinePlus Encyclopedia: Acute Myeloid Leukemia  - National Cancer Institute: Adult Acute Myeloid Leukemia Treatment  - National Cancer Institute: Leukemia  - National Heart Lung and Blood Institute: Bone Marrow Tests   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,acute promyelocytic leukemia,0000013,GHR,https://ghr.nlm.nih.gov/condition/acute-promyelocytic-leukemia,C0023487,T191,Disorders
What is (are) Adams-Oliver syndrome ?,0000014-1,information,"Adams-Oliver syndrome is a rare condition that is present at birth. The primary features are an abnormality in skin development (called aplasia cutis congenita) and malformations of the limbs. A variety of other features can occur in people with Adams-Oliver syndrome.  Most people with Adams-Oliver syndrome have aplasia cutis congenita, a condition characterized by localized areas of missing skin typically occurring on the top of the head (the skull vertex). In some cases, the bone under the skin is also underdeveloped. Individuals with this condition commonly have scarring and an absence of hair growth in the affected area.  Abnormalities of the hands and feet are also common in people with Adams-Oliver syndrome. These most often involve the fingers and toes and can include abnormal nails, fingers or toes that are fused together (syndactyly), and abnormally short or missing fingers or toes (brachydactyly or oligodactyly). In some cases, other bones in the hands, feet, or lower limbs are malformed or missing.  Some affected infants have a condition called cutis marmorata telangiectatica congenita. This disorder of the blood vessels causes a reddish or purplish net-like pattern on the skin. In addition, people with Adams-Oliver syndrome can develop high blood pressure in the blood vessels between the heart and the lungs (pulmonary hypertension), which can be life-threatening. Other blood vessel problems and heart defects can occur in affected individuals.  In some cases, people with Adams-Oliver syndrome have neurological problems, such as developmental delay, learning disabilities, or abnormalities in the structure of the brain.",Adams-Oliver syndrome,0000014,GHR,https://ghr.nlm.nih.gov/condition/adams-oliver-syndrome,C0265268,T019,Disorders
How many people are affected by Adams-Oliver syndrome ?,0000014-2,frequency,Adams-Oliver syndrome is a rare disorder; its prevalence is unknown.,Adams-Oliver syndrome,0000014,GHR,https://ghr.nlm.nih.gov/condition/adams-oliver-syndrome,C0265268,T019,Disorders
What are the genetic changes related to Adams-Oliver syndrome ?,0000014-3,genetic changes,"Mutations in the ARHGAP31, DLL4, DOCK6, EOGT, NOTCH1, or RBPJ gene can cause Adams-Oliver syndrome. Because some affected individuals do not have mutations in one of these genes, it is likely that other genes that have not been identified are also involved in this condition. Each of the known genes plays an important role during embryonic development, and changes in any one of them can impair this tightly controlled process, leading to the signs and symptoms of Adams-Oliver syndrome.  The proteins produced from the ARHGAP31 and DOCK6 genes are both involved in the regulation of proteins called GTPases, which transmit signals that are critical for various aspects of embryonic development. The ARHGAP31 and DOCK6 proteins appear to be especially important for GTPase regulation during development of the limbs, skull, and heart. GTPases are often called molecular switches because they can be turned on and off. The DOCK6 protein turns them on, and the ARHGAP31 protein turns them off. Mutations in the DOCK6 gene lead to production of an abnormally short DOCK6 protein that is likely unable to turn on GTPases, which reduces their activity. Mutations in the ARHGAP31 gene also decrease GTPase activity by leading to production of an abnormally active ARHGAP31 protein, which turns off GTPases when it normally would not. This decline in GTPase activity leads to the skin problems, bone malformations, and other features characteristic of Adams-Oliver syndrome.  The proteins produced from the NOTCH1, DLL4, and RBPJ genes are part of a signaling pathway known as the Notch pathway. Notch signaling controls how certain types of cells develop in the growing embryo, including those that form the bones, heart, muscles, nerves, and blood vessels. The Notch1 and DLL4 proteins fit together like a lock and its key to stimulate one part of the Notch pathway, which is important for development of blood vessels. The NOTCH1 and DLL4 gene mutations involved in Adams-Oliver syndrome likely impair Notch1 signaling, which may underlie blood vessel and heart abnormalities in some people with Adams-Oliver syndrome. Researchers suspect that the other features of the condition may be due to abnormal blood vessel development before birth.  Signaling through Notch1 and other Notch proteins stimulates the RBP-J protein, produced from the RBPJ gene, to attach (bind) to specific regions of DNA and control the activity of genes that play a role in cellular development in multiple tissues throughout the body. The RBPJ gene mutations involved in Adams-Oliver syndrome alter the region of the RBP-J protein that normally binds DNA. The altered protein is unable to bind to DNA, preventing it from turning on particular genes. These changes in gene activity impair the proper development of the skin, bones, and other tissues, leading to the features of Adams-Oliver syndrome.  Little is known about how mutations in the EOGT gene cause Adams-Oliver syndrome. The protein produced from this gene modifies certain proteins by transferring a molecule called N-acetylglucosamine to them. It is thought that the EOGT protein modifies Notch proteins, which stimulate the Notch signaling pathway. However, the impact of the modification on Notch signaling is unclear. At least three mutations in the EOGT gene have been identified in people with Adams-Oliver syndrome, but how the genetic changes contribute to the signs and symptoms of this disorder is still unknown.",Adams-Oliver syndrome,0000014,GHR,https://ghr.nlm.nih.gov/condition/adams-oliver-syndrome,C0265268,T019,Disorders
Is Adams-Oliver syndrome inherited ?,0000014-4,inheritance,"Adams-Oliver syndrome can have different inheritance patterns. When caused by mutations in the ARHGAP31, DLL4, NOTCH1, or RBPJ gene, the condition is inherited in an autosomal dominant pattern. Autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder. The altered gene is typically inherited from an affected parent. Some cases associated with NOTCH1 gene mutations result from new (de novo) mutations in the gene that occur during the formation of reproductive cells (eggs or sperm) or in early embryonic development. These cases occur in people with no history of the disorder in their family.  When caused by mutations in the DOCK6 or EOGT gene, Adams-Oliver syndrome is inherited in an autosomal recessive pattern. In conditions with this pattern of inheritance, both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Adams-Oliver syndrome,0000014,GHR,https://ghr.nlm.nih.gov/condition/adams-oliver-syndrome,C0265268,T019,Disorders
What are the treatments for Adams-Oliver syndrome ?,0000014-5,treatment,These resources address the diagnosis or management of Adams-Oliver syndrome:  - Contact a Family  - Gene Review: Gene Review: Adams-Oliver Syndrome  - Genetic Testing Registry: Adams-Oliver syndrome  - Genetic Testing Registry: Adams-Oliver syndrome 5  - Genetic Testing Registry: Adams-Oliver syndrome 6   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Adams-Oliver syndrome,0000014,GHR,https://ghr.nlm.nih.gov/condition/adams-oliver-syndrome,C0265268,T019,Disorders
What is (are) ADCY5-related dyskinesia ?,0000015-1,information,"ADCY5-related dyskinesia is a movement disorder; the term ""dyskinesia"" refers to abnormal involuntary movements. The abnormal movements that occur in ADCY5-related dyskinesia typically appear as sudden (paroxysmal) jerks, twitches, tremors, muscle tensing (dystonia), or writhing (choreiform) movements, and can affect the limbs, neck, and face.  The abnormal movements associated with ADCY5-related dyskinesia usually begin between infancy and late adolescence. They can occur continually during waking hours and in some cases also during sleep. Severely affected infants may experience weak muscle tone (hypotonia) and delay in development of motor skills such as crawling and walking; these individuals may have difficulties with activities of daily living and may eventually require a wheelchair. In more mildly affected individuals, the condition has little impact on walking and other motor skills, although the abnormal movements can lead to clumsiness or difficulty with social acceptance in school or other situations.  In some people with ADCY5-related dyskinesia, the disorder is generally stable throughout their lifetime. In others, it slowly gets worse (progresses) in both frequency and severity before stabilizing or even improving in middle age. Anxiety, fatigue, and other stress can temporarily increase the severity of the signs and symptoms of ADCY5-related dyskinesia, while some affected individuals may experience remission periods of days or weeks without abnormal movements. Life expectancy and intelligence are unaffected by this disorder.",ADCY5-related dyskinesia,0000015,GHR,https://ghr.nlm.nih.gov/condition/adcy5-related-dyskinesia,C0013384,T047,Disorders
How many people are affected by ADCY5-related dyskinesia ?,0000015-2,frequency,The prevalence of ADCY5-related dyskinesia is unknown. At least 50 affected individuals have been described in the medical literature.,ADCY5-related dyskinesia,0000015,GHR,https://ghr.nlm.nih.gov/condition/adcy5-related-dyskinesia,C0013384,T047,Disorders
What are the genetic changes related to ADCY5-related dyskinesia ?,0000015-3,genetic changes,"As its name suggests, ADCY5-related dyskinesia is caused by mutations in the ADCY5 gene. This gene provides instructions for making an enzyme called adenylate cyclase 5. This enzyme helps convert a molecule called adenosine triphosphate (ATP) to another molecule called cyclic adenosine monophosphate (cAMP). ATP is a molecule that supplies energy for cells' activities, including muscle contraction, and cAMP is involved in signaling for many cellular functions. Some ADCY5 gene mutations that cause ADCY5-related dyskinesia are thought to increase adenylate cyclase 5 enzyme activity and the level of cAMP within cells. Others prevent production of adenylate cyclase 5. It is unclear how either type of mutation leads to the abnormal movements that occur in this disorder.",ADCY5-related dyskinesia,0000015,GHR,https://ghr.nlm.nih.gov/condition/adcy5-related-dyskinesia,C0013384,T047,Disorders
Is ADCY5-related dyskinesia inherited ?,0000015-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",ADCY5-related dyskinesia,0000015,GHR,https://ghr.nlm.nih.gov/condition/adcy5-related-dyskinesia,C0013384,T047,Disorders
What are the treatments for ADCY5-related dyskinesia ?,0000015-5,treatment,"These resources address the diagnosis or management of ADCY5-related dyskinesia:  - Gene Review: Gene Review: ADCY5-Related Dyskinesia  - Genetic Testing Registry: Dyskinesia, familial, with facial myokymia  - National Ataxia Foundation: Movement Disorder Clinics   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",ADCY5-related dyskinesia,0000015,GHR,https://ghr.nlm.nih.gov/condition/adcy5-related-dyskinesia,C0013384,T047,Disorders
What is (are) adenine phosphoribosyltransferase deficiency ?,0000016-1,information,"Adenine phosphoribosyltransferase (APRT) deficiency is an inherited condition that affects the kidneys and urinary tract. The most common feature of this condition is recurrent kidney stones; urinary tract stones are also a frequent symptom. Kidney and urinary tract stones can create blockages in the urinary tract, causing pain during urination and difficulty releasing urine.  Affected individuals can develop features of this condition anytime from infancy to late adulthood. When the condition appears in infancy, the first sign is usually the presence of tiny grains of reddish-brown material in the baby's diaper caused by the passing of stones. Later, recurrent kidney and urinary tract stones can lead to problems with kidney function beginning as early as mid- to late childhood. Approximately half of individuals with APRT deficiency first experience signs and symptoms of the condition in adulthood. The first features in affected adults are usually kidney stones and related urinary problems. Other signs and symptoms of APRT deficiency caused by kidney and urinary tract stones include fever, urinary tract infection, blood in the urine (hematuria), abdominal cramps, nausea, and vomiting.  Without treatment, kidney function can decline, which may lead to end-stage renal disease (ESRD). ESRD is a life-threatening failure of kidney function that occurs when the kidneys are no longer able to filter fluids and waste products from the body effectively.  The features of this condition and their severity vary greatly among affected individuals, even among members of the same family. It is estimated that 15 to 20 percent of people with APRT deficiency do not have any signs or symptoms of the condition.",adenine phosphoribosyltransferase deficiency,0000016,GHR,https://ghr.nlm.nih.gov/condition/adenine-phosphoribosyltransferase-deficiency,C0268120,T047,Disorders
How many people are affected by adenine phosphoribosyltransferase deficiency ?,0000016-2,frequency,"APRT deficiency is estimated to affect 1 in 27,000 people in Japan. The condition is rarer in Europe, where it is thought to affect 1 in 50,000 to 100,000 people. The prevalence of APRT deficiency outside these populations is unknown.",adenine phosphoribosyltransferase deficiency,0000016,GHR,https://ghr.nlm.nih.gov/condition/adenine-phosphoribosyltransferase-deficiency,C0268120,T047,Disorders
What are the genetic changes related to adenine phosphoribosyltransferase deficiency ?,0000016-3,genetic changes,"Mutations in the APRT gene cause APRT deficiency. This gene provides instructions for making APRT, an enzyme that helps to convert a DNA building block (nucleotide) called adenine to a molecule called adenosine monophosphate (AMP). This conversion occurs when AMP is needed as a source of energy for cells.  APRT gene mutations lead to the production of an abnormal APRT enzyme with reduced function or prevent the production of any enzyme. A lack of functional enzyme impairs the conversion of adenine to AMP. As a result, adenine is converted to another molecule called 2,8-dihydroxyadenine (2,8-DHA). 2,8-DHA crystallizes in urine, forming stones in the kidneys and urinary tract. 2,8-DHA crystals are brownish in color, which explains why affected infants frequently have dark urine stains in their diapers. 2,8-DHA is toxic to kidneys, which may explain the possible decline in kidney function and the progression to ESRD.",adenine phosphoribosyltransferase deficiency,0000016,GHR,https://ghr.nlm.nih.gov/condition/adenine-phosphoribosyltransferase-deficiency,C0268120,T047,Disorders
Is adenine phosphoribosyltransferase deficiency inherited ?,0000016-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",adenine phosphoribosyltransferase deficiency,0000016,GHR,https://ghr.nlm.nih.gov/condition/adenine-phosphoribosyltransferase-deficiency,C0268120,T047,Disorders
What are the treatments for adenine phosphoribosyltransferase deficiency ?,0000016-5,treatment,These resources address the diagnosis or management of adenine phosphoribosyltransferase deficiency:  - Boston Children's Hospital: Pediatric Kidney Stones in Children  - Gene Review: Gene Review: Adenine Phosphoribosyltransferase Deficiency  - Genetic Testing Registry: Adenine phosphoribosyltransferase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,adenine phosphoribosyltransferase deficiency,0000016,GHR,https://ghr.nlm.nih.gov/condition/adenine-phosphoribosyltransferase-deficiency,C0268120,T047,Disorders
What is (are) adenosine deaminase deficiency ?,0000018-1,information,"Adenosine deaminase (ADA) deficiency is an inherited disorder that damages the immune system and causes severe combined immunodeficiency (SCID). People with SCID lack virtually all immune protection from bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. These infections are often caused by ""opportunistic"" organisms that ordinarily do not cause illness in people with a normal immune system.  The main symptoms of ADA deficiency are pneumonia, chronic diarrhea, and widespread skin rashes. Affected children also grow much more slowly than healthy children and some have developmental delay.  Most individuals with ADA deficiency are diagnosed with SCID in the first 6 months of life. Without treatment, these babies usually do not survive past age 2. In about 10 percent to 15 percent of cases, onset of immune deficiency is delayed to between 6 and 24 months of age (delayed onset) or even until adulthood (late onset). Immune deficiency in these later-onset cases tends to be less severe, causing primarily recurrent upper respiratory and ear infections. Over time, affected individuals may develop chronic lung damage, malnutrition, and other health problems.",adenosine deaminase deficiency,0000018,GHR,https://ghr.nlm.nih.gov/condition/adenosine-deaminase-deficiency,C1863239,T047,Disorders
How many people are affected by adenosine deaminase deficiency ?,0000018-2,frequency,"Adenosine deaminase deficiency is very rare and is estimated to occur in approximately 1 in 200,000 to 1,000,000 newborns worldwide. This disorder is responsible for approximately 15 percent of SCID cases.",adenosine deaminase deficiency,0000018,GHR,https://ghr.nlm.nih.gov/condition/adenosine-deaminase-deficiency,C1863239,T047,Disorders
What are the genetic changes related to adenosine deaminase deficiency ?,0000018-3,genetic changes,"Adenosine deaminase deficiency is caused by mutations in the ADA gene. This gene provides instructions for producing the enzyme adenosine deaminase. This enzyme is found throughout the body but is most active in specialized white blood cells called lymphocytes. These cells protect the body against potentially harmful invaders, such as bacteria and viruses, by making immune proteins called antibodies or by directly attacking infected cells. Lymphocytes are produced in specialized lymphoid tissues including the thymus, which is a gland located behind the breastbone, and lymph nodes, which are found throughout the body. Lymphocytes in the blood and in lymphoid tissues make up the immune system.  The function of the adenosine deaminase enzyme is to eliminate a molecule called deoxyadenosine, which is generated when DNA is broken down. Adenosine deaminase converts deoxyadenosine, which can be toxic to lymphocytes, to another molecule called deoxyinosine that is not harmful. Mutations in the ADA gene reduce or eliminate the activity of adenosine deaminase and allow the buildup of deoxyadenosine to levels that are toxic to lymphocytes.  Immature lymphocytes in the thymus are particularly vulnerable to a toxic buildup of deoxyadenosine. These cells die before they can mature to help fight infection. The number of lymphocytes in other lymphoid tissues is also greatly reduced. The loss of infection-fighting cells results in the signs and symptoms of SCID.",adenosine deaminase deficiency,0000018,GHR,https://ghr.nlm.nih.gov/condition/adenosine-deaminase-deficiency,C1863239,T047,Disorders
Is adenosine deaminase deficiency inherited ?,0000018-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",adenosine deaminase deficiency,0000018,GHR,https://ghr.nlm.nih.gov/condition/adenosine-deaminase-deficiency,C1863239,T047,Disorders
What are the treatments for adenosine deaminase deficiency ?,0000018-5,treatment,These resources address the diagnosis or management of ADA deficiency:  - American Society of Gene and Cell Therapy: Gene Therapy for Genetic Disorders  - Baby's First Test: Severe Combined Immunodeficiency  - Gene Review: Gene Review: Adenosine Deaminase Deficiency  - Genetic Testing Registry: Severe combined immunodeficiency due to ADA deficiency  - National Marrow Donor Program: SCID and Transplant   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,adenosine deaminase deficiency,0000018,GHR,https://ghr.nlm.nih.gov/condition/adenosine-deaminase-deficiency,C1863239,T047,Disorders
What is (are) adenosine monophosphate deaminase deficiency ?,0000019-1,information,"Adenosine monophosphate (AMP) deaminase deficiency is a condition that can affect the muscles used for movement (skeletal muscles). People with this condition do not make enough of an enzyme called AMP deaminase. In most people, AMP deaminase deficiency does not cause any symptoms. People who do experience symptoms typically have muscle pain (myalgia) or weakness after exercise or prolonged physical activity. They often get tired more quickly and stay tired longer than would normally be expected. Some affected individuals have more severe symptoms, but it is unclear whether these symptoms are due solely to a lack of AMP deaminase or additional factors. Muscle weakness is typically apparent beginning in childhood or early adulthood.  Researchers have proposed three types of AMP deaminase deficiency, which are distinguished by their symptoms and genetic cause.",adenosine monophosphate deaminase deficiency,0000019,GHR,https://ghr.nlm.nih.gov/condition/adenosine-monophosphate-deaminase-deficiency,C2931781,T047,Disorders
How many people are affected by adenosine monophosphate deaminase deficiency ?,0000019-2,frequency,"AMP deaminase deficiency is one of the most common inherited muscle disorders in white populations, affecting 1 in 50 to 100 people. The prevalence is lower in African Americans, affecting an estimated 1 in 40,000 people, and the condition is even less common in the Japanese population.",adenosine monophosphate deaminase deficiency,0000019,GHR,https://ghr.nlm.nih.gov/condition/adenosine-monophosphate-deaminase-deficiency,C2931781,T047,Disorders
What are the genetic changes related to adenosine monophosphate deaminase deficiency ?,0000019-3,genetic changes,"Mutations in the AMPD1 gene cause AMP deaminase deficiency. The AMPD1 gene provides instructions for producing an enzyme called AMP deaminase. This enzyme is found in skeletal muscle, where it plays a role in producing energy within muscle cells. Mutations in the AMPD1 gene disrupt the function of AMP deaminase and impair the muscle cells' ability to produce energy. This lack of energy can lead to myalgia or other muscle problems associated with AMP deaminase deficiency.  The three types of AMP deaminase deficiency are known as the inherited type, acquired type, and coincidental inherited type.  Individuals with the inherited type have a mutation in both copies of the AMPD1 gene in each cell. Most people are asymptomatic, meaning they have no symptoms. Some people with AMP deaminase deficiency experience muscle weakness or pain following exercise.  The acquired type occurs in people who have decreased levels of AMP deaminase due to the presence of a muscle or joint condition.  People with the coincidental inherited type have a mutation in both copies of the AMPD1 gene. Additionally, they have a separate joint or muscle disorder. Some individuals experience more severe joint or muscle symptoms related to their disorder if they have AMP deaminase deficiency than do people without this enzyme deficiency. Most, however, do not have any symptoms associated with AMP deaminase deficiency.  It is not known why most people with this condition do not experience symptoms. Researchers speculate that additional mutations in other genes may be involved.",adenosine monophosphate deaminase deficiency,0000019,GHR,https://ghr.nlm.nih.gov/condition/adenosine-monophosphate-deaminase-deficiency,C2931781,T047,Disorders
Is adenosine monophosphate deaminase deficiency inherited ?,0000019-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",adenosine monophosphate deaminase deficiency,0000019,GHR,https://ghr.nlm.nih.gov/condition/adenosine-monophosphate-deaminase-deficiency,C2931781,T047,Disorders
What are the treatments for adenosine monophosphate deaminase deficiency ?,0000019-5,treatment,These resources address the diagnosis or management of adenosine monophosphate deaminase deficiency:  - MedlinePlus Encyclopedia: Muscle aches  - MedlinePlus Encyclopedia: Weakness   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,adenosine monophosphate deaminase deficiency,0000019,GHR,https://ghr.nlm.nih.gov/condition/adenosine-monophosphate-deaminase-deficiency,C2931781,T047,Disorders
What is (are) adenylosuccinate lyase deficiency ?,0000020-1,information,"Adenylosuccinate lyase deficiency is a neurological disorder that causes brain dysfunction (encephalopathy) leading to delayed development of mental and movement abilities (psychomotor delay), autistic behaviors that affect communication and social interaction, and seizures. A characteristic feature that can help with diagnosis of this condition is the presence of chemicals called succinylaminoimidazole carboxamide riboside (SAICAr) and succinyladenosine (S-Ado) in body fluids.  Adenylosuccinate lyase deficiency is classified into three forms based on the severity of the signs and symptoms. The most severe is the neonatal form. Signs and symptoms of this form can be detected at or before birth and can include impaired growth during fetal development and a small head size (microcephaly). Affected newborns have severe encephalopathy, which leads to a lack of movement, difficulty feeding, and life-threatening respiratory problems. Some affected babies develop seizures that do not improve with treatment. Because of the severity of the encephalopathy, infants with this form of the condition generally do not survive more than a few weeks after birth.  Adenylosuccinate lyase deficiency type I (also known as the severe form) is the most common. The signs and symptoms of this form begin in the first months of life. Affected babies have severe psychomotor delay, weak muscle tone (hypotonia), and microcephaly. Many affected infants develop recurrent seizures that are difficult to treat, and some exhibit autistic behaviors, such as repetitive behaviors and a lack of eye contact.  In individuals with adenylosuccinate lyase deficiency type II (also known as the moderate or mild form), development is typically normal for the first few years of life but then slows. Psychomotor delay is considered mild or moderate. Some children with this form of the condition develop seizures and autistic behaviors.",adenylosuccinate lyase deficiency,0000020,GHR,https://ghr.nlm.nih.gov/condition/adenylosuccinate-lyase-deficiency,C0268126,T047,Disorders
How many people are affected by adenylosuccinate lyase deficiency ?,0000020-2,frequency,"Adenylosuccinate lyase deficiency is a rare disorder; fewer than 100 cases have been reported. The condition is most common in the Netherlands and Belgium, but it has been found worldwide.",adenylosuccinate lyase deficiency,0000020,GHR,https://ghr.nlm.nih.gov/condition/adenylosuccinate-lyase-deficiency,C0268126,T047,Disorders
What are the genetic changes related to adenylosuccinate lyase deficiency ?,0000020-3,genetic changes,"All forms of adenylosuccinate lyase deficiency are caused by mutations in the ADSL gene. This gene provides instructions for making an enzyme called adenylosuccinate lyase, which performs two steps in the process that produces purine nucleotides. These nucleotides are building blocks of DNA, its chemical cousin RNA, and molecules such as ATP that serve as energy sources in the cell. Adenylosuccinate lyase converts a molecule called succinylaminoimidazole carboxamide ribotide (SAICAR) to aminoimidazole carboxamide ribotide (AICAR) and converts succinyladenosine monophosphate (SAMP) to adenosine monophosphate (AMP).  Most of the mutations involved in adenylosuccinate lyase deficiency change single protein building blocks (amino acids) in the adenylosuccinate lyase enzyme, which impairs its function. Reduced function of this enzyme leads to buildup of SAICAR and SAMP, which are converted through a different reaction to succinylaminoimidazole carboxamide riboside (SAICAr) and succinyladenosine (S-Ado). Researchers believe that SAICAr and S-Ado are toxic; damage to brain tissue caused by one or both of these substances likely underlies the neurological problems that occur in adenylosuccinate lyase deficiency.  Studies suggest that the amount of SAICAr relative to S-Ado reflects the severity of adenylosuccinate lyase deficiency. Individuals with more SAICAr than S-Ado have more severe encephalopathy and psychomotor delay.",adenylosuccinate lyase deficiency,0000020,GHR,https://ghr.nlm.nih.gov/condition/adenylosuccinate-lyase-deficiency,C0268126,T047,Disorders
Is adenylosuccinate lyase deficiency inherited ?,0000020-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",adenylosuccinate lyase deficiency,0000020,GHR,https://ghr.nlm.nih.gov/condition/adenylosuccinate-lyase-deficiency,C0268126,T047,Disorders
What are the treatments for adenylosuccinate lyase deficiency ?,0000020-5,treatment,These resources address the diagnosis or management of adenylosuccinate lyase deficiency:  - Genetic Testing Registry: Adenylosuccinate lyase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,adenylosuccinate lyase deficiency,0000020,GHR,https://ghr.nlm.nih.gov/condition/adenylosuccinate-lyase-deficiency,C0268126,T047,Disorders
What is (are) adermatoglyphia ?,0000021-1,information,"Adermatoglyphia is the absence of ridges on the skin on the pads of the fingers and toes, as well as on the palms of the hands and soles of the feet. The patterns of these ridges (called dermatoglyphs) form whorls, arches, and loops that are the basis for each person's unique fingerprints. Because no two people have the same patterns, fingerprints have long been used as a way to identify individuals. However, people with adermatoglyphia do not have these ridges, and so they cannot be identified by their fingerprints. Adermatoglyphia has been called the ""immigration delay disease"" because affected individuals have had difficulty entering countries that require fingerprinting for identification.  In some families, adermatoglyphia occurs without any related signs and symptoms. In others, a lack of dermatoglyphs is associated with other features, typically affecting the skin. These can include small white bumps called milia on the face, blistering of the skin in areas exposed to heat or friction, and a reduced number of sweat glands on the hands and feet. Adermatoglyphia is also a feature of several rare syndromes classified as ectodermal dysplasias, including a condition called Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis that affects the skin, hair, sweat glands, and teeth.",adermatoglyphia,0000021,GHR,https://ghr.nlm.nih.gov/condition/adermatoglyphia,C1852150,T033,Disorders
How many people are affected by adermatoglyphia ?,0000021-2,frequency,Adermatoglyphia appears to be a rare condition. Only a few affected families have been identified worldwide.,adermatoglyphia,0000021,GHR,https://ghr.nlm.nih.gov/condition/adermatoglyphia,C1852150,T033,Disorders
What are the genetic changes related to adermatoglyphia ?,0000021-3,genetic changes,"Adermatoglyphia is caused by mutations in the SMARCAD1 gene. This gene provides information for making two versions of the SMARCAD1 protein: a full-length version that is active (expressed) in multiple tissues and a shorter version that is expressed only in the skin. Studies suggest that the full-length SMARCAD1 protein regulates the activity of a wide variety of genes involved in maintaining the stability of cells' genetic information. Little is known about the function of the skin-specific version of the SMARCAD1 protein, but it appears to play a critical role in dermatoglyph formation. Dermatoglyphs develop before birth and remain the same throughout life. The activity of this protein is likely one of several factors that determine each person's unique fingerprint pattern.  The SMARCAD1 gene mutations that cause adermatoglyphia affect only the skin-specific version of the SMARCAD1 protein. These mutations reduce the total amount of this protein available in skin cells. Although it is unclear how these genetic changes cause adermatoglyphia, researchers speculate that a shortage of the skin-specific version of the SMARCAD1 protein impairs signaling pathways needed for normal skin development and function, including the formation of dermatoglyphs.",adermatoglyphia,0000021,GHR,https://ghr.nlm.nih.gov/condition/adermatoglyphia,C1852150,T033,Disorders
Is adermatoglyphia inherited ?,0000021-4,inheritance,"Adermatoglyphia is inherited in an autosomal dominant pattern, which means one copy of the altered SMARCAD1 gene in each cell is sufficient to cause the condition. In many cases, an affected person has one parent with the condition.",adermatoglyphia,0000021,GHR,https://ghr.nlm.nih.gov/condition/adermatoglyphia,C1852150,T033,Disorders
What are the treatments for adermatoglyphia ?,0000021-5,treatment,These resources address the diagnosis or management of adermatoglyphia:  - Genetic Testing Registry: Adermatoglyphia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,adermatoglyphia,0000021,GHR,https://ghr.nlm.nih.gov/condition/adermatoglyphia,C1852150,T033,Disorders
What is (are) adiposis dolorosa ?,0000022-1,information,"Adiposis dolorosa is a condition characterized by painful folds of fatty (adipose) tissue or the growth of multiple noncancerous (benign) fatty tumors called lipomas. This condition occurs most often in women who are overweight or obese, and signs and symptoms typically appear between ages 35 and 50.  In people with adiposis dolorosa, abnormal fatty tissue or lipomas can occur anywhere on the body but are most often found on the torso, buttocks, and upper parts of the arms and legs. Lipomas usually feel like firm bumps (nodules) under the skin. The growths cause burning or aching that can be severe. In some people, the pain comes and goes, while in others it is continuous. Movement or pressure on adipose tissue or lipomas can make the pain worse.  Other signs and symptoms that have been reported to occur with adiposis dolorosa include general weakness and tiredness (fatigue), depression, irritability, confusion, recurrent seizures (epilepsy), and a progressive decline in intellectual function (dementia). These problems do not occur in everyone with adiposis dolorosa, and it is unclear whether they are directly related to the condition.",adiposis dolorosa,0000022,GHR,https://ghr.nlm.nih.gov/condition/adiposis-dolorosa,C0001529,T047,Disorders
How many people are affected by adiposis dolorosa ?,0000022-2,frequency,"Adiposis dolorosa is a rare condition whose prevalence is unknown. For reasons that are unclear, it occurs up to 30 times more often in women than in men.",adiposis dolorosa,0000022,GHR,https://ghr.nlm.nih.gov/condition/adiposis-dolorosa,C0001529,T047,Disorders
What are the genetic changes related to adiposis dolorosa ?,0000022-3,genetic changes,"The cause of adiposis dolorosa is unknown. The condition is thought to have a genetic component because a few families with multiple affected family members have been reported. However, no associated genes have been identified.  Several other possible causes of adiposis dolorosa have been suggested, although none have been confirmed. They include the use of medications called corticosteroids, dysfunction of the endocrine system (which produces hormones), or changes in the deposition and breakdown of fat (adipose tissue metabolism). Researchers have also suggested that adiposis dolorosa could be an autoimmune disorder, which occurs when the immune system malfunctions and attacks the body's own tissues and organs. However, there is no firm evidence that the condition is related to abnormal inflammation or other immune system malfunction.  It is unknown why adiposis dolorosa usually occurs in people who are overweight or obese, or why the signs and symptoms do not appear until mid-adulthood.",adiposis dolorosa,0000022,GHR,https://ghr.nlm.nih.gov/condition/adiposis-dolorosa,C0001529,T047,Disorders
Is adiposis dolorosa inherited ?,0000022-4,inheritance,"Most cases of adiposis dolorosa are sporadic, which means they occur in people with no history of the disorder in their family.  A small number of familial cases of adiposis dolorosa have been reported. When the condition runs in families, it appears to have an autosomal dominant pattern of inheritance because affected individuals inherit the condition from one affected parent. This pattern of inheritance suggests that one copy of an altered gene in each cell is sufficient to cause the disorder.",adiposis dolorosa,0000022,GHR,https://ghr.nlm.nih.gov/condition/adiposis-dolorosa,C0001529,T047,Disorders
What are the treatments for adiposis dolorosa ?,0000022-5,treatment,These resources address the diagnosis or management of adiposis dolorosa:  - Genetic Testing Registry: Lipomatosis dolorosa  - Merck Manual Consumer Version: Lipomas   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,adiposis dolorosa,0000022,GHR,https://ghr.nlm.nih.gov/condition/adiposis-dolorosa,C0001529,T047,Disorders
What is (are) adolescent idiopathic scoliosis ?,0000023-1,information,"Adolescent idiopathic scoliosis is an abnormal curvature of the spine that appears in late childhood or adolescence. Instead of growing straight, the spine develops a side-to-side curvature, usually in an elongated ""S"" or ""C"" shape; the bones of the spine are also slightly twisted or rotated.  Adolescent idiopathic scoliosis appears during the adolescent growth spurt, a time when children are growing rapidly. In many cases the abnormal spinal curve is stable, although in some children the curve is progressive (meaning it becomes more severe over time). For unknown reasons, severe and progressive curves occur more frequently in girls than in boys. However, mild spinal curvature is equally common in girls and boys.  Mild scoliosis generally does not cause pain, problems with movement, or difficulty breathing. It may only be diagnosed if it is noticed during a regular physical examination or a scoliosis screening at school. The most common signs of the condition include a tilt or unevenness (asymmetry) in the shoulders, hips, or waist, or having one leg that appears longer than the other. A small percentage of affected children develop more severe, pronounced spinal curvature.  Scoliosis can occur as a feature of other conditions, including a variety of genetic syndromes. However, adolescent idiopathic scoliosis typically occurs by itself, without signs and symptoms affecting other parts of the body.",adolescent idiopathic scoliosis,0000023,GHR,https://ghr.nlm.nih.gov/condition/adolescent-idiopathic-scoliosis,C2700406,T190,Disorders
How many people are affected by adolescent idiopathic scoliosis ?,0000023-2,frequency,Adolescent idiopathic scoliosis is the most common spinal abnormality in children. It affects an estimated 2 to 3 percent of children in the U.S.,adolescent idiopathic scoliosis,0000023,GHR,https://ghr.nlm.nih.gov/condition/adolescent-idiopathic-scoliosis,C2700406,T190,Disorders
What are the genetic changes related to adolescent idiopathic scoliosis ?,0000023-3,genetic changes,"The term ""idiopathic"" means that the cause of this condition is unknown. Adolescent idiopathic scoliosis probably results from a combination of genetic and environmental factors. Studies suggest that the abnormal spinal curvature may be related to hormonal problems, abnormal bone or muscle growth, nervous system abnormalities, or other factors that have not been identified.  Researchers suspect that many genes are involved in adolescent idiopathic scoliosis. Some of these genes likely contribute to causing the disorder, while others play a role in determining the severity of spinal curvature and whether the curve is stable or progressive. Although many genes have been studied, few clear and consistent genetic associations with adolescent idiopathic scoliosis have been identified.",adolescent idiopathic scoliosis,0000023,GHR,https://ghr.nlm.nih.gov/condition/adolescent-idiopathic-scoliosis,C2700406,T190,Disorders
Is adolescent idiopathic scoliosis inherited ?,0000023-4,inheritance,"Adolescent idiopathic scoliosis can be sporadic, which means it occurs in people without a family history of the condition, or it can cluster in families. The inheritance pattern of adolescent idiopathic scoliosis is unclear because many genetic and environmental factors appear to be involved. However, having a close relative (such as a parent or sibling) with adolescent idiopathic scoliosis increases a child's risk of developing the condition.",adolescent idiopathic scoliosis,0000023,GHR,https://ghr.nlm.nih.gov/condition/adolescent-idiopathic-scoliosis,C2700406,T190,Disorders
What are the treatments for adolescent idiopathic scoliosis ?,0000023-5,treatment,"These resources address the diagnosis or management of adolescent idiopathic scoliosis:  - Genetic Testing Registry: Scoliosis, idiopathic 1  - Genetic Testing Registry: Scoliosis, idiopathic 2  - Genetic Testing Registry: Scoliosis, idiopathic 3  - National Scoliosis Foundation: FAQs  - Scoliosis Research Society: Find A Specialist  - Scoliosis Research Society: For Adolescents   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",adolescent idiopathic scoliosis,0000023,GHR,https://ghr.nlm.nih.gov/condition/adolescent-idiopathic-scoliosis,C2700406,T190,Disorders
What is (are) adult polyglucosan body disease ?,0000024-1,information,"Adult polyglucosan body disease is a condition that affects the nervous system. People with this condition have problems walking due to reduced sensation in their legs (peripheral neuropathy) and progressive muscle weakness and stiffness (spasticity). Damage to the nerves that control bladder function, a condition called neurogenic bladder, causes affected individuals to have progressive difficulty controlling the flow of urine. About half of people with adult polyglucosan body disease experience a decline in intellectual function (dementia).  People with adult polyglucosan body disease typically first experience signs and symptoms related to the condition between ages 30 and 60.",adult polyglucosan body disease,0000024,GHR,https://ghr.nlm.nih.gov/condition/adult-polyglucosan-body-disease,C1849722,T047,Disorders
How many people are affected by adult polyglucosan body disease ?,0000024-2,frequency,"Adult polyglucosan body disease is a rare condition; although its exact prevalence is unknown, at least 50 affected individuals have been described in the medical literature.",adult polyglucosan body disease,0000024,GHR,https://ghr.nlm.nih.gov/condition/adult-polyglucosan-body-disease,C1849722,T047,Disorders
What are the genetic changes related to adult polyglucosan body disease ?,0000024-3,genetic changes,"Mutations in the GBE1 gene cause adult polyglucosan body disease. The GBE1 gene provides instructions for making the glycogen branching enzyme. This enzyme is involved in the production of a complex sugar called glycogen, which is a major source of stored energy in the body. Most GBE1 gene mutations result in a shortage (deficiency) of the glycogen branching enzyme, which leads to the production of abnormal glycogen molecules. These abnormal glycogen molecules, called polyglucosan bodies, accumulate within cells and cause damage. Nerve cells (neurons) appear to be particularly vulnerable to the accumulation of polyglucosan bodies in people with this disorder, leading to impaired neuronal function.  Some mutations in the GBE1 gene that cause adult polyglucosan body disease do not result in a shortage of glycogen branching enzyme. In people with these mutations, the activity of this enzyme is normal. How mutations cause the disease in these individuals is unclear. Other people with adult polyglucosan body disease do not have identified mutations in the GBE1 gene. In these individuals, the cause of the disease is unknown.",adult polyglucosan body disease,0000024,GHR,https://ghr.nlm.nih.gov/condition/adult-polyglucosan-body-disease,C1849722,T047,Disorders
Is adult polyglucosan body disease inherited ?,0000024-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",adult polyglucosan body disease,0000024,GHR,https://ghr.nlm.nih.gov/condition/adult-polyglucosan-body-disease,C1849722,T047,Disorders
What are the treatments for adult polyglucosan body disease ?,0000024-5,treatment,"These resources address the diagnosis or management of adult polyglucosan body disease:  - Gene Review: Gene Review: Adult Polyglucosan Body Disease  - Genetic Testing Registry: Polyglucosan body disease, adult  - MedlinePlus Encyclopedia: Neurogenic Bladder  - MedlinePlus Encyclopedia: Spasticity   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",adult polyglucosan body disease,0000024,GHR,https://ghr.nlm.nih.gov/condition/adult-polyglucosan-body-disease,C1849722,T047,Disorders
What is (are) adult-onset leukoencephalopathy with axonal spheroids and pigmented glia ?,0000025-1,information,"Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a neurological condition characterized by changes to certain areas of the brain. A hallmark of ALSP is leukoencephalopathy, which is the alteration of a type of brain tissue called white matter. White matter consists of nerve fibers (axons) covered by a substance called myelin that insulates and protects them. The axons extend from nerve cells (neurons) and transmit nerve impulses throughout the body. Areas of damage to this brain tissue (white matter lesions) can be seen with magnetic resonance imaging (MRI). Another feature of ALSP is swellings called spheroids in the axons of the brain, which are a sign of axon damage. Also common in ALSP are abnormally pigmented glial cells. Glial cells are specialized brain cells that protect and maintain neurons. Damage to myelin and neurons is thought to contribute to many of the neurological signs and symptoms in people with ALSP.  Symptoms of ALSP usually begin in a person's forties and worsen over time. Personality changes, including depression and a loss of social inhibitions, are among the earliest symptoms of ALSP. Affected individuals may develop memory loss and loss of executive function, which is the ability to plan and implement actions and develop problem-solving strategies. Loss of this function impairs skills such as impulse control, self-monitoring, and focusing attention appropriately. Some people with ALSP have mild seizures, usually only when the condition begins. As ALSP progresses, it causes a severe decline in thinking and reasoning abilities (dementia).  Over time, motor skills are affected, and people with ALSP may have difficulty walking. Many develop a pattern of movement abnormalities known as parkinsonism, which includes unusually slow movement (bradykinesia), involuntary trembling (tremor), and muscle stiffness (rigidity). The pattern of cognitive and motor problems are variable, even among individuals in the same family, although almost all affected individuals ultimately become unable to walk, speak, and care for themselves.  ALSP was previously thought to be two separate conditions, hereditary diffuse leukoencephalopathy with spheroids (HDLS) and familial pigmentary orthochromatic leukodystrophy (POLD), both of which cause very similar white matter damage and cognitive and movement problems. POLD was thought to be distinguished by the presence of pigmented glial cells and an absence of spheroids; however, people with HDLS can have pigmented cells, too, and people with POLD can have spheroids. HDLS and POLD are now considered to be part of the same disease spectrum, which researchers have recommended calling ALSP.",adult-onset leukoencephalopathy with axonal spheroids and pigmented glia,0000025,GHR,https://ghr.nlm.nih.gov/condition/adult-onset-leukoencephalopathy-with-axonal-spheroids-and-pigmented-glia,C0270612,T047,Disorders
How many people are affected by adult-onset leukoencephalopathy with axonal spheroids and pigmented glia ?,0000025-2,frequency,"ALSP is thought to be a rare disorder, although the prevalence is unknown. Because it can be mistaken for other disorders with similar symptoms, ALSP may be underdiagnosed.",adult-onset leukoencephalopathy with axonal spheroids and pigmented glia,0000025,GHR,https://ghr.nlm.nih.gov/condition/adult-onset-leukoencephalopathy-with-axonal-spheroids-and-pigmented-glia,C0270612,T047,Disorders
What are the genetic changes related to adult-onset leukoencephalopathy with axonal spheroids and pigmented glia ?,0000025-3,genetic changes,"ALSP is caused by mutations in the CSF1R gene. This gene provides instructions for making a protein called colony stimulating factor 1 receptor (CSF-1 receptor), which is found in the outer membrane of certain types of cells, including glial cells. The CSF-1 receptor triggers signaling pathways that control many important cellular processes, such as cell growth and division (proliferation) and maturation of the cell to take on specific functions (differentiation).  CSF1R gene mutations in ALSP lead to an altered CSF-1 receptor protein that is likely unable to stimulate cell signaling pathways. However, it is unclear how the gene mutations lead to white matter damage or cognitive and movement problems in people with ALSP.",adult-onset leukoencephalopathy with axonal spheroids and pigmented glia,0000025,GHR,https://ghr.nlm.nih.gov/condition/adult-onset-leukoencephalopathy-with-axonal-spheroids-and-pigmented-glia,C0270612,T047,Disorders
Is adult-onset leukoencephalopathy with axonal spheroids and pigmented glia inherited ?,0000025-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",adult-onset leukoencephalopathy with axonal spheroids and pigmented glia,0000025,GHR,https://ghr.nlm.nih.gov/condition/adult-onset-leukoencephalopathy-with-axonal-spheroids-and-pigmented-glia,C0270612,T047,Disorders
What are the treatments for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia ?,0000025-5,treatment,These resources address the diagnosis or management of ALSP:  - Gene Review: Gene Review: Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia  - Genetic Testing Registry: Hereditary diffuse leukoencephalopathy with spheroids  - MedlinePlus Encyclopedia: Dementia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,adult-onset leukoencephalopathy with axonal spheroids and pigmented glia,0000025,GHR,https://ghr.nlm.nih.gov/condition/adult-onset-leukoencephalopathy-with-axonal-spheroids-and-pigmented-glia,C0270612,T047,Disorders
What is (are) African iron overload ?,0000026-1,information,"African iron overload is a condition that involves absorption of too much iron from the diet. The excess iron is stored in the body's tissues and organs, particularly the liver, bone marrow, and spleen. Humans cannot increase the excretion of iron, although some iron is lost through bleeding or when cells of the intestine (enterocytes) are shed at the end of the cells' lifespan. Iron levels in the body are primarily regulated through control of how much iron is absorbed from the diet.  African iron overload results from a diet high in iron. It is particularly associated with consumption of a traditional African beer that contains dissolved iron from the metal drums in which it is brewed. Some evidence suggests that a genetic predisposition to absorbing too much iron may also be involved.  In African iron overload, excess iron typically accumulates in liver cells (hepatocytes) and certain immune cells called reticuloendothelial cells. Reticuloendothelial cells include macrophages in the bone marrow and spleen and Kuppfer cells, which are specialized macrophages found in the liver. Kuppfer cells and other macrophages help protect the body against foreign invaders such as viruses and bacteria.  When too much iron is absorbed, the resulting iron overload can eventually damage tissues and organs. Iron overload in the liver may lead to chronic liver disease (cirrhosis) in people with African iron overload. Cirrhosis increases the risk for developing a type of liver cancer called hepatocellular carcinoma. Iron overload in immune cells may affect their ability to fight infections. African iron overload is associated with an increased risk of developing infections such as tuberculosis.  People with African iron overload may have a slightly low number of red blood cells (mild anemia), possibly because the iron that accumulates in the liver, bone marrow, and spleen is less available for production of red blood cells. Affected individuals also have high levels of a protein called ferritin in their blood, which can be detected with a blood test. Ferritin stores and releases iron in cells, and cells produce more ferritin in response to excess amounts of iron.",African iron overload,0000026,GHR,https://ghr.nlm.nih.gov/condition/african-iron-overload,C0268063,T047,Disorders
How many people are affected by African iron overload ?,0000026-2,frequency,"African iron overload is common in rural areas of central and southern Africa; up to 10 percent of the population in these regions may be affected. Men seem to be affected more often than women, possibly due to some combination of differences in dietary iron consumption and gender differences in the processing of iron.  The prevalence of increased iron stores in people of African descent in other parts of the world is unknown; however, these individuals may be at higher risk of developing mildly increased iron stores than are people of European background.",African iron overload,0000026,GHR,https://ghr.nlm.nih.gov/condition/african-iron-overload,C0268063,T047,Disorders
What are the genetic changes related to African iron overload ?,0000026-3,genetic changes,"African iron overload was first noted in rural central and southern African populations among people who drink a traditional beer brewed in uncoated steel drums that allow iron (a component of steel) to leach into the beer. However, not all individuals who drink the beer develop African iron overload, and not all individuals of African descent with iron overload drink the beer. Therefore, researchers are seeking genetic differences that affect the risk of developing this condition.  Some studies have indicated that a variation in the SLC40A1 gene increases the risk of developing increased iron stores in people of African descent. This variation is found in 5 to 20 percent of people of African descent but is not generally found in other populations.  The SLC40A1 gene provides instructions for making a protein called ferroportin. This protein is involved in the process of iron absorption in the body. Iron from the diet is absorbed through the walls of the small intestine. Ferroportin then transports iron from the small intestine into the bloodstream, and the iron is carried by the blood to the tissues and organs of the body. Ferroportin also transports iron out of reticuloendothelial cells in the liver, spleen, and bone marrow. The amount of iron absorbed by the body depends on the amount of iron stored and released from intestinal cells and macrophages.  The SLC40A1 gene variation that some studies have associated with increased iron stores in people of African descent may affect the way ferroportin helps to regulate iron absorption in the body. However, researchers suggest that this variation is not associated with most cases of African iron overload.",African iron overload,0000026,GHR,https://ghr.nlm.nih.gov/condition/african-iron-overload,C0268063,T047,Disorders
Is African iron overload inherited ?,0000026-4,inheritance,"African iron overload seems to run in families, and high iron in a family's diet seems to be the major contributor to development of the condition. There also may be a genetic contribution, but the inheritance pattern is unknown. People with a specific variation in the SLC40A1 gene may inherit an increased risk of this condition, but not the condition itself. Not all people with this condition have the variation in the gene, and not all people with the variation will develop the disorder.",African iron overload,0000026,GHR,https://ghr.nlm.nih.gov/condition/african-iron-overload,C0268063,T047,Disorders
What are the treatments for African iron overload ?,0000026-5,treatment,These resources address the diagnosis or management of African iron overload:  - Genetic Testing Registry: African nutritional hemochromatosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,African iron overload,0000026,GHR,https://ghr.nlm.nih.gov/condition/african-iron-overload,C0268063,T047,Disorders
What is (are) age-related macular degeneration ?,0000027-1,information,"Age-related macular degeneration is an eye disease that is a leading cause of vision loss in older people in developed countries. The vision loss usually becomes noticeable in a person's sixties or seventies and tends to worsen over time.  Age-related macular degeneration mainly affects central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. The vision loss in this condition results from a gradual deterioration of light-sensing cells in the tissue at the back of the eye that detects light and color (the retina). Specifically, age-related macular degeneration affects a small area near the center of the retina, called the macula, which is responsible for central vision. Side (peripheral) vision and night vision are generally not affected.  Researchers have described two major types of age-related macular degeneration, known as the dry form and the wet form. The dry form is much more common, accounting for 85 to 90 percent of all cases of age-related macular degeneration. It is characterized by a buildup of yellowish deposits called drusen beneath the retina and slowly progressive vision loss. The condition typically affects vision in both eyes, although vision loss often occurs in one eye before the other.  The wet form of age-related macular degeneration is associated with severe vision loss that can worsen rapidly. This form of the condition is characterized by the growth of abnormal, fragile blood vessels underneath the macula. These vessels leak blood and fluid, which damages the macula and makes central vision appear blurry and distorted.",age-related macular degeneration,0000027,GHR,https://ghr.nlm.nih.gov/condition/age-related-macular-degeneration,C0242383,T047,Disorders
How many people are affected by age-related macular degeneration ?,0000027-2,frequency,"Age-related macular degeneration has an estimated prevalence of 1 in 2,000 people in the United States and other developed countries. The condition currently affects several million Americans, and the prevalence is expected to increase over the coming decades as the proportion of older people in the population increases.  For reasons that are unclear, age-related macular degeneration affects individuals of European descent more frequently than African Americans in the United States.",age-related macular degeneration,0000027,GHR,https://ghr.nlm.nih.gov/condition/age-related-macular-degeneration,C0242383,T047,Disorders
What are the genetic changes related to age-related macular degeneration ?,0000027-3,genetic changes,"Age-related macular degeneration results from a combination of genetic and environmental factors. Many of these factors have been identified, but some remain unknown.  Researchers have considered changes in many genes as possible risk factors for age-related macular degeneration. The best-studied of these genes are involved in a part of the body's immune response known as the complement system. This system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. Genetic changes in and around several complement system genes, including the CFH gene, contribute to a person's risk of developing age-related macular degeneration. It is unclear how these genetic changes are related to the retinal damage and vision loss characteristic of this condition.  Changes on the long (q) arm of chromosome 10 in a region known as 10q26 are also associated with an increased risk of age-related macular degeneration. The 10q26 region contains two genes of interest, ARMS2 and HTRA1. Changes in both genes have been studied as possible risk factors for the disease. However, because the two genes are so close together, it is difficult to tell which gene is associated with age-related macular degeneration risk, or whether increased risk results from variations in both genes.  Other genes that are associated with age-related macular degeneration include genes involved in transporting and processing high-density lipoprotein (HDL, also known as ""good"" cholesterol) and genes that have been associated with other forms of macular disease.  Researchers have also examined nongenetic factors that contribute to the risk of age-related macular degeneration. Age appears to be the most important risk factor; the chance of developing the condition increases significantly as a person gets older. Smoking is another established risk factor for age-related macular degeneration. Other factors that may increase the risk of this condition include high blood pressure, heart disease, a high-fat diet or one that is low in certain nutrients (such as antioxidants and zinc), obesity, and exposure to ultraviolet (UV) rays from sunlight. However, studies of these factors in age-related macular degeneration have had conflicting results",age-related macular degeneration,0000027,GHR,https://ghr.nlm.nih.gov/condition/age-related-macular-degeneration,C0242383,T047,Disorders
Is age-related macular degeneration inherited ?,0000027-4,inheritance,"Age-related macular degeneration usually does not have a clear-cut pattern of inheritance, although the condition appears to run in families in some cases. An estimated 15 to 20 percent of people with age-related macular degeneration have at least one first-degree relative (such as a sibling) with the condition.",age-related macular degeneration,0000027,GHR,https://ghr.nlm.nih.gov/condition/age-related-macular-degeneration,C0242383,T047,Disorders
What are the treatments for age-related macular degeneration ?,0000027-5,treatment,"These resources address the diagnosis or management of age-related macular degeneration:  - BrightFocus Foundation: Macular Degeneration Treatment  - Genetic Testing Registry: Age-related macular degeneration  - Genetic Testing Registry: Age-related macular degeneration 1  - Genetic Testing Registry: Age-related macular degeneration 10  - Genetic Testing Registry: Age-related macular degeneration 11  - Genetic Testing Registry: Age-related macular degeneration 2  - Genetic Testing Registry: Age-related macular degeneration 3  - Genetic Testing Registry: Age-related macular degeneration 4  - Genetic Testing Registry: Age-related macular degeneration 7  - Genetic Testing Registry: Age-related macular degeneration 9  - Genetic Testing Registry: Susceptibility to age-related macular degeneration, wet type  - Genetic Testing Registry: Susceptibility to neovascular type of age-related macular degeneration  - Macular Degeneration Partnership: Low Vision Rehabilitation  - Prevent Blindness America: Age-Related Macular Degeneration (AMD) Test - Amsler Grid   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",age-related macular degeneration,0000027,GHR,https://ghr.nlm.nih.gov/condition/age-related-macular-degeneration,C0242383,T047,Disorders
What is (are) Aicardi syndrome ?,0000028-1,information,"Aicardi syndrome is a disorder that occurs almost exclusively in females. It is characterized by three main features that occur together in most affected individuals. People with Aicardi syndrome have absent or underdeveloped tissue connecting the left and right halves of the brain (agenesis or dysgenesis of the corpus callosum). They have seizures beginning in infancy (infantile spasms), which tend to progress to recurrent seizures (epilepsy) that can be difficult to treat. Affected individuals also have chorioretinal lacunae, which are defects in the light-sensitive tissue at the back of the eye (retina).  People with Aicardi syndrome often have additional brain abnormalities, including asymmetry between the two sides of the brain, brain folds and grooves that are small in size or reduced in number, cysts, and enlargement of the fluid-filled cavities (ventricles) near the center of the brain. Some have an unusually small head (microcephaly). Most affected individuals have moderate to severe developmental delay and intellectual disability, although some people with this disorder have milder disability.  In addition to chorioretinal lacunae, people with Aicardi syndrome may have other eye abnormalities such as small or poorly developed eyes (microphthalmia) or a gap or hole (coloboma) in the optic nerve, a structure that carries information from the eye to the brain. These eye abnormalities may cause blindness in affected individuals.  Some people with Aicardi syndrome have unusual facial features including a short area between the upper lip and the nose (philtrum), a flat nose with an upturned tip, large ears, and sparse eyebrows. Other features of this condition include small hands, hand malformations, and spinal and rib abnormalities leading to progressive abnormal curvature of the spine (scoliosis). They often have gastrointestinal problems such as constipation or diarrhea, gastroesophageal reflux, and difficulty feeding.  The severity of Aicardi syndrome varies. Some people with this disorder have very severe epilepsy and may not survive past childhood. Less severely affected individuals may live into adulthood with milder signs and symptoms.",Aicardi syndrome,0000028,GHR,https://ghr.nlm.nih.gov/condition/aicardi-syndrome,C0175713,T047,Disorders
How many people are affected by Aicardi syndrome ?,0000028-2,frequency,"Aicardi syndrome is a very rare disorder. It occurs in about 1 in 105,000 to 167,000 newborns in the United States. Researchers estimate that there are approximately 4,000 affected individuals worldwide.",Aicardi syndrome,0000028,GHR,https://ghr.nlm.nih.gov/condition/aicardi-syndrome,C0175713,T047,Disorders
What are the genetic changes related to Aicardi syndrome ?,0000028-3,genetic changes,"The cause of Aicardi syndrome is unknown. Because it occurs almost exclusively in females, researchers believe that it is probably the result of a mutation in a gene on the X chromosome. People normally have 46 chromosomes in each cell. Two of the 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male or female sex characteristics. Genes on these chromosomes are also involved in other functions in the body. Females typically have two X chromosomes (46,XX), and males have one X chromosome and one Y chromosome (46,XY).  Early in embryonic development in females, one of the two X chromosomes is permanently inactivated in somatic cells (cells other than egg and sperm cells). X-inactivation ensures that females, like males, have only one active copy of the X chromosome in each body cell. Usually X-inactivation occurs randomly, so that each X chromosome is active in about half the body's cells. Sometimes X-inactivation is not random, and one X chromosome is active in more than half of cells. When X-inactivation does not occur randomly, it is called skewed X-inactivation.  Skewed X-inactivation sometimes occurs when there is a severe gene mutation in one of the X chromosomes in each cell. Because the cells where this chromosome is active will not be able to survive as well, X-inactivation will appear to be skewed. Skewed X-inactivation has been identified in girls with Aicardi syndrome, further supporting the idea that the disorder is caused by a mutation in a gene on the X chromosome. However, this gene has not been identified, and it is unknown how the genetic change that causes Aicardi syndrome results in the various signs and symptoms of this disorder.",Aicardi syndrome,0000028,GHR,https://ghr.nlm.nih.gov/condition/aicardi-syndrome,C0175713,T047,Disorders
Is Aicardi syndrome inherited ?,0000028-4,inheritance,"Nearly all known cases of Aicardi syndrome are sporadic, which means that they are not passed down through generations and occur in people with no history of the disorder in their family. The disorder is believed to result from new gene mutations.  Aicardi syndrome is classified as an X-linked dominant condition. While the gene associated with this disorder is not known, it is believed to be located on the X chromosome. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell is nearly always lethal very early in development, so almost all babies with Aicardi syndrome are female. However, a few affected males with an extra copy of the X chromosome in each cell (47,XXY) have been identified. Males with a 47,XXY chromosome pattern also have a condition called Klinefelter syndrome.",Aicardi syndrome,0000028,GHR,https://ghr.nlm.nih.gov/condition/aicardi-syndrome,C0175713,T047,Disorders
What are the treatments for Aicardi syndrome ?,0000028-5,treatment,These resources address the diagnosis or management of Aicardi syndrome:  - Baylor College of Medicine  - Gene Review: Gene Review: Aicardi Syndrome  - Genetic Testing Registry: Aicardi's syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Aicardi syndrome,0000028,GHR,https://ghr.nlm.nih.gov/condition/aicardi-syndrome,C0175713,T047,Disorders
What is (are) Aicardi-Goutieres syndrome ?,0000029-1,information,"Aicardi-Goutieres syndrome is a disorder that mainly affects the brain, the immune system, and the skin.  Most newborns with Aicardi-Goutieres syndrome do not show any signs or symptoms of the disorder at birth. However, about 20 percent are born with a combination of features that include an enlarged liver and spleen (hepatosplenomegaly), elevated blood levels of liver enzymes, a decrease in blood platelets (thrombocytopenia), and abnormal neurological responses. While this combination of signs and symptoms is typically associated with the immune system's response to congenital viral infection, no actual infection is found in these infants. For this reason, Aicardi-Goutieres syndrome is sometimes referred to as a ""mimic of congenital infection.""  Within the first year of life most individuals with Aicardi-Goutieres syndrome experience an episode of severe brain dysfunction (encephalopathy), typically lasting for several months. During this phase of the disorder, affected babies are usually extremely irritable and do not feed well. They may develop intermittent fevers in the absence of infection (sterile pyrexias) and may have seizures. They stop developing new skills and begin losing skills they had already acquired (developmental regression). Growth of the brain and skull slows down, resulting in an abnormally small head size (microcephaly). In this phase of the disorder, white blood cells and molecules associated with inflammation can be detected in the cerebrospinal fluid, which is the fluid that surrounds the brain and spinal cord (central nervous system). These abnormal findings are consistent with inflammation and tissue damage in the central nervous system.  The encephalopathic phase of Aicardi-Goutieres syndrome leaves behind permanent neurological damage that is usually severe. Medical imaging reveals deterioration of white matter in the brain (leukodystrophy). White matter consists of nerve fibers covered by myelin, which is a substance that insulates and protects nerves. Affected individuals also have abnormal deposits of calcium (calcification) in the brain.  Most people with Aicardi-Goutieres syndrome have profound intellectual disability. They also have significant neuromuscular problems including muscle stiffness (spasticity); involuntary tensing of various muscles (dystonia), especially those in the arms; and weak muscle tone (hypotonia) in the trunk.  About 40 percent of people with Aicardi-Goutieres syndrome have painful, itchy skin lesions, usually on the fingers, toes, and ears. These puffy, red lesions, which are called chilblains, are caused by inflammation of small blood vessels. They may be brought on or made worse by exposure to cold. Vision problems, joint stiffness, and mouth ulcers may also occur in this disorder.  As a result of the severe neurological problems usually associated with Aicardi-Goutieres syndrome, most people with this disorder do not survive past childhood. However, some affected individuals who have later onset and milder neurological problems may live into adulthood.",Aicardi-Goutieres syndrome,0000029,GHR,https://ghr.nlm.nih.gov/condition/aicardi-goutieres-syndrome,C0393591,T047,Disorders
How many people are affected by Aicardi-Goutieres syndrome ?,0000029-2,frequency,Aicardi-Goutieres syndrome is a rare disorder. Its exact prevalence is unknown.,Aicardi-Goutieres syndrome,0000029,GHR,https://ghr.nlm.nih.gov/condition/aicardi-goutieres-syndrome,C0393591,T047,Disorders
What are the genetic changes related to Aicardi-Goutieres syndrome ?,0000029-3,genetic changes,"Mutations in the TREX1, RNASEH2A, RNASEH2B, RNASEH2C, and SAMHD1 genes have been identified in people with Aicardi-Goutieres syndrome.  The TREX1, RNASEH2A, RNASEH2B, and RNASEH2C genes provide instructions for making nucleases, which are enzymes that help break up molecules of DNA and its chemical cousin RNA. Mutations in any of these genes are believed to result in an absent or dysfunctional nuclease enzyme. Researchers suggest that absent or impaired enzyme function may result in the accumulation of unneeded DNA and RNA in cells. These DNA and RNA molecules or fragments may be generated during the first stage of protein production (transcription), copying (replication) of cells' genetic material in preparation for cell division, DNA repair, cell death, and other processes. The unneeded DNA and RNA may be mistaken by cells for that of viral invaders, triggering immune system reactions that result in encephalopathy, skin lesions, and other signs and symptoms of Aicardi-Goutieres syndrome.  The SAMHD1 gene provides instructions for making a protein whose function is not well understood; however, it is believed to be involved in the immune system and the inflammatory process. Mutations in this gene likely result in a protein that does not function properly, resulting in immune system abnormalities, inflammatory damage to the brain and skin, and other characteristics of Aicardi-Goutieres syndrome.",Aicardi-Goutieres syndrome,0000029,GHR,https://ghr.nlm.nih.gov/condition/aicardi-goutieres-syndrome,C0393591,T047,Disorders
Is Aicardi-Goutieres syndrome inherited ?,0000029-4,inheritance,"Aicardi-Goutieres syndrome can have different inheritance patterns. In most cases it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Rarely, this condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. These cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",Aicardi-Goutieres syndrome,0000029,GHR,https://ghr.nlm.nih.gov/condition/aicardi-goutieres-syndrome,C0393591,T047,Disorders
What are the treatments for Aicardi-Goutieres syndrome ?,0000029-5,treatment,These resources address the diagnosis or management of Aicardi-Goutieres syndrome:  - Gene Review: Gene Review: Aicardi-Goutieres Syndrome  - Genetic Testing Registry: Aicardi Goutieres syndrome  - Genetic Testing Registry: Aicardi Goutieres syndrome 1  - Genetic Testing Registry: Aicardi Goutieres syndrome 2  - Genetic Testing Registry: Aicardi Goutieres syndrome 3  - Genetic Testing Registry: Aicardi Goutieres syndrome 4  - Genetic Testing Registry: Aicardi Goutieres syndrome 5   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Aicardi-Goutieres syndrome,0000029,GHR,https://ghr.nlm.nih.gov/condition/aicardi-goutieres-syndrome,C0393591,T047,Disorders
What is (are) Alagille syndrome ?,0000030-1,information,"Alagille syndrome is a genetic disorder that can affect the liver, heart, and other parts of the body.  One of the major features of Alagille syndrome is liver damage caused by abnormalities in the bile ducts. These ducts carry bile (which helps to digest fats) from the liver to the gallbladder and small intestine. In Alagille syndrome, the bile ducts may be narrow, malformed, and reduced in number (bile duct paucity). As a result, bile builds up in the liver and causes scarring that prevents the liver from working properly to eliminate wastes from the bloodstream. Signs and symptoms arising from liver damage in Alagille syndrome may include a yellowish tinge in the skin and the whites of the eyes (jaundice), itchy skin, and deposits of cholesterol in the skin (xanthomas).  Alagille syndrome is also associated with several heart problems, including impaired blood flow from the heart into the lungs (pulmonic stenosis). Pulmonic stenosis may occur along with a hole between the two lower chambers of the heart (ventricular septal defect) and other heart abnormalities. This combination of heart defects is called tetralogy of Fallot.  People with Alagille syndrome may have distinctive facial features including a broad, prominent forehead; deep-set eyes; and a small, pointed chin. The disorder may also affect the blood vessels within the brain and spinal cord (central nervous system) and the kidneys. Affected individuals may have an unusual butterfly shape of the bones of the spinal column (vertebrae) that can be seen in an x-ray.  Problems associated with Alagille syndrome generally become evident in infancy or early childhood. The severity of the disorder varies among affected individuals, even within the same family. Symptoms range from so mild as to go unnoticed to severe heart and/or liver disease requiring transplantation.  Some people with Alagille syndrome may have isolated signs of the disorder, such as a heart defect like tetralogy of Fallot, or a characteristic facial appearance. These individuals do not have liver disease or other features typical of the disorder.",Alagille syndrome,0000030,GHR,https://ghr.nlm.nih.gov/condition/alagille-syndrome,C0085280,T019,Disorders
How many people are affected by Alagille syndrome ?,0000030-2,frequency,"The estimated prevalence of Alagille syndrome is 1 in 70,000 newborns. This figure is based on diagnoses of liver disease in infants, and may be an underestimation because some people with Alagille syndrome do not develop liver disease during infancy.",Alagille syndrome,0000030,GHR,https://ghr.nlm.nih.gov/condition/alagille-syndrome,C0085280,T019,Disorders
What are the genetic changes related to Alagille syndrome ?,0000030-3,genetic changes,"In more than 90 percent of cases, mutations in the JAG1 gene cause Alagille syndrome. Another 7 percent of individuals with Alagille syndrome have small deletions of genetic material on chromosome 20 that include the JAG1 gene. A few people with Alagille syndrome have mutations in a different gene, called NOTCH2. The JAG1 and NOTCH2 genes provide instructions for making proteins that fit together to trigger interactions called Notch signaling between neighboring cells during embryonic development. This signaling influences how the cells are used to build body structures in the developing embryo. Changes in either the JAG1 gene or NOTCH2 gene probably disrupt the Notch signaling pathway. As a result, errors may occur during development, especially affecting the bile ducts, heart, spinal column, and certain facial features.",Alagille syndrome,0000030,GHR,https://ghr.nlm.nih.gov/condition/alagille-syndrome,C0085280,T019,Disorders
Is Alagille syndrome inherited ?,0000030-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered or deleted gene in each cell is sufficient to cause the disorder.  In approximately 30 to 50 percent of cases, an affected person inherits the mutation or deletion from one affected parent. Other cases result from new mutations in the gene or new deletions of genetic material on chromosome 20 that occur as random events during the formation of reproductive cells (eggs or sperm) or in early fetal development. These cases occur in people with no history of the disorder in their family.",Alagille syndrome,0000030,GHR,https://ghr.nlm.nih.gov/condition/alagille-syndrome,C0085280,T019,Disorders
What are the treatments for Alagille syndrome ?,0000030-5,treatment,These resources address the diagnosis or management of Alagille syndrome:  - Boston Children's Hospital  - Children's Hospital of Philadelphia  - Children's Hospital of Pittsburgh  - Gene Review: Gene Review: Alagille Syndrome  - Genetic Testing Registry: Alagille syndrome 1  - Genetic Testing Registry: Arteriohepatic dysplasia  - MedlinePlus Encyclopedia: Tetralogy of Fallot   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Alagille syndrome,0000030,GHR,https://ghr.nlm.nih.gov/condition/alagille-syndrome,C0085280,T019,Disorders
What is (are) Alexander disease ?,0000031-1,information,"Alexander disease is a rare disorder of the nervous system. It is one of a group of disorders, called leukodystrophies, that involve the destruction of myelin. Myelin is the fatty covering that insulates nerve fibers and promotes the rapid transmission of nerve impulses. If myelin is not properly maintained, the transmission of nerve impulses could be disrupted. As myelin deteriorates in leukodystrophies such as Alexander disease, nervous system functions are impaired.  Most cases of Alexander disease begin before age 2 and are described as the infantile form. Signs and symptoms of the infantile form typically include an enlarged brain and head size (megalencephaly), seizures, stiffness in the arms and/or legs (spasticity), intellectual disability, and developmental delay. Less frequently, onset occurs later in childhood (the juvenile form) or in adulthood. Common problems in juvenile and adult forms of Alexander disease include speech abnormalities, swallowing difficulties, seizures, and poor coordination (ataxia). Rarely, a neonatal form of Alexander disease occurs within the first month of life and is associated with severe intellectual disability and developmental delay, a buildup of fluid in the brain (hydrocephalus), and seizures.  Alexander disease is also characterized by abnormal protein deposits known as Rosenthal fibers. These deposits are found in specialized cells called astroglial cells, which support and nourish other cells in the brain and spinal cord (central nervous system).",Alexander disease,0000031,GHR,https://ghr.nlm.nih.gov/condition/alexander-disease,C0270726,T047,Disorders
How many people are affected by Alexander disease ?,0000031-2,frequency,The prevalence of Alexander disease is unknown. About 500 cases have been reported since the disorder was first described in 1949.,Alexander disease,0000031,GHR,https://ghr.nlm.nih.gov/condition/alexander-disease,C0270726,T047,Disorders
What are the genetic changes related to Alexander disease ?,0000031-3,genetic changes,"Mutations in the GFAP gene cause Alexander disease. The GFAP gene provides instructions for making a protein called glial fibrillary acidic protein. Several molecules of this protein bind together to form intermediate filaments, which provide support and strength to cells. Mutations in the GFAP gene lead to the production of a structurally altered glial fibrillary acidic protein. The altered protein is thought to impair the formation of normal intermediate filaments. As a result, the abnormal glial fibrillary acidic protein likely accumulates in astroglial cells, leading to the formation of Rosenthal fibers, which impair cell function. It is not well understood how impaired astroglial cells contribute to the abnormal formation or maintenance of myelin, leading to the signs and symptoms of Alexander disease.",Alexander disease,0000031,GHR,https://ghr.nlm.nih.gov/condition/alexander-disease,C0270726,T047,Disorders
Is Alexander disease inherited ?,0000031-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  Most cases result from new mutations in the gene. These cases occur in people with no history of the disorder in their family. Rarely, an affected person inherits the mutation from one affected parent.",Alexander disease,0000031,GHR,https://ghr.nlm.nih.gov/condition/alexander-disease,C0270726,T047,Disorders
What are the treatments for Alexander disease ?,0000031-5,treatment,These resources address the diagnosis or management of Alexander disease:  - Gene Review: Gene Review: Alexander Disease  - Genetic Testing Registry: Alexander's disease  - MedlinePlus Encyclopedia: Myelin   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Alexander disease,0000031,GHR,https://ghr.nlm.nih.gov/condition/alexander-disease,C0270726,T047,Disorders
What is (are) ALG1-congenital disorder of glycosylation ?,0000032-1,information,"ALG1-congenital disorder of glycosylation (ALG1-CDG, also known as congenital disorder of glycosylation type Ik) is an inherited disorder with varying signs and symptoms that typically develop during infancy and can affect several body systems.  Individuals with ALG1-CDG often have intellectual disability, delayed development, and weak muscle tone (hypotonia). Many affected individuals develop seizures that can be difficult to treat. Individuals with ALG1-CDG may also have movement problems such as involuntary rhythmic shaking (tremor) or difficulties with movement and balance (ataxia).  People with ALG1-CDG often have problems with blood clotting, which can lead to abnormal clotting or bleeding episodes. Additionally, affected individuals may produce abnormally low levels of proteins called antibodies (or immunoglobulins), particularly immunoglobulin G (IgG). Antibodies help protect the body against infection by foreign particles and germs. A reduction in antibodies can make it difficult for affected individuals to fight infections.  Some people with ALG1-CDG have physical abnormalities such as a small head size (microcephaly); unusual facial features; joint deformities called contractures; long, slender fingers and toes (arachnodactyly); or unusually fleshy pads at the tips of the fingers and toes. Eye problems that may occur in people with this condition include eyes that do not point in the same direction (strabismus) or involuntary eye movements (nystagmus). Rarely, affected individuals develop vision loss.  Less common abnormalities that occur in people with ALG1-CDG include respiratory problems, reduced sensation in their arms and legs (peripheral neuropathy), swelling (edema), and gastrointestinal difficulties.  The signs and symptoms of ALG1-CDG are often severe, with affected individuals surviving only into infancy or childhood. However, some people with this condition are more mildly affected and survive into adulthood.",ALG1-congenital disorder of glycosylation,0000032,GHR,https://ghr.nlm.nih.gov/condition/alg1-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
How many people are affected by ALG1-congenital disorder of glycosylation ?,0000032-2,frequency,ALG1-CDG appears to be a rare disorder; fewer than 30 affected individuals have been described in the scientific literature.,ALG1-congenital disorder of glycosylation,0000032,GHR,https://ghr.nlm.nih.gov/condition/alg1-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
What are the genetic changes related to ALG1-congenital disorder of glycosylation ?,0000032-3,genetic changes,"Mutations in the ALG1 gene cause ALG1-CDG. This gene provides instructions for making an enzyme that is involved in a process called glycosylation. During this process, complex chains of sugar molecules (oligosaccharides) are added to proteins and fats (lipids). Glycosylation modifies proteins and lipids so they can fully perform their functions. The enzyme produced from the ALG1 gene transfers a simple sugar called mannose to growing oligosaccharides at a particular step in the formation of the sugar chain. Once the correct number of sugar molecules are linked together, the oligosaccharide is attached to a protein or lipid.  ALG1 gene mutations lead to the production of an abnormal enzyme with reduced activity. The poorly functioning enzyme cannot add mannose to sugar chains efficiently, and the resulting oligosaccharides are often incomplete. Although the short oligosaccharides can be transferred to proteins and fats, the process is not as efficient as with the full-length oligosaccharide. The wide variety of signs and symptoms in ALG1-CDG are likely due to impaired glycosylation of proteins and lipids that are needed for normal function of many organs and tissues.",ALG1-congenital disorder of glycosylation,0000032,GHR,https://ghr.nlm.nih.gov/condition/alg1-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
Is ALG1-congenital disorder of glycosylation inherited ?,0000032-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",ALG1-congenital disorder of glycosylation,0000032,GHR,https://ghr.nlm.nih.gov/condition/alg1-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
What are the treatments for ALG1-congenital disorder of glycosylation ?,0000032-5,treatment,These resources address the diagnosis or management of ALG1-congenital disorder of glycosylation:  - Gene Review: Gene Review: Congenital Disorders of N-Linked Glycosylation Pathway Overview  - Genetic Testing Registry: Congenital disorder of glycosylation type 1K   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,ALG1-congenital disorder of glycosylation,0000032,GHR,https://ghr.nlm.nih.gov/condition/alg1-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
What is (are) ALG12-congenital disorder of glycosylation ?,0000033-1,information,"ALG12-congenital disorder of glycosylation (ALG12-CDG, also known as congenital disorder of glycosylation type Ig) is an inherited disorder with varying signs and symptoms that can affect several body systems. Individuals with ALG12-CDG typically develop signs and symptoms of the condition during infancy. They may have problems feeding and difficulty growing and gaining weight at the expected rate (failure to thrive). In addition, affected individuals often have intellectual disability, delayed development, and weak muscle tone (hypotonia), and some develop seizures.  Some people with ALG12-CDG have physical abnormalities such as a small head size (microcephaly) and unusual facial features. These features can include folds of skin that cover the inner corners of the eyes (epicanthal folds), a prominent nasal bridge, and abnormally shaped ears. Some males with ALG12-CDG have abnormal genitalia, such as a small penis (micropenis) and undescended testes.  People with ALG12-CDG often produce abnormally low levels of proteins called antibodies (or immunoglobulins), particularly immunoglobulin G (IgG). Antibodies help protect the body against infection by attaching to specific foreign particles and germs, marking them for destruction. A reduction in antibodies can make it difficult for affected individuals to fight infections.  Less common abnormalities seen in people with ALG12-CDG include a weakened heart muscle (cardiomyopathy) and poor bone development, which can lead to skeletal abnormalities.",ALG12-congenital disorder of glycosylation,0000033,GHR,https://ghr.nlm.nih.gov/condition/alg12-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
How many people are affected by ALG12-congenital disorder of glycosylation ?,0000033-2,frequency,ALG12-CDG is a rare condition; its prevalence is unknown. Only a handful of affected individuals have been described in the medical literature.,ALG12-congenital disorder of glycosylation,0000033,GHR,https://ghr.nlm.nih.gov/condition/alg12-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
What are the genetic changes related to ALG12-congenital disorder of glycosylation ?,0000033-3,genetic changes,"Mutations in the ALG12 gene cause ALG12-CDG. This gene provides instructions for making an enzyme that is involved in a process called glycosylation. During this process, complex chains of sugar molecules (oligosaccharides) are added to proteins and fats (lipids). Glycosylation modifies proteins and lipids so they can fully perform their functions. The enzyme produced from the ALG12 gene transfers a simple sugar called mannose to growing oligosaccharides at a particular step in the formation of the sugar chain. Once the correct number of sugar molecules are linked together, the oligosaccharide is attached to a protein or lipid.  ALG12 gene mutations lead to the production of an abnormal enzyme with reduced activity. Without a properly functioning enzyme, mannose cannot be added to the chain efficiently, and the resulting oligosaccharides are often incomplete. Although the short oligosaccharides can be transferred to proteins and fats, the process is not as efficient as with the full-length oligosaccharide. As a result, glycosylation is reduced. The wide variety of signs and symptoms in ALG12-CDG are likely due to impaired glycosylation of proteins and lipids that are needed for normal function of many organs and tissues, including the brain.",ALG12-congenital disorder of glycosylation,0000033,GHR,https://ghr.nlm.nih.gov/condition/alg12-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
Is ALG12-congenital disorder of glycosylation inherited ?,0000033-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",ALG12-congenital disorder of glycosylation,0000033,GHR,https://ghr.nlm.nih.gov/condition/alg12-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
What are the treatments for ALG12-congenital disorder of glycosylation ?,0000033-5,treatment,These resources address the diagnosis or management of ALG12-CDG:  - Gene Review: Gene Review: Congenital Disorders of N-Linked Glycosylation Pathway Overview  - Genetic Testing Registry: Congenital disorder of glycosylation type 1G   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,ALG12-congenital disorder of glycosylation,0000033,GHR,https://ghr.nlm.nih.gov/condition/alg12-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
What is (are) ALG6-congenital disorder of glycosylation ?,0000034-1,information,"ALG6-congenital disorder of glycosylation (ALG6-CDG, also known as congenital disorder of glycosylation type Ic) is an inherited condition that affects many parts of the body. The signs and symptoms of ALG6-CDG vary widely among people with the condition.  Individuals with ALG6-CDG typically develop signs and symptoms of the condition during infancy. They may have difficulty gaining weight and growing at the expected rate (failure to thrive). Affected infants often have weak muscle tone (hypotonia) and developmental delay.  People with ALG6-CDG may have seizures, problems with coordination and balance (ataxia), or stroke-like episodes that involve an extreme lack of energy (lethargy) and temporary paralysis. They may also develop blood clotting disorders. Some individuals with ALG6-CDG have eye abnormalities including eyes that do not look in the same direction (strabismus) and an eye disorder called retinitis pigmentosa, which causes vision loss. Females with ALG6-CDG have hypergonadotropic hypogonadism, which affects the production of hormones that direct sexual development. As a result, most females with ALG6-CDG do not go through puberty.",ALG6-congenital disorder of glycosylation,0000034,GHR,https://ghr.nlm.nih.gov/condition/alg6-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
How many people are affected by ALG6-congenital disorder of glycosylation ?,0000034-2,frequency,"The prevalence of ALG6-CDG is unknown, but it is thought to be the second most common type of congenital disorder of glycosylation. More than 30 cases of ALG6-CDG have been described in the scientific literature.",ALG6-congenital disorder of glycosylation,0000034,GHR,https://ghr.nlm.nih.gov/condition/alg6-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
What are the genetic changes related to ALG6-congenital disorder of glycosylation ?,0000034-3,genetic changes,"ALG6-CDG is caused by mutations in the ALG6 gene. This gene provides instructions for making an enzyme that is involved in a process called glycosylation. Glycosylation is the process by which sugar molecules (monosaccharides) and complex chains of sugar molecules (oligosaccharides) are added to proteins and fats. Glycosylation modifies proteins and fats so they can perform a wider variety of functions. The enzyme produced from the ALG6 gene transfers a simple sugar called glucose to the growing oligosaccharide. Once the correct number of sugar molecules are linked together, the oligosaccharide is attached to a protein or fat.  ALG6 gene mutations lead to the production of an abnormal enzyme with reduced or no activity. Without a properly functioning enzyme, glycosylation cannot proceed normally, and oligosaccharides are incomplete. As a result, glycosylation is reduced or absent. The wide variety of signs and symptoms in ALG6-CDG are likely due to impaired glycosylation of proteins and fats that are needed for normal function in many organs and tissues, including the brain, eyes, liver, and hormone-producing (endocrine) system.",ALG6-congenital disorder of glycosylation,0000034,GHR,https://ghr.nlm.nih.gov/condition/alg6-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
Is ALG6-congenital disorder of glycosylation inherited ?,0000034-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",ALG6-congenital disorder of glycosylation,0000034,GHR,https://ghr.nlm.nih.gov/condition/alg6-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
What are the treatments for ALG6-congenital disorder of glycosylation ?,0000034-5,treatment,These resources address the diagnosis or management of ALG6-CDG:  - Gene Review: Gene Review: Congenital Disorders of N-Linked Glycosylation Pathway Overview   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,ALG6-congenital disorder of glycosylation,0000034,GHR,https://ghr.nlm.nih.gov/condition/alg6-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
What is (are) alkaptonuria ?,0000035-1,information,"Alkaptonuria is an inherited condition that causes urine to turn black when exposed to air. Ochronosis, a buildup of dark pigment in connective tissues such as cartilage and skin, is also characteristic of the disorder. This blue-black pigmentation usually appears after age 30. People with alkaptonuria typically develop arthritis, particularly in the spine and large joints, beginning in early adulthood. Other features of this condition can include heart problems, kidney stones, and prostate stones.",alkaptonuria,0000035,GHR,https://ghr.nlm.nih.gov/condition/alkaptonuria,C0002066,T047,Disorders
How many people are affected by alkaptonuria ?,0000035-2,frequency,"This condition is rare, affecting 1 in 250,000 to 1 million people worldwide. Alkaptonuria is more common in certain areas of Slovakia (where it has an incidence of about 1 in 19,000 people) and in the Dominican Republic.",alkaptonuria,0000035,GHR,https://ghr.nlm.nih.gov/condition/alkaptonuria,C0002066,T047,Disorders
What are the genetic changes related to alkaptonuria ?,0000035-3,genetic changes,"Mutations in the HGD gene cause alkaptonuria. The HGD gene provides instructions for making an enzyme called homogentisate oxidase. This enzyme helps break down the amino acids phenylalanine and tyrosine, which are important building blocks of proteins. Mutations in the HGD gene impair the enzyme's role in this process. As a result, a substance called homogentisic acid, which is produced as phenylalanine and tyrosine are broken down, accumulates in the body. Excess homogentisic acid and related compounds are deposited in connective tissues, which causes cartilage and skin to darken. Over time, a buildup of this substance in the joints leads to arthritis. Homogentisic acid is also excreted in urine, making the urine turn dark when exposed to air.",alkaptonuria,0000035,GHR,https://ghr.nlm.nih.gov/condition/alkaptonuria,C0002066,T047,Disorders
Is alkaptonuria inherited ?,0000035-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",alkaptonuria,0000035,GHR,https://ghr.nlm.nih.gov/condition/alkaptonuria,C0002066,T047,Disorders
What are the treatments for alkaptonuria ?,0000035-5,treatment,These resources address the diagnosis or management of alkaptonuria:  - Gene Review: Gene Review: Alkaptonuria  - Genetic Testing Registry: Alkaptonuria  - MedlinePlus Encyclopedia: Alkaptonuria   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,alkaptonuria,0000035,GHR,https://ghr.nlm.nih.gov/condition/alkaptonuria,C0002066,T047,Disorders
What is (are) Allan-Herndon-Dudley syndrome ?,0000036-1,information,"Allan-Herndon-Dudley syndrome is a rare disorder of brain development that causes moderate to severe intellectual disability and problems with movement. This condition, which occurs exclusively in males, disrupts development from before birth. Although affected males have impaired speech and a limited ability to communicate, they seem to enjoy interaction with other people.  Most children with Allan-Herndon-Dudley syndrome have weak muscle tone (hypotonia) and underdevelopment of many muscles (muscle hypoplasia). As they get older, they usually develop joint deformities called contractures, which restrict the movement of certain joints. Abnormal muscle stiffness (spasticity), muscle weakness, and involuntary movements of the arms and legs also limit mobility. As a result, many people with Allan-Herndon-Dudley syndrome are unable to walk independently and become wheelchair-bound by adulthood.",Allan-Herndon-Dudley syndrome,0000036,GHR,https://ghr.nlm.nih.gov/condition/allan-herndon-dudley-syndrome,C0795889,T047,Disorders
How many people are affected by Allan-Herndon-Dudley syndrome ?,0000036-2,frequency,Allan-Herndon-Dudley syndrome appears to be a rare disorder. About 25 families with individuals affected by this condition have been reported worldwide.,Allan-Herndon-Dudley syndrome,0000036,GHR,https://ghr.nlm.nih.gov/condition/allan-herndon-dudley-syndrome,C0795889,T047,Disorders
What are the genetic changes related to Allan-Herndon-Dudley syndrome ?,0000036-3,genetic changes,"Mutations in the SLC16A2 gene cause Allan-Herndon-Dudley syndrome. The SLC16A2 gene, also known as MCT8, provides instructions for making a protein that plays a critical role in the development of the nervous system. This protein transports a particular hormone into nerve cells in the developing brain. This hormone, called triiodothyronine or T3, is produced by a butterfly-shaped gland in the lower neck called the thyroid. T3 appears to be critical for the normal formation and growth of nerve cells, as well as the development of junctions between nerve cells (synapses) where cell-to-cell communication occurs. T3 and other forms of thyroid hormone also help regulate the development of other organs and control the rate of chemical reactions in the body (metabolism).  Gene mutations alter the structure and function of the SLC16A2 protein. As a result, this protein is unable to transport T3 into nerve cells effectively. A lack of this critical hormone in certain parts of the brain disrupts normal brain development, resulting in intellectual disability and problems with movement. Because T3 is not taken up by nerve cells, excess amounts of this hormone continue to circulate in the bloodstream. Increased T3 levels in the blood may be toxic to some organs and contribute to the signs and symptoms of Allan-Herndon-Dudley syndrome.",Allan-Herndon-Dudley syndrome,0000036,GHR,https://ghr.nlm.nih.gov/condition/allan-herndon-dudley-syndrome,C0795889,T047,Disorders
Is Allan-Herndon-Dudley syndrome inherited ?,0000036-4,inheritance,"This condition is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In X-linked recessive inheritance, a female with one altered copy of the gene in each cell is called a carrier. She can pass on the mutated gene, but usually does not experience signs and symptoms of the disorder. Carriers of SLC16A2 mutations have normal intelligence and do not experience problems with movement. Some carriers have been diagnosed with thyroid disease, a condition which is relatively common in the general population. It is unclear whether thyroid disease is related to SLC16A2 gene mutations in these cases.",Allan-Herndon-Dudley syndrome,0000036,GHR,https://ghr.nlm.nih.gov/condition/allan-herndon-dudley-syndrome,C0795889,T047,Disorders
What are the treatments for Allan-Herndon-Dudley syndrome ?,0000036-5,treatment,These resources address the diagnosis or management of Allan-Herndon-Dudley syndrome:  - Gene Review: Gene Review: MCT8-Specific Thyroid Hormone Cell-Membrane Transporter Deficiency  - Genetic Testing Registry: Allan-Herndon-Dudley syndrome  - MedlinePlus Encyclopedia: Intellectual Disability  - MedlinePlus Encyclopedia: T3 Test   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Allan-Herndon-Dudley syndrome,0000036,GHR,https://ghr.nlm.nih.gov/condition/allan-herndon-dudley-syndrome,C0795889,T047,Disorders
What is (are) allergic asthma ?,0000037-1,information,"Asthma is a breathing disorder characterized by inflammation of the airways and recurrent episodes of breathing difficulty. These episodes, sometimes referred to as asthma attacks, are triggered by irritation of the inflamed airways. In allergic asthma, the attacks occur when substances known as allergens are inhaled, causing an allergic reaction. Allergens are harmless substances that the body's immune system mistakenly reacts to as though they are harmful. Common allergens include pollen, dust, animal dander, and mold. The immune response leads to the symptoms of asthma. Allergic asthma is the most common form of the disorder.  A hallmark of asthma is bronchial hyperresponsiveness, which means the airways are especially sensitive to irritants and respond excessively. Because of this hyperresponsiveness, attacks can be triggered by irritants other than allergens, such as physical activity, respiratory infections, or exposure to tobacco smoke, in people with allergic asthma.  An asthma attack is characterized by tightening of the muscles around the airways (bronchoconstriction), which narrows the airway and makes breathing difficult. Additionally, the immune reaction can lead to swelling of the airways and overproduction of mucus. During an attack, an affected individual can experience chest tightness, wheezing, shortness of breath, and coughing. Over time, the muscles around the airways can become enlarged (hypertrophied), further narrowing the airways.  Some people with allergic asthma have another allergic disorder, such as hay fever (allergic rhinitis) or food allergies. Asthma is sometimes part of a series of allergic disorders, referred to as the atopic march. Development of these conditions typically follows a pattern, beginning with eczema (atopic dermatitis), followed by food allergies, then hay fever, and finally asthma. However, not all individuals with asthma have progressed through the atopic march, and not all individuals with one allergic disease will develop others.",allergic asthma,0000037,GHR,https://ghr.nlm.nih.gov/condition/allergic-asthma,C0155877,T047,Disorders
How many people are affected by allergic asthma ?,0000037-2,frequency,"Approximately 235 million people worldwide have asthma. In the United States, the condition affects an estimated 8 percent of the population. In nearly 90 percent of children and 50 percent of adults with asthma, the condition is classified as allergic asthma.",allergic asthma,0000037,GHR,https://ghr.nlm.nih.gov/condition/allergic-asthma,C0155877,T047,Disorders
What are the genetic changes related to allergic asthma ?,0000037-3,genetic changes,"The cause of allergic asthma is complex. It is likely that a combination of multiple genetic and environmental factors contribute to development of the condition. Doctors believe genes are involved because having a family member with allergic asthma or another allergic disorder increases a person's risk of developing asthma.  Studies suggest that more than 100 genes may be associated with allergic asthma, but each seems to be a factor in only one or a few populations. Many of the associated genes are involved in the body's immune response. Others play a role in lung and airway function.  There is evidence that an unbalanced immune response underlies allergic asthma. While there is normally a balance between type 1 (or Th1) and type 2 (or Th2) immune reactions in the body, many individuals with allergic asthma predominantly have type 2 reactions. Type 2 reactions lead to the production of immune proteins called IgE antibodies and the generation of other factors that predispose to bronchial hyperresponsiveness. Normally, the body produces IgE antibodies in response to foreign invaders, particularly parasitic worms. For unknown reasons, in susceptible individuals, the body reacts to an allergen as if it is harmful, producing IgE antibodies specific to it. Upon later encounters with the allergen, IgE antibodies recognize it, which stimulates an immune response, causing bronchoconstriction, airway swelling, and mucus production.  Not everyone with a variation in one of the allergic asthma-associated genes develops the condition; exposure to certain environmental factors also contributes to its development. Studies suggest that these exposures trigger epigenetic changes to the DNA. Epigenetic changes modify DNA without changing the DNA sequence. They can affect gene activity and regulate the production of proteins, which may influence the development of allergies in susceptible individuals.",allergic asthma,0000037,GHR,https://ghr.nlm.nih.gov/condition/allergic-asthma,C0155877,T047,Disorders
Is allergic asthma inherited ?,0000037-4,inheritance,"Allergic asthma can be passed through generations in families, but the inheritance pattern is unknown. People with mutations in one or more of the associated genes inherit an increased risk of allergic asthma, not the condition itself. Because allergic asthma is a complex condition influenced by genetic and environmental factors, not all people with a mutation in an asthma-associated gene will develop the disorder.",allergic asthma,0000037,GHR,https://ghr.nlm.nih.gov/condition/allergic-asthma,C0155877,T047,Disorders
What are the treatments for allergic asthma ?,0000037-5,treatment,"These resources address the diagnosis or management of allergic asthma:  - American Academy of Allergy Asthma and Immunology: Asthma Treatment and Management  - Genetic Testing Registry: Asthma, atopic  - Genetic Testing Registry: Asthma, susceptibility to   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",allergic asthma,0000037,GHR,https://ghr.nlm.nih.gov/condition/allergic-asthma,C0155877,T047,Disorders
What is (are) Alpers-Huttenlocher syndrome ?,0000038-1,information,"Alpers-Huttenlocher syndrome is one of the most severe of a group of conditions called the POLG-related disorders. The conditions in this group feature a range of similar signs and symptoms involving muscle-, nerve-, and brain-related functions. Alpers-Huttenlocher syndrome typically becomes apparent in children between ages 2 and 4. People with this condition usually have three characteristic features: recurrent seizures that do not improve with treatment (intractable epilepsy), loss of mental and movement abilities (psychomotor regression), and liver disease.  People with Alpers-Huttenlocher syndrome usually have additional signs and symptoms. Most have problems with coordination and balance (ataxia) and disturbances in nerve function (neuropathy). Neuropathy can lead to abnormal or absent reflexes (areflexia). In addition, affected individuals may develop weak muscle tone (hypotonia) that worsens until they lose the ability to control their muscles and movement. Some people with Alpers-Huttenlocher syndrome lose the ability to walk, sit, or feed themselves. Other movement-related symptoms in affected individuals can include involuntary muscle twitches (myoclonus), uncontrollable movements of the limbs (choreoathetosis), or a pattern of movement abnormalities known as parkinsonism.  Affected individuals may have other brain-related signs and symptoms. Migraine headaches, often with visual sensations or auras, are common. Additionally, people with this condition may have decreased brain function that is demonstrated as sleepiness, inability to concentrate, irritability, or loss of language skills or memory. Some people with the condition may lose their eyesight or hearing. People with Alpers-Huttenlocher syndrome can survive from a few months to more than 10 years after the condition first appears.",Alpers-Huttenlocher syndrome,0000038,GHR,https://ghr.nlm.nih.gov/condition/alpers-huttenlocher-syndrome,C0205710,T047,Disorders
How many people are affected by Alpers-Huttenlocher syndrome ?,0000038-2,frequency,"The prevalence of Alpers-Huttenlocher syndrome is approximately 1 in 100,000 individuals.",Alpers-Huttenlocher syndrome,0000038,GHR,https://ghr.nlm.nih.gov/condition/alpers-huttenlocher-syndrome,C0205710,T047,Disorders
What are the genetic changes related to Alpers-Huttenlocher syndrome ?,0000038-3,genetic changes,"Alpers-Huttenlocher syndrome is caused by mutations in the POLG gene. This gene provides instructions for making one part, the alpha subunit, of a protein called polymerase gamma (pol ). Pol  functions in mitochondria, which are structures within cells that use oxygen to convert the energy from food into a form cells can use. Mitochondria each contain a small amount of DNA, known as mitochondrial DNA (mtDNA), which is essential for the normal function of these structures. Pol  ""reads"" sequences of mtDNA and uses them as templates to produce new copies of mtDNA in a process called DNA replication.  Most POLG gene mutations change single protein building blocks (amino acids) in the alpha subunit of pol . These changes result in a mutated pol  that has a reduced ability to replicate DNA. Although the mechanism is unknown, mutations in the POLG gene often result in a reduced number of copies of mtDNA (mtDNA depletion), particularly in muscle, brain, and liver cells. MtDNA depletion causes a decrease in cellular energy, which could account for the signs and symptoms of Alpers-Huttenlocher syndrome.  A mutation in the POLG gene has not been identified in approximately 13 percent of people diagnosed with Alpers-Huttenlocher syndrome. Researchers are working to identify other genes that may be responsible for the condition.",Alpers-Huttenlocher syndrome,0000038,GHR,https://ghr.nlm.nih.gov/condition/alpers-huttenlocher-syndrome,C0205710,T047,Disorders
Is Alpers-Huttenlocher syndrome inherited ?,0000038-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Alpers-Huttenlocher syndrome,0000038,GHR,https://ghr.nlm.nih.gov/condition/alpers-huttenlocher-syndrome,C0205710,T047,Disorders
What are the treatments for Alpers-Huttenlocher syndrome ?,0000038-5,treatment,These resources address the diagnosis or management of Alpers-Huttenlocher syndrome:  - Gene Review: Gene Review: POLG-Related Disorders  - Genetic Testing Registry: Progressive sclerosing poliodystrophy  - United Mitochondrial Disease Foundation: Diagnosis of Mitochondrial Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Alpers-Huttenlocher syndrome,0000038,GHR,https://ghr.nlm.nih.gov/condition/alpers-huttenlocher-syndrome,C0205710,T047,Disorders
What is (are) alpha thalassemia ?,0000039-1,information,"Alpha thalassemia is a blood disorder that reduces the production of hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen to cells throughout the body.  In people with the characteristic features of alpha thalassemia, a reduction in the amount of hemoglobin prevents enough oxygen from reaching the body's tissues. Affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, fatigue, and more serious complications.  Two types of alpha thalassemia can cause health problems. The more severe type is known as hemoglobin Bart hydrops fetalis syndrome or Hb Bart syndrome. The milder form is called HbH disease.  Hb Bart syndrome is characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. Additional signs and symptoms can include severe anemia, an enlarged liver and spleen (hepatosplenomegaly), heart defects, and abnormalities of the urinary system or genitalia. As a result of these serious health problems, most babies with this condition are stillborn or die soon after birth. Hb Bart syndrome can also cause serious complications for women during pregnancy, including dangerously high blood pressure with swelling (preeclampsia), premature delivery, and abnormal bleeding.  HbH disease causes mild to moderate anemia, hepatosplenomegaly, and yellowing of the eyes and skin (jaundice). Some affected individuals also have bone changes such as overgrowth of the upper jaw and an unusually prominent forehead. The features of HbH disease usually appear in early childhood, and affected individuals typically live into adulthood.",alpha thalassemia,0000039,GHR,https://ghr.nlm.nih.gov/condition/alpha-thalassemia,C0002312,T047,Disorders
How many people are affected by alpha thalassemia ?,0000039-2,frequency,"Alpha thalassemia is a fairly common blood disorder worldwide. Thousands of infants with Hb Bart syndrome and HbH disease are born each year, particularly in Southeast Asia. Alpha thalassemia also occurs frequently in people from Mediterranean countries, North Africa, the Middle East, India, and Central Asia.",alpha thalassemia,0000039,GHR,https://ghr.nlm.nih.gov/condition/alpha-thalassemia,C0002312,T047,Disorders
What are the genetic changes related to alpha thalassemia ?,0000039-3,genetic changes,"Alpha thalassemia typically results from deletions involving the HBA1 and HBA2 genes. Both of these genes provide instructions for making a protein called alpha-globin, which is a component (subunit) of hemoglobin.  People have two copies of the HBA1 gene and two copies of the HBA2 gene in each cell. Each copy is called an allele. For each gene, one allele is inherited from a person's father, and the other is inherited from a person's mother. As a result, there are four alleles that produce alpha-globin. The different types of alpha thalassemia result from the loss of some or all of these alleles.  Hb Bart syndrome, the most severe form of alpha thalassemia, results from the loss of all four alpha-globin alleles. HbH disease is caused by a loss of three of the four alpha-globin alleles. In these two conditions, a shortage of alpha-globin prevents cells from making normal hemoglobin. Instead, cells produce abnormal forms of hemoglobin called hemoglobin Bart (Hb Bart) or hemoglobin H (HbH). These abnormal hemoglobin molecules cannot effectively carry oxygen to the body's tissues. The substitution of Hb Bart or HbH for normal hemoglobin causes anemia and the other serious health problems associated with alpha thalassemia.  Two additional variants of alpha thalassemia are related to a reduced amount of alpha-globin. Because cells still produce some normal hemoglobin, these variants tend to cause few or no health problems. A loss of two of the four alpha-globin alleles results in alpha thalassemia trait. People with alpha thalassemia trait may have unusually small, pale red blood cells and mild anemia. A loss of one alpha-globin allele is found in alpha thalassemia silent carriers. These individuals typically have no thalassemia-related signs or symptoms.",alpha thalassemia,0000039,GHR,https://ghr.nlm.nih.gov/condition/alpha-thalassemia,C0002312,T047,Disorders
Is alpha thalassemia inherited ?,0000039-4,inheritance,"The inheritance of alpha thalassemia is complex. Each person inherits two alpha-globin alleles from each parent. If both parents are missing at least one alpha-globin allele, their children are at risk of having Hb Bart syndrome, HbH disease, or alpha thalassemia trait. The precise risk depends on how many alleles are missing and which combination of the HBA1 and HBA2 genes is affected.",alpha thalassemia,0000039,GHR,https://ghr.nlm.nih.gov/condition/alpha-thalassemia,C0002312,T047,Disorders
What are the treatments for alpha thalassemia ?,0000039-5,treatment,"These resources address the diagnosis or management of alpha thalassemia:  - Gene Review: Gene Review: Alpha-Thalassemia  - Genetic Testing Registry: alpha Thalassemia  - MedlinePlus Encyclopedia: Thalassemia  - University of California, San Francisco Fetal Treatment Center: Stem Cell Treatments   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",alpha thalassemia,0000039,GHR,https://ghr.nlm.nih.gov/condition/alpha-thalassemia,C0002312,T047,Disorders
What is (are) alpha thalassemia X-linked intellectual disability syndrome ?,0000040-1,information,"Alpha thalassemia X-linked intellectual disability syndrome is an inherited disorder that affects many parts of the body. This condition occurs almost exclusively in males.  Males with alpha thalassemia X-linked intellectual disability syndrome have intellectual disability and delayed development. Their speech is significantly delayed, and most never speak or sign more than a few words. Most affected children have weak muscle tone (hypotonia), which delays motor skills such as sitting, standing, and walking. Some people with this disorder are never able to walk independently.  Almost everyone with alpha thalassemia X-linked intellectual disability syndrome has distinctive facial features, including widely spaced eyes, a small nose with upturned nostrils, and low-set ears. The upper lip is shaped like an upside-down ""V,"" and the lower lip tends to be prominent. These facial characteristics are most apparent in early childhood. Over time, the facial features become coarser, including a flatter face with a shortened nose.  Most affected individuals have mild signs of a blood disorder called alpha thalassemia. This disorder reduces the production of hemoglobin, which is the protein in red blood cells that carries oxygen to cells throughout the body. A reduction in the amount of hemoglobin prevents enough oxygen from reaching the body's tissues. Rarely, affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, and fatigue.  Additional features of alpha thalassemia X-linked intellectual disability syndrome include an unusually small head size (microcephaly), short stature, and skeletal abnormalities. Many affected individuals have problems with the digestive system, such as a backflow of stomach acids into the esophagus (gastroesophageal reflux) and chronic constipation. Genital abnormalities are also common; affected males may have undescended testes and the opening of the urethra on the underside of the penis (hypospadias). In more severe cases, the external genitalia do not look clearly male or female (ambiguous genitalia).",alpha thalassemia X-linked intellectual disability syndrome,0000040,GHR,https://ghr.nlm.nih.gov/condition/alpha-thalassemia-x-linked-intellectual-disability-syndrome,C1845055,T048,Disorders
How many people are affected by alpha thalassemia X-linked intellectual disability syndrome ?,0000040-2,frequency,"Alpha thalassemia X-linked intellectual disability syndrome appears to be a rare condition, although its exact prevalence is unknown. More than 200 affected individuals have been reported.",alpha thalassemia X-linked intellectual disability syndrome,0000040,GHR,https://ghr.nlm.nih.gov/condition/alpha-thalassemia-x-linked-intellectual-disability-syndrome,C1845055,T048,Disorders
What are the genetic changes related to alpha thalassemia X-linked intellectual disability syndrome ?,0000040-3,genetic changes,"Alpha thalassemia X-linked intellectual disability syndrome results from mutations in the ATRX gene. This gene provides instructions for making a protein that plays an essential role in normal development. Although the exact function of the ATRX protein is unknown, studies suggest that it helps regulate the activity (expression) of other genes. Among these genes are HBA1 and HBA2, which are necessary for normal hemoglobin production.  Mutations in the ATRX gene change the structure of the ATRX protein, which likely prevents it from effectively regulating gene expression. Reduced activity of the HBA1 and HBA2 genes causes alpha thalassemia. Abnormal expression of other genes, which have not been identified, probably causes developmental delay, distinctive facial features, and the other signs and symptoms of alpha thalassemia X-linked intellectual disability syndrome.",alpha thalassemia X-linked intellectual disability syndrome,0000040,GHR,https://ghr.nlm.nih.gov/condition/alpha-thalassemia-x-linked-intellectual-disability-syndrome,C1845055,T048,Disorders
Is alpha thalassemia X-linked intellectual disability syndrome inherited ?,0000040-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The ATRX gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), one working copy of the ATRX gene can usually compensate for the mutated copy. Therefore, females who carry a single mutated ATRX gene almost never have signs of alpha thalassemia X-linked intellectual disability syndrome.  A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",alpha thalassemia X-linked intellectual disability syndrome,0000040,GHR,https://ghr.nlm.nih.gov/condition/alpha-thalassemia-x-linked-intellectual-disability-syndrome,C1845055,T048,Disorders
What are the treatments for alpha thalassemia X-linked intellectual disability syndrome ?,0000040-5,treatment,These resources address the diagnosis or management of alpha thalassemia X-linked intellectual disability syndrome:  - Gene Review: Gene Review: Alpha-Thalassemia X-Linked Intellectual Disability Syndrome  - Genetic Testing Registry: ATR-X syndrome  - MedlinePlus Encyclopedia: Ambiguous Genitalia  - MedlinePlus Encyclopedia: Hypospadias   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,alpha thalassemia X-linked intellectual disability syndrome,0000040,GHR,https://ghr.nlm.nih.gov/condition/alpha-thalassemia-x-linked-intellectual-disability-syndrome,C1845055,T048,Disorders
What is (are) alpha-1 antitrypsin deficiency ?,0000041-1,information,"Alpha-1 antitrypsin deficiency is an inherited disorder that may cause lung disease and liver disease. The signs and symptoms of the condition and the age at which they appear vary among individuals.  People with alpha-1 antitrypsin deficiency usually develop the first signs and symptoms of lung disease between ages 20 and 50. The earliest symptoms are shortness of breath following mild activity, reduced ability to exercise, and wheezing. Other signs and symptoms can include unintentional weight loss, recurring respiratory infections, fatigue, and rapid heartbeat upon standing. Affected individuals often develop emphysema, which is a lung disease caused by damage to the small air sacs in the lungs (alveoli). Characteristic features of emphysema include difficulty breathing, a hacking cough, and a barrel-shaped chest. Smoking or exposure to tobacco smoke accelerates the appearance of emphysema symptoms and damage to the lungs.  About 10 percent of infants with alpha-1 antitrypsin deficiency develop liver disease, which often causes yellowing of the skin and whites of the eyes (jaundice). Approximately 15 percent of adults with alpha-1 antitrypsin deficiency develop liver damage (cirrhosis) due to the formation of scar tissue in the liver. Signs of cirrhosis include a swollen abdomen, swollen feet or legs, and jaundice. Individuals with alpha-1 antitrypsin deficiency are also at risk of developing a type of liver cancer called hepatocellular carcinoma.  In rare cases, people with alpha-1 antitrypsin deficiency develop a skin condition called panniculitis, which is characterized by hardened skin with painful lumps or patches. Panniculitis varies in severity and can occur at any age.",alpha-1 antitrypsin deficiency,0000041,GHR,https://ghr.nlm.nih.gov/condition/alpha-1-antitrypsin-deficiency,C0221757,T047,Disorders
How many people are affected by alpha-1 antitrypsin deficiency ?,0000041-2,frequency,"Alpha-1 antitrypsin deficiency occurs worldwide, but its prevalence varies by population. This disorder affects about 1 in 1,500 to 3,500 individuals with European ancestry. It is uncommon in people of Asian descent. Many individuals with alpha-1 antitrypsin deficiency are likely undiagnosed, particularly people with a lung condition called chronic obstructive pulmonary disease (COPD). COPD can be caused by alpha-1 antitrypsin deficiency; however, the alpha-1 antitrypsin deficiency is often never diagnosed. Some people with alpha-1 antitrypsin deficiency are misdiagnosed with asthma.",alpha-1 antitrypsin deficiency,0000041,GHR,https://ghr.nlm.nih.gov/condition/alpha-1-antitrypsin-deficiency,C0221757,T047,Disorders
What are the genetic changes related to alpha-1 antitrypsin deficiency ?,0000041-3,genetic changes,"Mutations in the SERPINA1 gene cause alpha-1 antitrypsin deficiency. This gene provides instructions for making a protein called alpha-1 antitrypsin, which protects the body from a powerful enzyme called neutrophil elastase. Neutrophil elastase is released from white blood cells to fight infection, but it can attack normal tissues (especially the lungs) if not tightly controlled by alpha-1 antitrypsin.  Mutations in the SERPINA1 gene can lead to a shortage (deficiency) of alpha-1 antitrypsin or an abnormal form of the protein that cannot control neutrophil elastase. Without enough functional alpha-1 antitrypsin, neutrophil elastase destroys alveoli and causes lung disease. Abnormal alpha-1 antitrypsin can also accumulate in the liver and damage this organ.  Environmental factors, such as exposure to tobacco smoke, chemicals, and dust, likely impact the severity of alpha-1 antitrypsin deficiency.",alpha-1 antitrypsin deficiency,0000041,GHR,https://ghr.nlm.nih.gov/condition/alpha-1-antitrypsin-deficiency,C0221757,T047,Disorders
Is alpha-1 antitrypsin deficiency inherited ?,0000041-4,inheritance,"This condition is inherited in an autosomal codominant pattern. Codominance means that two different versions of the gene may be active (expressed), and both versions contribute to the genetic trait.  The most common version (allele) of the SERPINA1 gene, called M, produces normal levels of alpha-1 antitrypsin. Most people in the general population have two copies of the M allele (MM) in each cell. Other versions of the SERPINA1 gene lead to reduced levels of alpha-1 antitrypsin. For example, the S allele produces moderately low levels of this protein, and the Z allele produces very little alpha-1 antitrypsin. Individuals with two copies of the Z allele (ZZ) in each cell are likely to have alpha-1 antitrypsin deficiency. Those with the SZ combination have an increased risk of developing lung diseases (such as emphysema), particularly if they smoke.  Worldwide, it is estimated that 161 million people have one copy of the S or Z allele and one copy of the M allele in each cell (MS or MZ). Individuals with an MS (or SS) combination usually produce enough alpha-1 antitrypsin to protect the lungs. People with MZ alleles, however, have a slightly increased risk of impaired lung or liver function.",alpha-1 antitrypsin deficiency,0000041,GHR,https://ghr.nlm.nih.gov/condition/alpha-1-antitrypsin-deficiency,C0221757,T047,Disorders
What are the treatments for alpha-1 antitrypsin deficiency ?,0000041-5,treatment,These resources address the diagnosis or management of alpha-1 antitrypsin deficiency:  - Alpha-1 Foundation: Testing for Alpha-1  - Cleveland Clinic Respiratory Institute  - Gene Review: Gene Review: Alpha-1 Antitrypsin Deficiency  - GeneFacts: Alpha-1 Antitrypsin Deficiency: Diagnosis  - GeneFacts: Alpha-1 Antitrypsin Deficiency: Management  - Genetic Testing Registry: Alpha-1-antitrypsin deficiency  - MedlinePlus Encyclopedia: Alpha-1 antitrypsin deficiency  - MedlinePlus Encyclopedia: Pulmonary function tests  - MedlinePlus Encyclopedia: Wheezing   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,alpha-1 antitrypsin deficiency,0000041,GHR,https://ghr.nlm.nih.gov/condition/alpha-1-antitrypsin-deficiency,C0221757,T047,Disorders
What is (are) alpha-mannosidosis ?,0000042-1,information,"Alpha-mannosidosis is a rare inherited disorder that causes problems in many organs and tissues of the body. Affected individuals may have intellectual disability, distinctive facial features, and skeletal abnormalities. Characteristic facial features can include a large head, prominent forehead, low hairline, rounded eyebrows, large ears, flattened bridge of the nose, protruding jaw, widely spaced teeth, overgrown gums, and large tongue. The skeletal abnormalities that can occur in this disorder include reduced bone density (osteopenia), thickening of the bones at the top of the skull (calvaria), deformations of the bones in the spine (vertebrae), bowed legs or knock knees, and deterioration of the bones and joints.  Affected individuals may also experience difficulty in coordinating movements (ataxia); muscle weakness (myopathy); delay in developing motor skills such as sitting and walking; speech impairments; increased risk of infections; enlargement of the liver and spleen (hepatosplenomegaly); a buildup of fluid in the brain (hydrocephalus); hearing loss; and a clouding of the lens of the eye (cataract). Some people with alpha-mannosidosis experience psychiatric symptoms such as depression, anxiety, or hallucinations; episodes of psychiatric disturbance may be triggered by stressors such as having undergone surgery, emotional upset, or changes in routine.  The signs and symptoms of alpha-mannosidosis can range from mild to severe. The disorder may appear in infancy with rapid progression and severe neurological deterioration. Individuals with this early-onset form of alpha-mannosidosis often do not survive past childhood. In the most severe cases, an affected fetus may die before birth. Other individuals with alpha-mannosidosis experience milder signs and symptoms that appear later and progress more slowly. People with later-onset alpha-mannosidosis may survive into their fifties. The mildest cases may be detected only through laboratory testing and result in few if any symptoms.",alpha-mannosidosis,0000042,GHR,https://ghr.nlm.nih.gov/condition/alpha-mannosidosis,C0024748,T047,Disorders
How many people are affected by alpha-mannosidosis ?,0000042-2,frequency,"Alpha-mannosidosis is estimated to occur in approximately 1 in 500,000 people worldwide.",alpha-mannosidosis,0000042,GHR,https://ghr.nlm.nih.gov/condition/alpha-mannosidosis,C0024748,T047,Disorders
What are the genetic changes related to alpha-mannosidosis ?,0000042-3,genetic changes,"Mutations in the MAN2B1 gene cause alpha-mannosidosis. This gene provides instructions for making the enzyme alpha-mannosidase. This enzyme works in the lysosomes, which are compartments that digest and recycle materials in the cell. Within lysosomes, the enzyme helps break down complexes of sugar molecules (oligosaccharides) attached to certain proteins (glycoproteins). In particular, alpha-mannosidase helps break down oligosaccharides containing a sugar molecule called mannose.  Mutations in the MAN2B1 gene interfere with the ability of the alpha-mannosidase enzyme to perform its role in breaking down mannose-containing oligosaccharides. These oligosaccharides accumulate in the lysosomes and cause cells to malfunction and eventually die. Tissues and organs are damaged by the abnormal accumulation of oligosaccharides and the resulting cell death, leading to the characteristic features of alpha-mannosidosis.",alpha-mannosidosis,0000042,GHR,https://ghr.nlm.nih.gov/condition/alpha-mannosidosis,C0024748,T047,Disorders
Is alpha-mannosidosis inherited ?,0000042-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",alpha-mannosidosis,0000042,GHR,https://ghr.nlm.nih.gov/condition/alpha-mannosidosis,C0024748,T047,Disorders
What are the treatments for alpha-mannosidosis ?,0000042-5,treatment,These resources address the diagnosis or management of alpha-mannosidosis:  - Gene Review: Gene Review: Alpha-Mannosidosis  - Genetic Testing Registry: Deficiency of alpha-mannosidase   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,alpha-mannosidosis,0000042,GHR,https://ghr.nlm.nih.gov/condition/alpha-mannosidosis,C0024748,T047,Disorders
What is (are) alpha-methylacyl-CoA racemase deficiency ?,0000043-1,information,"Alpha-methylacyl-CoA racemase (AMACR) deficiency is a disorder that causes a variety of neurological problems that begin in adulthood and slowly get worse. People with AMACR deficiency may have a gradual loss in intellectual functioning (cognitive decline), seizures, and migraines. They may also have acute episodes of brain dysfunction (encephalopathy) similar to stroke, involving altered consciousness and areas of damage (lesions) in the brain. Other features of AMACR deficiency may include weakness and loss of sensation in the limbs due to nerve damage (sensorimotor neuropathy), muscle stiffness (spasticity), and difficulty coordinating movements (ataxia). Vision problems caused by deterioration of the light-sensitive layer at the back of the eye (the retina) can also occur in this disorder.",alpha-methylacyl-CoA racemase deficiency,0000043,GHR,https://ghr.nlm.nih.gov/condition/alpha-methylacyl-coa-racemase-deficiency,C3280428,T047,Disorders
How many people are affected by alpha-methylacyl-CoA racemase deficiency ?,0000043-2,frequency,AMACR deficiency is a rare disorder. Its prevalence is unknown. At least 10 cases have been described in the medical literature.,alpha-methylacyl-CoA racemase deficiency,0000043,GHR,https://ghr.nlm.nih.gov/condition/alpha-methylacyl-coa-racemase-deficiency,C3280428,T047,Disorders
What are the genetic changes related to alpha-methylacyl-CoA racemase deficiency ?,0000043-3,genetic changes,"AMACR deficiency is caused by mutations in the AMACR gene. This gene provides instructions for making an enzyme called alpha-methylacyl-CoA racemase (AMACR).  The AMACR enzyme is found in the energy-producing centers in cells (mitochondria) and in cell structures called peroxisomes. Peroxisomes contain a variety of enzymes that break down many different substances, including fatty acids and certain toxic compounds. They are also important for the production (synthesis) of fats (lipids) used in digestion and in the nervous system. In peroxisomes, the AMACR enzyme plays a role in the breakdown of a fatty acid called pristanic acid, which comes from meat and dairy foods in the diet. In mitochondria, AMACR is thought to help further break down the molecules derived from pristanic acid.  Most individuals with AMACR deficiency have an AMACR gene mutation that results in a lack (deficiency) of functional enzyme. The enzyme deficiency leads to accumulation of pristanic acid in the blood. However, it is unclear how this accumulation is related to the specific signs and symptoms of AMACR deficiency.",alpha-methylacyl-CoA racemase deficiency,0000043,GHR,https://ghr.nlm.nih.gov/condition/alpha-methylacyl-coa-racemase-deficiency,C3280428,T047,Disorders
Is alpha-methylacyl-CoA racemase deficiency inherited ?,0000043-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",alpha-methylacyl-CoA racemase deficiency,0000043,GHR,https://ghr.nlm.nih.gov/condition/alpha-methylacyl-coa-racemase-deficiency,C3280428,T047,Disorders
What are the treatments for alpha-methylacyl-CoA racemase deficiency ?,0000043-5,treatment,These resources address the diagnosis or management of AMACR deficiency:  - Genetic Testing Registry: Alpha-methylacyl-CoA racemase deficiency  - Kennedy Krieger Institute: Peroxisomal Diseases   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,alpha-methylacyl-CoA racemase deficiency,0000043,GHR,https://ghr.nlm.nih.gov/condition/alpha-methylacyl-coa-racemase-deficiency,C3280428,T047,Disorders
What is (are) Alport syndrome ?,0000044-1,information,"Alport syndrome is a genetic condition characterized by kidney disease, hearing loss, and eye abnormalities.  People with Alport syndrome experience progressive loss of kidney function. Almost all affected individuals have blood in their urine (hematuria), which indicates abnormal functioning of the kidneys. Many people with Alport syndrome also develop high levels of protein in their urine (proteinuria). The kidneys become less able to function as this condition progresses, resulting in end-stage renal disease (ESRD).  People with Alport syndrome frequently develop sensorineural hearing loss, which is caused by abnormalities of the inner ear, during late childhood or early adolescence. Affected individuals may also have misshapen lenses in the eyes (anterior lenticonus) and abnormal coloration of the light-sensitive tissue at the back of the eye (retina). These eye abnormalities seldom lead to vision loss.  Significant hearing loss, eye abnormalities, and progressive kidney disease are more common in males with Alport syndrome than in affected females.",Alport syndrome,0000044,GHR,https://ghr.nlm.nih.gov/condition/alport-syndrome,C1567741,T047,Disorders
How many people are affected by Alport syndrome ?,0000044-2,frequency,"Alport syndrome occurs in approximately 1 in 50,000 newborns.",Alport syndrome,0000044,GHR,https://ghr.nlm.nih.gov/condition/alport-syndrome,C1567741,T047,Disorders
What are the genetic changes related to Alport syndrome ?,0000044-3,genetic changes,"Mutations in the COL4A3, COL4A4, and COL4A5 genes cause Alport syndrome. These genes each provide instructions for making one component of a protein called type IV collagen. This protein plays an important role in the kidneys, specifically in structures called glomeruli. Glomeruli are clusters of specialized blood vessels that remove water and waste products from blood and create urine. Mutations in these genes result in abnormalities of the type IV collagen in glomeruli, which prevents the kidneys from properly filtering the blood and allows blood and protein to pass into the urine. Gradual scarring of the kidneys occurs, eventually leading to kidney failure in many people with Alport syndrome.  Type IV collagen is also an important component of inner ear structures, particularly the organ of Corti, that transform sound waves into nerve impulses for the brain. Alterations in type IV collagen often result in abnormal inner ear function, which can lead to hearing loss. In the eye, this protein is important for maintaining the shape of the lens and the normal color of the retina. Mutations that disrupt type IV collagen can result in misshapen lenses and an abnormally colored retina.",Alport syndrome,0000044,GHR,https://ghr.nlm.nih.gov/condition/alport-syndrome,C1567741,T047,Disorders
Is Alport syndrome inherited ?,0000044-4,inheritance,"Alport syndrome can have different inheritance patterns. About 80 percent of cases are caused by mutations in the COL4A5 gene and are inherited in an X-linked pattern. This gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the COL4A5 gene in each cell is sufficient to cause kidney failure and other severe symptoms of the disorder. In females (who have two X chromosomes), a mutation in one copy of the COL4A5 gene usually only results in hematuria, but some women experience more severe symptoms. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In approximately 15 percent of cases, Alport syndrome results from mutations in both copies of the COL4A3 or COL4A4 gene and is inherited in an autosomal recessive pattern. The parents of an individual with the autosomal recessive form of this condition each have one copy of the mutated gene and are called carriers. Some carriers are unaffected and others develop a less severe condition called thin basement membrane nephropathy, which is characterized by hematuria.  Alport syndrome has autosomal dominant inheritance in about 5 percent of cases. People with this form of Alport syndrome have one mutation in either the COL4A3 or COL4A4 gene in each cell. It remains unclear why some individuals with one mutation in the COL4A3 or COL4A4 gene have autosomal dominant Alport syndrome and others have thin basement membrane nephropathy.",Alport syndrome,0000044,GHR,https://ghr.nlm.nih.gov/condition/alport-syndrome,C1567741,T047,Disorders
What are the treatments for Alport syndrome ?,0000044-5,treatment,"These resources address the diagnosis or management of Alport syndrome:  - Gene Review: Gene Review: Alport Syndrome and Thin Basement Membrane Nephropathy  - Genetic Testing Registry: Alport syndrome  - Genetic Testing Registry: Alport syndrome, X-linked recessive  - Genetic Testing Registry: Alport syndrome, autosomal dominant  - Genetic Testing Registry: Alport syndrome, autosomal recessive  - MedlinePlus Encyclopedia: Alport Syndrome  - MedlinePlus Encyclopedia: End-Stage Kidney Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Alport syndrome,0000044,GHR,https://ghr.nlm.nih.gov/condition/alport-syndrome,C1567741,T047,Disorders
What is (are) Alstrm syndrome ?,0000045-1,information,"Alstrm syndrome is a rare condition that affects many body systems. Many of the signs and symptoms of this condition begin in infancy or early childhood, although some appear later in life.  Alstrm syndrome is characterized by a progressive loss of vision and hearing, a form of heart disease that enlarges and weakens the heart muscle (dilated cardiomyopathy), obesity, type 2 diabetes mellitus (the most common form of diabetes), and short stature. This disorder can also cause serious or life-threatening medical problems involving the liver, kidneys, bladder, and lungs. Some individuals with Alstrm syndrome have a skin condition called acanthosis nigricans, which causes the skin in body folds and creases to become thick, dark, and velvety. The signs and symptoms of Alstrm syndrome vary in severity, and not all affected individuals have all of the characteristic features of the disorder.",Alstrm syndrome,0000045,GHR,https://ghr.nlm.nih.gov/condition/alstrom-syndrome,C0039082,T047,Disorders
How many people are affected by Alstrm syndrome ?,0000045-2,frequency,More than 900 people with Alstrm syndrome have been reported worldwide.,Alstrm syndrome,0000045,GHR,https://ghr.nlm.nih.gov/condition/alstrom-syndrome,C0039082,T047,Disorders
What are the genetic changes related to Alstrm syndrome ?,0000045-3,genetic changes,"Mutations in the ALMS1 gene cause Alstrm syndrome. The ALMS1 gene provides instructions for making a protein whose function is unknown. Mutations in this gene probably lead to the production of an abnormally short, nonfunctional version of the ALMS1 protein. This protein is normally present at low levels in most tissues, so a loss of the protein's normal function may help explain why the signs and symptoms of Alstrm syndrome affect many parts of the body.",Alstrm syndrome,0000045,GHR,https://ghr.nlm.nih.gov/condition/alstrom-syndrome,C0039082,T047,Disorders
Is Alstrm syndrome inherited ?,0000045-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Alstrm syndrome,0000045,GHR,https://ghr.nlm.nih.gov/condition/alstrom-syndrome,C0039082,T047,Disorders
What are the treatments for Alstrm syndrome ?,0000045-5,treatment,These resources address the diagnosis or management of Alstrm syndrome:  - Gene Review: Gene Review: Alstrom Syndrome  - Genetic Testing Registry: Alstrom syndrome  - MedlinePlus Encyclopedia: Acanthosis Nigricans  - MedlinePlus Encyclopedia: Alstrm syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Alstrm syndrome,0000045,GHR,https://ghr.nlm.nih.gov/condition/alstrom-syndrome,C0039082,T047,Disorders
What is (are) alternating hemiplegia of childhood ?,0000046-1,information,"Alternating hemiplegia of childhood is a neurological condition characterized by recurrent episodes of temporary paralysis, often affecting one side of the body (hemiplegia). During some episodes, the paralysis alternates from one side of the body to the other or affects both sides at the same time. These episodes begin in infancy or early childhood, usually before 18 months of age, and the paralysis lasts from minutes to days.  In addition to paralysis, affected individuals can have sudden attacks of uncontrollable muscle activity; these can cause involuntary limb movements (choreoathetosis), muscle tensing (dystonia), movement of the eyes (nystagmus), or shortness of breath (dyspnea). People with alternating hemiplegia of childhood may also experience sudden redness and warmth (flushing) or unusual paleness (pallor) of the skin. These attacks can occur during or separately from episodes of hemiplegia.  The episodes of hemiplegia or uncontrolled movements can be triggered by certain factors, such as stress, extreme tiredness, cold temperatures, or bathing, although the trigger is not always known. A characteristic feature of alternating hemiplegia of childhood is that all symptoms disappear while the affected person is sleeping but can reappear shortly after awakening. The number and length of the episodes initially worsen throughout childhood but then begin to decrease over time. The uncontrollable muscle movements may disappear entirely, but the episodes of hemiplegia occur throughout life.  Alternating hemiplegia of childhood also causes mild to severe cognitive problems. Almost all affected individuals have some level of developmental delay and intellectual disability. Their cognitive functioning typically declines over time.",alternating hemiplegia of childhood,0000046,GHR,https://ghr.nlm.nih.gov/condition/alternating-hemiplegia-of-childhood,C0338488,T047,Disorders
How many people are affected by alternating hemiplegia of childhood ?,0000046-2,frequency,Alternating hemiplegia of childhood is a rare condition that affects approximately 1 in 1 million people.,alternating hemiplegia of childhood,0000046,GHR,https://ghr.nlm.nih.gov/condition/alternating-hemiplegia-of-childhood,C0338488,T047,Disorders
What are the genetic changes related to alternating hemiplegia of childhood ?,0000046-3,genetic changes,"Alternating hemiplegia of childhood is primarily caused by mutations in the ATP1A3 gene. Very rarely, a mutation in the ATP1A2 gene is involved in the condition. These genes provide instructions for making very similar proteins. They function as different forms of one piece, the alpha subunit, of a larger protein complex called Na+/K+ ATPase; the two versions of the complex are found in different parts of the brain. Both versions play a critical role in the normal function of nerve cells (neurons). Na+/K+ ATPase transports charged atoms (ions) into and out of neurons, which is an essential part of the signaling process that controls muscle movement.  Mutations in the ATP1A3 or ATP1A2 gene reduce the activity of the Na+/K+ ATPase, impairing its ability to transport ions normally. It is unclear how a malfunctioning Na+/K+ ATPase causes the episodes of paralysis or uncontrollable movements characteristic of alternating hemiplegia of childhood.",alternating hemiplegia of childhood,0000046,GHR,https://ghr.nlm.nih.gov/condition/alternating-hemiplegia-of-childhood,C0338488,T047,Disorders
Is alternating hemiplegia of childhood inherited ?,0000046-4,inheritance,"Alternating hemiplegia of childhood is considered an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases of alternating hemiplegia of childhood result from new mutations in the gene and occur in people with no history of the disorder in their family. However, the condition can also run in families. For unknown reasons, the signs and symptoms are typically milder when the condition is found in multiple family members than when a single individual is affected.",alternating hemiplegia of childhood,0000046,GHR,https://ghr.nlm.nih.gov/condition/alternating-hemiplegia-of-childhood,C0338488,T047,Disorders
What are the treatments for alternating hemiplegia of childhood ?,0000046-5,treatment,These resources address the diagnosis or management of alternating hemiplegia of childhood:  - The Great Ormond Street Hospital  - University of Utah School of Medicine   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,alternating hemiplegia of childhood,0000046,GHR,https://ghr.nlm.nih.gov/condition/alternating-hemiplegia-of-childhood,C0338488,T047,Disorders
What is (are) alveolar capillary dysplasia with misalignment of pulmonary veins ?,0000047-1,information,"Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a disorder affecting the development of the lungs and their blood vessels. The disorder affects the millions of small air sacs (alveoli) in the lungs and the tiny blood vessels (capillaries) in the alveoli. It is through these alveolar capillaries that inhaled oxygen enters the bloodstream for distribution throughout the body and carbon dioxide leaves the bloodstream to be exhaled.  In ACD/MPV, the alveolar capillaries fail to develop normally. The number of capillaries is drastically reduced, and existing capillaries are improperly positioned within the walls of the alveoli. These abnormalities in capillary number and location impede the exchange of oxygen and carbon dioxide.  Other abnormalities of the blood vessels in the lungs also occur in ACD/MPV. The veins that carry blood from the lungs into the heart (pulmonary veins) are improperly positioned and may be abnormally bundled together with arteries that carry blood from the heart to the lungs (pulmonary arteries). The muscle tissue in the walls of the pulmonary arteries may be overgrown, resulting in thicker artery walls and a narrower channel. These changes restrict normal blood flow, which causes high blood pressure in the pulmonary arteries (pulmonary hypertension) and requires the heart to pump harder.  Most infants with ACD/MPV are born with additional abnormalities. These may include abnormal twisting (malrotation) of the large intestine or other malformations of the gastrointestinal tract. Cardiovascular and genitourinary abnormalities are also common in affected individuals.  Infants with ACD/MPV typically develop respiratory distress within a few minutes to a few hours after birth. They experience shortness of breath and cyanosis, which is a bluish appearance of the skin, mucous membranes, or the area underneath the fingernails caused by a lack of oxygen in the blood. Without lung transplantation, infants with ACD/MPV have not been known to survive past one year of age, and most affected infants live only a few weeks.",alveolar capillary dysplasia with misalignment of pulmonary veins,0000047,GHR,https://ghr.nlm.nih.gov/condition/alveolar-capillary-dysplasia-with-misalignment-of-pulmonary-veins,C0334044,T190,Disorders
How many people are affected by alveolar capillary dysplasia with misalignment of pulmonary veins ?,0000047-2,frequency,ACD/MPV is a rare disorder; its incidence is unknown. Approximately 200 infants with this disorder have been identified worldwide.,alveolar capillary dysplasia with misalignment of pulmonary veins,0000047,GHR,https://ghr.nlm.nih.gov/condition/alveolar-capillary-dysplasia-with-misalignment-of-pulmonary-veins,C0334044,T190,Disorders
What are the genetic changes related to alveolar capillary dysplasia with misalignment of pulmonary veins ?,0000047-3,genetic changes,"ACD/MPV can be caused by mutations in the FOXF1 gene. The protein produced from the FOXF1 gene is a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of many other genes. The FOXF1 protein is important in development of the lungs and their blood vessels. The FOXF1 protein is also involved in the development of the gastrointestinal tract. Mutations in the FOXF1 gene that cause ACD/MPV result in an inactive protein that cannot regulate development, leading to abnormal formation of the pulmonary blood vessels and gastrointestinal tract.  ACD/MPV can also be caused by a deletion of genetic material on the long arm of chromosome 16 in a region known as 16q24.1. This region includes several genes, including the FOXF1 gene. Deletion of one copy of the FOXF1 gene in each cell reduces the production of the FOXF1 protein. A shortage of FOXF1 protein affects the development of pulmonary blood vessels and causes the main features of ACD/MPV. Researchers suggest that the loss of other genes in this region probably causes the additional abnormalities, such as heart defects, seen in some infants with this disorder. Like FOXF1, these genes also provide instructions for making transcription factors that regulate development of various body systems before birth.  In about 60 percent of affected infants, the genetic cause of ACD/MPV is unknown.",alveolar capillary dysplasia with misalignment of pulmonary veins,0000047,GHR,https://ghr.nlm.nih.gov/condition/alveolar-capillary-dysplasia-with-misalignment-of-pulmonary-veins,C0334044,T190,Disorders
Is alveolar capillary dysplasia with misalignment of pulmonary veins inherited ?,0000047-4,inheritance,"ACD/MPV is usually not inherited, and most affected people have no history of the disorder in their family. The genetic changes associated with this condition usually occur during the formation of reproductive cells (eggs and sperm) or in early fetal development. When the condition is caused by a FOXF1 gene mutation or deletion, one altered or missing gene in each cell is sufficient to cause the disorder. Individuals with ACD/MPV do not pass the genetic change on to their children because they do not live long enough to reproduce.  A few families have been identified in which more than one sibling has ACD/MPV. It is not clear how ACD/MPV is inherited in these families because no genetic changes have been identified.",alveolar capillary dysplasia with misalignment of pulmonary veins,0000047,GHR,https://ghr.nlm.nih.gov/condition/alveolar-capillary-dysplasia-with-misalignment-of-pulmonary-veins,C0334044,T190,Disorders
What are the treatments for alveolar capillary dysplasia with misalignment of pulmonary veins ?,0000047-5,treatment,These resources address the diagnosis or management of ACD/MPV:  - Genetic Testing Registry: Alveolar capillary dysplasia with misalignment of pulmonary veins  - MedlinePlus Encyclopedia: Alveolar Abnormalities   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,alveolar capillary dysplasia with misalignment of pulmonary veins,0000047,GHR,https://ghr.nlm.nih.gov/condition/alveolar-capillary-dysplasia-with-misalignment-of-pulmonary-veins,C0334044,T190,Disorders
What is (are) Alzheimer disease ?,0000048-1,information,"Alzheimer disease is a degenerative disease of the brain that causes dementia, which is a gradual loss of memory, judgment, and ability to function. This disorder usually appears in people older than age 65, but less common forms of the disease appear earlier in adulthood.  Memory loss is the most common sign of Alzheimer disease. Forgetfulness may be subtle at first, but the loss of memory worsens over time until it interferes with most aspects of daily living. Even in familiar settings, a person with Alzheimer disease may get lost or become confused. Routine tasks such as preparing meals, doing laundry, and performing other household chores can be challenging. Additionally, it may become difficult to recognize people and name objects. Affected people increasingly require help with dressing, eating, and personal care.  As the disorder progresses, some people with Alzheimer disease experience personality and behavioral changes and have trouble interacting in a socially appropriate manner. Other common symptoms include agitation, restlessness, withdrawal, and loss of language skills. People with this disease usually require total care during the advanced stages of the disease. Affected individuals usually survive 8 to 10 years after the appearance of symptoms, but the course of the disease can range from 1 to 25 years. Death usually results from pneumonia, malnutrition, or general body wasting (inanition).  Alzheimer disease can be classified as early-onset or late-onset. The signs and symptoms of the early-onset form appear before age 65, while the late-onset form appears after age 65. The early-onset form is much less common than the late-onset form, accounting for less than 5 percent of all cases of Alzheimer disease.",Alzheimer disease,0000048,GHR,https://ghr.nlm.nih.gov/condition/alzheimer-disease,C0002395,T047,Disorders
How many people are affected by Alzheimer disease ?,0000048-2,frequency,"Alzheimer disease currently affects an estimated 2.4 million to 4.5 million Americans. Because the risk of developing Alzheimer disease increases with age and more people are living longer, the number of people with this disease is expected to increase significantly in coming decades.",Alzheimer disease,0000048,GHR,https://ghr.nlm.nih.gov/condition/alzheimer-disease,C0002395,T047,Disorders
What are the genetic changes related to Alzheimer disease ?,0000048-3,genetic changes,"Most cases of early-onset Alzheimer disease are caused by gene mutations that can be passed from parent to child. Researchers have found that this form of the disorder can result from mutations in one of three genes: APP, PSEN1, or PSEN2. When any of these genes is altered, large amounts of a toxic protein fragment called amyloid beta peptide are produced in the brain. This peptide can build up in the brain to form clumps called amyloid plaques, which are characteristic of Alzheimer disease. A buildup of toxic amyloid beta peptide and amyloid plaques may lead to the death of nerve cells and the progressive signs and symptoms of this disorder.  Some evidence indicates that people with Down syndrome have an increased risk of developing Alzheimer disease. Down syndrome, a condition characterized by intellectual disability and other health problems, occurs when a person is born with an extra copy of chromosome 21 in each cell. As a result, people with Down syndrome have three copies of many genes in each cell, including the APP gene, instead of the usual two copies. Although the connection between Down syndrome and Alzheimer disease is unclear, the production of excess amyloid beta peptide in cells may account for the increased risk. People with Down syndrome account for less than 1 percent of all cases of Alzheimer disease.  The causes of late-onset Alzheimer disease are less clear. The late-onset form does not clearly run in families, although clusters of cases have been reported in some families. This disorder is probably related to variations in one or more genes in combination with lifestyle and environmental factors. A gene called APOE has been studied extensively as a risk factor for the disease. In particular, a variant of this gene called the e4 allele seems to increase an individual's risk for developing late-onset Alzheimer disease. Researchers are investigating many additional genes that may play a role in Alzheimer disease risk.",Alzheimer disease,0000048,GHR,https://ghr.nlm.nih.gov/condition/alzheimer-disease,C0002395,T047,Disorders
Is Alzheimer disease inherited ?,0000048-4,inheritance,"The early-onset form of Alzheimer disease is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the altered gene from one affected parent.  The inheritance pattern of late-onset Alzheimer disease is uncertain. People who inherit one copy of the APOE e4 allele have an increased chance of developing the disease; those who inherit two copies of the allele are at even greater risk. It is important to note that people with the APOE e4 allele inherit an increased risk of developing Alzheimer disease, not the disease itself. Not all people with Alzheimer disease have the e4 allele, and not all people who have the e4 allele will develop the disease.",Alzheimer disease,0000048,GHR,https://ghr.nlm.nih.gov/condition/alzheimer-disease,C0002395,T047,Disorders
What are the treatments for Alzheimer disease ?,0000048-5,treatment,"These resources address the diagnosis or management of Alzheimer disease:  - Alzheimer's Disease Research Center, Washington University School of Medicine  - Gene Review: Gene Review: Alzheimer Disease Overview  - Gene Review: Gene Review: Early-Onset Familial Alzheimer Disease  - Genetic Testing Registry: Alzheimer disease 2  - Genetic Testing Registry: Alzheimer disease, type 3  - Genetic Testing Registry: Alzheimer disease, type 4  - Genetic Testing Registry: Alzheimer's disease  - MedlinePlus Encyclopedia: Alzheimer's Disease  - Michigan Alzheimer's Disease Research Center  - University of California Davis Alzheimer's Disease Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Alzheimer disease,0000048,GHR,https://ghr.nlm.nih.gov/condition/alzheimer-disease,C0002395,T047,Disorders
What is (are) amelogenesis imperfecta ?,0000049-1,information,"Amelogenesis imperfecta is a disorder of tooth development. This condition causes teeth to be unusually small, discolored, pitted or grooved, and prone to rapid wear and breakage. Other dental abnormalities are also possible. These defects, which vary among affected individuals, can affect both primary (baby) teeth and permanent (adult) teeth.  Researchers have described at least 14 forms of amelogenesis imperfecta. These types are distinguished by their specific dental abnormalities and by their pattern of inheritance. Additionally, amelogenesis imperfecta can occur alone without any other signs and symptoms or it can occur as part of a syndrome that affects multiple parts of the body.",amelogenesis imperfecta,0000049,GHR,https://ghr.nlm.nih.gov/condition/amelogenesis-imperfecta,C0002452,T019,Disorders
How many people are affected by amelogenesis imperfecta ?,0000049-2,frequency,"The exact incidence of amelogenesis imperfecta is uncertain. Estimates vary widely, from 1 in 700 people in northern Sweden to 1 in 14,000 people in the United States.",amelogenesis imperfecta,0000049,GHR,https://ghr.nlm.nih.gov/condition/amelogenesis-imperfecta,C0002452,T019,Disorders
What are the genetic changes related to amelogenesis imperfecta ?,0000049-3,genetic changes,"Mutations in the AMELX, ENAM, MMP20, and FAM83H genes can cause amelogenesis imperfecta. The AMELX, ENAM, and MMP20 genes provide instructions for making proteins that are essential for normal tooth development. Most of these proteins are involved in the formation of enamel, which is the hard, calcium-rich material that forms the protective outer layer of each tooth. Although the function of the protein produced from the FAM83H gene is unknown, it is also believed to be involved in the formation of enamel. Mutations in any of these genes result in altered protein structure or prevent the production of any protein. As a result, tooth enamel is abnormally thin or soft and may have a yellow or brown color. Teeth with defective enamel are weak and easily damaged.  Mutations in the genes described above account for only about half of all cases of the condition, with FAM83H gene mutations causing the majority of these cases. In the remaining cases, the genetic cause has not been identified. Researchers are working to find mutations in other genes that are involved in this disorder.",amelogenesis imperfecta,0000049,GHR,https://ghr.nlm.nih.gov/condition/amelogenesis-imperfecta,C0002452,T019,Disorders
Is amelogenesis imperfecta inherited ?,0000049-4,inheritance,"Amelogenesis imperfecta can have different inheritance patterns depending on the gene that is altered. Many cases are caused by mutations in the FAM83H gene and are inherited in an autosomal dominant pattern. This type of inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. Some cases caused by mutations in the ENAM gene also have an autosomal dominant inheritance pattern.  Amelogenesis imperfecta can also be inherited in an autosomal recessive pattern; this form of the disorder can result from mutations in the ENAM or MMP20 gene. Autosomal recessive inheritance means two copies of the gene in each cell are altered. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  About 5 percent of amelogenesis imperfecta cases are caused by mutations in the AMELX gene and are inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In most cases, males with X-linked amelogenesis imperfecta experience more severe dental abnormalities than females with this form of this condition.  Other cases of amelogenesis imperfecta result from new gene mutations and occur in people with no history of the disorder in their family.",amelogenesis imperfecta,0000049,GHR,https://ghr.nlm.nih.gov/condition/amelogenesis-imperfecta,C0002452,T019,Disorders
What are the treatments for amelogenesis imperfecta ?,0000049-5,treatment,"These resources address the diagnosis or management of amelogenesis imperfecta:  - Genetic Testing Registry: Amelogenesis imperfecta - hypoplastic autosomal dominant - local  - Genetic Testing Registry: Amelogenesis imperfecta, hypocalcification type  - Genetic Testing Registry: Amelogenesis imperfecta, type 1E  - Genetic Testing Registry: Amelogenesis imperfecta, type IC  - MedlinePlus Encyclopedia: Amelogenesis imperfecta  - MedlinePlus Encyclopedia: Tooth - Abnormal Colors   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",amelogenesis imperfecta,0000049,GHR,https://ghr.nlm.nih.gov/condition/amelogenesis-imperfecta,C0002452,T019,Disorders
What is (are) aminoacylase 1 deficiency ?,0000050-1,information,"Aminoacylase 1 deficiency is an inherited disorder that can cause neurological problems; the pattern and severity of signs and symptoms vary widely among affected individuals. Individuals with this condition typically have delayed development of mental and motor skills (psychomotor delay). They can have movement problems, reduced muscle tone (hypotonia), mild intellectual disability, and seizures. However, some people with aminoacylase 1 deficiency have no health problems related to the condition. A key feature common to all people with aminoacylase 1 deficiency is high levels of modified protein building blocks (amino acids), called N-acetylated amino acids, in the urine.",aminoacylase 1 deficiency,0000050,GHR,https://ghr.nlm.nih.gov/condition/aminoacylase-1-deficiency,C1835922,T047,Disorders
How many people are affected by aminoacylase 1 deficiency ?,0000050-2,frequency,The prevalence of aminoacylase 1 deficiency is unknown.,aminoacylase 1 deficiency,0000050,GHR,https://ghr.nlm.nih.gov/condition/aminoacylase-1-deficiency,C1835922,T047,Disorders
What are the genetic changes related to aminoacylase 1 deficiency ?,0000050-3,genetic changes,"Aminoacylase 1 deficiency is caused by mutations in the ACY1 gene. This gene provides instructions for making an enzyme called aminoacylase 1, which is involved in the breakdown of proteins when they are no longer needed. Many proteins in the body have an acetyl group attached to one end. This modification, called N-acetylation, helps protect and stabilize the protein. Aminoacylase 1 performs the final step in the breakdown of these proteins by removing the acetyl group from certain amino acids. The amino acids can then be recycled and used to build other proteins.  Mutations in the ACY1 gene lead to an aminoacylase 1 enzyme with little or no function. Without this enzyme's function, acetyl groups are not efficiently removed from a subset of amino acids during the breakdown of proteins. The excess N-acetylated amino acids are released from the body in urine. It is not known how a reduction of aminoacylase 1 function leads to neurological problems in people with aminoacylase 1 deficiency.",aminoacylase 1 deficiency,0000050,GHR,https://ghr.nlm.nih.gov/condition/aminoacylase-1-deficiency,C1835922,T047,Disorders
Is aminoacylase 1 deficiency inherited ?,0000050-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",aminoacylase 1 deficiency,0000050,GHR,https://ghr.nlm.nih.gov/condition/aminoacylase-1-deficiency,C1835922,T047,Disorders
What are the treatments for aminoacylase 1 deficiency ?,0000050-5,treatment,These resources address the diagnosis or management of aminoacylase 1 deficiency:  - Genetic Testing Registry: Aminoacylase 1 deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,aminoacylase 1 deficiency,0000050,GHR,https://ghr.nlm.nih.gov/condition/aminoacylase-1-deficiency,C1835922,T047,Disorders
What is (are) Amish lethal microcephaly ?,0000051-1,information,"Amish lethal microcephaly is a disorder in which infants are born with a very small head and underdeveloped brain.  Infants with Amish lethal microcephaly have a sloping forehead and an extremely small head size. They may also have an unusually small lower jaw and chin (micrognathia) and an enlarged liver (hepatomegaly).  Affected infants may have seizures and difficulty maintaining their body temperature. Often they become very irritable starting in the second or third month of life. A compound called alpha-ketoglutaric acid can be detected in their urine (alpha-ketoglutaric aciduria), and during episodes of viral illness they tend to develop elevated levels of acid in the blood and tissues (metabolic acidosis). Infants with this disorder typically feed adequately but do not develop skills such as purposeful movement or the ability to track faces and sounds. Affected infants live only about six months.",Amish lethal microcephaly,0000051,GHR,https://ghr.nlm.nih.gov/condition/amish-lethal-microcephaly,C3151529,T047,Disorders
How many people are affected by Amish lethal microcephaly ?,0000051-2,frequency,Amish lethal microcephaly occurs in approximately 1 in 500 newborns in the Old Order Amish population of Pennsylvania. It has not been found outside this population.,Amish lethal microcephaly,0000051,GHR,https://ghr.nlm.nih.gov/condition/amish-lethal-microcephaly,C3151529,T047,Disorders
What are the genetic changes related to Amish lethal microcephaly ?,0000051-3,genetic changes,"Mutations in the SLC25A19 gene cause Amish lethal microcephaly.  The SLC25A19 gene provides instructions for producing a protein that is a member of the solute carrier (SLC) family of proteins. Proteins in the SLC family transport various compounds across the membranes surrounding the cell and its component parts. The protein produced from the SLC25A19 gene transports a molecule called thiamine pyrophosphate into the mitochondria, the energy-producing centers of cells. This compound is involved in the activity of a group of mitochondrial enzymes called the dehydrogenase complexes, one of which is the alpha-ketoglutarate dehydrogenase complex. The transport of thiamine pyrophosphate into the mitochondria is believed to be important in brain development.  All known individuals with Amish lethal microcephaly have a mutation in which the protein building block (amino acid) alanine is substituted for the amino acid glycine at position 177 of the SLC25A19 protein, written as Gly177Ala or G177A. Researchers believe that this mutation interferes with the transport of thiamine pyrophosphate into the mitochondria and the activity of the alpha-ketoglutarate dehydrogenase complex, resulting in the abnormal brain development and alpha-ketoglutaric aciduria seen in Amish lethal microcephaly.",Amish lethal microcephaly,0000051,GHR,https://ghr.nlm.nih.gov/condition/amish-lethal-microcephaly,C3151529,T047,Disorders
Is Amish lethal microcephaly inherited ?,0000051-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Amish lethal microcephaly,0000051,GHR,https://ghr.nlm.nih.gov/condition/amish-lethal-microcephaly,C3151529,T047,Disorders
What are the treatments for Amish lethal microcephaly ?,0000051-5,treatment,These resources address the diagnosis or management of Amish lethal microcephaly:  - Gene Review: Gene Review: Amish Lethal Microcephaly  - Genetic Testing Registry: Amish lethal microcephaly  - MedlinePlus Encyclopedia: Microcephaly   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Amish lethal microcephaly,0000051,GHR,https://ghr.nlm.nih.gov/condition/amish-lethal-microcephaly,C3151529,T047,Disorders
What is (are) amyotrophic lateral sclerosis ?,0000052-1,information,"Amyotrophic lateral sclerosis (ALS) is a progressive disease that affects motor neurons, which are specialized nerve cells that control muscle movement. These nerve cells are found in the spinal cord and the brain. In ALS, motor neurons die (atrophy) over time, leading to muscle weakness, a loss of muscle mass, and an inability to control movement.  There are many different types of ALS; these types are distinguished by their signs and symptoms and their genetic cause or lack of clear genetic association. Most people with ALS have a form of the condition that is described as sporadic, which means it occurs in people with no apparent history of the disorder in their family. People with sporadic ALS usually first develop features of the condition in their late fifties or early sixties. A small proportion of people with ALS, estimated at 5 to 10 percent, have a family history of ALS or a related condition called frontotemporal dementia (FTD), which is a progressive brain disorder that affects personality, behavior, and language. The signs and symptoms of familial ALS typically first appear in one's late forties or early fifties. Rarely, people with familial ALS develop symptoms in childhood or their teenage years. These individuals have a rare form of the disorder known as juvenile ALS.  The first signs and symptoms of ALS may be so subtle that they are overlooked. The earliest symptoms include muscle twitching, cramping, stiffness, or weakness. Affected individuals may develop slurred speech (dysarthria) and, later, difficulty chewing or swallowing (dysphagia). Many people with ALS experience malnutrition because of reduced food intake due to dysphagia and an increase in their body's energy demands (metabolism) due to prolonged illness. Muscles become weaker as the disease progresses, and arms and legs begin to look thinner as muscle tissue atrophies. Individuals with ALS eventually lose muscle strength and the ability to walk. Affected individuals eventually become wheelchair-dependent and increasingly require help with personal care and other activities of daily living. Over time, muscle weakness causes affected individuals to lose the use of their hands and arms. Breathing becomes difficult because the muscles of the respiratory system weaken. Most people with ALS die from respiratory failure within 2 to 10 years after the signs and symptoms of ALS first appear; however, disease progression varies widely among affected individuals.  Approximately 20 percent of individuals with ALS also develop FTD. Changes in personality and behavior may make it difficult for affected individuals to interact with others in a socially appropriate manner. Communication skills worsen as the disease progresses. It is unclear how the development of ALS and FTD are related. Individuals who develop both conditions are diagnosed as having ALS-FTD.  A rare form of ALS that often runs in families is known as ALS-parkinsonism-dementia complex (ALS-PDC). This disorder is characterized by the signs and symptoms of ALS, in addition to a pattern of movement abnormalities known as parkinsonism, and a progressive loss of intellectual function (dementia). Signs of parkinsonism include unusually slow movements (bradykinesia), stiffness, and tremors. Affected members of the same family can have different combinations of signs and symptoms.",amyotrophic lateral sclerosis,0000052,GHR,https://ghr.nlm.nih.gov/condition/amyotrophic-lateral-sclerosis,C0002736,T047,Disorders
How many people are affected by amyotrophic lateral sclerosis ?,0000052-2,frequency,"About 5,000 people in the United States are diagnosed with ALS each year. Worldwide, this disorder occurs in 2 to 5 per 100,000 individuals. Only a small percentage of cases have a known genetic cause.  Among the Chamorro people of Guam and people from the Kii Peninsula of Japan, ALS-PDC can be 100 times more frequent than ALS is in other populations. ALS-PDC has not been reported outside of these populations.",amyotrophic lateral sclerosis,0000052,GHR,https://ghr.nlm.nih.gov/condition/amyotrophic-lateral-sclerosis,C0002736,T047,Disorders
What are the genetic changes related to amyotrophic lateral sclerosis ?,0000052-3,genetic changes,"Mutations in several genes can cause familial ALS and contribute to the development of sporadic ALS. Mutations in the C9orf72 gene account for 30 to 40 percent of familial ALS in the United States and Europe. Worldwide, SOD1 gene mutations cause 15 to 20 percent of familial ALS, and TARDBP and FUS gene mutations each account for about 5 percent of cases. The other genes that have been associated with familial ALS each account for a small proportion of cases. It is estimated that 60 percent of individuals with familial ALS have an identified genetic mutation. The cause of the condition in the remaining individuals is unknown.  The C9orf72, SOD1, TARDBP, and FUS genes are key to the normal functioning of motor neurons and other cells. It is unclear how mutations in these genes contribute to the death of motor neurons, but it is thought that motor neurons are more sensitive to disruptions in function because of their large size. Most motor neurons affected by ALS have a buildup of protein clumps (aggregates); however, it is unknown whether these aggregates are involved in causing ALS or are a byproduct of the dying cell.  In some cases of familial ALS due to mutations in other genes, studies have identified the mechanisms that lead to ALS. Some gene mutations lead to a disruption in the development of axons, the specialized extensions of nerve cells (such as motor neurons) that transmit nerve impulses. The altered axons may impair transmission of impulses from nerves to muscles, leading to muscle weakness and atrophy. Other mutations lead to a slowing in the transport of materials needed for the proper function of axons in motor neurons, eventually causing the motor neurons to die. Additional gene mutations prevent the breakdown of toxic substances, leading to their buildup in nerve cells. The accumulation of toxic substances can damage motor neurons and eventually cause cell death. In some cases of ALS, it is unknown how the gene mutation causes the condition.  The cause of sporadic ALS is largely unknown but probably involves a combination of genetic and environmental factors. Variations in many genes, including the previously mentioned genes involved in transmission of nerve impulses and transportation of materials within neurons, increase the risk of developing ALS. Gene mutations that are risk factors for ALS may add, delete, or change DNA building blocks (nucleotides), resulting in the production of a protein with an altered or reduced function. While genetic variations have been associated with sporadic ALS, not all genetic factors have been identified and it is unclear how most genetic changes influence the development of the disease. People with a gene variation that increases their risk of ALS likely require additional genetic and environmental triggers to develop the disorder.",amyotrophic lateral sclerosis,0000052,GHR,https://ghr.nlm.nih.gov/condition/amyotrophic-lateral-sclerosis,C0002736,T047,Disorders
Is amyotrophic lateral sclerosis inherited ?,0000052-4,inheritance,"About 90 to 95 percent of ALS cases are sporadic, which means they are not inherited.  An estimated 5 to 10 percent of ALS is familial and caused by mutations in one of several genes. The pattern of inheritance varies depending on the gene involved. Most cases are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition. Some people who inherit a familial genetic mutation known to cause ALS never develop features of the condition. (This situation is known as reduced penetrance.) It is unclear why some people with a mutated gene develop the disease and other people with a mutated gene do not.  Less frequently, ALS is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Because an affected person's parents are not affected, autosomal recessive ALS is often mistaken for sporadic ALS even though it is caused by a familial genetic mutation.  Very rarely, ALS is inherited in an X-linked dominant pattern. X-linked conditions occur when the gene associated with the condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In most cases, males tend to develop the disease earlier and have a decreased life expectancy compared with females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",amyotrophic lateral sclerosis,0000052,GHR,https://ghr.nlm.nih.gov/condition/amyotrophic-lateral-sclerosis,C0002736,T047,Disorders
What are the treatments for amyotrophic lateral sclerosis ?,0000052-5,treatment,These resources address the diagnosis or management of amyotrophic lateral sclerosis:  - Gene Review: Gene Review: ALS2-Related Disorders  - Gene Review: Gene Review: Amyotrophic Lateral Sclerosis Overview  - Gene Review: Gene Review: C9orf72-Related Amyotrophic Lateral Sclerosis and Frontotemporal Dementia  - Gene Review: Gene Review: TARDBP-Related Amyotrophic Lateral Sclerosis  - Genetic Testing Registry: Amyotrophic lateral sclerosis  - Genetic Testing Registry: Amyotrophic lateral sclerosis type 1  - Massachusetts General Hospital: How is ALS Diagnosed?  - MedlinePlus Encyclopedia: Amyotrophic Lateral Sclerosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,amyotrophic lateral sclerosis,0000052,GHR,https://ghr.nlm.nih.gov/condition/amyotrophic-lateral-sclerosis,C0002736,T047,Disorders
What is (are) Andermann syndrome ?,0000053-1,information,"Andermann syndrome is a disorder that damages the nerves used for muscle movement and sensation (motor and sensory neuropathy). Absence (agenesis) or malformation of the tissue connecting the left and right halves of the brain (corpus callosum) also occurs in most people with this disorder.  People affected by Andermann syndrome have abnormal or absent reflexes (areflexia) and weak muscle tone (hypotonia). They experience muscle wasting (amyotrophy), severe progressive weakness and loss of sensation in the limbs, and rhythmic shaking (tremors). They typically begin walking between ages 3 and 4 and lose this ability by their teenage years. As they get older, people with this disorder frequently develop joint deformities called contractures, which restrict the movement of certain joints. Most affected individuals also develop abnormal curvature of the spine (scoliosis), which may require surgery.  Andermann syndrome also results in abnormal function of certain cranial nerves, which emerge directly from the brain and extend to various areas of the head and neck. Cranial nerve problems may result in facial muscle weakness, drooping eyelids (ptosis), and difficulty following movements with the eyes (gaze palsy).  Individuals with Andermann syndrome usually have intellectual disability, which may be mild to severe, and some experience seizures. They may also develop psychiatric symptoms such as depression, anxiety, agitation, paranoia, and hallucinations, which usually appear in adolescence.  Some people with Andermann syndrome have atypical physical features such as widely spaced eyes (ocular hypertelorism); a wide, short skull (brachycephaly); a high arch of the hard palate at the roof of the mouth; a big toe that crosses over the other toes; and partial fusion (syndactyly) of the second and third toes.  Andermann syndrome is associated with a shortened life expectancy, but affected individuals typically live into adulthood.",Andermann syndrome,0000053,GHR,https://ghr.nlm.nih.gov/condition/andermann-syndrome,C0795950,T019,Disorders
How many people are affected by Andermann syndrome ?,0000053-2,frequency,"Andermann syndrome is most often seen in the French-Canadian population of the Saguenay-Lac-St.-Jean and Charlevoix regions of northeastern Quebec. In this population, Andermann syndrome occurs in almost 1 in 2,000 newborns. Only a few individuals with this disorder have been identified in other regions of the world.",Andermann syndrome,0000053,GHR,https://ghr.nlm.nih.gov/condition/andermann-syndrome,C0795950,T019,Disorders
What are the genetic changes related to Andermann syndrome ?,0000053-3,genetic changes,"Mutations in the SLC12A6 gene cause Andermann syndrome. The SLC12A6 gene provides instructions for making a protein called a K-Cl cotransporter. This protein is involved in moving charged atoms (ions) of potassium (K) and chlorine (Cl) across the cell membrane. The positively charged potassium ions and negatively charged chlorine ions are moved together (cotransported), so that the charges inside and outside the cell membrane are unchanged (electroneutral).  Electroneutral cotransport of ions across cell membranes is involved in many functions of the body. While the specific function of the K-Cl cotransporter produced from the SLC12A6 gene is unknown, it seems to be critical for the development and maintenance of nerve tissue. It may be involved in regulating the amounts of potassium, chlorine, or water in cells and intercellular spaces. The K-Cl cotransporter protein may also help regulate the activity of other proteins that are sensitive to ion concentrations.  Mutations in the SLC12A6 gene that cause Andermann syndrome disrupt the function of the K-Cl cotransporter protein. The lack of functional protein normally produced from the SLC12A6 gene is believed to interfere with the development of the corpus callosum and maintenance of the nerves that transmit signals needed for movement and sensation, resulting in the signs and symptoms of Andermann syndrome.",Andermann syndrome,0000053,GHR,https://ghr.nlm.nih.gov/condition/andermann-syndrome,C0795950,T019,Disorders
Is Andermann syndrome inherited ?,0000053-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Andermann syndrome,0000053,GHR,https://ghr.nlm.nih.gov/condition/andermann-syndrome,C0795950,T019,Disorders
What are the treatments for Andermann syndrome ?,0000053-5,treatment,These resources address the diagnosis or management of Andermann syndrome:  - Gene Review: Gene Review: Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum  - Genetic Testing Registry: Andermann syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Andermann syndrome,0000053,GHR,https://ghr.nlm.nih.gov/condition/andermann-syndrome,C0795950,T019,Disorders
What is (are) Andersen-Tawil syndrome ?,0000054-1,information,"Anderson-Tawil syndrome is a disorder that causes episodes of muscle weakness (periodic paralysis), changes in heart rhythm (arrhythmia), and developmental abnormalities. The most common changes affecting the heart are ventricular arrhythmia, which is a disruption in the rhythm of the heart's lower chambers, and long QT syndrome. Long QT syndrome is a heart condition that causes the heart (cardiac) muscle to take longer than usual to recharge between beats. If untreated, the irregular heartbeats can lead to discomfort, fainting (syncope), or cardiac arrest.  Physical abnormalities associated with Andersen-Tawil syndrome typically affect the head, face, and limbs. These features often include a very small lower jaw (micrognathia), dental abnormalities, low-set ears, widely spaced eyes, and unusual curving of the fingers or toes (clinodactyly). Some affected people also have short stature and an abnormal curvature of the spine (scoliosis).  Two types of Andersen-Tawil syndrome are distinguished by their genetic causes. Type 1, which accounts for about 60 percent of all cases of the disorder, is caused by mutations in the KCNJ2 gene. The remaining 40 percent of cases are designated as type 2; the cause of these cases is unknown.",Andersen-Tawil syndrome,0000054,GHR,https://ghr.nlm.nih.gov/condition/andersen-tawil-syndrome,C1563715,T047,Disorders
How many people are affected by Andersen-Tawil syndrome ?,0000054-2,frequency,Andersen-Tawil syndrome is a rare genetic disorder; its incidence is unknown. About 100 people with this condition have been reported worldwide.,Andersen-Tawil syndrome,0000054,GHR,https://ghr.nlm.nih.gov/condition/andersen-tawil-syndrome,C1563715,T047,Disorders
What are the genetic changes related to Andersen-Tawil syndrome ?,0000054-3,genetic changes,"Mutations in the KCNJ2 gene cause Andersen-Tawil syndrome.  The KCNJ2 gene provides instructions for making a protein that forms a channel across cell membranes. This channel transports positively charged atoms (ions) of potassium into muscle cells. The movement of potassium ions through these channels is critical for maintaining the normal functions of muscles used for movement (skeletal muscles) and cardiac muscle. Mutations in the KCNJ2 gene alter the usual structure and function of potassium channels or prevent the channels from being inserted correctly into the cell membrane. Many mutations prevent a molecule called PIP2 from binding to the channels and effectively regulating their activity. These changes disrupt the flow of potassium ions in skeletal and cardiac muscle, leading to the periodic paralysis and irregular heart rhythm characteristic of Andersen-Tawil syndrome.  Researchers have not determined the role of the KCNJ2 gene in bone development, and it is not known how mutations in the gene lead to the developmental abnormalities often found in Andersen-Tawil syndrome.",Andersen-Tawil syndrome,0000054,GHR,https://ghr.nlm.nih.gov/condition/andersen-tawil-syndrome,C1563715,T047,Disorders
Is Andersen-Tawil syndrome inherited ?,0000054-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, a person with Andersen-Tawil syndrome inherits the mutation from one affected parent. Other cases result from new mutations in the KCNJ2 gene. These cases occur in people with no history of the disorder in their family.",Andersen-Tawil syndrome,0000054,GHR,https://ghr.nlm.nih.gov/condition/andersen-tawil-syndrome,C1563715,T047,Disorders
What are the treatments for Andersen-Tawil syndrome ?,0000054-5,treatment,These resources address the diagnosis or management of Andersen-Tawil syndrome:  - Gene Review: Gene Review: Andersen-Tawil Syndrome  - Genetic Testing Registry: Andersen Tawil syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Andersen-Tawil syndrome,0000054,GHR,https://ghr.nlm.nih.gov/condition/andersen-tawil-syndrome,C1563715,T047,Disorders
What is (are) androgen insensitivity syndrome ?,0000055-1,information,"Androgen insensitivity syndrome is a condition that affects sexual development before birth and during puberty. People with this condition are genetically male, with one X chromosome and one Y chromosome in each cell. Because their bodies are unable to respond to certain male sex hormones (called androgens), they may have mostly female sex characteristics or signs of both male and female sexual development.  Complete androgen insensitivity syndrome occurs when the body cannot use androgens at all. People with this form of the condition have the external sex characteristics of females, but do not have a uterus and therefore do not menstruate and are unable to conceive a child (infertile). They are typically raised as females and have a female gender identity. Affected individuals have male internal sex organs (testes) that are undescended, which means they are abnormally located in the pelvis or abdomen. Undescended testes can become cancerous later in life if they are not surgically removed. People with complete androgen insensitivity syndrome also have sparse or absent hair in the pubic area and under the arms.  The partial and mild forms of androgen insensitivity syndrome result when the body's tissues are partially sensitive to the effects of androgens. People with partial androgen insensitivity (also called Reifenstein syndrome) can have normal female sex characteristics, both male and female sex characteristics, or normal male sex characteristics. They may be raised as males or as females, and may have a male or a female gender identity. People with mild androgen insensitivity are born with male sex characteristics, but are often infertile and tend to experience breast enlargement at puberty.",androgen insensitivity syndrome,0000055,GHR,https://ghr.nlm.nih.gov/condition/androgen-insensitivity-syndrome,C0936016,T047,Disorders
How many people are affected by androgen insensitivity syndrome ?,0000055-2,frequency,"Complete androgen insensitivity syndrome affects 2 to 5 per 100,000 people who are genetically male. Partial androgen insensitivity is thought to be at least as common as complete androgen insensitivity. Mild androgen insensitivity is much less common.",androgen insensitivity syndrome,0000055,GHR,https://ghr.nlm.nih.gov/condition/androgen-insensitivity-syndrome,C0936016,T047,Disorders
What are the genetic changes related to androgen insensitivity syndrome ?,0000055-3,genetic changes,"Mutations in the AR gene cause androgen insensitivity syndrome. This gene provides instructions for making a protein called an androgen receptor. Androgen receptors allow cells to respond to androgens, which are hormones (such as testosterone) that direct male sexual development. Androgens and androgen receptors also have other important functions in both males and females, such as regulating hair growth and sex drive. Mutations in the AR gene prevent androgen receptors from working properly, which makes cells less responsive to androgens or prevents cells from using these hormones at all. Depending on the level of androgen insensitivity, an affected person's sex characteristics can vary from mostly female to mostly male.",androgen insensitivity syndrome,0000055,GHR,https://ghr.nlm.nih.gov/condition/androgen-insensitivity-syndrome,C0936016,T047,Disorders
Is androgen insensitivity syndrome inherited ?,0000055-4,inheritance,"This condition is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In genetic males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In genetic females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females.  About two-thirds of all cases of androgen insensitivity syndrome are inherited from mothers who carry an altered copy of the AR gene on one of their two X chromosomes. The remaining cases result from a new mutation that can occur in the mother's egg cell before the child is conceived or during early fetal development.",androgen insensitivity syndrome,0000055,GHR,https://ghr.nlm.nih.gov/condition/androgen-insensitivity-syndrome,C0936016,T047,Disorders
What are the treatments for androgen insensitivity syndrome ?,0000055-5,treatment,These resources address the diagnosis or management of androgen insensitivity syndrome:  - Gene Review: Gene Review: Androgen Insensitivity Syndrome  - Genetic Testing Registry: Androgen resistance syndrome  - MedlinePlus Encyclopedia: Androgen Insensitivity Syndrome  - MedlinePlus Encyclopedia: Intersex  - MedlinePlus Encyclopedia: Reifenstein Syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,androgen insensitivity syndrome,0000055,GHR,https://ghr.nlm.nih.gov/condition/androgen-insensitivity-syndrome,C0936016,T047,Disorders
What is (are) androgenetic alopecia ?,0000056-1,information,"Androgenetic alopecia is a common form of hair loss in both men and women. In men, this condition is also known as male-pattern baldness. Hair is lost in a well-defined pattern, beginning above both temples. Over time, the hairline recedes to form a characteristic ""M"" shape. Hair also thins at the crown (near the top of the head), often progressing to partial or complete baldness.  The pattern of hair loss in women differs from male-pattern baldness. In women, the hair becomes thinner all over the head, and the hairline does not recede. Androgenetic alopecia in women rarely leads to total baldness.  Androgenetic alopecia in men has been associated with several other medical conditions including coronary heart disease and enlargement of the prostate. Additionally, prostate cancer, disorders of insulin resistance (such as diabetes and obesity), and high blood pressure (hypertension) have been related to androgenetic alopecia. In women, this form of hair loss is associated with an increased risk of polycystic ovary syndrome (PCOS). PCOS is characterized by a hormonal imbalance that can lead to irregular menstruation, acne, excess hair elsewhere on the body (hirsutism), and weight gain.",androgenetic alopecia,0000056,GHR,https://ghr.nlm.nih.gov/condition/androgenetic-alopecia,C0162311,T047,Disorders
How many people are affected by androgenetic alopecia ?,0000056-2,frequency,"Androgenetic alopecia is a frequent cause of hair loss in both men and women. This form of hair loss affects an estimated 50 million men and 30 million women in the United States. Androgenetic alopecia can start as early as a person's teens and risk increases with age; more than 50 percent of men over age 50 have some degree of hair loss. In women, hair loss is most likely after menopause.",androgenetic alopecia,0000056,GHR,https://ghr.nlm.nih.gov/condition/androgenetic-alopecia,C0162311,T047,Disorders
What are the genetic changes related to androgenetic alopecia ?,0000056-3,genetic changes,"A variety of genetic and environmental factors likely play a role in causing androgenetic alopecia. Although researchers are studying risk factors that may contribute to this condition, most of these factors remain unknown. Researchers have determined that this form of hair loss is related to hormones called androgens, particularly an androgen called dihydrotestosterone. Androgens are important for normal male sexual development before birth and during puberty. Androgens also have other important functions in both males and females, such as regulating hair growth and sex drive.  Hair growth begins under the skin in structures called follicles. Each strand of hair normally grows for 2 to 6 years, goes into a resting phase for several months, and then falls out. The cycle starts over when the follicle begins growing a new hair. Increased levels of androgens in hair follicles can lead to a shorter cycle of hair growth and the growth of shorter and thinner strands of hair. Additionally, there is a delay in the growth of new hair to replace strands that are shed.  Although researchers suspect that several genes play a role in androgenetic alopecia, variations in only one gene, AR, have been confirmed in scientific studies. The AR gene provides instructions for making a protein called an androgen receptor. Androgen receptors allow the body to respond appropriately to dihydrotestosterone and other androgens. Studies suggest that variations in the AR gene lead to increased activity of androgen receptors in hair follicles. It remains unclear, however, how these genetic changes increase the risk of hair loss in men and women with androgenetic alopecia.  Researchers continue to investigate the connection between androgenetic alopecia and other medical conditions, such as coronary heart disease and prostate cancer in men and polycystic ovary syndrome in women. They believe that some of these disorders may be associated with elevated androgen levels, which may help explain why they tend to occur with androgen-related hair loss. Other hormonal, environmental, and genetic factors that have not been identified also may be involved.",androgenetic alopecia,0000056,GHR,https://ghr.nlm.nih.gov/condition/androgenetic-alopecia,C0162311,T047,Disorders
Is androgenetic alopecia inherited ?,0000056-4,inheritance,"The inheritance pattern of androgenetic alopecia is unclear because many genetic and environmental factors are likely to be involved. This condition tends to cluster in families, however, and having a close relative with patterned hair loss appears to be a risk factor for developing the condition.",androgenetic alopecia,0000056,GHR,https://ghr.nlm.nih.gov/condition/androgenetic-alopecia,C0162311,T047,Disorders
What are the treatments for androgenetic alopecia ?,0000056-5,treatment,"These resources address the diagnosis or management of androgenetic alopecia:  - Genetic Testing Registry: Baldness, male pattern  - MedlinePlus Encyclopedia: Female Pattern Baldness  - MedlinePlus Encyclopedia: Hair Loss  - MedlinePlus Encyclopedia: Male Pattern Baldness   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",androgenetic alopecia,0000056,GHR,https://ghr.nlm.nih.gov/condition/androgenetic-alopecia,C0162311,T047,Disorders
What is (are) anencephaly ?,0000057-1,information,"Anencephaly is a condition that prevents the normal development of the brain and the bones of the skull. This condition results when a structure called the neural tube fails to close during the first few weeks of embryonic development. The neural tube is a layer of cells that ultimately develops into the brain and spinal cord. Because anencephaly is caused by abnormalities of the neural tube, it is classified as a neural tube defect.  Because the neural tube fails to close properly, the developing brain and spinal cord are exposed to the amniotic fluid that surrounds the fetus in the womb. This exposure causes the nervous system tissue to break down (degenerate). As a result, people with anencephaly are missing large parts of the brain called the cerebrum and cerebellum. These brain regions are necessary for thinking, hearing, vision, emotion, and coordinating movement. The bones of the skull are also missing or incompletely formed.  Because these nervous system abnormalities are so severe, almost all babies with anencephaly die before birth or within a few hours or days after birth.",anencephaly,0000057,GHR,https://ghr.nlm.nih.gov/condition/anencephaly,C2021655,T019,Disorders
How many people are affected by anencephaly ?,0000057-2,frequency,"Anencephaly is one of the most common types of neural tube defect, affecting about 1 in 1,000 pregnancies. However, most of these pregnancies end in miscarriage, so the prevalence of this condition in newborns is much lower. An estimated 1 in 10,000 infants in the United States is born with anencephaly.",anencephaly,0000057,GHR,https://ghr.nlm.nih.gov/condition/anencephaly,C2021655,T019,Disorders
What are the genetic changes related to anencephaly ?,0000057-3,genetic changes,"Anencephaly is a complex condition that is likely caused by the interaction of multiple genetic and environmental factors. Some of these factors have been identified, but many remain unknown.  Changes in dozens of genes in individuals with anencephaly and in their mothers may influence the risk of developing this type of neural tube defect. The best-studied of these genes is MTHFR, which provides instructions for making a protein that is involved in processing the vitamin folate (also called vitamin B9). A shortage (deficiency) of this vitamin is an established risk factor for neural tube defects. Changes in other genes related to folate processing and genes involved in the development of the neural tube have also been studied as potential risk factors for anencephaly. However, none of these genes appears to play a major role in causing the condition.  Researchers have also examined environmental factors that could contribute to the risk of anencephaly. As mentioned above, folate deficiency appears to play a significant role. Studies have shown that women who take supplements containing folic acid (the synthetic form of folate) before they get pregnant and very early in their pregnancy are significantly less likely to have a baby with a neural tube defect, including anencephaly. Other possible maternal risk factors for anencephaly include diabetes mellitus, obesity, exposure to high heat (such as a fever or use of a hot tub or sauna) in early pregnancy, and the use of certain anti-seizure medications during pregnancy. However, it is unclear how these factors may influence the risk of anencephaly.",anencephaly,0000057,GHR,https://ghr.nlm.nih.gov/condition/anencephaly,C2021655,T019,Disorders
Is anencephaly inherited ?,0000057-4,inheritance,"Most cases of anencephaly are sporadic, which means they occur in people with no history of the disorder in their family. A small percentage of cases have been reported to run in families; however, the condition does not have a clear pattern of inheritance. For parents who have had a child with anencephaly, the risk of having another affected child is increased compared with the risk in the general population.",anencephaly,0000057,GHR,https://ghr.nlm.nih.gov/condition/anencephaly,C2021655,T019,Disorders
What are the treatments for anencephaly ?,0000057-5,treatment,"These resources address the diagnosis or management of anencephaly:  - Children's Hospital of Philadelphia  - Genetic Testing Registry: Anencephalus  - Genetic Testing Registry: Neural tube defect  - Genetic Testing Registry: Neural tube defects, folate-sensitive   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",anencephaly,0000057,GHR,https://ghr.nlm.nih.gov/condition/anencephaly,C2021655,T019,Disorders
What is (are) Angelman syndrome ?,0000058-1,information,"Angelman syndrome is a complex genetic disorder that primarily affects the nervous system. Characteristic features of this condition include delayed development, intellectual disability, severe speech impairment, and problems with movement and balance (ataxia). Most affected children also have recurrent seizures (epilepsy) and a small head size (microcephaly). Delayed development becomes noticeable by the age of 6 to 12 months, and other common signs and symptoms usually appear in early childhood.  Children with Angelman syndrome typically have a happy, excitable demeanor with frequent smiling, laughter, and hand-flapping movements. Hyperactivity, a short attention span, and a fascination with water are common. Most affected children also have difficulty sleeping and need less sleep than usual.  With age, people with Angelman syndrome become less excitable, and the sleeping problems tend to improve. However, affected individuals continue to have intellectual disability, severe speech impairment, and seizures throughout their lives. Adults with Angelman syndrome have distinctive facial features that may be described as ""coarse."" Other common features include unusually fair skin with light-colored hair and an abnormal side-to-side curvature of the spine (scoliosis). The life expectancy of people with this condition appears to be nearly normal.",Angelman syndrome,0000058,GHR,https://ghr.nlm.nih.gov/condition/angelman-syndrome,C0162635,T047,Disorders
How many people are affected by Angelman syndrome ?,0000058-2,frequency,"Angelman syndrome affects an estimated 1 in 12,000 to 20,000 people.",Angelman syndrome,0000058,GHR,https://ghr.nlm.nih.gov/condition/angelman-syndrome,C0162635,T047,Disorders
What are the genetic changes related to Angelman syndrome ?,0000058-3,genetic changes,"Many of the characteristic features of Angelman syndrome result from the loss of function of a gene called UBE3A. People normally inherit one copy of the UBE3A gene from each parent. Both copies of this gene are turned on (active) in many of the body's tissues. In certain areas of the brain, however, only the copy inherited from a person's mother (the maternal copy) is active. This parent-specific gene activation is caused by a phenomenon called genomic imprinting. If the maternal copy of the UBE3A gene is lost because of a chromosomal change or a gene mutation, a person will have no active copies of the gene in some parts of the brain.  Several different genetic mechanisms can inactivate or delete the maternal copy of the UBE3A gene. Most cases of Angelman syndrome (about 70 percent) occur when a segment of the maternal chromosome 15 containing this gene is deleted. In other cases (about 11 percent), Angelman syndrome is caused by a mutation in the maternal copy of the UBE3A gene.  In a small percentage of cases, Angelman syndrome results when a person inherits two copies of chromosome 15 from his or her father (paternal copies) instead of one copy from each parent. This phenomenon is called paternal uniparental disomy. Rarely, Angelman syndrome can also be caused by a chromosomal rearrangement called a translocation, or by a mutation or other defect in the region of DNA that controls activation of the UBE3A gene. These genetic changes can abnormally turn off (inactivate) UBE3A or other genes on the maternal copy of chromosome 15.  The causes of Angelman syndrome are unknown in 10 to 15 percent of affected individuals. Changes involving other genes or chromosomes may be responsible for the disorder in these cases.  In some people who have Angelman syndrome, the loss of a gene called OCA2 is associated with light-colored hair and fair skin. The OCA2 gene is located on the segment of chromosome 15 that is often deleted in people with this disorder. However, loss of the OCA2 gene does not cause the other signs and symptoms of Angelman syndrome. The protein produced from this gene helps determine the coloring (pigmentation) of the skin, hair, and eyes.",Angelman syndrome,0000058,GHR,https://ghr.nlm.nih.gov/condition/angelman-syndrome,C0162635,T047,Disorders
Is Angelman syndrome inherited ?,0000058-4,inheritance,"Most cases of Angelman syndrome are not inherited, particularly those caused by a deletion in the maternal chromosome 15 or by paternal uniparental disomy. These genetic changes occur as random events during the formation of reproductive cells (eggs and sperm) or in early embryonic development. Affected people typically have no history of the disorder in their family.  Rarely, a genetic change responsible for Angelman syndrome can be inherited. For example, it is possible for a mutation in the UBE3A gene or in the nearby region of DNA that controls gene activation to be passed from one generation to the next.",Angelman syndrome,0000058,GHR,https://ghr.nlm.nih.gov/condition/angelman-syndrome,C0162635,T047,Disorders
What are the treatments for Angelman syndrome ?,0000058-5,treatment,These resources address the diagnosis or management of Angelman syndrome:  - Gene Review: Gene Review: Angelman Syndrome  - Genetic Testing Registry: Angelman syndrome  - MedlinePlus Encyclopedia: Speech Disorders   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Angelman syndrome,0000058,GHR,https://ghr.nlm.nih.gov/condition/angelman-syndrome,C0162635,T047,Disorders
What is (are) anhidrotic ectodermal dysplasia with immune deficiency ?,0000059-1,information,"Anhidrotic ectodermal dysplasia with immune deficiency (EDA-ID) is a form of ectodermal dysplasia, which is a group of conditions characterized by abnormal development of ectodermal tissues including the skin, hair, teeth, and sweat glands. In addition, immune system function is reduced in people with EDA-ID. The signs and symptoms of EDA-ID are evident soon after birth.  Skin abnormalities in people with EDA-ID include areas that are dry, wrinkled, or darker in color than the surrounding skin. Affected individuals tend to have sparse scalp and body hair (hypotrichosis). EDA-ID is also characterized by missing teeth (hypodontia) or teeth that are small and pointed. Most people with EDA-ID have a reduced ability to sweat (hypohidrosis) because they have fewer sweat glands than normal or their sweat glands do not function properly. An inability to sweat (anhidrosis) can lead to a dangerously high body temperature (hyperthermia), particularly in hot weather.  The immune deficiency in EDA-ID varies among people with this condition. People with EDA-ID often produce abnormally low levels of proteins called antibodies or immunoglobulins. Antibodies help protect the body against infection by attaching to specific foreign particles and germs, marking them for destruction. A reduction in antibodies makes it difficult for people with this disorder to fight off infections. In EDA-ID, immune system cells called T cells and B cells have a decreased ability to recognize and respond to foreign invaders (such as bacteria, viruses, and yeast) that have sugar molecules attached to their surface (glycan antigens). Other key aspects of the immune system may also be impaired, leading to recurrent infections.  People with EDA-ID commonly get infections in the lungs (pneumonia), ears (otitis media), sinuses (sinusitis), lymph nodes (lymphadenitis), skin, bones, and GI tract. Approximately one quarter of individuals with EDA-ID have disorders involving abnormal inflammation, such as inflammatory bowel disease or rheumatoid arthritis.  The life expectancy of affected individuals depends of the severity of the immune deficiency; most people with this condition do not live past childhood.  There are two forms of this condition that have similar signs and symptoms and are distinguished by the modes of inheritance: X-linked recessive or autosomal dominant.",anhidrotic ectodermal dysplasia with immune deficiency,0000059,GHR,https://ghr.nlm.nih.gov/condition/anhidrotic-ectodermal-dysplasia-with-immune-deficiency,C0013575,T019,Disorders
How many people are affected by anhidrotic ectodermal dysplasia with immune deficiency ?,0000059-2,frequency,"The prevalence of the X-linked recessive type of EDA-ID is estimated to be 1 in 250,000 individuals. Only a few cases of the autosomal dominant form have been described in the scientific literature.",anhidrotic ectodermal dysplasia with immune deficiency,0000059,GHR,https://ghr.nlm.nih.gov/condition/anhidrotic-ectodermal-dysplasia-with-immune-deficiency,C0013575,T019,Disorders
What are the genetic changes related to anhidrotic ectodermal dysplasia with immune deficiency ?,0000059-3,genetic changes,"Mutations in the IKBKG gene cause X-linked recessive EDA-ID, and mutations in the NFKBIA gene cause autosomal dominant EDA-ID. The proteins produced from these two genes regulate nuclear factor-kappa-B. Nuclear factor-kappa-B is a group of related proteins (a protein complex) that binds to DNA and controls the activity of other genes, including genes that direct the body's immune responses and inflammatory reactions. It also protects cells from certain signals that would otherwise cause them to self-destruct (undergo apoptosis).  The IKBKG and NFKBIA gene mutations responsible for EDA-ID result in the production of proteins with impaired function, which reduces activation of nuclear factor-kappa-B. These changes disrupt certain signaling pathways within immune cells, resulting in immune deficiency. It is unclear how gene mutations alter the development of the skin, teeth, sweat glands, and other tissues, although it is likely caused by abnormal nuclear factor-kappa-B signaling in other types of cells.",anhidrotic ectodermal dysplasia with immune deficiency,0000059,GHR,https://ghr.nlm.nih.gov/condition/anhidrotic-ectodermal-dysplasia-with-immune-deficiency,C0013575,T019,Disorders
Is anhidrotic ectodermal dysplasia with immune deficiency inherited ?,0000059-4,inheritance,"When EDA-ID is caused by mutations in the IKBKG gene, it is inherited in an X-linked recessive pattern. The IKBKG gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of the IKBKG gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  When EDA-ID is caused by mutations in the NFKBIA gene, the condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",anhidrotic ectodermal dysplasia with immune deficiency,0000059,GHR,https://ghr.nlm.nih.gov/condition/anhidrotic-ectodermal-dysplasia-with-immune-deficiency,C0013575,T019,Disorders
What are the treatments for anhidrotic ectodermal dysplasia with immune deficiency ?,0000059-5,treatment,These resources address the diagnosis or management of anhidrotic ectodermal dysplasia with immune deficiency:  - Genetic Testing Registry: Anhidrotic ectodermal dysplasia with immune deficiency  - Genetic Testing Registry: Hypohidrotic ectodermal dysplasia with immune deficiency  - MedlinePlus Encyclopedia: Immunodeficiency Disorders   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,anhidrotic ectodermal dysplasia with immune deficiency,0000059,GHR,https://ghr.nlm.nih.gov/condition/anhidrotic-ectodermal-dysplasia-with-immune-deficiency,C0013575,T019,Disorders
What is (are) aniridia ?,0000060-1,information,"Aniridia is an eye disorder characterized by a complete or partial absence of the colored part of the eye (the iris). These iris abnormalities may cause the pupils to be abnormal or misshapen. Aniridia can cause reduction in the sharpness of vision (visual acuity) and increased sensitivity to light (photophobia).  People with aniridia can also have other eye problems. Increased pressure in the eye (glaucoma) typically appears in late childhood or early adolescence. Clouding of the lens of the eye (cataracts), occur in 50 percent to 85 percent of people with aniridia. In about 10 percent of affected people, the structures that carry information from the eyes to the brain (optic nerves) are underdeveloped. Individuals with aniridia may also have involuntary eye movements (nystagmus) or underdevelopment of the region at the back of the eye responsible for sharp central vision (foveal hypoplasia). Many of these eye problems contribute to progressive vision loss in affected individuals. The severity of symptoms is typically the same in both eyes.  Rarely, people with aniridia have behavioral problems, developmental delay, and problems detecting odors.",aniridia,0000060,GHR,https://ghr.nlm.nih.gov/condition/aniridia,C0003076,T019,Disorders
How many people are affected by aniridia ?,0000060-2,frequency,"Aniridia occurs in 1 in 50,000 to 100,000 newborns worldwide.",aniridia,0000060,GHR,https://ghr.nlm.nih.gov/condition/aniridia,C0003076,T019,Disorders
What are the genetic changes related to aniridia ?,0000060-3,genetic changes,"Aniridia is caused by mutations in the PAX6 gene. The PAX6 gene provides instructions for making a protein that is involved in the early development of the eyes, brain and spinal cord (central nervous system), and the pancreas. Within the brain, the PAX6 protein is involved in the development of a specialized group of brain cells that process smell (the olfactory bulb). The PAX6 protein attaches (binds) to specific regions of DNA and regulates the activity of other genes. On the basis of this role, the PAX6 protein is called a transcription factor. Following birth, the PAX6 protein regulates several genes that likely contribute to the maintenance of different eye structures.  Mutations in the PAX6 gene result in the production of a nonfunctional PAX6 protein that is unable to bind to DNA and regulate the activity of other genes. A lack of functional PAX6 protein disrupts the formation of the eyes during embryonic development.",aniridia,0000060,GHR,https://ghr.nlm.nih.gov/condition/aniridia,C0003076,T019,Disorders
Is aniridia inherited ?,0000060-4,inheritance,"Aniridia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In approximately two-thirds of cases, an affected person inherits the mutation from one affected parent. The remaining one-third of cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",aniridia,0000060,GHR,https://ghr.nlm.nih.gov/condition/aniridia,C0003076,T019,Disorders
What are the treatments for aniridia ?,0000060-5,treatment,These resources address the diagnosis or management of aniridia:  - Gene Review: Gene Review: Aniridia  - Genetic Testing Registry: Congenital aniridia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,aniridia,0000060,GHR,https://ghr.nlm.nih.gov/condition/aniridia,C0003076,T019,Disorders
What is (are) ankyloblepharon-ectodermal defects-cleft lip/palate syndrome ?,0000061-1,information,"Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a form of ectodermal dysplasia, a group of about 150 conditions characterized by abnormal development of ectodermal tissues including the skin, hair, nails, teeth, and sweat glands.  Among the most common features of AEC syndrome are missing patches of skin (erosions). In affected infants, skin erosions most commonly occur on the scalp. They tend to recur throughout childhood and into adulthood, frequently affecting the scalp, neck, hands, and feet. The skin erosions range from mild to severe and can lead to infection, scarring, and hair loss. Other ectodermal abnormalities in AEC syndrome include changes in skin coloring; brittle, sparse, or missing hair; misshapen or absent fingernails and toenails; and malformed or missing teeth. Affected individuals also report increased sensitivity to heat and a reduced ability to sweat.  Many infants with AEC syndrome are born with an eyelid condition known as ankyloblepharon filiforme adnatum, in which strands of tissue partially or completely fuse the upper and lower eyelids. Most people with AEC syndrome are also born with an opening in the roof of the mouth (a cleft palate), a split in the lip (a cleft lip), or both. Cleft lip or cleft palate can make it difficult for affected infants to suck, so these infants often have trouble feeding and do not grow and gain weight at the expected rate (failure to thrive).  Additional features of AEC syndrome can include limb abnormalities, most commonly fused fingers and toes (syndactyly). Less often, affected individuals have permanently bent fingers and toes (camptodactyly) or a deep split in the hands or feet with missing fingers or toes and fusion of the remaining digits (ectrodactyly). Hearing loss is common, occurring in more than 90 percent of children with AEC syndrome. Some affected individuals have distinctive facial features, such as small jaws that cannot open fully and a narrow space between the upper lip and nose (philtrum). Other signs and symptoms can include the opening of the urethra on the underside of the penis (hypospadias) in affected males, digestive problems, absent tear duct openings in the eyes, and chronic sinus or ear infections.  A condition known as Rapp-Hodgkin syndrome has signs and symptoms that overlap considerably with those of AEC syndrome. These two syndromes were classified as separate disorders until it was discovered that they both result from mutations in the same part of the same gene. Most researchers now consider Rapp-Hodgkin syndrome and AEC syndrome to be part of the same disease spectrum.",ankyloblepharon-ectodermal defects-cleft lip/palate syndrome,0000061,GHR,https://ghr.nlm.nih.gov/condition/ankyloblepharon-ectodermal-defects-cleft-lip-palate-syndrome,C0406709,T019,Disorders
How many people are affected by ankyloblepharon-ectodermal defects-cleft lip/palate syndrome ?,0000061-2,frequency,"AEC syndrome is a rare condition; its prevalence is unknown. All forms of ectodermal dysplasia together occur in about 1 in 100,000 newborns in the United States.",ankyloblepharon-ectodermal defects-cleft lip/palate syndrome,0000061,GHR,https://ghr.nlm.nih.gov/condition/ankyloblepharon-ectodermal-defects-cleft-lip-palate-syndrome,C0406709,T019,Disorders
What are the genetic changes related to ankyloblepharon-ectodermal defects-cleft lip/palate syndrome ?,0000061-3,genetic changes,"AEC syndrome is caused by mutations in the TP63 gene. This gene provides instructions for making a protein known as p63, which plays an essential role in early development. The p63 protein is a transcription factor, which means that it attaches (binds) to DNA and controls the activity of particular genes. The p63 protein turns many different genes on and off during development. It appears to be especially critical for the development of ectodermal structures, such as the skin, hair, teeth, and nails. Studies suggest that it also plays important roles in the development of the limbs, facial features, urinary system, and other organs and tissues.  The TP63 gene mutations responsible for AEC syndrome interfere with the ability of p63 to turn target genes on and off at the right times. It is unclear how these changes lead to abnormal ectodermal development and the specific features of AEC syndrome.",ankyloblepharon-ectodermal defects-cleft lip/palate syndrome,0000061,GHR,https://ghr.nlm.nih.gov/condition/ankyloblepharon-ectodermal-defects-cleft-lip-palate-syndrome,C0406709,T019,Disorders
Is ankyloblepharon-ectodermal defects-cleft lip/palate syndrome inherited ?,0000061-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",ankyloblepharon-ectodermal defects-cleft lip/palate syndrome,0000061,GHR,https://ghr.nlm.nih.gov/condition/ankyloblepharon-ectodermal-defects-cleft-lip-palate-syndrome,C0406709,T019,Disorders
What are the treatments for ankyloblepharon-ectodermal defects-cleft lip/palate syndrome ?,0000061-5,treatment,These resources address the diagnosis or management of AEC syndrome:  - Gene Review: Gene Review: TP63-Related Disorders  - Genetic Testing Registry: Hay-Wells syndrome of ectodermal dysplasia  - Genetic Testing Registry: Rapp-Hodgkin ectodermal dysplasia syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,ankyloblepharon-ectodermal defects-cleft lip/palate syndrome,0000061,GHR,https://ghr.nlm.nih.gov/condition/ankyloblepharon-ectodermal-defects-cleft-lip-palate-syndrome,C0406709,T019,Disorders
What is (are) ankylosing spondylitis ?,0000062-1,information,"Ankylosing spondylitis is a form of ongoing joint inflammation (chronic inflammatory arthritis) that primarily affects the spine. This condition is characterized by back pain and stiffness that typically appear in adolescence or early adulthood. Over time, back movement gradually becomes limited as the bones of the spine (vertebrae) fuse together. This progressive bony fusion is called ankylosis.  The earliest symptoms of ankylosing spondylitis result from inflammation of the joints between the pelvic bones (the ilia) and the base of the spine (the sacrum). These joints are called sacroiliac joints, and inflammation of these joints is known as sacroiliitis. The inflammation gradually spreads to the joints between the vertebrae, causing a condition called spondylitis. Ankylosing spondylitis can involve other joints as well, including the shoulders, hips, and, less often, the knees. As the disease progresses, it can affect the joints between the spine and ribs, restricting movement of the chest and making it difficult to breathe deeply. People with advanced disease are also more prone to fractures of the vertebrae.  Ankylosing spondylitis affects the eyes in up to 40 percent of cases, leading to episodes of eye inflammation called acute iritis. Acute iritis causes eye pain and increased sensitivity to light (photophobia). Rarely, ankylosing spondylitis can also cause serious complications involving the heart, lungs, and nervous system.",ankylosing spondylitis,0000062,GHR,https://ghr.nlm.nih.gov/condition/ankylosing-spondylitis,C0038013,T047,Disorders
How many people are affected by ankylosing spondylitis ?,0000062-2,frequency,"Ankylosing spondylitis is part of a group of related diseases known as spondyloarthropathies. In the United States, spondyloarthropathies affect 3.5 to 13 per 1,000 people.",ankylosing spondylitis,0000062,GHR,https://ghr.nlm.nih.gov/condition/ankylosing-spondylitis,C0038013,T047,Disorders
What are the genetic changes related to ankylosing spondylitis ?,0000062-3,genetic changes,"Ankylosing spondylitis is likely caused by a combination of genetic and environmental factors, most of which have not been identified. However, researchers have found variations in several genes that influence the risk of developing this disorder.  The HLA-B gene provides instructions for making a protein that plays an important role in the immune system. The HLA-B gene is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). The HLA-B gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. A variation of the HLA-B gene called HLA-B27 increases the risk of developing ankylosing spondylitis. Although many people with ankylosing spondylitis have the HLA-B27 variation, most people with this version of the HLA-B gene never develop the disorder. It is not known how HLA-B27 increases the risk of developing ankylosing spondylitis.  Variations in several additional genes, including ERAP1, IL1A, and IL23R, have also been associated with ankylosing spondylitis. Although these genes play critical roles in the immune system, it is unclear how variations in these genes affect a person's risk of developing ankylosing spondylitis. Changes in genes that have not yet been identified are also believed to affect the chances of developing ankylosing spondylitis and influence the progression of the disorder. Some of these genes likely play a role in the immune system, while others may have different functions. Researchers are working to identify these genes and clarify their role in ankylosing spondylitis.",ankylosing spondylitis,0000062,GHR,https://ghr.nlm.nih.gov/condition/ankylosing-spondylitis,C0038013,T047,Disorders
Is ankylosing spondylitis inherited ?,0000062-4,inheritance,"Although ankylosing spondylitis can occur in more than one person in a family, it is not a purely genetic disease. Multiple genetic and environmental factors likely play a part in determining the risk of developing this disorder. As a result, inheriting a genetic variation linked with ankylosing spondylitis does not mean that a person will develop the condition, even in families in which more than one family member has the disorder. For example, about 80 percent of children who inherit HLA-B27 from a parent with ankylosing spondylitis do not develop the disorder.",ankylosing spondylitis,0000062,GHR,https://ghr.nlm.nih.gov/condition/ankylosing-spondylitis,C0038013,T047,Disorders
What are the treatments for ankylosing spondylitis ?,0000062-5,treatment,These resources address the diagnosis or management of ankylosing spondylitis:  - Genetic Testing Registry: Ankylosing spondylitis  - MedlinePlus Encyclopedia: Ankylosing Spondylitis  - MedlinePlus Encyclopedia: HLA-B27 Antigen   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,ankylosing spondylitis,0000062,GHR,https://ghr.nlm.nih.gov/condition/ankylosing-spondylitis,C0038013,T047,Disorders
What is (are) antiphospholipid syndrome ?,0000063-1,information,"Antiphospholipid syndrome is a disorder characterized by an increased tendency to form abnormal blood clots (thromboses) that can block blood vessels. This clotting tendency is known as thrombophilia. In antiphospholipid syndrome, the thromboses can develop in nearly any blood vessel in the body, but most frequently occur in the vessels of the lower limbs. If a blood clot forms in the vessels in the brain, blood flow is impaired and can lead to stroke. Antiphospholipid syndrome is an autoimmune disorder. Autoimmune disorders occur when the immune system attacks the body's own tissues and organs.  Women with antiphospholipid syndrome are at increased risk of complications during pregnancy. These complications include pregnancy-induced high blood pressure (preeclampsia), an underdeveloped placenta (placental insufficiency), early delivery, or pregnancy loss (miscarriage). In addition, women with antiphospholipid syndrome are at greater risk of having a thrombosis during pregnancy than at other times during their lives. At birth, infants of mothers with antiphospholipid syndrome may be small and underweight.  A thrombosis or pregnancy complication is typically the first sign of antiphospholipid syndrome. This condition usually appears in early to mid-adulthood but can begin at any age.  Other signs and symptoms of antiphospholipid syndrome that affect blood cells and vessels include a reduced amount of blood clotting cells called platelets (thrombocytopenia), a shortage of red blood cells (anemia) due to their premature breakdown (hemolysis), and a purplish skin discoloration (livedo reticularis) caused by abnormalities in the tiny blood vessels of the skin. In addition, affected individuals may have open sores (ulcers) on the skin, migraine headaches, heart disease, or intellectual disability. Many people with antiphospholipid syndrome also have other autoimmune disorders such as systemic lupus erythematosus.  Rarely, people with antiphospholipid syndrome develop thromboses in multiple blood vessels throughout their body. These thromboses block blood flow in affected organs, which impairs their function and ultimately causes organ failure. These individuals are said to have catastrophic antiphospholipid syndrome (CAPS). CAPS typically affects the kidneys, lungs, brain, heart, and liver, and is fatal in over half of affected individuals. Less than 1 percent of individuals with antiphospholipid syndrome develop CAPS.",antiphospholipid syndrome,0000063,GHR,https://ghr.nlm.nih.gov/condition/antiphospholipid-syndrome,C0085278,T047,Disorders
How many people are affected by antiphospholipid syndrome ?,0000063-2,frequency,"The exact prevalence of antiphospholipid syndrome is unknown. This condition is thought to be fairly common, and may be responsible for up to one percent of all thromboses. It is estimated that 20 percent of individuals younger than age 50 who have a stroke have antiphospholipid syndrome. Ten to 15 percent of people with systemic lupus erythematosus have antiphospholipid syndrome. Similarly, 10 to 15 percent of women with recurrent miscarriages likely have this condition. Approximately 70 percent of individuals diagnosed with antiphospholipid syndrome are female.",antiphospholipid syndrome,0000063,GHR,https://ghr.nlm.nih.gov/condition/antiphospholipid-syndrome,C0085278,T047,Disorders
What are the genetic changes related to antiphospholipid syndrome ?,0000063-3,genetic changes,"The genetic cause of antiphospholipid syndrome is unknown. This condition is associated with the presence of three abnormal immune proteins (antibodies) in the blood: lupus anticoagulant, anticardiolipin, and anti-B2 glycoprotein I. Antibodies normally bind to specific foreign particles and germs, marking them for destruction, but the antibodies in antiphospholipid syndrome attack normal human proteins. When these antibodies attach (bind) to proteins, the proteins change shape and bind to other molecules and receptors on the surface of cells. Binding to cells, particularly immune cells, turns on (activates) the blood clotting pathway and other immune responses.  The production of lupus anticoagulant, anticardiolipin, and anti-B2 glycoprotein I may coincide with exposure to foreign invaders, such as viruses and bacteria, that are similar to normal human proteins. Exposure to these foreign invaders may cause the body to produce antibodies to fight the infection, but because the invaders are so similar to the body's own proteins, the antibodies also attack the human proteins. Similar triggers may occur during pregnancy when a woman's physiology, particularly her immune system, adapts to accommodate the developing fetus. These changes during pregnancy may explain the high rate of affected females.  Certain genetic variations (polymorphisms) in a few genes have been found in people with antiphospholipid syndrome and may predispose individuals to produce the specific antibodies known to contribute to the formation of thromboses. However, the contribution of these genetic changes to the development of the condition is unclear.  People who test positive for all three antibodies but have not had a thrombosis or recurrent miscarriages are said to be antiphospholipid carriers. These individuals are at greater risk of developing a thrombosis than is the general population.",antiphospholipid syndrome,0000063,GHR,https://ghr.nlm.nih.gov/condition/antiphospholipid-syndrome,C0085278,T047,Disorders
Is antiphospholipid syndrome inherited ?,0000063-4,inheritance,"Most cases of antiphospholipid syndrome are sporadic, which means they occur in people with no history of the disorder in their family. Rarely, the condition has been reported to run in families; however, it does not have a clear pattern of inheritance. Multiple genetic and environmental factors likely play a part in determining the risk of developing antiphospholipid syndrome.",antiphospholipid syndrome,0000063,GHR,https://ghr.nlm.nih.gov/condition/antiphospholipid-syndrome,C0085278,T047,Disorders
What are the treatments for antiphospholipid syndrome ?,0000063-5,treatment,These resources address the diagnosis or management of antiphospholipid syndrome:  - Genetic Testing Registry: Antiphospholipid syndrome  - Hughes Syndrome Foundation: Diagnosis: How To Get Tested  - Hughes Syndrome Foundation: Treatment and Medication: Current Advice and Information  - National Heart Lung and Blood Institute: How Is Antiphospholipid Antibody Syndrome Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,antiphospholipid syndrome,0000063,GHR,https://ghr.nlm.nih.gov/condition/antiphospholipid-syndrome,C0085278,T047,Disorders
What is (are) Apert syndrome ?,0000064-1,information,"Apert syndrome is a genetic disorder characterized by the premature fusion of certain skull bones (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face. In addition, a varied number of fingers and toes are fused together (syndactyly).  Many of the characteristic facial features of Apert syndrome result from the premature fusion of the skull bones. The head is unable to grow normally, which leads to a sunken appearance in the middle of the face, bulging and wide-set eyes, a beaked nose, and an underdeveloped upper jaw leading to crowded teeth and other dental problems. Shallow eye sockets can cause vision problems. Early fusion of the skull bones also affects the development of the brain, which can disrupt intellectual development. Cognitive abilities in people with Apert syndrome range from normal to mild or moderate intellectual disability.  Individuals with Apert syndrome have webbed or fused fingers and toes. The severity of the fusion varies; at a minimum, three digits on each hand and foot are fused together. In the most severe cases, all of the fingers and toes are fused. Less commonly, people with this condition may have extra fingers or toes (polydactyly). Additional signs and symptoms of Apert syndrome can include hearing loss, unusually heavy sweating (hyperhidrosis), oily skin with severe acne, patches of missing hair in the eyebrows, fusion of spinal bones in the neck (cervical vertebrae), and recurrent ear infections that may be associated with an opening in the roof of the mouth (a cleft palate).",Apert syndrome,0000064,GHR,https://ghr.nlm.nih.gov/condition/apert-syndrome,C0001193,T019,Disorders
How many people are affected by Apert syndrome ?,0000064-2,frequency,"Apert syndrome affects an estimated 1 in 65,000 to 88,000 newborns.",Apert syndrome,0000064,GHR,https://ghr.nlm.nih.gov/condition/apert-syndrome,C0001193,T019,Disorders
What are the genetic changes related to Apert syndrome ?,0000064-3,genetic changes,"Mutations in the FGFR2 gene cause Apert syndrome. This gene produces a protein called fibroblast growth factor receptor 2. Among its multiple functions, this protein signals immature cells to become bone cells during embryonic development. A mutation in a specific part of the FGFR2 gene alters the protein and causes prolonged signaling, which can promote the premature fusion of bones in the skull, hands, and feet.",Apert syndrome,0000064,GHR,https://ghr.nlm.nih.gov/condition/apert-syndrome,C0001193,T019,Disorders
Is Apert syndrome inherited ?,0000064-4,inheritance,"Apert syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Almost all cases of Apert syndrome result from new mutations in the gene, and occur in people with no history of the disorder in their family. Individuals with Apert syndrome, however, can pass along the condition to the next generation.",Apert syndrome,0000064,GHR,https://ghr.nlm.nih.gov/condition/apert-syndrome,C0001193,T019,Disorders
What are the treatments for Apert syndrome ?,0000064-5,treatment,These resources address the diagnosis or management of Apert syndrome:  - Gene Review: Gene Review: FGFR-Related Craniosynostosis Syndromes  - Genetic Testing Registry: Acrocephalosyndactyly type I  - MedlinePlus Encyclopedia: Apert syndrome  - MedlinePlus Encyclopedia: Webbing of the fingers or toes   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Apert syndrome,0000064,GHR,https://ghr.nlm.nih.gov/condition/apert-syndrome,C0001193,T019,Disorders
What is (are) arginase deficiency ?,0000065-1,information,"Arginase deficiency is an inherited disorder that causes the amino acid arginine (a building block of proteins) and ammonia to accumulate gradually in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.  Arginase deficiency usually becomes evident by about the age of 3. It most often appears as stiffness, especially in the legs, caused by abnormal tensing of the muscles (spasticity). Other symptoms may include slower than normal growth, developmental delay and eventual loss of developmental milestones, intellectual disability, seizures, tremor, and difficulty with balance and coordination (ataxia). Occasionally, high protein meals or stress caused by illness or periods without food (fasting) may cause ammonia to accumulate more quickly in the blood. This rapid increase in ammonia may lead to episodes of irritability, refusal to eat, and vomiting.  In some affected individuals, signs and symptoms of arginase deficiency may be less severe, and may not appear until later in life.",arginase deficiency,0000065,GHR,https://ghr.nlm.nih.gov/condition/arginase-deficiency,C0268548,T047,Disorders
How many people are affected by arginase deficiency ?,0000065-2,frequency,"Arginase deficiency is a very rare disorder; it has been estimated to occur once in every 300,000 to 1,000,000 individuals.",arginase deficiency,0000065,GHR,https://ghr.nlm.nih.gov/condition/arginase-deficiency,C0268548,T047,Disorders
What are the genetic changes related to arginase deficiency ?,0000065-3,genetic changes,"Mutations in the ARG1 gene cause arginase deficiency.  Arginase deficiency belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions that occurs in liver cells. This cycle processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys.  The ARG1 gene provides instructions for making an enzyme called arginase. This enzyme controls the final step of the urea cycle, which produces urea by removing nitrogen from arginine. In people with arginase deficiency, arginase is damaged or missing, and arginine is not broken down properly. As a result, urea cannot be produced normally, and excess nitrogen accumulates in the blood in the form of ammonia. The accumulation of ammonia and arginine are believed to cause the neurological problems and other signs and symptoms of arginase deficiency.",arginase deficiency,0000065,GHR,https://ghr.nlm.nih.gov/condition/arginase-deficiency,C0268548,T047,Disorders
Is arginase deficiency inherited ?,0000065-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",arginase deficiency,0000065,GHR,https://ghr.nlm.nih.gov/condition/arginase-deficiency,C0268548,T047,Disorders
What are the treatments for arginase deficiency ?,0000065-5,treatment,These resources address the diagnosis or management of arginase deficiency:  - Baby's First Test  - Gene Review: Gene Review: Arginase Deficiency  - Gene Review: Gene Review: Urea Cycle Disorders Overview  - Genetic Testing Registry: Arginase deficiency  - MedlinePlus Encyclopedia: Hereditary urea cycle abnormality   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,arginase deficiency,0000065,GHR,https://ghr.nlm.nih.gov/condition/arginase-deficiency,C0268548,T047,Disorders
What is (are) arginine:glycine amidinotransferase deficiency ?,0000066-1,information,"Arginine:glycine amidinotransferase deficiency is an inherited disorder that primarily affects the brain. People with this disorder have mild to moderate intellectual disability and delayed speech development. Some affected individuals develop autistic behaviors that affect communication and social interaction. They may experience seizures, especially when they have a fever.  Children with arginine:glycine amidinotransferase deficiency may not gain weight and grow at the expected rate (failure to thrive), and have delayed development of motor skills such as sitting and walking. Affected individuals may also have weak muscle tone and tend to tire easily.",arginine:glycine amidinotransferase deficiency,0000066,GHR,https://ghr.nlm.nih.gov/condition/arginineglycine-amidinotransferase-deficiency,C2675179,T047,Disorders
How many people are affected by arginine:glycine amidinotransferase deficiency ?,0000066-2,frequency,The prevalence of arginine:glycine amidinotransferase deficiency is unknown. The disorder has been identified in only a few families.,arginine:glycine amidinotransferase deficiency,0000066,GHR,https://ghr.nlm.nih.gov/condition/arginineglycine-amidinotransferase-deficiency,C2675179,T047,Disorders
What are the genetic changes related to arginine:glycine amidinotransferase deficiency ?,0000066-3,genetic changes,"Mutations in the GATM gene cause arginine:glycine amidinotransferase deficiency. The GATM gene provides instructions for making the enzyme arginine:glycine amidinotransferase. This enzyme participates in the two-step production (synthesis) of the compound creatine from the protein building blocks (amino acids) glycine, arginine, and methionine. Specifically, arginine:glycine amidinotransferase controls the first step of the process. In this step, a compound called guanidinoacetic acid is produced by transferring a cluster of nitrogen and hydrogen atoms called a guanidino group from arginine to glycine. Guanidinoacetic acid is converted to creatine in the second step of the process. Creatine is needed for the body to store and use energy properly.  GATM gene mutations impair the ability of the arginine:glycine amidinotransferase enzyme to participate in creatine synthesis, resulting in a shortage of creatine. The effects of arginine:glycine amidinotransferase deficiency are most severe in organs and tissues that require large amounts of energy, especially the brain.",arginine:glycine amidinotransferase deficiency,0000066,GHR,https://ghr.nlm.nih.gov/condition/arginineglycine-amidinotransferase-deficiency,C2675179,T047,Disorders
Is arginine:glycine amidinotransferase deficiency inherited ?,0000066-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",arginine:glycine amidinotransferase deficiency,0000066,GHR,https://ghr.nlm.nih.gov/condition/arginineglycine-amidinotransferase-deficiency,C2675179,T047,Disorders
What are the treatments for arginine:glycine amidinotransferase deficiency ?,0000066-5,treatment,These resources address the diagnosis or management of arginine:glycine amidinotransferase deficiency:  - Gene Review: Gene Review: Creatine Deficiency Syndromes  - Genetic Testing Registry: Arginine:glycine amidinotransferase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,arginine:glycine amidinotransferase deficiency,0000066,GHR,https://ghr.nlm.nih.gov/condition/arginineglycine-amidinotransferase-deficiency,C2675179,T047,Disorders
What is (are) argininosuccinic aciduria ?,0000067-1,information,"Argininosuccinic aciduria is an inherited disorder that causes ammonia to accumulate in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.  Argininosuccinic aciduria usually becomes evident in the first few days of life. An infant with argininosuccinic aciduria may be lacking in energy (lethargic) or unwilling to eat, and have poorly controlled breathing rate or body temperature. Some babies with this disorder experience seizures or unusual body movements, or go into a coma. Complications from argininosuccinic aciduria may include developmental delay and intellectual disability. Progressive liver damage, skin lesions, and brittle hair may also be seen.  Occasionally, an individual may inherit a mild form of the disorder in which ammonia accumulates in the bloodstream only during periods of illness or other stress.",argininosuccinic aciduria,0000067,GHR,https://ghr.nlm.nih.gov/condition/argininosuccinic-aciduria,C0268547,T047,Disorders
How many people are affected by argininosuccinic aciduria ?,0000067-2,frequency,"Argininosuccinic aciduria occurs in approximately 1 in 70,000 newborns.",argininosuccinic aciduria,0000067,GHR,https://ghr.nlm.nih.gov/condition/argininosuccinic-aciduria,C0268547,T047,Disorders
What are the genetic changes related to argininosuccinic aciduria ?,0000067-3,genetic changes,"Mutations in the ASL gene cause argininosuccinic aciduria.  Argininosuccinic aciduria belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions that occur in liver cells. It processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys.  In argininosuccinic aciduria, the enzyme that starts a specific reaction within the urea cycle is damaged or missing. The urea cycle cannot proceed normally, and nitrogen accumulates in the bloodstream in the form of ammonia.  Ammonia is especially damaging to the nervous system, so argininosuccinic aciduria causes neurological problems as well as eventual damage to the liver.",argininosuccinic aciduria,0000067,GHR,https://ghr.nlm.nih.gov/condition/argininosuccinic-aciduria,C0268547,T047,Disorders
Is argininosuccinic aciduria inherited ?,0000067-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",argininosuccinic aciduria,0000067,GHR,https://ghr.nlm.nih.gov/condition/argininosuccinic-aciduria,C0268547,T047,Disorders
What are the treatments for argininosuccinic aciduria ?,0000067-5,treatment,These resources address the diagnosis or management of argininosuccinic aciduria:  - Baby's First Test  - Gene Review: Gene Review: Argininosuccinate Lyase Deficiency  - Gene Review: Gene Review: Urea Cycle Disorders Overview  - Genetic Testing Registry: Argininosuccinate lyase deficiency  - MedlinePlus Encyclopedia: Hereditary urea cycle abnormality   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,argininosuccinic aciduria,0000067,GHR,https://ghr.nlm.nih.gov/condition/argininosuccinic-aciduria,C0268547,T047,Disorders
What is (are) aromatase deficiency ?,0000068-1,information,"Aromatase deficiency is a condition characterized by reduced levels of the female sex hormone estrogen and increased levels of the male sex hormone testosterone.  Females with aromatase deficiency have a typical female chromosome pattern (46,XX) but are born with external genitalia that do not appear clearly female or male (ambiguous genitalia). These individuals typically have normal internal reproductive organs, but develop ovarian cysts early in childhood, which impair the release of egg cells from the ovaries (ovulation). In adolescence, most affected females do not develop secondary sexual characteristics, such as breast growth and menstrual periods. They tend to develop acne and excessive body hair growth (hirsutism).  Men with this condition have a typical male chromosome pattern (46,XY) and are born with male external genitalia. Some men with this condition have decreased sex drive, abnormal sperm production, or testes that are small or undescended (cryptorchidism).  There are other features associated with aromatase deficiency that can affect both males and females. Affected individuals are abnormally tall because of excessive growth of long bones in the arms and legs. The abnormal bone growth results in slowed mineralization of bones (delayed bone age) and thinning of the bones (osteoporosis), which can lead to bone fractures with little trauma. Males and females with aromatase deficiency can have abnormally high blood sugar (hyperglycemia) because the body does not respond correctly to the hormone insulin. In addition, they can have excessive weight gain and a fatty liver.  Women who are pregnant with fetuses that have aromatase deficiency often experience mild symptoms of the disorder even though they themselves do not have the disorder. These women may develop hirsutism, acne, an enlarged clitoris (clitoromegaly), and a deep voice. These features can appear as early as 12 weeks of pregnancy and go away soon after delivery.",aromatase deficiency,0000068,GHR,https://ghr.nlm.nih.gov/condition/aromatase-deficiency,C1970109,T047,Disorders
How many people are affected by aromatase deficiency ?,0000068-2,frequency,The prevalence of aromatase deficiency is unknown; approximately 20 cases have been described in the medical literature.,aromatase deficiency,0000068,GHR,https://ghr.nlm.nih.gov/condition/aromatase-deficiency,C1970109,T047,Disorders
What are the genetic changes related to aromatase deficiency ?,0000068-3,genetic changes,"Mutations in the CYP19A1 gene cause aromatase deficiency. The CYP19A1 gene provides instructions for making an enzyme called aromatase. This enzyme converts a class of hormones called androgens, which are involved in male sexual development, to different forms of estrogen. In females, estrogen guides female sexual development before birth and during puberty. In both males and females, estrogen plays a role in regulating bone growth and blood sugar levels. During fetal development, aromatase converts androgens to estrogens in the placenta, which is the link between the mother's blood supply and the fetus. This conversion in the placenta prevents androgens from directing sexual development in female fetuses. After birth, the conversion of androgens to estrogens takes place in multiple tissues.  CYP19A1 gene mutations that cause aromatase deficiency decrease or eliminate aromatase activity. A shortage of functional aromatase results in an inability to convert androgens to estrogens before birth and throughout life. As a result, there is a decrease in estrogen production and an increase in the levels of androgens, including testosterone. In affected individuals, these abnormal hormone levels lead to impaired female sexual development, unusual bone growth, insulin resistance, and other signs and symptoms of aromatase deficiency. In women who are pregnant with an affected fetus, excess androgens in the placenta pass into the woman's bloodstream, which may cause her to have temporary signs and symptoms of aromatase deficiency.",aromatase deficiency,0000068,GHR,https://ghr.nlm.nih.gov/condition/aromatase-deficiency,C1970109,T047,Disorders
Is aromatase deficiency inherited ?,0000068-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",aromatase deficiency,0000068,GHR,https://ghr.nlm.nih.gov/condition/aromatase-deficiency,C1970109,T047,Disorders
What are the treatments for aromatase deficiency ?,0000068-5,treatment,These resources address the diagnosis or management of aromatase deficiency:  - Genetic Testing Registry: Aromatase deficiency  - MedlinePlus Encyclopedia: Ovarian Overproduction of Androgens   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,aromatase deficiency,0000068,GHR,https://ghr.nlm.nih.gov/condition/aromatase-deficiency,C1970109,T047,Disorders
What is (are) aromatase excess syndrome ?,0000069-1,information,"Aromatase excess syndrome is a condition characterized by elevated levels of the female sex hormone estrogen in both males and females. Males with aromatase excess syndrome experience breast enlargement (gynecomastia) in late childhood or adolescence. The bones of affected males grow and develop more quickly and stop growing sooner than usual (advanced bone age). As a result males have an early growth spurt, typically during late childhood, with short stature as an adult. Affected females rarely show signs and symptoms of the condition, but they may have increased breast growth (macromastia), irregular menstrual periods, and short stature. The ability to have children (fertility) is usually normal in both males and females with aromatase excess syndrome.",aromatase excess syndrome,0000069,GHR,https://ghr.nlm.nih.gov/condition/aromatase-excess-syndrome,C1970109,T047,Disorders
How many people are affected by aromatase excess syndrome ?,0000069-2,frequency,The prevalence of aromatase excess syndrome is unknown; more than 20 cases have been described in the medical literature.,aromatase excess syndrome,0000069,GHR,https://ghr.nlm.nih.gov/condition/aromatase-excess-syndrome,C1970109,T047,Disorders
What are the genetic changes related to aromatase excess syndrome ?,0000069-3,genetic changes,"Rearrangements of genetic material involving the CYP19A1 gene cause aromatase excess syndrome. The CYP19A1 gene provides instructions for making an enzyme called aromatase. This enzyme converts a class of hormones called androgens, which are involved in male sexual development, to different forms of estrogen. In females, estrogen guides female sexual development before birth and during puberty. In both males and females, estrogen plays a role in regulating bone growth.  The condition can result from several types of genetic rearrangements involving the CYP19A1 gene. These rearrangements alter the activity of the gene and lead to an increase in aromatase production. In affected males, the increased aromatase and subsequent conversion of androgens to estrogen are responsible for the gynecomastia and limited bone growth characteristic of aromatase excess syndrome. Increased estrogen in females can cause symptoms such as irregular menstrual periods and short stature.",aromatase excess syndrome,0000069,GHR,https://ghr.nlm.nih.gov/condition/aromatase-excess-syndrome,C1970109,T047,Disorders
Is aromatase excess syndrome inherited ?,0000069-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means a genetic rearrangement involving one copy of the CYP19A1 gene in each cell is sufficient to cause the disorder.  In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new genetic changes and occur in people with no history of the disorder in their family.",aromatase excess syndrome,0000069,GHR,https://ghr.nlm.nih.gov/condition/aromatase-excess-syndrome,C1970109,T047,Disorders
What are the treatments for aromatase excess syndrome ?,0000069-5,treatment,"These resources address the diagnosis or management of aromatase excess syndrome:  - Genetic Testing Registry: Familial gynecomastia, due to increased aromatase activity   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",aromatase excess syndrome,0000069,GHR,https://ghr.nlm.nih.gov/condition/aromatase-excess-syndrome,C1970109,T047,Disorders
What is (are) aromatic l-amino acid decarboxylase deficiency ?,0000070-1,information,"Aromatic l-amino acid decarboxylase (AADC) deficiency is an inherited disorder that affects the way signals are passed between certain cells in the nervous system.  Signs and symptoms of AADC deficiency generally appear in the first year of life. Affected infants may have severe developmental delay, weak muscle tone (hypotonia), muscle stiffness, difficulty moving, and involuntary writhing movements of the limbs (athetosis). They may be lacking in energy (lethargic), feed poorly, startle easily, and have sleep disturbances. People with AADC deficiency may also experience episodes called oculogyric crises that involve abnormal rotation of the eyeballs; extreme irritability and agitation; and pain, muscle spasms, and uncontrolled movements, especially of the head and neck.  AADC deficiency may affect the autonomic nervous system, which controls involuntary body processes such as the regulation of blood pressure and body temperature. Resulting signs and symptoms can include droopy eyelids (ptosis), constriction of the pupils of the eyes (miosis), inappropriate or impaired sweating, nasal congestion, drooling, reduced ability to control body temperature, low blood pressure (hypotension), backflow of acidic stomach contents into the esophagus (gastroesophageal reflux), low blood sugar (hypoglycemia), fainting (syncope), and cardiac arrest.  Signs and symptoms of AADC deficiency tend to worsen late in the day or when the individual is tired, and improve after sleep.",aromatic l-amino acid decarboxylase deficiency,0000070,GHR,https://ghr.nlm.nih.gov/condition/aromatic-l-amino-acid-decarboxylase-deficiency,C0342686,T047,Disorders
How many people are affected by aromatic l-amino acid decarboxylase deficiency ?,0000070-2,frequency,AADC deficiency is a rare disorder. Only about 100 people with this condition have been described in the medical literature worldwide; about 20 percent of these individuals are from Taiwan.,aromatic l-amino acid decarboxylase deficiency,0000070,GHR,https://ghr.nlm.nih.gov/condition/aromatic-l-amino-acid-decarboxylase-deficiency,C0342686,T047,Disorders
What are the genetic changes related to aromatic l-amino acid decarboxylase deficiency ?,0000070-3,genetic changes,"Mutations in the DDC gene cause AADC deficiency. The DDC gene provides instructions for making the AADC enzyme, which is important in the nervous system. This enzyme helps produce dopamine and serotonin from other molecules. Dopamine and serotonin are neurotransmitters, which are chemical messengers that transmit signals between nerve cells, both in the brain and spinal cord (central nervous system) and in other parts of the body (peripheral nervous system).  Mutations in the DDC gene result in reduced activity of the AADC enzyme. Without enough of this enzyme, nerve cells produce less dopamine and serotonin. Dopamine and serotonin are necessary for normal nervous system function, and changes in the levels of these neurotransmitters contribute to the developmental delay, intellectual disability, abnormal movements, and autonomic dysfunction seen in people with AADC deficiency.",aromatic l-amino acid decarboxylase deficiency,0000070,GHR,https://ghr.nlm.nih.gov/condition/aromatic-l-amino-acid-decarboxylase-deficiency,C0342686,T047,Disorders
Is aromatic l-amino acid decarboxylase deficiency inherited ?,0000070-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",aromatic l-amino acid decarboxylase deficiency,0000070,GHR,https://ghr.nlm.nih.gov/condition/aromatic-l-amino-acid-decarboxylase-deficiency,C0342686,T047,Disorders
What are the treatments for aromatic l-amino acid decarboxylase deficiency ?,0000070-5,treatment,These resources address the diagnosis or management of aromatic l-amino acid decarboxylase deficiency:  - Genetic Testing Registry: Deficiency of aromatic-L-amino-acid decarboxylase   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,aromatic l-amino acid decarboxylase deficiency,0000070,GHR,https://ghr.nlm.nih.gov/condition/aromatic-l-amino-acid-decarboxylase-deficiency,C0342686,T047,Disorders
What is (are) arrhythmogenic right ventricular cardiomyopathy ?,0000071-1,information,"Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a form of heart disease that usually appears in adulthood. ARVC is a disorder of the myocardium, which is the muscular wall of the heart. This condition causes part of the myocardium to break down over time, increasing the risk of an abnormal heartbeat (arrhythmia) and sudden death.  ARVC may not cause any symptoms in its early stages. However, affected individuals may still be at risk of sudden death, especially during strenuous exercise. When symptoms occur, they most commonly include a sensation of fluttering or pounding in the chest (palpitations), light-headedness, and fainting (syncope). Over time, ARVC can also cause shortness of breath and abnormal swelling in the legs or abdomen. If the myocardium becomes severely damaged in the later stages of the disease, it can lead to heart failure.",arrhythmogenic right ventricular cardiomyopathy,0000071,GHR,https://ghr.nlm.nih.gov/condition/arrhythmogenic-right-ventricular-cardiomyopathy,C0349788,T019,Disorders
How many people are affected by arrhythmogenic right ventricular cardiomyopathy ?,0000071-2,frequency,"ARVC occurs in an estimated 1 in 1,000 to 1 in 1,250 people. This disorder may be underdiagnosed because it can be difficult to detect in people with mild or no symptoms.",arrhythmogenic right ventricular cardiomyopathy,0000071,GHR,https://ghr.nlm.nih.gov/condition/arrhythmogenic-right-ventricular-cardiomyopathy,C0349788,T019,Disorders
What are the genetic changes related to arrhythmogenic right ventricular cardiomyopathy ?,0000071-3,genetic changes,"ARVC can result from mutations in at least eight genes. Many of these genes are involved in the function of desmosomes, which are structures that attach heart muscle cells to one another. Desmosomes provide strength to the myocardium and play a role in signaling between neighboring cells.  Mutations in the genes responsible for ARVC often impair the normal function of desmosomes. Without normal desmosomes, cells of the myocardium detach from one another and die, particularly when the heart muscle is placed under stress (such as during vigorous exercise). These changes primarily affect the myocardium surrounding the right ventricle, one of the two lower chambers of the heart. The damaged myocardium is gradually replaced by fat and scar tissue. As this abnormal tissue builds up, the walls of the right ventricle become stretched out, preventing the heart from pumping blood effectively. These changes also disrupt the electrical signals that control the heartbeat, which can lead to arrhythmia.  Gene mutations have been found in 30 to 40 percent of people with ARVC. Mutations in a gene called PKP2 are most common. In people without an identified mutation, the cause of the disorder is unknown. Researchers are looking for additional genetic factors, particularly those involved in the function of desmosomes, that may play a role in causing ARVC.",arrhythmogenic right ventricular cardiomyopathy,0000071,GHR,https://ghr.nlm.nih.gov/condition/arrhythmogenic-right-ventricular-cardiomyopathy,C0349788,T019,Disorders
Is arrhythmogenic right ventricular cardiomyopathy inherited ?,0000071-4,inheritance,"Up to half of all cases of ARVC appear to run in families. Most familial cases of the disease have an autosomal dominant pattern of inheritance, which means one copy of an altered gene in each cell is sufficient to cause the disorder.  Rarely, ARVC has an autosomal recessive pattern of inheritance, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",arrhythmogenic right ventricular cardiomyopathy,0000071,GHR,https://ghr.nlm.nih.gov/condition/arrhythmogenic-right-ventricular-cardiomyopathy,C0349788,T019,Disorders
What are the treatments for arrhythmogenic right ventricular cardiomyopathy ?,0000071-5,treatment,"These resources address the diagnosis or management of ARVC:  - Brigham and Women's Hospital  - Cleveland Clinic: How Are Arrhythmias Treated?  - Gene Review: Gene Review: Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy  - Genetic Testing Registry: Arrhythmogenic right ventricular cardiomyopathy  - Genetic Testing Registry: Arrhythmogenic right ventricular cardiomyopathy, type 1  - Genetic Testing Registry: Arrhythmogenic right ventricular cardiomyopathy, type 10  - Genetic Testing Registry: Arrhythmogenic right ventricular cardiomyopathy, type 11  - Genetic Testing Registry: Arrhythmogenic right ventricular cardiomyopathy, type 12  - Genetic Testing Registry: Arrhythmogenic right ventricular cardiomyopathy, type 2  - Genetic Testing Registry: Arrhythmogenic right ventricular cardiomyopathy, type 3  - Genetic Testing Registry: Arrhythmogenic right ventricular cardiomyopathy, type 4  - Genetic Testing Registry: Arrhythmogenic right ventricular cardiomyopathy, type 5  - Genetic Testing Registry: Arrhythmogenic right ventricular cardiomyopathy, type 6  - Genetic Testing Registry: Arrhythmogenic right ventricular cardiomyopathy, type 7  - Genetic Testing Registry: Arrhythmogenic right ventricular cardiomyopathy, type 8  - Genetic Testing Registry: Arrhythmogenic right ventricular cardiomyopathy, type 9  - Genetic Testing Registry: Arrhythmogenic right ventricular dysplasia, familial, 11, with mild palmoplantar keratoderma and woolly hair  - St. Luke's-Roosevelt Hospital Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",arrhythmogenic right ventricular cardiomyopathy,0000071,GHR,https://ghr.nlm.nih.gov/condition/arrhythmogenic-right-ventricular-cardiomyopathy,C0349788,T019,Disorders
What is (are) arterial tortuosity syndrome ?,0000072-1,information,"Arterial tortuosity syndrome is a disorder that affects connective tissue. Connective tissue provides strength and flexibility to structures throughout the body, including blood vessels, skin, joints, and the gastrointestinal tract.  As its name suggests, arterial tortuosity syndrome is characterized by blood vessel abnormalities, particularly abnormal twists and turns (tortuosity) of the blood vessels that carry blood from the heart to the rest of the body (the arteries). Tortuosity arises from abnormal elongation of the arteries; since the end points of the arteries are fixed, the extra length twists and curves. Other blood vessel abnormalities that may occur in this disorder include constriction (stenosis) and abnormal bulging (aneurysm) of vessels, as well as small clusters of enlarged blood vessels just under the skin (telangiectasia).  Complications resulting from the abnormal arteries can be life-threatening. Rupture of an aneurysm or sudden tearing (dissection) of the layers in an arterial wall can result in massive loss of blood from the circulatory system. Blockage of blood flow to vital organs such as the heart, lungs, or brain can lead to heart attacks, respiratory problems, and strokes. Stenosis of the arteries forces the heart to work harder to pump blood and may lead to heart failure. As a result of these complications, arterial tortuosity syndrome is often fatal in childhood, although some individuals with mild cases of the disorder live into adulthood.  Features of arterial tortuosity syndrome outside the circulatory system are caused by abnormal connective tissue in other parts of the body. These features include joints that are either loose and very flexible (hypermobile) or that have deformities limiting movement (contractures), and unusually soft and stretchable skin. Some affected individuals have long, slender fingers and toes (arachnodactyly); curvature of the spine (scoliosis); or a chest that is either sunken (pectus excavatum) or protruding (pectus carinatum). They may have protrusion of organs through gaps in muscles (hernias), elongation of the intestines, or pouches called diverticula in the intestinal walls.  People with arterial tortuosity syndrome often look older than their age and have distinctive facial features including a long, narrow face with droopy cheeks; eye openings that are narrowed (blepharophimosis) with outside corners that point downward (downslanting palpebral fissures); a beaked nose with soft cartilage; a high, arched roof of the mouth (palate); a small lower jaw (micrognathia); and large ears. The cornea, which is the clear front covering of the eye, may be cone-shaped and abnormally thin (keratoconus).",arterial tortuosity syndrome,0000072,GHR,https://ghr.nlm.nih.gov/condition/arterial-tortuosity-syndrome,C1859726,T047,Disorders
How many people are affected by arterial tortuosity syndrome ?,0000072-2,frequency,Arterial tortuosity syndrome is a rare disorder; its prevalence is unknown. About 100 cases have been reported in the medical literature.,arterial tortuosity syndrome,0000072,GHR,https://ghr.nlm.nih.gov/condition/arterial-tortuosity-syndrome,C1859726,T047,Disorders
What are the genetic changes related to arterial tortuosity syndrome ?,0000072-3,genetic changes,"Arterial tortuosity syndrome is caused by mutations in the SLC2A10 gene. This gene provides instructions for making a protein called GLUT10. The level of GLUT10 appears to be involved in the regulation of a process called the transforming growth factor-beta (TGF-) signaling pathway. This pathway is involved in cell growth and division (proliferation) and the process by which cells mature to carry out special functions (differentiation). The TGF- signaling pathway is also involved in bone and blood vessel development and the formation of the extracellular matrix, an intricate lattice of proteins and other molecules that forms in the spaces between cells and defines the structure and properties of connective tissues.  SLC2A10 gene mutations that cause arterial tortuosity syndrome reduce or eliminate GLUT10 function. By mechanisms that are not well understood, a lack (deficiency) of functional GLUT10 protein leads to overactivity (upregulation) of TGF- signaling. Excessive growth signaling results in elongation of the arteries, leading to tortuosity. Overactive TGF- signaling also interferes with normal formation of the connective tissues in other parts of the body, leading to the additional signs and symptoms of arterial tortuosity syndrome.",arterial tortuosity syndrome,0000072,GHR,https://ghr.nlm.nih.gov/condition/arterial-tortuosity-syndrome,C1859726,T047,Disorders
Is arterial tortuosity syndrome inherited ?,0000072-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",arterial tortuosity syndrome,0000072,GHR,https://ghr.nlm.nih.gov/condition/arterial-tortuosity-syndrome,C1859726,T047,Disorders
What are the treatments for arterial tortuosity syndrome ?,0000072-5,treatment,"These resources address the diagnosis or management of arterial tortuosity syndrome:  - Gene Review: Gene Review: Arterial Tortuosity Syndrome  - Genetic Testing Registry: Arterial tortuosity syndrome  - Johns Hopkins McKusick-Nathans Institute of Genetic Medicine  - National Heart, Lung, and Blood Institute: How is an Aneurysm Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",arterial tortuosity syndrome,0000072,GHR,https://ghr.nlm.nih.gov/condition/arterial-tortuosity-syndrome,C1859726,T047,Disorders
What is (are) Arts syndrome ?,0000073-1,information,"Arts syndrome is a disorder that causes serious neurological problems in males. Females can also be affected by this condition, but they typically have much milder symptoms.  Boys with Arts syndrome have profound sensorineural hearing loss, which is a complete or almost complete loss of hearing caused by abnormalities in the inner ear. Other features of the disorder include weak muscle tone (hypotonia), impaired muscle coordination (ataxia), developmental delay, and intellectual disability. In early childhood, affected boys develop vision loss caused by degeneration of nerves that carry information from the eyes to the brain (optic nerve atrophy). They also experience loss of sensation and weakness in the limbs (peripheral neuropathy).  Boys with Arts syndrome also usually have recurrent infections, especially involving the respiratory system. Because of these infections and their complications, affected boys often do not survive past early childhood.  In females with Arts syndrome, hearing loss that begins in adulthood may be the only symptom.",Arts syndrome,0000073,GHR,https://ghr.nlm.nih.gov/condition/arts-syndrome,C0796028,T047,Disorders
How many people are affected by Arts syndrome ?,0000073-2,frequency,Arts syndrome appears to be extremely rare. Only a few families with this disorder have been described in the medical literature.,Arts syndrome,0000073,GHR,https://ghr.nlm.nih.gov/condition/arts-syndrome,C0796028,T047,Disorders
What are the genetic changes related to Arts syndrome ?,0000073-3,genetic changes,"Mutations in the PRPS1 gene cause Arts syndrome. The PRPS1 gene provides instructions for making an enzyme called phosphoribosyl pyrophosphate synthetase 1, or PRPP synthetase 1. This enzyme is involved in producing purines and pyrimidines, which are building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in the cell.  The PRPS1 gene mutations that cause Arts syndrome replace single protein building blocks (amino acids) in the PRPP synthetase 1 enzyme. The resulting enzyme is probably unstable, reducing or eliminating its ability to perform its function. The disruption of purine and pyrimidine production may impair energy storage and transport in cells. Impairment of these processes may have a particularly severe effect on tissues that require a large amount of energy, such as the nervous system, resulting in the neurological problems characteristic of Arts syndrome. The reason for the increased risk of respiratory infections in Arts syndrome is unclear.",Arts syndrome,0000073,GHR,https://ghr.nlm.nih.gov/condition/arts-syndrome,C0796028,T047,Disorders
Is Arts syndrome inherited ?,0000073-4,inheritance,"This condition is inherited in an X-linked pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell sometimes causes features of the disorder; in other cases, these females do not experience any symptoms.  In the small number of Arts syndrome cases that have been identified, affected individuals have inherited the mutation from a mother who carries an altered copy of the PRPS1 gene.",Arts syndrome,0000073,GHR,https://ghr.nlm.nih.gov/condition/arts-syndrome,C0796028,T047,Disorders
What are the treatments for Arts syndrome ?,0000073-5,treatment,"These resources address the diagnosis or management of Arts syndrome:  - Gene Review: Gene Review: Arts Syndrome  - Genetic Testing Registry: Arts syndrome  - MedlinePlus Encyclopedia: Hearing Loss  - MedlinePlus Encyclopedia: Movement, Uncoordinated  - MedlinePlus Encyclopedia: Optic Nerve Atrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Arts syndrome,0000073,GHR,https://ghr.nlm.nih.gov/condition/arts-syndrome,C0796028,T047,Disorders
What is (are) aspartylglucosaminuria ?,0000074-1,information,"Aspartylglucosaminuria is a condition that causes a progressive decline in mental functioning.  Infants with aspartylglucosaminuria appear healthy at birth, and development is typically normal throughout early childhood. The first sign of this condition, evident around the age of 2 or 3, is usually delayed speech. Mild intellectual disability then becomes apparent, and learning occurs at a slowed pace. Intellectual disability progressively worsens in adolescence. Most people with this disorder lose much of the speech they have learned, and affected adults usually have only a few words in their vocabulary. Adults with aspartylglucosaminuria may develop seizures or problems with movement.  People with this condition may also have bones that become progressively weak and prone to fracture (osteoporosis), an unusually large range of joint movement (hypermobility), and loose skin. Affected individuals tend to have a characteristic facial appearance that includes widely spaced eyes (ocular hypertelorism), small ears, and full lips. The nose is short and broad and the face is usually square-shaped. Children with this condition may be tall for their age, but lack of a growth spurt in puberty typically causes adults to be short. Affected children also tend to have frequent upper respiratory infections. Individuals with aspartylglucosaminuria usually survive into mid-adulthood.",aspartylglucosaminuria,0000074,GHR,https://ghr.nlm.nih.gov/condition/aspartylglucosaminuria,C0268225,T047,Disorders
How many people are affected by aspartylglucosaminuria ?,0000074-2,frequency,"Aspartylglucosaminuria is estimated to affect 1 in 18,500 people in Finland. This condition is less common outside of Finland, but the incidence is unknown.",aspartylglucosaminuria,0000074,GHR,https://ghr.nlm.nih.gov/condition/aspartylglucosaminuria,C0268225,T047,Disorders
What are the genetic changes related to aspartylglucosaminuria ?,0000074-3,genetic changes,"Mutations in the AGA gene cause aspartylglucosaminuria. The AGA gene provides instructions for producing an enzyme called aspartylglucosaminidase. This enzyme is active in lysosomes, which are structures inside cells that act as recycling centers. Within lysosomes, the enzyme helps break down complexes of sugar molecules (oligosaccharides) attached to certain proteins (glycoproteins).  AGA gene mutations result in the absence or shortage of the aspartylglucosaminidase enzyme in lysosomes, preventing the normal breakdown of glycoproteins. As a result, glycoproteins can build up within the lysosomes. Excess glycoproteins disrupt the normal functions of the cell and can result in destruction of the cell. A buildup of glycoproteins seems to particularly affect nerve cells in the brain; loss of these cells causes many of the signs and symptoms of aspartylglucosaminuria.",aspartylglucosaminuria,0000074,GHR,https://ghr.nlm.nih.gov/condition/aspartylglucosaminuria,C0268225,T047,Disorders
Is aspartylglucosaminuria inherited ?,0000074-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",aspartylglucosaminuria,0000074,GHR,https://ghr.nlm.nih.gov/condition/aspartylglucosaminuria,C0268225,T047,Disorders
What are the treatments for aspartylglucosaminuria ?,0000074-5,treatment,These resources address the diagnosis or management of aspartylglucosaminuria:  - Genetic Testing Registry: Aspartylglycosaminuria   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,aspartylglucosaminuria,0000074,GHR,https://ghr.nlm.nih.gov/condition/aspartylglucosaminuria,C0268225,T047,Disorders
What is (are) Asperger syndrome ?,0000075-1,information,"Asperger syndrome is a disorder on the autism spectrum, which is a group of conditions characterized by impaired communication and social interaction. Asperger syndrome is on the mild, or ""high-functioning,"" end of the autism spectrum. Many affected individuals learn to compensate for their differences and live independent and successful lives. However, the behavioral challenges associated with this condition often lead to social isolation and difficulties at school, at work, and in personal relationships.  People with Asperger syndrome have average or above-average intelligence. In contrast to people with other disorders on the autism spectrum, they are not delayed in their language development. However, their ability to carry on a conversation is often impaired by a tendency to take idioms or humorous statements literally and an inability to read non-verbal cues such as body language to understand what others are feeling. They may speak in a monotone voice, have unusual mannerisms, or choose unusual topics of conversation.  Individuals with Asperger syndrome tend to develop an intense interest in a particular subject. This interest may be a traditional hobby or academic discipline, and many people with Asperger syndrome develop advanced abilities in fields such as music, science, mathematics, or computer programming. However, they might also focus on an unusual interest such as bus routes or a particular type of household appliance. Often they are able to remember enormous amounts of detail on their subject of interest. They may want to share this large amount of information with others and may resist diversion to other topics.  People with Asperger syndrome tend to be rigid about their established routines and may strongly resist disruptions such as changes in schedule. They may also have difficulty tolerating sensory stimuli such as noise or lights.  Other features of Asperger syndrome may include mild impairment of motor skills. For example, basic skills such as crawling and walking may be somewhat delayed. Affected individuals may also have coordination problems that impair their ability to engage in such activities as playing ball games or riding a bicycle. This physical clumsiness may lead to further social isolation of children with Asperger syndrome.  Signs and symptoms of Asperger syndrome may become apparent by the age of 3, when most children begin to develop social skills such as learning to play with others. Some affected children may come to medical attention due to delayed motor skills. In most cases, children with Asperger syndrome are diagnosed during the elementary school years, as their social behavior continues to diverge from the typical developmental path. Difficulties with social skills generally continue into adulthood, and affected individuals are at increased risk of other behavioral or psychiatric disorders such as attention deficit-hyperactivity disorder (ADHD), depression, anxiety, and obsessive-compulsive disorder.",Asperger syndrome,0000075,GHR,https://ghr.nlm.nih.gov/condition/asperger-syndrome,C0236792,T048,Disorders
How many people are affected by Asperger syndrome ?,0000075-2,frequency,"The prevalence of Asperger syndrome is not well established. Estimates range from 1 in 250 to 1 in 5,000 children. Three to four times as many males are affected than females.  Because of changes in the way developmental disorders are classified, Asperger syndrome was not often diagnosed in adults until recently, and the prevalence is often perceived to be rising as more people are recognized to have features of the condition. Many mildly affected individuals likely continue to be undiagnosed.",Asperger syndrome,0000075,GHR,https://ghr.nlm.nih.gov/condition/asperger-syndrome,C0236792,T048,Disorders
What are the genetic changes related to Asperger syndrome ?,0000075-3,genetic changes,"While genetic factors are believed to contribute to the development of Asperger syndrome, no related genes have been confirmed. It is unclear whether certain gene variations that are being studied in other autism spectrum disorders will play a role in Asperger syndrome. It appears likely that a combination of genetic variations and environmental factors influence the development of this complex condition.  Asperger syndrome is a disorder of brain development. Researchers have identified differences in the structure and function of specific regions of the brain between children with Asperger syndrome and unaffected children. These differences likely arise during development before birth, when cells in the brain are migrating to their proper places.  The differences in brain development that occur in Asperger syndrome appear to affect areas of the brain involved in thought, behavior, and emotions, such as the prefrontal cortex, the amygdala, and the fusiform face area. In particular, cognitive functions called theory of mind, central coherence, and executive function are affected.  Theory of mind is the ability to understand that other people have their own ideas, emotions, and perceptions, and to empathize with them. It is related to the proper functioning of a brain mechanism called the mirror neuron system, which is normally active both when certain actions are performed and when others are observed performing the same actions. Researchers believe that the mirror neuron system is impaired in people with Asperger syndrome.  Central coherence is the ability to integrate individual perceptions into a larger context, commonly known as ""seeing the big picture."" For example, a person with Asperger syndrome may be able to describe individual trees in great detail without recognizing that they are part of a forest.  Executive function is the ability to plan and implement actions and develop problem-solving strategies. This function includes skills such as impulse control, self-monitoring, focusing attention appropriately, and cognitive flexibility. People with deficits in these skills may have difficulty in some activities of daily living and in social interactions.  The differences in cognitive functioning observed in people with Asperger syndrome are believed to give rise to the behavioral patterns characteristic of this condition.",Asperger syndrome,0000075,GHR,https://ghr.nlm.nih.gov/condition/asperger-syndrome,C0236792,T048,Disorders
Is Asperger syndrome inherited ?,0000075-4,inheritance,"Autism spectrum disorders including Asperger syndrome have a tendency to run in families, but the inheritance pattern is unknown.",Asperger syndrome,0000075,GHR,https://ghr.nlm.nih.gov/condition/asperger-syndrome,C0236792,T048,Disorders
What are the treatments for Asperger syndrome ?,0000075-5,treatment,These resources address the diagnosis or management of Asperger syndrome:  - Genetic Testing Registry: Asperger syndrome 1  - Genetic Testing Registry: Asperger syndrome 2  - Genetic Testing Registry: Asperger syndrome 3  - Genetic Testing Registry: Asperger syndrome 4  - Genetic Testing Registry: Asperger syndrome X-linked 1  - Genetic Testing Registry: Asperger syndrome X-linked 2  - Genetic Testing Registry: Asperger's disorder  - MedlinePlus Encyclopedia: Asperger Syndrome  - National Institute of Mental Health: How is ASD treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Asperger syndrome,0000075,GHR,https://ghr.nlm.nih.gov/condition/asperger-syndrome,C0236792,T048,Disorders
What is (are) asphyxiating thoracic dystrophy ?,0000076-1,information,"Asphyxiating thoracic dystrophy, also known as Jeune syndrome, is an inherited disorder of bone growth characterized by a narrow chest, short ribs, shortened bones in the arms and legs, short stature, and extra fingers and toes (polydactyly). Additional skeletal abnormalities can include unusually shaped collarbones (clavicles) and pelvic bones, and and cone-shaped ends of the long bones in the arms and legs. Many infants with this condition are born with an extremely narrow, bell-shaped chest that can restrict the growth and expansion of the lungs. Life-threatening problems with breathing result, and people with asphyxiating thoracic dystrophy may live only into infancy or early childhood. However, in people who survive beyond the first few years, the narrow chest and related breathing problems can improve with age.  Some people with asphyxiating thoracic dystrophy are born with less severe skeletal abnormalities and have only mild breathing difficulties, such as rapid breathing or shortness of breath. These individuals may live into adolescence or adulthood. After infancy, people with this condition may develop life-threatening kidney (renal) abnormalities that cause the kidneys to malfunction or fail. Heart defects and a narrowing of the airway (subglottic stenosis) are also possible. Other, less common features of asphyxiating thoracic dystrophy include liver disease, fluid-filled sacs (cysts) in the pancreas, dental abnormalities, and an eye disease called retinal dystrophy that can lead to vision loss.",asphyxiating thoracic dystrophy,0000076,GHR,https://ghr.nlm.nih.gov/condition/asphyxiating-thoracic-dystrophy,C0333606,T019,Disorders
How many people are affected by asphyxiating thoracic dystrophy ?,0000076-2,frequency,"Asphyxiating thoracic dystrophy affects an estimated 1 in 100,000 to 130,000 people.",asphyxiating thoracic dystrophy,0000076,GHR,https://ghr.nlm.nih.gov/condition/asphyxiating-thoracic-dystrophy,C0333606,T019,Disorders
What are the genetic changes related to asphyxiating thoracic dystrophy ?,0000076-3,genetic changes,"Mutations in at least 11 genes have been found to cause asphyxiating thoracic dystrophy. Genetic changes in the IFT80 gene were the first to be associated with this condition. Later, researchers discovered that mutations in another gene, DYNC2H1, account for up to half of all cases. Mutations in other genes each cause a small percentage of cases. In total, about 70 percent of people with asphyxiating thoracic dystrophy have mutations in one of the known genes.  The genes associated with asphyxiating thoracic dystrophy provide instructions for making proteins that are found in cell structures called cilia. Cilia are microscopic, finger-like projections that stick out from the surface of cells. The proteins are involved in a process called intraflagellar transport (IFT), by which materials are carried to and from the tips of cilia. IFT is essential for the assembly and maintenance of these cell structures. Cilia play central roles in many different chemical signaling pathways, including a series of reactions called the Sonic Hedgehog pathway. These pathways are important for the growth and division (proliferation) and maturation (differentiation) of cells. In particular, Sonic Hedgehog appears to be essential for the proliferation and differentiation of cells that ultimately give rise to cartilage and bone.  Mutations in the genes associated with asphyxiating thoracic dystrophy impair IFT, which disrupts the normal assembly or function of cilia. As a result, cilia are missing or abnormal in many different kinds of cells. Researchers speculate that these changes alter signaling through certain signaling pathways, including the Sonic Hedgehog pathway, which may underlie the abnormalities of bone growth characteristic of asphyxiating thoracic dystrophy. Abnormal cilia in other tissues, such as the kidneys, liver, and retinas, cause the other signs and symptoms of the condition.  Asphyxiating thoracic dystrophy is part of a group of disorders known as skeletal ciliopathies or ciliary chondrodysplasias, all of which are caused by problems with cilia and involve bone abnormalities. Several of these disorders, including asphyxiating thoracic dystrophy, are sometimes classified more specifically as short rib-polydactyly syndromes (SRPSs) based on their signs and symptoms. Some researchers believe that SRPSs would be more accurately described as a spectrum with a range of features rather than as separate disorders.",asphyxiating thoracic dystrophy,0000076,GHR,https://ghr.nlm.nih.gov/condition/asphyxiating-thoracic-dystrophy,C0333606,T019,Disorders
Is asphyxiating thoracic dystrophy inherited ?,0000076-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",asphyxiating thoracic dystrophy,0000076,GHR,https://ghr.nlm.nih.gov/condition/asphyxiating-thoracic-dystrophy,C0333606,T019,Disorders
What are the treatments for asphyxiating thoracic dystrophy ?,0000076-5,treatment,These resources address the diagnosis or management of asphyxiating thoracic dystrophy:  - Genetic Testing Registry: Asphyxiating thoracic dystrophy 2  - Genetic Testing Registry: Asphyxiating thoracic dystrophy 4  - Genetic Testing Registry: Asphyxiating thoracic dystrophy 5  - Genetic Testing Registry: Jeune thoracic dystrophy  - Genetic Testing Registry: Short-rib thoracic dysplasia 1 with or without polydactyly  - Jeune's Center at Nationwide Children's Hospital  - MedlinePlus Encyclopedia: Chronic Renal Failure  - MedlinePlus Encyclopedia: Polydactyly   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,asphyxiating thoracic dystrophy,0000076,GHR,https://ghr.nlm.nih.gov/condition/asphyxiating-thoracic-dystrophy,C0333606,T019,Disorders
What is (are) ataxia neuropathy spectrum ?,0000077-1,information,"Ataxia neuropathy spectrum is part of a group of conditions called the POLG-related disorders. The conditions in this group feature a range of similar signs and symptoms involving muscle-, nerve-, and brain-related functions. Ataxia neuropathy spectrum now includes the conditions previously called mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO).  As the name implies, people with ataxia neuropathy spectrum typically have problems with coordination and balance (ataxia) and disturbances in nerve function (neuropathy). The neuropathy can be classified as sensory, motor, or a combination of the two (mixed). Sensory neuropathy causes numbness, tingling, or pain in the arms and legs, and motor neuropathy refers to disturbance in the nerves used for muscle movement.  Most people with ataxia neuropathy spectrum also have severe brain dysfunction (encephalopathy) and seizures. Some affected individuals have weakness of the external muscles of the eye (ophthalmoplegia), which leads to drooping eyelids (ptosis). Other signs and symptoms can include involuntary muscle twitches (myoclonus), liver disease, depression, migraine headaches, or blindness.",ataxia neuropathy spectrum,0000077,GHR,https://ghr.nlm.nih.gov/condition/ataxia-neuropathy-spectrum,C3683791,T047,Disorders
How many people are affected by ataxia neuropathy spectrum ?,0000077-2,frequency,The prevalence of ataxia neuropathy spectrum is unknown.,ataxia neuropathy spectrum,0000077,GHR,https://ghr.nlm.nih.gov/condition/ataxia-neuropathy-spectrum,C3683791,T047,Disorders
What are the genetic changes related to ataxia neuropathy spectrum ?,0000077-3,genetic changes,"Ataxia neuropathy spectrum is caused by mutations in the POLG gene or, rarely, the C10orf2 gene.  The POLG gene provides instructions for making one part, the alpha subunit, of a protein called polymerase gamma (pol ). The C10orf2 gene provides instructions for making a protein called Twinkle. Pol  and Twinkle function in mitochondria, which are structures within cells that use oxygen to convert the energy from food into a form cells can use. Mitochondria each contain a small amount of DNA, known as mitochondrial DNA (mtDNA), which is essential for the normal function of these structures. Pol  and Twinkle are both integral to the process of DNA replication by which new copies of mtDNA are produced.  Mutated pol  or mutated Twinkle reduce mtDNA replication. Although the mechanisms are unknown, mutations in the POLG gene often result in fewer copies of mtDNA (mtDNA depletion), and mutations in the C10orf2 gene often result in deletions of large regions of mtDNA (mtDNA deletion). MtDNA depletion or deletion occurs most commonly in muscle, brain, or liver cells. MtDNA depletion causes a decrease in cellular energy, which could account for the signs and symptoms of ataxia neuropathy spectrum. It is unclear what role mtDNA deletions play in the signs and symptoms of the condition.",ataxia neuropathy spectrum,0000077,GHR,https://ghr.nlm.nih.gov/condition/ataxia-neuropathy-spectrum,C3683791,T047,Disorders
Is ataxia neuropathy spectrum inherited ?,0000077-4,inheritance,"Ataxia neuropathy spectrum can have different inheritance patterns depending on the associated gene.  Mutations in the POLG gene cause a form of the condition that is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Mutations in the C10orf2 gene cause a form of the condition that is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",ataxia neuropathy spectrum,0000077,GHR,https://ghr.nlm.nih.gov/condition/ataxia-neuropathy-spectrum,C3683791,T047,Disorders
What are the treatments for ataxia neuropathy spectrum ?,0000077-5,treatment,"These resources address the diagnosis or management of ataxia neuropathy spectrum:  - Gene Review: Gene Review: POLG-Related Disorders  - Genetic Testing Registry: Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis  - National Ataxia Foundation: Gene Testing for Hereditary Ataxia  - United Mitochondrial Disease Foundation: Diagnosis of Mitochondrial Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",ataxia neuropathy spectrum,0000077,GHR,https://ghr.nlm.nih.gov/condition/ataxia-neuropathy-spectrum,C3683791,T047,Disorders
What is (are) ataxia with oculomotor apraxia ?,0000078-1,information,"Ataxia with oculomotor apraxia is a condition characterized by progressive problems with movement. The hallmark of this condition is difficulty coordinating movements (ataxia), which is often the first symptom. Most affected people also have oculomotor apraxia, which makes it difficult to move their eyes side-to-side. People with oculomotor apraxia have to turn their head to see things in their side (peripheral) vision.  There are multiple types of ataxia with oculomotor apraxia. The types are very similar but are caused by mutations in different genes. The two most common types (types 1 and 2) share features, in addition to ataxia and oculomotor apraxia, that include involuntary jerking movements (chorea), muscle twitches (myoclonus), and disturbances in nerve function (neuropathy). In type 1, ataxia beings around age 4; in type 2, ataxia begins around age 15. Chorea and myoclonus tend to disappear gradually in type 1; these movement problems persist throughout life in type 2. Individuals with type 1 often develop wasting (atrophy) in their hands and feet, which further impairs movement. Nearly all individuals with ataxia with oculomotor apraxia develop neuropathy, which leads to absent reflexes and weakness. Neuropathy causes many individuals with this condition to require wheelchair assistance, typically 10 to 15 years after the start of movement problems. Intelligence is usually not affected by this condition, but some people have intellectual disability.  People with ataxia with oculomotor apraxia type 1 tend to have decreased amounts of a protein called albumin, which transports molecules in the blood. This decrease in albumin likely causes an increase in the amount of cholesterol circulating in the bloodstream. Increased cholesterol levels may raise a person's risk of developing heart disease. People with ataxia with oculomotor apraxia type 2 have increased blood cholesterol, but they have normal albumin levels. Individuals with type 2 tend to have high amounts of a protein called alpha-fetoprotein (AFP) in their blood. (An increase in the level of this protein is normally seen in the bloodstream of pregnant women.) Affected individuals may also have high amounts of a protein called creatine phosphokinase (CPK) in their blood. This protein is found mainly in muscle tissue. The effect of abnormally high levels of AFP or CPK in people with ataxia with oculomotor apraxia type 2 is unknown.",ataxia with oculomotor apraxia,0000078,GHR,https://ghr.nlm.nih.gov/condition/ataxia-with-oculomotor-apraxia,C0271270,T047,Disorders
How many people are affected by ataxia with oculomotor apraxia ?,0000078-2,frequency,"Ataxia with oculomotor apraxia is a rare condition. Type 1 is a common form of ataxia in Portugal and Japan. Type 2 is estimated to occur in 1 in 900,000 individuals worldwide.",ataxia with oculomotor apraxia,0000078,GHR,https://ghr.nlm.nih.gov/condition/ataxia-with-oculomotor-apraxia,C0271270,T047,Disorders
What are the genetic changes related to ataxia with oculomotor apraxia ?,0000078-3,genetic changes,"Mutations in the APTX and SETX genes cause ataxia with oculomotor apraxia types 1 and 2, respectively. These genes provide instructions for making proteins that are involved in DNA repair.  Mutations in the APTX or SETX gene decrease the amount of functional protein that is available to repair damaged DNA, which leads to the accumulation of breaks in DNA. These breaks can be caused by natural and medical radiation or other environmental exposures, and also occur when chromosomes exchange genetic material in preparation for cell division. DNA damage that is not repaired causes the cell to be unstable and can lead to cell death. It is thought that nerve cells in the brain are particularly affected by cell death because these cells do not copy (replicate) themselves to replace cells that have been lost. The part of the brain involved in coordinating movements (the cerebellum) is especially affected. It is thought that the loss of brain cells in the cerebellum causes the movement problems characteristic of ataxia with oculomotor apraxia.  Mutations in other genes are responsible for the rare types of ataxia with oculomotor apraxia.",ataxia with oculomotor apraxia,0000078,GHR,https://ghr.nlm.nih.gov/condition/ataxia-with-oculomotor-apraxia,C0271270,T047,Disorders
Is ataxia with oculomotor apraxia inherited ?,0000078-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",ataxia with oculomotor apraxia,0000078,GHR,https://ghr.nlm.nih.gov/condition/ataxia-with-oculomotor-apraxia,C0271270,T047,Disorders
What are the treatments for ataxia with oculomotor apraxia ?,0000078-5,treatment,These resources address the diagnosis or management of ataxia with oculomotor apraxia:  - Gene Review: Gene Review: Ataxia with Oculomotor Apraxia Type 1  - Gene Review: Gene Review: Ataxia with Oculomotor Apraxia Type 2  - Genetic Testing Registry: Adult onset ataxia with oculomotor apraxia  - Genetic Testing Registry: Ataxia-oculomotor apraxia 3  - Genetic Testing Registry: Ataxia-oculomotor apraxia 4  - Genetic Testing Registry: Spinocerebellar ataxia autosomal recessive 1  - MedlinePlus Encyclopedia: Apraxia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,ataxia with oculomotor apraxia,0000078,GHR,https://ghr.nlm.nih.gov/condition/ataxia-with-oculomotor-apraxia,C0271270,T047,Disorders
What is (are) ataxia with vitamin E deficiency ?,0000079-1,information,"Ataxia with vitamin E deficiency is a disorder that impairs the body's ability to use vitamin E obtained from the diet. Vitamin E is an antioxidant, which means that it protects cells in the body from the damaging effects of unstable molecules called free radicals. A shortage (deficiency) of vitamin E can lead to neurological problems, such as difficulty coordinating movements (ataxia) and speech (dysarthria), loss of reflexes in the legs (lower limb areflexia), and a loss of sensation in the extremities (peripheral neuropathy). Some people with this condition have developed an eye disorder called retinitis pigmentosa that causes vision loss. Most people who have ataxia with vitamin E deficiency start to experience problems with movement between the ages of 5 and 15 years. The movement problems tend to worsen with age.",ataxia with vitamin E deficiency,0000079,GHR,https://ghr.nlm.nih.gov/condition/ataxia-with-vitamin-e-deficiency,C1848533,T047,Disorders
How many people are affected by ataxia with vitamin E deficiency ?,0000079-2,frequency,"Ataxia with vitamin E deficiency is a rare condition; however, its prevalence is unknown.",ataxia with vitamin E deficiency,0000079,GHR,https://ghr.nlm.nih.gov/condition/ataxia-with-vitamin-e-deficiency,C1848533,T047,Disorders
What are the genetic changes related to ataxia with vitamin E deficiency ?,0000079-3,genetic changes,"Mutations in the TTPA gene cause ataxia with vitamin E deficiency. The TTPA gene provides instructions for making the -tocopherol transfer protein (TTP), which is found in the liver and brain. This protein controls distribution of vitamin E obtained from the diet (also called -tocopherol) to cells and tissues throughout the body. Vitamin E helps cells prevent damage that might be done by free radicals.  TTPA gene mutations impair the activity of the TTP protein, resulting in an inability to retain and use dietary vitamin E. As a result, vitamin E levels in the blood are greatly reduced and free radicals accumulate within cells. Nerve cells (neurons) in the brain and spinal cord (central nervous system) are particularly vulnerable to the damaging effects of free radicals and these cells die off when they are deprived of vitamin E. Nerve cell damage can lead to problems with movement and other features of ataxia with vitamin E deficiency.",ataxia with vitamin E deficiency,0000079,GHR,https://ghr.nlm.nih.gov/condition/ataxia-with-vitamin-e-deficiency,C1848533,T047,Disorders
Is ataxia with vitamin E deficiency inherited ?,0000079-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",ataxia with vitamin E deficiency,0000079,GHR,https://ghr.nlm.nih.gov/condition/ataxia-with-vitamin-e-deficiency,C1848533,T047,Disorders
What are the treatments for ataxia with vitamin E deficiency ?,0000079-5,treatment,These resources address the diagnosis or management of ataxia with vitamin E deficiency:  - Gene Review: Gene Review: Ataxia with Vitamin E Deficiency  - Genetic Testing Registry: Ataxia with vitamin E deficiency  - MedlinePlus Encyclopedia: Retinitis pigmentosa  - MedlinePlus Encyclopedia: Vitamin E   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,ataxia with vitamin E deficiency,0000079,GHR,https://ghr.nlm.nih.gov/condition/ataxia-with-vitamin-e-deficiency,C1848533,T047,Disorders
What is (are) ataxia-telangiectasia ?,0000080-1,information,"Ataxia-telangiectasia is a rare inherited disorder that affects the nervous system, immune system, and other body systems. This disorder is characterized by progressive difficulty with coordinating movements (ataxia) beginning in early childhood, usually before age 5. Affected children typically develop difficulty walking, problems with balance and hand coordination, involuntary jerking movements (chorea), muscle twitches (myoclonus), and disturbances in nerve function (neuropathy). The movement problems typically cause people to require wheelchair assistance by adolescence. People with this disorder also have slurred speech and trouble moving their eyes to look side-to-side (oculomotor apraxia). Small clusters of enlarged blood vessels called telangiectases, which occur in the eyes and on the surface of the skin, are also characteristic of this condition.  Affected individuals tend to have high amounts of a protein called alpha-fetoprotein (AFP) in their blood. The level of this protein is normally increased in the bloodstream of pregnant women, but it is unknown why individuals with ataxia-telangiectasia have elevated AFP or what effects it has in these individuals.  People with ataxia-telangiectasia often have a weakened immune system, and many develop chronic lung infections. They also have an increased risk of developing cancer, particularly cancer of blood-forming cells (leukemia) and cancer of immune system cells (lymphoma). Affected individuals are very sensitive to the effects of radiation exposure, including medical x-rays. The life expectancy of people with ataxia-telangiectasia varies greatly, but affected individuals typically live into early adulthood.",ataxia-telangiectasia,0000080,GHR,https://ghr.nlm.nih.gov/condition/ataxia-telangiectasia,C0004135,T019,Disorders
How many people are affected by ataxia-telangiectasia ?,0000080-2,frequency,"Ataxia-telangiectasia occurs in 1 in 40,000 to 100,000 people worldwide.",ataxia-telangiectasia,0000080,GHR,https://ghr.nlm.nih.gov/condition/ataxia-telangiectasia,C0004135,T019,Disorders
What are the genetic changes related to ataxia-telangiectasia ?,0000080-3,genetic changes,"Mutations in the ATM gene cause ataxia-telangiectasia. The ATM gene provides instructions for making a protein that helps control cell division and is involved in DNA repair. This protein plays an important role in the normal development and activity of several body systems, including the nervous system and immune system. The ATM protein assists cells in recognizing damaged or broken DNA strands and coordinates DNA repair by activating enzymes that fix the broken strands. Efficient repair of damaged DNA strands helps maintain the stability of the cell's genetic information.  Mutations in the ATM gene reduce or eliminate the function of the ATM protein. Without this protein, cells become unstable and die. Cells in the part of the brain involved in coordinating movements (the cerebellum) are particularly affected by loss of the ATM protein. The loss of these brain cells causes some of the movement problems characteristic of ataxia-telangiectasia. Mutations in the ATM gene also prevent cells from responding correctly to DNA damage, which allows breaks in DNA strands to accumulate and can lead to the formation of cancerous tumors.",ataxia-telangiectasia,0000080,GHR,https://ghr.nlm.nih.gov/condition/ataxia-telangiectasia,C0004135,T019,Disorders
Is ataxia-telangiectasia inherited ?,0000080-4,inheritance,"Ataxia-telangiectasia is inherited in an autosomal recessive pattern, which means both copies of the ATM gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.  About 1 percent of the United States population carries one mutated copy and one normal copy of the ATM gene in each cell. These individuals are called carriers. Although ATM mutation carriers do not have ataxia-telangiectasia, they are more likely than people without an ATM mutation to develop cancer; female carriers are particularly at risk for developing breast cancer. Carriers of a mutation in the ATM gene also may have an increased risk of heart disease.",ataxia-telangiectasia,0000080,GHR,https://ghr.nlm.nih.gov/condition/ataxia-telangiectasia,C0004135,T019,Disorders
What are the treatments for ataxia-telangiectasia ?,0000080-5,treatment,These resources address the diagnosis or management of ataxia-telangiectasia:  - Gene Review: Gene Review: Ataxia-Telangiectasia  - Genetic Testing Registry: Ataxia-telangiectasia syndrome  - MedlinePlus Encyclopedia: Ataxia-Telangiectasia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,ataxia-telangiectasia,0000080,GHR,https://ghr.nlm.nih.gov/condition/ataxia-telangiectasia,C0004135,T019,Disorders
What is (are) atelosteogenesis type 1 ?,0000081-1,information,"Atelosteogenesis type 1 is a disorder that affects the development of bones throughout the body. Affected individuals are born with inward- and upward-turning feet (clubfeet) and dislocations of the hips, knees, and elbows. Bones in the spine, rib cage, pelvis, and limbs may be underdeveloped or in some cases absent. As a result of the limb bone abnormalities, individuals with this condition have very short arms and legs. Characteristic facial features include a prominent forehead, wide-set eyes (hypertelorism), an upturned nose with a grooved tip, and a very small lower jaw and chin (micrognathia). Affected individuals may also have an opening in the roof of the mouth (a cleft palate). Males with this condition can have undescended testes.  Individuals with atelosteogenesis type 1 typically have an underdeveloped rib cage that affects the development and functioning of the lungs. As a result, affected individuals are usually stillborn or die shortly after birth from respiratory failure.",atelosteogenesis type 1,0000081,GHR,https://ghr.nlm.nih.gov/condition/atelosteogenesis-type-1,C0265283,T019,Disorders
How many people are affected by atelosteogenesis type 1 ?,0000081-2,frequency,Atelosteogenesis type 1 is a rare disorder; its exact prevalence is unknown. Only a few dozen affected individuals have been identified.,atelosteogenesis type 1,0000081,GHR,https://ghr.nlm.nih.gov/condition/atelosteogenesis-type-1,C0265283,T019,Disorders
What are the genetic changes related to atelosteogenesis type 1 ?,0000081-3,genetic changes,"Mutations in the FLNB gene cause atelosteogenesis type 1. The FLNB gene provides instructions for making a protein called filamin B. This protein helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. Filamin B attaches (binds) to another protein called actin and helps the actin to form the branching network of filaments that makes up the cytoskeleton. Filamin B also links actin to many other proteins to perform various functions within the cell, including the cell signaling that helps determine how the cytoskeleton will change as tissues grow and take shape during development.  Filamin B is especially important in the development of the skeleton before birth. It is active (expressed) in the cell membranes of cartilage-forming cells (chondrocytes). Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, a process called ossification, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose, airways (trachea and bronchi), and external ears. Filamin B appears to be important for normal cell growth and division (proliferation) and maturation (differentiation) of chondrocytes and for the ossification of cartilage.  FLNB gene mutations that cause atelosteogenesis type 1 change single protein building blocks (amino acids) in the filamin B protein or delete a small section of the protein sequence, resulting in an abnormal protein. This abnormal protein appears to have a new, atypical function that interferes with the proliferation or differentiation of chondrocytes, impairing ossification and leading to the signs and symptoms of atelosteogenesis type 1.",atelosteogenesis type 1,0000081,GHR,https://ghr.nlm.nih.gov/condition/atelosteogenesis-type-1,C0265283,T019,Disorders
Is atelosteogenesis type 1 inherited ?,0000081-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Almost all cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",atelosteogenesis type 1,0000081,GHR,https://ghr.nlm.nih.gov/condition/atelosteogenesis-type-1,C0265283,T019,Disorders
What are the treatments for atelosteogenesis type 1 ?,0000081-5,treatment,These resources address the diagnosis or management of atelosteogenesis type 1:  - Gene Review: Gene Review: FLNB-Related Disorders  - Genetic Testing Registry: Atelosteogenesis type 1   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,atelosteogenesis type 1,0000081,GHR,https://ghr.nlm.nih.gov/condition/atelosteogenesis-type-1,C0265283,T019,Disorders
What is (are) atelosteogenesis type 2 ?,0000082-1,information,"Atelosteogenesis type 2 is a severe disorder of cartilage and bone development. Infants born with this condition have very short arms and legs, a narrow chest, and a prominent, rounded abdomen. This disorder is also characterized by an opening in the roof of the mouth (a cleft palate), distinctive facial features, an inward- and upward-turning foot (clubfoot), and unusually positioned thumbs (hitchhiker thumbs).  The signs and symptoms of atelosteogenesis type 2 are similar to those of another skeletal disorder called diastrophic dysplasia; however, atelosteogenesis type 2 is typically more severe. As a result of serious health problems, infants with this disorder are usually stillborn or die soon after birth from respiratory failure. Some infants, however, have lived for a short time with intensive medical support.",atelosteogenesis type 2,0000082,GHR,https://ghr.nlm.nih.gov/condition/atelosteogenesis-type-2,C1850554,T047,Disorders
How many people are affected by atelosteogenesis type 2 ?,0000082-2,frequency,Atelosteogenesis type 2 is an extremely rare genetic disorder; its incidence is unknown.,atelosteogenesis type 2,0000082,GHR,https://ghr.nlm.nih.gov/condition/atelosteogenesis-type-2,C1850554,T047,Disorders
What are the genetic changes related to atelosteogenesis type 2 ?,0000082-3,genetic changes,"Atelosteogenesis type 2 is one of several skeletal disorders caused by mutations in the SLC26A2 gene. This gene provides instructions for making a protein that is essential for the normal development of cartilage and for its conversion to bone. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Mutations in the SLC26A2 gene disrupt the structure of developing cartilage, preventing bones from forming properly and resulting in the skeletal problems characteristic of atelosteogenesis type 2.",atelosteogenesis type 2,0000082,GHR,https://ghr.nlm.nih.gov/condition/atelosteogenesis-type-2,C1850554,T047,Disorders
Is atelosteogenesis type 2 inherited ?,0000082-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",atelosteogenesis type 2,0000082,GHR,https://ghr.nlm.nih.gov/condition/atelosteogenesis-type-2,C1850554,T047,Disorders
What are the treatments for atelosteogenesis type 2 ?,0000082-5,treatment,These resources address the diagnosis or management of atelosteogenesis type 2:  - Gene Review: Gene Review: Atelosteogenesis Type 2  - Genetic Testing Registry: Atelosteogenesis type 2   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,atelosteogenesis type 2,0000082,GHR,https://ghr.nlm.nih.gov/condition/atelosteogenesis-type-2,C1850554,T047,Disorders
What is (are) atelosteogenesis type 3 ?,0000083-1,information,"Atelosteogenesis type 3 is a disorder that affects the development of bones throughout the body. Affected individuals are born with inward- and upward-turning feet (clubfeet) and dislocations of the hips, knees, and elbows. Bones in the spine, rib cage, pelvis, and limbs may be underdeveloped or in some cases absent. As a result of the limb bone abnormalities, individuals with this condition have very short arms and legs. Their hands and feet are wide, with broad fingers and toes that may be permanently bent (camptodactyly) or fused together (syndactyly). Characteristic facial features include a broad forehead, wide-set eyes (hypertelorism), and an underdeveloped nose. About half of affected individuals have an opening in the roof of the mouth (a cleft palate.)  Individuals with atelosteogenesis type 3 typically have an underdeveloped rib cage that affects the development and functioning of the lungs. As a result, affected individuals are usually stillborn or die shortly after birth from respiratory failure. Some affected individuals survive longer, usually with intensive medical support. They typically experience further respiratory problems as a result of weakness of the airways that can lead to partial closing, short pauses in breathing (apnea), or frequent infections. People with atelosteogenesis type 3 who survive past the newborn period may have learning disabilities and delayed language skills, which are probably caused by low levels of oxygen in the brain due to respiratory problems. As a result of their orthopedic abnormalities, they also have delayed development of motor skills such as standing and walking.",atelosteogenesis type 3,0000083,GHR,https://ghr.nlm.nih.gov/condition/atelosteogenesis-type-3,C3668942,T047,Disorders
How many people are affected by atelosteogenesis type 3 ?,0000083-2,frequency,Atelosteogenesis type 3 is a rare disorder; its exact prevalence is unknown. About two dozen affected individuals have been identified.,atelosteogenesis type 3,0000083,GHR,https://ghr.nlm.nih.gov/condition/atelosteogenesis-type-3,C3668942,T047,Disorders
What are the genetic changes related to atelosteogenesis type 3 ?,0000083-3,genetic changes,"Mutations in the FLNB gene cause atelosteogenesis type 3. The FLNB gene provides instructions for making a protein called filamin B. This protein helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. Filamin B attaches (binds) to another protein called actin and helps the actin to form the branching network of filaments that makes up the cytoskeleton. It also links actin to many other proteins to perform various functions within the cell, including the cell signaling that helps determine how the cytoskeleton will change as tissues grow and take shape during development.  Filamin B is especially important in the development of the skeleton before birth. It is active (expressed) in the cell membranes of cartilage-forming cells (chondrocytes). Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone (a process called ossification), except for the cartilage that continues to cover and protect the ends of bones and is present in the nose, airways (trachea and bronchi), and external ears. Filamin B appears to be important for normal cell growth and division (proliferation) and maturation (differentiation) of chondrocytes and for the ossification of cartilage.  FLNB gene mutations that cause atelosteogenesis type 3 change single protein building blocks (amino acids) in the filamin B protein or delete a small section of the protein sequence, resulting in an abnormal protein. This abnormal protein appears to have a new, atypical function that interferes with the proliferation or differentiation of chondrocytes, impairing ossification and leading to the signs and symptoms of atelosteogenesis type 3.",atelosteogenesis type 3,0000083,GHR,https://ghr.nlm.nih.gov/condition/atelosteogenesis-type-3,C3668942,T047,Disorders
Is atelosteogenesis type 3 inherited ?,0000083-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",atelosteogenesis type 3,0000083,GHR,https://ghr.nlm.nih.gov/condition/atelosteogenesis-type-3,C3668942,T047,Disorders
What are the treatments for atelosteogenesis type 3 ?,0000083-5,treatment,These resources address the diagnosis or management of atelosteogenesis type 3:  - Gene Review: Gene Review: FLNB-Related Disorders  - Genetic Testing Registry: Atelosteogenesis type 3   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,atelosteogenesis type 3,0000083,GHR,https://ghr.nlm.nih.gov/condition/atelosteogenesis-type-3,C3668942,T047,Disorders
What is (are) atopic dermatitis ?,0000084-1,information,"Atopic dermatitis (also known as atopic eczema) is a disorder characterized by inflammation of the skin (dermatitis). The condition usually begins in early infancy, and it often disappears before adolescence. However, in some affected individuals the condition continues into adulthood or does not begin until adulthood. Hallmarks of atopic dermatitis include dry, itchy skin and red rashes that can come and go. The rashes can occur on any part of the body, although the pattern tends to be different at different ages. In affected infants, the rashes commonly occur on the face, scalp, hands, and feet. In children, the rashes are usually found in the bend of the elbows and knees and on the front of the neck. In adolescents and adults, the rashes typically occur on the wrists, ankles, and eyelids in addition to the bend of the elbows and knees. Scratching the itchy skin can lead to oozing and crusting of the rashes and thickening and hardening (lichenification) of the skin. The itchiness can be so severe as to disturb sleep and impair a person's quality of life.  The word ""atopic"" indicates an association with allergies. While atopic dermatitis is not always due to an allergic reaction, it is commonly associated with other allergic disorders: up to 60 percent of people with atopic dermatitis develop asthma or hay fever (allergic rhinitis) later in life, and up to 30 percent have food allergies. Atopic dermatitis is often the beginning of a series of allergic disorders, referred to as the atopic march. Development of these disorders typically follows a pattern, beginning with atopic dermatitis, followed by food allergies, then hay fever, and finally asthma. However, not all individuals with atopic dermatitis will progress through the atopic march, and not all individuals with one allergic disease will develop others.  Individuals with atopic dermatitis have an increased risk of developing other conditions related to inflammation, such as inflammatory bowel disease and rheumatoid arthritis. They are also more likely than individuals of the general public to have a behavioral or psychiatric disorder, such as attention deficit hyperactivity disorder (ADHD) or depression.",atopic dermatitis,0000084,GHR,https://ghr.nlm.nih.gov/condition/atopic-dermatitis,C0013595,T047,Disorders
How many people are affected by atopic dermatitis ?,0000084-2,frequency,Atopic dermatitis is a common disorder that affects 10 to 20 percent of children and 5 to 10 percent of adults.,atopic dermatitis,0000084,GHR,https://ghr.nlm.nih.gov/condition/atopic-dermatitis,C0013595,T047,Disorders
What are the genetic changes related to atopic dermatitis ?,0000084-3,genetic changes,"The genetics of atopic dermatitis are not completely understood. Studies suggest that several genes can be involved in development of the condition. The strongest association is with the FLG gene, which is mutated in 20 to 30 percent of people with atopic dermatitis compared with 8 to 10 percent of the general population without atopic dermatitis.  The FLG gene provides instructions for making a protein called profilaggrin, which is cut (cleaved) to produce multiple copies of the filaggrin protein. Filaggrin is involved in creating the structure of the outermost layer of skin, creating a strong barrier to keep in water and keep out foreign substances, including toxins, bacteria, and substances that can cause allergic reactions (allergens), such as pollen and dust. Further processing of the filaggrin protein produces other molecules that are part of the skin's ""natural moisturizing factor,"" which helps maintain hydration of the outermost layer of skin.  Mutations in the FLG gene lead to production of an abnormally short profilaggrin molecule that cannot be cleaved to produce filaggrin proteins. The resulting shortage of filaggrin can impair the barrier function of the skin. In addition, a lack of natural moisturizing factor allows excess water loss through the skin, which can lead to dry skin.  Research shows that impairment of the skin's barrier function contributes to development of allergic disorders. An allergic reaction occurs when the body mistakenly recognizes a harmless substance, such as pollen, as a danger and stimulates an immune response to it. Research suggests that without a properly functioning barrier, allergens are able to get into the body through the skin. For unknown reasons, in susceptible individuals the body reacts as if the allergen is harmful and produces immune proteins called IgE antibodies specific to the allergen. Upon later encounters with the allergen, IgE antibodies recognize it, which stimulates an immune response, causing the symptoms of allergies, such as itchy, watery eyes or breathing difficulty. Although atopic dermatitis is not initially caused by an allergic reaction, flare-ups of the rashes can be triggered by allergens. The impaired barrier function caused by FLG gene mutations also contributes to the increased risk of asthma and other allergic disorders in people with atopic dermatitis.  Mutations in many other genes, most of which have not been identified, are likely associated with development of atopic dermatitis. Researchers suspect these genes are involved in the skin's barrier function or in the function of the immune system. However, not everyone with a mutation in FLG or another associated gene develops atopic dermatitis; exposure to certain environmental factors also contributes to the development of the disorder. Studies suggest that these exposures trigger epigenetic changes to the DNA. Epigenetic changes modify DNA without changing the DNA sequence. They can affect gene activity and regulate the production of proteins, which may influence the development of allergies in susceptible individuals.",atopic dermatitis,0000084,GHR,https://ghr.nlm.nih.gov/condition/atopic-dermatitis,C0013595,T047,Disorders
Is atopic dermatitis inherited ?,0000084-4,inheritance,"Allergic disorders tend to run in families; having a parent with atopic dermatitis, asthma, or hay fever raises the chances a person will develop atopic dermatitis. When associated with FLG gene mutations, atopic dermatitis follows an autosomal dominant inheritance pattern, which means one copy of the altered FLG gene in each cell is sufficient to increase the risk of the disorder. Individuals with two altered copies of the gene are more likely to develop the disorder and can have more severe signs and symptoms than individuals with a single altered copy. When associated with other genetic factors, the inheritance pattern is unclear.  People with changes in one of the genes associated with atopic dermatitis, including FLG, inherit an increased risk of this condition, not the condition itself. Not all people with this condition have a mutation in an associated gene, and not all people with a variation in an associated gene will develop the disorder.",atopic dermatitis,0000084,GHR,https://ghr.nlm.nih.gov/condition/atopic-dermatitis,C0013595,T047,Disorders
What are the treatments for atopic dermatitis ?,0000084-5,treatment,These resources address the diagnosis or management of atopic dermatitis:  - American Academy of Dermatology: Atopic Dermatitis: Tips for Managing   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,atopic dermatitis,0000084,GHR,https://ghr.nlm.nih.gov/condition/atopic-dermatitis,C0013595,T047,Disorders
What is (are) atypical hemolytic-uremic syndrome ?,0000085-1,information,"Atypical hemolytic-uremic syndrome is a disease that primarily affects kidney function. This condition, which can occur at any age, causes abnormal blood clots (thrombi) to form in small blood vessels in the kidneys. These clots can cause serious medical problems if they restrict or block blood flow. Atypical hemolytic-uremic syndrome is characterized by three major features related to abnormal clotting: hemolytic anemia, thrombocytopenia, and kidney failure.  Hemolytic anemia occurs when red blood cells break down (undergo hemolysis) prematurely. In atypical hemolytic-uremic syndrome, red blood cells can break apart as they squeeze past clots within small blood vessels. Anemia results if these cells are destroyed faster than the body can replace them. This condition can lead to unusually pale skin (pallor), yellowing of the eyes and skin (jaundice), fatigue, shortness of breath, and a rapid heart rate.  Thrombocytopenia is a reduced level of circulating platelets, which are cell fragments that normally assist with blood clotting. In people with atypical hemolytic-uremic syndrome, fewer platelets are available in the bloodstream because a large number of platelets are used to make abnormal clots. Thrombocytopenia can cause easy bruising and abnormal bleeding.  As a result of clot formation in small blood vessels, people with atypical hemolytic-uremic syndrome experience kidney damage and acute kidney failure that lead to end-stage renal disease (ESRD) in about half of all cases. These life-threatening complications prevent the kidneys from filtering fluids and waste products from the body effectively.  Atypical hemolytic-uremic syndrome should be distinguished from a more common condition called typical hemolytic-uremic syndrome. The two disorders have different causes and different signs and symptoms. Unlike the atypical form, the typical form is caused by infection with certain strains of Escherichia coli bacteria that produce toxic substances called Shiga-like toxins. The typical form is characterized by severe diarrhea and most often affects children younger than 10. The typical form is less likely than the atypical form to involve recurrent attacks of kidney damage that lead to ESRD.",atypical hemolytic-uremic syndrome,0000085,GHR,https://ghr.nlm.nih.gov/condition/atypical-hemolytic-uremic-syndrome,C0741302,T047,Disorders
How many people are affected by atypical hemolytic-uremic syndrome ?,0000085-2,frequency,"The incidence of atypical hemolytic-uremic syndrome is estimated to be 1 in 500,000 people per year in the United States. The atypical form is probably about 10 times less common than the typical form.",atypical hemolytic-uremic syndrome,0000085,GHR,https://ghr.nlm.nih.gov/condition/atypical-hemolytic-uremic-syndrome,C0741302,T047,Disorders
What are the genetic changes related to atypical hemolytic-uremic syndrome ?,0000085-3,genetic changes,"Atypical hemolytic-uremic syndrome often results from a combination of environmental and genetic factors. Mutations in at least seven genes appear to increase the risk of developing the disorder. Mutations in a gene called CFH are most common; they have been found in about 30 percent of all cases of atypical hemolytic-uremic syndrome. Mutations in the other genes have each been identified in a smaller percentage of cases.  The genes associated with atypical hemolytic-uremic syndrome provide instructions for making proteins involved in a part of the body's immune response known as the complement system. This system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. The complement system must be carefully regulated so it targets only unwanted materials and does not attack the body's healthy cells. The regulatory proteins associated with atypical hemolytic-uremic syndrome protect healthy cells by preventing activation of the complement system when it is not needed.  Mutations in the genes associated with atypical hemolytic-uremic syndrome lead to uncontrolled activation of the complement system. The overactive system attacks cells that line blood vessels in the kidneys, causing inflammation and the formation of abnormal clots. These abnormalities lead to kidney damage and, in many cases, kidney failure and ESRD.  Although gene mutations increase the risk of atypical hemolytic-uremic syndrome, studies suggest that they are often not sufficient to cause the disease. In people with certain genetic changes, the signs and symptoms of the disorder may be triggered by factors including certain medications (such as anticancer drugs), chronic diseases, viral or bacterial infections, cancers, organ transplantation, or pregnancy.  Some people with atypical hemolytic-uremic syndrome do not have any known genetic changes or environmental triggers for the disease. In these cases, the disorder is described as idiopathic.",atypical hemolytic-uremic syndrome,0000085,GHR,https://ghr.nlm.nih.gov/condition/atypical-hemolytic-uremic-syndrome,C0741302,T047,Disorders
Is atypical hemolytic-uremic syndrome inherited ?,0000085-4,inheritance,"Most cases of atypical hemolytic-uremic syndrome are sporadic, which means that they occur in people with no apparent history of the disorder in their family. Less than 20 percent of all cases have been reported to run in families. When the disorder is familial, it can have an autosomal dominant or an autosomal recessive pattern of inheritance.  Autosomal dominant inheritance means one copy of an altered gene in each cell is sufficient to increase the risk of the disorder. In some cases, an affected person inherits the mutation from one affected parent. However, most people with the autosomal dominant form of atypical hemolytic-uremic syndrome have no history of the disorder in their family. Because not everyone who inherits a gene mutation will develop the signs and symptoms of the disease, an affected individual may have unaffected relatives who carry a copy of the mutation.  Autosomal recessive inheritance means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",atypical hemolytic-uremic syndrome,0000085,GHR,https://ghr.nlm.nih.gov/condition/atypical-hemolytic-uremic-syndrome,C0741302,T047,Disorders
What are the treatments for atypical hemolytic-uremic syndrome ?,0000085-5,treatment,These resources address the diagnosis or management of atypical hemolytic-uremic syndrome:  - Gene Review: Gene Review: Atypical Hemolytic-Uremic Syndrome  - Genetic Testing Registry: Atypical hemolytic uremic syndrome  - Genetic Testing Registry: Atypical hemolytic-uremic syndrome 1  - Genetic Testing Registry: Atypical hemolytic-uremic syndrome 2  - Genetic Testing Registry: Atypical hemolytic-uremic syndrome 3  - Genetic Testing Registry: Atypical hemolytic-uremic syndrome 4  - Genetic Testing Registry: Atypical hemolytic-uremic syndrome 5  - Genetic Testing Registry: Atypical hemolytic-uremic syndrome 6  - MedlinePlus Encyclopedia: Hemolytic Anemia  - MedlinePlus Encyclopedia: Hemolytic-Uremic Syndrome  - MedlinePlus Encyclopedia: Thrombocytopenia  - National Institute of Diabetes and Digestive and Kidney Diseases: Kidney Failure: Choosing a Treatment That's Right for You   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,atypical hemolytic-uremic syndrome,0000085,GHR,https://ghr.nlm.nih.gov/condition/atypical-hemolytic-uremic-syndrome,C0741302,T047,Disorders
What is (are) auriculo-condylar syndrome ?,0000086-1,information,"Auriculo-condylar syndrome is a condition that affects facial development, particularly development of the ears and lower jaw (mandible).  Most people with auriculo-condylar syndrome have malformed outer ears (""auriculo-"" refers to the ears). A hallmark of this condition is an ear abnormality called a ""question-mark ear,"" in which the ears have a distinctive question-mark shape caused by a split that separates the upper part of the ear from the earlobe. Other ear abnormalities that can occur in auriculo-condylar syndrome include cupped ears, ears with fewer folds and grooves than usual (described as ""simple""), narrow ear canals, small skin tags in front of or behind the ears, and ears that are rotated backward. Some affected individuals also have hearing loss.  Abnormalities of the mandible are another characteristic feature of auriculo-condylar syndrome. These abnormalities often include an unusually small chin (micrognathia) and malfunction of the temporomandibular joint (TMJ), which connects the lower jaw to the skull. Problems with the TMJ affect how the upper and lower jaws fit together and can make it difficult to open and close the mouth. The term ""condylar"" in the name of the condition refers to the mandibular condyle, which is the upper portion of the mandible that forms part of the TMJ.  Other features of auriculo-condylar syndrome can include prominent cheeks, an unusually small mouth (microstomia), differences in the size and shape of facial structures between the right and left sides of the face (facial asymmetry), and an opening in the roof of the mouth (cleft palate). These features vary, even among affected members of the same family.",auriculo-condylar syndrome,0000086,GHR,https://ghr.nlm.nih.gov/condition/auriculo-condylar-syndrome,C1865295,T047,Disorders
How many people are affected by auriculo-condylar syndrome ?,0000086-2,frequency,Auriculo-condylar syndrome appears to be a rare disorder. More than two dozen affected individuals have been described in the medical literature.,auriculo-condylar syndrome,0000086,GHR,https://ghr.nlm.nih.gov/condition/auriculo-condylar-syndrome,C1865295,T047,Disorders
What are the genetic changes related to auriculo-condylar syndrome ?,0000086-3,genetic changes,"Auriculo-condylar syndrome can be caused by mutations in either the GNAI3 or PLCB4 gene. These genes provide instructions for making proteins that are involved in chemical signaling within cells. They help transmit information from outside the cell to inside the cell, which instructs the cell to grow, divide, or take on specialized functions.  Studies suggest that the proteins produced from the GNAI3 and PLCB4 genes contribute to the development of the first and second pharyngeal arches, which are structures in the embryo that ultimately develop into the jawbones, facial muscles, middle ear bones, ear canals, outer ears, and related tissues. Mutations in these genes alter the formation of the lower jaw: instead of developing normally, the lower jaw becomes shaped more like the smaller upper jaw (maxilla). This abnormal shape leads to micrognathia and problems with TMJ function. Researchers are working to determine how mutations in these genes lead to the other developmental abnormalities associated with auriculo-condylar syndrome.  In some people with the characteristic features of auriculo-condylar syndrome, a mutation in the GNAI3 or PLCB4 gene has not been found. The cause of the condition is unknown in these individuals.",auriculo-condylar syndrome,0000086,GHR,https://ghr.nlm.nih.gov/condition/auriculo-condylar-syndrome,C1865295,T047,Disorders
Is auriculo-condylar syndrome inherited ?,0000086-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is typically sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  Some people who have one altered copy of the GNAI3 or PLCB4 gene have no features related to auriculo-condylar syndrome. (This situation is known as reduced penetrance.) It is unclear why some people with a mutated gene develop the condition and other people with a mutated gene do not.",auriculo-condylar syndrome,0000086,GHR,https://ghr.nlm.nih.gov/condition/auriculo-condylar-syndrome,C1865295,T047,Disorders
What are the treatments for auriculo-condylar syndrome ?,0000086-5,treatment,These resources address the diagnosis or management of auriculo-condylar syndrome:  - Genetic Testing Registry: Auriculocondylar syndrome 1  - Genetic Testing Registry: Auriculocondylar syndrome 2  - MedlinePlus Encyclopedia: Cleft Lip and Palate  - MedlinePlus Encyclopedia: Pinna Abnormalities and Low-Set Ears   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,auriculo-condylar syndrome,0000086,GHR,https://ghr.nlm.nih.gov/condition/auriculo-condylar-syndrome,C1865295,T047,Disorders
What is (are) autoimmune Addison disease ?,0000087-1,information,"Autoimmune Addison disease affects the function of the adrenal glands, which are small hormone-producing glands located on top of each kidney. It is classified as an autoimmune disorder because it results from a malfunctioning immune system that attacks the adrenal glands. As a result, the production of several hormones is disrupted, which affects many body systems.  The signs and symptoms of autoimmune Addison disease can begin at any time, although they most commonly begin between ages 30 and 50. Common features of this condition include extreme tiredness (fatigue), nausea, decreased appetite, and weight loss. In addition, many affected individuals have low blood pressure (hypotension), which can lead to dizziness when standing up quickly; muscle cramps; and a craving for salty foods. A characteristic feature of autoimmune Addison disease is abnormally dark areas of skin (hyperpigmentation), especially in regions that experience a lot of friction, such as the armpits, elbows, knuckles, and palm creases. The lips and the inside lining of the mouth can also be unusually dark. Because of an imbalance of hormones involved in development of sexual characteristics, women with this condition may lose their underarm and pubic hair.  Other signs and symptoms of autoimmune Addison disease include low levels of sugar (hypoglycemia) and sodium (hyponatremia) and high levels of potassium (hyperkalemia) in the blood. Affected individuals may also have a shortage of red blood cells (anemia) and an increase in the number of white blood cells (lymphocytosis), particularly those known as eosinophils (eosinophilia).  Autoimmune Addison disease can lead to a life-threatening adrenal crisis, characterized by vomiting, abdominal pain, back or leg cramps, and severe hypotension leading to shock. The adrenal crisis is often triggered by a stressor, such as surgery, trauma, or infection.  Individuals with autoimmune Addison disease or their family members often have another autoimmune disorder, most commonly autoimmune thyroid disease or type 1 diabetes.",autoimmune Addison disease,0000087,GHR,https://ghr.nlm.nih.gov/condition/autoimmune-addison-disease,C2103602,T047,Disorders
How many people are affected by autoimmune Addison disease ?,0000087-2,frequency,"Addison disease affects approximately 11 to 14 in 100,000 people of European descent. The autoimmune form of the disorder is the most common form in developed countries, accounting for up to 90 percent of cases.",autoimmune Addison disease,0000087,GHR,https://ghr.nlm.nih.gov/condition/autoimmune-addison-disease,C2103602,T047,Disorders
What are the genetic changes related to autoimmune Addison disease ?,0000087-3,genetic changes,"The cause of autoimmune Addison disease is complex and not completely understood. A combination of environmental and genetic factors plays a role in the disorder, and changes in multiple genes are thought to affect the risk of developing the condition.  The genes that have been associated with autoimmune Addison disease participate in the body's immune response. The most commonly associated genes belong to a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Each HLA gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. The most well-known risk factor for autoimmune Addison disease is a variant of the HLA-DRB1 gene called HLA-DRB1*04:04. This and other disease-associated HLA gene variants likely contribute to an inappropriate immune response that leads to autoimmune Addison disease, although the mechanism is unknown.  Normally, the immune system responds only to proteins made by foreign invaders, not to the body's own proteins. In autoimmune Addison disease, however, an immune response is triggered by a normal adrenal gland protein, typically a protein called 21-hydroxylase. This protein plays a key role in producing certain hormones in the adrenal glands. The prolonged immune attack triggered by 21-hydroxylase damages the adrenal glands (specifically the outer layers of the glands known, collectively, as the adrenal cortex), preventing hormone production. A shortage of adrenal hormones (adrenal insufficiency) disrupts several normal functions in the body, leading to hypoglycemia, hyponatremia, hypotension, muscle cramps, skin hyperpigmentation and other features of autoimmune Addison disease.  Rarely, Addison disease is not caused by an autoimmune reaction. Other causes include infections that damage the adrenal glands, such as tuberculosis, or tumors in the adrenal glands. Addison disease can also be one of several features of other genetic conditions, including X-linked adrenoleukodystrophy and autoimmune polyglandular syndrome, type 1, which are caused by mutations in other genes.",autoimmune Addison disease,0000087,GHR,https://ghr.nlm.nih.gov/condition/autoimmune-addison-disease,C2103602,T047,Disorders
Is autoimmune Addison disease inherited ?,0000087-4,inheritance,"A predisposition to develop autoimmune Addison disease is passed through generations in families, but the inheritance pattern is unknown.",autoimmune Addison disease,0000087,GHR,https://ghr.nlm.nih.gov/condition/autoimmune-addison-disease,C2103602,T047,Disorders
What are the treatments for autoimmune Addison disease ?,0000087-5,treatment,These resources address the diagnosis or management of autoimmune Addison disease:  - Genetic Testing Registry: Addison's disease  - MedlinePlus Encyclopedia: Addison's Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,autoimmune Addison disease,0000087,GHR,https://ghr.nlm.nih.gov/condition/autoimmune-addison-disease,C2103602,T047,Disorders
What is (are) autoimmune lymphoproliferative syndrome ?,0000088-1,information,"Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder in which the body cannot properly regulate the number of immune system cells (lymphocytes). ALPS is characterized by the production of an abnormally large number of lymphocytes (lymphoproliferation). Accumulation of excess lymphocytes results in enlargement of the lymph nodes (lymphadenopathy), the liver (hepatomegaly), and the spleen (splenomegaly).  People with ALPS have an increased risk of developing cancer of the immune system cells (lymphoma) and may also be at increased risk of developing other cancers.  Autoimmune disorders are also common in ALPS. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. Most of the autoimmune disorders associated with ALPS target and damage blood cells. For example, the immune system may attack red blood cells (autoimmune hemolytic anemia), white blood cells (autoimmune neutropenia), or platelets (autoimmune thrombocytopenia). Less commonly, autoimmune disorders that affect other organs and tissues occur in people with ALPS. These disorders can damage the kidneys (glomerulonephritis), liver (autoimmune hepatitis), eyes (uveitis), nerves (Guillain-Barre syndrome), or the connective tissues (systemic lupus erythematosus) that provide strength and flexibility to structures throughout the body.  Skin problems, usually rashes or hives (urticaria), can occur in ALPS. Occasionally, affected individuals develop hardened skin with painful lumps or patches (panniculitis). Other rare signs and symptoms of ALPS include joint inflammation (arthritis), inflammation of blood vessels (vasculitis), mouth sores (oral ulcers), or an early loss of ovarian function (premature ovarian failure) may also occur in this disorder. Affected individuals can also develop neurological damage (organic brain syndrome) with symptoms that may include headaches, seizures, or a decline in intellectual functions (dementia).  ALPS can have different patterns of signs and symptoms, which are sometimes considered separate forms of the disorder. In the most common form, lymphoproliferation generally becomes apparent during childhood. Enlargement of the lymph nodes and spleen frequently occur in affected individuals. Autoimmune disorders typically develop several years later, most frequently as a combination of hemolytic anemia and thrombocytopenia, also called Evans syndrome. People with this classic form of ALPS have a greatly increased risk of developing lymphoma compared with the general population.  Other types of ALPS are very rare. In some affected individuals, severe lymphoproliferation begins around the time of birth, and autoimmune disorders and lymphoma develop at an early age. People with this pattern of signs and symptoms generally do not live beyond childhood. Another form of ALPS involves lymphoproliferation and the tendency to develop systemic lupus erythematosus. Individuals with this form of the disorder do not have an enlarged spleen.  Some people have signs and symptoms that resemble those of ALPS, but the specific pattern of these signs and symptoms or the genetic cause may be different than in other forms. Researchers disagree whether individuals with these non-classic forms should be considered to have ALPS or a separate condition.",autoimmune lymphoproliferative syndrome,0000088,GHR,https://ghr.nlm.nih.gov/condition/autoimmune-lymphoproliferative-syndrome,C1328840,T047,Disorders
How many people are affected by autoimmune lymphoproliferative syndrome ?,0000088-2,frequency,ALPS is a rare disorder; its prevalence is unknown. More than 200 affected individuals have been identified worldwide.,autoimmune lymphoproliferative syndrome,0000088,GHR,https://ghr.nlm.nih.gov/condition/autoimmune-lymphoproliferative-syndrome,C1328840,T047,Disorders
What are the genetic changes related to autoimmune lymphoproliferative syndrome ?,0000088-3,genetic changes,"Mutations in the FAS gene cause ALPS in approximately 75 percent of affected individuals. The FAS gene provides instructions for making a protein involved in cell signaling that results in the self-destruction of cells (apoptosis).  When the immune system is turned on (activated) to fight an infection, large numbers of lymphocytes are produced. Normally, these lymphocytes undergo apoptosis when they are no longer required. FAS gene mutations result in an abnormal protein that interferes with apoptosis. Excess lymphocytes accumulate in the body's tissues and organs and often begin attacking them, leading to autoimmune disorders. Interference with apoptosis allows cells to multiply without control, leading to the lymphomas and other cancers that occur in people with this disorder.  ALPS may also be caused by mutations in additional genes, some of which have not been identified.",autoimmune lymphoproliferative syndrome,0000088,GHR,https://ghr.nlm.nih.gov/condition/autoimmune-lymphoproliferative-syndrome,C1328840,T047,Disorders
Is autoimmune lymphoproliferative syndrome inherited ?,0000088-4,inheritance,"In most people with ALPS, including the majority of those with FAS gene mutations, this condition is inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. In these cases, an affected person usually inherits the mutation from one affected parent. Other cases with an autosomal dominant pattern result from new (de novo) gene mutations that occur early in embryonic development in people with no history of the disorder in their family.  In a small number of cases, including some cases caused by FAS gene mutations, ALPS is inherited in an autosomal recessive pattern, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  ALPS can also arise from a mutation in lymphocytes that is not inherited but instead occurs during an individual's lifetime. This alteration is called a somatic mutation.",autoimmune lymphoproliferative syndrome,0000088,GHR,https://ghr.nlm.nih.gov/condition/autoimmune-lymphoproliferative-syndrome,C1328840,T047,Disorders
What are the treatments for autoimmune lymphoproliferative syndrome ?,0000088-5,treatment,"These resources address the diagnosis or management of ALPS:  - Gene Review: Gene Review: Autoimmune Lymphoproliferative Syndrome  - Genetic Testing Registry: Autoimmune lymphoproliferative syndrome  - Genetic Testing Registry: Autoimmune lymphoproliferative syndrome type 1, autosomal recessive  - Genetic Testing Registry: Autoimmune lymphoproliferative syndrome, type 1a  - Genetic Testing Registry: Autoimmune lymphoproliferative syndrome, type 1b  - Genetic Testing Registry: Autoimmune lymphoproliferative syndrome, type 2  - Genetic Testing Registry: RAS-associated autoimmune leukoproliferative disorder  - National Institute of Allergy and Infectious Diseases (NIAID): ALPS Treatment   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",autoimmune lymphoproliferative syndrome,0000088,GHR,https://ghr.nlm.nih.gov/condition/autoimmune-lymphoproliferative-syndrome,C1328840,T047,Disorders
"What is (are) autoimmune polyglandular syndrome, type 1 ?",0000089-1,information,"Autoimmune polyglandular syndrome, type 1 is an inherited condition that affects many of the body's organs. It is one of many autoimmune diseases, which are disorders that occur when the immune system malfunctions and attacks the body's tissues and organs by mistake.  In most cases, the signs and symptoms of autoimmune polyglandular syndrome, type 1 begin in childhood or adolescence. This condition is characterized by three specific features: mucocutaneous candidiasis, hypoparathyroidism, and Addison disease. Affected individuals typically have at least two of these features, and many have all three.  Mucocutaneous candidiasis is a fungal infection that affects the skin and mucous membranes, such as the moist lining of the nose and mouth. In children with autoimmune polyglandular syndrome, type 1, these infections last a long time and tend to recur. Many affected children also develop hypoparathyroidism, which is a malfunction of the parathyroid glands. These glands secrete a hormone that regulates the body's use of calcium and phosphorus. Hypoparathyroidism can cause a tingling sensation in the lips, fingers, and toes; muscle pain and cramping; weakness; and fatigue. The third major feature, Addison disease, results from a malfunction of the small hormone-producing glands on top of each kidney (adrenal glands). The main features of Addison disease include fatigue, muscle weakness, loss of appetite, weight loss, low blood pressure, and changes in skin coloring.  Autoimmune polyglandular syndrome, type 1 can cause a variety of additional signs and symptoms, although they occur less often. Complications of this disorder can affect the skin and nails, the gonads (ovaries and testicles), the eyes, a butterfly-shaped gland at the base of the neck called the thyroid, and the digestive system. Type 1 diabetes also occurs in some patients with this condition.","autoimmune polyglandular syndrome, type 1",0000089,GHR,https://ghr.nlm.nih.gov/condition/autoimmune-polyglandular-syndrome-type-1,C0039082,T047,Disorders
"How many people are affected by autoimmune polyglandular syndrome, type 1 ?",0000089-2,frequency,"Autoimmune polyglandular syndrome, type 1 is thought to be a rare condition, with about 500 cases reported worldwide. This condition occurs more frequently in certain populations, including Iranian Jews, Sardinians, and Finns.","autoimmune polyglandular syndrome, type 1",0000089,GHR,https://ghr.nlm.nih.gov/condition/autoimmune-polyglandular-syndrome-type-1,C0039082,T047,Disorders
"What are the genetic changes related to autoimmune polyglandular syndrome, type 1 ?",0000089-3,genetic changes,"Mutations in the AIRE gene cause autoimmune polyglandular syndrome, type 1.  The AIRE gene provides instructions for making a protein called the autoimmune regulator. As its name suggests, this protein plays a critical role in regulating certain aspects of immune system function. Specifically, it helps the body distinguish its own proteins and cells from those of foreign invaders (such as bacteria and viruses). This distinction is critical because to remain healthy, a person's immune system must be able to identify and destroy potentially harmful invaders while sparing the body's normal tissues.  Mutations in the AIRE gene reduce or eliminate the function of the autoimmune regulator protein. Without enough of this protein, the immune system can turn against itself and attack the body's own organs. This reaction, which is known as autoimmunity, results in inflammation and can damage otherwise healthy cells and tissues. Damage to the adrenal glands, parathyroid glands, and other organs underlies many of the major features of autoimmune polyglandular syndrome, type 1. It remains unclear why people with this condition tend to get candidiasis infections.  Although most of the characteristic features of autoimmune polyglandular syndrome, type 1 result from mutations in the AIRE gene, researchers believe that variations in other genes may help explain why the signs and symptoms of this condition can vary among affected individuals.","autoimmune polyglandular syndrome, type 1",0000089,GHR,https://ghr.nlm.nih.gov/condition/autoimmune-polyglandular-syndrome-type-1,C0039082,T047,Disorders
"Is autoimmune polyglandular syndrome, type 1 inherited ?",0000089-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.","autoimmune polyglandular syndrome, type 1",0000089,GHR,https://ghr.nlm.nih.gov/condition/autoimmune-polyglandular-syndrome-type-1,C0039082,T047,Disorders
"What are the treatments for autoimmune polyglandular syndrome, type 1 ?",0000089-5,treatment,"These resources address the diagnosis or management of autoimmune polyglandular syndrome, type 1:  - Genetic Testing Registry: Autoimmune polyglandular syndrome type 1, autosomal dominant  - Genetic Testing Registry: Autoimmune polyglandular syndrome type 1, with reversible metaphyseal dysplasia  - Genetic Testing Registry: Polyglandular autoimmune syndrome, type 1  - MedlinePlus Encyclopedia: Addison's Disease  - MedlinePlus Encyclopedia: Autoimmune Disorders  - MedlinePlus Encyclopedia: Cutaneous Candidiasis  - MedlinePlus Encyclopedia: Hypoparathyroidism   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","autoimmune polyglandular syndrome, type 1",0000089,GHR,https://ghr.nlm.nih.gov/condition/autoimmune-polyglandular-syndrome-type-1,C0039082,T047,Disorders
What is (are) autosomal dominant congenital stationary night blindness ?,0000090-1,information,"Autosomal dominant congenital stationary night blindness is a disorder of the retina, which is the specialized tissue at the back of the eye that detects light and color. People with this condition typically have difficulty seeing and distinguishing objects in low light (night blindness). For example, they are not able to identify road signs at night and some people cannot see stars in the night sky. Affected individuals have normal daytime vision and typically do not have other vision problems related to this disorder.  The night blindness associated with this condition is congenital, which means it is present from birth. This vision impairment tends to remain stable (stationary); it does not worsen over time.",autosomal dominant congenital stationary night blindness,0000090,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-congenital-stationary-night-blindness,C0339535,T019,Disorders
How many people are affected by autosomal dominant congenital stationary night blindness ?,0000090-2,frequency,"Autosomal dominant congenital stationary night blindness is likely a rare disease; however, its prevalence is unknown.",autosomal dominant congenital stationary night blindness,0000090,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-congenital-stationary-night-blindness,C0339535,T019,Disorders
What are the genetic changes related to autosomal dominant congenital stationary night blindness ?,0000090-3,genetic changes,"Mutations in the RHO, GNAT1, or PDE6B gene cause autosomal dominant congenital stationary night blindness. The proteins produced from these genes are necessary for normal vision, particularly in low-light conditions. These proteins are found in specialized light receptor cells in the retina called rods. Rods transmit visual signals from the eye to the brain when light is dim.  The RHO gene provides instructions for making a protein called rhodopsin, which is turned on (activated) by light entering the eye. Rhodopsin then attaches (binds) to and activates the protein produced from the GNAT1 gene, alpha ()-transducin. The -transducin protein then triggers the activation of a protein called cGMP-PDE, which is made up of multiple parts (subunits) including a subunit produced from the PDE6B gene. Activated cGMP-PDE triggers a series of chemical reactions that create electrical signals. These signals are transmitted from rod cells to the brain, where they are interpreted as vision.  Mutations in the RHO, GNAT1, or PDE6B gene disrupt the normal signaling that occurs within rod cells. As a result, the rods cannot effectively transmit signals to the brain, leading to a lack of visual perception in low light.",autosomal dominant congenital stationary night blindness,0000090,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-congenital-stationary-night-blindness,C0339535,T019,Disorders
Is autosomal dominant congenital stationary night blindness inherited ?,0000090-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",autosomal dominant congenital stationary night blindness,0000090,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-congenital-stationary-night-blindness,C0339535,T019,Disorders
What are the treatments for autosomal dominant congenital stationary night blindness ?,0000090-5,treatment,These resources address the diagnosis or management of autosomal dominant congenital stationary night blindness:  - Genetic Testing Registry: Congenital stationary night blindness   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,autosomal dominant congenital stationary night blindness,0000090,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-congenital-stationary-night-blindness,C0339535,T019,Disorders
What is (are) autosomal dominant hyper-IgE syndrome ?,0000091-1,information,"Autosomal dominant hyper-IgE syndrome (AD-HIES), also known as Job syndrome, is a condition that affects several body systems, particularly the immune system. Recurrent infections are common in people with this condition. Affected individuals tend to have frequent bouts of pneumonia, which are caused by certain kinds of bacteria that infect the lungs and cause inflammation. These infections often result in the formation of air-filled cysts (pneumatoceles) in the lungs. Recurrent skin infections and an inflammatory skin disorder called eczema are also very common in AD-HIES. These skin problems cause rashes, blisters, accumulations of pus (abscesses), open sores, and scaling.  AD-HIES is characterized by abnormally high levels of an immune system protein called immunoglobulin E (IgE) in the blood. IgE normally triggers an immune response against foreign invaders in the body, particularly parasitic worms, and plays a role in allergies. It is unclear why people with AD-HIES have such high levels of IgE.  AD-HIES also affects other parts of the body, including the bones and teeth. Many people with AD-HIES have skeletal abnormalities such as an unusually large range of joint movement (hyperextensibility), an abnormal curvature of the spine (scoliosis), reduced bone density (osteopenia), and a tendency for bones to fracture easily. Dental abnormalities are also common in this condition. The primary (baby) teeth do not fall out at the usual time during childhood but are retained as the adult teeth grow in. Other signs and symptoms of AD-HIES can include abnormalities of the arteries that supply blood to the heart muscle (coronary arteries), distinctive facial features, and structural abnormalities of the brain, which do not affect a person's intelligence.",autosomal dominant hyper-IgE syndrome,0000091,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-hyper-ige-syndrome,C0022398,,Disorders
How many people are affected by autosomal dominant hyper-IgE syndrome ?,0000091-2,frequency,"This condition is rare, affecting fewer than 1 per million people.",autosomal dominant hyper-IgE syndrome,0000091,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-hyper-ige-syndrome,C0022398,,Disorders
What are the genetic changes related to autosomal dominant hyper-IgE syndrome ?,0000091-3,genetic changes,"Mutations in the STAT3 gene cause most cases of AD-HIES. This gene provides instructions for making a protein that plays an important role in several body systems. To carry out its roles, the STAT3 protein attaches to DNA and helps control the activity of particular genes. In the immune system, the STAT3 protein regulates genes that are involved in the maturation of immune system cells, especially T cells. These cells help control the body's response to foreign invaders such as bacteria and fungi.  Changes in the STAT3 gene alter the structure and function of the STAT3 protein, impairing its ability to control the activity of other genes. A shortage of functional STAT3 blocks the maturation of T cells (specifically a subset known as Th17 cells) and other immune cells. The resulting immune system abnormalities make people with AD-HIES highly susceptible to infections, particularly bacterial and fungal infections of the lungs and skin. The STAT3 protein is also involved in the formation of cells that build and break down bone tissue, which could help explain why STAT3 gene mutations lead to the skeletal and dental abnormalities characteristic of this condition. It is unclear how STAT3 gene mutations lead to increased IgE levels.  When AD-HIES is not caused by STAT3 gene mutations, the genetic cause of the condition is unknown.",autosomal dominant hyper-IgE syndrome,0000091,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-hyper-ige-syndrome,C0022398,,Disorders
Is autosomal dominant hyper-IgE syndrome inherited ?,0000091-4,inheritance,"AD-HIES has an autosomal dominant pattern of inheritance, which means one copy of an altered gene in each cell is sufficient to cause the disorder. In about half of all cases caused by STAT3 gene mutations, an affected person inherits the genetic change from an affected parent. Other cases result from new mutations in this gene. These cases occur in people with no history of the disorder in their family.",autosomal dominant hyper-IgE syndrome,0000091,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-hyper-ige-syndrome,C0022398,,Disorders
What are the treatments for autosomal dominant hyper-IgE syndrome ?,0000091-5,treatment,These resources address the diagnosis or management of autosomal dominant hyper-IgE syndrome:  - Gene Review: Gene Review: Autosomal Dominant Hyper IgE Syndrome  - Genetic Testing Registry: Hyperimmunoglobulin E syndrome  - MedlinePlus Encyclopedia: Hyperimmunoglobulin E syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,autosomal dominant hyper-IgE syndrome,0000091,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-hyper-ige-syndrome,C0022398,,Disorders
What is (are) autosomal dominant hypocalcemia ?,0000092-1,information,"Autosomal dominant hypocalcemia is characterized by low levels of calcium in the blood (hypocalcemia). Affected individuals can have an imbalance of other molecules in the blood as well, including too much phosphate (hyperphosphatemia) or too little magnesium (hypomagnesemia). Some people with autosomal dominant hypocalcemia also have low levels of a hormone called parathyroid hormone (hypoparathyroidism). This hormone is involved in the regulation of calcium levels in the blood. Abnormal levels of calcium and other molecules in the body can lead to a variety of signs and symptoms, although about half of affected individuals have no associated health problems.  The most common features of autosomal dominant hypocalcemia include muscle spasms in the hands and feet (carpopedal spasms) and muscle cramping, prickling or tingling sensations (paresthesias), or twitching of the nerves and muscles (neuromuscular irritability) in various parts of the body. More severely affected individuals develop seizures, usually in infancy or childhood. Sometimes, these symptoms occur only during episodes of illness or fever.  Some people with autosomal dominant hypocalcemia have high levels of calcium in their urine (hypercalciuria), which can lead to deposits of calcium in the kidneys (nephrocalcinosis) or the formation of kidney stones (nephrolithiasis). These conditions can damage the kidneys and impair their function. Sometimes, abnormal deposits of calcium form in the brain, typically in structures called basal ganglia, which help control movement.  A small percentage of severely affected individuals have features of a kidney disorder called Bartter syndrome in addition to hypocalcemia. These features can include a shortage of potassium (hypokalemia) and magnesium and a buildup of the hormone aldosterone (hyperaldosteronism) in the blood. The abnormal balance of molecules can raise the pH of the blood, which is known as metabolic alkalosis. The combination of features of these two conditions is sometimes referred to as autosomal dominant hypocalcemia with Bartter syndrome or Bartter syndrome type V.  There are two types of autosomal dominant hypocalcemia distinguished by their genetic cause. The signs and symptoms of the two types are generally the same.",autosomal dominant hypocalcemia,0000092,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-hypocalcemia,C0020598,T046,Disorders
How many people are affected by autosomal dominant hypocalcemia ?,0000092-2,frequency,The prevalence of autosomal dominant hypocalcemia is unknown. The condition is likely underdiagnosed because it often causes no signs or symptoms.,autosomal dominant hypocalcemia,0000092,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-hypocalcemia,C0020598,T046,Disorders
What are the genetic changes related to autosomal dominant hypocalcemia ?,0000092-3,genetic changes,"Autosomal dominant hypocalcemia is primarily caused by mutations in the CASR gene; these cases are known as type 1. A small percentage of cases, known as type 2, are caused by mutations in the GNA11 gene. The proteins produced from these genes work together to regulate the amount of calcium in the blood.  The CASR gene provides instructions for making a protein called the calcium-sensing receptor (CaSR). Calcium molecules attach (bind) to the CaSR protein, which allows this protein to monitor and regulate the amount of calcium in the blood. G11, which is produced from the GNA11 gene, is one component of a signaling protein that works in conjunction with CaSR. When a certain concentration of calcium is reached, CaSR stimulates G11 to send signals to block processes that increase the amount of calcium in the blood.  Mutations in the CASR or GNA11 gene lead to overactivity of the respective protein. The altered CaSR protein is more sensitive to calcium, meaning even low levels of calcium can trigger it to stimulate G11 signaling. Similarly, the altered G11 protein continues to send signals to prevent calcium increases, even when levels in the blood are very low. As a result, calcium levels in the blood remain low, causing hypocalcemia. Calcium plays an important role in the control of muscle movement, and a shortage of this molecule can lead to cramping or twitching of the muscles. Impairment of the processes that increase calcium can also disrupt the normal regulation of other molecules, such as phosphate and magnesium, leading to other signs of autosomal dominant hypocalcemia. Studies show that the lower the amount of calcium in the blood, the more severe the symptoms of the condition are.",autosomal dominant hypocalcemia,0000092,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-hypocalcemia,C0020598,T046,Disorders
Is autosomal dominant hypocalcemia inherited ?,0000092-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In most cases, an affected person inherits the mutation from one affected parent. A small number of cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",autosomal dominant hypocalcemia,0000092,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-hypocalcemia,C0020598,T046,Disorders
What are the treatments for autosomal dominant hypocalcemia ?,0000092-5,treatment,These resources address the diagnosis or management of autosomal dominant hypocalcemia:  - Genetic Testing Registry: Autosomal dominant hypocalcemia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,autosomal dominant hypocalcemia,0000092,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-hypocalcemia,C0020598,T046,Disorders
What is (are) autosomal dominant nocturnal frontal lobe epilepsy ?,0000093-1,information,"Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is an uncommon form of epilepsy that runs in families. This disorder causes seizures that usually occur at night (nocturnally) while an affected person is sleeping. Some people with ADNFLE also have seizures during the day.  The seizures characteristic of ADNFLE tend to occur in clusters, with each one lasting from a few seconds to a few minutes. Some people have mild seizures that simply cause them to wake up from sleep. Others have more severe episodes that can include sudden, repetitive movements such as flinging or throwing motions of the arms and bicycling movements of the legs. The person may get out of bed and wander around, which can be mistaken for sleepwalking. The person may also cry out or make moaning, gasping, or grunting sounds. These episodes are sometimes misdiagnosed as nightmares, night terrors, or panic attacks.  In some types of epilepsy, including ADNFLE, a pattern of neurological symptoms called an aura often precedes a seizure. The most common symptoms associated with an aura in people with ADNFLE are tingling, shivering, a sense of fear, dizziness (vertigo), and a feeling of falling or being pushed. Some affected people have also reported a feeling of breathlessness, overly fast breathing (hyperventilation), or choking. It is unclear what brings on seizures in people with ADNFLE. Episodes may be triggered by stress or fatigue, but in most cases the seizures do not have any recognized triggers.  The seizures associated with ADNFLE can begin anytime from infancy to mid-adulthood, but most begin in childhood. The episodes tend to become milder and less frequent with age. In most affected people, the seizures can be effectively controlled with medication.  Most people with ADNFLE are intellectually normal, and there are no problems with their brain function between seizures. However, some people with ADNFLE have experienced psychiatric disorders (such as schizophrenia), behavioral problems, or intellectual disability. It is unclear whether these additional features are directly related to epilepsy in these individuals.",autosomal dominant nocturnal frontal lobe epilepsy,0000093,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-nocturnal-frontal-lobe-epilepsy,C3696898,T047,Disorders
How many people are affected by autosomal dominant nocturnal frontal lobe epilepsy ?,0000093-2,frequency,ADNFLE appears to be an uncommon form of epilepsy; its prevalence is unknown. This condition has been reported in more than 100 families worldwide.,autosomal dominant nocturnal frontal lobe epilepsy,0000093,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-nocturnal-frontal-lobe-epilepsy,C3696898,T047,Disorders
What are the genetic changes related to autosomal dominant nocturnal frontal lobe epilepsy ?,0000093-3,genetic changes,"Mutations in the CHRNA2, CHRNA4, and CHRNB2 genes can cause ADNFLE. These genes provide instructions for making different parts (subunits) of a larger molecule called a neuronal nicotinic acetylcholine receptor (nAChR). This receptor plays an important role in chemical signaling between nerve cells (neurons) in the brain.  Communication between neurons depends on chemicals called neurotransmitters, which are released from one neuron and taken up by neighboring neurons. Researchers believe that mutations in the CHRNA2, CHRNA4, and CHRNB2 genes affect the normal release and uptake of certain neurotransmitters in the brain. The resulting changes in signaling between neurons likely trigger the abnormal brain activity associated with seizures.  The seizures associated with ADNFLE begin in areas of the brain called the frontal lobes. These regions of the brain are involved in many critical functions, including reasoning, planning, judgment, and problem-solving. It is unclear why mutations in the CHRNA2, CHRNA4, and CHRNB2 genes cause seizures in the frontal lobes rather than elsewhere in the brain. Researchers are also working to determine why these seizures occur most often during sleep.  The genetic cause of ADNFLE has been identified in only a small percentage of affected families. In some cases, a gene other than those that make up the nAChR are involved. In the remaining families, the cause of the condition is unknown. Researchers are searching for other genetic changes, including mutations in other subunits of nAChR, that may underlie the condition.",autosomal dominant nocturnal frontal lobe epilepsy,0000093,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-nocturnal-frontal-lobe-epilepsy,C3696898,T047,Disorders
Is autosomal dominant nocturnal frontal lobe epilepsy inherited ?,0000093-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to raise the risk of developing epilepsy. About 70 percent of people who inherit a mutation in the CHRNA2, CHRNA4, or CHRNB2 gene will develop seizures. In most cases, an affected person has one affected parent and other relatives with the condition. Other cases are described as sporadic, which means an affected person has no family history of the disorder.",autosomal dominant nocturnal frontal lobe epilepsy,0000093,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-nocturnal-frontal-lobe-epilepsy,C3696898,T047,Disorders
What are the treatments for autosomal dominant nocturnal frontal lobe epilepsy ?,0000093-5,treatment,"These resources address the diagnosis or management of ADNFLE:  - Gene Review: Gene Review: Autosomal Dominant Nocturnal Frontal Lobe Epilepsy  - Genetic Testing Registry: Epilepsy, nocturnal frontal lobe, type 1  - Genetic Testing Registry: Epilepsy, nocturnal frontal lobe, type 2  - Genetic Testing Registry: Epilepsy, nocturnal frontal lobe, type 3  - Genetic Testing Registry: Epilepsy, nocturnal frontal lobe, type 4  - MedlinePlus Encyclopedia: Epilepsy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",autosomal dominant nocturnal frontal lobe epilepsy,0000093,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-nocturnal-frontal-lobe-epilepsy,C3696898,T047,Disorders
What is (are) autosomal dominant partial epilepsy with auditory features ?,0000094-1,information,"Autosomal dominant partial epilepsy with auditory features (ADPEAF) is an uncommon form of epilepsy that runs in families. This disorder causes seizures usually characterized by sound-related (auditory) symptoms such as buzzing, humming, or ringing. Some people experience more complex sounds during a seizure, such as specific voices or music, or changes in the volume of sounds. Some people with ADPEAF suddenly become unable to understand language before losing consciousness during a seizure. This inability to understand speech is known as receptive aphasia. Less commonly, seizures may cause visual hallucinations, a disturbance in the sense of smell, a feeling of dizziness or spinning (vertigo), or other symptoms affecting the senses.  Seizures associated with ADPEAF usually begin in adolescence or young adulthood. They may be triggered by specific sounds, such as a ringing telephone or speech, but in most cases the seizures do not have any recognized triggers. In most affected people, seizures are infrequent and effectively controlled with medication.  Most people with ADPEAF have seizures described as simple partial seizures, which do not cause a loss of consciousness. These seizures are thought to begin in a part of the brain called the lateral temporal lobe. In some people, seizure activity may spread from the lateral temporal lobe to affect other regions of the brain. If seizure activity spreads to affect the entire brain, it causes a loss of consciousness, muscle stiffening, and rhythmic jerking. Episodes that begin as partial seizures and spread throughout the brain are known as secondarily generalized seizures.",autosomal dominant partial epilepsy with auditory features,0000094,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-partial-epilepsy-with-auditory-features,C1838062,T047,Disorders
How many people are affected by autosomal dominant partial epilepsy with auditory features ?,0000094-2,frequency,"This condition appears to be uncommon, although its prevalence is unknown.",autosomal dominant partial epilepsy with auditory features,0000094,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-partial-epilepsy-with-auditory-features,C1838062,T047,Disorders
What are the genetic changes related to autosomal dominant partial epilepsy with auditory features ?,0000094-3,genetic changes,"Mutations in the LGI1 gene cause ADPEAF. This gene provides instructions for making a protein called Lgi1 or epitempin, which is found primarily in nerve cells (neurons) in the brain. Although researchers have proposed several functions for this protein, its precise role in the brain remains uncertain.  Mutations in the LGI1 gene likely disrupt the function of epitempin. It is unclear how the altered protein leads to seizure activity in the brain.  LGI1 mutations have been identified in about half of all families diagnosed with ADPEAF. In the remaining families, the cause of the condition is unknown. Researchers are searching for other genetic changes that may underlie the condition.",autosomal dominant partial epilepsy with auditory features,0000094,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-partial-epilepsy-with-auditory-features,C1838062,T047,Disorders
Is autosomal dominant partial epilepsy with auditory features inherited ?,0000094-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered LGI1 gene in each cell is sufficient to raise the risk of developing epilepsy. About two-thirds of people who inherit a mutation in this gene will develop seizures. In most cases, an affected person has one affected parent and other relatives with the condition.",autosomal dominant partial epilepsy with auditory features,0000094,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-partial-epilepsy-with-auditory-features,C1838062,T047,Disorders
What are the treatments for autosomal dominant partial epilepsy with auditory features ?,0000094-5,treatment,"These resources address the diagnosis or management of ADPEAF:  - Gene Review: Gene Review: Autosomal Dominant Partial Epilepsy with Auditory Features  - Genetic Testing Registry: Epilepsy, lateral temporal lobe, autosomal dominant  - MedlinePlus Encyclopedia: Partial (Focal) Seizure  - MedlinePlus Encyclopedia: Seizures   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",autosomal dominant partial epilepsy with auditory features,0000094,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-partial-epilepsy-with-auditory-features,C1838062,T047,Disorders
What is (are) autosomal dominant vitreoretinochoroidopathy ?,0000095-1,information,"Autosomal dominant vitreoretinochoroidopathy (ADVIRC) is a disorder that affects several parts of the eyes, including the clear gel that fills the eye (the vitreous), the light-sensitive tissue that lines the back of the eye (the retina), and the network of blood vessels within the retina (the choroid). The eye abnormalities in ADVIRC can lead to varying degrees of vision impairment, from mild reduction to complete loss, although some people with the condition have normal vision.  The signs and symptoms of ADVIRC vary, even among members of the same family. Many affected individuals have microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved. The area behind the cornea can also be abnormally small, which is described as a shallow anterior chamber. Individuals with ADVIRC can develop increased pressure in the eyes (glaucoma) or clouding of the lens of the eye (cataract). In addition, some people have breakdown (degeneration) of the vitreous or the choroid.  A characteristic feature of ADVIRC, visible with a special eye exam, is a circular band of excess coloring (hyperpigmentation) in the retina. This feature can help physicians diagnose the disorder. Affected individuals may also have white spots on the retina.",autosomal dominant vitreoretinochoroidopathy,0000095,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-vitreoretinochoroidopathy,C1860406,T047,Disorders
How many people are affected by autosomal dominant vitreoretinochoroidopathy ?,0000095-2,frequency,ADVIRC is considered a rare disease. Its prevalence is unknown.,autosomal dominant vitreoretinochoroidopathy,0000095,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-vitreoretinochoroidopathy,C1860406,T047,Disorders
What are the genetic changes related to autosomal dominant vitreoretinochoroidopathy ?,0000095-3,genetic changes,"ADVIRC is caused by mutations in the BEST1 gene. The protein produced from this gene, called bestrophin-1, is thought to play a critical role in normal vision. Bestrophin-1 is found in a thin layer of cells at the back of the eye called the retinal pigment epithelium. This cell layer supports and nourishes the retina and is involved in growth and development of the eye, maintenance of the retina, and the normal function of specialized cells called photoreceptors that detect light and color. In the retinal pigment epithelium, bestrophin-1 functions as a channel that transports charged chlorine atoms (chloride ions) across the cell membrane.  Mutations in the BEST1 gene alter how the gene's instructions are used to make bestrophin-1, which leads to production of versions of the protein that are missing certain segments or have extra segments. It is not clear how these versions of bestrophin affect chloride ion transport or lead to the eye abnormalities characteristic of ADVIRC. Researchers suspect that the abnormalities are related to defects in the retinal pigment epithelium or the photoreceptors.",autosomal dominant vitreoretinochoroidopathy,0000095,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-vitreoretinochoroidopathy,C1860406,T047,Disorders
Is autosomal dominant vitreoretinochoroidopathy inherited ?,0000095-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.",autosomal dominant vitreoretinochoroidopathy,0000095,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-vitreoretinochoroidopathy,C1860406,T047,Disorders
What are the treatments for autosomal dominant vitreoretinochoroidopathy ?,0000095-5,treatment,These resources address the diagnosis or management of autosomal dominant vitreoretinochoroidopathy:  - American Foundation for the Blind: Living with Vision Loss  - Genetic Testing Registry: Vitreoretinochoroidopathy dominant   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,autosomal dominant vitreoretinochoroidopathy,0000095,GHR,https://ghr.nlm.nih.gov/condition/autosomal-dominant-vitreoretinochoroidopathy,C1860406,T047,Disorders
What is (are) autosomal recessive axonal neuropathy with neuromyotonia ?,0000096-1,information,"Autosomal recessive axonal neuropathy with neuromyotonia is a disorder that affects the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound.  Axonal neuropathy, a characteristic feature of this condition, is caused by damage to a particular part of peripheral nerves called axons, which are the extensions of nerve cells (neurons) that transmit nerve impulses. In people with autosomal recessive axonal neuropathy with neuromyotonia, the damage primarily causes progressive weakness and wasting (atrophy) of muscles in the feet, legs, and hands. Muscle weakness may be especially apparent during exercise (exercise intolerance) and can lead to an unusual walking style (gait), frequent falls, and joint deformities (contractures) in the hands and feet. In some affected individuals, axonal neuropathy also causes decreased sensitivity to touch, heat, or cold, particularly in the lower arms or legs.  Another feature of this condition is neuromyotonia (also known as Isaac syndrome). Neuromyotonia results from overactivation (hyperexcitability) of peripheral nerves, which leads to delayed relaxation of muscles after voluntary tensing (contraction), muscle cramps, and involuntary rippling movement of the muscles (myokymia).",autosomal recessive axonal neuropathy with neuromyotonia,0000096,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-axonal-neuropathy-with-neuromyotonia,C0270921,T047,Disorders
How many people are affected by autosomal recessive axonal neuropathy with neuromyotonia ?,0000096-2,frequency,"Autosomal recessive axonal neuropathy with neuromyotonia is a rare form of inherited peripheral neuropathy. This group of conditions affects an estimated 1 in 2,500 people. The prevalence of autosomal recessive axonal neuropathy with neuromyotonia is unknown.",autosomal recessive axonal neuropathy with neuromyotonia,0000096,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-axonal-neuropathy-with-neuromyotonia,C0270921,T047,Disorders
What are the genetic changes related to autosomal recessive axonal neuropathy with neuromyotonia ?,0000096-3,genetic changes,"Autosomal recessive axonal neuropathy with neuromyotonia is caused by mutations in the HINT1 gene. This gene provides instructions for making a protein that is involved in the function of the nervous system; however its specific role is not well understood. Laboratory studies show that the HINT1 protein has the ability to carry out a chemical reaction called hydrolysis that breaks down certain molecules; however, it is not known what effects the reaction has in the body.  HINT1 gene mutations that cause autosomal recessive axonal neuropathy with neuromyotonia lead to production of a HINT1 protein with little or no function. Sometimes the abnormal protein is broken down prematurely. Researchers are working to determine how loss of functional HINT1 protein affects the peripheral nerves and leads to the signs and symptoms of this condition.",autosomal recessive axonal neuropathy with neuromyotonia,0000096,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-axonal-neuropathy-with-neuromyotonia,C0270921,T047,Disorders
Is autosomal recessive axonal neuropathy with neuromyotonia inherited ?,0000096-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",autosomal recessive axonal neuropathy with neuromyotonia,0000096,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-axonal-neuropathy-with-neuromyotonia,C0270921,T047,Disorders
What are the treatments for autosomal recessive axonal neuropathy with neuromyotonia ?,0000096-5,treatment,These resources address the diagnosis or management of autosomal recessive axonal neuropathy with neuromyotonia:  - Genetic Testing Registry: Gamstorp-Wohlfart syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,autosomal recessive axonal neuropathy with neuromyotonia,0000096,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-axonal-neuropathy-with-neuromyotonia,C0270921,T047,Disorders
What is (are) autosomal recessive cerebellar ataxia type 1 ?,0000097-1,information,"Autosomal recessive cerebellar ataxia type 1 (ARCA1) is a condition characterized by progressive problems with movement due to a loss (atrophy) of nerve cells in the part of the brain that coordinates movement (the cerebellum). Signs and symptoms of the disorder first appear in early to mid-adulthood. People with this condition initially experience impaired speech (dysarthria), problems with coordination and balance (ataxia), or both. They may also have difficulty with movements that involve judging distance or scale (dysmetria). Other features of ARCA1 include abnormal eye movements (nystagmus) and problems following the movements of objects with the eyes. The movement problems are slowly progressive, often resulting in the need for a cane, walker, or wheelchair.",autosomal recessive cerebellar ataxia type 1,0000097,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-cerebellar-ataxia-type-1,C0007758,T047,Disorders
How many people are affected by autosomal recessive cerebellar ataxia type 1 ?,0000097-2,frequency,"More than 100 people have been diagnosed with ARCA1. This condition was first discovered in individuals from the Beauce and Bas-Saint-Laurent regions of Quebec, Canada, but it has since been found in populations worldwide.",autosomal recessive cerebellar ataxia type 1,0000097,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-cerebellar-ataxia-type-1,C0007758,T047,Disorders
What are the genetic changes related to autosomal recessive cerebellar ataxia type 1 ?,0000097-3,genetic changes,"Mutations in the SYNE1 gene cause ARCA1. The SYNE1 gene provides instructions for making a protein called Syne-1 that is found in many tissues, but it seems to be especially critical in the brain. Within the brain, the Syne-1 protein appears to play a role in the maintenance of the cerebellum, which is the part of the brain that coordinates movement. The Syne-1 protein is active (expressed) in Purkinje cells, which are located in the cerebellum and are involved in chemical signaling between nerve cells (neurons).  SYNE1 gene mutations that cause ARCA1 result in an abnormally short, dysfunctional version of the Syne-1 protein. The defective protein is thought to impair Purkinje cell function and disrupt signaling between neurons in the cerebellum. The loss of brain cells in the cerebellum causes the movement problems characteristic of ARCA1, but it is unclear how this cell loss is related to impaired Purkinje cell function.",autosomal recessive cerebellar ataxia type 1,0000097,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-cerebellar-ataxia-type-1,C0007758,T047,Disorders
Is autosomal recessive cerebellar ataxia type 1 inherited ?,0000097-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",autosomal recessive cerebellar ataxia type 1,0000097,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-cerebellar-ataxia-type-1,C0007758,T047,Disorders
What are the treatments for autosomal recessive cerebellar ataxia type 1 ?,0000097-5,treatment,"These resources address the diagnosis or management of ARCA1:  - Gene Review: Gene Review: SYNE1-Related Autosomal Recessive Cerebellar Ataxia  - Genetic Testing Registry: Spinocerebellar ataxia, autosomal recessive 8  - Johns Hopkins Medicine Department of Neurology and Neurosurgery: What is Ataxia?  - MedlinePlus Encyclopedia: Dysarthria--Care   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",autosomal recessive cerebellar ataxia type 1,0000097,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-cerebellar-ataxia-type-1,C0007758,T047,Disorders
What is (are) autosomal recessive congenital methemoglobinemia ?,0000098-1,information,"Autosomal recessive congenital methemoglobinemia is an inherited condition that mainly affects the function of red blood cells. Specifically, it alters a molecule within these cells called hemoglobin. Hemoglobin carries oxygen to cells and tissues throughout the body. In people with autosomal recessive congenital methemoglobinemia, some of the normal hemoglobin is replaced by an abnormal form called methemoglobin, which is unable to deliver oxygen to the body's tissues. As a result, tissues in the body become oxygen deprived, leading to a bluish appearance of the skin, lips, and nails (cyanosis).  There are two forms of autosomal recessive congenital methemoglobinemia: types I and II. People with type I have cyanosis from birth and may experience weakness or shortness of breath related to the shortage of oxygen in their tissues. People with type II have cyanosis as well as severe neurological problems. After a few months of apparently normal development, children with type II develop severe brain dysfunction (encephalopathy), uncontrolled muscle tensing (dystonia), and involuntary limb movements (choreoathetosis); also, the size of their head remains small and does not grow in proportion with their body (microcephaly). People with type II have severe intellectual disability; they can recognize faces and usually babble but speak no words. They can sit unassisted and grip objects but have impaired motor skills that leave them unable to walk. In type II, growth is often slowed. Abnormal facial muscle movements can interfere with swallowing, which can lead to feeding difficulties and further slow growth.  People with autosomal recessive congenital methemoglobinemia type I have a normal life expectancy, but people with type II often do not survive past early adulthood.",autosomal recessive congenital methemoglobinemia,0000098,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-congenital-methemoglobinemia,C0272087,T019,Disorders
How many people are affected by autosomal recessive congenital methemoglobinemia ?,0000098-2,frequency,The incidence of autosomal recessive congenital methemoglobinemia is unknown.,autosomal recessive congenital methemoglobinemia,0000098,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-congenital-methemoglobinemia,C0272087,T019,Disorders
What are the genetic changes related to autosomal recessive congenital methemoglobinemia ?,0000098-3,genetic changes,"Autosomal recessive congenital methemoglobinemia is caused by mutations in the CYB5R3 gene. This gene provides instruction for making an enzyme called cytochrome b5 reductase 3. This enzyme is involved in transferring negatively charged particles called electrons from one molecule to another. Two versions (isoforms) of this enzyme are produced from the CYB5R3 gene. The soluble isoform is present only in red blood cells, and the membrane-bound isoform is found in all other cell types.  Each hemoglobin molecule contains four iron atoms, which are needed to carry oxygen. In normal red blood cells, the iron in hemoglobin is ferrous (Fe2+), but it can spontaneously become ferric (Fe3+). When hemoglobin contains ferric iron, it is methemoglobin. The soluble isoform of cytochrome b5 reductase 3 changes ferric iron back to ferrous iron so hemoglobin can deliver oxygen to tissues. Normally, red blood cells contain less than 2 percent methemoglobin.  The membrane-bound isoform is widely used in the body. This isoform is necessary for many chemical reactions, including the breakdown and formation of fatty acids, the formation of cholesterol, and the breakdown of various molecules and drugs.  CYB5R3 gene mutations that cause autosomal recessive congenital methemoglobinemia type I typically reduce enzyme activity or stability. As a result, the enzyme cannot efficiently change ferric iron to ferrous iron, leading to a 10 to 50 percent increase in methemoglobin within red blood cells. This increase in methemoglobin and the corresponding decrease in normal hemoglobin reduces the amount of oxygen delivered to tissues. The altered enzyme activity affects only red blood cells because other cells can compensate for a decrease in enzyme activity, but red blood cells cannot.  Mutations that cause autosomal recessive congenital methemoglobinemia type II usually result in a complete loss of enzyme activity. Cells cannot compensate for a complete loss of this enzyme, which results in a 10 to 70 percent increase in methemoglobin within red blood cells. This increase in methemoglobin and the corresponding decrease in normal hemoglobin leads to cyanosis. The lack of enzyme activity in other cells leads to the neurological features associated with type II. Researchers suspect that the neurological problems are caused by impaired fatty acid and cholesterol formation, which reduces the production of a fatty substance called myelin. Myelin insulates nerve cells and promotes the rapid transmission of nerve impulses. This reduced ability to form myelin (hypomyelination) leads to a loss of nerve cells, particularly in the brain. The loss of these cells likely contributes to the encephalopathy and movement disorders characteristic of autosomal recessive congenital methemoglobinemia type II.",autosomal recessive congenital methemoglobinemia,0000098,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-congenital-methemoglobinemia,C0272087,T019,Disorders
Is autosomal recessive congenital methemoglobinemia inherited ?,0000098-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",autosomal recessive congenital methemoglobinemia,0000098,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-congenital-methemoglobinemia,C0272087,T019,Disorders
What are the treatments for autosomal recessive congenital methemoglobinemia ?,0000098-5,treatment,"These resources address the diagnosis or management of autosomal recessive congenital methemoglobinemia:  - Genetic Testing Registry: METHEMOGLOBINEMIA, TYPE I  - Genetic Testing Registry: Methemoglobinemia type 2  - KidsHealth from Nemours: Blood Test: Hemoglobin  - MedlinePlus Encyclopedia: Hemoglobin  - MedlinePlus Encyclopedia: Methemoglobinemia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",autosomal recessive congenital methemoglobinemia,0000098,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-congenital-methemoglobinemia,C0272087,T019,Disorders
What is (are) autosomal recessive congenital stationary night blindness ?,0000099-1,information,"Autosomal recessive congenital stationary night blindness is a disorder of the retina, which is the specialized tissue at the back of the eye that detects light and color. People with this condition typically have difficulty seeing and distinguishing objects in low light (night blindness). For example, they may not be able to identify road signs at night or see stars in the night sky. They also often have other vision problems, including loss of sharpness (reduced acuity), nearsightedness (myopia), involuntary movements of the eyes (nystagmus), and eyes that do not look in the same direction (strabismus).  The vision problems associated with this condition are congenital, which means they are present from birth. They tend to remain stable (stationary) over time.",autosomal recessive congenital stationary night blindness,0000099,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-congenital-stationary-night-blindness,C0339535,T019,Disorders
How many people are affected by autosomal recessive congenital stationary night blindness ?,0000099-2,frequency,"Autosomal recessive congenital stationary night blindness is likely a rare disease; however, its prevalence is unknown.",autosomal recessive congenital stationary night blindness,0000099,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-congenital-stationary-night-blindness,C0339535,T019,Disorders
What are the genetic changes related to autosomal recessive congenital stationary night blindness ?,0000099-3,genetic changes,"Mutations in several genes can cause autosomal recessive congenital stationary night blindness. Each of these genes provide instructions for making proteins that are found in the retina. These proteins are involved in sending (transmitting) visual signals from cells called rods, which are specialized for vision in low light, to cells called bipolar cells, which relay the signals to other retinal cells. This signaling is an essential step in the transmission of visual information from the eyes to the brain.  Mutations in two genes, GRM6 and TRPM1, cause most cases of this condition. These genes provide instructions for making proteins that are necessary for bipolar cells to receive and relay signals. Mutations in other genes involved in the same bipolar cell signaling pathway are likely responsible for a small percentage of cases of autosomal recessive congenital stationary night blindness.  Gene mutations that cause autosomal recessive congenital stationary night blindness disrupt the transmission of visual signals between rod cells and bipolar cells or interfere with the bipolar cells' ability to pass on these signals. As a result, visual information received by rod cells cannot be effectively transmitted to the brain, leading to difficulty seeing in low light. The cause of the other vision problems associated with this condition is unclear. It has been suggested that the mechanisms that underlie night blindness can interfere with other visual systems, causing myopia, reduced visual acuity, and other impairments.  Some people with autosomal recessive congenital stationary night blindness have no identified mutation in any of the known genes. The cause of the disorder in these individuals is unknown.",autosomal recessive congenital stationary night blindness,0000099,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-congenital-stationary-night-blindness,C0339535,T019,Disorders
Is autosomal recessive congenital stationary night blindness inherited ?,0000099-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",autosomal recessive congenital stationary night blindness,0000099,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-congenital-stationary-night-blindness,C0339535,T019,Disorders
What are the treatments for autosomal recessive congenital stationary night blindness ?,0000099-5,treatment,"These resources address the diagnosis or management of autosomal recessive congenital stationary night blindness:  - Genetic Testing Registry: Congenital stationary night blindness, type 1B  - Genetic Testing Registry: Congenital stationary night blindness, type 1C  - Genetic Testing Registry: Congenital stationary night blindness, type 1D  - Genetic Testing Registry: Congenital stationary night blindness, type 1E  - Genetic Testing Registry: Congenital stationary night blindness, type 1F  - Genetic Testing Registry: Congenital stationary night blindness, type 2B   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",autosomal recessive congenital stationary night blindness,0000099,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-congenital-stationary-night-blindness,C0339535,T019,Disorders
What is (are) autosomal recessive hyper-IgE syndrome ?,0000100-1,information,"Autosomal recessive hyper-IgE syndrome (AR-HIES) is a disorder of the immune system. A hallmark feature of the condition is recurrent infections that are severe and can be life-threatening. Skin infections can be caused by bacteria, viruses, or fungi. These infections cause rashes, blisters, accumulations of pus (abscesses), open sores, and scaling. People with AR-HIES also tend to have frequent bouts of pneumonia and other respiratory tract infections.  Other immune system-related problems in people with AR-HIES include an inflammatory skin disorder called eczema, food or environmental allergies, and asthma. In some affected individuals, the immune system malfunctions and attacks the body's own tissues and organs, causing autoimmune disease. For example, autoimmunity can lead to abnormal destruction of red blood cells (hemolytic anemia) in people with AR-HIES.  AR-HIES is characterized by abnormally high levels of an immune system protein called immunoglobulin E (IgE) in the blood; the levels are more than 10 times higher than normal. IgE normally triggers an immune response against foreign invaders in the body, particularly parasitic worms, and plays a role in allergies. It is unclear why people with AR-HIES have such high levels of this protein. People with AR-HIES also have highly elevated numbers of certain white blood cells called eosinophils (hypereosinophilia). Eosinophils aid in the immune response and are involved in allergic reactions.  Some people with AR-HIES have neurological problems, such as paralysis that affects the face or one side of the body (hemiplegia). Blockage of blood flow in the brain or abnormal bleeding in the brain, both of which can lead to stroke, can also occur in AR-HIES.  People with AR-HIES have a greater-than-average risk of developing cancer, particularly cancers of the blood or skin.",autosomal recessive hyper-IgE syndrome,0000100,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-hyper-ige-syndrome,C0022398,,Disorders
How many people are affected by autosomal recessive hyper-IgE syndrome ?,0000100-2,frequency,AR-HIES is a rare disorder whose prevalence is unknown.,autosomal recessive hyper-IgE syndrome,0000100,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-hyper-ige-syndrome,C0022398,,Disorders
What are the genetic changes related to autosomal recessive hyper-IgE syndrome ?,0000100-3,genetic changes,"AR-HIES is usually caused by mutations in the DOCK8 gene. The protein produced from this gene plays a critical role in the survival and function of several types of immune system cells. One of the protein's functions is to help maintain the structure and integrity of immune cells called T cells and NK cells, which recognize and attack foreign invaders, particularly as these cells travel to sites of infection within the body. In addition, DOCK8 is involved in chemical signaling pathways that stimulate other immune cells called B cells to mature and produce antibodies, which are specialized proteins that attach to foreign particles and germs, marking them for destruction.  DOCK8 gene mutations result in the production of little or no functional DOCK8 protein. Shortage of this protein impairs normal immune cell development and function. It is thought that T cells and NK cells lacking DOCK8 cannot maintain their shape as they move through dense spaces, such as those found within the skin. The abnormal cells die, resulting in reduced numbers of these cells. A shortage of these immune cells impairs the immune response to foreign invaders, accounting for the severe viral skin infections common in AR-HIES. A lack of DOCK8 also impairs B cell maturation and the production of antibodies. A lack of this type of immune response leads to recurrent respiratory tract infections in people with this disorder. It is unclear how DOCK8 gene mutations are involved in other features of AR-HIES, such as the elevation of IgE levels, autoimmunity, and neurological problems.  Some people with AR-HIES do not have mutations in the DOCK8 gene. The genetic cause of the condition in these individuals is unknown.",autosomal recessive hyper-IgE syndrome,0000100,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-hyper-ige-syndrome,C0022398,,Disorders
Is autosomal recessive hyper-IgE syndrome inherited ?,0000100-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",autosomal recessive hyper-IgE syndrome,0000100,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-hyper-ige-syndrome,C0022398,,Disorders
What are the treatments for autosomal recessive hyper-IgE syndrome ?,0000100-5,treatment,These resources address the diagnosis or management of autosomal recessive hyper-IgE syndrome:  - Genetic Testing Registry: Hyperimmunoglobulin E syndrome  - MedlinePlus Encyclopedia: Hyperimmunoglobulin E Syndrome  - Merck Manual Professional Version: Hyperimmunoglobulin E Syndrome  - PID UK: Hyperimmunoglobulin E Syndromes Treatment and Immunizations   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,autosomal recessive hyper-IgE syndrome,0000100,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-hyper-ige-syndrome,C0022398,,Disorders
What is (are) autosomal recessive hypotrichosis ?,0000101-1,information,"Autosomal recessive hypotrichosis is a condition that affects hair growth. People with this condition have sparse hair (hypotrichosis) on the scalp beginning in infancy. This hair is usually coarse, dry, and tightly curled (often described as woolly hair). Scalp hair may also be lighter in color than expected and is fragile and easily broken. Affected individuals often cannot grow hair longer than a few inches. The eyebrows, eyelashes, and other body hair may be sparse as well. Over time, the hair problems can remain stable or progress to complete scalp hair loss (alopecia) and a decrease in body hair.  Rarely, people with autosomal recessive hypotrichosis have skin problems affecting areas with sparse hair, such as redness (erythema), itchiness (pruritus), or missing patches of skin (erosions) on the scalp. In areas of poor hair growth, they may also develop bumps called hyperkeratotic follicular papules that develop around hair follicles, which are specialized structures in the skin where hair growth occurs.",autosomal recessive hypotrichosis,0000101,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-hypotrichosis,C0020678,T047,Disorders
How many people are affected by autosomal recessive hypotrichosis ?,0000101-2,frequency,"The worldwide prevalence of autosomal recessive hypotrichosis is unknown. In Japan, the condition is estimated to affect 1 in 10,000 individuals.",autosomal recessive hypotrichosis,0000101,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-hypotrichosis,C0020678,T047,Disorders
What are the genetic changes related to autosomal recessive hypotrichosis ?,0000101-3,genetic changes,"Autosomal recessive hypotrichosis can be caused by mutations in the LIPH, LPAR6, or DSG4 gene. These genes provide instructions for making proteins that are involved in the growth and division (proliferation) and maturation (differentiation) of cells within hair follicles. These cell processes are important for the normal development of hair follicles and for hair growth; as the cells in the hair follicle divide, the hair strand (shaft) is pushed upward and extends beyond the skin, causing the hair to grow. The proteins produced from the LIPH, LPAR6, and DSG4 genes are also found in the outermost layer of skin (the epidermis) and glands in the skin that produce a substance that protects the skin and hair (sebaceous glands).  Mutations in the LIPH, LPAR6, or DSG4 gene result in the production of abnormal proteins that cannot aid in the development of hair follicles. As a result, hair follicles are structurally abnormal and often underdeveloped. Irregular hair follicles alter the structure and growth of hair shafts, leading to woolly, fragile hair that is easily broken. A lack of these proteins in the epidermis likely contributes to the skin problems sometimes seen in affected individuals.  In some areas of the body, other proteins can compensate for the function of the missing protein, so not all areas with hair are affected and not all individuals have skin problems.",autosomal recessive hypotrichosis,0000101,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-hypotrichosis,C0020678,T047,Disorders
Is autosomal recessive hypotrichosis inherited ?,0000101-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",autosomal recessive hypotrichosis,0000101,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-hypotrichosis,C0020678,T047,Disorders
What are the treatments for autosomal recessive hypotrichosis ?,0000101-5,treatment,These resources address the diagnosis or management of autosomal recessive hypotrichosis:  - American Academy of Dermatology: Hair Loss: Tips for Managing  - Genetic Testing Registry: Hypotrichosis 8   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,autosomal recessive hypotrichosis,0000101,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-hypotrichosis,C0020678,T047,Disorders
What is (are) autosomal recessive primary microcephaly ?,0000102-1,information,"Autosomal recessive primary microcephaly (often shortened to MCPH, which stands for ""microcephaly primary hereditary"") is a condition in which infants are born with a very small head and a small brain. The term ""microcephaly"" comes from the Greek words for ""small head.""  Infants with MCPH have an unusually small head circumference compared to other infants of the same sex and age. Head circumference is the distance around the widest part of the head, measured by placing a measuring tape above the eyebrows and ears and around the back of the head. Affected infants' brain volume is also smaller than usual, although they usually do not have any major abnormalities in the structure of the brain. The head and brain grow throughout childhood and adolescence, but they continue to be much smaller than normal.  MCPH causes intellectual disability, which is typically mild to moderate and does not become more severe with age. Most affected individuals have delayed speech and language skills. Motor skills, such as sitting, standing, and walking, may also be mildly delayed.  People with MCPH usually have few or no other features associated with the condition. Some have a narrow, sloping forehead; mild seizures; problems with attention or behavior; or short stature compared to others in their family. The condition typically does not affect any other major organ systems or cause other health problems.",autosomal recessive primary microcephaly,0000102,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-primary-microcephaly,C3711387,T047,Disorders
How many people are affected by autosomal recessive primary microcephaly ?,0000102-2,frequency,"The prevalence of all forms of microcephaly that are present from birth (primary microcephaly) ranges from 1 in 30,000 to 1 in 250,000 newborns worldwide. About 200 families with MCPH have been reported in the medical literature. This condition is more common in several specific populations, such as in northern Pakistan, where it affects an estimated 1 in 10,000 newborns.",autosomal recessive primary microcephaly,0000102,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-primary-microcephaly,C3711387,T047,Disorders
What are the genetic changes related to autosomal recessive primary microcephaly ?,0000102-3,genetic changes,"MCPH can result from mutations in at least seven genes. Mutations in the ASPM gene are the most common cause of the disorder, accounting for about half of all cases.  The genes associated with MCPH play important roles in early brain development, particularly in determining brain size. Studies suggest that the proteins produced from many of these genes help regulate cell division in the developing brain.  Mutations in any of the genes associated with MCPH impair early brain development. As a result, affected infants have fewer nerve cells (neurons) than normal and are born with an unusually small brain. The reduced brain size underlies the small head size, intellectual disability, and developmental delays seen in many affected individuals.",autosomal recessive primary microcephaly,0000102,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-primary-microcephaly,C3711387,T047,Disorders
Is autosomal recessive primary microcephaly inherited ?,0000102-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",autosomal recessive primary microcephaly,0000102,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-primary-microcephaly,C3711387,T047,Disorders
What are the treatments for autosomal recessive primary microcephaly ?,0000102-5,treatment,These resources address the diagnosis or management of MCPH:  - Gene Review: Gene Review: Primary Autosomal Recessive Microcephalies and Seckel Syndrome Spectrum Disorders  - Genetic Testing Registry: Primary autosomal recessive microcephaly 1  - Genetic Testing Registry: Primary autosomal recessive microcephaly 2  - Genetic Testing Registry: Primary autosomal recessive microcephaly 3  - Genetic Testing Registry: Primary autosomal recessive microcephaly 4  - Genetic Testing Registry: Primary autosomal recessive microcephaly 5  - Genetic Testing Registry: Primary autosomal recessive microcephaly 6  - Genetic Testing Registry: Primary autosomal recessive microcephaly 7  - MedlinePlus Encyclopedia: Head Circumference   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,autosomal recessive primary microcephaly,0000102,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-primary-microcephaly,C3711387,T047,Disorders
What is (are) autosomal recessive spastic ataxia of Charlevoix-Saguenay ?,0000103-1,information,"Autosomal recessive spastic ataxia of Charlevoix-Saguenay, more commonly known as ARSACS, is a condition affecting muscle movement. People with ARSACS typically have abnormal tensing of the muscles (spasticity), difficulty coordinating movements (ataxia), muscle wasting (amyotrophy), involuntary eye movements (nystagmus), and speech difficulties (dysarthria). Other problems may include deformities of the fingers and feet, reduced sensation and weakness in the arms and legs (peripheral neuropathy), yellow streaks of fatty tissue in the light-sensitive tissue at the back of the eye (hypermyelination of the retina), and less commonly, leaks in one of the valves that control blood flow through the heart (mitral valve prolapse). An unsteady gait is the first symptom of ARSACS. It usually appears between the age of 12 months and 18 months, as toddlers are learning to walk. The signs and symptoms worsen over the years, with increased spasticity and ataxia of the arms and legs. In some cases spasticity disappears, but this apparent improvement is thought to be due to degeneration of nerves in the arms and legs. Most affected individuals require a wheelchair by the time they are in their thirties or forties.  This condition was first seen in people of the Charlevoix-Saguenay region of Quebec, Canada. The majority of people with ARSACS live in Quebec or have recent ancestors from Quebec. People with ARSACS have also been identified in Japan, Turkey, Tunisia, Spain, Italy, and Belgium. The signs and symptoms of ARSACS seen in other countries differ from those in Quebec. In people with ARSACS outside of Quebec, hypermyelination of the retina is seen less often, intelligence may be below normal, and symptoms tend to appear at a later age.",autosomal recessive spastic ataxia of Charlevoix-Saguenay,0000103,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-spastic-ataxia-of-charlevoix-saguenay,C1849140,T047,Disorders
How many people are affected by autosomal recessive spastic ataxia of Charlevoix-Saguenay ?,0000103-2,frequency,"The incidence of ARSACS in the Charlevoix-Saguenay region of Quebec is estimated to be 1 in 1,500 to 2,000 individuals. Outside of Quebec, ARSACS is rare, but the incidence is unknown.",autosomal recessive spastic ataxia of Charlevoix-Saguenay,0000103,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-spastic-ataxia-of-charlevoix-saguenay,C1849140,T047,Disorders
What are the genetic changes related to autosomal recessive spastic ataxia of Charlevoix-Saguenay ?,0000103-3,genetic changes,"Mutations in the SACS gene cause ARSACS. The SACS gene provides instructions for producing a protein called sacsin. Sacsin is found in the brain, skin cells, muscles used for movement (skeletal muscles), and at low levels in the pancreas, but the specific function of the protein is unknown. Research suggests that sacsin might play a role in folding newly produced proteins into the proper 3-dimensional shape because it shares similar regions with other proteins that perform this function. Mutations in the SACS gene cause the production of an unstable sacsin protein that does not function normally. It is unclear how the abnormal sacsin protein affects the brain and skeletal muscles and results in the signs and symptoms of ARSACS.",autosomal recessive spastic ataxia of Charlevoix-Saguenay,0000103,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-spastic-ataxia-of-charlevoix-saguenay,C1849140,T047,Disorders
Is autosomal recessive spastic ataxia of Charlevoix-Saguenay inherited ?,0000103-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",autosomal recessive spastic ataxia of Charlevoix-Saguenay,0000103,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-spastic-ataxia-of-charlevoix-saguenay,C1849140,T047,Disorders
What are the treatments for autosomal recessive spastic ataxia of Charlevoix-Saguenay ?,0000103-5,treatment,These resources address the diagnosis or management of ARSACS:  - Gene Review: Gene Review: ARSACS  - Genetic Testing Registry: Spastic ataxia Charlevoix-Saguenay type   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,autosomal recessive spastic ataxia of Charlevoix-Saguenay,0000103,GHR,https://ghr.nlm.nih.gov/condition/autosomal-recessive-spastic-ataxia-of-charlevoix-saguenay,C1849140,T047,Disorders
What is (are) Axenfeld-Rieger syndrome ?,0000104-1,information,"Axenfeld-Rieger syndrome is primarily an eye disorder, although it can also affect other parts of the body. This condition is characterized by abnormalities of the front part of the eye, an area known as the anterior segment. For example, the colored part of the eye (the iris), may be thin or poorly developed. The iris normally has a single central hole, called the pupil, through which light enters the eye. People with Axenfeld-Rieger syndrome often have a pupil that is off-center (corectopia) or extra holes in the iris that can look like multiple pupils (polycoria). This condition can also cause abnormalities of the cornea, which is the clear front covering of the eye.  About half of affected individuals develop glaucoma, a serious condition that increases pressure inside the eye. When glaucoma occurs with Axenfeld-Rieger syndrome, it most often develops in late childhood or adolescence, although it can occur as early as infancy. Glaucoma can cause vision loss or blindness.  The signs and symptoms of Axenfeld-Rieger syndrome can also affect other parts of the body. Many affected individuals have distinctive facial features such as widely spaced eyes (hypertelorism); a flattened mid-face with a broad, flat nasal bridge; and a prominent forehead. The condition is also associated with dental abnormalities including unusually small teeth (microdontia) or fewer than normal teeth (oligodontia). Some people with Axenfeld-Rieger syndrome have extra folds of skin around their belly button (redundant periumbilical skin). Other, less common features can include heart defects, the opening of the urethra on the underside of the penis (hypospadias), narrowing of the anus (anal stenosis), and abnormalities of the pituitary gland that can result in slow growth.  Researchers have described at least three types of Axenfeld-Rieger syndrome. The types, which are numbered 1 through 3, are distinguished by their genetic cause.",Axenfeld-Rieger syndrome,0000104,GHR,https://ghr.nlm.nih.gov/condition/axenfeld-rieger-syndrome,C3495488,T047,Disorders
How many people are affected by Axenfeld-Rieger syndrome ?,0000104-2,frequency,"Axenfeld-Rieger syndrome has an estimated prevalence of 1 in 200,000 people.",Axenfeld-Rieger syndrome,0000104,GHR,https://ghr.nlm.nih.gov/condition/axenfeld-rieger-syndrome,C3495488,T047,Disorders
What are the genetic changes related to Axenfeld-Rieger syndrome ?,0000104-3,genetic changes,"Axenfeld-Rieger syndrome results from mutations in at least two known genes, PITX2 and FOXC1. PITX2 gene mutations cause type 1, and FOXC1 gene mutations cause type 3. The gene associated with type 2 is likely located on chromosome 13, but it has not been identified. The proteins produced from the PITX2 and FOXC1 genes are transcription factors, which means they attach (bind) to DNA and help control the activity of other genes. These transcription factors are active before birth in the developing eye and in other parts of the body. They appear to play important roles in embryonic development, particularly in the formation of structures in the anterior segment of the eye.  Mutations in either the PITX2 or FOXC1 gene disrupt the activity of other genes that are needed for normal development. Impaired regulation of these genes leads to problems in the formation of the anterior segment of the eye and other parts of the body. These developmental abnormalities underlie the characteristic features of Axenfeld-Rieger syndrome. Affected individuals with PITX2 gene mutations are more likely than those with FOXC1 gene mutations to have abnormalities affecting parts of the body other than the eye.  Some people with Axenfeld-Rieger syndrome do not have identified mutations in the PITX2 or FOXC1 genes. In these individuals, the cause of the condition is unknown. Other as-yet-unidentified genes may also cause Axenfeld-Rieger syndrome.",Axenfeld-Rieger syndrome,0000104,GHR,https://ghr.nlm.nih.gov/condition/axenfeld-rieger-syndrome,C3495488,T047,Disorders
Is Axenfeld-Rieger syndrome inherited ?,0000104-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Axenfeld-Rieger syndrome,0000104,GHR,https://ghr.nlm.nih.gov/condition/axenfeld-rieger-syndrome,C3495488,T047,Disorders
What are the treatments for Axenfeld-Rieger syndrome ?,0000104-5,treatment,These resources address the diagnosis or management of Axenfeld-Rieger syndrome:  - Genetic Testing Registry: Axenfeld-Rieger syndrome type 1  - Genetic Testing Registry: Axenfeld-Rieger syndrome type 2  - Genetic Testing Registry: Axenfeld-Rieger syndrome type 3  - Genetic Testing Registry: Rieger syndrome  - Glaucoma Research Foundation: Care and Treatment   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Axenfeld-Rieger syndrome,0000104,GHR,https://ghr.nlm.nih.gov/condition/axenfeld-rieger-syndrome,C3495488,T047,Disorders
What is (are) Baller-Gerold syndrome ?,0000105-1,information,"Baller-Gerold syndrome is a rare condition characterized by the premature fusion of certain skull bones (craniosynostosis) and abnormalities of bones in the arms and hands.  People with Baller-Gerold syndrome have prematurely fused skull bones, most often along the coronal suture, the growth line that goes over the head from ear to ear. Other sutures of the skull may be fused as well. These changes result in an abnormally shaped head, a prominent forehead, and bulging eyes with shallow eye sockets (ocular proptosis). Other distinctive facial features can include widely spaced eyes (hypertelorism), a small mouth, and a saddle-shaped or underdeveloped nose.  Bone abnormalities in the hands include missing fingers (oligodactyly) and malformed or absent thumbs. Partial or complete absence of bones in the forearm is also common. Together, these hand and arm abnormalities are called radial ray malformations.  People with Baller-Gerold syndrome may have a variety of additional signs and symptoms including slow growth beginning in infancy, small stature, and malformed or missing kneecaps (patellae). A skin rash often appears on the arms and legs a few months after birth. This rash spreads over time, causing patchy changes in skin coloring, areas of thinning skin (atrophy), and small clusters of blood vessels just under the skin (telangiectases). These chronic skin problems are collectively known as poikiloderma.  The varied signs and symptoms of Baller-Gerold syndrome overlap with features of other disorders, namely Rothmund-Thomson syndrome and RAPADILINO syndrome. These syndromes are also characterized by radial ray defects, skeletal abnormalities, and slow growth. All of these conditions can be caused by mutations in the same gene. Based on these similarities, researchers are investigating whether Baller-Gerold syndrome, Rothmund-Thomson syndrome, and RAPADILINO syndrome are separate disorders or part of a single syndrome with overlapping signs and symptoms.",Baller-Gerold syndrome,0000105,GHR,https://ghr.nlm.nih.gov/condition/baller-gerold-syndrome,C0265308,T047,Disorders
How many people are affected by Baller-Gerold syndrome ?,0000105-2,frequency,"The prevalence of Baller-Gerold syndrome is unknown, but this rare condition probably affects fewer than 1 per million people. Fewer than 40 cases have been reported in the medical literature.",Baller-Gerold syndrome,0000105,GHR,https://ghr.nlm.nih.gov/condition/baller-gerold-syndrome,C0265308,T047,Disorders
What are the genetic changes related to Baller-Gerold syndrome ?,0000105-3,genetic changes,"Mutations in the RECQL4 gene cause some cases of Baller-Gerold syndrome. This gene provides instructions for making one member of a protein family called RecQ helicases. Helicases are enzymes that bind to DNA and temporarily unwind the two spiral strands (double helix) of the DNA molecule. This unwinding is necessary for copying (replicating) DNA in preparation for cell division, and for repairing damaged DNA. The RECQL4 protein helps stabilize genetic information in the body's cells and plays a role in replicating and repairing DNA.  Mutations in the RECQL4 gene prevent cells from producing any RECQL4 protein or change the way the protein is pieced together, which disrupts its usual function. A shortage of this protein may prevent normal DNA replication and repair, causing widespread damage to a person's genetic information over time. It is unclear how a loss of this protein's activity leads to the signs and symptoms of Baller-Gerold syndrome.  This condition has been associated with prenatal (before birth) exposure to a drug called sodium valproate. This medication is used to treat epilepsy and certain psychiatric disorders. Some infants whose mothers took sodium valproate during pregnancy were born with the characteristic features of Baller-Gerold syndrome, such as an unusual skull shape, distinctive facial features, and abnormalities of the arms and hands. However, it is unclear if exposure to the medication caused the condition.",Baller-Gerold syndrome,0000105,GHR,https://ghr.nlm.nih.gov/condition/baller-gerold-syndrome,C0265308,T047,Disorders
Is Baller-Gerold syndrome inherited ?,0000105-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Baller-Gerold syndrome,0000105,GHR,https://ghr.nlm.nih.gov/condition/baller-gerold-syndrome,C0265308,T047,Disorders
What are the treatments for Baller-Gerold syndrome ?,0000105-5,treatment,These resources address the diagnosis or management of Baller-Gerold syndrome:  - Gene Review: Gene Review: Baller-Gerold Syndrome  - Genetic Testing Registry: Baller-Gerold syndrome  - MedlinePlus Encyclopedia: Craniosynostosis  - MedlinePlus Encyclopedia: Skull of a Newborn (image)   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Baller-Gerold syndrome,0000105,GHR,https://ghr.nlm.nih.gov/condition/baller-gerold-syndrome,C0265308,T047,Disorders
What is (are) Bannayan-Riley-Ruvalcaba syndrome ?,0000106-1,information,"Bannayan-Riley-Ruvalcaba syndrome is a genetic condition characterized by a large head size (macrocephaly), multiple noncancerous tumors and tumor-like growths called hamartomas, and dark freckles on the penis in males. The signs and symptoms of Bannayan-Riley-Ruvalcaba syndrome are present from birth or become apparent in early childhood.  At least half of affected infants have macrocephaly, and many also have a high birth weight and a large body size (macrosomia). Growth usually slows during childhood, so affected adults are of normal height and body size. About half of all children with Bannayan-Riley-Ruvalcaba syndrome have intellectual disability or delayed development, particularly the development of speech and of motor skills such as sitting, crawling, and walking. These delays may improve with age.  About half of all people with Bannayan-Riley-Ruvalcaba syndrome develop hamartomas in their intestines, known as hamartomatous polyps. Other noncancerous growths often associated with Bannayan-Riley-Ruvalcaba syndrome include fatty tumors called lipomas and angiolipomas that develop under the skin. Some affected individuals also develop hemangiomas, which are red or purplish growths that consist of tangles of abnormal blood vessels. People with Bannayan-Riley-Ruvalcaba syndrome may also have an increased risk of developing certain cancers, although researchers are still working to determine the cancer risks associated with this condition.  Other signs and symptoms that have been reported in people with Bannayan-Riley-Ruvalcaba syndrome include weak muscle tone (hypotonia) and other muscle abnormalities, thyroid problems, and seizures. Skeletal abnormalities have also been described with this condition, including an unusually large range of joint movement (hyperextensibility), abnormal side-to-side curvature of the spine (scoliosis), and a sunken chest (pectus excavatum).  The features of Bannayan-Riley-Ruvalcaba syndrome overlap with those of another disorder called Cowden syndrome. People with Cowden syndrome develop hamartomas and other noncancerous growths; they also have an increased risk of developing certain types of cancer. Both conditions can be caused by mutations in the PTEN gene. Some people with Bannayan-Riley-Ruvalcaba syndrome have had relatives diagnosed with Cowden syndrome, and other individuals have had the characteristic features of both conditions. Based on these similarities, researchers have proposed that Bannayan-Riley-Ruvalcaba syndrome and Cowden syndrome represent a spectrum of overlapping features known as PTEN hamartoma tumor syndrome instead of two distinct conditions.",Bannayan-Riley-Ruvalcaba syndrome,0000106,GHR,https://ghr.nlm.nih.gov/condition/bannayan-riley-ruvalcaba-syndrome,C0265326,T019,Disorders
How many people are affected by Bannayan-Riley-Ruvalcaba syndrome ?,0000106-2,frequency,"The prevalence of Bannayan-Riley-Ruvalcaba syndrome is unknown, although it appears to be rare. Several dozen cases have been reported in the medical literature. Researchers suspect that the disorder is underdiagnosed because its signs and symptoms vary and some of them are subtle.",Bannayan-Riley-Ruvalcaba syndrome,0000106,GHR,https://ghr.nlm.nih.gov/condition/bannayan-riley-ruvalcaba-syndrome,C0265326,T019,Disorders
What are the genetic changes related to Bannayan-Riley-Ruvalcaba syndrome ?,0000106-3,genetic changes,"About 60 percent of all cases of Bannayan-Riley-Ruvalcaba syndrome result from mutations in the PTEN gene. Another 10 percent of cases are caused by a large deletion of genetic material that includes part or all of this gene. The protein produced from the PTEN gene is a tumor suppressor, which means that it normally prevents cells from growing and dividing (proliferating) too rapidly or in an uncontrolled way. If this protein is missing or defective, cell proliferation is not regulated effectively. Uncontrolled cell division can lead to the formation of hamartomas and other cancerous and noncancerous tumors. The protein produced from the PTEN gene likely has other important functions within cells; however, it is unclear how mutations in this gene can cause the other features of Bannayan-Riley-Ruvalcaba syndrome, such as macrocephaly, developmental delay, and muscle and skeletal abnormalities.  When Bannayan-Riley-Ruvalcaba syndrome is not caused by mutations or deletions of the PTEN gene, the cause of the condition is unknown.",Bannayan-Riley-Ruvalcaba syndrome,0000106,GHR,https://ghr.nlm.nih.gov/condition/bannayan-riley-ruvalcaba-syndrome,C0265326,T019,Disorders
Is Bannayan-Riley-Ruvalcaba syndrome inherited ?,0000106-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Bannayan-Riley-Ruvalcaba syndrome,0000106,GHR,https://ghr.nlm.nih.gov/condition/bannayan-riley-ruvalcaba-syndrome,C0265326,T019,Disorders
What are the treatments for Bannayan-Riley-Ruvalcaba syndrome ?,0000106-5,treatment,These resources address the diagnosis or management of Bannayan-Riley-Ruvalcaba syndrome:  - Gene Review: Gene Review: PTEN Hamartoma Tumor Syndrome (PHTS)  - Genetic Testing Registry: Bannayan-Riley-Ruvalcaba syndrome  - University of Iowa: Bannayan-Ruvalcaba-Riley Syndrome (BRRS): A Guide for Patients and Their Families   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Bannayan-Riley-Ruvalcaba syndrome,0000106,GHR,https://ghr.nlm.nih.gov/condition/bannayan-riley-ruvalcaba-syndrome,C0265326,T019,Disorders
What is (are) Baraitser-Winter syndrome ?,0000107-1,information,"Baraitser-Winter syndrome is a condition that affects the development of many parts of the body, particularly the face and the brain.  An unusual facial appearance is the most common characteristic of Baraitser-Winter syndrome. Distinctive facial features can include widely spaced eyes (hypertelorism), large eyelid openings, droopy eyelids (ptosis), high-arched eyebrows, a broad nasal bridge and tip of the nose, a long space between the nose and upper lip (philtrum), full cheeks, and a pointed chin.  Structural brain abnormalities are also present in most people with Baraitser-Winter syndrome. These abnormalities are related to impaired neuronal migration, a process by which nerve cells (neurons) move to their proper positions in the developing brain. The most frequent brain abnormality associated with Baraitser-Winter syndrome is pachygyria, which is an area of the brain that has an abnormally smooth surface with fewer folds and grooves. Less commonly, affected individuals have lissencephaly, which is similar to pachygyria but involves the entire brain surface. These structural changes can cause mild to severe intellectual disability, developmental delay, and seizures.  Other features of Baraitser-Winter syndrome can include short stature, ear abnormalities and hearing loss, heart defects, presence of an extra (duplicated) thumb, and abnormalities of the kidneys and urinary system. Some affected individuals have limited movement of large joints, such as the elbows and knees, which may be present at birth or develop over time. Rarely, people with Baraitser-Winter syndrome have involuntary muscle tensing (dystonia).",Baraitser-Winter syndrome,0000107,GHR,https://ghr.nlm.nih.gov/condition/baraitser-winter-syndrome,C0796084,,Disorders
How many people are affected by Baraitser-Winter syndrome ?,0000107-2,frequency,Baraitser-Winter syndrome is a rare condition. Fewer than 50 cases have been reported in the medical literature.,Baraitser-Winter syndrome,0000107,GHR,https://ghr.nlm.nih.gov/condition/baraitser-winter-syndrome,C0796084,,Disorders
What are the genetic changes related to Baraitser-Winter syndrome ?,0000107-3,genetic changes,"Baraitser-Winter syndrome can result from mutations in either the ACTB or ACTG1 gene. These genes provide instructions for making proteins called beta ()-actin and gamma ()-actin, respectively. These proteins are active (expressed) in cells throughout the body. They are organized into a network of fibers called the actin cytoskeleton, which makes up the cell's structural framework. The actin cytoskeleton has several critical functions, including determining cell shape and allowing cells to move.  Mutations in the ACTB or ACTG1 gene alter the function of -actin or -actin. The malfunctioning actin causes changes in the actin cytoskeleton that modify the structure and organization of cells and affect their ability to move. Because these two actin proteins are present in cells throughout the body and are involved in many cell activities, problems with their function likely impact many aspects of development, including neuronal migration. These changes underlie the variety of signs and symptoms associated with Baraitser-Winter syndrome.",Baraitser-Winter syndrome,0000107,GHR,https://ghr.nlm.nih.gov/condition/baraitser-winter-syndrome,C0796084,,Disorders
Is Baraitser-Winter syndrome inherited ?,0000107-4,inheritance,"This condition is described as autosomal dominant, which means one copy of the altered gene in each cell is sufficient to cause the disorder. The condition almost always results from new (de novo) mutations in the ACTB or ACTG1 gene and occurs in people with no history of the disorder in their family.",Baraitser-Winter syndrome,0000107,GHR,https://ghr.nlm.nih.gov/condition/baraitser-winter-syndrome,C0796084,,Disorders
What are the treatments for Baraitser-Winter syndrome ?,0000107-5,treatment,These resources address the diagnosis or management of Baraitser-Winter syndrome:  - Gene Review: Gene Review: Baraitser-Winter Cerebrofrontofacial Syndrome  - Genetic Testing Registry: Baraitser-Winter Syndrome 2   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Baraitser-Winter syndrome,0000107,GHR,https://ghr.nlm.nih.gov/condition/baraitser-winter-syndrome,C0796084,,Disorders
What is (are) Bardet-Biedl syndrome ?,0000108-1,information,"Bardet-Biedl syndrome is a disorder that affects many parts of the body. The signs and symptoms of this condition vary among affected individuals, even among members of the same family.  Vision loss is one of the major features of Bardet-Biedl syndrome. Loss of vision occurs as the light-sensing tissue at the back of the eye (the retina) gradually deteriorates. Problems with night vision become apparent by mid-childhood, followed by blind spots that develop in the side (peripheral) vision. Over time, these blind spots enlarge and merge to produce tunnel vision. Most people with Bardet-Biedl syndrome also develop blurred central vision (poor visual acuity) and become legally blind by adolescence or early adulthood.  Obesity is another characteristic feature of Bardet-Biedl syndrome. Abnormal weight gain typically begins in early childhood and continues to be an issue throughout life. Complications of obesity can include type 2 diabetes, high blood pressure (hypertension), and abnormally high cholesterol levels (hypercholesterolemia).  Other major signs and symptoms of Bardet-Biedl syndrome include the presence of extra fingers or toes (polydactyly), intellectual disability or learning problems, and abnormalities of the genitalia. Most affected males produce reduced amounts of sex hormones (hypogonadism), and they are usually unable to father biological children (infertile). Many people with Bardet-Biedl syndrome also have kidney abnormalities, which can be serious or life-threatening.  Additional features of Bardet-Biedl syndrome can include impaired speech, delayed development of motor skills such as standing and walking, behavioral problems such as emotional immaturity and inappropriate outbursts, and clumsiness or poor coordination. Distinctive facial features, dental abnormalities, unusually short or fused fingers or toes, and a partial or complete loss of the sense of smell (anosmia) have also been reported in some people with Bardet-Biedl syndrome. Additionally, this condition can affect the heart, liver, and digestive system.",Bardet-Biedl syndrome,0000108,GHR,https://ghr.nlm.nih.gov/condition/bardet-biedl-syndrome,C0752166,T047,Disorders
How many people are affected by Bardet-Biedl syndrome ?,0000108-2,frequency,"In most of North America and Europe, Bardet-Biedl syndrome has a prevalence of 1 in 140,000 to 1 in 160,000 newborns. The condition is more common on the island of Newfoundland (off the east coast of Canada), where it affects an estimated 1 in 17,000 newborns. It also occurs more frequently in the Bedouin population of Kuwait, affecting about 1 in 13,500 newborns.",Bardet-Biedl syndrome,0000108,GHR,https://ghr.nlm.nih.gov/condition/bardet-biedl-syndrome,C0752166,T047,Disorders
What are the genetic changes related to Bardet-Biedl syndrome ?,0000108-3,genetic changes,"Bardet-Biedl syndrome can result from mutations in at least 14 different genes (often called BBS genes). These genes are known or suspected to play critical roles in cell structures called cilia. Cilia are microscopic, finger-like projections that stick out from the surface of many types of cells. They are involved in cell movement and many different chemical signaling pathways. Cilia are also necessary for the perception of sensory input (such as sight, hearing, and smell). The proteins produced from BBS genes are involved in the maintenance and function of cilia.  Mutations in BBS genes lead to problems with the structure and function of cilia. Defects in these cell structures probably disrupt important chemical signaling pathways during development and lead to abnormalities of sensory perception. Researchers believe that defective cilia are responsible for most of the features of Bardet-Biedl syndrome.  About one-quarter of all cases of Bardet-Biedl syndrome result from mutations in the BBS1 gene. Another 20 percent of cases are caused by mutations in the BBS10 gene. The other BBS genes each account for only a small percentage of all cases of this condition. In about 25 percent of people with Bardet-Biedl syndrome, the cause of the disorder is unknown.  In affected individuals who have mutations in one of the BBS genes, mutations in additional genes may be involved in causing or modifying the course of the disorder. Studies suggest that these modifying genes may be known BBS genes or other genes. The additional genetic changes could help explain the variability in the signs and symptoms of Bardet-Biedl syndrome. However, this phenomenon appears to be uncommon, and it has not been found consistently in scientific studies.",Bardet-Biedl syndrome,0000108,GHR,https://ghr.nlm.nih.gov/condition/bardet-biedl-syndrome,C0752166,T047,Disorders
Is Bardet-Biedl syndrome inherited ?,0000108-4,inheritance,"Bardet-Biedl syndrome is typically inherited in an autosomal recessive pattern, which means both copies of a BBS gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Bardet-Biedl syndrome,0000108,GHR,https://ghr.nlm.nih.gov/condition/bardet-biedl-syndrome,C0752166,T047,Disorders
What are the treatments for Bardet-Biedl syndrome ?,0000108-5,treatment,These resources address the diagnosis or management of Bardet-Biedl syndrome:  - Gene Review: Gene Review: Bardet-Biedl Syndrome  - Genetic Testing Registry: Bardet-Biedl syndrome  - MedlinePlus Encyclopedia: Obesity  - MedlinePlus Encyclopedia: Polydactyly   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Bardet-Biedl syndrome,0000108,GHR,https://ghr.nlm.nih.gov/condition/bardet-biedl-syndrome,C0752166,T047,Disorders
What is (are) Bart-Pumphrey syndrome ?,0000109-1,information,"Bart-Pumphrey syndrome is characterized by nail and skin abnormalities and hearing loss.  People with Bart-Pumphrey syndrome typically have a white discoloration of the nails (leukonychia); the nails may also be thick and crumbly. Affected individuals often have wart-like (verrucous) skin growths called knuckle pads on the knuckles of the fingers and toes. They may also have thickening of the skin on the palms of the hands and soles of the feet (palmoplantar keratoderma). The skin abnormalities generally become noticeable during childhood.  The hearing loss associated with Bart-Pumphrey syndrome ranges from moderate to profound and is typically present from birth (congenital).  The signs and symptoms of this disorder may vary even within the same family; while almost all affected individuals have hearing loss, they may have different combinations of the other associated features.",Bart-Pumphrey syndrome,0000109,GHR,https://ghr.nlm.nih.gov/condition/bart-pumphrey-syndrome,C0266004,T019,Disorders
How many people are affected by Bart-Pumphrey syndrome ?,0000109-2,frequency,Bart-Pumphrey syndrome is a rare disorder; its exact prevalence is unknown. Only a few affected families and individual cases have been identified.,Bart-Pumphrey syndrome,0000109,GHR,https://ghr.nlm.nih.gov/condition/bart-pumphrey-syndrome,C0266004,T019,Disorders
What are the genetic changes related to Bart-Pumphrey syndrome ?,0000109-3,genetic changes,"Bart-Pumphrey syndrome is caused by mutations in the GJB2 gene. This gene provides instructions for making a protein called gap junction beta 2, more commonly known as connexin 26. Connexin 26 is a member of the connexin protein family. Connexin proteins form channels called gap junctions that permit the transport of nutrients, charged atoms (ions), and signaling molecules between neighboring cells that are in contact with each other. Gap junctions made with connexin 26 transport potassium ions and certain small molecules.  Connexin 26 is found in cells throughout the body, including the inner ear and the skin. In the inner ear, channels made from connexin 26 are found in a snail-shaped structure called the cochlea. These channels may help to maintain the proper level of potassium ions required for the conversion of sound waves to electrical nerve impulses. This conversion is essential for normal hearing. In addition, connexin 26 may be involved in the maturation of certain cells in the cochlea. Connexin 26 also plays a role in the growth, maturation, and stability of the outermost layer of skin (the epidermis).  The GJB2 gene mutations that cause Bart-Pumphrey syndrome change single protein building blocks (amino acids) in the connexin 26 protein. The altered protein probably disrupts the function of normal connexin 26 in cells, and may interfere with the function of other connexin proteins. This disruption could affect skin growth and also impair hearing by disturbing the conversion of sound waves to nerve impulses.",Bart-Pumphrey syndrome,0000109,GHR,https://ghr.nlm.nih.gov/condition/bart-pumphrey-syndrome,C0266004,T019,Disorders
Is Bart-Pumphrey syndrome inherited ?,0000109-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",Bart-Pumphrey syndrome,0000109,GHR,https://ghr.nlm.nih.gov/condition/bart-pumphrey-syndrome,C0266004,T019,Disorders
What are the treatments for Bart-Pumphrey syndrome ?,0000109-5,treatment,"These resources address the diagnosis or management of Bart-Pumphrey syndrome:  - Foundation for Ichthyosis and Related Skin Types: Palmoplantar Keratoderma  - Genetic Testing Registry: Knuckle pads, deafness AND leukonychia syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Bart-Pumphrey syndrome,0000109,GHR,https://ghr.nlm.nih.gov/condition/bart-pumphrey-syndrome,C0266004,T019,Disorders
What is (are) Barth syndrome ?,0000110-1,information,"Barth syndrome is a rare condition characterized by an enlarged and weakened heart (dilated cardiomyopathy), weakness in muscles used for movement (skeletal myopathy), recurrent infections due to small numbers of white blood cells (neutropenia), and short stature. Barth syndrome occurs almost exclusively in males.  In males with Barth syndrome, dilated cardiomyopathy is often present at birth or develops within the first months of life. Over time, the heart muscle becomes increasingly weakened and is less able to pump blood. Individuals with Barth syndrome may have elastic fibers in place of muscle fibers in some areas of the heart muscle, which contributes to the cardiomyopathy. This condition is called endocardial fibroelastosis; it results in thickening of the muscle and impairs its ability to pump blood. In people with Barth syndrome, the heart problems can lead to heart failure. In rare cases, the cardiomyopathy gets better over time and affected individuals eventually have no symptoms of heart disease.  In Barth syndrome, skeletal myopathy, particularly of the muscles closest to the center of the body (proximal muscles), is usually noticeable from birth and causes low muscle tone (hypotonia). The muscle weakness often causes delay of motor skills such as crawling and walking. Additionally, affected individuals tend to experience extreme tiredness (fatigue) during strenuous physical activity.  Most males with Barth syndrome have neutropenia. The levels of white blood cells can be consistently low (persistent), can vary from normal to low (intermittent), or can cycle between regular episodes of normal and low (cyclical). Neutropenia makes it more difficult for the body to fight off foreign invaders such as bacteria and viruses, so affected individuals have an increased risk of recurrent infections.  Newborns with Barth syndrome are often smaller than normal, and their growth continues to be slow throughout life. Some boys with this condition experience a growth spurt in puberty and are of average height as adults, but many men with Barth syndrome continue to have short stature in adulthood.  Males with Barth syndrome often have distinctive facial features including prominent cheeks. Affected individuals typically have normal intelligence but often have difficulty performing tasks involving math or visual-spatial skills such as puzzles.  Males with Barth syndrome have increased levels of a substance called 3-methylglutaconic acid in their blood and urine. The amount of the acid does not appear to influence the signs and symptoms of the condition. Barth syndrome is one of a group of metabolic disorders that can be diagnosed by the presence of increased levels of 3-methylglutaconic acid in urine (3-methylglutaconic aciduria).  Even though most features of Barth syndrome are present at birth or in infancy, affected individuals may not experience health problems until later in life. The age at which individuals with Barth syndrome display symptoms or are diagnosed varies greatly. The severity of signs and symptoms among affected individuals is also highly variable.  Males with Barth syndrome have a reduced life expectancy. Many affected children die of heart failure or infection in infancy or early childhood, but those who live into adulthood can survive into their late forties.",Barth syndrome,0000110,GHR,https://ghr.nlm.nih.gov/condition/barth-syndrome,C0574083,T047,Disorders
How many people are affected by Barth syndrome ?,0000110-2,frequency,"Barth syndrome is estimated to affect 1 in 300,000 to 400,000 individuals worldwide. More than 150 cases have been described in the scientific literature.",Barth syndrome,0000110,GHR,https://ghr.nlm.nih.gov/condition/barth-syndrome,C0574083,T047,Disorders
What are the genetic changes related to Barth syndrome ?,0000110-3,genetic changes,"Mutations in the TAZ gene cause Barth syndrome. The TAZ gene provides instructions for making a protein called tafazzin. Tafazzin is located in structures called mitochondria, which are the energy-producing centers of cells. Tafazzin is involved in altering a fat (lipid) called cardiolipin, which plays critical roles in the mitochondrial inner membrane. Once altered by tafazzin, cardiolipin is key in maintaining mitochondrial shape, energy production, and protein transport within cells.  TAZ gene mutations result in the production of tafazzin proteins with little or no function. As a result, tafazzin cannot alter cardiolipin. A lack of functional cardiolipin impairs normal mitochondrial shape and functions. Tissues with high energy demands, such as the heart and skeletal muscles, are most susceptible to cell death due to reduced energy production in mitochondria. Additionally, abnormally shaped mitochondria are found in affected white blood cells, which could affect their ability to grow (proliferate) and mature (differentiate), leading to neutropenia. Dysfunctional mitochondria likely lead to other signs and symptoms of Barth syndrome.",Barth syndrome,0000110,GHR,https://ghr.nlm.nih.gov/condition/barth-syndrome,C0574083,T047,Disorders
Is Barth syndrome inherited ?,0000110-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",Barth syndrome,0000110,GHR,https://ghr.nlm.nih.gov/condition/barth-syndrome,C0574083,T047,Disorders
What are the treatments for Barth syndrome ?,0000110-5,treatment,These resources address the diagnosis or management of Barth syndrome:  - Cleveland Clinic: Dilated Cardiomyopathy  - Gene Review: Gene Review: Barth Syndrome  - Genetic Testing Registry: 3-Methylglutaconic aciduria type 2  - Johns Hopkins Children's Center: Neutrophil Disorders  - MedlinePlus Encyclopedia: Neutropenia--Infants   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Barth syndrome,0000110,GHR,https://ghr.nlm.nih.gov/condition/barth-syndrome,C0574083,T047,Disorders
What is (are) Bartter syndrome ?,0000111-1,information,"Bartter syndrome is a group of very similar kidney disorders that cause an imbalance of potassium, sodium, chloride, and related molecules in the body.  In some cases, Bartter syndrome becomes apparent before birth. The disorder can cause polyhydramnios, which is an increased volume of fluid surrounding the fetus (amniotic fluid). Polyhydramnios increases the risk of premature birth.  Beginning in infancy, affected individuals often fail to grow and gain weight at the expected rate (failure to thrive). They lose excess amounts of salt (sodium chloride) in their urine, which leads to dehydration, constipation, and increased urine production (polyuria). In addition, large amounts of calcium are lost through the urine (hypercalciuria), which can cause weakening of the bones (osteopenia). Some of the calcium is deposited in the kidneys as they are concentrating urine, leading to hardening of the kidney tissue (nephrocalcinosis). Bartter syndrome is also characterized by low levels of potassium in the blood (hypokalemia), which can result in muscle weakness, cramping, and fatigue. Rarely, affected children develop hearing loss caused by abnormalities in the inner ear (sensorineural deafness).  Two major forms of Bartter syndrome are distinguished by their age of onset and severity. One form begins before birth (antenatal) and is often life-threatening. The other form, often called the classical form, begins in early childhood and tends to be less severe. Once the genetic causes of Bartter syndrome were identified, researchers also split the disorder into different types based on the genes involved. Types I, II, and IV have the features of antenatal Bartter syndrome. Because type IV is also associated with hearing loss, it is sometimes called antenatal Bartter syndrome with sensorineural deafness. Type III usually has the features of classical Bartter syndrome.",Bartter syndrome,0000111,GHR,https://ghr.nlm.nih.gov/condition/bartter-syndrome,C0004775,T047,Disorders
How many people are affected by Bartter syndrome ?,0000111-2,frequency,"The exact prevalence of this disorder is unknown, although it likely affects about 1 per million people worldwide. The condition appears to be more common in Costa Rica and Kuwait than in other populations.",Bartter syndrome,0000111,GHR,https://ghr.nlm.nih.gov/condition/bartter-syndrome,C0004775,T047,Disorders
What are the genetic changes related to Bartter syndrome ?,0000111-3,genetic changes,"Bartter syndrome can be caused by mutations in at least five genes. Mutations in the SLC12A1 gene cause type I. Type II results from mutations in the KCNJ1 gene. Mutations in the CLCNKB gene are responsible for type III. Type IV can result from mutations in the BSND gene or from a combination of mutations in the CLCNKA and CLCNKB genes.  The genes associated with Bartter syndrome play important roles in normal kidney function. The proteins produced from these genes are involved in the kidneys' reabsorption of salt. Mutations in any of the five genes impair the kidneys' ability to reabsorb salt, leading to the loss of excess salt in the urine (salt wasting). Abnormalities of salt transport also affect the reabsorption of other charged atoms (ions), including potassium and calcium. The resulting imbalance of ions in the body leads to the major features of Bartter syndrome.  In some people with Bartter syndrome, the genetic cause of the disorder is unknown. Researchers are searching for additional genes that may be associated with this condition.",Bartter syndrome,0000111,GHR,https://ghr.nlm.nih.gov/condition/bartter-syndrome,C0004775,T047,Disorders
Is Bartter syndrome inherited ?,0000111-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Bartter syndrome,0000111,GHR,https://ghr.nlm.nih.gov/condition/bartter-syndrome,C0004775,T047,Disorders
What are the treatments for Bartter syndrome ?,0000111-5,treatment,"These resources address the diagnosis or management of Bartter syndrome:  - Genetic Testing Registry: Bartter syndrome antenatal type 1  - Genetic Testing Registry: Bartter syndrome antenatal type 2  - Genetic Testing Registry: Bartter syndrome type 3  - Genetic Testing Registry: Bartter syndrome type 4  - Genetic Testing Registry: Bartter syndrome, type 4b  - Genetic Testing Registry: Bartter's syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Bartter syndrome,0000111,GHR,https://ghr.nlm.nih.gov/condition/bartter-syndrome,C0004775,T047,Disorders
What is (are) Beare-Stevenson cutis gyrata syndrome ?,0000112-1,information,"Beare-Stevenson cutis gyrata syndrome is a genetic disorder characterized by skin abnormalities and the premature fusion of certain bones of the skull (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face.  Many of the characteristic facial features of Beare-Stevenson cutis gyrata syndrome result from the premature fusion of the skull bones. The head is unable to grow normally, which leads to a cloverleaf-shaped skull, wide-set and bulging eyes, ear abnormalities, and an underdeveloped upper jaw. Early fusion of the skull bones also affects the growth of the brain, causing delayed development and intellectual disability.  A skin abnormality called cutis gyrata is also characteristic of this disorder. The skin has a furrowed and wrinkled appearance, particularly on the face, near the ears, and on the palms and soles of the feet. Additionally, thick, dark, velvety areas of skin (acanthosis nigricans) are sometimes found on the hands and feet and in the genital region.  Additional signs and symptoms of Beare-Stevenson cutis gyrata syndrome can include a blockage of the nasal passages (choanal atresia), overgrowth of the umbilical stump (tissue that normally falls off shortly after birth, leaving the belly button), and abnormalities of the genitalia and anus. The medical complications associated with this condition are often life-threatening in infancy or early childhood.",Beare-Stevenson cutis gyrata syndrome,0000112,GHR,https://ghr.nlm.nih.gov/condition/beare-stevenson-cutis-gyrata-syndrome,C3805479,T019,Disorders
How many people are affected by Beare-Stevenson cutis gyrata syndrome ?,0000112-2,frequency,Beare-Stevenson cutis gyrata syndrome is a rare genetic disorder; its incidence is unknown. Fewer than 20 people with this condition have been reported worldwide.,Beare-Stevenson cutis gyrata syndrome,0000112,GHR,https://ghr.nlm.nih.gov/condition/beare-stevenson-cutis-gyrata-syndrome,C3805479,T019,Disorders
What are the genetic changes related to Beare-Stevenson cutis gyrata syndrome ?,0000112-3,genetic changes,"Mutations in the FGFR2 gene cause Beare-Stevenson cutis gyrata syndrome. This gene produces a protein called fibroblast growth factor receptor 2, which plays an important role in signaling a cell to respond to its environment, perhaps by dividing or maturing. A mutation in the FGFR2 gene alters the protein and promotes prolonged signaling, which is thought to interfere with skeletal and skin development.  Some individuals with Beare-Stevenson cutis gyrata syndrome do not have identified mutations in the FGFR2 gene. In these cases, the cause of the condition is unknown.",Beare-Stevenson cutis gyrata syndrome,0000112,GHR,https://ghr.nlm.nih.gov/condition/beare-stevenson-cutis-gyrata-syndrome,C3805479,T019,Disorders
Is Beare-Stevenson cutis gyrata syndrome inherited ?,0000112-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. All reported cases have resulted from new mutations in the gene, and occurred in people with no history of the disorder in their family.",Beare-Stevenson cutis gyrata syndrome,0000112,GHR,https://ghr.nlm.nih.gov/condition/beare-stevenson-cutis-gyrata-syndrome,C3805479,T019,Disorders
What are the treatments for Beare-Stevenson cutis gyrata syndrome ?,0000112-5,treatment,These resources address the diagnosis or management of Beare-Stevenson cutis gyrata syndrome:  - Gene Review: Gene Review: FGFR-Related Craniosynostosis Syndromes  - Genetic Testing Registry: Cutis Gyrata syndrome of Beare and Stevenson  - MedlinePlus Encyclopedia: Acanthosis Nigricans  - MedlinePlus Encyclopedia: Craniosynostosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Beare-Stevenson cutis gyrata syndrome,0000112,GHR,https://ghr.nlm.nih.gov/condition/beare-stevenson-cutis-gyrata-syndrome,C3805479,T019,Disorders
What is (are) Beckwith-Wiedemann syndrome ?,0000113-1,information,"Beckwith-Wiedemann syndrome is a condition that affects many parts of the body. It is classified as an overgrowth syndrome, which means that affected infants are considerably larger than normal (macrosomia) and tend to be taller than their peers during childhood. Growth begins to slow by about age 8, and adults with this condition are not unusually tall. In some children with Beckwith-Wiedemann syndrome, specific parts of the body on one side or the other may grow abnormally large, leading to an asymmetric or uneven appearance. This unusual growth pattern, which is known as hemihyperplasia, usually becomes less apparent over time.  The signs and symptoms of Beckwith-Wiedemann syndrome vary among affected individuals. Some children with this condition are born with an opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the belly-button. Other abdominal wall defects, such as a soft out-pouching around the belly-button (an umbilical hernia), are also common. Some infants with Beckwith-Wiedemann syndrome have an abnormally large tongue (macroglossia), which may interfere with breathing, swallowing, and speaking. Other major features of this condition include abnormally large abdominal organs (visceromegaly), creases or pits in the skin near the ears, low blood sugar (hypoglycemia) in infancy, and kidney abnormalities.  Children with Beckwith-Wiedemann syndrome are at an increased risk of developing several types of cancerous and noncancerous tumors, particularly a form of kidney cancer called Wilms tumor and a form of liver cancer called hepatoblastoma. Tumors develop in about 10 percent of people with this condition and almost always appear in childhood.  Most children and adults with Beckwith-Wiedemann syndrome do not have serious medical problems associated with the condition. Their life expectancy is usually normal.",Beckwith-Wiedemann syndrome,0000113,GHR,https://ghr.nlm.nih.gov/condition/beckwith-wiedemann-syndrome,C0004903,T019,Disorders
How many people are affected by Beckwith-Wiedemann syndrome ?,0000113-2,frequency,"Beckwith-Wiedemann syndrome affects an estimated 1 in 13,700 newborns worldwide. The condition may actually be more common than this estimate because some people with mild symptoms are never diagnosed.",Beckwith-Wiedemann syndrome,0000113,GHR,https://ghr.nlm.nih.gov/condition/beckwith-wiedemann-syndrome,C0004903,T019,Disorders
What are the genetic changes related to Beckwith-Wiedemann syndrome ?,0000113-3,genetic changes,"The genetic causes of Beckwith-Wiedemann syndrome are complex. The condition usually results from the abnormal regulation of genes in a particular region of chromosome 11. People normally inherit one copy of this chromosome from each parent. For most genes on chromosome 11, both copies of the gene are expressed, or ""turned on,"" in cells. For some genes, however, only the copy inherited from a person's father (the paternally inherited copy) is expressed. For other genes, only the copy inherited from a person's mother (the maternally inherited copy) is expressed. These parent-specific differences in gene expression are caused by a phenomenon called genomic imprinting. Abnormalities involving genes on chromosome 11 that undergo genomic imprinting are responsible for most cases of Beckwith-Wiedemann syndrome.  At least half of all cases result from changes in a process called methylation. Methylation is a chemical reaction that attaches small molecules called methyl groups to certain segments of DNA. In genes that undergo genomic imprinting, methylation is one way that a gene's parent of origin is marked during the formation of egg and sperm cells. Beckwith-Wiedemann syndrome is often associated with changes in regions of DNA on chromosome 11 called imprinting centers (ICs). ICs control the methylation of several genes that are involved in normal growth, including the CDKN1C, H19, IGF2, and KCNQ1OT1 genes. Abnormal methylation disrupts the regulation of these genes, which leads to overgrowth and the other characteristic features of Beckwith-Wiedemann syndrome.  About twenty percent of cases of Beckwith-Wiedemann syndrome are caused by a genetic change known as paternal uniparental disomy (UPD). Paternal UPD causes people to have two active copies of paternally inherited genes rather than one active copy from the father and one inactive copy from the mother. People with paternal UPD are also missing genes that are active only on the maternally inherited copy of the chromosome. In Beckwith-Wiedemann syndrome, paternal UPD usually occurs early in embryonic development and affects only some of the body's cells. This phenomenon is called mosaicism. Mosaic paternal UPD leads to an imbalance in active paternal and maternal genes on chromosome 11, which underlies the signs and symptoms of the disorder.  Less commonly, mutations in the CDKN1C gene cause Beckwith-Wiedemann syndrome. This gene provides instructions for making a protein that helps control growth before birth. Mutations in the CDKN1C gene prevent this protein from restraining growth, which leads to the abnormalities characteristic of Beckwith-Wiedemann syndrome.  About 1 percent of all people with Beckwith-Wiedemann syndrome have a chromosomal abnormality such as a rearrangement (translocation), abnormal copying (duplication), or loss (deletion) of genetic material from chromosome 11. Like the other genetic changes responsible for Beckwith-Wiedemann syndrome, these abnormalities disrupt the normal regulation of certain genes on this chromosome.",Beckwith-Wiedemann syndrome,0000113,GHR,https://ghr.nlm.nih.gov/condition/beckwith-wiedemann-syndrome,C0004903,T019,Disorders
Is Beckwith-Wiedemann syndrome inherited ?,0000113-4,inheritance,"In about 85 percent of cases of Beckwith-Wiedemann syndrome, only one person in a family has been diagnosed with the condition. However, parents of one child with Beckwith-Wiedemann syndrome may be at risk of having other children with the disorder. This risk depends on the genetic cause of the condition.  Another 10 to 15 percent of people with Beckwith-Wiedemann syndrome are part of families with more than one affected family member. In most of these families, the condition appears to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of an altered gene in each cell is typically sufficient to cause the disorder. In most of these cases, individuals with Beckwith-Wiedemann syndrome inherit the genetic change from their mothers. Occasionally, a person who inherits the altered gene will not have any of the characteristic signs and symptoms of the condition.  Rarely, Beckwith-Wiedemann syndrome results from changes in the structure of chromosome 11. Some of these chromosomal abnormalities are inherited from a parent, while others occur as random events during the formation of reproductive cells (eggs and sperm) or in the earliest stages of development before birth.",Beckwith-Wiedemann syndrome,0000113,GHR,https://ghr.nlm.nih.gov/condition/beckwith-wiedemann-syndrome,C0004903,T019,Disorders
What are the treatments for Beckwith-Wiedemann syndrome ?,0000113-5,treatment,These resources address the diagnosis or management of Beckwith-Wiedemann syndrome:  - Gene Review: Gene Review: Beckwith-Wiedemann Syndrome  - Genetic Testing Registry: Beckwith-Wiedemann syndrome  - MedlinePlus Encyclopedia: Beckwith-Wiedemann syndrome  - MedlinePlus Encyclopedia: Macroglossia  - MedlinePlus Encyclopedia: Omphalocele   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Beckwith-Wiedemann syndrome,0000113,GHR,https://ghr.nlm.nih.gov/condition/beckwith-wiedemann-syndrome,C0004903,T019,Disorders
What is (are) Behet disease ?,0000114-1,information,"Behet disease is an inflammatory condition that affects many parts of the body. The health problems associated with Behet disease result from widespread inflammation of blood vessels (vasculitis). This inflammation most commonly affects the mouth, genitals, skin, and eyes.  Painful mouth sores called aphthous ulcers are usually the first sign of Behet disease. These sores occur on the lips and tongue and inside the cheeks. The ulcers look like common canker sores, and they typically heal within one to two weeks. About 75 percent of all people with Behet disease develop similar ulcers on the genitals. These ulcers occur most frequently on the scrotum in men and on the labia in women.  Behet disease can also cause painful bumps and sores on the skin. Most affected individuals develop pus-filled bumps that resemble acne. These bumps can occur anywhere on the body. Some affected people also have red, tender nodules called erythema nodosum. These nodules usually develop on the legs but can also occur on the face, neck, and arms.  An inflammation of the eye called uveitis is found in more than half of people with Behet disease. Eye problems are more common in younger people with the disease and affect men more often than women. Uveitis can result in blurry vision and an extreme sensitivity to light (photophobia). Rarely, inflammation can also cause eye pain and redness. If untreated, the eye problems associated with Behet disease can lead to blindness.  Less commonly, Behet disease can affect the joints, gastrointestinal tract, large blood vessels, and brain and spinal cord (central nervous system). Central nervous system abnormalities are among the most serious complications of Behet disease. Related symptoms can include headaches, confusion, personality changes, memory loss, impaired speech, and problems with balance and movement.  The signs and symptoms of Behet disease usually begin in a person's twenties or thirties, although they can appear at any age. Some affected people have relatively mild symptoms that are limited to sores in the mouth and on the genitals. Others have more severe symptoms affecting many parts of the body, including the central nervous system. The features of Behet disease typically come and go over a period of months or years. In most affected individuals, the health problems associated with this disorder improve with age.",Behet disease,0000114,GHR,https://ghr.nlm.nih.gov/condition/behcet-disease,C0012634,T047,Disorders
How many people are affected by Behet disease ?,0000114-2,frequency,"Behet disease is most common in Mediterranean countries, the Middle East, Japan, and other parts of Asia. However, it has been found in populations worldwide.  The highest prevalence of Behet disease has been reported in Turkey, where the disorder affects up to 420 in 100,000 people. The disorder is much less common in northern European countries and the United States, where it generally affects fewer than 1 in 100,000 people.",Behet disease,0000114,GHR,https://ghr.nlm.nih.gov/condition/behcet-disease,C0012634,T047,Disorders
What are the genetic changes related to Behet disease ?,0000114-3,genetic changes,"The cause of Behet disease is unknown. The condition probably results from a combination of genetic and environmental factors, most of which have not been identified. However, a particular variation in the HLA-B gene has been strongly associated with the risk of developing Behet disease.  The HLA-B gene provides instructions for making a protein that plays an important role in the immune system. The HLA-B gene is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). The HLA-B gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. A variation of the HLA-B gene called HLA-B51 increases the risk of developing Behet disease. Although many people with Behet disease have the HLA-B51 variation, most people with this version of the HLA-B gene never develop the disorder. It is unknown how HLA-B51 increases the risk of developing Behet disease.  Researchers have considered many other genetic and environmental factors as possible contributors to Behet disease. Studies have examined several genes related to immune system function, although no gene except HLA-B has been definitively associated with an increased risk of Behet disease. It appears likely that environmental factors, such as certain bacterial or viral infections, play a role in triggering the disease in people who are at risk. However, the influence of genetic and environmental factors on the development of this complex disorder remains unclear.",Behet disease,0000114,GHR,https://ghr.nlm.nih.gov/condition/behcet-disease,C0012634,T047,Disorders
Is Behet disease inherited ?,0000114-4,inheritance,"Most cases of Behet disease are sporadic, which means they occur in people with no history of the disorder in their family. A small percentage of all cases have been reported to run in families; however, the condition does not have a clear pattern of inheritance.",Behet disease,0000114,GHR,https://ghr.nlm.nih.gov/condition/behcet-disease,C0012634,T047,Disorders
What are the treatments for Behet disease ?,0000114-5,treatment,These resources address the diagnosis or management of Behet disease:  - American Behcet's Disease Association: Diagnosis  - American Behcet's Disease Association: Treatments  - Genetic Testing Registry: Behcet's syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Behet disease,0000114,GHR,https://ghr.nlm.nih.gov/condition/behcet-disease,C0012634,T047,Disorders
What is (are) benign chronic pemphigus ?,0000115-1,information,"Benign chronic pemphigus, often called Hailey-Hailey disease, is a rare skin condition that usually appears in early adulthood. The disorder is characterized by red, raw, and blistered areas of skin that occur most often in skin folds, such as the groin, armpits, neck, and under the breasts. These inflamed areas can become crusty or scaly and may itch and burn. The skin problems tend to worsen with exposure to moisture (such as sweat), friction, and hot weather.  The severity of benign chronic pemphigus varies from relatively mild episodes of skin irritation to widespread, persistent areas of raw and blistered skin that interfere with daily activities. Affected skin may become infected with bacteria or fungi, leading to pain and odor. Although the condition is described as ""benign"" (noncancerous), in rare cases the skin lesions may develop into a form of skin cancer called squamous cell carcinoma.  Many affected individuals also have white lines running the length of their fingernails. These lines do not cause any problems, but they can be useful for diagnosing benign chronic pemphigus.",benign chronic pemphigus,0000115,GHR,https://ghr.nlm.nih.gov/condition/benign-chronic-pemphigus,C0085106,T047,Disorders
How many people are affected by benign chronic pemphigus ?,0000115-2,frequency,Benign chronic pemphigus is a rare condition; its prevalence is unknown.,benign chronic pemphigus,0000115,GHR,https://ghr.nlm.nih.gov/condition/benign-chronic-pemphigus,C0085106,T047,Disorders
What are the genetic changes related to benign chronic pemphigus ?,0000115-3,genetic changes,"Benign chronic pemphigus results from mutations in the ATP2C1 gene. This gene provides instructions for producing a protein called hSPCA1, which is found in many types of cells. The hSPCA1 protein helps cells store calcium until it is needed. Calcium has several critical functions in cells, including regulating cell growth and division and helping cells stick to one another (cell adhesion). The hSPCA1 protein appears to be particularly important for the normal function of cells called keratinocytes, which are found in the outer layer of the skin (the epidermis).  Mutations in the ATP2C1 gene reduce the amount of functional hSPCA1 protein in cells. This abnormality impairs cells' ability to store calcium normally. For unknown reasons, this abnormal calcium storage affects keratinocytes more than other types of cells. The abnormal regulation of calcium impairs many cell functions, including cell adhesion. As a result, keratinocytes do not stick tightly to one another, which causes the epidermis to become fragile and less resistant to minor trauma. Because the skin is easily damaged, it develops raw, blistered areas, particularly in skin folds where there is moisture and friction.",benign chronic pemphigus,0000115,GHR,https://ghr.nlm.nih.gov/condition/benign-chronic-pemphigus,C0085106,T047,Disorders
Is benign chronic pemphigus inherited ?,0000115-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",benign chronic pemphigus,0000115,GHR,https://ghr.nlm.nih.gov/condition/benign-chronic-pemphigus,C0085106,T047,Disorders
What are the treatments for benign chronic pemphigus ?,0000115-5,treatment,These resources address the diagnosis or management of benign chronic pemphigus:  - American Osteopathic College of Dermatology  - Genetic Testing Registry: Familial benign pemphigus   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,benign chronic pemphigus,0000115,GHR,https://ghr.nlm.nih.gov/condition/benign-chronic-pemphigus,C0085106,T047,Disorders
What is (are) benign essential blepharospasm ?,0000116-1,information,"Benign essential blepharospasm is a condition characterized by abnormal blinking or spasms of the eyelids. This condition is a type of dystonia, which is a group of movement disorders involving uncontrolled tensing of the muscles (muscle contractions), rhythmic shaking (tremors), and other involuntary movements. Benign essential blepharospasm is different from the common, temporary eyelid twitching that can be caused by fatigue, stress, or caffeine.  The signs and symptoms of benign essential blepharospasm usually appear in mid- to late adulthood and gradually worsen. The first symptoms of the condition include an increased frequency of blinking, dry eyes, and eye irritation that is aggravated by wind, air pollution, sunlight, and other irritants. These symptoms may begin in one eye, but they ultimately affect both eyes. As the condition progresses, spasms of the muscles surrounding the eyes cause involuntary winking or squinting. Affected individuals have increasing difficulty keeping their eyes open, which can lead to severe vision impairment.  In more than half of all people with benign essential blepharospasm, the symptoms of dystonia spread beyond the eyes to affect other facial muscles and muscles in other areas of the body. When people with benign essential blepharospasm also experience involuntary muscle spasms affecting the tongue and jaw (oromandibular dystonia), the combination of signs and symptoms is known as Meige syndrome.",benign essential blepharospasm,0000116,GHR,https://ghr.nlm.nih.gov/condition/benign-essential-blepharospasm,C2930898,T047,Disorders
How many people are affected by benign essential blepharospasm ?,0000116-2,frequency,"Benign essential blepharospasm affects an estimated 20,000 to 50,000 people in the United States. For unknown reasons, it occurs in women more than twice as often as it occurs in men.",benign essential blepharospasm,0000116,GHR,https://ghr.nlm.nih.gov/condition/benign-essential-blepharospasm,C2930898,T047,Disorders
What are the genetic changes related to benign essential blepharospasm ?,0000116-3,genetic changes,"The causes of benign essential blepharospasm are unknown, although the disorder likely results from a combination of genetic and environmental factors. Certain genetic changes probably increase the likelihood of developing this condition, and environmental factors may trigger the signs and symptoms in people who are at risk.  Studies suggest that this condition may be related to other forms of adult-onset dystonia, including uncontrolled twisting of the neck muscles (spasmodic torticollis) and spasms of the hand and finger muscles (writer's cramp). Researchers suspect that benign essential blepharospasm and similar forms of dystonia are associated with malfunction of the basal ganglia, which are structures deep within the brain that help start and control movement.  Although genetic factors are almost certainly involved in benign essential blepharospasm, no genes have been clearly associated with the condition. Several studies have looked at the relationship between common variations (polymorphisms) in the DRD5 and TOR1A genes and the risk of developing benign essential blepharospasm. These studies have had conflicting results, with some showing an association and others finding no connection. Researchers are working to determine which genetic factors are related to this disorder.",benign essential blepharospasm,0000116,GHR,https://ghr.nlm.nih.gov/condition/benign-essential-blepharospasm,C2930898,T047,Disorders
Is benign essential blepharospasm inherited ?,0000116-4,inheritance,"Most cases of benign essential blepharospasm are sporadic, which means that the condition occurs in people with no history of this disorder or other forms of dystonia in their family.  Less commonly, benign essential blepharospasm has been found to run in families. In some of these families, the condition appears to have an autosomal dominant pattern of inheritance, which means that one copy of an altered gene in each cell is sufficient to cause the disorder. However, no causative genes have been identified.",benign essential blepharospasm,0000116,GHR,https://ghr.nlm.nih.gov/condition/benign-essential-blepharospasm,C2930898,T047,Disorders
What are the treatments for benign essential blepharospasm ?,0000116-5,treatment,These resources address the diagnosis or management of benign essential blepharospasm:  - Benign Essential Blepharospasm Research Foundation: Botulinum Toxin for Treatment of Blepharospasm  - Dystonia Medical Research Foundation: Treatments for dystonia  - Genetic Testing Registry: Blepharospasm  - MedlinePlus Encyclopedia: Eyelid Twitch   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,benign essential blepharospasm,0000116,GHR,https://ghr.nlm.nih.gov/condition/benign-essential-blepharospasm,C2930898,T047,Disorders
What is (are) benign familial neonatal seizures ?,0000117-1,information,"Benign familial neonatal seizures (BFNS) is a condition characterized by recurrent seizures in newborn babies. The seizures begin around day 3 of life and usually go away within 1 to 4 months. The seizures can involve only one side of the brain (focal seizures) or both sides (generalized seizures). Many infants with this condition have generalized tonic-clonic seizures (also known as grand mal seizures). This type of seizure involves both sides of the brain and affects the entire body, causing muscle rigidity, convulsions, and loss of consciousness.  A test called an electroencephalogram (EEG) is used to measure the electrical activity of the brain. Abnormalities on an EEG test, measured during no seizure activity, can indicate a risk for seizures. However, infants with BFNS usually have normal EEG readings. In some affected individuals, the EEG shows a specific abnormality called the theta pointu alternant pattern. By age 2, most affected individuals who had EEG abnormalities have a normal EEG reading.  Typically, seizures are the only symptom of BFNS, and most people with this condition develop normally. However, some affected individuals develop intellectual disability that becomes noticeable in early childhood. A small percentage of people with BFNS also have a condition called myokymia, which is an involuntary rippling movement of the muscles. In addition, in about 15 percent of people with BFNS, recurrent seizures (epilepsy) will come back later in life after the seizures associated with BFNS have gone away. The age that epilepsy begins is variable.",benign familial neonatal seizures,0000117,GHR,https://ghr.nlm.nih.gov/condition/benign-familial-neonatal-seizures,C0220669,T047,Disorders
How many people are affected by benign familial neonatal seizures ?,0000117-2,frequency,"Benign familial neonatal seizures occurs in approximately 1 in 100,000 newborns.",benign familial neonatal seizures,0000117,GHR,https://ghr.nlm.nih.gov/condition/benign-familial-neonatal-seizures,C0220669,T047,Disorders
What are the genetic changes related to benign familial neonatal seizures ?,0000117-3,genetic changes,"Mutations in two genes, KCNQ2 and KCNQ3, have been found to cause BFNS. Mutations in the KCNQ2 gene are a much more common cause of the condition than mutations in the KCNQ3 gene.  The KCNQ2 and KCNQ3 genes provide instructions for making proteins that interact to form potassium channels. Potassium channels, which transport positively charged atoms (ions) of potassium into and out of cells, play a key role in a cell's ability to generate and transmit electrical signals.  Channels made with the KCNQ2 and KCNQ3 proteins are active in nerve cells (neurons) in the brain, where they transport potassium ions out of cells. These channels transmit a particular type of electrical signal called the M-current, which prevents the neuron from continuing to send signals to other neurons. The M-current ensures that the neuron is not constantly active, or excitable.  Mutations in the KCNQ2 or KCNQ3 gene result in a reduced or altered M-current, which leads to excessive excitability of neurons. Seizures develop when neurons in the brain are abnormally excited. It is unclear why the seizures stop around the age of 4 months. It has been suggested that potassium channels formed from the KCNQ2 and KCNQ3 proteins play a major role in preventing excessive excitability of neurons in newborns, but other mechanisms develop during infancy.  About 70 percent of people with BFNS have a mutation in either the KCNQ2 or the KCNQ3 gene. Researchers are working to identify other gene mutations involved in this condition.",benign familial neonatal seizures,0000117,GHR,https://ghr.nlm.nih.gov/condition/benign-familial-neonatal-seizures,C0220669,T047,Disorders
Is benign familial neonatal seizures inherited ?,0000117-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent. A few cases result from new mutations in the KCNQ2 gene. These cases occur in people with no history of benign familial neonatal seizures in their family.",benign familial neonatal seizures,0000117,GHR,https://ghr.nlm.nih.gov/condition/benign-familial-neonatal-seizures,C0220669,T047,Disorders
What are the treatments for benign familial neonatal seizures ?,0000117-5,treatment,These resources address the diagnosis or management of BFNS:  - Boston Children's Hospital: My Child Has...Seizures and Epilepsy  - Epilepsy Action: Benign Neonatal Convulsions  - Gene Review: Gene Review: KCNQ2-Related Disorders  - Gene Review: Gene Review: KCNQ3-Related Disorders  - Genetic Testing Registry: Benign familial neonatal seizures  - Genetic Testing Registry: Benign familial neonatal seizures 1  - Genetic Testing Registry: Benign familial neonatal seizures 2  - MedlinePlus Encyclopedia: EEG   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,benign familial neonatal seizures,0000117,GHR,https://ghr.nlm.nih.gov/condition/benign-familial-neonatal-seizures,C0220669,T047,Disorders
What is (are) benign recurrent intrahepatic cholestasis ?,0000118-1,information,"Benign recurrent intrahepatic cholestasis (BRIC) is characterized by episodes of liver dysfunction called cholestasis. During these episodes, the liver cells have a reduced ability to release a digestive fluid called bile. Because the problems with bile release occur within the liver (intrahepatic), the condition is described as intrahepatic cholestasis. Episodes of cholestasis can last from weeks to months, and the time between episodes, during which there are usually no symptoms, can vary from weeks to years.  The first episode of cholestasis usually occurs in an affected person's teens or twenties. An attack typically begins with severe itchiness (pruritus), followed by yellowing of the skin and whites of the eyes (jaundice) a few weeks later. Other general signs and symptoms that occur during these episodes include a vague feeling of discomfort (malaise), irritability, nausea, vomiting, and a lack of appetite. A common feature of BRIC is the reduced absorption of fat in the body, which leads to excess fat in the feces (steatorrhea). Because of a lack of fat absorption and loss of appetite, affected individuals often lose weight during episodes of cholestasis.  BRIC is divided into two types, BRIC1 and BRIC2, based on the genetic cause of the condition. The signs and symptoms are the same in both types.  This condition is called benign because it does not cause lasting damage to the liver. However, episodes of liver dysfunction occasionally develop into a more severe, permanent form of liver disease known as progressive familial intrahepatic cholestasis (PFIC). BRIC and PFIC are sometimes considered to be part of a spectrum of intrahepatic cholestasis disorders of varying severity.",benign recurrent intrahepatic cholestasis,0000118,GHR,https://ghr.nlm.nih.gov/condition/benign-recurrent-intrahepatic-cholestasis,C0149841,T047,Disorders
How many people are affected by benign recurrent intrahepatic cholestasis ?,0000118-2,frequency,"BRIC is a rare disorder. Although the prevalence is unknown, this condition is less common than the related disorder PFIC, which affects approximately 1 in 50,000 to 100,000 people worldwide.",benign recurrent intrahepatic cholestasis,0000118,GHR,https://ghr.nlm.nih.gov/condition/benign-recurrent-intrahepatic-cholestasis,C0149841,T047,Disorders
What are the genetic changes related to benign recurrent intrahepatic cholestasis ?,0000118-3,genetic changes,"Mutations in the ATP8B1 gene cause benign recurrent intrahepatic cholestasis type 1 (BRIC1), and mutations in the ABCB11 gene cause benign recurrent intrahepatic cholestasis type 2 (BRIC2). These two genes are involved in the release (secretion) of bile, a fluid produced by the liver that helps digest fats.  The ATP8B1 gene provides instructions for making a protein that helps to control the distribution of certain fats, called lipids, in the membranes of liver cells. This function likely plays a role in maintaining an appropriate balance of bile acids, a component of bile. This process, known as bile acid homeostasis, is critical for the normal secretion of bile and the proper functioning of liver cells. Although the mechanism is unclear, mutations in the ATP8B1 gene result in the buildup of bile acids in liver cells. The imbalance of bile acids leads to the signs and symptoms of BRIC1.  The ABCB11 gene provides instructions for making a protein called the bile salt export pump (BSEP). This protein is found in the liver, and its main role is to move bile salts (a component of bile) out of liver cells. Mutations in the ABCB11 gene result in a reduction of BSEP function. This reduction leads to a decrease of bile salt secretion, which causes the features of BRIC2.  The factors that trigger episodes of BRIC are unknown.  Some people with BRIC do not have a mutation in the ATP8B1 or ABCB11 gene. In these individuals, the cause of the condition is unknown.",benign recurrent intrahepatic cholestasis,0000118,GHR,https://ghr.nlm.nih.gov/condition/benign-recurrent-intrahepatic-cholestasis,C0149841,T047,Disorders
Is benign recurrent intrahepatic cholestasis inherited ?,0000118-4,inheritance,"Both types of BRIC are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Some people with BRIC have no family history of the disorder. These cases arise from mutations in the ATP8B1 or ABCB11 gene that occur in the body's cells after conception and are not inherited.",benign recurrent intrahepatic cholestasis,0000118,GHR,https://ghr.nlm.nih.gov/condition/benign-recurrent-intrahepatic-cholestasis,C0149841,T047,Disorders
What are the treatments for benign recurrent intrahepatic cholestasis ?,0000118-5,treatment,These resources address the diagnosis or management of benign recurrent intrahepatic cholestasis:  - Gene Review: Gene Review: ATP8B1 Deficiency  - Genetic Testing Registry: Benign recurrent intrahepatic cholestasis 1  - Genetic Testing Registry: Benign recurrent intrahepatic cholestasis 2  - Merck Manual Home Health Edition: Cholestasis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,benign recurrent intrahepatic cholestasis,0000118,GHR,https://ghr.nlm.nih.gov/condition/benign-recurrent-intrahepatic-cholestasis,C0149841,T047,Disorders
What is (are) beta thalassemia ?,0000119-1,information,"Beta thalassemia is a blood disorder that reduces the production of hemoglobin. Hemoglobin is the iron-containing protein in red blood cells that carries oxygen to cells throughout the body.  In people with beta thalassemia, low levels of hemoglobin lead to a lack of oxygen in many parts of the body. Affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, fatigue, and more serious complications. People with beta thalassemia are at an increased risk of developing abnormal blood clots.  Beta thalassemia is classified into two types depending on the severity of symptoms: thalassemia major (also known as Cooley's anemia) and thalassemia intermedia. Of the two types, thalassemia major is more severe.  The signs and symptoms of thalassemia major appear within the first 2 years of life. Children develop life-threatening anemia. They do not gain weight and grow at the expected rate (failure to thrive) and may develop yellowing of the skin and whites of the eyes (jaundice). Affected individuals may have an enlarged spleen, liver, and heart, and their bones may be misshapen. Some adolescents with thalassemia major experience delayed puberty. Many people with thalassemia major have such severe symptoms that they need frequent blood transfusions to replenish their red blood cell supply. Over time, an influx of iron-containing hemoglobin from chronic blood transfusions can lead to a buildup of iron in the body, resulting in liver, heart, and hormone problems.  Thalassemia intermedia is milder than thalassemia major. The signs and symptoms of thalassemia intermedia appear in early childhood or later in life. Affected individuals have mild to moderate anemia and may also have slow growth and bone abnormalities.",beta thalassemia,0000119,GHR,https://ghr.nlm.nih.gov/condition/beta-thalassemia,C0005283,T047,Disorders
How many people are affected by beta thalassemia ?,0000119-2,frequency,"Beta thalassemia is a fairly common blood disorder worldwide. Thousands of infants with beta thalassemia are born each year. Beta thalassemia occurs most frequently in people from Mediterranean countries, North Africa, the Middle East, India, Central Asia, and Southeast Asia.",beta thalassemia,0000119,GHR,https://ghr.nlm.nih.gov/condition/beta-thalassemia,C0005283,T047,Disorders
What are the genetic changes related to beta thalassemia ?,0000119-3,genetic changes,"Mutations in the HBB gene cause beta thalassemia. The HBB gene provides instructions for making a protein called beta-globin. Beta-globin is a component (subunit) of hemoglobin. Hemoglobin consists of four protein subunits, typically two subunits of beta-globin and two subunits of another protein called alpha-globin.  Some mutations in the HBB gene prevent the production of any beta-globin. The absence of beta-globin is referred to as beta-zero (B0) thalassemia. Other HBB gene mutations allow some beta-globin to be produced but in reduced amounts. A reduced amount of beta-globin is called beta-plus (B+) thalassemia. Having either B0 or B+ thalassemia does not necessarily predict disease severity, however; people with both types have been diagnosed with thalassemia major and thalassemia intermedia.  A lack of beta-globin leads to a reduced amount of functional hemoglobin. Without sufficient hemoglobin, red blood cells do not develop normally, causing a shortage of mature red blood cells. The low number of mature red blood cells leads to anemia and other associated health problems in people with beta thalassemia.",beta thalassemia,0000119,GHR,https://ghr.nlm.nih.gov/condition/beta-thalassemia,C0005283,T047,Disorders
Is beta thalassemia inherited ?,0000119-4,inheritance,"Thalassemia major and thalassemia intermedia are inherited in an autosomal recessive pattern, which means both copies of the HBB gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Sometimes, however, people with only one HBB gene mutation in each cell develop mild anemia. These mildly affected people are said to have thalassemia minor.  In a small percentage of families, the HBB gene mutation is inherited in an autosomal dominant manner. In these cases, one copy of the altered gene in each cell is sufficient to cause the signs and symptoms of beta thalassemia.",beta thalassemia,0000119,GHR,https://ghr.nlm.nih.gov/condition/beta-thalassemia,C0005283,T047,Disorders
What are the treatments for beta thalassemia ?,0000119-5,treatment,"These resources address the diagnosis or management of beta thalassemia:  - Gene Review: Gene Review: Beta-Thalassemia  - Genetic Testing Registry: Beta-thalassemia, dominant inclusion body type  - Genetic Testing Registry: beta Thalassemia  - MedlinePlus Encyclopedia: Thalassemia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",beta thalassemia,0000119,GHR,https://ghr.nlm.nih.gov/condition/beta-thalassemia,C0005283,T047,Disorders
What is (are) beta-ketothiolase deficiency ?,0000120-1,information,"Beta-ketothiolase deficiency is an inherited disorder in which the body cannot effectively process a protein building block (amino acid) called isoleucine. This disorder also impairs the body's ability to process ketones, which are molecules produced during the breakdown of fats.  The signs and symptoms of beta-ketothiolase deficiency typically appear between the ages of 6 months and 24 months. Affected children experience episodes of vomiting, dehydration, difficulty breathing, extreme tiredness (lethargy), and, occasionally, seizures. These episodes, which are called ketoacidotic attacks, sometimes lead to coma. Ketoacidotic attacks are frequently triggered by infections, periods without food (fasting), or increased intake of protein-rich foods.",beta-ketothiolase deficiency,0000120,GHR,https://ghr.nlm.nih.gov/condition/beta-ketothiolase-deficiency,C1536500,T047,Disorders
How many people are affected by beta-ketothiolase deficiency ?,0000120-2,frequency,Beta-ketothiolase deficiency appears to be very rare. It is estimated to affect fewer than 1 in 1 million newborns.,beta-ketothiolase deficiency,0000120,GHR,https://ghr.nlm.nih.gov/condition/beta-ketothiolase-deficiency,C1536500,T047,Disorders
What are the genetic changes related to beta-ketothiolase deficiency ?,0000120-3,genetic changes,"Mutations in the ACAT1 gene cause beta-ketothiolase deficiency. This gene provides instructions for making an enzyme that is found in the energy-producing centers within cells (mitochondria). This enzyme plays an essential role in breaking down proteins and fats from the diet. Specifically, the ACAT1 enzyme helps process isoleucine, which is a building block of many proteins, and ketones, which are produced during the breakdown of fats.  Mutations in the ACAT1 gene reduce or eliminate the activity of the ACAT1 enzyme. A shortage of this enzyme prevents the body from processing proteins and fats properly. As a result, related compounds can build up to toxic levels in the blood. These substances cause the blood to become too acidic (ketoacidosis), which can damage the body's tissues and organs, particularly in the nervous system.",beta-ketothiolase deficiency,0000120,GHR,https://ghr.nlm.nih.gov/condition/beta-ketothiolase-deficiency,C1536500,T047,Disorders
Is beta-ketothiolase deficiency inherited ?,0000120-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",beta-ketothiolase deficiency,0000120,GHR,https://ghr.nlm.nih.gov/condition/beta-ketothiolase-deficiency,C1536500,T047,Disorders
What are the treatments for beta-ketothiolase deficiency ?,0000120-5,treatment,These resources address the diagnosis or management of beta-ketothiolase deficiency:  - Baby's First Test  - Genetic Testing Registry: Deficiency of acetyl-CoA acetyltransferase   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,beta-ketothiolase deficiency,0000120,GHR,https://ghr.nlm.nih.gov/condition/beta-ketothiolase-deficiency,C1536500,T047,Disorders
What is (are) beta-mannosidosis ?,0000121-1,information,"Beta-mannosidosis is a rare inherited disorder affecting the way certain sugar molecules are processed in the body.  Signs and symptoms of beta-mannosidosis vary widely in severity, and the age of onset ranges between infancy and adolescence. Almost all individuals with beta-mannosidosis experience intellectual disability, and some have delayed motor development and seizures. Affected individuals may be extremely introverted, prone to depression, or have behavioral problems such as hyperactivity, impulsivity or aggression.  People with beta-mannosidosis may experience an increased risk of respiratory and ear infections, hearing loss, speech impairment, swallowing difficulties, poor muscle tone (hypotonia), and reduced sensation or other nervous system abnormalities in the extremities (peripheral neuropathy). They may also exhibit distinctive facial features and clusters of enlarged blood vessels forming small, dark red spots on the skin (angiokeratomas).",beta-mannosidosis,0000121,GHR,https://ghr.nlm.nih.gov/condition/beta-mannosidosis,C0342849,T019,Disorders
How many people are affected by beta-mannosidosis ?,0000121-2,frequency,"Beta-mannosidosis is believed to be a very rare disorder. Approximately 20 affected individuals have been reported worldwide. It is difficult to determine the specific incidence of beta-mannosidosis, because people with mild or non-specific symptoms may never be diagnosed.",beta-mannosidosis,0000121,GHR,https://ghr.nlm.nih.gov/condition/beta-mannosidosis,C0342849,T019,Disorders
What are the genetic changes related to beta-mannosidosis ?,0000121-3,genetic changes,"Mutations in the MANBA gene cause beta-mannosidosis.  The MANBA gene provides instructions for making the enzyme beta-mannosidase. This enzyme works in the lysosomes, which are compartments that digest and recycle materials in the cell. Within lysosomes, the enzyme helps break down complexes of sugar molecules (oligosaccharides) attached to certain proteins (glycoproteins). Beta-mannosidase is involved in the last step of this process, helping to break down complexes of two sugar molecules (disaccharides) containing a sugar molecule called mannose.  Mutations in the MANBA gene interfere with the ability of the beta-mannosidase enzyme to perform its role in breaking down mannose-containing disaccharides. These disaccharides gradually accumulate in the lysosomes and cause cells to malfunction, resulting in the signs and symptoms of beta-mannosidosis.",beta-mannosidosis,0000121,GHR,https://ghr.nlm.nih.gov/condition/beta-mannosidosis,C0342849,T019,Disorders
Is beta-mannosidosis inherited ?,0000121-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",beta-mannosidosis,0000121,GHR,https://ghr.nlm.nih.gov/condition/beta-mannosidosis,C0342849,T019,Disorders
What are the treatments for beta-mannosidosis ?,0000121-5,treatment,These resources address the diagnosis or management of beta-mannosidosis:  - Genetic Testing Registry: Beta-D-mannosidosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,beta-mannosidosis,0000121,GHR,https://ghr.nlm.nih.gov/condition/beta-mannosidosis,C0342849,T019,Disorders
What is (are) beta-ureidopropionase deficiency ?,0000122-1,information,"Beta-ureidopropionase deficiency is a disorder that causes excessive amounts of molecules called N-carbamyl-beta-aminoisobutyric acid and N-carbamyl-beta-alanine to be released in the urine. Neurological problems ranging from mild to severe also occur in some affected individuals.  People with beta-ureidopropionase deficiency can have low muscle tone (hypotonia), seizures, speech difficulties, developmental delay, intellectual disability, and autistic behaviors that affect communication and social interaction. Some people with this condition have an abnormally small head size (microcephaly); they may also have brain abnormalities that can be seen with medical imaging. Deterioration of the optic nerve, which carries visual information from the eyes to the brain, can lead to vision loss in this condition.  In some people with beta-ureidopropionase deficiency, the disease causes no neurological problems and can only be diagnosed by laboratory testing.",beta-ureidopropionase deficiency,0000122,GHR,https://ghr.nlm.nih.gov/condition/beta-ureidopropionase-deficiency,C1291512,T047,Disorders
How many people are affected by beta-ureidopropionase deficiency ?,0000122-2,frequency,"The prevalence of beta-ureidopropionase deficiency is unknown. A small number of affected individuals from populations around the world have been described in the medical literature. In Japan, the prevalence of beta-ureidopropionase deficiency has been estimated as 1 in 6,000 people. Researchers suggest that in many affected individuals with absent or mild neurological problems, the condition may never be diagnosed.",beta-ureidopropionase deficiency,0000122,GHR,https://ghr.nlm.nih.gov/condition/beta-ureidopropionase-deficiency,C1291512,T047,Disorders
What are the genetic changes related to beta-ureidopropionase deficiency ?,0000122-3,genetic changes,"Beta-ureidopropionase deficiency is caused by mutations in the UPB1 gene, which provides instructions for making an enzyme called beta-ureidopropionase. This enzyme is involved in the breakdown of molecules called pyrimidines, which are building blocks of DNA and its chemical cousin RNA.  The beta-ureidopropionase enzyme is involved in the last step of the process that breaks down pyrimidines. This step converts N-carbamyl-beta-aminoisobutyric acid to beta-aminoisobutyric acid and also breaks down N-carbamyl-beta-alanine to beta-alanine, ammonia, and carbon dioxide. Both beta-aminoisobutyric acid and beta-alanine are thought to play roles in the nervous system. Beta-aminoisobutyric acid increases the production of a protein called leptin, which has been found to help protect brain cells from damage caused by toxins, inflammation, and other factors. Research suggests that beta-alanine is involved in sending signals between nerve cells (synaptic transmission) and in controlling the level of a chemical messenger (neurotransmitter) called dopamine.  UPB1 gene mutations can reduce or eliminate beta-ureidopropionase enzyme activity. Loss of this enzyme function reduces the production of beta-aminoisobutyric acid and beta-alanine, and leads to an excess of their precursor molecules, N-carbamyl-beta-aminoisobutyric acid and N-carbamyl-beta-alanine, which are released in the urine. Reduced production of beta-aminoisobutyric acid and beta-alanine may impair the function of these molecules in the nervous system, leading to neurological problems in some people with beta-ureidopropionase deficiency. The extent of the reduction in enzyme activity caused by a particular UPB1 gene mutation, along with other genetic and environmental factors, may determine whether people with beta-ureidopropionase deficiency develop neurological problems and the severity of these problems.",beta-ureidopropionase deficiency,0000122,GHR,https://ghr.nlm.nih.gov/condition/beta-ureidopropionase-deficiency,C1291512,T047,Disorders
Is beta-ureidopropionase deficiency inherited ?,0000122-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",beta-ureidopropionase deficiency,0000122,GHR,https://ghr.nlm.nih.gov/condition/beta-ureidopropionase-deficiency,C1291512,T047,Disorders
What are the treatments for beta-ureidopropionase deficiency ?,0000122-5,treatment,These resources address the diagnosis or management of beta-ureidopropionase deficiency:  - Genetic Testing Registry: Deficiency of beta-ureidopropionase   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,beta-ureidopropionase deficiency,0000122,GHR,https://ghr.nlm.nih.gov/condition/beta-ureidopropionase-deficiency,C1291512,T047,Disorders
What is (are) Bietti crystalline dystrophy ?,0000123-1,information,"Bietti crystalline dystrophy is a disorder in which numerous small, yellow or white crystal-like deposits of fatty (lipid) compounds accumulate in the light-sensitive tissue that lines the back of the eye (the retina). The deposits damage the retina, resulting in progressive vision loss.  People with Bietti crystalline dystrophy typically begin noticing vision problems in their teens or twenties. They experience a loss of sharp vision (reduction in visual acuity) and difficulty seeing in dim light (night blindness). They usually lose areas of vision (visual field loss), most often side (peripheral) vision. Color vision may also be impaired.  The vision problems may worsen at different rates in each eye, and the severity and progression of symptoms varies widely among affected individuals, even within the same family. However, most people with this condition become legally blind by their forties or fifties. Most affected individuals retain some degree of vision, usually in the center of the visual field, although it is typically blurry and cannot be corrected by glasses or contact lenses. Vision impairment that cannot be improved with corrective lenses is called low vision.",Bietti crystalline dystrophy,0000123,GHR,https://ghr.nlm.nih.gov/condition/bietti-crystalline-dystrophy,C1859486,T047,Disorders
How many people are affected by Bietti crystalline dystrophy ?,0000123-2,frequency,"Bietti crystalline dystrophy has been estimated to occur in 1 in 67,000 people. It is more common in people of East Asian descent, especially those of Chinese and Japanese background. Researchers suggest that Bietti crystalline dystrophy may be underdiagnosed because its symptoms are similar to those of other eye disorders that progressively damage the retina.",Bietti crystalline dystrophy,0000123,GHR,https://ghr.nlm.nih.gov/condition/bietti-crystalline-dystrophy,C1859486,T047,Disorders
What are the genetic changes related to Bietti crystalline dystrophy ?,0000123-3,genetic changes,"Bietti crystalline dystrophy is caused by mutations in the CYP4V2 gene. This gene provides instructions for making a member of the cytochrome P450 family of enzymes. These enzymes are involved in the formation and breakdown of various molecules and chemicals within cells. The CYP4V2 enzyme is involved in a multi-step process called fatty acid oxidation in which lipids are broken down and converted into energy, but the enzyme's specific function is not well understood. CYP4V2 gene mutations that cause Bietti crystalline dystrophy impair or eliminate the function of this enzyme and are believed to affect lipid breakdown. However, it is unknown how they lead to the specific signs and symptoms of Bietti crystalline dystrophy. For unknown reasons, the severity of the signs and symptoms differs significantly among individuals with the same CYP4V2 gene mutation.",Bietti crystalline dystrophy,0000123,GHR,https://ghr.nlm.nih.gov/condition/bietti-crystalline-dystrophy,C1859486,T047,Disorders
Is Bietti crystalline dystrophy inherited ?,0000123-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Bietti crystalline dystrophy,0000123,GHR,https://ghr.nlm.nih.gov/condition/bietti-crystalline-dystrophy,C1859486,T047,Disorders
What are the treatments for Bietti crystalline dystrophy ?,0000123-5,treatment,These resources address the diagnosis or management of Bietti crystalline dystrophy:  - Gene Review: Gene Review: Bietti Crystalline Dystrophy  - Genetic Testing Registry: Bietti crystalline corneoretinal dystrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Bietti crystalline dystrophy,0000123,GHR,https://ghr.nlm.nih.gov/condition/bietti-crystalline-dystrophy,C1859486,T047,Disorders
What is (are) biotin-thiamine-responsive basal ganglia disease ?,0000124-1,information,"Biotin-thiamine-responsive basal ganglia disease is a disorder that affects the nervous system, including a group of structures in the brain called the basal ganglia, which help control movement. As its name suggests, the condition may improve if the vitamins biotin and thiamine are given as treatment. Without early and lifelong vitamin treatment, people with biotin-thiamine-responsive basal ganglia disease experience a variety of neurological problems that gradually get worse. The occurrence of specific neurological problems and their severity vary even among affected individuals within the same family.  The signs and symptoms of biotin-thiamine-responsive basal ganglia disease usually begin between the ages of 3 and 10, but the disorder can appear at any age. Many of the neurological problems that can occur in biotin-thiamine-responsive basal ganglia disease affect movement, and can include involuntary tensing of various muscles (dystonia), muscle rigidity, muscle weakness on one or both sides of the body (hemiparesis or quadriparesis), problems coordinating movements (ataxia), and exaggerated reflexes (hyperreflexia). Movement problems can also affect the face, and may include the inability to move facial muscles due to facial nerve paralysis (supranuclear facial palsy), paralysis of the eye muscles (external ophthalmoplegia), difficulty chewing or swallowing (dysphagia), and slurred speech. Affected individuals may also experience confusion, loss of previously learned skills, intellectual disability, and seizures. Severe cases may result in coma and become life-threatening.  Typically, the neurological symptoms occur as increasingly severe episodes, which may be triggered by fever, injury, or other stresses on the body. Less commonly, the signs and symptoms persist at the same level or slowly increase in severity over time rather than occurring as episodes that come and go. In these individuals, the neurological problems are usually limited to dystonia, seizure disorders, and delay in the development of mental and motor skills (psychomotor delay).",biotin-thiamine-responsive basal ganglia disease,0000124,GHR,https://ghr.nlm.nih.gov/condition/biotin-thiamine-responsive-basal-ganglia-disease,C1843807,T019,Disorders
How many people are affected by biotin-thiamine-responsive basal ganglia disease ?,0000124-2,frequency,Biotin-thiamine-responsive basal ganglia disease is a rare disorder; its prevalence is unknown. Approximately 48 cases have been reported in the medical literature; most of these are individuals from Arab populations.,biotin-thiamine-responsive basal ganglia disease,0000124,GHR,https://ghr.nlm.nih.gov/condition/biotin-thiamine-responsive-basal-ganglia-disease,C1843807,T019,Disorders
What are the genetic changes related to biotin-thiamine-responsive basal ganglia disease ?,0000124-3,genetic changes,"Biotin-thiamine-responsive basal ganglia disease is caused by mutations in the SLC19A3 gene. This gene provides instructions for making a protein called a thiamine transporter, which moves thiamine into cells. Thiamine, also known as vitamin B1, is obtained from the diet and is necessary for proper functioning of the nervous system.  Mutations in the SLC19A3 gene likely result in a protein with impaired ability to transport thiamine into cells, resulting in decreased absorption of the vitamin and leading to neurological dysfunction. In this disorder, abnormalities affect several parts of the brain. Using medical imaging, generalized swelling as well as specific areas of damage (lesions) in the brain can often be seen, including in the basal ganglia. The relationship between these specific brain abnormalities and the abnormal thiamine transporter is unknown.  It is unclear how biotin is related to this disorder. Some researchers suggest that the excess biotin given along with thiamine as treatment for the disorder may increase the amount of thiamine transporter that is produced, partially compensating for the impaired efficiency of the abnormal protein. Others propose that biotin transporter proteins may interact with thiamine transporters in such a way that biotin levels influence the course of the disease.",biotin-thiamine-responsive basal ganglia disease,0000124,GHR,https://ghr.nlm.nih.gov/condition/biotin-thiamine-responsive-basal-ganglia-disease,C1843807,T019,Disorders
Is biotin-thiamine-responsive basal ganglia disease inherited ?,0000124-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",biotin-thiamine-responsive basal ganglia disease,0000124,GHR,https://ghr.nlm.nih.gov/condition/biotin-thiamine-responsive-basal-ganglia-disease,C1843807,T019,Disorders
What are the treatments for biotin-thiamine-responsive basal ganglia disease ?,0000124-5,treatment,These resources address the diagnosis or management of biotin-thiamine-responsive basal ganglia disease:  - Gene Review: Gene Review: Biotin-Thiamine-Responsive Basal Ganglia Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,biotin-thiamine-responsive basal ganglia disease,0000124,GHR,https://ghr.nlm.nih.gov/condition/biotin-thiamine-responsive-basal-ganglia-disease,C1843807,T019,Disorders
What is (are) biotinidase deficiency ?,0000125-1,information,"Biotinidase deficiency is an inherited disorder in which the body is unable to recycle the vitamin biotin. If this condition is not recognized and treated, its signs and symptoms typically appear within the first few months of life, although it can also become apparent later in childhood.  Profound biotinidase deficiency, the more severe form of the condition, can cause seizures, weak muscle tone (hypotonia), breathing problems, hearing and vision loss, problems with movement and balance (ataxia), skin rashes, hair loss (alopecia), and a fungal infection called candidiasis. Affected children also have delayed development. Lifelong treatment can prevent these complications from occurring or improve them if they have already developed.  Partial biotinidase deficiency is a milder form of this condition. Without treatment, affected children may experience hypotonia, skin rashes, and hair loss, but these problems may appear only during illness, infection, or other times of stress.",biotinidase deficiency,0000125,GHR,https://ghr.nlm.nih.gov/condition/biotinidase-deficiency,C0220754,T019,Disorders
How many people are affected by biotinidase deficiency ?,0000125-2,frequency,"Profound or partial biotinidase deficiency occurs in approximately 1 in 60,000 newborns",biotinidase deficiency,0000125,GHR,https://ghr.nlm.nih.gov/condition/biotinidase-deficiency,C0220754,T019,Disorders
What are the genetic changes related to biotinidase deficiency ?,0000125-3,genetic changes,"Mutations in the BTD gene cause biotinidase deficiency. The BTD gene provides instructions for making an enzyme called biotinidase. This enzyme recycles biotin, a B vitamin found in foods such as liver, egg yolks, and milk. Biotinidase removes biotin that is bound to proteins in food, leaving the vitamin in its free (unbound) state. Free biotin is needed by enzymes called biotin-dependent carboxylases to break down fats, proteins, and carbohydrates. Because several of these enzymes are impaired in biotinidase deficiency, the condition is considered a form of multiple carboxylase deficiency.  Mutations in the BTD gene reduce or eliminate the activity of biotinidase. Profound biotinidase deficiency results when the activity of biotinidase is reduced to less than 10 percent of normal. Partial biotinidase deficiency occurs when biotinidase activity is reduced to between 10 percent and 30 percent of normal. Without enough of this enzyme, biotin cannot be recycled. The resulting shortage of free biotin impairs the activity of biotin-dependent carboxylases, leading to a buildup of potentially toxic compounds in the body. If the condition is not treated promptly, this buildup damages various cells and tissues, causing the signs and symptoms described above.",biotinidase deficiency,0000125,GHR,https://ghr.nlm.nih.gov/condition/biotinidase-deficiency,C0220754,T019,Disorders
Is biotinidase deficiency inherited ?,0000125-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the BTD gene in each cell have mutations. The parents of an individual with biotinidase deficiency each carry one copy of the mutated gene, but they typically do not have any health problems associated with the condition.",biotinidase deficiency,0000125,GHR,https://ghr.nlm.nih.gov/condition/biotinidase-deficiency,C0220754,T019,Disorders
What are the treatments for biotinidase deficiency ?,0000125-5,treatment,These resources address the diagnosis or management of biotinidase deficiency:  - Baby's First Test  - Gene Review: Gene Review: Biotinidase Deficiency  - Genetic Testing Registry: Biotinidase deficiency  - MedlinePlus Encyclopedia: Pantothenic Acid and Biotin   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,biotinidase deficiency,0000125,GHR,https://ghr.nlm.nih.gov/condition/biotinidase-deficiency,C0220754,T019,Disorders
What is (are) Birt-Hogg-Dub syndrome ?,0000126-1,information,"Birt-Hogg-Dub syndrome is a rare disorder that affects the skin and lungs and increases the risk of certain types of tumors. Its signs and symptoms vary among affected individuals.  Birt-Hogg-Dub syndrome is characterized by multiple noncancerous (benign) skin tumors, particularly on the face, neck, and upper chest. These growths typically first appear in a person's twenties or thirties and become larger and more numerous over time. Affected individuals also have an increased chance of developing cysts in the lungs and an abnormal accumulation of air in the chest cavity (pneumothorax) that may result in the collapse of a lung. Additionally, Birt-Hogg-Dub syndrome is associated with an elevated risk of developing cancerous or noncancerous kidney tumors. Other types of cancer have also been reported in affected individuals, but it is unclear whether these tumors are actually a feature of Birt-Hogg-Dub syndrome.",Birt-Hogg-Dub syndrome,0000126,GHR,https://ghr.nlm.nih.gov/condition/birt-hogg-dube-syndrome,C0039082,T047,Disorders
How many people are affected by Birt-Hogg-Dub syndrome ?,0000126-2,frequency,Birt-Hogg-Dub syndrome is rare; its exact incidence is unknown. This condition has been reported in more than 400 families.,Birt-Hogg-Dub syndrome,0000126,GHR,https://ghr.nlm.nih.gov/condition/birt-hogg-dube-syndrome,C0039082,T047,Disorders
What are the genetic changes related to Birt-Hogg-Dub syndrome ?,0000126-3,genetic changes,"Mutations in the FLCN gene cause Birt-Hogg-Dub syndrome. This gene provides instructions for making a protein called folliculin. The normal function of this protein is unknown, but researchers believe that it may act as a tumor suppressor. Tumor suppressors prevent cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in the FLCN gene may interfere with the ability of folliculin to restrain cell growth and division, leading to uncontrolled cell growth and the formation of noncancerous and cancerous tumors. Researchers have not determined how FLCN mutations increase the risk of lung problems, such as pneumothorax.",Birt-Hogg-Dub syndrome,0000126,GHR,https://ghr.nlm.nih.gov/condition/birt-hogg-dube-syndrome,C0039082,T047,Disorders
Is Birt-Hogg-Dub syndrome inherited ?,0000126-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered FLCN gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent. Less commonly, the condition results from a new mutation in the gene and occurs in people with no history of the disorder in their family.  Having a single mutated copy of the FLCN gene in each cell is enough to cause the skin tumors and lung problems associated with Birt-Hogg-Dub syndrome. However, both copies of the FLCN gene are often mutated in the kidney tumors that occur with this condition. One of the mutations is inherited from a parent, while the other occurs by chance in a kidney cell during a person's lifetime. These genetic changes disable both copies of the FLCN gene, which allows kidney cells to divide uncontrollably and form tumors.",Birt-Hogg-Dub syndrome,0000126,GHR,https://ghr.nlm.nih.gov/condition/birt-hogg-dube-syndrome,C0039082,T047,Disorders
What are the treatments for Birt-Hogg-Dub syndrome ?,0000126-5,treatment,These resources address the diagnosis or management of Birt-Hogg-Dub syndrome:  - BHD Foundation: Practical Considerations  - Gene Review: Gene Review: Birt-Hogg-Dube Syndrome  - Genetic Testing Registry: Multiple fibrofolliculomas  - MedlinePlus Encyclopedia: Collapsed Lung   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Birt-Hogg-Dub syndrome,0000126,GHR,https://ghr.nlm.nih.gov/condition/birt-hogg-dube-syndrome,C0039082,T047,Disorders
What is (are) Bjrnstad syndrome ?,0000127-1,information,"Bjrnstad syndrome is a rare disorder characterized by abnormal hair and hearing problems. Affected individuals have a condition known as pili torti, which means ""twisted hair,"" so named because the strands appear twisted when viewed under a microscope. The hair is brittle and breaks easily, leading to short hair that grows slowly. In Bjrnstad syndrome, pili torti usually affects only the hair on the head; eyebrows, eyelashes, and hair on other parts of the body are normal. The proportion of hairs affected and the severity of brittleness and breakage can vary. This hair abnormality commonly begins before the age of 2. It may become milder with age, particularly after puberty.  People with Bjrnstad syndrome also have hearing problems that become evident in early childhood. The hearing loss, which is caused by changes in the inner ear (sensorineural deafness), can range from mild to severe. Mildly affected individuals may be unable to hear sounds at certain frequencies, while severely affected individuals may not be able to hear at all.",Bjrnstad syndrome,0000127,GHR,https://ghr.nlm.nih.gov/condition/bjornstad-syndrome,C0039082,T047,Disorders
How many people are affected by Bjrnstad syndrome ?,0000127-2,frequency,"Bjrnstad syndrome is a rare condition, although its prevalence is unknown. It has been found in populations worldwide.",Bjrnstad syndrome,0000127,GHR,https://ghr.nlm.nih.gov/condition/bjornstad-syndrome,C0039082,T047,Disorders
What are the genetic changes related to Bjrnstad syndrome ?,0000127-3,genetic changes,"Bjrnstad syndrome is caused by mutations in the BCS1L gene. The protein produced from this gene is found in cell structures called mitochondria, which convert the energy from food into a form that cells can use. In mitochondria, the BCS1L protein plays a role in oxidative phosphorylation, which is a multistep process through which cells derive much of their energy. The BCS1L protein is critical for the formation of a group of proteins known as complex III, which is one of several protein complexes involved in this process. As a byproduct of its action in oxidative phosphorylation, complex III produces reactive oxygen species, which are harmful molecules that can damage DNA and tissues.  BCS1L gene mutations involved in Bjrnstad syndrome alter the BCS1L protein and impair its ability to aid in complex III formation. The resulting decrease in complex III activity reduces oxidative phosphorylation. For unknown reasons, overall production of reactive oxygen species is increased, although production by complex III is reduced. Researchers believe that tissues in the inner ears and hair follicles are particularly sensitive to reactive oxygen species and are damaged by the abnormal amount of these molecules, leading to the characteristic features of Bjrnstad syndrome.",Bjrnstad syndrome,0000127,GHR,https://ghr.nlm.nih.gov/condition/bjornstad-syndrome,C0039082,T047,Disorders
Is Bjrnstad syndrome inherited ?,0000127-4,inheritance,"Bjrnstad syndrome is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Bjrnstad syndrome,0000127,GHR,https://ghr.nlm.nih.gov/condition/bjornstad-syndrome,C0039082,T047,Disorders
What are the treatments for Bjrnstad syndrome ?,0000127-5,treatment,These resources address the diagnosis or management of Bjrnstad syndrome:  - Centers for Disease Control and Prevention: Hearing Loss in Children: Screening and Diagnosis  - Genetic Testing Registry: Pili torti-deafness syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Bjrnstad syndrome,0000127,GHR,https://ghr.nlm.nih.gov/condition/bjornstad-syndrome,C0039082,T047,Disorders
What is (are) bladder cancer ?,0000128-1,information,"Bladder cancer is a disease in which certain cells in the bladder become abnormal and multiply without control or order. The bladder is a hollow, muscular organ in the lower abdomen that stores urine until it is ready to be excreted from the body. The most common type of bladder cancer begins in cells lining the inside of the bladder and is called transitional cell carcinoma (TCC).  Bladder cancer may cause blood in the urine, pain during urination, frequent urination, or the feeling that one needs to urinate without results. These signs and symptoms are not specific to bladder cancer, however. They also can be caused by noncancerous conditions such as infections.",bladder cancer,0000128,GHR,https://ghr.nlm.nih.gov/condition/bladder-cancer,C0699885,T191,Disorders
How many people are affected by bladder cancer ?,0000128-2,frequency,"In the United States, bladder cancer is the fourth most common type of cancer in men and the ninth most common cancer in women. About 45,000 men and 17,000 women are diagnosed with bladder cancer each year.",bladder cancer,0000128,GHR,https://ghr.nlm.nih.gov/condition/bladder-cancer,C0699885,T191,Disorders
What are the genetic changes related to bladder cancer ?,0000128-3,genetic changes,"As with most cancers, the exact causes of bladder cancer are not known; however, many risk factors are associated with this disease. Many of the major risk factors are environmental, such as smoking and exposure to certain industrial chemicals. Studies suggest that chronic bladder inflammation, a parasitic infection called schistosomiasis, and some medications used to treat cancer are other environmental risk factors associated with bladder cancer.  Genetic factors are also likely to play an important role in determining bladder cancer risk. Researchers have studied the effects of mutations in several genes, including FGFR3, RB1, HRAS, TP53, and TSC1, on the formation and growth of bladder tumors. Each of these genes plays a critical role in regulating cell division by preventing cells from dividing too rapidly or in an uncontrolled way. Alterations in these genes may help explain why some bladder cancers grow and spread more rapidly than others.  Deletions of part or all of chromosome 9 are common events in bladder tumors. Researchers believe that several genes that control cell growth and division are probably located on chromosome 9. They are working to determine whether a loss of these genes plays a role in the development and progression of bladder cancer.  Most of the genetic changes associated with bladder cancer develop in bladder tissue during a person's lifetime, rather than being inherited from a parent. Some people, however, appear to inherit a reduced ability to break down certain chemicals, which makes them more sensitive to the cancer-causing effects of tobacco smoke and industrial chemicals.",bladder cancer,0000128,GHR,https://ghr.nlm.nih.gov/condition/bladder-cancer,C0699885,T191,Disorders
Is bladder cancer inherited ?,0000128-4,inheritance,"Bladder cancer is typically not inherited. Most often, tumors result from genetic mutations that occur in bladder cells during a person's lifetime. These noninherited genetic changes are called somatic mutations.",bladder cancer,0000128,GHR,https://ghr.nlm.nih.gov/condition/bladder-cancer,C0699885,T191,Disorders
What are the treatments for bladder cancer ?,0000128-5,treatment,These resources address the diagnosis or management of bladder cancer:  - Genetic Testing Registry: Malignant tumor of urinary bladder  - MedlinePlus Encyclopedia: Bladder Cancer   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,bladder cancer,0000128,GHR,https://ghr.nlm.nih.gov/condition/bladder-cancer,C0699885,T191,Disorders
What is (are) Blau syndrome ?,0000129-1,information,"Blau syndrome is an inflammatory disorder that primarily affects the skin, joints, and eyes. Signs and symptoms begin in childhood, usually before age 4.  A form of skin inflammation called granulomatous dermatitis is typically the earliest sign of Blau syndrome. This skin condition causes a persistent rash that can be scaly or involve hard lumps (nodules) that can be felt under the skin. The rash is usually found on the torso, arms, and legs.  Arthritis is another common feature of Blau syndrome. In affected individuals, arthritis is characterized by inflammation of the lining of joints (the synovium). This inflammation, known as synovitis, is associated with swelling and joint pain. Synovitis usually begins in the joints of the hands, feet, wrists, and ankles. As the condition worsens, it can restrict movement by decreasing the range of motion in many joints.  Most people with Blau syndrome also develop uveitis, which is swelling and inflammation of the middle layer of the eye (the uvea). The uvea includes the colored portion of the eye (the iris) and related tissues that underlie the white part of the eye (the sclera). Uveitis can cause eye irritation and pain, increased sensitivity to bright light (photophobia), and blurred vision. Other structures in the eye can also become inflamed, including the outermost protective layer of the eye (the conjunctiva), the tear glands, the specialized light-sensitive tissue that lines the back of the eye (the retina), and the nerve that carries information from the eye to the brain (the optic nerve). Inflammation of any of these structures can lead to severe vision impairment or blindness.  Less commonly, Blau syndrome can affect other parts of the body, including the liver, kidneys, brain, blood vessels, lungs, and heart. Inflammation involving these organs and tissues can cause life-threatening complications.",Blau syndrome,0000129,GHR,https://ghr.nlm.nih.gov/condition/blau-syndrome,C1861303,T047,Disorders
How many people are affected by Blau syndrome ?,0000129-2,frequency,"Although Blau syndrome appears to be uncommon, its prevalence is unknown.",Blau syndrome,0000129,GHR,https://ghr.nlm.nih.gov/condition/blau-syndrome,C1861303,T047,Disorders
What are the genetic changes related to Blau syndrome ?,0000129-3,genetic changes,"Blau syndrome results from mutations in the NOD2 gene. The protein produced from this gene helps defend the body from foreign invaders, such as viruses and bacteria, by playing several essential roles in the immune response, including inflammatory reactions. An inflammatory reaction occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight microbial invaders and facilitate tissue repair.  The NOD2 gene mutations that cause Blau syndrome result in a NOD2 protein that is overactive, which can trigger an abnormal inflammatory reaction. However, it is unclear how overactivation of the NOD2 protein causes the specific pattern of inflammation affecting the joints, eyes, and skin that is characteristic of Blau syndrome.",Blau syndrome,0000129,GHR,https://ghr.nlm.nih.gov/condition/blau-syndrome,C1861303,T047,Disorders
Is Blau syndrome inherited ?,0000129-4,inheritance,"Blau syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most affected individuals have one parent with the condition.  In some cases, people with the characteristic features of Blau syndrome do not have a family history of the condition. Some researchers believe that these individuals have a non-inherited version of the disorder called early-onset sarcoidosis.",Blau syndrome,0000129,GHR,https://ghr.nlm.nih.gov/condition/blau-syndrome,C1861303,T047,Disorders
What are the treatments for Blau syndrome ?,0000129-5,treatment,"These resources address the diagnosis or management of Blau syndrome:  - Genetic Testing Registry: Blau syndrome  - Genetic Testing Registry: Sarcoidosis, early-onset  - Merck Manual Consumer Version: Overview of Dermatitis  - Merck Manual Consumer Version: Uveitis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Blau syndrome,0000129,GHR,https://ghr.nlm.nih.gov/condition/blau-syndrome,C1861303,T047,Disorders
"What is (are) blepharophimosis, ptosis, and epicanthus inversus syndrome ?",0000130-1,information,"Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is a condition that mainly affects development of the eyelids. People with this condition have a narrowing of the eye opening (blepharophimosis), droopy eyelids (ptosis), and an upward fold of the skin of the lower eyelid near the inner corner of the eye (epicanthus inversus). In addition, there is an increased distance between the inner corners of the eyes (telecanthus). Because of these eyelid abnormalities, the eyelids cannot open fully, and vision may be limited.  Other structures in the eyes and face may be mildly affected by BPES. Affected individuals are at an increased risk of developing vision problems such as nearsightedness (myopia) or farsightedness (hyperopia) beginning in childhood. They may also have eyes that do not point in the same direction (strabismus) or ""lazy eye"" (amblyopia) affecting one or both eyes. People with BPES may also have distinctive facial features including a broad nasal bridge, low-set ears, or a shortened distance between the nose and upper lip (a short philtrum).  There are two types of BPES, which are distinguished by their signs and symptoms. Both types I and II include the eyelid malformations and other facial features. Type I is also associated with an early loss of ovarian function (primary ovarian insufficiency) in women, which causes their menstrual periods to become less frequent and eventually stop before age 40. Primary ovarian insufficiency can lead to difficulty conceiving a child (subfertility) or a complete inability to conceive (infertility).","blepharophimosis, ptosis, and epicanthus inversus syndrome",0000130,GHR,https://ghr.nlm.nih.gov/condition/blepharophimosis-ptosis-and-epicanthus-inversus-syndrome,C0005744,T019,Disorders
"How many people are affected by blepharophimosis, ptosis, and epicanthus inversus syndrome ?",0000130-2,frequency,The prevalence of BPES is unknown.,"blepharophimosis, ptosis, and epicanthus inversus syndrome",0000130,GHR,https://ghr.nlm.nih.gov/condition/blepharophimosis-ptosis-and-epicanthus-inversus-syndrome,C0005744,T019,Disorders
"What are the genetic changes related to blepharophimosis, ptosis, and epicanthus inversus syndrome ?",0000130-3,genetic changes,"Mutations in the FOXL2 gene cause BPES types I and II. The FOXL2 gene provides instructions for making a protein that is active in the eyelids and ovaries. The FOXL2 protein is likely involved in the development of muscles in the eyelids. Before birth and in adulthood, the protein regulates the growth and development of certain ovarian cells and the breakdown of specific molecules.  It is difficult to predict the type of BPES that will result from the many FOXL2 gene mutations. However, mutations that result in a partial loss of FOXL2 protein function generally cause BPES type II. These mutations probably impair regulation of normal development of muscles in the eyelids, resulting in malformed eyelids that cannot open fully. Mutations that lead to a complete loss of FOXL2 protein function often cause BPES type I. These mutations impair the regulation of eyelid development as well as various activities in the ovaries, resulting in eyelid malformation and abnormally accelerated maturation of certain ovarian cells and the premature death of egg cells.","blepharophimosis, ptosis, and epicanthus inversus syndrome",0000130,GHR,https://ghr.nlm.nih.gov/condition/blepharophimosis-ptosis-and-epicanthus-inversus-syndrome,C0005744,T019,Disorders
"Is blepharophimosis, ptosis, and epicanthus inversus syndrome inherited ?",0000130-4,inheritance,"This condition is typically inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.","blepharophimosis, ptosis, and epicanthus inversus syndrome",0000130,GHR,https://ghr.nlm.nih.gov/condition/blepharophimosis-ptosis-and-epicanthus-inversus-syndrome,C0005744,T019,Disorders
"What are the treatments for blepharophimosis, ptosis, and epicanthus inversus syndrome ?",0000130-5,treatment,"These resources address the diagnosis or management of BPES:  - Gene Review: Gene Review: Blepharophimosis, Ptosis, and Epicanthus Inversus  - Genetic Testing Registry: Blepharophimosis, ptosis, and epicanthus inversus  - MedlinePlus Encyclopedia: Ptosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","blepharophimosis, ptosis, and epicanthus inversus syndrome",0000130,GHR,https://ghr.nlm.nih.gov/condition/blepharophimosis-ptosis-and-epicanthus-inversus-syndrome,C0005744,T019,Disorders
What is (are) Bloom syndrome ?,0000131-1,information,"Bloom syndrome is an inherited disorder characterized by short stature, a skin rash that develops after exposure to the sun, and a greatly increased risk of cancer.  People with Bloom syndrome are usually smaller than 97 percent of the population in both height and weight from birth, and they rarely exceed 5 feet tall in adulthood.  Affected individuals have skin that is sensitive to sun exposure, and they usually develop a butterfly-shaped patch of reddened skin across the nose and cheeks. A skin rash can also appear on other areas that are typically exposed to the sun, such as the back of the hands and the forearms. Small clusters of enlarged blood vessels (telangiectases) often appear in the rash; telangiectases can also occur in the eyes. Other skin features include patches of skin that are lighter or darker than the surrounding areas (hypopigmentation or hyperpigmentation respectively). These patches appear on areas of the skin that are not exposed to the sun, and their development is not related to the rashes.  People with Bloom syndrome have an increased risk of cancer. They can develop any type of cancer, but the cancers arise earlier in life than they do in the general population, and affected individuals often develop more than one type of cancer.  Individuals with Bloom syndrome have a high-pitched voice and distinctive facial features including a long, narrow face; a small lower jaw; and prominent nose and ears. Other features can include learning disabilities, an increased risk of diabetes, chronic obstructive pulmonary disease (COPD), and mild immune system abnormalities leading to recurrent infections of the upper respiratory tract, ears, and lungs during infancy. Men with Bloom syndrome usually do not produce sperm and as a result are unable to father children (infertile). Women with the disorder generally have reduced fertility and experience menopause at an earlier age than usual.",Bloom syndrome,0000131,GHR,https://ghr.nlm.nih.gov/condition/bloom-syndrome,C0005859,T019,Disorders
How many people are affected by Bloom syndrome ?,0000131-2,frequency,"Bloom syndrome is a rare disorder. Only a few hundred affected individuals have been described in the medical literature, about one-third of whom are of Central and Eastern European (Ashkenazi) Jewish background.",Bloom syndrome,0000131,GHR,https://ghr.nlm.nih.gov/condition/bloom-syndrome,C0005859,T019,Disorders
What are the genetic changes related to Bloom syndrome ?,0000131-3,genetic changes,"Mutations in the BLM gene cause Bloom syndrome. The BLM gene provides instructions for making a member of a protein family called RecQ helicases. Helicases are enzymes that attach (bind) to DNA and unwind the two spiral strands (double helix) of the DNA molecule. This unwinding is necessary for several processes in the cell nucleus, including copying (replicating) DNA in preparation for cell division and repairing damaged DNA. Because RecQ helicases help maintain the structure and integrity of DNA, they are known as the ""caretakers of the genome.""  When a cell prepares to divide to form two cells, the DNA that makes up the chromosomes is copied so that each new cell will have two copies of each chromosome, one from each parent. The copied DNA from each chromosome is arranged into two identical structures, called sister chromatids, which are attached to one another during the early stages of cell division. Sister chromatids occasionally exchange small sections of DNA during this time, a process known as sister chromatid exchange. Researchers suggest that these exchanges may be a response to DNA damage during the copying process. The BLM protein helps to prevent excess sister chromatid exchanges and is also involved in other processes that help maintain the stability of the DNA during the copying process.  BLM gene mutations result in the absence of functional BLM protein. As a result, the frequency of sister chromatid exchange is about 10 times higher than average. Exchange of DNA between chromosomes derived from the individual's mother and father are also increased in people with BLM gene mutations. In addition, chromosome breakage occurs more frequently in affected individuals. All of these changes are associated with gaps and breaks in the genetic material that impair normal cell activities and cause the health problems associated with this condition. Without the BLM protein, the cell is less able to repair DNA damage caused by ultraviolet light, which results in increased sun sensitivity. Genetic changes that allow cells to divide in an uncontrolled way lead to the cancers that occur in people with Bloom syndrome.",Bloom syndrome,0000131,GHR,https://ghr.nlm.nih.gov/condition/bloom-syndrome,C0005859,T019,Disorders
Is Bloom syndrome inherited ?,0000131-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Bloom syndrome,0000131,GHR,https://ghr.nlm.nih.gov/condition/bloom-syndrome,C0005859,T019,Disorders
What are the treatments for Bloom syndrome ?,0000131-5,treatment,These resources address the diagnosis or management of Bloom syndrome:  - Gene Review: Gene Review: Bloom's Syndrome  - Genetic Testing Registry: Bloom syndrome  - MedlinePlus Encyclopedia: Short Stature   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Bloom syndrome,0000131,GHR,https://ghr.nlm.nih.gov/condition/bloom-syndrome,C0005859,T019,Disorders
What is (are) boomerang dysplasia ?,0000132-1,information,"Boomerang dysplasia is a disorder that affects the development of bones throughout the body. Affected individuals are born with inward- and upward-turning feet (clubfeet) and dislocations of the hips, knees, and elbows. Bones in the spine, rib cage, pelvis, and limbs may be underdeveloped or in some cases absent. As a result of the limb bone abnormalities, individuals with this condition have very short arms and legs. Pronounced bowing of the upper leg bones (femurs) gives them a ""boomerang"" shape.  Some individuals with boomerang dysplasia have a sac-like protrusion of the brain (encephalocele). They may also have an opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the navel. Affected individuals typically have a distinctive nose that is broad with very small nostrils and an underdeveloped partition between the nostrils (septum).  Individuals with boomerang dysplasia typically have an underdeveloped rib cage that affects the development and functioning of the lungs. As a result, affected individuals are usually stillborn or die shortly after birth from respiratory failure.",boomerang dysplasia,0000132,GHR,https://ghr.nlm.nih.gov/condition/boomerang-dysplasia,C0334044,T046,Disorders
How many people are affected by boomerang dysplasia ?,0000132-2,frequency,Boomerang dysplasia is a rare disorder; its exact prevalence is unknown. Approximately 10 affected individuals have been identified.,boomerang dysplasia,0000132,GHR,https://ghr.nlm.nih.gov/condition/boomerang-dysplasia,C0334044,T046,Disorders
What are the genetic changes related to boomerang dysplasia ?,0000132-3,genetic changes,"Mutations in the FLNB gene cause boomerang dysplasia. The FLNB gene provides instructions for making a protein called filamin B. This protein helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. Filamin B attaches (binds) to another protein called actin and helps the actin to form the branching network of filaments that makes up the cytoskeleton. It also links actin to many other proteins to perform various functions within the cell, including the cell signaling that helps determine how the cytoskeleton will change as tissues grow and take shape during development.  Filamin B is especially important in the development of the skeleton before birth. It is active (expressed) in the cell membranes of cartilage-forming cells (chondrocytes). Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone (a process called ossification), except for the cartilage that continues to cover and protect the ends of bones and is present in the nose, airways (trachea and bronchi), and external ears. Filamin B appears to be important for normal cell growth and division (proliferation) and maturation (differentiation) of chondrocytes and for the ossification of cartilage.  FLNB gene mutations that cause boomerang dysplasia change single protein building blocks (amino acids) in the filamin B protein or delete a small section of the protein sequence, resulting in an abnormal protein. This abnormal protein appears to have a new, atypical function that interferes with the proliferation or differentiation of chondrocytes, impairing ossification and leading to the signs and symptoms of boomerang dysplasia.",boomerang dysplasia,0000132,GHR,https://ghr.nlm.nih.gov/condition/boomerang-dysplasia,C0334044,T046,Disorders
Is boomerang dysplasia inherited ?,0000132-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Almost all cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",boomerang dysplasia,0000132,GHR,https://ghr.nlm.nih.gov/condition/boomerang-dysplasia,C0334044,T046,Disorders
What are the treatments for boomerang dysplasia ?,0000132-5,treatment,These resources address the diagnosis or management of boomerang dysplasia:  - Gene Review: Gene Review: FLNB-Related Disorders  - Genetic Testing Registry: Boomerang dysplasia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,boomerang dysplasia,0000132,GHR,https://ghr.nlm.nih.gov/condition/boomerang-dysplasia,C0334044,T046,Disorders
What is (are) Bowen-Conradi syndrome ?,0000133-1,information,"Bowen-Conradi syndrome is a disorder that affects many parts of the body and is usually fatal in infancy. Affected individuals have a low birth weight, experience feeding problems, and grow very slowly. Their head is unusually small overall (microcephaly), but is longer than expected compared with its width (dolichocephaly). Characteristic facial features include a prominent, high-bridged nose and an unusually small jaw (micrognathia) and chin. Affected individuals typically have pinky fingers that are curved toward or away from the ring finger (fifth finger clinodactyly) or permanently flexed (camptodactyly), feet with soles that are rounded outward (rocker-bottom feet), and restricted joint movement.  Other features that occur in some affected individuals include seizures; structural abnormalities of the kidneys, heart, brain, or other organs; and an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate). Affected males may have the opening of the urethra on the underside of the penis (hypospadias) or undescended testes (cryptorchidism).  Babies with Bowen-Conradi syndrome do not achieve developmental milestones such as smiling or sitting, and they usually do not survive more than 6 months.",Bowen-Conradi syndrome,0000133,GHR,https://ghr.nlm.nih.gov/condition/bowen-conradi-syndrome,C0039082,T047,Disorders
How many people are affected by Bowen-Conradi syndrome ?,0000133-2,frequency,Bowen-Conradi syndrome is common in the Hutterite population in Canada and the United States; it occurs in approximately 1 per 355 newborns in all three Hutterite sects (leuts). A few individuals from outside the Hutterite community with signs and symptoms similar to Bowen-Conradi syndrome have been described in the medical literature. Researchers differ as to whether these individuals have Bowen-Conradi syndrome or a similar but distinct disorder.,Bowen-Conradi syndrome,0000133,GHR,https://ghr.nlm.nih.gov/condition/bowen-conradi-syndrome,C0039082,T047,Disorders
What are the genetic changes related to Bowen-Conradi syndrome ?,0000133-3,genetic changes,"Bowen-Conradi syndrome is caused by a mutation in the EMG1 gene. This gene provides instructions for making a protein that is involved in the production of cellular structures called ribosomes, which process the cell's genetic instructions to create new proteins. Ribosomes are assembled in a cell compartment called the nucleolus.  The particular EMG1 gene mutation known to cause Bowen-Conradi syndrome is thought to make the protein unstable, resulting in a decrease in the amount of EMG1 protein that is available in the nucleolus. A shortage of this protein in the nucleolus would impair ribosome production, which may reduce cell growth and division (proliferation); however, it is unknown how EMG1 gene mutations lead to the particular signs and symptoms of Bowen-Conradi syndrome.",Bowen-Conradi syndrome,0000133,GHR,https://ghr.nlm.nih.gov/condition/bowen-conradi-syndrome,C0039082,T047,Disorders
Is Bowen-Conradi syndrome inherited ?,0000133-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Bowen-Conradi syndrome,0000133,GHR,https://ghr.nlm.nih.gov/condition/bowen-conradi-syndrome,C0039082,T047,Disorders
What are the treatments for Bowen-Conradi syndrome ?,0000133-5,treatment,These resources address the diagnosis or management of Bowen-Conradi syndrome:  - Genetic Testing Registry: Bowen-Conradi syndrome  - MedlinePlus Encyclopedia: Feeding Tube--Infants   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Bowen-Conradi syndrome,0000133,GHR,https://ghr.nlm.nih.gov/condition/bowen-conradi-syndrome,C0039082,T047,Disorders
What is (are) bradyopsia ?,0000134-1,information,"Bradyopsia is a rare condition that affects vision. The term ""bradyopsia"" is from the Greek words for slow vision. In affected individuals, the eyes adapt more slowly than usual to changing light conditions. For example, people with this condition are blinded for several seconds when going from a dark environment into a bright one, such as when walking out of a darkened movie theater into daylight. Their eyes also have trouble adapting from bright light to dark conditions, such as when driving into a dark tunnel on a sunny day.  Some people with bradyopsia also have difficulty seeing some moving objects, particularly small objects moving against a bright background. As a result, they often have trouble watching or participating in sports with a ball, such as soccer or tennis. People with bradyopsia can have reduced sharpness (acuity) of vision, although acuity may depend on the conditions under which vision is tested. Visual acuity may appear to be severely affected if it is tested under bright lights, but it can be near normal if tested in a dim environment. The ability to see colors and distinguish between them is normal.  The vision problems associated with bradyopsia become apparent in early childhood. They are usually stable, which means they do not worsen over time.",bradyopsia,0000134,GHR,https://ghr.nlm.nih.gov/condition/bradyopsia,C1842073,T047,Disorders
How many people are affected by bradyopsia ?,0000134-2,frequency,Bradyopsia appears to be rare. Only a few affected individuals worldwide have been described in the medical literature.,bradyopsia,0000134,GHR,https://ghr.nlm.nih.gov/condition/bradyopsia,C1842073,T047,Disorders
What are the genetic changes related to bradyopsia ?,0000134-3,genetic changes,"Bradyopsia can be caused by mutations in the RGS9 gene or in the RGS9BP gene (which is also known as R9AP). These genes provide instructions for making proteins that are necessary for normal vision. The proteins are found in light-detecting cells in the eye called photoreceptors. When light enters the eye, it stimulates specialized pigments in these cells. This stimulation triggers a series of chemical reactions that produce an electrical signal, which is interpreted by the brain as vision. Once photoreceptors have been stimulated by light, they must return to their resting state before they can be stimulated again. The RGS9 and RGS9BP proteins play an essential role in returning photoreceptors to their resting state quickly after light exposure.  Mutations in either the RGS9 or RGS9BP gene prevent photoreceptors from recovering quickly after responding to light. Normally they return to their resting state in a fraction of a second, but in people with mutations in one of these genes, it can take ten seconds or longer. During that time, the photoreceptors cannot respond to light. This delay causes temporary blindness in response to changing light conditions and interferes with seeing small objects when they are in motion.  In some people with bradyopsia, no mutations in the RGS9 or RGS9BP gene have been found. The cause of the condition in these individuals is unknown.",bradyopsia,0000134,GHR,https://ghr.nlm.nih.gov/condition/bradyopsia,C1842073,T047,Disorders
Is bradyopsia inherited ?,0000134-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",bradyopsia,0000134,GHR,https://ghr.nlm.nih.gov/condition/bradyopsia,C1842073,T047,Disorders
What are the treatments for bradyopsia ?,0000134-5,treatment,These resources address the diagnosis or management of bradyopsia:  - Children's Hospital of Pittsburgh: Electroretinogram  - Genetic Testing Registry: Prolonged electroretinal response suppression  - MedlinePlus Encyclopedia: Electroretinography  - Prevent Blindness: Living Well with Low Vision   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,bradyopsia,0000134,GHR,https://ghr.nlm.nih.gov/condition/bradyopsia,C1842073,T047,Disorders
What is (are) branchio-oculo-facial syndrome ?,0000135-1,information,"Branchio-oculo-facial syndrome is a condition that affects development before birth, particularly of structures in the face and neck. Its characteristic features include skin anomalies on the neck, malformations of the eyes and ears, and distinctive facial features.  ""Branchio-"" refers to the branchial arches, which are structures in the developing embryo that give rise to tissues in the face and neck. In people with branchio-oculo-facial syndrome, the first and second branchial arches do not develop properly, leading to abnormal patches of skin, typically on the neck or near the ears. These patches can be unusually thin, hairy, or red and densely packed with blood vessels (hemangiomatous). In a small number of individuals, tissue from a gland called the thymus is abnormally located on the skin of the neck (dermal thymus). Problems with branchial arch development underlie many of the other features of branchio-oculo-facial syndrome.  ""Oculo-"" refers to the eyes. Many people with branchio-oculo-facial syndrome have malformations of the eyes that can lead to vision impairment. These abnormalities include unusually small eyeballs (microphthalmia), no eyeballs (anophthalmia), a gap or split in structures that make up the eyes (coloboma), or blockage of the tear ducts (nasolacrimal duct stenosis).  Problems with development of the face lead to distinctive facial features in people with branchio-oculo-facial syndrome. Many affected individuals have a split in the upper lip (cleft lip) or a pointed upper lip that resembles a poorly repaired cleft lip (often called a pseudocleft lip) with or without an opening in the roof of the mouth (cleft palate). Other facial characteristics include widely spaced eyes (hypertelorism), an increased distance between the inner corners of the eyes (telecanthus), outside corners of the eyes that point upward (upslanting palpebral fissures), a broad nose with a flattened tip, and weakness of the muscles in the lower face. The ears are also commonly affected, resulting in malformed or prominent ears. Abnormalities of the inner ear or of the tiny bones in the ears (ossicles) can cause hearing loss in people with this condition.  Branchio-oculo-facial syndrome can affect other structures and tissues as well. Some affected individuals have kidney abnormalities, such as malformed kidneys or multiple kidney cysts. Nail and teeth abnormalities also occur, and some people with this condition have prematurely graying hair.",branchio-oculo-facial syndrome,0000135,GHR,https://ghr.nlm.nih.gov/condition/branchio-oculo-facial-syndrome,C0376524,T019,Disorders
How many people are affected by branchio-oculo-facial syndrome ?,0000135-2,frequency,"Branchio-oculo-facial syndrome is a rare condition, although the prevalence is unknown.",branchio-oculo-facial syndrome,0000135,GHR,https://ghr.nlm.nih.gov/condition/branchio-oculo-facial-syndrome,C0376524,T019,Disorders
What are the genetic changes related to branchio-oculo-facial syndrome ?,0000135-3,genetic changes,"Branchio-oculo-facial syndrome is caused by mutations in the TFAP2A gene. This gene provides instructions for making a protein called transcription factor AP-2 alpha (AP-2). As its name suggests, this protein is a transcription factor, which means it attaches (binds) to specific regions of DNA and helps control the activity of particular genes. Transcription factor AP-2 regulates genes that are involved in several cellular processes, such as cell division and the self-destruction of cells that are no longer needed (apoptosis). This protein is critical during development before birth, particularly of the branchial arches, which form the structures of the face and neck.  Most TFAP2A gene mutations that cause branchio-oculo-facial syndrome change single protein building blocks (amino acids) in the transcription factor AP-2 protein. These changes tend to occur in a region of the protein that allows it to bind to DNA. Without this function, transcription factor AP-2 cannot control the activity of genes during development, which disrupts the development of the eyes, ears, and face and causes the features of branchio-oculo-facial syndrome.",branchio-oculo-facial syndrome,0000135,GHR,https://ghr.nlm.nih.gov/condition/branchio-oculo-facial-syndrome,C0376524,T019,Disorders
Is branchio-oculo-facial syndrome inherited ?,0000135-4,inheritance,"Branchio-oculo-facial syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In about half of cases, an affected person inherits the mutation from one affected parent. The remaining cases occur in people whose parents do not have a mutation in the TFAP2A gene. In these situations, the mutation likely occurs as a random event during the formation of reproductive cells (eggs and sperm) in a parent or in early fetal development of the affected individual.",branchio-oculo-facial syndrome,0000135,GHR,https://ghr.nlm.nih.gov/condition/branchio-oculo-facial-syndrome,C0376524,T019,Disorders
What are the treatments for branchio-oculo-facial syndrome ?,0000135-5,treatment,These resources address the diagnosis or management of branchio-oculo-facial syndrome:  - Gene Review: Gene Review: Branchiooculofacial Syndrome  - Genetic Testing Registry: Branchiooculofacial syndrome  - MedlinePlus Encyclopedia: Cleft Lip and Palate   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,branchio-oculo-facial syndrome,0000135,GHR,https://ghr.nlm.nih.gov/condition/branchio-oculo-facial-syndrome,C0376524,T019,Disorders
What is (are) branchiootorenal/branchiootic syndrome ?,0000136-1,information,"Branchiootorenal (BOR) syndrome is a condition that disrupts the development of tissues in the neck and causes malformations of the ears and kidneys. The signs and symptoms of this condition vary widely, even among members of the same family. Branchiootic (BO) syndrome includes many of the same features as BOR syndrome, but affected individuals do not have kidney abnormalities. The two conditions are otherwise so similar that researchers often consider them together (BOR/BO syndrome or branchiootorenal spectrum disorders).  ""Branchio-"" refers to the second branchial arch, which is a structure in the developing embryo that gives rise to tissues in the front and side of the neck. In people with BOR/BO syndrome, abnormal development of the second branchial arch can result in the formation of masses in the neck called branchial cleft cysts. Some affected people have abnormal holes or pits called fistulae in the side of the neck just above the collarbone. Fistulae can form tunnels into the neck, exiting in the mouth near the tonsil. Branchial cleft cysts and fistulae can cause health problems if they become infected, so they are often removed surgically.  ""Oto-"" and ""-otic"" refer to the ear; most people with BOR/BO syndrome have hearing loss and other ear abnormalities. The hearing loss can be sensorineural, meaning it is caused by abnormalities in the inner ear; conductive, meaning it results from changes in the small bones in the middle ear; or mixed, meaning it is caused by a combination of inner ear and middle ear abnormalities. Some affected people have tiny holes in the skin or extra bits of tissue just in front of the ear. These are called preauricular pits and preauricular tags, respectively.  ""Renal"" refers to the kidneys; BOR syndrome (but not BO syndrome) causes abnormalities of kidney structure and function. These abnormalities range from mild to severe and can affect one or both kidneys. In some cases, end-stage renal disease (ESRD) develops later in life. This serious condition occurs when the kidneys become unable to filter fluids and waste products from the body effectively.",branchiootorenal/branchiootic syndrome,0000136,GHR,https://ghr.nlm.nih.gov/condition/branchiootorenal-branchiootic-syndrome,C1865143,T047,Disorders
How many people are affected by branchiootorenal/branchiootic syndrome ?,0000136-2,frequency,"Researchers estimate that BOR/BO syndrome affects about 1 in 40,000 people.",branchiootorenal/branchiootic syndrome,0000136,GHR,https://ghr.nlm.nih.gov/condition/branchiootorenal-branchiootic-syndrome,C1865143,T047,Disorders
What are the genetic changes related to branchiootorenal/branchiootic syndrome ?,0000136-3,genetic changes,"Mutations in three genes, EYA1, SIX1, and SIX5, have been reported in people with BOR/BO syndrome. About 40 percent of people with this condition have a mutation in the EYA1 gene. SIX1 gene mutations are a much less common cause of the disorder. SIX5 gene mutations have been found in a small number of people with BOR syndrome, although researchers question whether mutations in this gene cause the condition. Some affected individuals originally reported to have SIX5 gene mutations were later found to have EYA1 gene mutations as well, and researchers suspect that the EYA1 gene mutations may be the actual cause of the condition in these people.  The proteins produced from the EYA1, SIX1, and SIX5 genes play important roles in development before birth. The EYA1 protein interacts with several other proteins, including SIX1 and SIX5, to regulate the activity of genes involved in many aspects of embryonic development. Research suggests that these protein interactions are essential for the normal formation of many organs and tissues, including the second branchial arch, ears, and kidneys. Mutations in the EYA1, SIX1, or SIX5 gene may disrupt the proteins' ability to interact with one another and regulate gene activity. The resulting genetic changes affect the development of organs and tissues before birth, which leads to the characteristic features of BOR/BO syndrome.  Some people with BOR/BO syndrome do not have an identified mutation in any of the genes listed above. In these cases, the cause of the condition is unknown.",branchiootorenal/branchiootic syndrome,0000136,GHR,https://ghr.nlm.nih.gov/condition/branchiootorenal-branchiootic-syndrome,C1865143,T047,Disorders
Is branchiootorenal/branchiootic syndrome inherited ?,0000136-4,inheritance,"BOR/BO syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In about 90 percent of cases, an affected person inherits the mutation from one affected parent. The remaining cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",branchiootorenal/branchiootic syndrome,0000136,GHR,https://ghr.nlm.nih.gov/condition/branchiootorenal-branchiootic-syndrome,C1865143,T047,Disorders
What are the treatments for branchiootorenal/branchiootic syndrome ?,0000136-5,treatment,These resources address the diagnosis or management of branchiootorenal/branchiootic syndrome:  - Gene Review: Gene Review: Branchiootorenal Spectrum Disorders  - Genetic Testing Registry: Branchiootic syndrome  - Genetic Testing Registry: Branchiootic syndrome 2  - Genetic Testing Registry: Branchiootic syndrome 3  - Genetic Testing Registry: Branchiootorenal syndrome 2  - Genetic Testing Registry: Melnick-Fraser syndrome  - MedlinePlus Encyclopedia: Branchial Cleft Cyst  - MedlinePlus Encyclopedia: End-Stage Kidney Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,branchiootorenal/branchiootic syndrome,0000136,GHR,https://ghr.nlm.nih.gov/condition/branchiootorenal-branchiootic-syndrome,C1865143,T047,Disorders
What is (are) breast cancer ?,0000137-1,information,"Breast cancer is a disease in which certain cells in the breast become abnormal and multiply uncontrollably to form a tumor. Although breast cancer is much more common in women, this form of cancer can also develop in men. In both women and men, the most common form of breast cancer begins in cells lining the milk ducts (ductal cancer). In women, cancer can also develop in the glands that produce milk (lobular cancer). Most men have little or no lobular tissue, so lobular cancer in men is very rare.  In its early stages, breast cancer usually does not cause pain and may exhibit no noticeable symptoms. As the cancer progresses, signs and symptoms can include a lump or thickening in or near the breast; a change in the size or shape of the breast; nipple discharge, tenderness, or retraction (turning inward); and skin irritation, dimpling, or scaliness. However, these changes can occur as part of many different conditions. Having one or more of these symptoms does not mean that a person definitely has breast cancer.  In some cases, cancerous tumors can invade surrounding tissue and spread to other parts of the body. If breast cancer spreads, cancerous cells most often appear in the bones, liver, lungs, or brain. Tumors that begin at one site and then spread to other areas of the body are called metastatic cancers.  A small percentage of all breast cancers cluster in families. These cancers are described as hereditary and are associated with inherited gene mutations. Hereditary breast cancers tend to develop earlier in life than noninherited (sporadic) cases, and new (primary) tumors are more likely to develop in both breasts.",breast cancer,0000137,GHR,https://ghr.nlm.nih.gov/condition/breast-cancer,C0006142,T191,Disorders
How many people are affected by breast cancer ?,0000137-2,frequency,"Breast cancer is the second most commonly diagnosed cancer in women. (Only skin cancer is more common.) About one in eight women in the United States will develop invasive breast cancer in her lifetime. Researchers estimate that more than 230,000 new cases of invasive breast cancer will be diagnosed in U.S. women in 2015.  Male breast cancer represents less than 1 percent of all breast cancer diagnoses. Scientists estimate that about 2,300 new cases of breast cancer will be diagnosed in men in 2015.  Particular gene mutations associated with breast cancer are more common among certain geographic or ethnic groups, such as people of Ashkenazi (central or eastern European) Jewish heritage and people of Norwegian, Icelandic, or Dutch ancestry.",breast cancer,0000137,GHR,https://ghr.nlm.nih.gov/condition/breast-cancer,C0006142,T191,Disorders
What are the genetic changes related to breast cancer ?,0000137-3,genetic changes,"Cancers occur when a buildup of mutations in critical genesthose that control cell growth and division or repair damaged DNAallow cells to grow and divide uncontrollably to form a tumor. In most cases of breast cancer, these genetic changes are acquired during a person's lifetime and are present only in certain cells in the breast. These changes, which are called somatic mutations, are not inherited. Somatic mutations in many different genes have been found in breast cancer cells. Less commonly, gene mutations present in essentially all of the body's cells increase the risk of developing breast cancer. These genetic changes, which are classified as germline mutations, are usually inherited from a parent. In people with germline mutations, changes in other genes, together with environmental and lifestyle factors, also influence whether a person will develop breast cancer.  Some breast cancers that cluster in families are associated with inherited mutations in particular genes, such as BRCA1 or BRCA2. These genes are described as ""high penetrance"" because they are associated with a high risk of developing breast cancer, ovarian cancer, and several other types of cancer in women who have mutations. Men with mutations in these genes also have an increased risk of developing several forms of cancer, including breast cancer. The proteins produced from the BRCA1 and BRCA2 genes are involved in fixing damaged DNA, which helps to maintain the stability of a cell's genetic information. They are described as tumor suppressors because they help keep cells from growing and dividing too fast or in an uncontrolled way. Mutations in these genes impair DNA repair, allowing potentially damaging mutations to persist in DNA. As these defects accumulate, they can trigger cells to grow and divide without control or order to form a tumor.  A significantly increased risk of breast cancer is also a feature of several rare genetic syndromes. These include Cowden syndrome, which is most often caused by mutations in the PTEN gene; hereditary diffuse gastric cancer, which results from mutations in the CDH1 gene; Li-Fraumeni syndrome, which is usually caused by mutations in the TP53 gene; and Peutz-Jeghers syndrome, which typically results from mutations in the STK11 gene. The proteins produced from these genes act as tumor suppressors. Mutations in any of these genes can allow cells to grow and divide unchecked, leading to the development of a cancerous tumor. Like BRCA1 and BRCA2, these genes are considered ""high penetrance"" because mutations greatly increase a person's chance of developing cancer. In addition to breast cancer, mutations in these genes increase the risk of several other types of cancer over a person's lifetime. Some of the conditions also include other signs and symptoms, such as the growth of noncancerous (benign) tumors.  Mutations in dozens of other genes have been studied as possible risk factors for breast cancer. These genes are described as ""low penetrance"" or ""moderate penetrance"" because changes in each of these genes appear to make only a small or moderate contribution to overall breast cancer risk. Some of these genes provide instructions for making proteins that interact with the proteins produced from the BRCA1 or BRCA2 genes. Others act through different pathways. Researchers suspect that the combined influence of variations in these genes may significantly impact a person's risk of developing breast cancer.  In many families, the genetic changes associated with hereditary breast cancer are unknown. Identifying additional genetic risk factors for breast cancer is an active area of medical research.  In addition to genetic changes, researchers have identified many personal and environmental factors that contribute to a person's risk of developing breast cancer. These factors include gender, age, ethnic background, a history of previous breast cancer, certain changes in breast tissue, and hormonal and reproductive factors. A history of breast cancer in closely related family members is also an important risk factor, particularly if the cancer occurred in early adulthood.",breast cancer,0000137,GHR,https://ghr.nlm.nih.gov/condition/breast-cancer,C0006142,T191,Disorders
Is breast cancer inherited ?,0000137-4,inheritance,"Most cases of breast cancer are not caused by inherited genetic factors. These cancers are associated with somatic mutations in breast cells that are acquired during a person's lifetime, and they do not cluster in families.  In hereditary breast cancer, the way that cancer risk is inherited depends on the gene involved. For example, mutations in the BRCA1 and BRCA2 genes are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase a person's chance of developing cancer. Although breast cancer is more common in women than in men, the mutated gene can be inherited from either the mother or the father.  In the other syndromes discussed above, the gene mutations that increase cancer risk also have an autosomal dominant pattern of inheritance. It is important to note that people inherit an increased likelihood of developing cancer, not the disease itself. Not all people who inherit mutations in these genes will ultimately develop cancer.  In many cases of breast cancer that clusters in families, the genetic basis for the disease and the mechanism of inheritance are unclear.",breast cancer,0000137,GHR,https://ghr.nlm.nih.gov/condition/breast-cancer,C0006142,T191,Disorders
What are the treatments for breast cancer ?,0000137-5,treatment,These resources address the diagnosis or management of breast cancer:  - Gene Review: Gene Review: BRCA1 and BRCA2 Hereditary Breast/Ovarian Cancer  - Gene Review: Gene Review: Hereditary Diffuse Gastric Cancer  - Gene Review: Gene Review: Li-Fraumeni Syndrome  - Gene Review: Gene Review: PTEN Hamartoma Tumor Syndrome (PHTS)  - Gene Review: Gene Review: Peutz-Jeghers Syndrome  - Genetic Testing Registry: Familial cancer of breast  - Genomics Education Programme (UK): Hereditary Breast and Ovarian Cancer  - National Cancer Institute: Breast Cancer Risk Assessment Tool  - National Cancer Institute: Genetic Testing for BRCA1 and BRCA2: It's Your Choice  - National Cancer Institute: Genetic Testing for Hereditary Cancer Syndromes   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,breast cancer,0000137,GHR,https://ghr.nlm.nih.gov/condition/breast-cancer,C0006142,T191,Disorders
What is (are) Brody myopathy ?,0000138-1,information,"Brody myopathy is a condition that affects the skeletal muscles, which are the muscles used for movement. Affected individuals experience muscle cramping and stiffening after exercise or other strenuous activity, especially in cold temperatures. These symptoms typically begin in childhood. They are usually painless, but in some cases can cause mild discomfort. The muscles usually relax after a few minutes of rest. Most commonly affected are the muscles of the arms, legs, and face (particularly the eyelids).  In some people with Brody myopathy, exercise leads to the breakdown of muscle tissue (rhabdomyolysis). The destruction of muscle tissue releases a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria). Myoglobin causes the urine to be red or brown.",Brody myopathy,0000138,GHR,https://ghr.nlm.nih.gov/condition/brody-myopathy,C1832918,T047,Disorders
How many people are affected by Brody myopathy ?,0000138-2,frequency,"Brody myopathy is a rare condition, although its exact prevalence is unknown.",Brody myopathy,0000138,GHR,https://ghr.nlm.nih.gov/condition/brody-myopathy,C1832918,T047,Disorders
What are the genetic changes related to Brody myopathy ?,0000138-3,genetic changes,"Mutations in the ATP2A1 gene cause Brody myopathy. The ATP2A1 gene provides instructions for making an enzyme called sarco(endo)plasmic reticulum calcium-ATPase 1 (SERCA1). The SERCA1 enzyme is found in skeletal muscle cells, specifically in the membrane of a structure called the sarcoplasmic reticulum. This structure plays a major role in muscle contraction and relaxation by storing and releasing positively charged calcium atoms (calcium ions). When calcium ions are transported out of the sarcoplasmic reticulum, muscles contract; when calcium ions are transported into the sarcoplasmic reticulum, muscles relax. The SERCA1 enzyme transports calcium ions from the cell into the sarcoplasmic reticulum, triggering muscle relaxation.  ATP2A1 gene mutations lead to the production of a SERCA1 enzyme with decreased or no function. As a result, calcium ions are slow to enter the sarcoplasmic reticulum and muscle relaxation is delayed. After exercise or strenuous activity, during which the muscles rapidly contract and relax, people with Brody myopathy develop muscle cramps because their muscles cannot fully relax.",Brody myopathy,0000138,GHR,https://ghr.nlm.nih.gov/condition/brody-myopathy,C1832918,T047,Disorders
Is Brody myopathy inherited ?,0000138-4,inheritance,"Brody myopathy is usually inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Some people with autosomal recessive Brody myopathy do not have an identified mutation in the ATP2A1 gene; the cause of the disease in these individuals is unknown.",Brody myopathy,0000138,GHR,https://ghr.nlm.nih.gov/condition/brody-myopathy,C1832918,T047,Disorders
What are the treatments for Brody myopathy ?,0000138-5,treatment,These resources address the diagnosis or management of Brody myopathy:  - Genetic Testing Registry: Brody myopathy  - New York Presbyterian Hospital: Myopathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Brody myopathy,0000138,GHR,https://ghr.nlm.nih.gov/condition/brody-myopathy,C1832918,T047,Disorders
What is (are) Brooke-Spiegler syndrome ?,0000139-1,information,"Brooke-Spiegler syndrome is a condition involving multiple skin tumors that develop from structures associated with the skin (skin appendages), such as sweat glands and hair follicles. People with Brooke-Spiegler syndrome may develop several types of tumors, including growths called spiradenomas, trichoepitheliomas, and cylindromas. Spiradenomas develop in sweat glands. Trichoepitheliomas arise from hair follicles. The origin of cylindromas has been unclear; while previously thought to derive from sweat glands, they are now generally believed to begin in hair follicles. The tumors associated with Brooke-Spiegler syndrome are generally noncancerous (benign), but occasionally they may become cancerous (malignant). Affected individuals are also at increased risk of developing tumors in tissues other than skin appendages, particularly benign or malignant tumors of the salivary glands.  People with Brooke-Spiegler syndrome typically begin developing tumors in early adulthood. The tumors are most often found on the head and neck. They grow larger and increase in number over time. In severe cases, the tumors may get in the way of the eyes, ears, nose, or mouth and affect vision, hearing, or other functions. The tumors can be disfiguring and may contribute to depression or other psychological problems. For reasons that are unclear, females with Brooke-Spiegler syndrome are often more severely affected than males.",Brooke-Spiegler syndrome,0000139,GHR,https://ghr.nlm.nih.gov/condition/brooke-spiegler-syndrome,C1857941,T047,Disorders
How many people are affected by Brooke-Spiegler syndrome ?,0000139-2,frequency,Brooke-Spiegler syndrome is a rare disorder; its prevalence is unknown.,Brooke-Spiegler syndrome,0000139,GHR,https://ghr.nlm.nih.gov/condition/brooke-spiegler-syndrome,C1857941,T047,Disorders
What are the genetic changes related to Brooke-Spiegler syndrome ?,0000139-3,genetic changes,"Brooke-Spiegler syndrome is caused by mutations in the CYLD gene. This gene provides instructions for making a protein that helps regulate nuclear factor-kappa-B. Nuclear factor-kappa-B is a group of related proteins that help protect cells from self-destruction (apoptosis) in response to certain signals. In regulating the action of nuclear factor-kappa-B, the CYLD protein allows cells to respond properly to signals to self-destruct when appropriate, such as when the cells become abnormal. By this mechanism, the CYLD protein acts as a tumor suppressor, which means that it helps prevent cells from growing and dividing too fast or in an uncontrolled way.  People with Brooke-Spiegler syndrome are born with a mutation in one of the two copies of the CYLD gene in each cell. This mutation prevents the cell from making functional CYLD protein from the altered copy of the gene. However, enough protein is usually produced from the other, normal copy of the gene to regulate cell growth effectively. For tumors to develop, a second mutation or deletion of genetic material involving the other copy of the CYLD gene must occur in certain cells during a person's lifetime.  When both copies of the CYLD gene are mutated in a particular cell, that cell cannot produce any functional CYLD protein. The loss of this protein allows the cell to grow and divide in an uncontrolled way to form a tumor. In people with Brooke-Spiegler syndrome, a second CYLD mutation typically occurs in multiple cells over an affected person's lifetime. The loss of CYLD protein in different types of cells in the skin leads to the growth of a variety of skin appendage tumors.  Some researchers consider Brooke-Spiegler syndrome and two related conditions called multiple familial trichoepithelioma and familial cylindromatosis, which are also caused by CYLD gene mutations, to be different forms of the same disorder. It is unclear why mutations in the CYLD gene cause different patterns of skin appendage tumors in each of these conditions, or why the tumors are generally confined to the skin in these disorders.",Brooke-Spiegler syndrome,0000139,GHR,https://ghr.nlm.nih.gov/condition/brooke-spiegler-syndrome,C1857941,T047,Disorders
Is Brooke-Spiegler syndrome inherited ?,0000139-4,inheritance,"Susceptibility to Brooke-Spiegler syndrome has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell increases the risk of developing this condition. However, a second, non-inherited mutation is required for development of skin appendage tumors in this disorder.",Brooke-Spiegler syndrome,0000139,GHR,https://ghr.nlm.nih.gov/condition/brooke-spiegler-syndrome,C1857941,T047,Disorders
What are the treatments for Brooke-Spiegler syndrome ?,0000139-5,treatment,These resources address the diagnosis or management of Brooke-Spiegler syndrome:  - Genetic Testing Registry: Spiegler-Brooke syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Brooke-Spiegler syndrome,0000139,GHR,https://ghr.nlm.nih.gov/condition/brooke-spiegler-syndrome,C1857941,T047,Disorders
What is (are) Brugada syndrome ?,0000140-1,information,"Brugada syndrome is a condition that causes a disruption of the heart's normal rhythm. Specifically, this disorder can lead to irregular heartbeats in the heart's lower chambers (ventricles), which is an abnormality called ventricular arrhythmia. If untreated, the irregular heartbeats can cause fainting (syncope), seizures, difficulty breathing, or sudden death. These complications typically occur when an affected person is resting or asleep.  Brugada syndrome usually becomes apparent in adulthood, although it can develop any time throughout life. Signs and symptoms related to arrhythmias, including sudden death, can occur from early infancy to late adulthood. Sudden death typically occurs around age 40. This condition may explain some cases of sudden infant death syndrome (SIDS), which is a major cause of death in babies younger than 1 year. SIDS is characterized by sudden and unexplained death, usually during sleep.  Sudden unexplained nocturnal death syndrome (SUNDS) is a condition characterized by unexpected cardiac arrest in young adults, usually at night during sleep. This condition was originally described in Southeast Asian populations, where it is a major cause of death. Researchers have determined that SUNDS and Brugada syndrome are the same disorder.",Brugada syndrome,0000140,GHR,https://ghr.nlm.nih.gov/condition/brugada-syndrome,C1142166,T047,Disorders
How many people are affected by Brugada syndrome ?,0000140-2,frequency,"The exact prevalence of Brugada syndrome is unknown, although it is estimated to affect 5 in 10,000 people worldwide. This condition occurs much more frequently in people of Asian ancestry, particularly in Japanese and Southeast Asian populations.  Although Brugada syndrome affects both men and women, the condition appears to be 8 to 10 times more common in men. Researchers suspect that testosterone, a sex hormone present at much higher levels in men, may account for this difference.",Brugada syndrome,0000140,GHR,https://ghr.nlm.nih.gov/condition/brugada-syndrome,C1142166,T047,Disorders
What are the genetic changes related to Brugada syndrome ?,0000140-3,genetic changes,"Brugada syndrome can be caused by mutations in one of several genes. The most commonly mutated gene in this condition is SCN5A, which is altered in approximately 30 percent of affected individuals. This gene provides instructions for making a sodium channel, which normally transports positively charged sodium atoms (ions) into heart muscle cells. This type of ion channel plays a critical role in maintaining the heart's normal rhythm. Mutations in the SCN5A gene alter the structure or function of the channel, which reduces the flow of sodium ions into cells. A disruption in ion transport alters the way the heart beats, leading to the abnormal heart rhythm characteristic of Brugada syndrome.  Mutations in other genes can also cause Brugada syndrome. Together, these other genetic changes account for less than two percent of cases of the condition. Some of the additional genes involved in Brugada syndrome provide instructions for making proteins that ensure the correct location or function of sodium channels in heart muscle cells. Proteins produced by other genes involved in the condition form or help regulate ion channels that transport calcium or potassium into or out of heart muscle cells. As with sodium channels, proper flow of ions through calcium and potassium channels in the heart muscle helps maintain a regular heartbeat. Mutations in these genes disrupt the flow of ions, impairing the heart's normal rhythm.  In affected people without an identified gene mutation, the cause of Brugada syndrome is often unknown. In some cases, certain drugs may cause a nongenetic (acquired) form of the disorder. Drugs that can induce an altered heart rhythm include medications used to treat some forms of arrhythmia, a condition called angina (which causes chest pain), high blood pressure, depression, and other mental illnesses. Abnormally high blood levels of calcium (hypercalcemia) or potassium (hyperkalemia), as well as unusually low potassium levels (hypokalemia), also have been associated with acquired Brugada syndrome. In addition to causing a nongenetic form of this disorder, these factors may trigger symptoms in people with an underlying mutation in SCN5A or another gene.",Brugada syndrome,0000140,GHR,https://ghr.nlm.nih.gov/condition/brugada-syndrome,C1142166,T047,Disorders
Is Brugada syndrome inherited ?,0000140-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.",Brugada syndrome,0000140,GHR,https://ghr.nlm.nih.gov/condition/brugada-syndrome,C1142166,T047,Disorders
What are the treatments for Brugada syndrome ?,0000140-5,treatment,These resources address the diagnosis or management of Brugada syndrome:  - Gene Review: Gene Review: Brugada Syndrome  - Genetic Testing Registry: Brugada syndrome  - Genetic Testing Registry: Brugada syndrome 1  - MedlinePlus Encyclopedia: Arrhythmias   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Brugada syndrome,0000140,GHR,https://ghr.nlm.nih.gov/condition/brugada-syndrome,C1142166,T047,Disorders
What is (are) Buschke-Ollendorff syndrome ?,0000141-1,information,"Buschke-Ollendorff syndrome is a hereditary disorder of connective tissues, which are tissues that provide strength and flexibility to structures throughout the body. Specifically, the condition is characterized by skin growths called connective tissue nevi and a bone abnormality known as osteopoikilosis.  Connective tissue nevi are small, noncancerous lumps on the skin. They tend to appear in childhood and are widespread in people with Buschke-Ollendorff syndrome. The most common form of these nevi are elastomas, which are made up of a type of stretchy connective tissue called elastic fibers. Less commonly, affected individuals have nevi called collagenomas, which are made up of another type of connective tissue called collagen.  Osteopoikilosis, which is from the Greek words for ""spotted bones,"" is a skeletal abnormality characterized by small, round areas of increased bone density that appear as brighter spots on x-rays. Osteopoikilosis usually occurs near the ends of the long bones of the arms and legs, and in the bones of the hands, feet, and pelvis. The areas of increased bone density appear during childhood. They do not cause pain or other health problems.",Buschke-Ollendorff syndrome,0000141,GHR,https://ghr.nlm.nih.gov/condition/buschke-ollendorff-syndrome,C0265514,T047,Disorders
How many people are affected by Buschke-Ollendorff syndrome ?,0000141-2,frequency,"Buschke-Ollendorff syndrome has an estimated incidence of 1 in 20,000 people worldwide.",Buschke-Ollendorff syndrome,0000141,GHR,https://ghr.nlm.nih.gov/condition/buschke-ollendorff-syndrome,C0265514,T047,Disorders
What are the genetic changes related to Buschke-Ollendorff syndrome ?,0000141-3,genetic changes,"Buschke-Ollendorff syndrome results from mutations in the LEMD3 gene. This gene provides instructions for making a protein that helps control signaling through two chemical pathways known as the bone morphogenic protein (BMP) and transforming growth factor-beta (TGF-) pathways. These signaling pathways regulate various cellular processes and are involved in the growth of cells, including new bone cells.  Mutations in the LEMD3 gene reduce the amount of functional LEMD3 protein that is produced. A shortage of this protein prevents it from controlling BMP and TGF- signaling effectively, leading to increased signaling through both of these pathways. Studies suggest that the enhanced signaling increases the formation of bone tissue, resulting in areas of overly dense bone. It is unclear how it is related to the development of connective tissue nevi in people with Buschke-Ollendorff syndrome.",Buschke-Ollendorff syndrome,0000141,GHR,https://ghr.nlm.nih.gov/condition/buschke-ollendorff-syndrome,C0265514,T047,Disorders
Is Buschke-Ollendorff syndrome inherited ?,0000141-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In many cases, an affected person has a parent and other family members with the condition. While most people with Buschke-Ollendorff syndrome have both connective tissue nevi and osteopoikilosis, some affected families include individuals who have the skin abnormalities alone or the bone abnormalities alone. When osteopoikilosis occurs without connective tissue nevi, the condition is often called isolated osteopoikilosis.",Buschke-Ollendorff syndrome,0000141,GHR,https://ghr.nlm.nih.gov/condition/buschke-ollendorff-syndrome,C0265514,T047,Disorders
What are the treatments for Buschke-Ollendorff syndrome ?,0000141-5,treatment,These resources address the diagnosis or management of Buschke-Ollendorff syndrome:  - Genetic Testing Registry: Dermatofibrosis lenticularis disseminata   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Buschke-Ollendorff syndrome,0000141,GHR,https://ghr.nlm.nih.gov/condition/buschke-ollendorff-syndrome,C0265514,T047,Disorders
What is (are) C3 glomerulopathy ?,0000142-1,information,"C3 glomerulopathy is a group of related conditions that cause the kidneys to malfunction. The major features of C3 glomerulopathy include high levels of protein in the urine (proteinuria), blood in the urine (hematuria), reduced amounts of urine, low levels of protein in the blood, and swelling in many areas of the body. Affected individuals may have particularly low levels of a protein called complement component 3 (or C3) in the blood.  The kidney problems associated with C3 glomerulopathy tend to worsen over time. About half of affected individuals develop end-stage renal disease (ESRD) within 10 years after their diagnosis. ESRD is a life-threatening condition that prevents the kidneys from filtering fluids and waste products from the body effectively.  Researchers have identified two major forms of C3 glomerulopathy: dense deposit disease and C3 glomerulonephritis. Although the two disorders cause similar kidney problems, the features of dense deposit disease tend to appear earlier than those of C3 glomerulonephritis, usually in adolescence. However, the signs and symptoms of either disease may not begin until adulthood.  One of the two forms of C3 glomerulopathy, dense deposit disease, can also be associated with other conditions unrelated to kidney function. For example, people with dense deposit disease may have acquired partial lipodystrophy, a condition characterized by a lack of fatty (adipose) tissue under the skin in the upper part of the body. Additionally, some people with dense deposit disease develop a buildup of yellowish deposits called drusen in the light-sensitive tissue at the back of the eye (the retina). These deposits usually appear in childhood or adolescence and can cause vision problems later in life.",C3 glomerulopathy,0000142,GHR,https://ghr.nlm.nih.gov/condition/c3-glomerulopathy,C0268731,T047,Disorders
How many people are affected by C3 glomerulopathy ?,0000142-2,frequency,"C3 glomerulopathy is very rare, affecting 1 to 2 per million people worldwide. It is equally common in men and women.",C3 glomerulopathy,0000142,GHR,https://ghr.nlm.nih.gov/condition/c3-glomerulopathy,C0268731,T047,Disorders
What are the genetic changes related to C3 glomerulopathy ?,0000142-3,genetic changes,"C3 glomerulopathy is associated with changes in many genes. Most of these genes provide instructions for making proteins that help regulate a part of the body's immune response known as the complement system. This system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. The complement system must be carefully regulated so it targets only unwanted materials and does not damage the body's healthy cells.  A specific mutation in one of the complement system-related genes, CFHR5, has been found to cause C3 glomerulopathy in people from the Mediterranean island of Cyprus. Mutation in the C3 and CFH genes, as well as other complement system-related genes, have been found to cause the condition in other populations. The known mutations account for only a small percentage of all cases of C3 glomerulopathy. In most cases, the cause of the condition is unknown.  Several normal variants (polymorphisms) in complement system-related genes are associated with an increased likelihood of developing C3 glomerulopathy. In some cases, the increased risk is related to a group of specific variants in several genes, a combination known as a C3 glomerulopathy at-risk haplotype. While these polymorphisms increase the risk of C3 glomerulopathy, many people who inherit these genetic changes will never develop the condition.  The genetic changes related to C3 glomerulopathy ""turn up,"" or increase the activation of, the complement system. The overactive system damages structures called glomeruli in the kidneys. These structures are clusters of tiny blood vessels that help filter waste products from the blood. Damage to glomeruli prevents the kidneys from filtering waste products normally and can lead to ESRD. Studies suggest that uncontrolled activation of the complement system also causes the other health problems that can occur with dense deposit disease, including acquired partial lipodystrophy and a buildup of drusen in the retina. Researchers are working to determine how these associated health problems are related to overactivity of the complement system.  Studies suggest that C3 glomerulopathy can also result from the presence of specialized proteins called autoantibodies. Autoantibodies cause the condition by altering the activity of proteins involved in regulating the complement system.",C3 glomerulopathy,0000142,GHR,https://ghr.nlm.nih.gov/condition/c3-glomerulopathy,C0268731,T047,Disorders
Is C3 glomerulopathy inherited ?,0000142-4,inheritance,"Most cases of C3 glomerulopathy are sporadic, which means they occur in people with no history of the disorder in their family. Only a few reported families have had more than one family member with C3 glomerulopathy. However, many affected people have had close relatives with autoimmune diseases, which occur when the immune system malfunctions and attacks the body's tissues and organs. The connection between C3 glomerulopathy and autoimmune diseases is not fully understood.",C3 glomerulopathy,0000142,GHR,https://ghr.nlm.nih.gov/condition/c3-glomerulopathy,C0268731,T047,Disorders
What are the treatments for C3 glomerulopathy ?,0000142-5,treatment,"These resources address the diagnosis or management of C3 glomerulopathy:  - Gene Review: Gene Review: Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II  - Genetic Testing Registry: C3 Glomerulonephritis  - Genetic Testing Registry: CFHR5 deficiency  - Genetic Testing Registry: CFHR5-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II  - Genetic Testing Registry: Factor H deficiency  - Genetic Testing Registry: Mesangiocapillary glomerulonephritis, type II  - National Institute of Diabetes and Digestive and Kidney Diseases: Kidney Failure: Choosing a Treatment That's Right for You   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",C3 glomerulopathy,0000142,GHR,https://ghr.nlm.nih.gov/condition/c3-glomerulopathy,C0268731,T047,Disorders
What is (are) Caffey disease ?,0000143-1,information,"Caffey disease, also called infantile cortical hyperostosis, is a bone disorder that most often occurs in babies. Excessive new bone formation (hyperostosis) is characteristic of Caffey disease. The bone abnormalities mainly affect the jawbone, shoulder blades (scapulae), collarbones (clavicles), and the shafts (diaphyses) of long bones in the arms and legs. Affected bones may double or triple in width, which can be seen by x-ray imaging. In some cases two bones that are next to each other, such as two ribs or the pairs of long bones in the forearms (radius and ulna) or lower legs (tibia and fibula) become fused together. Babies with Caffey disease also have swelling of joints and of soft tissues such as muscles, with pain and redness in the affected areas. Affected infants can also be feverish and irritable.  The signs and symptoms of Caffey disease are usually apparent by the time an infant is 5 months old. In rare cases, skeletal abnormalities can be detected by ultrasound imaging during the last few weeks of development before birth. Lethal prenatal cortical hyperostosis, a more severe disorder that appears earlier in development and is often fatal before or shortly after birth, is sometimes called lethal prenatal Caffey disease; however, it is generally considered to be a separate disorder.  For unknown reasons, the swelling and pain associated with Caffey disease typically go away within a few months. Through a normal process called bone remodeling, which replaces old bone tissue with new bone, the excess bone is usually reabsorbed by the body and undetectable on x-ray images by the age of 2. However, if two adjacent bones have fused, they may remain that way, possibly resulting in complications. For example, fused rib bones can lead to curvature of the spine (scoliosis) or limit expansion of the chest, resulting in breathing problems.  Most people with Caffey disease have no further problems related to the disorder after early childhood. Occasionally, another episode of hyperostosis occurs years later. In addition, some adults who had Caffey disease in infancy have other abnormalities of the bones and connective tissues, which provide strength and flexibility to structures throughout the body. Affected adults may have loose joints (joint laxity), stretchy (hyperextensible) skin, or be prone to protrusion of organs through gaps in muscles (hernias).",Caffey disease,0000143,GHR,https://ghr.nlm.nih.gov/condition/caffey-disease,C0020497,T047,Disorders
How many people are affected by Caffey disease ?,0000143-2,frequency,"Caffey disease has been estimated to occur in approximately 3 per 1,000 infants worldwide. A few hundred cases have been described in the medical literature. Researchers believe this condition is probably underdiagnosed because it usually goes away by itself in early childhood.",Caffey disease,0000143,GHR,https://ghr.nlm.nih.gov/condition/caffey-disease,C0020497,T047,Disorders
What are the genetic changes related to Caffey disease ?,0000143-3,genetic changes,"A mutation in the COL1A1 gene causes Caffey disease. The COL1A1 gene provides instructions for making part of a large molecule called type I collagen. Collagens are a family of proteins that strengthen and support many tissues in the body, including cartilage, bone, tendon, and skin. In these tissues, type I collagen is found in the spaces around cells. The collagen molecules are cross-linked in long, thin, fibrils that are very strong and flexible. Type I collagen is the most abundant form of collagen in the human body.  The COL1A1 gene mutation that causes Caffey disease replaces the protein building block (amino acid) arginine with the amino acid cysteine at protein position 836 (written as Arg836Cys or R836C). This mutation results in the production of type I collagen fibrils that are variable in size and shape, but it is unknown how these changes lead to the signs and symptoms of Caffey disease.",Caffey disease,0000143,GHR,https://ghr.nlm.nih.gov/condition/caffey-disease,C0020497,T047,Disorders
Is Caffey disease inherited ?,0000143-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is usually sufficient to cause the disorder. About 20 percent of people who have the mutation that causes Caffey disease do not experience its signs or symptoms; this phenomenon is called incomplete penetrance.  In some cases, an affected person inherits the mutation that causes Caffey disease from a parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",Caffey disease,0000143,GHR,https://ghr.nlm.nih.gov/condition/caffey-disease,C0020497,T047,Disorders
What are the treatments for Caffey disease ?,0000143-5,treatment,These resources address the diagnosis or management of Caffey disease:  - Cedars-Sinai: Skeletal Dysplasia  - Gene Review: Gene Review: Caffey Disease  - Genetic Testing Registry: Infantile cortical hyperostosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Caffey disease,0000143,GHR,https://ghr.nlm.nih.gov/condition/caffey-disease,C0020497,T047,Disorders
What is (are) campomelic dysplasia ?,0000144-1,information,"Campomelic dysplasia is a severe disorder that affects development of the skeleton, reproductive system, and other parts of the body. This condition is often life-threatening in the newborn period.  The term ""campomelic"" comes from the Greek words for ""bent limb."" Affected individuals are typically born with bowing of the long bones in the legs, and occasionally, bowing in the arms. Bowing can cause characteristic skin dimples to form over the curved bone, especially on the lower legs. People with campomelic dysplasia usually have short legs, dislocated hips, underdeveloped shoulder blades, 11 pairs of ribs instead of 12, bone abnormalities in the neck, and inward- and upward-turning feet (clubfeet). These skeletal abnormalities begin developing before birth and can often be seen on ultrasound. When affected individuals have features of this disorder but do not have bowed limbs, they are said to have acampomelic campomelic dysplasia.  Many people with campomelic dysplasia have external genitalia that do not look clearly male or clearly female (ambiguous genitalia). Approximately 75 percent of affected individuals with a typical male chromosome pattern (46,XY) have ambiguous genitalia or normal female genitalia. Internal reproductive organs may not correspond with the external genitalia; the internal organs can be male (testes), female (ovaries), or a combination of the two. For example, an individual with female external genitalia may have testes or a combination of testes and ovaries.  Affected individuals have distinctive facial features, including a small chin, prominent eyes, and a flat face. They also have a large head compared to their body size. A particular group of physical features, called Pierre Robin sequence, is common in people with campomelic dysplasia. Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate), a tongue that is placed further back than normal (glossoptosis), and a small lower jaw (micrognathia). People with campomelic dysplasia are often born with weakened cartilage that forms the upper respiratory tract. This abnormality, called laryngotracheomalacia, partially blocks the airway and causes difficulty breathing. Laryngotracheomalacia contributes to the poor survival of infants with campomelic dysplasia.  Only a few people with campomelic dysplasia survive past infancy. As these individuals age, they may develop an abnormal curvature of the spine (scoliosis) and other spine abnormalities that compress the spinal cord. People with campomelic dysplasia may also have short stature and hearing loss.",campomelic dysplasia,0000144,GHR,https://ghr.nlm.nih.gov/condition/campomelic-dysplasia,C1861922,T019,Disorders
How many people are affected by campomelic dysplasia ?,0000144-2,frequency,"The prevalence of campomelic dysplasia is uncertain; estimates range from 1 in 40,000 to 200,000 people.",campomelic dysplasia,0000144,GHR,https://ghr.nlm.nih.gov/condition/campomelic-dysplasia,C1861922,T019,Disorders
What are the genetic changes related to campomelic dysplasia ?,0000144-3,genetic changes,"Mutations in or near the SOX9 gene cause campomelic dysplasia. This gene provides instructions for making a protein that plays a critical role in the formation of many different tissues and organs during embryonic development. The SOX9 protein regulates the activity of other genes, especially those that are important for development of the skeleton and reproductive organs.  Most cases of campomelic dysplasia are caused by mutations within the SOX9 gene. These mutations prevent the production of the SOX9 protein or result in a protein with impaired function. About 5 percent of cases are caused by chromosome abnormalities that occur near the SOX9 gene; these cases tend to be milder than those caused by mutations within the SOX9 gene. The chromosome abnormalities disrupt regions of DNA that normally regulate the activity of the SOX9 gene. All of these genetic changes prevent the SOX9 protein from properly controlling the genes essential for normal development of the skeleton, reproductive system, and other parts of the body. Abnormal development of these structures causes the signs and symptoms of campomelic dysplasia.",campomelic dysplasia,0000144,GHR,https://ghr.nlm.nih.gov/condition/campomelic-dysplasia,C1861922,T019,Disorders
Is campomelic dysplasia inherited ?,0000144-4,inheritance,"Campomelic dysplasia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in or near the SOX9 gene and occur in people with no history of the disorder in their family. Rarely, affected individuals inherit a chromosome abnormality from a parent who may or may not show mild signs and symptoms of campomelic dysplasia.",campomelic dysplasia,0000144,GHR,https://ghr.nlm.nih.gov/condition/campomelic-dysplasia,C1861922,T019,Disorders
What are the treatments for campomelic dysplasia ?,0000144-5,treatment,These resources address the diagnosis or management of campomelic dysplasia:  - European Skeletal Dysplasia Network  - Gene Review: Gene Review: Campomelic Dysplasia  - Genetic Testing Registry: Camptomelic dysplasia  - MedlinePlus Encyclopedia: Ambiguous Genitalia  - MedlinePlus Encyclopedia: Pierre-Robin Syndrome  - The Hospital for Sick Children   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,campomelic dysplasia,0000144,GHR,https://ghr.nlm.nih.gov/condition/campomelic-dysplasia,C1861922,T019,Disorders
What is (are) Camurati-Engelmann disease ?,0000145-1,information,"Camurati-Engelmann disease is a condition that mainly affects the bones. People with this disease have increased bone density, particularly affecting the long bones of the arms and legs. In some cases, the skull and hip bones are also affected. The thickened bones can lead to pain in the arms and legs, a waddling walk, muscle weakness, and extreme tiredness. An increase in the density of the skull results in increased pressure on the brain and can cause a variety of neurological problems, including headaches, hearing loss, vision problems, dizziness (vertigo), ringing in the ears (tinnitus), and facial paralysis. The added pressure that thickened bones put on the muscular and skeletal systems can cause abnormal curvature of the spine (scoliosis), joint deformities (contractures), knock knees, and flat feet (pes planus). Other features of Camurati-Engelmann disease include abnormally long limbs in proportion to height, a decrease in muscle mass and body fat, and delayed puberty.  The age at which affected individuals first experience symptoms varies greatly; however, most people with this condition develop pain or weakness by adolescence. In some instances, people have the gene mutation that causes Camurati-Engelmann disease but never develop the characteristic features of this condition.",Camurati-Engelmann disease,0000145,GHR,https://ghr.nlm.nih.gov/condition/camurati-engelmann-disease,C0011989,T019,Disorders
How many people are affected by Camurati-Engelmann disease ?,0000145-2,frequency,The prevalence of Camurati-Engelmann disease is unknown. Approximately 200 cases have been reported worldwide.,Camurati-Engelmann disease,0000145,GHR,https://ghr.nlm.nih.gov/condition/camurati-engelmann-disease,C0011989,T019,Disorders
What are the genetic changes related to Camurati-Engelmann disease ?,0000145-3,genetic changes,"Mutations in the TGFB1 gene cause Camurati-Engelmann disease. The TGFB1 gene provides instructions for producing a protein called transforming growth factor beta-1 (TGF-1). The TGF-1 protein helps control the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement (motility), and the self-destruction of cells (apoptosis). The TGF-1 protein is found throughout the body and plays a role in development before birth, the formation of blood vessels, the regulation of muscle tissue and body fat development, wound healing, and immune system function. TGF-1 is particularly abundant in tissues that make up the skeleton, where it helps regulate bone growth, and in the intricate lattice that forms in the spaces between cells (the extracellular matrix).  Within cells, the TGF-1 protein is turned off (inactive) until it receives a chemical signal to become active. The TGFB1 gene mutations that cause Camurati-Engelmann disease result in the production of a TGF-1 protein that is always turned on (active). Overactive TGF-1 proteins lead to increased bone density and decreased body fat and muscle tissue, contributing to the signs and symptoms of Camurati-Engelmann disease.  Some individuals with Camurati-Engelmann disease do not have identified mutations in the TGFB1 gene. In these cases, the cause of the condition is unknown.",Camurati-Engelmann disease,0000145,GHR,https://ghr.nlm.nih.gov/condition/camurati-engelmann-disease,C0011989,T019,Disorders
Is Camurati-Engelmann disease inherited ?,0000145-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Camurati-Engelmann disease,0000145,GHR,https://ghr.nlm.nih.gov/condition/camurati-engelmann-disease,C0011989,T019,Disorders
What are the treatments for Camurati-Engelmann disease ?,0000145-5,treatment,These resources address the diagnosis or management of Camurati-Engelmann disease:  - Gene Review: Gene Review: Camurati-Engelmann Disease  - Genetic Testing Registry: Diaphyseal dysplasia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Camurati-Engelmann disease,0000145,GHR,https://ghr.nlm.nih.gov/condition/camurati-engelmann-disease,C0011989,T019,Disorders
What is (are) Canavan disease ?,0000146-1,information,"Canavan disease is a rare inherited disorder that damages the ability of nerve cells (neurons) in the brain to send and receive messages. This disease is one of a group of genetic disorders called leukodystrophies. Leukodystrophies disrupt the growth or maintenance of the myelin sheath, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses.  Neonatal/infantile Canavan disease is the most common and most severe form of the condition. Affected infants appear normal for the first few months of life, but by age 3 to 5 months, problems with development become noticeable. These infants usually do not develop motor skills such as turning over, controlling head movement, and sitting without support. Other common features of this condition include weak muscle tone (hypotonia), an unusually large head size (macrocephaly), and irritability. Feeding and swallowing difficulties, seizures, and sleep disturbances may also develop.  The mild/juvenile form of Canavan disease is less common. Affected individuals have mildly delayed development of speech and motor skills starting in childhood. These delays may be so mild and nonspecific that they are never recognized as being caused by Canavan disease.  The life expectancy for people with Canavan disease varies. Most people with the neonatal/infantile form live only into childhood, although some survive into adolescence or beyond. People with the mild/juvenile form do not appear to have a shortened lifespan.",Canavan disease,0000146,GHR,https://ghr.nlm.nih.gov/condition/canavan-disease,C0206307,T047,Disorders
How many people are affected by Canavan disease ?,0000146-2,frequency,"While this condition occurs in people of all ethnic backgrounds, it is most common in people of Ashkenazi (eastern and central European) Jewish heritage. Studies suggest that this disorder affects 1 in 6,400 to 13,500 people in the Ashkenazi Jewish population. The incidence in other populations is unknown.",Canavan disease,0000146,GHR,https://ghr.nlm.nih.gov/condition/canavan-disease,C0206307,T047,Disorders
What are the genetic changes related to Canavan disease ?,0000146-3,genetic changes,"Mutations in the ASPA gene cause Canavan disease. The ASPA gene provides instructions for making an enzyme called aspartoacylase. This enzyme normally breaks down a compound called N-acetyl-L-aspartic acid (NAA), which is predominantly found in neurons in the brain. The function of NAA is unclear. Researchers had suspected that it played a role in the production of the myelin sheath, but recent studies suggest that NAA does not have this function. The enzyme may instead be involved in the transport of water molecules out of neurons.  Mutations in the ASPA gene reduce the function of aspartoacylase, which prevents the normal breakdown of NAA. The mutations that cause the neonatal/infantile form of Canavan disease severely impair the enzyme's activity, allowing NAA to build up to high levels in the brain. The mutations that cause the mild/juvenile form of the disorder have milder effects on the enzyme's activity, leading to less accumulation of NAA.  An excess of NAA in the brain is associated with the signs and symptoms of Canavan disease. Studies suggest that if NAA is not broken down properly, the resulting chemical imbalance interferes with the formation of the myelin sheath as the nervous system develops. A buildup of NAA also leads to the progressive destruction of existing myelin sheaths. Nerves without this protective covering malfunction, which disrupts normal brain development.",Canavan disease,0000146,GHR,https://ghr.nlm.nih.gov/condition/canavan-disease,C0206307,T047,Disorders
Is Canavan disease inherited ?,0000146-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Canavan disease,0000146,GHR,https://ghr.nlm.nih.gov/condition/canavan-disease,C0206307,T047,Disorders
What are the treatments for Canavan disease ?,0000146-5,treatment,"These resources address the diagnosis or management of Canavan disease:  - Gene Review: Gene Review: Canavan Disease  - Genetic Testing Registry: Canavan disease, mild  - Genetic Testing Registry: Spongy degeneration of central nervous system  - MedlinePlus Encyclopedia: Canavan Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Canavan disease,0000146,GHR,https://ghr.nlm.nih.gov/condition/canavan-disease,C0206307,T047,Disorders
What is (are) Cant syndrome ?,0000147-1,information,"Cant syndrome is a rare condition characterized by excess hair growth (hypertrichosis), a distinctive facial appearance, heart defects, and several other abnormalities. The features of the disorder vary among affected individuals.  People with Cant syndrome have thick scalp hair that extends onto the forehead and grows down onto the cheeks in front of the ears. They also have increased body hair, especially on the back, arms, and legs. Most affected individuals have a large head (macrocephaly) and distinctive facial features that are described as ""coarse."" These include a broad nasal bridge, skin folds covering the inner corner of the eyes (epicanthal folds), and a wide mouth with full lips. As affected individuals get older, the face lengthens, the chin becomes more prominent, and the eyes become deep-set.  Many infants with Cant syndrome are born with a heart defect such as an enlarged heart (cardiomegaly) or patent ductus arteriosus (PDA). The ductus arteriosus is a connection between two major arteries, the aorta and the pulmonary artery. This connection is open during fetal development and normally closes shortly after birth. However, the ductus arteriosus remains open, or patent, in babies with PDA. Other heart problems have also been found in people with Cant syndrome, including an abnormal buildup of fluid around the heart (pericardial effusion) and high blood pressure in the blood vessels that carry blood from the heart to the lungs (pulmonary hypertension).  Additional features of this condition include distinctive skeletal abnormalities, a large body size (macrosomia) at birth, a reduced amount of fat under the skin (subcutaneous fat) beginning in childhood, deep horizontal creases in the palms of the hands and soles of the feet, and an increased susceptibility to respiratory infections. Other signs and symptoms that have been reported include abnormal swelling in the body's tissues (lymphedema), side-to-side curvature of the spine (scoliosis), and reduced bone density (osteopenia). Some affected children have weak muscle tone (hypotonia) that delays the development of motor skills such as sitting, standing, and walking. Most have mildly delayed speech, and some affected children have mild intellectual disability or learning problems.",Cant syndrome,0000147,GHR,https://ghr.nlm.nih.gov/condition/cantu-syndrome,C0039082,T047,Disorders
How many people are affected by Cant syndrome ?,0000147-2,frequency,Cant syndrome is a rare condition. About three dozen affected individuals have been reported in the medical literature.,Cant syndrome,0000147,GHR,https://ghr.nlm.nih.gov/condition/cantu-syndrome,C0039082,T047,Disorders
What are the genetic changes related to Cant syndrome ?,0000147-3,genetic changes,"Cant syndrome results from mutations in the ABCC9 gene. This gene provides instructions for making one part (subunit) of a channel that transports charged potassium atoms (potassium ions) across cell membranes. Mutations in the ABCC9 gene alter the structure of the potassium channel, which causes the channel to open when it should be closed. It is unknown how this problem with potassium channel function leads to excess hair growth, heart defects, and the other features of Cant syndrome.",Cant syndrome,0000147,GHR,https://ghr.nlm.nih.gov/condition/cantu-syndrome,C0039082,T047,Disorders
Is Cant syndrome inherited ?,0000147-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered ABCC9 gene in each cell is sufficient to cause the disorder.  Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family. In a few reported cases, an affected person has inherited the mutation from one affected parent.",Cant syndrome,0000147,GHR,https://ghr.nlm.nih.gov/condition/cantu-syndrome,C0039082,T047,Disorders
What are the treatments for Cant syndrome ?,0000147-5,treatment,These resources address the diagnosis or management of Cant syndrome:  - Gene Review: Gene Review: Cant syndrome  - Genetic Testing Registry: Hypertrichotic osteochondrodysplasia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Cant syndrome,0000147,GHR,https://ghr.nlm.nih.gov/condition/cantu-syndrome,C0039082,T047,Disorders
What is (are) cap myopathy ?,0000148-1,information,"Cap myopathy is a disorder that primarily affects skeletal muscles, which are muscles that the body uses for movement. People with cap myopathy have muscle weakness (myopathy) and poor muscle tone (hypotonia) throughout the body, but they are most severely affected in the muscles of the face, neck, and limbs. The muscle weakness, which begins at birth or during childhood, can worsen over time.  Affected individuals may have feeding and swallowing difficulties in infancy. They typically have delayed development of motor skills such as sitting, crawling, standing, and walking. They may fall frequently, tire easily, and have difficulty running, climbing stairs, or jumping. In some cases, the muscles used for breathing are affected, and life-threatening breathing difficulties can occur.  People with cap myopathy may have a high arch in the roof of the mouth (high-arched palate), severely drooping eyelids (ptosis), and a long face. Some affected individuals develop an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis).  The name cap myopathy comes from characteristic abnormal cap-like structures that can be seen in muscle cells when muscle tissue is viewed under a microscope. The severity of cap myopathy is related to the percentage of muscle cells that have these caps. Individuals in whom 70 to 75 percent of muscle cells have caps typically have severe breathing problems and may not survive childhood, while those in whom 10 to 30 percent of muscle cells have caps have milder symptoms and can live into adulthood.",cap myopathy,0000148,GHR,https://ghr.nlm.nih.gov/condition/cap-myopathy,C3710589,T019,Disorders
How many people are affected by cap myopathy ?,0000148-2,frequency,Cap myopathy is a rare disorder that has been identified in only a small number of individuals. Its exact prevalence is unknown.,cap myopathy,0000148,GHR,https://ghr.nlm.nih.gov/condition/cap-myopathy,C3710589,T019,Disorders
What are the genetic changes related to cap myopathy ?,0000148-3,genetic changes,"Mutations in the ACTA1, TPM2, or TPM3 genes can cause cap myopathy. These genes provide instructions for producing proteins that play important roles in skeletal muscles.  The ACTA1 gene provides instructions for making a protein called skeletal alpha ()-actin, which is part of the actin protein family. Actin proteins are important for cell movement and the tensing of muscle fibers (muscle contraction). Thin filaments made up of actin molecules and thick filaments made up of another protein called myosin are the primary components of muscle fibers and are important for muscle contraction. Attachment (binding) and release of the overlapping thick and thin filaments allows them to move relative to each other so that the muscles can contract. The mutation in the ACTA1 gene that causes cap myopathy results in an abnormal protein that may interfere with the proper assembly of thin filaments. The cap structures in muscle cells characteristic of this disorder are composed of disorganized thin filaments.  The TPM2 and TPM3 genes provide instructions for making proteins that are members of the tropomyosin protein family. Tropomyosin proteins regulate muscle contraction by attaching to actin and controlling its binding to myosin. The specific effects of TPM2 and TPM3 gene mutations are unclear, but researchers suggest they may interfere with normal actin-myosin binding between the thin and thick filaments, impairing muscle contraction and resulting in the muscle weakness that occurs in cap myopathy.",cap myopathy,0000148,GHR,https://ghr.nlm.nih.gov/condition/cap-myopathy,C3710589,T019,Disorders
Is cap myopathy inherited ?,0000148-4,inheritance,"Cap myopathy is an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases are not inherited; they result from new mutations in the gene and occur in people with no history of the disorder in their family.",cap myopathy,0000148,GHR,https://ghr.nlm.nih.gov/condition/cap-myopathy,C3710589,T019,Disorders
What are the treatments for cap myopathy ?,0000148-5,treatment,These resources address the diagnosis or management of cap myopathy:  - Genetic Testing Registry: TPM2-related cap myopathy  - Genetic Testing Registry: cap myopathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,cap myopathy,0000148,GHR,https://ghr.nlm.nih.gov/condition/cap-myopathy,C3710589,T019,Disorders
What is (are) capillary malformation-arteriovenous malformation syndrome ?,0000149-1,information,"Capillary malformation-arteriovenous malformation syndrome (CM-AVM) is a disorder of the vascular system, which is the body's complex network of blood vessels. The vascular system consists of arteries, which carry oxygen-rich blood from the heart to the body's various organs and tissues; veins, which carry blood back to the heart; and capillaries, which are tiny blood vessels that connect arteries and veins.  CM-AVM is characterized by capillary malformations (CMs), which are composed of enlarged capillaries that increase blood flow near the surface of the skin. These malformations look like multiple small, round, pink or red spots on the skin. In most affected individuals, capillary malformations occur on the face, arms, and legs. These spots may be visible from birth or may develop during childhood. By themselves, capillary malformations usually do not cause any health problems.  In some people with CM-AVM, capillary malformations are the only sign of the disorder. However, other affected individuals also have more serious vascular abnormalities known as arteriovenous malformations (AVMs) and arteriovenous fistulas (AVFs). AVMs and AVFs are abnormal connections between arteries, veins, and capillaries that affect blood circulation. Depending on where they occur in the body, these abnormalities can be associated with complications including abnormal bleeding, migraine headaches, seizures, and heart failure. In some cases the complications can be life-threatening. In people with CM-AVM, complications of AVMs and AVFs tend to appear in infancy or early childhood; however, some of these vascular abnormalities never cause any symptoms.  Some vascular abnormalities seen in CM-AVM are similar to those that occur in a condition called Parkes Weber syndrome. In addition to vascular abnormalities, Parkes Weber syndrome usually involves overgrowth of one limb. CM-AVM and some cases of Parkes Weber syndrome have the same genetic cause.",capillary malformation-arteriovenous malformation syndrome,0000149,GHR,https://ghr.nlm.nih.gov/condition/capillary-malformation-arteriovenous-malformation-syndrome,C1842180,T019,Disorders
How many people are affected by capillary malformation-arteriovenous malformation syndrome ?,0000149-2,frequency,"CM-AVM is thought to occur in at least 1 in 100,000 people of northern European origin. The prevalence of the condition in other populations is unknown.",capillary malformation-arteriovenous malformation syndrome,0000149,GHR,https://ghr.nlm.nih.gov/condition/capillary-malformation-arteriovenous-malformation-syndrome,C1842180,T019,Disorders
What are the genetic changes related to capillary malformation-arteriovenous malformation syndrome ?,0000149-3,genetic changes,"CM-AVM is caused by mutations in the RASA1 gene. This gene provides instructions for making a protein known as p120-RasGAP, which is involved in transmitting chemical signals from outside the cell to the nucleus. These signals help control several important cell functions, including cell growth and division (proliferation), the process by which cells mature to carry out specific functions (differentiation), and cell movement. The role of the p120-RasGAP protein is not fully understood, although it appears to be essential for the normal development of the vascular system.  Mutations in the RASA1 gene lead to the production of a nonfunctional version of the p120-RasGAP protein. A loss of this protein's activity disrupts tightly regulated chemical signaling during development. However, it is unclear how these changes lead to the specific vascular abnormalities seen in people with CM-AVM.",capillary malformation-arteriovenous malformation syndrome,0000149,GHR,https://ghr.nlm.nih.gov/condition/capillary-malformation-arteriovenous-malformation-syndrome,C1842180,T019,Disorders
Is capillary malformation-arteriovenous malformation syndrome inherited ?,0000149-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",capillary malformation-arteriovenous malformation syndrome,0000149,GHR,https://ghr.nlm.nih.gov/condition/capillary-malformation-arteriovenous-malformation-syndrome,C1842180,T019,Disorders
What are the treatments for capillary malformation-arteriovenous malformation syndrome ?,0000149-5,treatment,These resources address the diagnosis or management of CM-AVM:  - Gene Review: Gene Review: RASA1-Related Disorders  - Genetic Testing Registry: Capillary malformation-arteriovenous malformation   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,capillary malformation-arteriovenous malformation syndrome,0000149,GHR,https://ghr.nlm.nih.gov/condition/capillary-malformation-arteriovenous-malformation-syndrome,C1842180,T019,Disorders
What is (are) carbamoyl phosphate synthetase I deficiency ?,0000150-1,information,"Carbamoyl phosphate synthetase I deficiency is an inherited disorder that causes ammonia to accumulate in the blood (hyperammonemia). Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The brain is especially sensitive to the effects of excess ammonia.  In the first few days of life, infants with carbamoyl phosphate synthetase I deficiency typically exhibit the effects of hyperammonemia, which may include unusual sleepiness, poorly regulated breathing rate or body temperature, unwillingness to feed, vomiting after feeding, unusual body movements, seizures, or coma. Affected individuals who survive the newborn period may experience recurrence of these symptoms if diet is not carefully managed or if they experience infections or other stressors. They may also have delayed development and intellectual disability.  In some people with carbamoyl phosphate synthetase I deficiency, signs and symptoms may be less severe and appear later in life.",carbamoyl phosphate synthetase I deficiency,0000150,GHR,https://ghr.nlm.nih.gov/condition/carbamoyl-phosphate-synthetase-i-deficiency,C0751753,T047,Disorders
How many people are affected by carbamoyl phosphate synthetase I deficiency ?,0000150-2,frequency,"Carbamoyl phosphate synthetase I deficiency is a rare disorder; its overall incidence is unknown. Researchers in Japan have estimated that it occurs in 1 in 800,000 newborns in that country.",carbamoyl phosphate synthetase I deficiency,0000150,GHR,https://ghr.nlm.nih.gov/condition/carbamoyl-phosphate-synthetase-i-deficiency,C0751753,T047,Disorders
What are the genetic changes related to carbamoyl phosphate synthetase I deficiency ?,0000150-3,genetic changes,"Mutations in the CPS1 gene cause carbamoyl phosphate synthetase I deficiency. The CPS1 gene provides instructions for making the enzyme carbamoyl phosphate synthetase I. This enzyme participates in the urea cycle, which is a sequence of biochemical reactions that occurs in liver cells. The urea cycle processes excess nitrogen, generated when protein is broken down by the body, to make a compound called urea that is excreted by the kidneys. The specific role of the carbamoyl phosphate synthetase I enzyme is to control the first step of the urea cycle, a reaction in which excess nitrogen compounds are incorporated into the cycle to be processed.  Carbamoyl phosphate synthetase I deficiency belongs to a class of genetic diseases called urea cycle disorders. In this condition, the carbamoyl phosphate synthetase I enzyme is at low levels (deficient) or absent, and the urea cycle cannot proceed normally. As a result, nitrogen accumulates in the bloodstream in the form of toxic ammonia instead of being converted to less toxic urea and excreted. Ammonia is especially damaging to the brain, and excess ammonia causes neurological problems and other signs and symptoms of carbamoyl phosphate synthetase I deficiency.",carbamoyl phosphate synthetase I deficiency,0000150,GHR,https://ghr.nlm.nih.gov/condition/carbamoyl-phosphate-synthetase-i-deficiency,C0751753,T047,Disorders
Is carbamoyl phosphate synthetase I deficiency inherited ?,0000150-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",carbamoyl phosphate synthetase I deficiency,0000150,GHR,https://ghr.nlm.nih.gov/condition/carbamoyl-phosphate-synthetase-i-deficiency,C0751753,T047,Disorders
What are the treatments for carbamoyl phosphate synthetase I deficiency ?,0000150-5,treatment,"These resources address the diagnosis or management of carbamoyl phosphate synthetase I deficiency:  - Baby's First Test  - Gene Review: Gene Review: Urea Cycle Disorders Overview  - Genetic Testing Registry: Congenital hyperammonemia, type I  - MedlinePlus Encyclopedia: Hereditary Urea Cycle Abnormality   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",carbamoyl phosphate synthetase I deficiency,0000150,GHR,https://ghr.nlm.nih.gov/condition/carbamoyl-phosphate-synthetase-i-deficiency,C0751753,T047,Disorders
What is (are) cardiofaciocutaneous syndrome ?,0000151-1,information,"Cardiofaciocutaneous syndrome is a disorder that affects many parts of the body, particularly the heart (cardio-), facial features (facio-), and the skin and hair (cutaneous). People with this condition also have delayed development and intellectual disability, usually ranging from moderate to severe.  Heart defects occur in most people with cardiofaciocutaneous syndrome. The heart problems most commonly associated with this condition include malformations of one of the heart valves that impairs blood flow from the heart to the lungs (pulmonic stenosis), a hole between the two upper chambers of the heart (atrial septal defect), and a form of heart disease that enlarges and weakens the heart muscle (hypertrophic cardiomyopathy).  Cardiofaciocutaneous syndrome is also characterized by distinctive facial features. These include a high forehead that narrows at the temples, a short nose, widely spaced eyes (ocular hypertelorism), outside corners of the eyes that point downward (down-slanting palpebral fissures), droopy eyelids (ptosis), a small chin, and low-set ears. Overall, the face is broad and long, and the facial features are sometimes described as ""coarse.""  Skin abnormalities occur in almost everyone with cardiofaciocutaneous syndrome. Many affected people have dry, rough skin; dark-colored moles (nevi); wrinkled palms and soles; and a skin condition called keratosis pilaris, which causes small bumps to form on the arms, legs, and face. People with cardiofaciocutaneous syndrome also tend to have thin, dry, curly hair and sparse or absent eyelashes and eyebrows.  Infants with cardiofaciocutaneous syndrome typically have weak muscle tone (hypotonia), feeding difficulties, and a failure to grow and gain weight at the normal rate (failure to thrive). Additional features of this disorder in children and adults can include an unusually large head (macrocephaly), short stature, problems with vision, and seizures.  The signs and symptoms of cardiofaciocutaneous syndrome overlap significantly with those of two other genetic conditions, Costello syndrome and Noonan syndrome. The three conditions are distinguished by their genetic cause and specific patterns of signs and symptoms; however, it can be difficult to tell these conditions apart, particularly in infancy. Unlike Costello syndrome, which significantly increases a person's cancer risk, cancer does not appear to be a major feature of cardiofaciocutaneous syndrome.",cardiofaciocutaneous syndrome,0000151,GHR,https://ghr.nlm.nih.gov/condition/cardiofaciocutaneous-syndrome,C1275081,T019,Disorders
How many people are affected by cardiofaciocutaneous syndrome ?,0000151-2,frequency,Cardiofaciocutaneous syndrome is a very rare condition whose incidence is unknown. Researchers estimate that 200 to 300 people worldwide have this condition.,cardiofaciocutaneous syndrome,0000151,GHR,https://ghr.nlm.nih.gov/condition/cardiofaciocutaneous-syndrome,C1275081,T019,Disorders
What are the genetic changes related to cardiofaciocutaneous syndrome ?,0000151-3,genetic changes,"Cardiofaciocutaneous syndrome can be caused by mutations in several genes. Mutations in the BRAF gene are most common, accounting for 75 to 80 percent of all cases. Another 10 to 15 percent of cases result from mutations in one of two similar genes, MAP2K1 and MAP2K2. Fewer than 5 percent of cases are caused by mutations in the KRAS gene.  The BRAF, MAP2K1, MAP2K2, and KRAS genes provide instructions for making proteins that work together to transmit chemical signals from outside the cell to the cell's nucleus. This chemical signaling pathway, known as the RAS/MAPK pathway, is essential for normal development before birth. It helps control the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement, and the self-destruction of cells (apoptosis).  Mutations in any of these genes can result in the characteristic features of cardiofaciocutaneous syndrome. The protein made from the mutated gene is overactive, which alters tightly regulated chemical signaling during development. The altered signaling interferes with the development of many organs and tissues, leading to the signs and symptoms of cardiofaciocutaneous syndrome.  Some people with the signs and symptoms of cardiofaciocutaneous syndrome do not have an identified mutation in the BRAF, MAP2K1, MAP2K2, or KRAS gene. In these cases, affected individuals may actually have Costello syndrome or Noonan syndrome, which are also caused by mutations in genes involved in RAS/MAPK signaling. The proteins produced from these genes are all part of the same chemical signaling pathway, which helps explain why mutations in different genes can cause conditions with such similar signs and symptoms. The group of related conditions that includes cardiofaciocutaneous syndrome, Costello syndrome, and Noonan syndrome is often called the RASopathies.",cardiofaciocutaneous syndrome,0000151,GHR,https://ghr.nlm.nih.gov/condition/cardiofaciocutaneous-syndrome,C1275081,T019,Disorders
Is cardiofaciocutaneous syndrome inherited ?,0000151-4,inheritance,"Cardiofaciocutaneous syndrome is considered to be an autosomal dominant condition, which means one copy of an altered gene in each cell is sufficient to cause the disorder.  Cardiofaciocutaneous syndrome usually results from new gene mutations and occurs in people with no history of the disorder in their family. In a few reported cases, an affected person has inherited the condition from an affected parent.",cardiofaciocutaneous syndrome,0000151,GHR,https://ghr.nlm.nih.gov/condition/cardiofaciocutaneous-syndrome,C1275081,T019,Disorders
What are the treatments for cardiofaciocutaneous syndrome ?,0000151-5,treatment,These resources address the diagnosis or management of cardiofaciocutaneous syndrome:  - Gene Review: Gene Review: Cardiofaciocutaneous Syndrome  - Genetic Testing Registry: Cardiofaciocutaneous syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,cardiofaciocutaneous syndrome,0000151,GHR,https://ghr.nlm.nih.gov/condition/cardiofaciocutaneous-syndrome,C1275081,T019,Disorders
What is (are) Carney complex ?,0000152-1,information,"Carney complex is a disorder characterized by an increased risk of several types of tumors. Affected individuals also usually have changes in skin coloring (pigmentation). Signs and symptoms of this condition commonly begin in the teens or early adulthood.  Individuals with Carney complex are at increased risk of developing noncancerous (benign) tumors called myxomas in the heart (cardiac myxoma) and other parts of the body. Cardiac myxomas may be found in any of the four chambers of the heart and can develop in more than one chamber. These tumors can block the flow of blood through the heart, causing serious complications or sudden death. Myxomas may also develop on the skin and in internal organs. Skin myxomas appear as small bumps on the surface of the skin or as lumps underneath the skin. In Carney complex, myxomas have a tendency to recur after they are removed.  Individuals with Carney complex also develop tumors in hormone-producing (endocrine) glands, such as the adrenal glands located on top of each kidney. People with this condition may develop a specific type of adrenal disease called primary pigmented nodular adrenocortical disease (PPNAD). PPNAD causes the adrenal glands to produce an excess of the hormone cortisol. High levels of cortisol (hypercortisolism) can lead to the development of Cushing syndrome. This syndrome causes weight gain in the face and upper body, slowed growth in children, fragile skin, fatigue, and other health problems.  People with Carney complex may also develop tumors of other endocrine tissues, including the thyroid, testes, and ovaries. A tumor called an adenoma may form in the pituitary gland, which is located at the base of the brain. A pituitary adenoma usually results in the production of too much growth hormone. Excess growth hormone leads to acromegaly, a condition characterized by large hands and feet, arthritis, and ""coarse"" facial features.  Some people with Carney complex develop a rare tumor called psammomatous melanotic schwannoma. This tumor occurs in specialized cells called Schwann cells, which wrap around and insulate nerves. This tumor is usually benign, but in some cases it can become cancerous (malignant).  Almost all people with Carney complex have areas of unusual skin pigmentation. Brown skin spots called lentigines may appear anywhere on the body but tend to occur around the lips, eyes, or genitalia. In addition, some affected individuals have at least one blue-black mole called a blue nevus.",Carney complex,0000152,GHR,https://ghr.nlm.nih.gov/condition/carney-complex,C0406810,T047,Disorders
How many people are affected by Carney complex ?,0000152-2,frequency,Carney complex is a rare disorder; fewer than 750 affected individuals have been identified.,Carney complex,0000152,GHR,https://ghr.nlm.nih.gov/condition/carney-complex,C0406810,T047,Disorders
What are the genetic changes related to Carney complex ?,0000152-3,genetic changes,"Mutations in the PRKAR1A gene cause most cases of Carney complex. This gene provides instructions for making one part (subunit) of an enzyme called protein kinase A, which promotes cell growth and division (proliferation). The subunit produced from the PRKAR1A gene, called type 1 alpha, helps control whether protein kinase A is turned on or off.  Most mutations in the PRKAR1A gene that cause Carney complex result in an abnormal type 1 alpha subunit that is quickly broken down (degraded) by the cell. The lack of this subunit causes protein kinase A to be turned on more often than normal, which leads to uncontrolled cell proliferation. The signs and symptoms of Carney complex are related to the unregulated growth of cells in many parts of the body.  Some individuals with Carney complex do not have identified mutations in the PRKAR1A gene. In many of these cases, the disorder is associated with a specific region on the short (p) arm of chromosome 2, designated as 2p16. Researchers have not discovered the gene within this region that is responsible for Carney complex.",Carney complex,0000152,GHR,https://ghr.nlm.nih.gov/condition/carney-complex,C0406810,T047,Disorders
Is Carney complex inherited ?,0000152-4,inheritance,"Carney complex is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In approximately 80 percent of cases, an affected person inherits the mutation from one affected parent. The remaining cases result from new mutations in the gene and occur in people with no history of Carney complex in their family.",Carney complex,0000152,GHR,https://ghr.nlm.nih.gov/condition/carney-complex,C0406810,T047,Disorders
What are the treatments for Carney complex ?,0000152-5,treatment,"These resources address the diagnosis or management of Carney complex:  - Gene Review: Gene Review: Carney Complex  - Genetic Testing Registry: Carney complex  - Genetic Testing Registry: Carney complex, type 1  - Genetic Testing Registry: Carney complex, type 2  - MedlinePlus Encyclopedia: Atrial Myxoma  - MedlinePlus Encyclopedia: Pituitary Tumor   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Carney complex,0000152,GHR,https://ghr.nlm.nih.gov/condition/carney-complex,C0406810,T047,Disorders
What is (are) carnitine palmitoyltransferase I deficiency ?,0000153-1,information,"Carnitine palmitoyltransferase I (CPT I) deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). The severity of this condition varies among affected individuals.  Signs and symptoms of CPT I deficiency often appear during early childhood. Affected individuals usually have low blood sugar (hypoglycemia) and a low level of ketones, which are produced during the breakdown of fats and used for energy. Together these signs are called hypoketotic hypoglycemia. People with CPT I deficiency can also have an enlarged liver (hepatomegaly), liver malfunction, and elevated levels of carnitine in the blood. Carnitine, a natural substance acquired mostly through the diet, is used by cells to process fats and produce energy. Individuals with CPT I deficiency are at risk for nervous system damage, liver failure, seizures, coma, and sudden death.  Problems related to CPT I deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.",carnitine palmitoyltransferase I deficiency,0000153,GHR,https://ghr.nlm.nih.gov/condition/carnitine-palmitoyltransferase-i-deficiency,C1829703,T047,Disorders
How many people are affected by carnitine palmitoyltransferase I deficiency ?,0000153-2,frequency,CPT I deficiency is a rare disorder; fewer than 50 affected individuals have been identified. This disorder may be more common in the Hutterite and Inuit populations.,carnitine palmitoyltransferase I deficiency,0000153,GHR,https://ghr.nlm.nih.gov/condition/carnitine-palmitoyltransferase-i-deficiency,C1829703,T047,Disorders
What are the genetic changes related to carnitine palmitoyltransferase I deficiency ?,0000153-3,genetic changes,"Mutations in the CPT1A gene cause CPT I deficiency. This gene provides instructions for making an enzyme called carnitine palmitoyltransferase 1A, which is found in the liver. Carnitine palmitoyltransferase 1A is essential for fatty acid oxidation, which is the multistep process that breaks down (metabolizes) fats and converts them into energy. Fatty acid oxidation takes place within mitochondria, which are the energy-producing centers in cells. A group of fats called long-chain fatty acids cannot enter mitochondria unless they are attached to carnitine. Carnitine palmitoyltransferase 1A connects carnitine to long-chain fatty acids so they can enter mitochondria and be used to produce energy. During periods of fasting, long-chain fatty acids are an important energy source for the liver and other tissues.  Mutations in the CPT1A gene severely reduce or eliminate the activity of carnitine palmitoyltransferase 1A. Without enough of this enzyme, carnitine is not attached to long-chain fatty acids. As a result, these fatty acids cannot enter mitochondria and be converted into energy. Reduced energy production can lead to some of the features of CPT I deficiency, such as hypoketotic hypoglycemia. Fatty acids may also build up in cells and damage the liver, heart, and brain. This abnormal buildup causes the other signs and symptoms of the disorder.",carnitine palmitoyltransferase I deficiency,0000153,GHR,https://ghr.nlm.nih.gov/condition/carnitine-palmitoyltransferase-i-deficiency,C1829703,T047,Disorders
Is carnitine palmitoyltransferase I deficiency inherited ?,0000153-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",carnitine palmitoyltransferase I deficiency,0000153,GHR,https://ghr.nlm.nih.gov/condition/carnitine-palmitoyltransferase-i-deficiency,C1829703,T047,Disorders
What are the treatments for carnitine palmitoyltransferase I deficiency ?,0000153-5,treatment,These resources address the diagnosis or management of CPT I deficiency:  - Baby's First Test  - FOD (Fatty Oxidation Disorders) Family Support Group: Diagnostic Approach to Disorders of Fat Oxidation - Information for Clinicians  - Gene Review: Gene Review: Carnitine Palmitoyltransferase 1A Deficiency  - Genetic Testing Registry: Carnitine palmitoyltransferase I deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,carnitine palmitoyltransferase I deficiency,0000153,GHR,https://ghr.nlm.nih.gov/condition/carnitine-palmitoyltransferase-i-deficiency,C1829703,T047,Disorders
What is (are) carnitine palmitoyltransferase II deficiency ?,0000154-1,information,"Carnitine palmitoyltransferase II (CPT II) deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). There are three main types of CPT II deficiency: a lethal neonatal form, a severe infantile hepatocardiomuscular form, and a myopathic form.  The lethal neonatal form of CPT II deficiency becomes apparent soon after birth. Infants with this form of the disorder develop respiratory failure, seizures, liver failure, a weakened heart muscle (cardiomyopathy), and an irregular heart beat (arrhythmia). Affected individuals also have low blood sugar (hypoglycemia) and a low level of ketones, which are produced during the breakdown of fats and used for energy. Together these signs are called hypoketotic hypoglycemia. In many cases, the brain and kidneys are also structurally abnormal. Infants with the lethal neonatal form of CPT II deficiency usually live for a few days to a few months.  The severe infantile hepatocardiomuscular form of CPT II deficiency affects the liver, heart, and muscles. Signs and symptoms usually appear within the first year of life. This form involves recurring episodes of hypoketotic hypoglycemia, seizures, an enlarged liver (hepatomegaly), cardiomyopathy, and arrhythmia. Problems related to this form of CPT II deficiency can be triggered by periods of fasting or by illnesses such as viral infections. Individuals with the severe infantile hepatocardiomuscular form of CPT II deficiency are at risk for liver failure, nervous system damage, coma, and sudden death.  The myopathic form is the least severe type of CPT II deficiency. This form is characterized by recurrent episodes of muscle pain (myalgia) and weakness and is associated with the breakdown of muscle tissue (rhabdomyolysis). The destruction of muscle tissue releases a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria). Myoglobin causes the urine to be red or brown. This protein can also damage the kidneys, in some cases leading to life-threatening kidney failure. Episodes of myalgia and rhabdomyolysis may be triggered by exercise, stress, exposure to extreme temperatures, infections, or fasting. The first episode usually occurs during childhood or adolescence. Most people with the myopathic form of CPT II deficiency have no signs or symptoms of the disorder between episodes.",carnitine palmitoyltransferase II deficiency,0000154,GHR,https://ghr.nlm.nih.gov/condition/carnitine-palmitoyltransferase-ii-deficiency,C0342790,T047,Disorders
How many people are affected by carnitine palmitoyltransferase II deficiency ?,0000154-2,frequency,"CPT II deficiency is a rare disorder. The lethal neonatal form has been described in at least 18 families, while the severe infantile hepatocardiomuscular form has been identified in approximately 30 families. The myopathic form occurs most frequently, with more than 300 reported cases.",carnitine palmitoyltransferase II deficiency,0000154,GHR,https://ghr.nlm.nih.gov/condition/carnitine-palmitoyltransferase-ii-deficiency,C0342790,T047,Disorders
What are the genetic changes related to carnitine palmitoyltransferase II deficiency ?,0000154-3,genetic changes,"Mutations in the CPT2 gene cause CPT II deficiency. This gene provides instructions for making an enzyme called carnitine palmitoyltransferase 2. This enzyme is essential for fatty acid oxidation, which is the multistep process that breaks down (metabolizes) fats and converts them into energy. Fatty acid oxidation takes place within mitochondria, which are the energy-producing centers in cells. A group of fats called long-chain fatty acids must be attached to a substance known as carnitine to enter mitochondria. Once these fatty acids are inside mitochondria, carnitine palmitoyltransferase 2 removes the carnitine and prepares them for fatty acid oxidation. Fatty acids are a major source of energy for the heart and muscles. During periods of fasting, fatty acids are also an important energy source for the liver and other tissues.  Mutations in the CPT2 gene reduce the activity of carnitine palmitoyltransferase 2. Without enough of this enzyme, carnitine is not removed from long-chain fatty acids. As a result, these fatty acids cannot be metabolized to produce energy. Reduced energy production can lead to some of the features of CPT II deficiency, such as hypoketotic hypoglycemia, myalgia, and weakness. Fatty acids and long-chain acylcarnitines (fatty acids still attached to carnitine) may also build up in cells and damage the liver, heart, and muscles. This abnormal buildup causes the other signs and symptoms of the disorder.",carnitine palmitoyltransferase II deficiency,0000154,GHR,https://ghr.nlm.nih.gov/condition/carnitine-palmitoyltransferase-ii-deficiency,C0342790,T047,Disorders
Is carnitine palmitoyltransferase II deficiency inherited ?,0000154-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",carnitine palmitoyltransferase II deficiency,0000154,GHR,https://ghr.nlm.nih.gov/condition/carnitine-palmitoyltransferase-ii-deficiency,C0342790,T047,Disorders
What are the treatments for carnitine palmitoyltransferase II deficiency ?,0000154-5,treatment,"These resources address the diagnosis or management of CPT II deficiency:  - Baby's First Test  - FOD (Fatty Oxidation Disorders) Family Support Group: Diagnostic Approach to Disorders of Fat Oxidation - Information for Clinicians  - Gene Review: Gene Review: Carnitine Palmitoyltransferase II Deficiency  - Genetic Testing Registry: CARNITINE PALMITOYLTRANSFERASE II DEFICIENCY, LATE-ONSET  - Genetic Testing Registry: CARNITINE PALMITOYLTRANSFERASE II DEFICIENCY, LETHAL NEONATAL  - Genetic Testing Registry: Carnitine palmitoyltransferase II deficiency  - Genetic Testing Registry: Carnitine palmitoyltransferase II deficiency, infantile   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",carnitine palmitoyltransferase II deficiency,0000154,GHR,https://ghr.nlm.nih.gov/condition/carnitine-palmitoyltransferase-ii-deficiency,C0342790,T047,Disorders
What is (are) carnitine-acylcarnitine translocase deficiency ?,0000155-1,information,"Carnitine-acylcarnitine translocase (CACT) deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). Signs and symptoms of this disorder usually begin soon after birth and may include breathing problems, seizures, and an irregular heartbeat (arrhythmia). Affected individuals typically have low blood sugar (hypoglycemia) and a low level of ketones, which are produced during the breakdown of fats and used for energy. Together these signs are called hypoketotic hypoglycemia. People with CACT deficiency also usually have excess ammonia in the blood (hyperammonemia), an enlarged liver (hepatomegaly), and a weakened heart muscle (cardiomyopathy).  Many infants with CACT deficiency do not survive the newborn period. Some affected individuals have a less severe form of the condition and do not develop signs and symptoms until early childhood. These individuals are at risk for liver failure, nervous system damage, coma, and sudden death.",carnitine-acylcarnitine translocase deficiency,0000155,GHR,https://ghr.nlm.nih.gov/condition/carnitine-acylcarnitine-translocase-deficiency,C0342791,T047,Disorders
How many people are affected by carnitine-acylcarnitine translocase deficiency ?,0000155-2,frequency,CACT deficiency is very rare; at least 30 cases have been reported.,carnitine-acylcarnitine translocase deficiency,0000155,GHR,https://ghr.nlm.nih.gov/condition/carnitine-acylcarnitine-translocase-deficiency,C0342791,T047,Disorders
What are the genetic changes related to carnitine-acylcarnitine translocase deficiency ?,0000155-3,genetic changes,"Mutations in the SLC25A20 gene cause CACT deficiency. This gene provides instructions for making a protein called carnitine-acylcarnitine translocase (CACT). This protein is essential for fatty acid oxidation, a multistep process that breaks down (metabolizes) fats and converts them into energy. Fatty acid oxidation takes place within mitochondria, which are the energy-producing centers in cells. A group of fats called long-chain fatty acids must be attached to a substance known as carnitine to enter mitochondria. Once these fatty acids are joined with carnitine, the CACT protein transports them into mitochondria. Fatty acids are a major source of energy for the heart and muscles. During periods of fasting, fatty acids are also an important energy source for the liver and other tissues.  Although mutations in the SLC25A20 gene change the structure of the CACT protein in different ways, they all lead to a shortage (deficiency) of the transporter. Without enough functional CACT protein, long-chain fatty acids cannot be transported into mitochondria. As a result, these fatty acids are not converted to energy. Reduced energy production can lead to some of the features of CACT deficiency, such as hypoketotic hypoglycemia. Fatty acids and long-chain acylcarnitines (fatty acids still attached to carnitine) may also build up in cells and damage the liver, heart, and muscles. This abnormal buildup causes the other signs and symptoms of the disorder.",carnitine-acylcarnitine translocase deficiency,0000155,GHR,https://ghr.nlm.nih.gov/condition/carnitine-acylcarnitine-translocase-deficiency,C0342791,T047,Disorders
Is carnitine-acylcarnitine translocase deficiency inherited ?,0000155-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",carnitine-acylcarnitine translocase deficiency,0000155,GHR,https://ghr.nlm.nih.gov/condition/carnitine-acylcarnitine-translocase-deficiency,C0342791,T047,Disorders
What are the treatments for carnitine-acylcarnitine translocase deficiency ?,0000155-5,treatment,These resources address the diagnosis or management of CACT deficiency:  - Baby's First Test  - FOD (Fatty Oxidation Disorders) Family Support Group: Diagnostic Approach to Disorders of Fat Oxidation - Information for Clinicians  - Genetic Testing Registry: Carnitine acylcarnitine translocase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,carnitine-acylcarnitine translocase deficiency,0000155,GHR,https://ghr.nlm.nih.gov/condition/carnitine-acylcarnitine-translocase-deficiency,C0342791,T047,Disorders
What is (are) Carpenter syndrome ?,0000156-1,information,"Carpenter syndrome is a condition characterized by the premature fusion of certain skull bones (craniosynostosis), abnormalities of the fingers and toes, and other developmental problems.  Craniosynostosis prevents the skull from growing normally, frequently giving the head a pointed appearance (acrocephaly). In severely affected individuals, the abnormal fusion of the skull bones results in a deformity called a cloverleaf skull. Craniosynostosis can cause differences between the two sides of the head and face (craniofacial asymmetry). Early fusion of the skull bones can affect the development of the brain and lead to increased pressure within the skull (intracranial pressure). Premature fusion of the skull bones can cause several characteristic facial features in people with Carpenter syndrome. Distinctive facial features may include a flat nasal bridge, outside corners of the eyes that point downward (down-slanting palpebral fissures), low-set and abnormally shaped ears, underdeveloped upper and lower jaws, and abnormal eye shape. Some affected individuals also have dental abnormalities including small primary (baby) teeth. Vision problems also frequently occur.  Abnormalities of the fingers and toes include fusion of the skin between two or more fingers or toes (cutaneous syndactyly), unusually short fingers or toes (brachydactyly), or extra fingers or toes (polydactyly). In Carpenter syndrome, cutaneous syndactyly is most common between the third (middle) and fourth (ring) fingers, and polydactyly frequently occurs next to the big or second toe or the fifth (pinky) finger.  People with Carpenter syndrome often have intellectual disability, which can range from mild to profound. However, some individuals with this condition have normal intelligence. The cause of intellectual disability is unknown, as the severity of craniosynostosis does not appear to be related to the severity of intellectual disability.  Other features of Carpenter syndrome include obesity that begins in childhood, a soft out-pouching around the belly-button (umbilical hernia), hearing loss, and heart defects. Additional skeletal abnormalities such as deformed hips, a rounded upper back that also curves to the side (kyphoscoliosis), and knees that are angled inward (genu valgum) frequently occur. Nearly all affected males have genital abnormalities, most frequently undescended testes (cryptorchidism).  A few people with Carpenter syndrome have organs or tissues within their chest and abdomen that are in mirror-image reversed positions. This abnormal placement may affect several internal organs (situs inversus); just the heart (dextrocardia), placing the heart on the right side of the body instead of on the left; or only the major (great) arteries of the heart, altering blood flow.  The signs and symptoms of this disorder vary considerably, even within the same family. The life expectancy for individuals with Carpenter syndrome is shortened but extremely variable.  The signs and symptoms of Carpenter syndrome are similar to another genetic condition called Greig cephalopolysyndactyly syndrome. The overlapping features, which include craniosynostosis, polydactyly, and heart abnormalities, can cause these two conditions to be misdiagnosed; genetic testing is often required for an accurate diagnosis.",Carpenter syndrome,0000156,GHR,https://ghr.nlm.nih.gov/condition/carpenter-syndrome,C0085860,T019,Disorders
How many people are affected by Carpenter syndrome ?,0000156-2,frequency,Carpenter syndrome is thought to be a rare condition; approximately 70 cases have been described in the scientific literature.,Carpenter syndrome,0000156,GHR,https://ghr.nlm.nih.gov/condition/carpenter-syndrome,C0085860,T019,Disorders
What are the genetic changes related to Carpenter syndrome ?,0000156-3,genetic changes,"Mutations in the RAB23 or MEGF8 gene cause Carpenter syndrome.  The RAB23 gene provides instructions for making a protein that is involved in a process called vesicle trafficking, which moves proteins and other molecules within cells in sac-like structures called vesicles. The Rab23 protein transports vesicles from the cell membrane to their proper location inside the cell. Vesicle trafficking is important for the transport of materials that are needed to trigger signaling during development. For example, the Rab23 protein regulates a developmental pathway called the hedgehog signaling pathway that is critical in cell growth (proliferation), cell specialization, and the normal shaping (patterning) of many parts of the body.  The MEGF8 gene provides instructions for making a protein whose function is unclear. Based on its structure, the Megf8 protein may be involved in cell processes such as sticking cells together (cell adhesion) and helping proteins interact with each other. Researchers also suspect that the Megf8 protein plays a role in normal body patterning.  Mutations in the RAB23 or MEGF8 gene lead to the production of proteins with little or no function. It is unclear how disruptions in protein function lead to the features of Carpenter syndrome, but it is likely that interference with normal body patterning plays a role. For reasons that are unknown, people with MEGF8 gene mutations are more likely to have dextrocardia and other organ positioning abnormalities and less severe craniosynostosis than individuals with RAB23 gene mutations.",Carpenter syndrome,0000156,GHR,https://ghr.nlm.nih.gov/condition/carpenter-syndrome,C0085860,T019,Disorders
Is Carpenter syndrome inherited ?,0000156-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Carpenter syndrome,0000156,GHR,https://ghr.nlm.nih.gov/condition/carpenter-syndrome,C0085860,T019,Disorders
What are the treatments for Carpenter syndrome ?,0000156-5,treatment,These resources address the diagnosis or management of Carpenter syndrome:  - Genetic Testing Registry: Carpenter syndrome 1  - Genetic Testing Registry: Carpenter syndrome 2  - Great Ormond Street Hospital for Children (UK): Craniosynostosis Information  - Johns Hopkins Medicine: Craniosynostosis Treatment Options  - MedlinePlus Encyclopedia: Craniosynostosis Repair  - MedlinePlus Encyclopedia: Dextrocardia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Carpenter syndrome,0000156,GHR,https://ghr.nlm.nih.gov/condition/carpenter-syndrome,C0085860,T019,Disorders
What is (are) cartilage-hair hypoplasia ?,0000157-1,information,"Cartilage-hair hypoplasia is a disorder of bone growth characterized by short stature (dwarfism) with other skeletal abnormalities; fine, sparse hair (hypotrichosis); and abnormal immune system function (immune deficiency) that can lead to recurrent infections.  People with cartilage-hair hypoplasia have unusually short limbs and short stature from birth. They typically have malformations in the cartilage near the ends of the long bones in the arms and legs (metaphyseal chondrodysplasia), which then affects development of the bone itself. Most people with cartilage-hair hypoplasia are unusually flexible in some joints, but they may have difficulty extending their elbows fully.  Affected individuals have hair that is lighter in color than that of other family members because the core of each hair, which contains some of the pigment that contributes the hair's color, is missing. The missing core also makes each strand of hair thinner, causing the hair to have a sparse appearance overall. Unusually light-colored skin (hypopigmentation), malformed nails, and dental abnormalities may also be seen in this disorder.  The extent of the immune deficiency in cartilage-hair hypoplasia varies from mild to severe. Affected individuals with the most severe immune problems are considered to have severe combined immunodeficiency (SCID). People with SCID lack virtually all immune protection from bacteria, viruses, and fungi and are prone to repeated and persistent infections that can be very serious or life-threatening. These infections are often caused by ""opportunistic"" organisms that ordinarily do not cause illness in people with a normal immune system. Most people with cartilage-hair hypoplasia, even those who have milder immune deficiency, experience infections of the respiratory system, ears, and sinuses. In particular, the chicken pox virus (varicella) often causes dangerous infections in people with this disorder. Autoimmune disorders, which occur when the immune system malfunctions and attacks the body's tissues and organs, occur in some people with cartilage-hair hypoplasia. Affected individuals are also at an increased risk of developing cancer, particularly certain skin cancers (basal cell carcinomas), cancer of blood-forming cells (leukemia), and cancer of immune system cells (lymphoma).  Some people with cartilage-hair hypoplasia experience gastrointestinal problems. These problems may include an inability to properly absorb nutrients or intolerance of a protein called gluten found in wheat and other grains (celiac disease). Affected individuals may have Hirschsprung disease, an intestinal disorder that causes severe constipation, intestinal blockage, and enlargement of the colon. Narrowing of the anus (anal stenosis) or blockage of the esophagus (esophageal atresia) may also occur.",cartilage-hair hypoplasia,0000157,GHR,https://ghr.nlm.nih.gov/condition/cartilage-hair-hypoplasia,C0220748,T019,Disorders
How many people are affected by cartilage-hair hypoplasia ?,0000157-2,frequency,"Cartilage-hair hypoplasia occurs most often in the Old Order Amish population, where it affects about 1 in 1,300 newborns. In people of Finnish descent, its incidence is approximately 1 in 20,000. Outside of these populations, the condition is rare, and its specific incidence is not known. It has been reported in individuals of European and Japanese descent.",cartilage-hair hypoplasia,0000157,GHR,https://ghr.nlm.nih.gov/condition/cartilage-hair-hypoplasia,C0220748,T019,Disorders
What are the genetic changes related to cartilage-hair hypoplasia ?,0000157-3,genetic changes,"Cartilage-hair hypoplasia is caused by mutations in the RMRP gene. Unlike many genes, the RMRP gene does not contain instructions for making a protein. Instead, a molecule called a noncoding RNA, a chemical cousin of DNA, is produced from the RMRP gene. This RNA attaches (binds) to several proteins, forming an enzyme complex called mitochondrial RNA-processing endoribonuclease, or RNase MRP.  The RNase MRP enzyme is thought to be involved in several important processes in the cell. For example, it likely helps copy (replicate) the DNA found in the energy-producing centers of cells (mitochondria). The RNase MRP enzyme probably also processes ribosomal RNA, which is required for assembling protein building blocks (amino acids) into functioning proteins. In addition, this enzyme helps control the cell cycle, which is the cell's way of replicating itself in an organized, step-by-step fashion.  Mutations in the RMRP gene likely result in the production of a noncoding RNA that is unstable. This unstable molecule cannot bind to some of the proteins needed to make the RNase MRP enzyme complex. These changes are believed to affect the activity of the enzyme, which interferes with its important functions within cells. Disruption of the RNase MRP enzyme complex causes the signs and symptoms of cartilage-hair hypoplasia.",cartilage-hair hypoplasia,0000157,GHR,https://ghr.nlm.nih.gov/condition/cartilage-hair-hypoplasia,C0220748,T019,Disorders
Is cartilage-hair hypoplasia inherited ?,0000157-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",cartilage-hair hypoplasia,0000157,GHR,https://ghr.nlm.nih.gov/condition/cartilage-hair-hypoplasia,C0220748,T019,Disorders
What are the treatments for cartilage-hair hypoplasia ?,0000157-5,treatment,"These resources address the diagnosis or management of cartilage-hair hypoplasia:  - Gene Review: Gene Review: Cartilage-Hair Hypoplasia - Anauxetic Dysplasia Spectrum Disorders  - Genetic Testing Registry: Metaphyseal chondrodysplasia, McKusick type   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",cartilage-hair hypoplasia,0000157,GHR,https://ghr.nlm.nih.gov/condition/cartilage-hair-hypoplasia,C0220748,T019,Disorders
What is (are) CASK-related intellectual disability ?,0000158-1,information,"CASK-related intellectual disability is a disorder of brain development that has two main forms: microcephaly with pontine and cerebellar hypoplasia (MICPCH), and X-linked intellectual disability (XL-ID) with or without nystagmus. Within each of these forms, males typically have more severe signs and symptoms than do females; the more severe MICPCH mostly affects females, likely because only a small number of males survive to birth.  People with MICPCH often have an unusually small head at birth, and the head does not grow at the same rate as the rest of the body, so it appears that the head is getting smaller as the body grows (progressive microcephaly). Individuals with this condition have underdevelopment (hypoplasia) of areas of the brain called the cerebellum and the pons. The cerebellum is the part of the brain that coordinates movement. The pons is located at the base of the brain in an area called the brainstem, where it transmits signals from the cerebellum to the rest of the brain.  Individuals with MICPCH have intellectual disability that is usually severe. They may have sleep disturbances and exhibit self-biting, hand flapping, or other abnormal repetitive behaviors. Seizures are also common in this form of the disorder.  People with MICPCH do not usually develop language skills, and most do not learn to walk. They have hearing loss caused by nerve problems in the inner ear (sensorineural hearing loss), and most also have abnormalities affecting the eyes. These abnormalities include underdevelopment of the nerves that carry information from the eyes to the brain (optic nerve hypoplasia), breakdown of the light-sensing tissue at the back of the eyes (retinopathy), and eyes that do not look in the same direction (strabismus). Characteristic facial features may include arched eyebrows; a short, broad nose; a lengthened area between the nose and mouth (philtrum); a protruding upper jaw (maxilla); a short chin; and large ears.  Individuals with MICPCH may have weak muscle tone (hypotonia) in the torso along with increased muscle tone (hypertonia) and stiffness (spasticity) in the limbs. Movement problems such as involuntary tensing of various muscles (dystonia) may also occur in this form of the disorder.  XL-ID with or without nystagmus (rapid, involuntary eye movements) is a milder form of CASK-related intellectual disability. The intellectual disability in this form of the disorder can range from mild to severe; some affected females have normal intelligence. About half of affected individuals have nystagmus. Seizures and rhythmic shaking (tremors) may also occur in this form.",CASK-related intellectual disability,0000158,GHR,https://ghr.nlm.nih.gov/condition/cask-related-intellectual-disability,C0445223,T048,Disorders
How many people are affected by CASK-related intellectual disability ?,0000158-2,frequency,"The prevalence of CASK-related intellectual disability is unknown. More than 50 females with MICPCH have been described in the medical literature, while only a few affected males have been described.  By contrast, more than 20 males but only a few females have been diagnosed with the milder form of the disorder, XL-ID with or without nystagmus. This form of the disorder may go unrecognized in mildly affected females.",CASK-related intellectual disability,0000158,GHR,https://ghr.nlm.nih.gov/condition/cask-related-intellectual-disability,C0445223,T048,Disorders
What are the genetic changes related to CASK-related intellectual disability ?,0000158-3,genetic changes,"CASK-related intellectual disability, as its name suggests, is caused by mutations in the CASK gene. This gene provides instructions for making a protein called calcium/calmodulin-dependent serine protein kinase (CASK). The CASK protein is primarily found in nerve cells (neurons) in the brain, where it helps control the activity (expression) of other genes that are involved in brain development. It also helps regulate the movement of chemicals called neurotransmitters and of charged atoms (ions), which are necessary for signaling between neurons. Research suggests that the CASK protein may also interact with the protein produced from another gene, FRMD7, to promote development of the nerves that control eye movement (the oculomotor neural network).  Mutations in the CASK gene affect the role of the CASK protein in brain development and function, resulting in the signs and symptoms of CASK-related intellectual disability. The severe form of this disorder, MICPCH, is caused by mutations that eliminate CASK function, while mutations that impair the function of this protein cause the milder form, XL-ID with or without nystagmus. Affected individuals with nystagmus may have CASK gene mutations that disrupt the interaction between the CASK protein and the protein produced from the FRMD7 gene, leading to problems with the development of the oculomotor neural network and resulting in abnormal eye movements.",CASK-related intellectual disability,0000158,GHR,https://ghr.nlm.nih.gov/condition/cask-related-intellectual-disability,C0445223,T048,Disorders
Is CASK-related intellectual disability inherited ?,0000158-4,inheritance,"This condition is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In females, who have two copies of the X chromosome, one altered copy of the gene in each cell is sufficient to cause the disorder. In males, who have only one X chromosome, a mutation in the only copy of the gene in each cell causes the condition. In most cases, males experience more severe symptoms of the disorder than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",CASK-related intellectual disability,0000158,GHR,https://ghr.nlm.nih.gov/condition/cask-related-intellectual-disability,C0445223,T048,Disorders
What are the treatments for CASK-related intellectual disability ?,0000158-5,treatment,These resources address the diagnosis or management of CASK-related intellectual disability:  - Gene Review: Gene Review: CASK-Related Disorders  - Genetic Testing Registry: Mental retardation and microcephaly with pontine and cerebellar hypoplasia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,CASK-related intellectual disability,0000158,GHR,https://ghr.nlm.nih.gov/condition/cask-related-intellectual-disability,C0445223,T048,Disorders
What is (are) catecholaminergic polymorphic ventricular tachycardia ?,0000159-1,information,"Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a condition characterized by an abnormal heart rhythm (arrhythmia). As the heart rate increases in response to physical activity or emotional stress, it can trigger an abnormally fast and irregular heartbeat called ventricular tachycardia. Episodes of ventricular tachycardia can cause light-headedness, dizziness, and fainting (syncope). In people with CPVT, these episodes typically begin in childhood.  If CPVT is not recognized and treated, an episode of ventricular tachycardia may cause the heart to stop beating (cardiac arrest), leading to sudden death. Researchers suspect that CPVT may be a significant cause of sudden death in children and young adults without recognized heart abnormalities.",catecholaminergic polymorphic ventricular tachycardia,0000159,GHR,https://ghr.nlm.nih.gov/condition/catecholaminergic-polymorphic-ventricular-tachycardia,C1631597,T047,Disorders
How many people are affected by catecholaminergic polymorphic ventricular tachycardia ?,0000159-2,frequency,"The prevalence of CPVT is estimated to be about 1 in 10,000 people. However, the true prevalence of this condition is unknown.",catecholaminergic polymorphic ventricular tachycardia,0000159,GHR,https://ghr.nlm.nih.gov/condition/catecholaminergic-polymorphic-ventricular-tachycardia,C1631597,T047,Disorders
What are the genetic changes related to catecholaminergic polymorphic ventricular tachycardia ?,0000159-3,genetic changes,"CPVT can result from mutations in two genes, RYR2 and CASQ2. RYR2 gene mutations cause about half of all cases, while mutations in the CASQ2 gene account for 1 percent to 2 percent of cases. In people without an identified mutation in one of these genes, the genetic cause of the disorder is unknown.  The RYR2 and CASQ2 genes provide instructions for making proteins that help maintain a regular heartbeat. For the heart to beat normally, heart muscle cells called myocytes must tense (contract) and relax in a coordinated way. Both the RYR2 and CASQ2 proteins are involved in handling calcium within myocytes, which is critical for the regular contraction of these cells.  Mutations in either the RYR2 or CASQ2 gene disrupt the handling of calcium within myocytes. During exercise or emotional stress, impaired calcium regulation in the heart can lead to ventricular tachycardia in people with CPVT.",catecholaminergic polymorphic ventricular tachycardia,0000159,GHR,https://ghr.nlm.nih.gov/condition/catecholaminergic-polymorphic-ventricular-tachycardia,C1631597,T047,Disorders
Is catecholaminergic polymorphic ventricular tachycardia inherited ?,0000159-4,inheritance,"When CPVT results from mutations in the RYR2 gene, it has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder. In about half of cases, an affected person inherits an RYR2 gene mutation from one affected parent. The remaining cases result from new mutations in the RYR2 gene and occur in people with no history of the disorder in their family.  When CPVT is caused by mutations in the CASQ2 gene, the condition has an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means that both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",catecholaminergic polymorphic ventricular tachycardia,0000159,GHR,https://ghr.nlm.nih.gov/condition/catecholaminergic-polymorphic-ventricular-tachycardia,C1631597,T047,Disorders
What are the treatments for catecholaminergic polymorphic ventricular tachycardia ?,0000159-5,treatment,"These resources address the diagnosis or management of catecholaminergic polymorphic ventricular tachycardia:  - Cleveland Clinic: Management of Arrhythmias  - Gene Review: Gene Review: Catecholaminergic Polymorphic Ventricular Tachycardia  - Genetic Testing Registry: Catecholaminergic polymorphic ventricular tachycardia  - Genetic Testing Registry: Ventricular tachycardia, catecholaminergic polymorphic, 2  - MedlinePlus Encyclopedia: Fainting  - MedlinePlus Encyclopedia: Ventricular Tachycardia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",catecholaminergic polymorphic ventricular tachycardia,0000159,GHR,https://ghr.nlm.nih.gov/condition/catecholaminergic-polymorphic-ventricular-tachycardia,C1631597,T047,Disorders
What is (are) CATSPER1-related nonsyndromic male infertility ?,0000160-1,information,"CATSPER1-related nonsyndromic male infertility is a condition that affects the function of sperm, leading to an inability to father children. Males with this condition produce sperm that have decreased movement (motility). Affected men may also produce a smaller than usual number of sperm cells or sperm cells that are abnormally shaped. Men with CATSPER1-related nonsyndromic male infertility do not have any other symptoms related to this condition.",CATSPER1-related nonsyndromic male infertility,0000160,GHR,https://ghr.nlm.nih.gov/condition/catsper1-related-nonsyndromic-male-infertility,C0445223,T047,Disorders
How many people are affected by CATSPER1-related nonsyndromic male infertility ?,0000160-2,frequency,The prevalence of CATSPER1-related nonsyndromic male infertility is unknown.,CATSPER1-related nonsyndromic male infertility,0000160,GHR,https://ghr.nlm.nih.gov/condition/catsper1-related-nonsyndromic-male-infertility,C0445223,T047,Disorders
What are the genetic changes related to CATSPER1-related nonsyndromic male infertility ?,0000160-3,genetic changes,"Mutations in the CATSPER1 gene cause CATSPER1-related nonsyndromic male infertility. The CATSPER1 gene provides instructions for producing a protein that is found in the tail of sperm cells. The CATSPER1 protein is involved in the movement of the sperm tail, which propels the sperm forward and is required for sperm cells to push through the outside membrane of the egg cell during fertilization.  CATSPER1 gene mutations result in the production of a CATSPER1 protein that may be altered, nonfunctional, or quickly broken down (degraded) by the cell. Sperm cells missing a functional CATSPER1 protein have decreased motion in their tails and move more slowly than normal. Sperm cells lacking functional CATSPER1 protein cannot push through the outside membrane of the egg cell. As a result, sperm cells cannot reach the inside of the egg cell to achieve fertilization.",CATSPER1-related nonsyndromic male infertility,0000160,GHR,https://ghr.nlm.nih.gov/condition/catsper1-related-nonsyndromic-male-infertility,C0445223,T047,Disorders
Is CATSPER1-related nonsyndromic male infertility inherited ?,0000160-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show symptoms of the condition.  Males with two CATSPER1 gene mutations in each cell have CATSPER1-related nonsyndromic male infertility. Females with two CATSPER1 gene mutations in each cell have no symptoms because the mutations only affect sperm function, and women do not produce sperm.",CATSPER1-related nonsyndromic male infertility,0000160,GHR,https://ghr.nlm.nih.gov/condition/catsper1-related-nonsyndromic-male-infertility,C0445223,T047,Disorders
What are the treatments for CATSPER1-related nonsyndromic male infertility ?,0000160-5,treatment,These resources address the diagnosis or management of CATSPER1-related nonsyndromic male infertility:  - Cleveland Clinic: Male Infertility  - Gene Review: Gene Review: CATSPER-Related Male Infertility  - Genetic Testing Registry: CATSPER-Related Male Infertility  - MedlinePlus Health Topic: Assisted Reproductive Technology  - RESOLVE: The National Infertility Association: Semen Analysis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,CATSPER1-related nonsyndromic male infertility,0000160,GHR,https://ghr.nlm.nih.gov/condition/catsper1-related-nonsyndromic-male-infertility,C0445223,T047,Disorders
What is (are) caudal regression syndrome ?,0000161-1,information,"Caudal regression syndrome is a disorder that impairs the development of the lower (caudal) half of the body. Affected areas can include the lower back and limbs, the genitourinary tract, and the gastrointestinal tract.  In this disorder, the bones of the lower spine (vertebrae) are frequently misshapen or missing, and the corresponding sections of the spinal cord are also irregular or missing. Affected individuals may have incomplete closure of the vertebrae around the spinal cord, a fluid-filled sac on the back covered by skin that may or may not contain part of the spinal cord, or tufts of hair at the base of the spine. People with caudal regression syndrome can also have an abnormal side-to-side curvature of the spine (scoliosis). The spinal abnormalities may affect the size and shape of the chest, leading to breathing problems in some individuals.  Individuals with caudal regression syndrome may have small hip bones with a limited range of motion. The buttocks tend to be flat and dimpled. The bones of the legs are typically underdeveloped, most frequently the upper leg bones (femurs). In some individuals, the legs are bent with the knees pointing out to the side and the feet tucked underneath the hips (sometimes called a frog leg-like position). Affected individuals may be born with inward- and upward-turning feet (clubfeet), or the feet may be outward- and upward-turning (calcaneovalgus). Some people experience decreased sensation in their lower limbs.  Abnormalities in the genitourinary tract in caudal regression syndrome are extremely varied. Often the kidneys are malformed; defects include a missing kidney (unilateral renal agenesis), kidneys that are fused together (horseshoe kidney), or duplication of the tubes that carry urine from each kidney to the bladder (ureteral duplication). These kidney abnormalities can lead to frequent urinary tract infections and progressive kidney failure. Additionally, affected individuals may have protrusion of the bladder through an opening in the abdominal wall (bladder exstrophy). Damage to the nerves that control bladder function, a condition called neurogenic bladder, causes affected individuals to have progressive difficulty controlling the flow of urine. Genital abnormalities in males can include the urethra opening on the underside of the penis (hypospadia) or undescended testes (cryptorchidism). Females may have an abnormal connection between the rectum and vagina (rectovaginal fistula). In severe cases, both males and females have a lack of development of the genitalia (genital agenesis).  People with caudal regression syndrome may have abnormal twisting (malrotation) of the large intestine, an obstruction of the anal opening (imperforate anus), soft out-pouchings in the lower abdomen (inguinal hernias), or other malformations of the gastrointestinal tract. Affected individuals are often constipated and may experience loss of control of bladder and bowel function.",caudal regression syndrome,0000161,GHR,https://ghr.nlm.nih.gov/condition/caudal-regression-syndrome,C0684320,T019,Disorders
How many people are affected by caudal regression syndrome ?,0000161-2,frequency,"Caudal regression syndrome is estimated to occur in 1 to 2.5 per 100,000 newborns. This condition is much more common in infants born to mothers with diabetes when it affects an estimated 1 in 350 newborns.",caudal regression syndrome,0000161,GHR,https://ghr.nlm.nih.gov/condition/caudal-regression-syndrome,C0684320,T019,Disorders
What are the genetic changes related to caudal regression syndrome ?,0000161-3,genetic changes,"Caudal regression syndrome is a complex condition that may have different causes in different people. The condition is likely caused by the interaction of multiple genetic and environmental factors. One risk factor for the development of caudal regression syndrome is the presence of diabetes in the mother. It is thought that increased blood sugar levels and other metabolic problems related to diabetes may have a harmful effect on a developing fetus, increasing the likelihood of developing caudal regression syndrome. The risks to the fetus are further increased if the mother's diabetes is poorly managed. Caudal regression syndrome also occurs in infants of non-diabetic mothers, so researchers are trying to identify other factors that contribute to the development of this complex disorder.  Some researchers believe that a disruption of fetal development around day 28 of pregnancy causes caudal regression syndrome. The developmental problem is thought to affect the middle layer of embryonic tissue known as the mesoderm. Disruption of normal mesoderm development impairs normal formation of parts of the skeleton, gastrointestinal system, and genitourinary system.  Other researchers think that caudal regression syndrome results from the presence of an abnormal artery in the abdomen, which diverts blood flow away from the lower areas of the developing fetus. Decreased blood flow to these areas is thought to interfere with their development and result in the signs and symptoms of caudal regression syndrome.  Some scientists believe that the abnormal development of the mesoderm causes the reduction of blood flow, while other scientists believe that the reduction in blood flow causes the abnormal mesoderm development. Many scientists think that the cause of caudal regression syndrome is a combination of abnormal mesoderm development and decreased blood flow to the caudal areas of the fetus.",caudal regression syndrome,0000161,GHR,https://ghr.nlm.nih.gov/condition/caudal-regression-syndrome,C0684320,T019,Disorders
Is caudal regression syndrome inherited ?,0000161-4,inheritance,"Caudal regression syndrome occurs sporadically, which means it occurs in people with no history of the condition in their family. Multiple genetic and environmental factors likely play a part in determining the risk of developing this condition.",caudal regression syndrome,0000161,GHR,https://ghr.nlm.nih.gov/condition/caudal-regression-syndrome,C0684320,T019,Disorders
What are the treatments for caudal regression syndrome ?,0000161-5,treatment,These resources address the diagnosis or management of caudal regression syndrome:  - MedlinePlus Encyclopedia: Bladder Exstrophy Repair  - MedlinePlus Encyclopedia: Clubfoot  - MedlinePlus Encyclopedia: Inguinal Hernia Repair  - MedlinePlus Encyclopedia: Neurogenic Bladder   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,caudal regression syndrome,0000161,GHR,https://ghr.nlm.nih.gov/condition/caudal-regression-syndrome,C0684320,T019,Disorders
What is (are) CAV3-related distal myopathy ?,0000162-1,information,"CAV3-related distal myopathy is one form of distal myopathy, a group of disorders characterized by weakness and loss of function affecting the muscles farthest from the center of the body (distal muscles), such as those of the hands and feet. People with CAV3-related distal myopathy experience wasting (atrophy) and weakness of the small muscles in the hands and feet that generally become noticeable in adulthood. A bump or other sudden impact on the muscles, especially those in the forearms, may cause them to exhibit repetitive tensing (percussion-induced rapid contraction). The rapid contractions can continue for up to 30 seconds and may be painful. Overgrowth (hypertrophy) of the calf muscles can also occur in CAV3-related distal myopathy. The muscles closer to the center of the body (proximal muscles) such as the thighs and upper arms are normal in this condition.",CAV3-related distal myopathy,0000162,GHR,https://ghr.nlm.nih.gov/condition/cav3-related-distal-myopathy,C0751336,T047,Disorders
How many people are affected by CAV3-related distal myopathy ?,0000162-2,frequency,The prevalence of CAV3-related distal myopathy is unknown. Only a few affected individuals have been described in the medical literature.,CAV3-related distal myopathy,0000162,GHR,https://ghr.nlm.nih.gov/condition/cav3-related-distal-myopathy,C0751336,T047,Disorders
What are the genetic changes related to CAV3-related distal myopathy ?,0000162-3,genetic changes,"CAV3-related distal myopathy is part of a group of conditions called caveolinopathies, which are muscle disorders caused by mutations in the CAV3 gene. The CAV3 gene provides instructions for making a protein called caveolin-3, which is found in the membrane surrounding muscle cells. This protein is the main component of caveolae, which are small pouches in the muscle cell membrane. Within the caveolae, the caveolin-3 protein acts as a scaffold to organize other molecules that are important for cell signaling and maintenance of the cell structure.  CAV3 gene mutations result in a shortage of caveolin-3 protein in the muscle cell membrane and a reduction in the number of caveolae. Researchers suggest that a shortage of caveolae impairs the structural integrity of muscle cells, interferes with cell signaling, and causes the self-destruction of cells (apoptosis). The resulting degeneration of muscle tissue leads to the signs and symptoms of CAV3-related distal myopathy.  In addition to CAV3-related distal myopathy, CAV3 gene mutations can cause other caveolinopathies including limb-girdle muscular dystrophy, rippling muscle disease, isolated hyperCKemia, and a heart disorder called hypertrophic cardiomyopathy. Several CAV3 gene mutations have been found to cause different caveolinopathies in different individuals. It is unclear why a single CAV3 gene mutation may cause different patterns of signs and symptoms, even within the same family.",CAV3-related distal myopathy,0000162,GHR,https://ghr.nlm.nih.gov/condition/cav3-related-distal-myopathy,C0751336,T047,Disorders
Is CAV3-related distal myopathy inherited ?,0000162-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with CAV3-related distal myopathy or another caveolinopathy. Rare cases result from new mutations in the gene and occur in people with no history of caveolinopathies in their family.",CAV3-related distal myopathy,0000162,GHR,https://ghr.nlm.nih.gov/condition/cav3-related-distal-myopathy,C0751336,T047,Disorders
What are the treatments for CAV3-related distal myopathy ?,0000162-5,treatment,"These resources address the diagnosis or management of CAV3-related distal myopathy:  - Gene Review: Gene Review: Caveolinopathies  - Genetic Testing Registry: CAV3-Related Distal Myopathy  - Genetic Testing Registry: Distal myopathy, Tateyama type  - MedlinePlus Encyclopedia: Electromyography  - MedlinePlus Encyclopedia: Muscle Biopsy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",CAV3-related distal myopathy,0000162,GHR,https://ghr.nlm.nih.gov/condition/cav3-related-distal-myopathy,C0751336,T047,Disorders
What is (are) celiac disease ?,0000163-1,information,"Celiac disease is a condition in which the immune system is abnormally sensitive to gluten, a protein found in wheat, rye, and barley. Celiac disease is an autoimmune disorder; autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. Without a strict, lifelong gluten-free diet, inflammation resulting from immune system overactivity may cause a wide variety of signs and symptoms involving many parts of the body.  Celiac disease can develop at any age after an individual starts eating foods containing gluten. The classic symptoms of the condition result from inflammation affecting the gastrointestinal tract. This inflammation damages the villi, which are small, finger-like projections that line the small intestine and provide a greatly increased surface area to absorb nutrients. In celiac disease, the villi become shortened and eventually flatten out. Intestinal damage causes diarrhea and poor absorption of nutrients, which may lead to weight loss. Abdominal pain, swelling (distention), and food intolerances are common in celiac disease. Inflammation associated with celiac disease may lead to an increased risk of developing certain gastrointestinal cancers such as cancers of the small intestine or esophagus.  Inflammation and poor nutrient absorption may lead to problems affecting many other organs and systems of the body in affected individuals. These health problems may include iron deficiency that results in a low number of red blood cells (anemia), vitamin deficiencies, low bone mineral density (osteoporosis), itchy skin rashes (dermatitis herpetiformis), defects in the enamel of the teeth, chronic fatigue, joint pain, poor growth, delayed puberty, infertility, or repeated miscarriages. Neurological problems have also been associated with celiac disease; these include migraine headaches, depression, attention deficit hyperactivity disorder (ADHD), and recurrent seizures (epilepsy). Many people with celiac disease have one or more of these varied health problems but do not have gastrointestinal symptoms. This form of the condition is called nonclassic celiac disease. Researchers now believe that nonclassic celiac disease is actually more common than the classic form.  Celiac disease often goes undiagnosed because many of its signs and symptoms are nonspecific, which means they may occur in many disorders. Most people who have one or more of these nonspecific health problems do not have celiac disease. On average, a diagnosis of celiac disease is not made until 6 to 10 years after symptoms begin.  Some people have silent celiac disease, in which they have no symptoms of the disorder. However, people with silent celiac disease do have immune proteins in their blood (antibodies) that are common in celiac disease. They also have inflammatory damage to their small intestine that can be detected with a biopsy.  In a small number of cases, celiac disease does not improve with a gluten-free diet and progresses to a condition called refractory sprue. Refractory sprue is characterized by chronic inflammation of the gastrointestinal tract, poor absorption of nutrients, and an increased risk of developing a type of cancer of the immune cells called T-cell lymphoma.",celiac disease,0000163,GHR,https://ghr.nlm.nih.gov/condition/celiac-disease,C0007570,T047,Disorders
How many people are affected by celiac disease ?,0000163-2,frequency,Celiac disease is a common disorder. Its prevalence has been estimated at about 1 in 100 people worldwide.,celiac disease,0000163,GHR,https://ghr.nlm.nih.gov/condition/celiac-disease,C0007570,T047,Disorders
What are the genetic changes related to celiac disease ?,0000163-3,genetic changes,"The risk of developing celiac disease is increased by certain variants of the HLA-DQA1 and HLA-DQB1 genes. These genes provide instructions for making proteins that play a critical role in the immune system. The HLA-DQA1 and HLA-DQB1 genes belong to a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders such as viruses and bacteria.  The proteins produced from the HLA-DQA1 and HLA-DQB1 genes attach (bind) to each other to form a functional protein complex called an antigen-binding DQ heterodimer. This complex, which is present on the surface of certain immune system cells, attaches to protein fragments (peptides) outside the cell. If the immune system recognizes the peptides as foreign (such as viral or bacterial peptides), it triggers a response to attack the invading viruses or bacteria.  Celiac disease is associated with an inappropriate immune response to a segment of the gluten protein called gliadin. This inappropriate activation of the immune system causes inflammation that damages the body's organs and tissues and leads to the signs and symptoms of celiac disease.  Almost all people with celiac disease have specific variants of the HLA-DQA1 and HLA-DQB1 genes, which seem to increase the risk of an inappropriate immune response to gliadin. However, these variants are also found in 30 percent of the general population, and only 3 percent of individuals with the gene variants develop celiac disease.  It appears likely that other contributors, such as environmental factors and changes in other genes, also influence the development of this complex disorder.",celiac disease,0000163,GHR,https://ghr.nlm.nih.gov/condition/celiac-disease,C0007570,T047,Disorders
Is celiac disease inherited ?,0000163-4,inheritance,"Celiac disease tends to cluster in families. Parents, siblings, or children (first-degree relatives) of people with celiac disease have between a 4 and 15 percent chance of developing the disorder. However, the inheritance pattern is unknown.",celiac disease,0000163,GHR,https://ghr.nlm.nih.gov/condition/celiac-disease,C0007570,T047,Disorders
What are the treatments for celiac disease ?,0000163-5,treatment,"These resources address the diagnosis or management of celiac disease:  - Beth Israel Deaconess: Celiac Center  - Columbia University Celiac Disease Center  - Gene Review: Gene Review: Celiac Disease  - Genetic Testing Registry: Celiac disease  - Massachusetts General Hospital Center for Celiac Research and Treatment  - MedlinePlus Encyclopedia: Celiac Disease Nutritional Considerations  - North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition: Gluten-Free Diet Guide  - University of Chicago Celiac Disease Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",celiac disease,0000163,GHR,https://ghr.nlm.nih.gov/condition/celiac-disease,C0007570,T047,Disorders
What is (are) central core disease ?,0000164-1,information,"Central core disease is a disorder that affects muscles used for movement (skeletal muscles). This condition causes muscle weakness that ranges from almost unnoticeable to very severe.  Most people with central core disease experience persistent, mild muscle weakness that does not worsen with time. This weakness affects the muscles near the center of the body (proximal muscles), particularly muscles in the upper legs and hips. Muscle weakness causes affected infants to appear ""floppy"" and can delay the development of motor skills such as sitting, standing, and walking. In severe cases, affected infants experience profoundly weak muscle tone (hypotonia) and serious or life-threatening breathing problems. Central core disease is also associated with skeletal abnormalities such as abnormal curvature of the spine (scoliosis), hip dislocation, and joint deformities called contractures that restrict the movement of certain joints.  Many people with central core disease also have an increased risk of developing a severe reaction to certain drugs used during surgery and other invasive procedures. This reaction is called malignant hyperthermia. Malignant hyperthermia occurs in response to some anesthetic gases, which are used to block the sensation of pain, and with a particular type of muscle relaxant. If given these drugs, people at risk for malignant hyperthermia may experience muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), a high fever, increased acid levels in the blood and other tissues (acidosis), and a rapid heart rate. The complications of malignant hyperthermia can be life-threatening unless they are treated promptly.  Central core disease gets its name from disorganized areas called cores, which are found in the center of muscle fibers in many affected individuals. These abnormal regions can only be seen under a microscope. Although the presence of cores can help doctors diagnose central core disease, it is unclear how they are related to muscle weakness and the other features of this condition.",central core disease,0000164,GHR,https://ghr.nlm.nih.gov/condition/central-core-disease,C0751951,T047,Disorders
How many people are affected by central core disease ?,0000164-2,frequency,"Central core disease is probably an uncommon condition, although its incidence is unknown.",central core disease,0000164,GHR,https://ghr.nlm.nih.gov/condition/central-core-disease,C0751951,T047,Disorders
What are the genetic changes related to central core disease ?,0000164-3,genetic changes,"Mutations in the RYR1 gene cause central core disease.  The RYR1 gene provides instructions for making a protein called ryanodine receptor 1. This protein plays an essential role in skeletal muscles. For the body to move normally, these muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of charged atoms (ions) into muscle cells. The ryanodine receptor 1 protein forms a channel that releases calcium ions stored within muscle cells. The resulting increase in calcium ion concentration inside muscle cells stimulates muscle fibers to contract, allowing the body to move.  Mutations in the RYR1 gene change the structure of ryanodine receptor 1, allowing calcium ions to ""leak"" through the abnormal channel or impairing the channel's ability to release stored calcium ions at the correct time. This disruption in calcium ion transport prevents muscles from contracting normally, leading to the muscle weakness characteristic of central core disease.",central core disease,0000164,GHR,https://ghr.nlm.nih.gov/condition/central-core-disease,C0751951,T047,Disorders
Is central core disease inherited ?,0000164-4,inheritance,"Central core disease is most often inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.  Less commonly, central core disease is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but typically do not show signs and symptoms of the condition. People who carry one mutated copy of the RYR1 gene, however, may be at increased risk for malignant hyperthermia.",central core disease,0000164,GHR,https://ghr.nlm.nih.gov/condition/central-core-disease,C0751951,T047,Disorders
What are the treatments for central core disease ?,0000164-5,treatment,These resources address the diagnosis or management of central core disease:  - Gene Review: Gene Review: Central Core Disease  - Genetic Testing Registry: Central core disease  - MedlinePlus Encyclopedia: Hypotonia  - MedlinePlus Encyclopedia: Malignant Hyperthermia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,central core disease,0000164,GHR,https://ghr.nlm.nih.gov/condition/central-core-disease,C0751951,T047,Disorders
What is (are) centronuclear myopathy ?,0000165-1,information,"Centronuclear myopathy is a condition characterized by muscle weakness (myopathy) and wasting (atrophy) in the skeletal muscles, which are the muscles used for movement. The severity of centronuclear myopathy varies among affected individuals, even among members of the same family.  People with centronuclear myopathy begin experiencing muscle weakness at any time from birth to early adulthood. The muscle weakness slowly worsens over time and can lead to delayed development of motor skills, such as crawling or walking; muscle pain during exercise; and difficulty walking. Some affected individuals may need wheelchair assistance as the muscles atrophy and weakness becomes more severe. In rare instances, the muscle weakness improves over time.  Some people with centronuclear myopathy experience mild to severe breathing problems related to the weakness of muscles needed for breathing. People with centronuclear myopathy may have droopy eyelids (ptosis) and weakness in other facial muscles, including the muscles that control eye movement. People with this condition may also have foot abnormalities, a high arch in the roof of the mouth (high-arched palate), and abnormal side-to-side curvature of the spine (scoliosis). Rarely, individuals with centronuclear myopathy have a weakened heart muscle (cardiomyopathy), disturbances in nerve function (neuropathy), or intellectual disability.  A key feature of centronuclear myopathy is the displacement of the nucleus in muscle cells, which can be viewed under a microscope. Normally the nucleus is found at the edges of the rod-shaped muscle cells, but in people with centronuclear myopathy the nucleus is located in the center of these cells. How the change in location of the nucleus affects muscle cell function is unknown.",centronuclear myopathy,0000165,GHR,https://ghr.nlm.nih.gov/condition/centronuclear-myopathy,C0752282,T047,Disorders
How many people are affected by centronuclear myopathy ?,0000165-2,frequency,Centronuclear myopathy is a rare condition; its exact prevalence is unknown.,centronuclear myopathy,0000165,GHR,https://ghr.nlm.nih.gov/condition/centronuclear-myopathy,C0752282,T047,Disorders
What are the genetic changes related to centronuclear myopathy ?,0000165-3,genetic changes,"Centronuclear myopathy is most often caused by mutations in the DNM2, BIN1, or TTN gene. The proteins produced from the DNM2 and BIN1 genes are involved in endocytosis, a process that brings substances into the cell. The protein produced from the BIN1 gene plays an additional role in the formation of tube-like structures called transverse tubules (or T tubules), which are found within the membrane of muscle fibers. These tubules help transmit the electrical impulses necessary for normal muscle tensing (contraction) and relaxation. The protein produced from the DNM2 gene also regulates the actin cytoskeleton, which makes up the muscle fiber's structural framework. DNM2 and BIN1 gene mutations lead to abnormal muscle fibers that cannot contract and relax normally, resulting in muscle weakness.  The TTN gene provides instructions for making a protein called titin that is an essential component of muscle fiber structures called sarcomeres. Sarcomeres are the basic units of muscle contraction; they are made of proteins that generate the mechanical force needed for muscles to contract. TTN gene mutations decrease or alter titin's activity in muscle fibers. It is unclear how these mutations lead to centronuclear myopathy, but it is likely that the altered protein cannot interact with other proteins in the sarcomere, leading to dysfunction of the sarcomere. Abnormal sarcomeres prevent muscle fibers from contracting and relaxing normally, resulting in muscle weakness.  Some people with centronuclear myopathy do not have identified mutations in the DNM2, BIN1, or TTN genes. Mutations in other genes associated with this condition are found in a small percentage of cases. Some males with signs and symptoms of severe centronuclear myopathy may have a condition called X-linked myotubular myopathy, which is similar to centronuclear myopathy, and is often considered a subtype of the condition, but has a different genetic cause. In some people with centronuclear myopathy, the cause of the disorder is unknown. Researchers are looking for additional genes that are associated with centronuclear myopathy.",centronuclear myopathy,0000165,GHR,https://ghr.nlm.nih.gov/condition/centronuclear-myopathy,C0752282,T047,Disorders
Is centronuclear myopathy inherited ?,0000165-4,inheritance,"When centronuclear myopathy is caused by mutations in the DNM2 gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered DNM2 gene in each cell is sufficient to cause the disorder. Rarely, BIN1 gene mutations that are inherited in an autosomal dominant pattern can cause centronuclear myopathy.  Centronuclear myopathy caused by TTN gene mutations and most cases caused by BIN1 gene mutations are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Other cases of centronuclear myopathy that are not caused by these genes are typically inherited in an autosomal recessive manner, although some follow an autosomal dominant pattern.",centronuclear myopathy,0000165,GHR,https://ghr.nlm.nih.gov/condition/centronuclear-myopathy,C0752282,T047,Disorders
What are the treatments for centronuclear myopathy ?,0000165-5,treatment,"These resources address the diagnosis or management of centronuclear myopathy:  - Genetic Testing Registry: Autosomal recessive centronuclear myopathy  - Genetic Testing Registry: Myopathy, centronuclear  - Genetic Testing Registry: Myopathy, centronuclear, 1  - Genetic Testing Registry: Myopathy, centronuclear, 4  - Genetic Testing Registry: Myopathy, centronuclear, 5   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",centronuclear myopathy,0000165,GHR,https://ghr.nlm.nih.gov/condition/centronuclear-myopathy,C0752282,T047,Disorders
What is (are) cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy ?,0000166-1,information,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, usually called CADASIL, is an inherited condition that causes stroke and other impairments. This condition affects blood flow in small blood vessels, particularly cerebral vessels within the brain. The muscle cells surrounding these blood vessels (vascular smooth muscle cells) are abnormal and gradually die. In the brain, the resulting blood vessel damage (arteriopathy) can cause migraines, often with visual sensations or auras, or recurrent seizures (epilepsy).  Damaged blood vessels reduce blood flow and can cause areas of tissue death (infarcts) throughout the body. An infarct in the brain can lead to a stroke. In individuals with CADASIL, a stroke can occur at any time from childhood to late adulthood, but typically happens during mid-adulthood. People with CADASIL often have more than one stroke in their lifetime. Recurrent strokes can damage the brain over time. Strokes that occur in the subcortical region of the brain, which is involved in reasoning and memory, can cause progressive loss of intellectual function (dementia) and changes in mood and personality.  Many people with CADASIL also develop leukoencephalopathy, which is a change in a type of brain tissue called white matter that can be seen with magnetic resonance imaging (MRI).  The age at which the signs and symptoms of CADASIL first begin varies greatly among affected individuals, as does the severity of these features.  CADASIL is not associated with the common risk factors for stroke and heart attack, such as high blood pressure and high cholesterol, although some affected individuals might also have these health problems.",cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,0000166,GHR,https://ghr.nlm.nih.gov/condition/cerebral-autosomal-dominant-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy,C0270612,T046,Disorders
How many people are affected by cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy ?,0000166-2,frequency,"CADASIL is likely a rare condition; however, its prevalence is unknown.",cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,0000166,GHR,https://ghr.nlm.nih.gov/condition/cerebral-autosomal-dominant-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy,C0270612,T046,Disorders
What are the genetic changes related to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy ?,0000166-3,genetic changes,"Mutations in the NOTCH3 gene cause CADASIL. The NOTCH3 gene provides instructions for producing the Notch3 receptor protein, which is important for the normal function and survival of vascular smooth muscle cells. When certain molecules attach (bind) to Notch3 receptors, the receptors send signals to the nucleus of the cell. These signals then turn on (activate) particular genes within vascular smooth muscle cells.  NOTCH3 gene mutations lead to the production of an abnormal Notch3 receptor protein that impairs the function and survival of vascular smooth muscle cells. Disruption of Notch3 functioning can lead to the self-destruction (apoptosis) of these cells. In the brain, the loss of vascular smooth muscle cells results in blood vessel damage that can cause the signs and symptoms of CADASIL.",cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,0000166,GHR,https://ghr.nlm.nih.gov/condition/cerebral-autosomal-dominant-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy,C0270612,T046,Disorders
Is cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy inherited ?,0000166-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered NOTCH3 gene in each cell is sufficient to cause the disorder.  In most cases, an affected person inherits the mutation from one affected parent. A few rare cases may result from new mutations in the NOTCH3 gene. These cases occur in people with no history of the disorder in their family.",cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,0000166,GHR,https://ghr.nlm.nih.gov/condition/cerebral-autosomal-dominant-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy,C0270612,T046,Disorders
What are the treatments for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy ?,0000166-5,treatment,These resources address the diagnosis or management of CADASIL:  - Butler Hospital: Treatment and Management of CADASIL  - Gene Review: Gene Review: CADASIL  - Genetic Testing Registry: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy  - MedlinePlus Encyclopedia: Multi-Infarct Dementia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,0000166,GHR,https://ghr.nlm.nih.gov/condition/cerebral-autosomal-dominant-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy,C0270612,T046,Disorders
What is (are) cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy ?,0000167-1,information,"Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, commonly known as CARASIL, is an inherited condition that causes stroke and other impairments.  Abnormalities affecting the brain and other parts of the nervous system become apparent in an affected person's twenties or thirties. Often, muscle stiffness (spasticity) in the legs and problems with walking are the first signs of the disorder. About half of affected individuals have a stroke or similar episode before age 40. As the disease progresses, most people with CARASIL also develop mood and personality changes, a decline in thinking ability (dementia), memory loss, and worsening problems with movement.  Other characteristic features of CARASIL include premature hair loss (alopecia) and attacks of low back pain. The hair loss often begins during adolescence and is limited to the scalp. Back pain, which develops in early to mid-adulthood, results from the breakdown (degeneration) of the discs that separate the bones of the spine (vertebrae) from one another.  The signs and symptoms of CARASIL worsen slowly with time. Over the course of several years, affected individuals become less able to control their emotions and communicate with others. They increasingly require help with personal care and other activities of daily living; after a few years, they become unable to care for themselves. Most affected individuals die within a decade after signs and symptoms first appear, although few people with the disease have survived for 20 to 30 years.",cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy,0000167,GHR,https://ghr.nlm.nih.gov/condition/cerebral-autosomal-recessive-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy,C0270612,T046,Disorders
How many people are affected by cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy ?,0000167-2,frequency,"CARASIL appears to be a rare condition. It has been identified in about 50 people, primarily in Japan and China.",cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy,0000167,GHR,https://ghr.nlm.nih.gov/condition/cerebral-autosomal-recessive-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy,C0270612,T046,Disorders
What are the genetic changes related to cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy ?,0000167-3,genetic changes,"CARASIL is caused by mutations in the HTRA1 gene. This gene provides instructions for making an enzyme that is found in many of the body's organs and tissues. One of the major functions of the HTRA1 enzyme is to regulate signaling by proteins in the transforming growth factor-beta (TGF-) family. TGF- signaling is essential for many critical cell functions. It also plays an important role in the formation of new blood vessels (angiogenesis).  In people with CARASIL, mutations in the HTRA1 gene prevent the effective regulation of TGF- signaling. Researchers suspect that abnormally increased TGF- signaling alters the structure of small blood vessels, particularly in the brain. These blood vessel abnormalities (described as arteriopathy) greatly increase the risk of stroke and lead to the death of nerve cells (neurons) in many areas of the brain. Dysregulation of TGF- signaling may also underlie the hair loss and back pain seen in people with CARASIL, although the relationship between abnormal TGF- signaling and these features is less clear.",cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy,0000167,GHR,https://ghr.nlm.nih.gov/condition/cerebral-autosomal-recessive-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy,C0270612,T046,Disorders
Is cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy inherited ?,0000167-4,inheritance,"As its name suggests, this condition is inherited in an autosomal recessive pattern. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy,0000167,GHR,https://ghr.nlm.nih.gov/condition/cerebral-autosomal-recessive-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy,C0270612,T046,Disorders
What are the treatments for cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy ?,0000167-5,treatment,These resources address the diagnosis or management of CARASIL:  - Gene Review: Gene Review: CARASIL  - Genetic Testing Registry: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy,0000167,GHR,https://ghr.nlm.nih.gov/condition/cerebral-autosomal-recessive-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy,C0270612,T046,Disorders
What is (are) cerebral cavernous malformation ?,0000168-1,information,"Cerebral cavernous malformations are collections of small blood vessels (capillaries) in the brain that are enlarged and irregular in structure. These capillaries have abnormally thin walls, and they lack other support tissues, such as elastic fibers, which normally make them stretchy. As a result, the blood vessels are prone to leakage, which can cause the health problems related to this condition. Cavernous malformations can occur anywhere in the body, but usually produce serious signs and symptoms only when they occur in the brain and spinal cord (which are described as cerebral).  Approximately 25 percent of individuals with cerebral cavernous malformations never experience any related health problems. Other people with this condition may experience serious signs and symptoms such as headaches, seizures, paralysis, hearing or vision loss, and bleeding in the brain (cerebral hemorrhage). Severe brain hemorrhages can result in death. The location and number of cerebral cavernous malformations determine the severity of this disorder. These malformations can change in size and number over time.  There are two forms of the condition: familial and sporadic. The familial form is passed from parent to child, and affected individuals typically have multiple cerebral cavernous malformations. The sporadic form occurs in people with no family history of the disorder. These individuals typically have only one malformation.",cerebral cavernous malformation,0000168,GHR,https://ghr.nlm.nih.gov/condition/cerebral-cavernous-malformation,C2919945,T190,Disorders
How many people are affected by cerebral cavernous malformation ?,0000168-2,frequency,Cerebral cavernous malformations affect about 0.5 percent of the population worldwide.,cerebral cavernous malformation,0000168,GHR,https://ghr.nlm.nih.gov/condition/cerebral-cavernous-malformation,C2919945,T190,Disorders
What are the genetic changes related to cerebral cavernous malformation ?,0000168-3,genetic changes,"Mutations in at least three genes, KRIT1 (also known as CCM1), CCM2, and PDCD10 (also known as CCM3), cause familial cerebral cavernous malformations.  The precise functions of these genes are not fully understood. Studies show that the proteins produced from these genes are found in the junctions connecting neighboring blood vessel cells. The proteins interact with each other as part of a complex that strengthens the interactions between cells and limits leakage from the blood vessels. Mutations in any of the three genes impair the function of the protein complex, resulting in weakened cell-to-cell junctions and increased leakage from vessels as seen in cerebral cavernous malformations.  Mutations in these three genes account for 85 to 95 percent of all cases of familial cerebral cavernous malformations. The remaining 5 to 15 percent of cases may be due to mutations in unidentified genes or to other unknown causes. Mutations in the KRIT1, CCM2, and PDCD10 genes are not involved in sporadic cerebral cavernous malformations. The cause of this form of the condition is unknown.",cerebral cavernous malformation,0000168,GHR,https://ghr.nlm.nih.gov/condition/cerebral-cavernous-malformation,C2919945,T190,Disorders
Is cerebral cavernous malformation inherited ?,0000168-4,inheritance,"This condition has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In the familial form, an affected person inherits the mutation from one affected parent.  Most people with cerebral cavernous malformations have the sporadic form of the disorder. These cases occur in people with no history of the disorder in their family.",cerebral cavernous malformation,0000168,GHR,https://ghr.nlm.nih.gov/condition/cerebral-cavernous-malformation,C2919945,T190,Disorders
What are the treatments for cerebral cavernous malformation ?,0000168-5,treatment,These resources address the diagnosis or management of cerebral cavernous malformation:  - Angioma Alliance: Imaging and Diagnostics  - Gene Review: Gene Review: Familial Cerebral Cavernous Malformation  - Genetic Testing Registry: Cerebral cavernous malformation  - Genetic Testing Registry: Cerebral cavernous malformations 1  - Genetic Testing Registry: Cerebral cavernous malformations 2  - Genetic Testing Registry: Cerebral cavernous malformations 3  - MedlinePlus Encyclopedia: Cerebral angiography   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,cerebral cavernous malformation,0000168,GHR,https://ghr.nlm.nih.gov/condition/cerebral-cavernous-malformation,C2919945,T190,Disorders
What is (are) cerebrotendinous xanthomatosis ?,0000170-1,information,"Cerebrotendinous xanthomatosis is a fat (lipid) storage disorder that affects many areas of the body. People with this disorder cannot break down certain lipids effectively, specifically different forms of cholesterol, so these fats accumulate in various areas of the body. Xanthomatosis refers to the formation of fatty yellow nodules (xanthomas). Cerebrotendinous refers to the typical locations of the xanthomas (cerebro- meaning the brain and -tendinous meaning connective tissue called tendons that attach muscle to bone).  Other features of cerebrotendinous xanthomatosis include chronic diarrhea during infancy, clouding of the lens of the eye (cataracts) developing in late childhood, progressively brittle bones that are prone to fracture, and neurological problems in adulthood, such as dementia, seizures, hallucinations, depression, and difficulty with coordinating movements (ataxia) and speech (dysarthria). The neurological symptoms are thought to be caused by an accumulation of fats and an increasing number of xanthomas in the brain. Xanthomas can also accumulate in the fatty substance that insulates and protects nerves (myelin), disrupting nerve signaling in the brain. Disorders that involve the destruction of myelin are known as leukodystrophies. Degeneration (atrophy) of brain tissue caused by excess lipid deposits also contributes to the neurological problems.  Xanthomas in the tendons (most commonly in the Achilles tendon, which connects the heel of the foot to the calf muscles) begin to form in early adulthood. Tendon xanthomas may cause discomfort and interfere with tendon flexibility. People with cerebrotendinous xanthomatosis are also at an increased risk of developing cardiovascular disease. If untreated, the signs and symptoms related to the accumulation of lipids throughout the body worsen over time; however, the course of this condition varies greatly among those who are affected.",cerebrotendinous xanthomatosis,0000170,GHR,https://ghr.nlm.nih.gov/condition/cerebrotendinous-xanthomatosis,C0238052,T047,Disorders
How many people are affected by cerebrotendinous xanthomatosis ?,0000170-2,frequency,"The incidence of cerebrotendinous xanthomatosis is estimated to be 3 to 5 per 100,000 people worldwide. This condition is more common in the Moroccan Jewish population with an incidence of 1 in 108 individuals.",cerebrotendinous xanthomatosis,0000170,GHR,https://ghr.nlm.nih.gov/condition/cerebrotendinous-xanthomatosis,C0238052,T047,Disorders
What are the genetic changes related to cerebrotendinous xanthomatosis ?,0000170-3,genetic changes,"Mutations in the CYP27A1 gene cause cerebrotendinous xanthomatosis. The CYP27A1 gene provides instructions for producing an enzyme called sterol 27-hydroxylase. This enzyme works in the pathway that breaks down cholesterol to form acids used in the digestion of fats (bile acids). Mutations in sterol 27-hydroxylase impair its ability to break down cholesterol to a specific bile acid called chenodeoxycholic acid. As a result, a molecule called cholestanol, which is similar to cholesterol, accumulates in xanthomas, blood, nerve cells, and the brain. Cholesterol levels are not increased in the blood, but they are elevated in various tissues throughout the body. The accumulation of cholesterol and cholestanol in the brain, tendons, and other tissues causes the signs and symptoms of cerebrotendinous xanthomatosis.",cerebrotendinous xanthomatosis,0000170,GHR,https://ghr.nlm.nih.gov/condition/cerebrotendinous-xanthomatosis,C0238052,T047,Disorders
Is cerebrotendinous xanthomatosis inherited ?,0000170-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",cerebrotendinous xanthomatosis,0000170,GHR,https://ghr.nlm.nih.gov/condition/cerebrotendinous-xanthomatosis,C0238052,T047,Disorders
What are the treatments for cerebrotendinous xanthomatosis ?,0000170-5,treatment,These resources address the diagnosis or management of cerebrotendinous xanthomatosis:  - Gene Review: Gene Review: Cerebrotendinous Xanthomatosis  - Genetic Testing Registry: Cholestanol storage disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,cerebrotendinous xanthomatosis,0000170,GHR,https://ghr.nlm.nih.gov/condition/cerebrotendinous-xanthomatosis,C0238052,T047,Disorders
What is (are) Chanarin-Dorfman syndrome ?,0000171-1,information,"Chanarin-Dorfman syndrome is a condition in which fats (lipids) are stored abnormally in the body. Affected individuals cannot break down certain fats called triglycerides, and these fats accumulate in organs and tissues, including skin, liver, muscles, intestine, eyes, and ears. People with this condition also have dry, scaly skin (ichthyosis), which is usually present at birth. Additional features of this condition include an enlarged liver (hepatomegaly), clouding of the lens of the eyes (cataracts), difficulty with coordinating movements (ataxia), hearing loss, short stature, muscle weakness (myopathy), involuntary movement of the eyes (nystagmus), and mild intellectual disability.  The signs and symptoms vary greatly among individuals with Chanarin-Dorfman syndrome. Some people may have ichthyosis only, while others may have problems affecting many areas of the body.",Chanarin-Dorfman syndrome,0000171,GHR,https://ghr.nlm.nih.gov/condition/chanarin-dorfman-syndrome,C0268238,T047,Disorders
How many people are affected by Chanarin-Dorfman syndrome ?,0000171-2,frequency,Chanarin-Dorfman syndrome is a rare condition; its incidence is unknown.,Chanarin-Dorfman syndrome,0000171,GHR,https://ghr.nlm.nih.gov/condition/chanarin-dorfman-syndrome,C0268238,T047,Disorders
What are the genetic changes related to Chanarin-Dorfman syndrome ?,0000171-3,genetic changes,"Mutations in the ABHD5 gene cause Chanarin-Dorfman syndrome. The ABHD5 gene provides instructions for making a protein that turns on (activates) the ATGL enzyme, which breaks down triglycerides. Triglycerides are the main source of stored energy in cells. These fats must be broken down into simpler molecules called fatty acids before they can be used for energy.  ABHD5 gene mutations impair the protein's ability to activate the ATGL enzyme. An inactive enzyme makes the breakdown of triglycerides impossible, causing them to accumulate in tissues throughout the body. The buildup of triglycerides results in the signs and symptoms of Chanarin-Dorfman syndrome.",Chanarin-Dorfman syndrome,0000171,GHR,https://ghr.nlm.nih.gov/condition/chanarin-dorfman-syndrome,C0268238,T047,Disorders
Is Chanarin-Dorfman syndrome inherited ?,0000171-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Chanarin-Dorfman syndrome,0000171,GHR,https://ghr.nlm.nih.gov/condition/chanarin-dorfman-syndrome,C0268238,T047,Disorders
What are the treatments for Chanarin-Dorfman syndrome ?,0000171-5,treatment,These resources address the diagnosis or management of Chanarin-Dorfman syndrome:  - Genetic Testing Registry: Triglyceride storage disease with ichthyosis  - MedlinePlus Encyclopedia: Ichthyosis vulgaris   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Chanarin-Dorfman syndrome,0000171,GHR,https://ghr.nlm.nih.gov/condition/chanarin-dorfman-syndrome,C0268238,T047,Disorders
What is (are) Char syndrome ?,0000172-1,information,"Char syndrome is a condition that affects the development of the face, heart, and limbs. It is characterized by a combination of three major features: a distinctive facial appearance, a heart defect called patent ductus arteriosus, and hand abnormalities.  Most people with Char syndrome have a characteristic facial appearance that includes flattened cheek bones and a flat nasal bridge (the area of the nose between the eyes). The tip of the nose is also flat and broad. The eyes are wide-set with droopy eyelids (ptosis) and outside corners that point downward (down-slanting palpebral fissures). Additional facial differences include a shortened distance between the nose and upper lip (a short philtrum), a triangular-shaped mouth, and thick, prominent lips.  Patent ductus arteriosus is a common heart defect in newborns, and it occurs in most babies with Char syndrome. Before birth, the ductus arteriosus forms a connection between two major arteries (the aorta and the pulmonary artery). This connection normally closes shortly after birth, but it remains open in babies with patent ductus arteriosus. If untreated, this heart defect causes infants to breathe rapidly, feed poorly, and gain weight slowly. In severe cases, it can lead to heart failure. People with patent ductus arteriosus also have an increased risk of infection.  Hand abnormalities are another feature of Char syndrome. In most people with this condition, the middle section of the fifth (pinky) finger is shortened or absent. Other abnormalities of the hands and feet have been reported but are less common.",Char syndrome,0000172,GHR,https://ghr.nlm.nih.gov/condition/char-syndrome,C1868570,T047,Disorders
How many people are affected by Char syndrome ?,0000172-2,frequency,"Char syndrome is rare, although its exact incidence is unknown. Only a few families with this condition have been identified worldwide.",Char syndrome,0000172,GHR,https://ghr.nlm.nih.gov/condition/char-syndrome,C1868570,T047,Disorders
What are the genetic changes related to Char syndrome ?,0000172-3,genetic changes,"Mutations in the TFAP2B gene cause Char syndrome. This gene provides instructions for making a protein known as transcription factor AP-2. A transcription factor is a protein that attaches (binds) to specific regions of DNA and helps control the activity of particular genes. Transcription factor AP-2 regulates genes that are involved in development before birth. In particular, this protein appears to play a role in the normal formation of structures in the face, heart, and limbs.  TFAP2B mutations alter the structure of transcription factor AP-2. Some of these mutations prevent the protein from binding to DNA, while other mutations render it unable to regulate the activity of other genes. A loss of this protein's function disrupts the normal development of several parts of the body before birth, resulting in the major features of Char syndrome.",Char syndrome,0000172,GHR,https://ghr.nlm.nih.gov/condition/char-syndrome,C1868570,T047,Disorders
Is Char syndrome inherited ?,0000172-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene and occur in people with no history of the disorder in their family.",Char syndrome,0000172,GHR,https://ghr.nlm.nih.gov/condition/char-syndrome,C1868570,T047,Disorders
What are the treatments for Char syndrome ?,0000172-5,treatment,These resources address the diagnosis or management of Char syndrome:  - Gene Review: Gene Review: Char Syndrome  - Genetic Testing Registry: Char syndrome  - MedlinePlus Encyclopedia: Patent Ductus Arteriosus   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Char syndrome,0000172,GHR,https://ghr.nlm.nih.gov/condition/char-syndrome,C1868570,T047,Disorders
What is (are) Charcot-Marie-Tooth disease ?,0000173-1,information,"Charcot-Marie-Tooth disease is a group of progressive disorders that affect the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound. Damage to the peripheral nerves can result in loss of sensation and wasting (atrophy) of muscles in the feet, legs, and hands.  Charcot-Marie-Tooth disease usually becomes apparent in adolescence or early adulthood, but onset may occur anytime from early childhood through late adulthood. Symptoms of Charcot-Marie-Tooth disease vary in severity, even among members of the same family. Some people never realize they have the disorder, but most have a moderate amount of physical disability. A small percentage of people experience severe weakness or other problems which, in rare cases, can be life-threatening. In most affected individuals, however, Charcot-Marie-Tooth disease does not affect life expectancy.  Typically, the earliest symptoms of Charcot-Marie-Tooth disease involve balance difficulties, clumsiness, and muscle weakness in the feet. Affected individuals may have foot abnormalities such as high arches (pes cavus), flat feet (pes planus), or curled toes (hammer toes). They often have difficulty flexing the foot or walking on the heel of the foot. These difficulties may cause a higher than normal step (or gait) and increase the risk of ankle injuries and tripping.  As the disease progresses, muscles in the lower legs usually weaken, but leg and foot problems rarely require the use of a wheelchair. Affected individuals may also develop weakness in the hands, causing difficulty with daily activities such as writing, fastening buttons, and turning doorknobs. People with this disorder typically experience a decreased sensitivity to touch, heat, and cold in the feet and lower legs, but occasionally feel aching or burning sensations. In some cases, affected individuals experience gradual hearing loss, deafness, or loss of vision.  There are several types of Charcot-Marie-Tooth disease. Type 1 Charcot-Marie-Tooth disease (CMT1) is characterized by abnormalities in myelin, the fatty substance that covers nerve cells, protecting them and helping to conduct nerve impulses. These abnormalities slow the transmission of nerve impulses. Type 2 Charcot-Marie-Tooth disease (CMT2) is characterized by abnormalities in the fiber, or axon, that extends from a nerve cell body and transmits nerve impulses. These abnormalities reduce the strength of the nerve impulse. Type 4 Charcot-Marie-Tooth disease (CMT4) affects either the axon or myelin and is distinguished from the other types by its pattern of inheritance. In intermediate forms of Charcot-Marie-Tooth disease, the nerve impulses are both slowed and reduced in strength, probably due to abnormalities in both axons and myelin. Type X Charcot-Marie-Tooth disease (CMTX) is caused by mutations in a gene on the X chromosome, one of the two sex chromosomes. Within the various types of Charcot-Marie-Tooth disease, subtypes (such as CMT1A, CMT1B, CMT2A, CMT4A, and CMTX1) are distinguished by the specific gene that is altered.  Sometimes other, more historical names are used to describe this disorder. For example, Roussy-Levy syndrome is a form of Charcot-Marie-Tooth disease defined by the additional feature of rhythmic shaking (tremors). Dejerine-Sottas syndrome is a term sometimes used to describe a severe, early childhood form of Charcot-Marie-Tooth disease; it is also sometimes called Charcot-Marie-Tooth disease type 3 (CMT3). Depending on the specific gene that is altered, this severe, early onset form of the disorder may also be classified as CMT1 or CMT4. CMTX5 is also known as Rosenberg-Chutorian syndrome. Some researchers believe that this condition is not actually a form of Charcot-Marie-Tooth disease. Instead, they classify it as a separate disorder characterized by peripheral nerve problems, deafness, and vision loss.",Charcot-Marie-Tooth disease,0000173,GHR,https://ghr.nlm.nih.gov/condition/charcot-marie-tooth-disease,C0007959,T047,Disorders
How many people are affected by Charcot-Marie-Tooth disease ?,0000173-2,frequency,"Charcot-Marie-Tooth disease is the most common inherited disorder that involves the peripheral nerves, affecting an estimated 150,000 people in the United States. It occurs in populations worldwide with a prevalence of about 1 in 2,500 individuals.",Charcot-Marie-Tooth disease,0000173,GHR,https://ghr.nlm.nih.gov/condition/charcot-marie-tooth-disease,C0007959,T047,Disorders
What are the genetic changes related to Charcot-Marie-Tooth disease ?,0000173-3,genetic changes,"Charcot-Marie-Tooth disease is caused by mutations in many different genes. These genes provide instructions for making proteins that are involved in the function of peripheral nerves in the feet, legs, and hands. The gene mutations that cause Charcot-Marie-Tooth disease affect the function of the proteins in ways that are not fully understood; however, they likely impair axons, which transmit nerve impulses, or affect the specialized cells that produce myelin. As a result, peripheral nerve cells slowly lose the ability to stimulate the muscles and to transmit sensory signals to the brain.  The list of genes associated with Charcot-Marie-Tooth disease continues to grow as researchers study this disorder. Different mutations within a particular gene may cause signs and symptoms of differing severities or lead to different types of Charcot-Marie-Tooth disease.  CMT1 is caused by mutations in the following genes: PMP22 (CMT1A and CMT1E), MPZ (CMT1B), LITAF (CMT1C), EGR2 (CMT1D), and NEFL (CMT1F).  CMT2 can result from alterations in many genes, including MFN2 and KIF1B (CMT2A); RAB7A (CMT2B); LMNA (CMT2B1); TRPV4 (CMT2C); BSCL2 and GARS (CMT2D); NEFL (CMT2E); HSPB1 (CMT2F); MPZ (CMT2I and CMT2J); GDAP1 (CMT2K); and HSPB8 (CMT2L). Certain DNM2 gene mutations also cause a form of CMT2.  CMT4 is caused by mutations in the following genes: GDAP1 (CMT4A), MTMR2 (CMT4B1), SBF2 (CMT4B2), SH3TC2 (CMT4C), NDRG1 (CMT4D), EGR2 (CMT4E), PRX (CMT4F), FGD4 (CMT4H), and FIG4 (CMT4J).  Intermediate forms of the disorder can be caused by alterations in genes including DNM2, MPZ, YARS, and GDAP1. CMTX is caused by mutations in genes including GJB1 (CMTX1) and PRPS1 (CMTX5). Mutations in additional genes, some of which have not been identified, also cause various forms of Charcot-Marie-Tooth disease.",Charcot-Marie-Tooth disease,0000173,GHR,https://ghr.nlm.nih.gov/condition/charcot-marie-tooth-disease,C0007959,T047,Disorders
Is Charcot-Marie-Tooth disease inherited ?,0000173-4,inheritance,"The pattern of inheritance varies with the type of Charcot-Marie-Tooth disease. CMT1, most cases of CMT2, and most intermediate forms are inherited in an autosomal dominant pattern. This pattern of inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one affected parent.  CMT4, a few CMT2 subtypes, and some intermediate forms are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.  CMTX is inherited in an X-linked dominant pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome. The inheritance is dominant if one copy of the altered gene is sufficient to cause the condition. In most cases, affected males, who have the alteration on their only copy of the X chromosome, experience more severe symptoms of the disorder than females, who have two X chromosomes. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. All daughters of affected men will have one altered X chromosome, but they may only have mild symptoms of the disorder.  Some cases of Charcot-Marie-Tooth disease result from a new mutation and occur in people with no history of the disorder in their family.",Charcot-Marie-Tooth disease,0000173,GHR,https://ghr.nlm.nih.gov/condition/charcot-marie-tooth-disease,C0007959,T047,Disorders
What are the treatments for Charcot-Marie-Tooth disease ?,0000173-5,treatment,"These resources address the diagnosis or management of Charcot-Marie-Tooth disease:  - Gene Review: Gene Review: Charcot-Marie-Tooth Hereditary Neuropathy Overview  - Gene Review: Gene Review: Charcot-Marie-Tooth Neuropathy Type 1  - Gene Review: Gene Review: Charcot-Marie-Tooth Neuropathy Type 2  - Gene Review: Gene Review: Charcot-Marie-Tooth Neuropathy Type 2A  - Gene Review: Gene Review: Charcot-Marie-Tooth Neuropathy Type 2E/1F  - Gene Review: Gene Review: Charcot-Marie-Tooth Neuropathy Type 4  - Gene Review: Gene Review: Charcot-Marie-Tooth Neuropathy Type 4A  - Gene Review: Gene Review: Charcot-Marie-Tooth Neuropathy Type 4C  - Gene Review: Gene Review: Charcot-Marie-Tooth Neuropathy X Type 1  - Gene Review: Gene Review: Charcot-Marie-Tooth Neuropathy X Type 5  - Gene Review: Gene Review: DNM2-Related Intermediate Charcot-Marie-Tooth Neuropathy  - Gene Review: Gene Review: GARS-Associated Axonal Neuropathy  - Gene Review: Gene Review: TRPV4-Associated Disorders  - Genetic Testing Registry: Charcot-Marie-Tooth disease  - Genetic Testing Registry: Charcot-Marie-Tooth disease dominant intermediate 3  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 1B  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 2B  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 2B1  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 2B2  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 2C  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 2D  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 2E  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 2F  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 2I  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 2J  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 2K  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 2P  - Genetic Testing Registry: Charcot-Marie-Tooth disease, X-linked recessive, type 5  - Genetic Testing Registry: Charcot-Marie-Tooth disease, axonal, type 2O  - Genetic Testing Registry: Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, autosomal recessive  - Genetic Testing Registry: Charcot-Marie-Tooth disease, dominant intermediate C  - Genetic Testing Registry: Charcot-Marie-Tooth disease, dominant intermediate E  - Genetic Testing Registry: Charcot-Marie-Tooth disease, recessive intermediate A  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 1C  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 2A1  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 2A2  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 2L  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 2N  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 4A  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 4B1  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 4B2  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 4C  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 4D  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 4H  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 4J  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type I  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type IA  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type ID  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type IE  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type IF  - Genetic Testing Registry: Congenital hypomyelinating neuropathy  - Genetic Testing Registry: DNM2-related intermediate Charcot-Marie-Tooth neuropathy  - Genetic Testing Registry: Dejerine-Sottas disease  - Genetic Testing Registry: Roussy-Lvy syndrome  - Genetic Testing Registry: X-linked hereditary motor and sensory neuropathy  - MedlinePlus Encyclopedia: Charcot-Marie-Tooth Disease  - MedlinePlus Encyclopedia: Hammer Toe  - MedlinePlus Encyclopedia: High Arch   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Charcot-Marie-Tooth disease,0000173,GHR,https://ghr.nlm.nih.gov/condition/charcot-marie-tooth-disease,C0007959,T047,Disorders
What is (are) CHARGE syndrome ?,0000174-1,information,"CHARGE syndrome is a disorder that affects many areas of the body. CHARGE stands for coloboma, heart defect, atresia choanae (also known as choanal atresia), retarded growth and development, genital abnormality, and ear abnormality. The pattern of malformations varies among individuals with this disorder, and infants often have multiple life-threatening medical conditions. The diagnosis of CHARGE syndrome is based on a combination of major and minor characteristics.  The major characteristics of CHARGE syndrome are more specific to this disorder than are the minor characteristics. Many individuals with CHARGE syndrome have a hole in one of the structures of the eye (coloboma), which forms during early development. A coloboma may be present in one or both eyes and can affect a person's vision, depending on its size and location. Some people also have small eyes (microphthalmia). One or both nasal passages may be narrowed (choanal stenosis) or completely blocked (choanal atresia). Individuals with CHARGE syndrome frequently have cranial nerve abnormalities. The cranial nerves emerge directly from the brain and extend to various areas of the head and neck, controlling muscle movement and transmitting sensory information. Abnormal function of certain cranial nerves can cause swallowing problems, facial paralysis, a sense of smell that is diminished (hyposmia) or completely absent (anosmia), and mild to profound hearing loss. People with CHARGE syndrome also typically have middle and inner ear abnormalities and unusually shaped ears.  The minor characteristics of CHARGE syndrome are not specific to this disorder; they are frequently present in people without CHARGE syndrome. The minor characteristics include heart defects, slow growth starting in late infancy, developmental delay, and an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate). Individuals frequently have hypogonadotropic hypogonadism, which affects the production of hormones that direct sexual development. Males are often born with an unusually small penis (micropenis) and undescended testes (cryptorchidism). External genitalia abnormalities are seen less often in females with CHARGE syndrome. Puberty can be incomplete or delayed. Individuals may have a tracheoesophageal fistula, which is an abnormal connection (fistula) between the esophagus and the trachea. People with CHARGE syndrome also have distinctive facial features, including a square-shaped face and difference in the appearance between the right and left sides of the face (facial asymmetry). Individuals have a wide range of cognitive function, from normal intelligence to major learning disabilities with absent speech and poor communication.",CHARGE syndrome,0000174,GHR,https://ghr.nlm.nih.gov/condition/charge-syndrome,C0265354,T019,Disorders
How many people are affected by CHARGE syndrome ?,0000174-2,frequency,"CHARGE syndrome occurs in approximately 1 in 8,500 to 10,000 individuals.",CHARGE syndrome,0000174,GHR,https://ghr.nlm.nih.gov/condition/charge-syndrome,C0265354,T019,Disorders
What are the genetic changes related to CHARGE syndrome ?,0000174-3,genetic changes,"Mutations in the CHD7 gene cause more than half of all cases of CHARGE syndrome. The CHD7 gene provides instructions for making a protein that most likely regulates gene activity (expression) by a process known as chromatin remodeling. Chromatin is the complex of DNA and protein that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. Chromatin remodeling is one way gene expression is regulated during development. When DNA is tightly packed, gene expression is lower than when DNA is loosely packed.  Most mutations in the CHD7 gene lead to the production of an abnormally short, nonfunctional CHD7 protein, which presumably disrupts chromatin remodeling and the regulation of gene expression. Changes in gene expression during embryonic development likely cause the signs and symptoms of CHARGE syndrome.  About one-third of individuals with CHARGE syndrome do not have an identified mutation in the CHD7 gene. Researchers suspect that other genetic and environmental factors may be involved in these individuals.",CHARGE syndrome,0000174,GHR,https://ghr.nlm.nih.gov/condition/charge-syndrome,C0265354,T019,Disorders
Is CHARGE syndrome inherited ?,0000174-4,inheritance,"CHARGE syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the CHD7 gene and occur in people with no history of the disorder in their family. In rare cases, an affected person inherits the mutation from an affected parent.",CHARGE syndrome,0000174,GHR,https://ghr.nlm.nih.gov/condition/charge-syndrome,C0265354,T019,Disorders
What are the treatments for CHARGE syndrome ?,0000174-5,treatment,These resources address the diagnosis or management of CHARGE syndrome:  - Gene Review: Gene Review: CHARGE Syndrome  - Genetic Testing Registry: CHARGE association  - MedlinePlus Encyclopedia: Choanal atresia  - MedlinePlus Encyclopedia: Coloboma  - MedlinePlus Encyclopedia: Facial Paralysis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,CHARGE syndrome,0000174,GHR,https://ghr.nlm.nih.gov/condition/charge-syndrome,C0265354,T019,Disorders
What is (are) Chediak-Higashi syndrome ?,0000175-1,information,"Chediak-Higashi syndrome is a condition that affects many parts of the body, particularly the immune system. This disease damages immune system cells, leaving them less able to fight off invaders such as viruses and bacteria. As a result, most people with Chediak-Higashi syndrome have repeated and persistent infections starting in infancy or early childhood. These infections tend to be very serious or life-threatening.  Chediak-Higashi syndrome is also characterized by a condition called oculocutaneous albinism, which causes abnormally light coloring (pigmentation) of the skin, hair, and eyes. Affected individuals typically have fair skin and light-colored hair, often with a metallic sheen. Oculocutaneous albinism also causes vision problems such as reduced sharpness; rapid, involuntary eye movements (nystagmus); and increased sensitivity to light (photophobia).  Many people with Chediak-Higashi syndrome have problems with blood clotting (coagulation) that lead to easy bruising and abnormal bleeding. In adulthood, Chediak-Higashi syndrome can also affect the nervous system, causing weakness, clumsiness, difficulty with walking, and seizures.  If the disease is not successfully treated, most children with Chediak-Higashi syndrome reach a stage of the disorder known as the accelerated phase. This severe phase of the disease is thought to be triggered by a viral infection. In the accelerated phase, white blood cells (which normally help fight infection) divide uncontrollably and invade many of the body's organs. The accelerated phase is associated with fever, episodes of abnormal bleeding, overwhelming infections, and organ failure. These medical problems are usually life-threatening in childhood.  A small percentage of people with Chediak-Higashi syndrome have a milder form of the condition that appears later in life. People with the adult form of the disorder have less noticeable changes in pigmentation and are less likely to have recurrent, severe infections. They do, however, have a significant risk of progressive neurological problems such as tremors, difficulty with movement and balance (ataxia), reduced sensation and weakness in the arms and legs (peripheral neuropathy), and a decline in intellectual functioning.",Chediak-Higashi syndrome,0000175,GHR,https://ghr.nlm.nih.gov/condition/chediak-higashi-syndrome,C0039082,T047,Disorders
How many people are affected by Chediak-Higashi syndrome ?,0000175-2,frequency,Chediak-Higashi syndrome is a rare disorder. About 200 cases of the condition have been reported worldwide.,Chediak-Higashi syndrome,0000175,GHR,https://ghr.nlm.nih.gov/condition/chediak-higashi-syndrome,C0039082,T047,Disorders
What are the genetic changes related to Chediak-Higashi syndrome ?,0000175-3,genetic changes,"Chediak-Higashi syndrome is caused by mutations in the LYST gene. This gene provides instructions for making a protein known as the lysosomal trafficking regulator. Researchers believe that this protein plays a role in the transport (trafficking) of materials into structures called lysosomes and similar cell structures. Lysosomes act as recycling centers within cells. They use digestive enzymes to break down toxic substances, digest bacteria that invade the cell, and recycle worn-out cell components.  Mutations in the LYST gene impair the normal function of the lysosomal trafficking regulator protein, which disrupts the size, structure, and function of lysosomes and related structures in cells throughout the body. In many cells, the lysosomes are abnormally large and interfere with normal cell functions. For example, enlarged lysosomes in certain immune system cells prevent these cells from responding appropriately to bacteria and other foreign invaders. As a result, the malfunctioning immune system cannot protect the body from infections.  In pigment cells called melanocytes, cellular structures called melanosomes (which are related to lysosomes) are abnormally large. Melanosomes produce and distribute a pigment called melanin, which is the substance that gives skin, hair, and eyes their color. People with Chediak-Higashi syndrome have oculocutaneous albinism because melanin is trapped within the giant melanosomes and is unable to contribute to skin, hair, and eye pigmentation.  Researchers believe that abnormal lysosome-like structures inside blood cells called platelets underlie the abnormal bruising and bleeding seen in people with Chediak-Higashi syndrome. Similarly, abnormal lysosomes in nerve cells probably cause the neurological problems associated with this disease.",Chediak-Higashi syndrome,0000175,GHR,https://ghr.nlm.nih.gov/condition/chediak-higashi-syndrome,C0039082,T047,Disorders
Is Chediak-Higashi syndrome inherited ?,0000175-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Chediak-Higashi syndrome,0000175,GHR,https://ghr.nlm.nih.gov/condition/chediak-higashi-syndrome,C0039082,T047,Disorders
What are the treatments for Chediak-Higashi syndrome ?,0000175-5,treatment,These resources address the diagnosis or management of Chediak-Higashi syndrome:  - Gene Review: Gene Review: Chediak-Higashi Syndrome  - Genetic Testing Registry: Chdiak-Higashi syndrome  - Immune Deficiency Foundation: Stem Cell and Gene Therapy  - International Patient Organisation for Primary Immunodeficiencies (IPOPI): Treatments for Primary Immunodeficiencies: A Guide for Patients and Their Families  - MedlinePlus Encyclopedia: Chediak-Higashi syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Chediak-Higashi syndrome,0000175,GHR,https://ghr.nlm.nih.gov/condition/chediak-higashi-syndrome,C0039082,T047,Disorders
What is (are) cherubism ?,0000176-1,information,"Cherubism is a disorder characterized by abnormal bone tissue in the lower part of the face. Beginning in early childhood, both the lower jaw (the mandible) and the upper jaw (the maxilla) become enlarged as bone is replaced with painless, cyst-like growths. These growths give the cheeks a swollen, rounded appearance and often interfere with normal tooth development. In some people the condition is so mild that it may not be noticeable, while other cases are severe enough to cause problems with vision, breathing, speech, and swallowing. Enlargement of the jaw usually continues throughout childhood and stabilizes during puberty. The abnormal growths are gradually replaced with normal bone in early adulthood. As a result, many affected adults have a normal facial appearance.  Most people with cherubism have few, if any, signs and symptoms affecting other parts of the body. Rarely, however, this condition occurs as part of another genetic disorder. For example, cherubism can occur with Ramon syndrome, which also involves short stature, intellectual disability, and overgrowth of the gums (gingival fibrosis). Additionally, cherubism has been reported in rare cases of Noonan syndrome (a developmental disorder characterized by unusual facial characteristics, short stature, and heart defects) and fragile X syndrome (a condition primarily affecting males that causes learning disabilities and cognitive impairment).",cherubism,0000176,GHR,https://ghr.nlm.nih.gov/condition/cherubism,C0008029,T047,Disorders
How many people are affected by cherubism ?,0000176-2,frequency,The incidence of cherubism is unknown. At least 250 cases have been reported worldwide.,cherubism,0000176,GHR,https://ghr.nlm.nih.gov/condition/cherubism,C0008029,T047,Disorders
What are the genetic changes related to cherubism ?,0000176-3,genetic changes,"Mutations in the SH3BP2 gene have been identified in about 80 percent of people with cherubism. In most of the remaining cases, the genetic cause of the condition is unknown.  The SH3BP2 gene provides instructions for making a protein whose exact function is unclear. The protein plays a role in transmitting chemical signals within cells, particularly cells involved in the replacement of old bone tissue with new bone (bone remodeling) and certain immune system cells.  Mutations in the SH3BP2 gene lead to the production of an overly active version of this protein. The effects of SH3BP2 mutations are still under study, but researchers believe that the abnormal protein disrupts critical signaling pathways in cells associated with the maintenance of bone tissue and in some immune system cells. The overactive protein likely causes inflammation in the jaw bones and triggers the production of osteoclasts, which are cells that break down bone tissue during bone remodeling. An excess of these bone-eating cells contributes to the destruction of bone in the upper and lower jaws. A combination of bone loss and inflammation likely underlies the cyst-like growths characteristic of cherubism.",cherubism,0000176,GHR,https://ghr.nlm.nih.gov/condition/cherubism,C0008029,T047,Disorders
Is cherubism inherited ?,0000176-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",cherubism,0000176,GHR,https://ghr.nlm.nih.gov/condition/cherubism,C0008029,T047,Disorders
What are the treatments for cherubism ?,0000176-5,treatment,These resources address the diagnosis or management of cherubism:  - Gene Review: Gene Review: Cherubism  - Genetic Testing Registry: Fibrous dysplasia of jaw   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,cherubism,0000176,GHR,https://ghr.nlm.nih.gov/condition/cherubism,C0008029,T047,Disorders
What is (are) childhood myocerebrohepatopathy spectrum ?,0000177-1,information,"Childhood myocerebrohepatopathy spectrum, commonly called MCHS, is part of a group of conditions called the POLG-related disorders. The conditions in this group feature a range of similar signs and symptoms involving muscle-, nerve-, and brain-related functions. MCHS typically becomes apparent in children from a few months to 3 years old. People with this condition usually have problems with their muscles (myo-), brain (cerebro-), and liver (hepato-).  Common signs and symptoms of MCHS include muscle weakness (myopathy), developmental delay or a deterioration of intellectual function, and liver disease. Another possible sign of this condition is a toxic buildup of lactic acid in the body (lactic acidosis). Often, affected children are unable to gain weight and grow at the expected rate (failure to thrive).  Additional signs and symptoms of MCHS can include a form of kidney disease called renal tubular acidosis, inflammation of the pancreas (pancreatitis), recurrent episodes of nausea and vomiting (cyclic vomiting), or hearing loss.",childhood myocerebrohepatopathy spectrum,0000177,GHR,https://ghr.nlm.nih.gov/condition/childhood-myocerebrohepatopathy-spectrum,C3713421,T047,Disorders
How many people are affected by childhood myocerebrohepatopathy spectrum ?,0000177-2,frequency,The prevalence of childhood myocerebrohepatopathy spectrum is unknown.,childhood myocerebrohepatopathy spectrum,0000177,GHR,https://ghr.nlm.nih.gov/condition/childhood-myocerebrohepatopathy-spectrum,C3713421,T047,Disorders
What are the genetic changes related to childhood myocerebrohepatopathy spectrum ?,0000177-3,genetic changes,"MCHS is caused by mutations in the POLG gene. This gene provides instructions for making one part, the alpha subunit, of a protein called polymerase gamma (pol ). Pol  functions in mitochondria, which are structures within cells that use oxygen to convert the energy from food into a form cells can use. Mitochondria each contain a small amount of DNA, known as mitochondrial DNA (mtDNA), which is essential for the normal function of these structures. Pol  ""reads"" sequences of mtDNA and uses them as templates to produce new copies of mtDNA in a process called DNA replication.  Most POLG gene mutations change single protein building blocks (amino acids) in the alpha subunit of pol . These changes result in a mutated pol  that has a reduced ability to replicate DNA. Although the mechanism is unknown, mutations in the POLG gene often result in fewer copies of mtDNA (mtDNA depletion), particularly in muscle, brain, or liver cells. MtDNA depletion causes a decrease in cellular energy, which could account for the signs and symptoms of MCHS.",childhood myocerebrohepatopathy spectrum,0000177,GHR,https://ghr.nlm.nih.gov/condition/childhood-myocerebrohepatopathy-spectrum,C3713421,T047,Disorders
Is childhood myocerebrohepatopathy spectrum inherited ?,0000177-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",childhood myocerebrohepatopathy spectrum,0000177,GHR,https://ghr.nlm.nih.gov/condition/childhood-myocerebrohepatopathy-spectrum,C3713421,T047,Disorders
What are the treatments for childhood myocerebrohepatopathy spectrum ?,0000177-5,treatment,These resources address the diagnosis or management of MCHS:  - Gene Review: Gene Review: POLG-Related Disorders  - United Mitochondrial Disease Foundation: Diagnosis of Mitochondrial Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,childhood myocerebrohepatopathy spectrum,0000177,GHR,https://ghr.nlm.nih.gov/condition/childhood-myocerebrohepatopathy-spectrum,C3713421,T047,Disorders
What is (are) CHMP2B-related frontotemporal dementia ?,0000178-1,information,"CHMP2B-related frontotemporal dementia is a progressive brain disorder that affects personality, behavior, and language. The symptoms of this disorder usually become noticeable in a person's fifties or sixties, and affected people survive about 3 to 21 years after the appearance of symptoms.  Changes in personality and behavior are the most common early signs of CHMP2B-related frontotemporal dementia. These changes include inappropriate emotional responses, restlessness, loss of initiative, and neglect of personal hygiene. Affected individuals may overeat sweet foods or place non-food items into their mouths (hyperorality). Additionally, it may become difficult for affected individuals to interact with others in a socially appropriate manner. They increasingly require help with personal care and other activities of daily living.  Many people with CHMP2B-related frontotemporal dementia develop progressive problems with speech and language (aphasia). They may have trouble speaking, although they can often understand others' speech and written text. Affected individuals may also have difficulty using numbers (dyscalculia). In the later stages of the disease, many completely lose the ability to communicate.  Several years after signs and symptoms first appear, some people with CHMP2B-related frontotemporal dementia develop problems with movement. These movement abnormalities include rigidity, tremors, uncontrolled muscle tensing (dystonia), and involuntary muscle spasms (myoclonus). As the disease progresses, most affected individuals become unable to walk.",CHMP2B-related frontotemporal dementia,0000178,GHR,https://ghr.nlm.nih.gov/condition/chmp2b-related-frontotemporal-dementia,C0236642,T047,Disorders
How many people are affected by CHMP2B-related frontotemporal dementia ?,0000178-2,frequency,CHMP2B-related frontotemporal dementia has been reported in one large family in Denmark and a few unrelated individuals from other countries. This disease appears to be a rare form of frontotemporal dementia.,CHMP2B-related frontotemporal dementia,0000178,GHR,https://ghr.nlm.nih.gov/condition/chmp2b-related-frontotemporal-dementia,C0236642,T047,Disorders
What are the genetic changes related to CHMP2B-related frontotemporal dementia ?,0000178-3,genetic changes,"CHMP2B-related frontotemporal dementia results from mutations in the CHMP2B gene. This gene provides instructions for making a protein called charged multivesicular body protein 2B. This protein is active in the brain, where it plays an essential role in transporting proteins that need to be broken down (degraded).  Mutations in the CHMP2B gene lead to the production of an abnormal version of charged multivesicular body protein 2B. Most of the mutations that cause CHMP2B-related frontotemporal dementia result in the production of an abnormal protein that is missing a critical segment at one end. This segment keeps the protein turned off (inactive) when it is not needed. Without this segment, the protein is constantly turned on (active), which disrupts the transport and degradation of other proteins. These abnormalities ultimately lead to the death of nerve cells (neurons) in the brain.  A gradual loss of neurons throughout the brain is characteristic of CHMP2B-related frontotemporal dementia. Many of the features of this disease result from neuronal death in regions near the front of the brain called the frontal and temporal lobes. The frontal lobes are involved in reasoning, planning, judgment, and problem-solving, while the temporal lobes help process hearing, speech, memory, and emotion. It is unclear why the signs and symptoms of this disease are related primarily to the frontal and temporal lobes.",CHMP2B-related frontotemporal dementia,0000178,GHR,https://ghr.nlm.nih.gov/condition/chmp2b-related-frontotemporal-dementia,C0236642,T047,Disorders
Is CHMP2B-related frontotemporal dementia inherited ?,0000178-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",CHMP2B-related frontotemporal dementia,0000178,GHR,https://ghr.nlm.nih.gov/condition/chmp2b-related-frontotemporal-dementia,C0236642,T047,Disorders
What are the treatments for CHMP2B-related frontotemporal dementia ?,0000178-5,treatment,"These resources address the diagnosis or management of CHMP2B-related frontotemporal dementia:  - Family Caregiver Alliance  - Gene Review: Gene Review: Frontotemporal Dementia, Chromosome 3-Linked  - Genetic Testing Registry: Frontotemporal Dementia, Chromosome 3-Linked   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",CHMP2B-related frontotemporal dementia,0000178,GHR,https://ghr.nlm.nih.gov/condition/chmp2b-related-frontotemporal-dementia,C0236642,T047,Disorders
What is (are) cholesteryl ester storage disease ?,0000179-1,information,"Cholesteryl ester storage disease is a rare inherited condition involving the breakdown and use of fats and cholesterol in the body (lipid metabolism). In affected individuals, harmful amounts of lipids accumulate in cells and tissues throughout the body. The liver is most severely affected. An enlarged liver (hepatomegaly) is one of the key signs of the disease. In addition, chronic liver disease (cirrhosis) can develop. An accumulation of fatty deposits on the artery walls (atherosclerosis) is usually seen early in life. The deposits narrow the arteries and can eventually block them, increasing the chance of having a heart attack or stroke.  The symptoms of cholesteryl ester storage disease are highly variable. Some people have such mild symptoms that they go undiagnosed until late adulthood, while others can have liver dysfunction in early childhood. The expected lifespan of those with cholesteryl ester storage disease depends on the severity of the associated complications.",cholesteryl ester storage disease,0000179,GHR,https://ghr.nlm.nih.gov/condition/cholesteryl-ester-storage-disease,C0008384,T047,Disorders
How many people are affected by cholesteryl ester storage disease ?,0000179-2,frequency,Cholesteryl ester storage disease appears to be a rare disorder. About 50 individuals affected by this condition have been reported worldwide.,cholesteryl ester storage disease,0000179,GHR,https://ghr.nlm.nih.gov/condition/cholesteryl-ester-storage-disease,C0008384,T047,Disorders
What are the genetic changes related to cholesteryl ester storage disease ?,0000179-3,genetic changes,"Mutations in the LIPA gene cause cholesteryl ester storage disease.  The LIPA gene provides instructions for making an enzyme called lysosomal acid lipase. This enzyme is found in the lysosomes (compartments that digest and recycle materials in the cell), where it breaks down lipids such as cholesteryl esters and triglycerides.  In the body, cholesterol works with high-density lipoproteins (HDL), often referred to as ""good cholesterol."" High-density lipoproteins carry cholesterol from the body's tissues to the liver for removal. When the cholesterol is attached to a fatty acid it is a cholesteryl ester. Normally, cholesteryl esters are broken down by lysosomal acid lipase into cholesterol and a fatty acid. Then the cholesterol can be transported by HDL to the liver for removal.  Mutations in the LIPA gene lead to a shortage of lysosomal acid lipase and prevent the body from using lipids properly. Without the activity of lysosomal acid lipase, the cholesteryl esters stay in the blood and tissues and are not able to be transported to the liver for excretion. The resulting buildup of triglycerides, cholesteryl esters, and other fats within the cells and tissues cause the signs and symptoms of cholesteryl ester storage disease.",cholesteryl ester storage disease,0000179,GHR,https://ghr.nlm.nih.gov/condition/cholesteryl-ester-storage-disease,C0008384,T047,Disorders
Is cholesteryl ester storage disease inherited ?,0000179-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",cholesteryl ester storage disease,0000179,GHR,https://ghr.nlm.nih.gov/condition/cholesteryl-ester-storage-disease,C0008384,T047,Disorders
What are the treatments for cholesteryl ester storage disease ?,0000179-5,treatment,These resources address the diagnosis or management of cholesteryl ester storage disease:  - Genetic Testing Registry: Lysosomal acid lipase deficiency  - MedlinePlus Encyclopedia: Atherosclerosis  - MedlinePlus Encyclopedia: Cirrhosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,cholesteryl ester storage disease,0000179,GHR,https://ghr.nlm.nih.gov/condition/cholesteryl-ester-storage-disease,C0008384,T047,Disorders
What is (are) CHOPS syndrome ?,0000180-1,information,"CHOPS syndrome is a disorder involving multiple abnormalities that are present from birth (congenital). The name ""CHOPS"" is an abbreviation for a list of features of the disorder including cognitive impairment, coarse facial features, heart defects, obesity, lung (pulmonary) involvement, short stature, and skeletal abnormalities.  Children with CHOPS syndrome have intellectual disability and delayed development of skills such as sitting and walking. Characteristic facial features include a round face; thick hair; thick eyebrows that grow together in the middle (synophrys); wide-set, bulging eyes with long eyelashes; a short nose; and down-turned corners of the mouth.  Most affected individuals are born with a heart defect called patent ductus arteriosus (PDA). The ductus arteriosus is a connection between two major arteries, the aorta and the pulmonary artery. This connection is open during fetal development and normally closes shortly after birth. However, the ductus arteriosus remains open, or patent, in babies with PDA. If untreated, this heart defect causes infants to breathe rapidly, feed poorly, and gain weight slowly; in severe cases, it can lead to heart failure. Multiple heart abnormalities have sometimes been found in children with CHOPS syndrome. In addition to PDA, affected individuals may have ventricular septal defect, which is a defect in the muscular wall (septum) that separates the right and left sides of the heart's lower chamber.  People with CHOPS syndrome have abnormalities of the throat and airways that cause momentary cessation of breathing while asleep (obstructive sleep apnea). These abnormalities can also cause affected individuals to breathe food or fluids into the lungs accidentally, which can lead to a potentially life-threatening bacterial lung infection (aspiration pneumonia) and chronic lung disease. Affected individuals are shorter than more than 97 percent of their peers and are overweight for their height. They also have skeletal differences including unusually short fingers and toes (brachydactyly) and abnormally-shaped spinal bones (vertebrae).  Other features that can occur in CHOPS syndrome include a small head size (microcephaly); hearing loss; clouding of the lens of the eye (cataract); a single, horseshoe-shaped kidney; and, in affected males, undescended testes (cryptorchidism).",CHOPS syndrome,0000180,GHR,https://ghr.nlm.nih.gov/condition/chops-syndrome,C0039082,T047,Disorders
How many people are affected by CHOPS syndrome ?,0000180-2,frequency,CHOPS syndrome is a rare disorder whose prevalence is unknown. Only a few affected individuals have been described in the medical literature.,CHOPS syndrome,0000180,GHR,https://ghr.nlm.nih.gov/condition/chops-syndrome,C0039082,T047,Disorders
What are the genetic changes related to CHOPS syndrome ?,0000180-3,genetic changes,"CHOPS syndrome is caused by mutations in the AFF4 gene. This gene provides instructions for making part of a protein complex called the super elongation complex (SEC). During embryonic development, the SEC is involved in an activity called transcription, which is the first step in the production of proteins from genes. By re-starting the transcription of certain genes after pauses that normally occur during the process, the SEC helps ensure that development proceeds appropriately before birth.  Mutations in the AFF4 gene are thought to result in an AFF4 protein that is not broken down when it is no longer needed, so more AFF4 protein is available than usual. The excess AFF4 protein interferes with normal pauses in transcription. This dysregulation of transcription leads to problems in the development of multiple organs and tissues, resulting in the signs and symptoms of CHOPS syndrome.",CHOPS syndrome,0000180,GHR,https://ghr.nlm.nih.gov/condition/chops-syndrome,C0039082,T047,Disorders
Is CHOPS syndrome inherited ?,0000180-4,inheritance,"CHOPS syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. All known cases of this condition result from new (de novo) mutations in the gene that occur during the formation of reproductive cells (eggs or sperm) or in early embryonic development. Affected individuals have no history of the disorder in their family.",CHOPS syndrome,0000180,GHR,https://ghr.nlm.nih.gov/condition/chops-syndrome,C0039082,T047,Disorders
What are the treatments for CHOPS syndrome ?,0000180-5,treatment,These resources address the diagnosis or management of CHOPS syndrome:  - Genetic Testing Registry: Chops syndrome  - MedlinePlus Encyclopedia: Congenital Heart Defect -- Corrective Surgery   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,CHOPS syndrome,0000180,GHR,https://ghr.nlm.nih.gov/condition/chops-syndrome,C0039082,T047,Disorders
What is (are) chordoma ?,0000181-1,information,"A chordoma is a rare type of cancerous tumor that can occur anywhere along the spine, from the base of the skull to the tailbone. Chordomas grow slowly, gradually extending into the bone and soft tissue around them. They often recur after treatment, and in about 40 percent of cases the cancer spreads (metastasizes) to other areas of the body, such as the lungs.  Approximately half of all chordomas occur at the base of the spine (sacrum), about one third occur in the base of the skull (occiput), and the rest occur in the cervical (neck), thoracic (upper back), or lumbar (lower back) vertebrae of the spine. As the chordoma grows, it puts pressure on the adjacent areas of the brain or spinal cord, leading to the signs and symptoms of the disorder. A chordoma anywhere along the spine may cause pain, weakness, or numbness in the back, arms, or legs. A chordoma at the base of the skull (occipital chordoma) may lead to double vision (diplopia) and headaches. A chordoma that occurs in the tailbone (coccygeal chordoma) may result in a lump large enough to be felt through the skin and may cause problems with bladder or bowel function.  Chordomas typically occur in adults between ages 40 and 70. About 5 percent of chordomas are diagnosed in children. For reasons that are unclear, males are affected about twice as often as females.",chordoma,0000181,GHR,https://ghr.nlm.nih.gov/condition/chordoma,C0008487,T191,Disorders
How many people are affected by chordoma ?,0000181-2,frequency,"Chordomas are rare, occurring in approximately 1 per million individuals each year. Chordomas comprise fewer than 1 percent of tumors affecting the brain and spinal cord.",chordoma,0000181,GHR,https://ghr.nlm.nih.gov/condition/chordoma,C0008487,T191,Disorders
What are the genetic changes related to chordoma ?,0000181-3,genetic changes,"Changes in the T gene have been associated with chordoma. An inherited duplication of the T gene identified in a few families is associated with an increased risk of developing a chordoma. Duplications or increases in activity (expression) of the T gene have also been identified in people with chordoma who have no history of the disorder in their family. In these individuals, the changes occur only in the tumor cells and are not inherited.  The T gene provides instructions for making a protein called brachyury. Brachyury is a member of a protein family called T-box proteins, which play critical roles during embryonic development. T-box proteins regulate the activity of other genes by attaching (binding) to specific regions of DNA. On the basis of this action, T-box proteins are called transcription factors.  The brachyury protein is especially important for the early development of the spine. In human embryos, a structure called the notochord is the precursor of the spinal column. The notochord disappears before birth, but in a small percentage of individuals, some of its cells remain in the base of the skull or in the spine. In rare cases these cells begin to grow and divide uncontrollably, invading the nearby bone and soft tissue and resulting in the development of a chordoma.  Duplications and increases in expression of the T gene both result in the production of excess brachyury protein. The specific mechanism by which excess brachyury protein contributes to the development of chordomas is unclear. Some people with chordoma do not have changes in the T gene, and the cause of the disorder in these individuals is unknown.",chordoma,0000181,GHR,https://ghr.nlm.nih.gov/condition/chordoma,C0008487,T191,Disorders
Is chordoma inherited ?,0000181-4,inheritance,"When development of a chordoma is associated with a duplication of the T gene inherited from a parent, one copy of the altered gene in each cell is sufficient to increase the risk of the disorder, which is an inheritance pattern called autosomal dominant. People with this duplication inherit an increased risk of this condition, not the condition itself.  Other cases of chordoma are sporadic, which means they occur in people with no history of the condition in their family.",chordoma,0000181,GHR,https://ghr.nlm.nih.gov/condition/chordoma,C0008487,T191,Disorders
What are the treatments for chordoma ?,0000181-5,treatment,These resources address the diagnosis or management of chordoma:  - Chordoma Foundation: Treatment  - Duke Spine Center  - Genetic Testing Registry: Chordoma  - Massachusetts General Hospital   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,chordoma,0000181,GHR,https://ghr.nlm.nih.gov/condition/chordoma,C0008487,T191,Disorders
What is (are) chorea-acanthocytosis ?,0000182-1,information,"Chorea-acanthocytosis is primarily a neurological disorder that affects movement in many parts of the body. Chorea refers to the involuntary jerking movements made by people with this disorder. People with this condition also have abnormal star-shaped red blood cells (acanthocytosis). This condition is one of a group of conditions called neuroacanthocytoses that involve neurological problems and abnormal red blood cells.  In addition to chorea, another common feature of chorea-acanthocytosis is involuntary tensing of various muscles (dystonia), such as those in the limbs, face, mouth, tongue, and throat. These muscle twitches can cause vocal tics (such as grunting), involuntary belching, and limb spasms. Eating can also be impaired as tongue and throat twitches can interfere with chewing and swallowing food. People with chorea-acanthocytosis may uncontrollably bite their tongue, lips, and inside of the mouth. Nearly half of all people with chorea-acanthocytosis have seizures.  Individuals with chorea-acanthocytosis may develop difficulty processing, learning, and remembering information (cognitive impairment). They may have reduced sensation and weakness in their arms and legs (peripheral neuropathy) and muscle weakness (myopathy). Impaired muscle and nerve functioning commonly cause speech difficulties in individuals with this condition, and can lead to an inability to speak.  Behavioral changes are a common feature of chorea-acanthocytosis and may be the first sign of this condition. These behavioral changes may include changes in personality, obsessive-compulsive disorder (OCD), lack of self-restraint, and the inability to take care of oneself.  The signs and symptoms of chorea-acanthocytosis usually begin in early to mid-adulthood. The movement problems of this condition worsen with age. Loss of cells (atrophy) in certain brain regions is the major cause of the neurological problems seen in people with chorea-acanthocytosis.",chorea-acanthocytosis,0000182,GHR,https://ghr.nlm.nih.gov/condition/chorea-acanthocytosis,C0393576,T047,Disorders
How many people are affected by chorea-acanthocytosis ?,0000182-2,frequency,"It is estimated that 500 to 1,000 people worldwide have chorea-acanthocytosis.",chorea-acanthocytosis,0000182,GHR,https://ghr.nlm.nih.gov/condition/chorea-acanthocytosis,C0393576,T047,Disorders
What are the genetic changes related to chorea-acanthocytosis ?,0000182-3,genetic changes,"Mutations in the VPS13A gene cause chorea-acanthocytosis. The VPS13A gene provides instructions for producing a protein called chorein; the function of this protein in the body is unknown. Some researchers believe that chorein plays a role in the movement of proteins within cells. Most VPS13A gene mutations lead to the production of an abnormally small, nonfunctional version of chorein. The VPS13A gene is active (expressed) throughout the body; it is unclear why mutations in this gene affect only the brain and red blood cells.",chorea-acanthocytosis,0000182,GHR,https://ghr.nlm.nih.gov/condition/chorea-acanthocytosis,C0393576,T047,Disorders
Is chorea-acanthocytosis inherited ?,0000182-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",chorea-acanthocytosis,0000182,GHR,https://ghr.nlm.nih.gov/condition/chorea-acanthocytosis,C0393576,T047,Disorders
What are the treatments for chorea-acanthocytosis ?,0000182-5,treatment,These resources address the diagnosis or management of chorea-acanthocytosis:  - Gene Review: Gene Review: Chorea-Acanthocytosis  - Genetic Testing Registry: Choreoacanthocytosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,chorea-acanthocytosis,0000182,GHR,https://ghr.nlm.nih.gov/condition/chorea-acanthocytosis,C0393576,T047,Disorders
What is (are) choroideremia ?,0000183-1,information,"Choroideremia is a condition characterized by progressive vision loss that mainly affects males. The first symptom of this condition is usually an impairment of night vision (night blindness), which can occur in early childhood. A progressive narrowing of the field of vision (tunnel vision) follows, as well as a decrease in the ability to see details (visual acuity). These vision problems are due to an ongoing loss of cells (atrophy) in the specialized light-sensitive tissue that lines the back of the eye (retina) and a nearby network of blood vessels (the choroid). The vision impairment in choroideremia worsens over time, but the progression varies among affected individuals. However, all individuals with this condition will develop blindness, most commonly in late adulthood.",choroideremia,0000183,GHR,https://ghr.nlm.nih.gov/condition/choroideremia,C0008525,T047,Disorders
How many people are affected by choroideremia ?,0000183-2,frequency,"The prevalence of choroideremia is estimated to be 1 in 50,000 to 100,000 people. However, it is likely that this condition is underdiagnosed because of its similarities to other eye disorders. Choroideremia is thought to account for approximately 4 percent of all blindness.",choroideremia,0000183,GHR,https://ghr.nlm.nih.gov/condition/choroideremia,C0008525,T047,Disorders
What are the genetic changes related to choroideremia ?,0000183-3,genetic changes,"Mutations in the CHM gene cause choroideremia. The CHM gene provides instructions for producing the Rab escort protein-1 (REP-1). As an escort protein, REP-1 attaches to molecules called Rab proteins within the cell and directs them to the membranes of various cell compartments (organelles). Rab proteins are involved in the movement of proteins and organelles within cells (intracellular trafficking). Mutations in the CHM gene lead to an absence of REP-1 protein or the production of a REP-1 protein that cannot carry out its protein escort function. This lack of functional REP-1 prevents Rab proteins from reaching and attaching (binding) to the organelle membranes. Without the aid of Rab proteins in intracellular trafficking, cells die prematurely.  The REP-1 protein is active (expressed) throughout the body, as is a similar protein, REP-2. Research suggests that when REP-1 is absent or nonfunctional, REP-2 can perform the protein escort duties of REP-1 in many of the body's tissues. Very little REP-2 protein is present in the retina, however, so it cannot compensate for the loss of REP-1 in this tissue. Loss of REP-1 function and subsequent misplacement of Rab proteins within the cells of the retina causes the progressive vision loss characteristic of choroideremia.",choroideremia,0000183,GHR,https://ghr.nlm.nih.gov/condition/choroideremia,C0008525,T047,Disorders
Is choroideremia inherited ?,0000183-4,inheritance,"Choroideremia is inherited in an X-linked recessive pattern. The CHM gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In X-linked recessive inheritance, a female with one mutated copy of the gene in each cell is called a carrier. She can pass on the altered gene, but usually does not experience signs and symptoms of the disorder. Females who carry a CHM mutation may show small areas of cell loss within the retina that can be observed during a thorough eye examination. These changes can impair vision later in life.",choroideremia,0000183,GHR,https://ghr.nlm.nih.gov/condition/choroideremia,C0008525,T047,Disorders
What are the treatments for choroideremia ?,0000183-5,treatment,These resources address the diagnosis or management of choroideremia:  - Gene Review: Gene Review: Choroideremia  - Genetic Testing Registry: Choroideremia  - MedlinePlus Encyclopedia: Vision - night blindness  - MedlinePlus Encyclopedia: Visual field   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,choroideremia,0000183,GHR,https://ghr.nlm.nih.gov/condition/choroideremia,C0008525,T047,Disorders
What is (are) Christianson syndrome ?,0000184-1,information,"Christianson syndrome is a disorder that primarily affects the nervous system. This condition becomes apparent in infancy. Its characteristic features include delayed development, intellectual disability, an inability to speak, problems with balance and coordination (ataxia), and difficulty standing or walking. Individuals who do learn to walk lose the ability in childhood. Most affected children also have recurrent seizures (epilepsy), beginning between ages 1 and 2.  Other features seen in many people with Christianson syndrome include a small head size (microcephaly); a long, narrow face with prominent nose, jaw, and ears; an open mouth and uncontrolled drooling; and abnormal eye movements. Affected children often have a happy demeanor with frequent smiling and spontaneous laughter.",Christianson syndrome,0000184,GHR,https://ghr.nlm.nih.gov/condition/christianson-syndrome,C3812402,T047,Disorders
How many people are affected by Christianson syndrome ?,0000184-2,frequency,"Christianson syndrome is a rare condition, although the exact prevalence is unknown. The condition was first described in a South African family and has since been found people in other parts of the world.",Christianson syndrome,0000184,GHR,https://ghr.nlm.nih.gov/condition/christianson-syndrome,C3812402,T047,Disorders
What are the genetic changes related to Christianson syndrome ?,0000184-3,genetic changes,"Christianson syndrome is caused by mutations in the SLC9A6 gene, which provides instructions for making a protein called sodium/hydrogen exchanger 6 (Na+/H+ exchanger 6 or NHE6). The NHE6 protein is found in the membrane surrounding endosomes, which are compartments within cells that recycle proteins and other materials. The NHE6 protein acts as a channel to exchange positively charged atoms (ions) of sodium (Na+) with hydrogen ions (H+). By controlling the amount of hydrogen ions, the NHE6 protein helps regulate the relative acidity (pH) inside endosomes, which is important for the recycling function of these compartments. The NHE6 protein may have additional functions, such as helping to move proteins to the correct location in the cell (protein trafficking).  Mutations in the SLC9A6 gene typically lead to an abnormally short NHE6 protein that is nonfunctional or that is broken down quickly in cells, resulting in the absence of functional NHE6 channels. As a result, the pH in endosomes is not properly maintained. It is unclear how unregulated endosomal pH leads to neurological problems in people with Christianson syndrome. Some studies have shown that protein trafficking by endosomes is important for learning and memory, but the role of endosomal pH or the NHE6 protein in this process has not been identified.",Christianson syndrome,0000184,GHR,https://ghr.nlm.nih.gov/condition/christianson-syndrome,C3812402,T047,Disorders
Is Christianson syndrome inherited ?,0000184-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In X-linked recessive inheritance, a female with one mutated copy of the gene in each cell is called a carrier. She can pass on the altered gene but usually does not experience signs and symptoms of the disorder. Occasionally, however, females who carry an SLC9A6 gene mutation have mild learning disabilities. It is unclear if these disabilities are related to the gene mutation or occur by chance.",Christianson syndrome,0000184,GHR,https://ghr.nlm.nih.gov/condition/christianson-syndrome,C3812402,T047,Disorders
What are the treatments for Christianson syndrome ?,0000184-5,treatment,These resources address the diagnosis or management of Christianson syndrome:  - Genetic Testing Registry: Christianson syndrome  - MedlinePlus Encyclopedia: Seizures   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Christianson syndrome,0000184,GHR,https://ghr.nlm.nih.gov/condition/christianson-syndrome,C3812402,T047,Disorders
What is (are) chronic atrial and intestinal dysrhythmia ?,0000185-1,information,"Chronic atrial and intestinal dysrhythmia (CAID) is a disorder affecting the heart and the digestive system. CAID disrupts the normal rhythm of the heartbeat; affected individuals have a heart rhythm abnormality called sick sinus syndrome. The disorder also impairs the rhythmic muscle contractions that propel food through the intestines (peristalsis), causing a digestive condition called intestinal pseudo-obstruction. The heart and digestive issues develop at the same time, usually by age 20.  Sick sinus syndrome (also known as sinus node dysfunction) is an abnormality of the sinoatrial (SA) node, which is an area of specialized cells in the heart that functions as a natural pacemaker. The SA node generates electrical impulses that start each heartbeat. These signals travel from the SA node to the rest of the heart, signaling the heart (cardiac) muscle to contract and pump blood. In people with sick sinus syndrome, the SA node does not function normally, which usually causes the heartbeat to be too slow (bradycardia), although occasionally the heartbeat is too fast (tachycardia) or rapidly switches from being too fast to being too slow (tachycardia-bradycardia syndrome). Symptoms related to abnormal heartbeats can include dizziness, light-headedness, fainting (syncope), a sensation of fluttering or pounding in the chest (palpitations), and confusion or memory problems. During exercise, many affected individuals experience chest pain, difficulty breathing, or excessive tiredness (fatigue).  In intestinal pseudo-obstruction, impairment of peristalsis leads to a buildup of partially digested food in the intestines, abdominal swelling (distention) and pain, nausea, vomiting, and constipation or diarrhea. Affected individuals experience loss of appetite and impaired ability to absorb nutrients, which may lead to malnutrition. These symptoms resemble those caused by an intestinal blockage (obstruction) such as a tumor, but in intestinal pseudo-obstruction no such blockage is found.",chronic atrial and intestinal dysrhythmia,0000185,GHR,https://ghr.nlm.nih.gov/condition/chronic-atrial-and-intestinal-dysrhythmia,C0003811,T033,Disorders
How many people are affected by chronic atrial and intestinal dysrhythmia ?,0000185-2,frequency,The prevalence of CAID is unknown. At least 17 affected individuals have been described in the medical literature.,chronic atrial and intestinal dysrhythmia,0000185,GHR,https://ghr.nlm.nih.gov/condition/chronic-atrial-and-intestinal-dysrhythmia,C0003811,T033,Disorders
What are the genetic changes related to chronic atrial and intestinal dysrhythmia ?,0000185-3,genetic changes,"CAID is caused by mutations in the SGO1 gene. This gene provides instructions for making part of a protein complex called cohesin. This protein complex helps control the placement of chromosomes during cell division. Before cells divide, they must copy all of their chromosomes. The copied DNA from each chromosome is arranged into two identical structures, called sister chromatids, which are attached to one another during the early stages of cell division. Cohesin holds the sister chromatids together, and in doing so helps maintain the stability of chromosomal structure during cell division.  Researchers suggest that SGO1 gene mutations may result in a cohesin complex that is less able to hold sister chromatids together, resulting in decreased chromosomal stability during cell division. This instability is thought to cause early aging (senescence) of cells in the intestinal muscle and in the SA node, resulting in problems maintaining proper rhythmic movements of the heart and intestines and leading to the signs and symptoms of CAID.  It is unclear why SGO1 gene mutations specifically affect the heart and intestines in CAID. Researchers suggest that the activity (expression) of the SGO1 gene in certain embryonic tissues or a particular function of the SGO1 protein in the SA node and in cells that help control peristalsis may account for the features of the disorder.",chronic atrial and intestinal dysrhythmia,0000185,GHR,https://ghr.nlm.nih.gov/condition/chronic-atrial-and-intestinal-dysrhythmia,C0003811,T033,Disorders
Is chronic atrial and intestinal dysrhythmia inherited ?,0000185-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",chronic atrial and intestinal dysrhythmia,0000185,GHR,https://ghr.nlm.nih.gov/condition/chronic-atrial-and-intestinal-dysrhythmia,C0003811,T033,Disorders
What are the treatments for chronic atrial and intestinal dysrhythmia ?,0000185-5,treatment,"These resources address the diagnosis or management of chronic atrial and intestinal dysrhythmia:  - Children's Hospital of Pittsburgh: Chronic Intestinal Pseudo-obstruction  - Genetic Testing Registry: Chronic atrial and intestinal dysrhythmia  - MedlinePlus Encyclopedia: Heart Pacemakers  - MedlinePlus Health Topic: Nutritional Support  - MedlinePlus Health Topic: Pacemakers and Implantable Defibrillators  - National Heart, Lung, and Blood Institute: What is a Pacemaker?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",chronic atrial and intestinal dysrhythmia,0000185,GHR,https://ghr.nlm.nih.gov/condition/chronic-atrial-and-intestinal-dysrhythmia,C0003811,T033,Disorders
What is (are) chronic granulomatous disease ?,0000186-1,information,"Chronic granulomatous disease is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. Immunodeficiencies are conditions in which the immune system is not able to protect the body from foreign invaders such as bacteria and fungi. Individuals with chronic granulomatous disease may have recurrent bacterial and fungal infections. People with this condition may also have areas of inflammation (granulomas) in various tissues that can result in damage to those tissues. The features of chronic granulomatous disease usually first appear in childhood, although some individuals do not show symptoms until later in life.  People with chronic granulomatous disease typically have at least one serious bacterial or fungal infection every 3 to 4 years. The lungs are the most frequent area of infection; pneumonia is a common feature of this condition. Individuals with chronic granulomatous disease may develop a type of fungal pneumonia, called mulch pneumonitis, which causes fever and shortness of breath after exposure to decaying organic materials such as mulch, hay, or dead leaves. Exposure to these organic materials and the numerous fungi involved in their decomposition causes people with chronic granulomatous disease to develop fungal infections in their lungs. Other common areas of infection in people with chronic granulomatous disease include the skin, liver, and lymph nodes.  Inflammation can occur in many different areas of the body in people with chronic granulomatous disease. Most commonly, granulomas occur in the gastrointestinal tract and the genitourinary tract. In many cases the intestinal wall is inflamed, causing a form of inflammatory bowel disease that varies in severity but can lead to stomach pain, diarrhea, bloody stool, nausea, and vomiting. Other common areas of inflammation in people with chronic granulomatous disease include the stomach, colon, and rectum, as well as the mouth, throat, and skin. Additionally, granulomas within the gastrointestinal tract can lead to tissue breakdown and pus production (abscesses). Inflammation in the stomach can prevent food from passing through to the intestines (gastric outlet obstruction), leading to an inability to digest food. These digestive problems cause vomiting after eating and weight loss. In the genitourinary tract, inflammation can occur in the kidneys and bladder. Inflammation of the lymph nodes (lymphadenitis) and bone marrow (osteomyelitis), which both produce immune cells, can lead to further impairment of the immune system.  Rarely, people with chronic granulomatous disease develop autoimmune disorders, which occur when the immune system malfunctions and attacks the body's own tissues and organs.  Repeated episodes of infection and inflammation reduce the life expectancy of individuals with chronic granulomatous disease; however, with treatment, most affected individuals live into mid- to late adulthood.",chronic granulomatous disease,0000186,GHR,https://ghr.nlm.nih.gov/condition/chronic-granulomatous-disease,C0018203,T047,Disorders
How many people are affected by chronic granulomatous disease ?,0000186-2,frequency,"Chronic granulomatous disease is estimated to occur in 1 in 200,000 to 250,000 people worldwide.",chronic granulomatous disease,0000186,GHR,https://ghr.nlm.nih.gov/condition/chronic-granulomatous-disease,C0018203,T047,Disorders
What are the genetic changes related to chronic granulomatous disease ?,0000186-3,genetic changes,"Mutations in the CYBA, CYBB, NCF1, NCF2, or NCF4 gene can cause chronic granulomatous disease. There are five types of this condition that are distinguished by the gene that is involved. The proteins produced from the affected genes are parts (subunits) of an enzyme complex called NADPH oxidase, which plays an essential role in the immune system. Specifically, NADPH oxidase is primarily active in immune system cells called phagocytes. These cells catch and destroy foreign invaders such as bacteria and fungi. Within phagocytes, NADPH oxidase is involved in the production of a toxic molecule called superoxide. Superoxide is used to generate other toxic substances, which play a role in killing foreign invaders and preventing them from reproducing in the body and causing illness. NADPH oxidase is also thought to regulate the activity of immune cells called neutrophils. These cells play a role in adjusting the inflammatory response to optimize healing and reduce injury to the body.  Mutations in the CYBA, CYBB, NCF1, NCF2, and NCF4 genes result in the production of proteins with little or no function or the production of no protein at all. Mutations in the genes that cause chronic granulomatous disease that prevent the production of any functional protein are designated ""0"". For example, mutations in the CYBB gene that lead to no functional beta chain are designated CYBB0. Mutations that lead to a reduction of the amount of protein produced are designated ""-"", for example, CYBB-.  Without any one of its subunit proteins, NADPH oxidase cannot assemble or function properly. As a result, phagocytes are unable to kill foreign invaders and neutrophil activity is not regulated. A lack of NADPH oxidase leaves affected individuals vulnerable to many types of infection and excessive inflammation.  Some people with chronic granulomatous disease do not have an identified mutation in any of these genes. The cause of the condition in these individuals is unknown.",chronic granulomatous disease,0000186,GHR,https://ghr.nlm.nih.gov/condition/chronic-granulomatous-disease,C0018203,T047,Disorders
Is chronic granulomatous disease inherited ?,0000186-4,inheritance,"When chronic granulomatous disease is caused by mutations in the CYBB gene, the condition is inherited in an X-linked recessive pattern. The CYBB gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. Rarely, females with one altered copy of the CYBB gene have mild symptoms of chronic granulomatous disease, such as an increased frequency of bacterial or fungal infections.  When chronic granulomatous disease is caused by CYBA, NCF1, NCF2, or NCF4 gene mutations, the condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Men and women are affected by autosomal recessive conditions equally.",chronic granulomatous disease,0000186,GHR,https://ghr.nlm.nih.gov/condition/chronic-granulomatous-disease,C0018203,T047,Disorders
What are the treatments for chronic granulomatous disease ?,0000186-5,treatment,"These resources address the diagnosis or management of chronic granulomatous disease:  - American Academy of Allergy, Asthma, and Immunology  - Gene Review: Gene Review: Chronic Granulomatous Disease  - Genetic Testing Registry: Chronic granulomatous disease, X-linked  - Genetic Testing Registry: Chronic granulomatous disease, autosomal recessive cytochrome b-positive, type 1  - Genetic Testing Registry: Chronic granulomatous disease, autosomal recessive cytochrome b-positive, type 2  - Genetic Testing Registry: Chronic granulomatous disease, autosomal recessive cytochrome b-positive, type 3  - Genetic Testing Registry: Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative  - MedlinePlus Encyclopedia: Chronic Granulomatous Disease  - Primary Immune Deficiency Treatment Consortium   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",chronic granulomatous disease,0000186,GHR,https://ghr.nlm.nih.gov/condition/chronic-granulomatous-disease,C0018203,T047,Disorders
What is (are) CHST3-related skeletal dysplasia ?,0000187-1,information,"CHST3-related skeletal dysplasia is a genetic condition characterized by bone and joint abnormalities that worsen over time. Affected individuals have short stature throughout life, with an adult height under 4 and a half feet. Joint dislocations, most often affecting the knees, hips, and elbows, are present at birth (congenital). Other bone and joint abnormalities can include an inward- and upward-turning foot (clubfoot), a limited range of motion in large joints, and abnormal curvature of the spine. The features of CHST3-related skeletal dysplasia are usually limited to the bones and joints; however, minor heart defects have been reported in a few affected individuals.  Researchers have not settled on a preferred name for this condition. It is sometimes known as autosomal recessive Larsen syndrome based on its similarity to another skeletal disorder called Larsen syndrome. Other names that have been used to describe the condition include spondyloepiphyseal dysplasia, Omani type; humero-spinal dysostosis; and chondrodysplasia with multiple dislocations. Recently, researchers have proposed the umbrella term CHST3-related skeletal dysplasia to refer to bone and joint abnormalities resulting from mutations in the CHST3 gene.",CHST3-related skeletal dysplasia,0000187,GHR,https://ghr.nlm.nih.gov/condition/chst3-related-skeletal-dysplasia,C0410528,T019,Disorders
How many people are affected by CHST3-related skeletal dysplasia ?,0000187-2,frequency,The prevalence of CHST3-related skeletal dysplasia is unknown. More than 30 affected individuals have been reported.,CHST3-related skeletal dysplasia,0000187,GHR,https://ghr.nlm.nih.gov/condition/chst3-related-skeletal-dysplasia,C0410528,T019,Disorders
What are the genetic changes related to CHST3-related skeletal dysplasia ?,0000187-3,genetic changes,"As its name suggests, CHST3-related skeletal dysplasia results from mutations in the CHST3 gene. This gene provides instructions for making an enzyme called C6ST-1, which is essential for the normal development of cartilage. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Mutations in the CHST3 gene reduce or eliminate the activity of the C6ST-1 enzyme. A shortage of this enzyme disrupts the normal development of cartilage and bone, resulting in the abnormalities associated with CHST3-related skeletal dysplasia.",CHST3-related skeletal dysplasia,0000187,GHR,https://ghr.nlm.nih.gov/condition/chst3-related-skeletal-dysplasia,C0410528,T019,Disorders
Is CHST3-related skeletal dysplasia inherited ?,0000187-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",CHST3-related skeletal dysplasia,0000187,GHR,https://ghr.nlm.nih.gov/condition/chst3-related-skeletal-dysplasia,C0410528,T019,Disorders
What are the treatments for CHST3-related skeletal dysplasia ?,0000187-5,treatment,These resources address the diagnosis or management of CHST3-related skeletal dysplasia:  - Gene Review: Gene Review: CHST3-Related Skeletal Dysplasia  - Genetic Testing Registry: Spondyloepiphyseal dysplasia with congenital joint dislocations   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,CHST3-related skeletal dysplasia,0000187,GHR,https://ghr.nlm.nih.gov/condition/chst3-related-skeletal-dysplasia,C0410528,T019,Disorders
What is (are) chylomicron retention disease ?,0000188-1,information,"Chylomicron retention disease is an inherited disorder that affects the absorption of dietary fats, cholesterol, and certain fat-soluble vitamins. As food is digested after a meal, molecules called chylomicrons are formed to carry fat and cholesterol from the intestine into the bloodstream. Chylomicrons are also necessary for the absorption of certain fat-soluble vitamins, such as vitamin E and vitamin D. A lack of chylomicron transport causes severely decreased absorption (malabsorption) of dietary fats and fat-soluble vitamins. Sufficient levels of fats, cholesterol, and vitamins are necessary for normal growth and development.  The signs and symptoms of chylomicron retention disease appear in the first few months of life. They can include failure to gain weight and grow at the expected rate (failure to thrive); diarrhea; and fatty, foul-smelling stools (steatorrhea). Other features of this disorder may develop later in childhood and often impair the function of the nervous system. Affected people may eventually develop decreased reflexes (hyporeflexia) and a decreased ability to feel vibrations.",chylomicron retention disease,0000188,GHR,https://ghr.nlm.nih.gov/condition/chylomicron-retention-disease,C0795956,T047,Disorders
How many people are affected by chylomicron retention disease ?,0000188-2,frequency,Chylomicron retention disease is a rare condition with approximately 40 cases described worldwide.,chylomicron retention disease,0000188,GHR,https://ghr.nlm.nih.gov/condition/chylomicron-retention-disease,C0795956,T047,Disorders
What are the genetic changes related to chylomicron retention disease ?,0000188-3,genetic changes,"Mutations in the SAR1B gene cause chylomicron retention disease. The SAR1B gene provides instructions for making a protein that is involved in transporting chylomicrons within enterocytes, which are cells that line the intestine and absorb nutrients.  SAR1B gene mutations impair the release of chylomicrons into the bloodstream. A lack of chylomicrons in the blood prevents dietary fats and fat-soluble vitamins from being used by the body, leading to the nutritional and developmental problems seen in people with chylomicron retention disease.",chylomicron retention disease,0000188,GHR,https://ghr.nlm.nih.gov/condition/chylomicron-retention-disease,C0795956,T047,Disorders
Is chylomicron retention disease inherited ?,0000188-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",chylomicron retention disease,0000188,GHR,https://ghr.nlm.nih.gov/condition/chylomicron-retention-disease,C0795956,T047,Disorders
What are the treatments for chylomicron retention disease ?,0000188-5,treatment,These resources address the diagnosis or management of chylomicron retention disease:  - Genetic Testing Registry: Chylomicron retention disease  - MedlinePlus Encyclopedia: Malabsorption   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,chylomicron retention disease,0000188,GHR,https://ghr.nlm.nih.gov/condition/chylomicron-retention-disease,C0795956,T047,Disorders
What is (are) citrullinemia ?,0000189-1,information,"Citrullinemia is an inherited disorder that causes ammonia and other toxic substances to accumulate in the blood. Two forms of citrullinemia have been described; they have different signs and symptoms and are caused by mutations in different genes.  Type I citrullinemia (also known as classic citrullinemia) usually becomes evident in the first few days of life. Affected infants typically appear normal at birth, but as ammonia builds up in the body they experience a progressive lack of energy (lethargy), poor feeding, vomiting, seizures, and loss of consciousness. These medical problems are life-threatening in many cases. Less commonly, a milder form of type I citrullinemia can develop later in childhood or adulthood. This later-onset form is associated with intense headaches, partial loss of vision, problems with balance and muscle coordination (ataxia), and lethargy. Some people with gene mutations that cause type I citrullinemia never experience signs and symptoms of the disorder.  Type II citrullinemia chiefly affects the nervous system, causing confusion, restlessness, memory loss, abnormal behaviors (such as aggression, irritability, and hyperactivity), seizures, and coma. In some cases, the signs and symptoms of this disorder appear during adulthood (adult-onset). These signs and symptoms can be life-threatening, and are known to be triggered by certain medications, infections, surgery, and alcohol intake in people with adult-onset type II citrullinemia.  The features of adult-onset type II citrullinemia may also develop in people who as infants had a liver disorder called neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). This liver condition is also known as neonatal-onset type II citrullinemia. NICCD blocks the flow of bile (a digestive fluid produced by the liver) and prevents the body from processing certain nutrients properly. In many cases, the signs and symptoms of NICCD resolve within a year. Years or even decades later, however, some of these people develop the characteristic features of adult-onset type II citrullinemia.",citrullinemia,0000189,GHR,https://ghr.nlm.nih.gov/condition/citrullinemia,C0175683,T047,Disorders
How many people are affected by citrullinemia ?,0000189-2,frequency,"Type I citrullinemia is the most common form of the disorder, affecting about 1 in 57,000 people worldwide. Type II citrullinemia is found primarily in the Japanese population, where it occurs in an estimated 1 in 100,000 to 230,000 individuals. Type II also has been reported in other populations, including people from East Asia and the Middle East.",citrullinemia,0000189,GHR,https://ghr.nlm.nih.gov/condition/citrullinemia,C0175683,T047,Disorders
What are the genetic changes related to citrullinemia ?,0000189-3,genetic changes,"Mutations in the ASS1 and SLC25A13 genes cause citrullinemia.  Citrullinemia belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of chemical reactions that takes place in liver cells. These reactions process excess nitrogen that is generated when protein is used by the body. The excess nitrogen is used to make a compound called urea, which is excreted in urine.  Mutations in the ASS1 gene cause type I citrullinemia. This gene provides instructions for making an enzyme, argininosuccinate synthase 1, that is responsible for one step of the urea cycle. Mutations in the ASS1 gene reduce the activity of the enzyme, which disrupts the urea cycle and prevents the body from processing nitrogen effectively. Excess nitrogen (in the form of ammonia) and other byproducts of the urea cycle accumulate in the bloodstream. Ammonia is particularly toxic to the nervous system, which helps explain the neurologic symptoms (such as lethargy, seizures, and ataxia) that are often seen in type I citrullinemia.  Mutations in the SLC25A13 gene are responsible for adult-onset type II citrullinemia and NICCD. This gene provides instructions for making a protein called citrin. Within cells, citrin helps transport molecules used in the production and breakdown of simple sugars, the production of proteins, and the urea cycle. Molecules transported by citrin are also involved in making nucleotides, which are the building blocks of DNA and its chemical cousin, RNA. Mutations in the SLC25A13 gene typically prevent cells from making any functional citrin, which inhibits the urea cycle and disrupts the production of proteins and nucleotides. The resulting buildup of ammonia and other toxic substances leads to the signs and symptoms of adult-onset type II citrullinemia. A lack of citrin also leads to the features of NICCD, although ammonia does not build up in the bloodstream of infants with this condition.",citrullinemia,0000189,GHR,https://ghr.nlm.nih.gov/condition/citrullinemia,C0175683,T047,Disorders
Is citrullinemia inherited ?,0000189-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",citrullinemia,0000189,GHR,https://ghr.nlm.nih.gov/condition/citrullinemia,C0175683,T047,Disorders
What are the treatments for citrullinemia ?,0000189-5,treatment,"These resources address the diagnosis or management of citrullinemia:  - Baby's First Test: Citrullinemia, Type I  - Baby's First Test: Citrullinemia, Type II  - Gene Review: Gene Review: Citrin Deficiency  - Gene Review: Gene Review: Citrullinemia Type I  - Gene Review: Gene Review: Urea Cycle Disorders Overview  - Genetic Testing Registry: Citrullinemia type I  - Genetic Testing Registry: Citrullinemia type II  - Genetic Testing Registry: Neonatal intrahepatic cholestasis caused by citrin deficiency  - MedlinePlus Encyclopedia: Hereditary Urea Cycle Abnormality   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",citrullinemia,0000189,GHR,https://ghr.nlm.nih.gov/condition/citrullinemia,C0175683,T047,Disorders
What is (are) cleidocranial dysplasia ?,0000190-1,information,"Cleidocranial dysplasia is a condition that primarily affects the development of the bones and teeth. Signs and symptoms of cleidocranial dysplasia can vary widely in severity, even within the same family.  Individuals with cleidocranial dysplasia usually have underdeveloped or absent collarbones (clavicles). As a result, their shoulders are narrow and sloping, can be brought unusually close together in front of the body, and in some cases the shoulders can be made to meet in the middle of the body. Delayed closing of the spaces between the bones of the skull (fontanels) is also characteristic of this condition. The fontanels usually close in early childhood, but may remain open into adulthood in people with this disorder.  Affected individuals may be 3 to 6 inches shorter than other members of their family, and may have short, tapered fingers and broad thumbs; short forearms; flat feet; knock knees; and an abnormal curvature of the spine (scoliosis). Characteristic facial features may include a wide, short skull (brachycephaly); a prominent forehead; wide-set eyes (hypertelorism); a flat nose; and a small upper jaw.  Individuals with cleidocranial dysplasia may have decreased bone density (osteopenia) and may develop osteoporosis, a condition that makes bones progressively more brittle and prone to fracture, at a relatively early age. Women with cleidocranial dysplasia have an increased risk of requiring a cesarean section when delivering a baby, due to a narrow pelvis preventing passage of the infant's head.  Dental abnormalities seen in cleidocranial dysplasia may include delayed loss of the primary (baby) teeth; delayed appearance of the secondary (adult) teeth; unusually shaped, peg-like teeth; misalignment of the teeth and jaws (malocclusion); and extra teeth, sometimes accompanied by cysts in the gums.  In addition to skeletal and dental abnormalities, people with cleidocranial dysplasia may have hearing loss and be prone to sinus and ear infections. Some young children with this condition are mildly delayed in the development of motor skills such as crawling and walking, but intelligence is unaffected.",cleidocranial dysplasia,0000190,GHR,https://ghr.nlm.nih.gov/condition/cleidocranial-dysplasia,C0008928,T047,Disorders
How many people are affected by cleidocranial dysplasia ?,0000190-2,frequency,Cleidocranial dysplasia occurs in approximately 1 per million individuals worldwide.,cleidocranial dysplasia,0000190,GHR,https://ghr.nlm.nih.gov/condition/cleidocranial-dysplasia,C0008928,T047,Disorders
What are the genetic changes related to cleidocranial dysplasia ?,0000190-3,genetic changes,"The RUNX2 gene provides instructions for making a protein that is involved in bone and cartilage development and maintenance. This protein is a transcription factor, which means it attaches (binds) to specific regions of DNA and helps control the activity of particular genes. Researchers believe that the RUNX2 protein acts as a ""master switch,"" regulating a number of other genes involved in the development of cells that build bones (osteoblasts).  Some mutations change one protein building block (amino acid) in the RUNX2 protein. Other mutations introduce a premature stop signal that results in an abnormally short protein. Occasionally, the entire gene is missing.  These genetic changes reduce or eliminate the activity of the protein produced from one copy of the RUNX2 gene in each cell, decreasing the total amount of functional RUNX2 protein. This shortage of functional RUNX2 protein interferes with normal bone and cartilage development, resulting in the signs and symptoms of cleidocranial dysplasia. In rare cases, affected individuals may experience additional, unusual symptoms resulting from the loss of other genes near RUNX2.  In about one-third of individuals with cleidocranial dysplasia, no mutation in the RUNX2 gene has been found. The cause of the condition in these individuals is unknown.",cleidocranial dysplasia,0000190,GHR,https://ghr.nlm.nih.gov/condition/cleidocranial-dysplasia,C0008928,T047,Disorders
Is cleidocranial dysplasia inherited ?,0000190-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.",cleidocranial dysplasia,0000190,GHR,https://ghr.nlm.nih.gov/condition/cleidocranial-dysplasia,C0008928,T047,Disorders
What are the treatments for cleidocranial dysplasia ?,0000190-5,treatment,These resources address the diagnosis or management of cleidocranial dysplasia:  - Gene Review: Gene Review: Cleidocranial Dysplasia  - Genetic Testing Registry: Cleidocranial dysostosis  - MedlinePlus Encyclopedia: Cleidocranial dysostosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,cleidocranial dysplasia,0000190,GHR,https://ghr.nlm.nih.gov/condition/cleidocranial-dysplasia,C0008928,T047,Disorders
What is (are) Clouston syndrome ?,0000192-1,information,"Clouston syndrome is a form of ectodermal dysplasia, a group of about 150 conditions characterized by abnormal development of some or all of the ectodermal structures, which include the skin, hair, nails, teeth, and sweat glands. Specifically, Clouston syndrome is characterized by abnormalities of the hair, nails, and skin, with the teeth and sweat glands being unaffected.  In infants with Clouston syndrome, scalp hair is sparse, patchy, and lighter in color than the hair of other family members; it is also fragile and easily broken. By puberty, the hair problems may worsen until all the hair on the scalp is lost (total alopecia). The eyelashes, eyebrows, underarm (axillary) hair, and pubic hair are also sparse or absent.  Abnormal growth of fingernails and toenails (nail dystrophy) is also characteristic of Clouston syndrome. The nails may appear white in the first years of life. They grow slowly and gradually become thick and misshapen. In some people with Clouston syndrome, nail dystrophy is the most noticeable feature of the disorder.  Many people with Clouston syndrome have thick skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis); areas of the skin, especially over the joints, that are darker in color than the surrounding skin (hyperpigmentation); and widened and rounded tips of the fingers (clubbing).",Clouston syndrome,0000192,GHR,https://ghr.nlm.nih.gov/condition/clouston-syndrome,C0162361,T019,Disorders
How many people are affected by Clouston syndrome ?,0000192-2,frequency,The prevalence of Clouston syndrome is unknown. Cases have been reported in many populations; the disorder is especially common among people of French-Canadian descent.,Clouston syndrome,0000192,GHR,https://ghr.nlm.nih.gov/condition/clouston-syndrome,C0162361,T019,Disorders
What are the genetic changes related to Clouston syndrome ?,0000192-3,genetic changes,"Clouston syndrome is caused by mutations in the GJB6 gene. This gene provides instructions for making a protein called gap junction beta 6, more commonly known as connexin 30. Connexin 30 is a member of the connexin protein family. Connexin proteins form channels called gap junctions, which permit the transport of nutrients, charged atoms (ions), and signaling molecules between neighboring cells. The size of the gap junction and the types of particles that move through it are determined by the particular connexin proteins that make up the channel. Gap junctions made with connexin 30 transport potassium ions and certain small molecules.  Connexin 30 is found in several different tissues throughout the body, including the skin (especially on the palms of the hands and soles of the feet), hair follicles, and nail beds, and plays a role in the growth and development of these tissues.  GJB6 gene mutations that cause Clouston syndrome change single protein building blocks (amino acids) in the connexin 30 protein. Although the effects of these mutations are not fully understood, they lead to abnormalities in the growth, division, and maturation of cells in the hair follicles, nails, and skin.",Clouston syndrome,0000192,GHR,https://ghr.nlm.nih.gov/condition/clouston-syndrome,C0162361,T019,Disorders
Is Clouston syndrome inherited ?,0000192-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",Clouston syndrome,0000192,GHR,https://ghr.nlm.nih.gov/condition/clouston-syndrome,C0162361,T019,Disorders
What are the treatments for Clouston syndrome ?,0000192-5,treatment,These resources address the diagnosis or management of Clouston syndrome:  - Gene Review: Gene Review: Hidrotic Ectodermal Dysplasia 2  - Genetic Testing Registry: Hidrotic ectodermal dysplasia syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Clouston syndrome,0000192,GHR,https://ghr.nlm.nih.gov/condition/clouston-syndrome,C0162361,T019,Disorders
What is (are) Coats plus syndrome ?,0000193-1,information,"Coats plus syndrome is an inherited condition characterized by an eye disorder called Coats disease plus abnormalities of the brain, bones, gastrointestinal system, and other parts of the body.  Coats disease affects the retina, which is the tissue at the back of the eye that detects light and color. The disorder causes blood vessels in the retina to be abnormally enlarged (dilated) and twisted. The abnormal vessels leak fluid, which can eventually cause the layers of the retina to separate (retinal detachment). These eye abnormalities often result in vision loss.  People with Coats plus syndrome also have brain abnormalities including abnormal deposits of calcium (calcification), the development of fluid-filled pockets called cysts, and loss of a type of brain tissue known as white matter (leukodystrophy). These brain abnormalities worsen over time, causing slow growth, movement disorders, seizures, and a decline in intellectual function.  Other features of Coats plus syndrome include low bone density (osteopenia), which causes bones to be fragile and break easily, and a shortage of red blood cells (anemia), which can lead to unusually pale skin (pallor) and extreme tiredness (fatigue). Affected individuals can also have serious or life-threatening complications including abnormal bleeding in the gastrointestinal tract, high blood pressure in the vein that supplies blood to the liver (portal hypertension), and liver failure. Less common features of Coats plus syndrome can include sparse, prematurely gray hair; malformations of the fingernails and toenails; and abnormalities of skin coloring (pigmentation), such as light brown patches called caf-au-lait spots.  Coats plus syndrome and a disorder called leukoencephalopathy with calcifications and cysts (LCC; also called Labrune syndrome) have sometimes been grouped together under the umbrella term cerebroretinal microangiopathy with calcifications and cysts (CRMCC) because they feature very similar brain abnormalities. However, researchers recently found that Coats plus syndrome and LCC have different genetic causes, and they are now generally described as separate disorders instead of variants of a single condition.",Coats plus syndrome,0000193,GHR,https://ghr.nlm.nih.gov/condition/coats-plus-syndrome,C2677299,T047,Disorders
How many people are affected by Coats plus syndrome ?,0000193-2,frequency,Coats plus syndrome appears to be a rare disorder. Its prevalence is unknown.,Coats plus syndrome,0000193,GHR,https://ghr.nlm.nih.gov/condition/coats-plus-syndrome,C2677299,T047,Disorders
What are the genetic changes related to Coats plus syndrome ?,0000193-3,genetic changes,"Coats plus syndrome results from mutations in the CTC1 gene. This gene provides instructions for making a protein that plays an important role in structures known as telomeres, which are found at the ends of chromosomes. Telomeres are short, repetitive segments of DNA that help protect chromosomes from abnormally sticking together or breaking down (degrading). In most cells, telomeres become progressively shorter as the cell divides. After a certain number of cell divisions, the telomeres become so short that they trigger the cell to stop dividing or to self-destruct (undergo apoptosis). The CTC1 protein works as part of a group of proteins known as the CST complex, which is involved in the copying (replication) of telomeres. The CST complex helps prevent telomeres from being degraded in some cells as the cells divide.  Mutations in the CTC1 gene impair the function of the CST complex, which affects the replication of telomeres. However, it is unclear how CTC1 gene mutations impact telomere structure and function. Some studies have found that people with CTC1 gene mutations have abnormally short telomeres, while other studies have found no change in telomere length. Researchers are working to determine how telomeres are different in people with CTC1 gene mutations and how these changes could underlie the varied signs and symptoms of Coats plus syndrome.",Coats plus syndrome,0000193,GHR,https://ghr.nlm.nih.gov/condition/coats-plus-syndrome,C2677299,T047,Disorders
Is Coats plus syndrome inherited ?,0000193-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Coats plus syndrome,0000193,GHR,https://ghr.nlm.nih.gov/condition/coats-plus-syndrome,C2677299,T047,Disorders
What are the treatments for Coats plus syndrome ?,0000193-5,treatment,These resources address the diagnosis or management of Coats plus syndrome:  - Genetic Testing Registry: Cerebroretinal microangiopathy with calcifications and cysts   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Coats plus syndrome,0000193,GHR,https://ghr.nlm.nih.gov/condition/coats-plus-syndrome,C2677299,T047,Disorders
What is (are) Cockayne syndrome ?,0000194-1,information,"Cockayne syndrome is a rare disorder characterized by short stature and an appearance of premature aging. Features of this disorder include a failure to gain weight and grow at the expected rate (failure to thrive), abnormally small head size (microcephaly), and impaired development of the nervous system. Affected individuals have an extreme sensitivity to sunlight (photosensitivity), and even a small amount of sun exposure can cause a sunburn. Other possible signs and symptoms include hearing loss, eye abnormalities, severe tooth decay, bone abnormalities, and changes in the brain that can be seen on brain scans.  Cockayne syndrome can be divided into subtypes, which are distinguished by the severity and age of onset of symptoms. Classical, or type I, Cockayne syndrome is characterized by an onset of symptoms in early childhood (usually after age 1 year). Type II Cockayne syndrome has much more severe symptoms that are apparent at birth (congenital). Type II Cockayne syndrome is sometimes called cerebro-oculo-facio-skeletal (COFS) syndrome or Pena-Shokeir syndrome type II. Type III Cockayne syndrome has the mildest symptoms of the three types and appears later in childhood.",Cockayne syndrome,0000194,GHR,https://ghr.nlm.nih.gov/condition/cockayne-syndrome,C0009207,T047,Disorders
How many people are affected by Cockayne syndrome ?,0000194-2,frequency,Cockayne syndrome occurs in about 2 per million newborns in the United States and Europe.,Cockayne syndrome,0000194,GHR,https://ghr.nlm.nih.gov/condition/cockayne-syndrome,C0009207,T047,Disorders
What are the genetic changes related to Cockayne syndrome ?,0000194-3,genetic changes,"Cockayne syndrome can result from mutations in either the ERCC6 gene (also known as the CSB gene) or the ERCC8 gene (also known as the CSA gene). These genes provide instructions for making proteins that are involved in repairing damaged DNA. DNA can be damaged by ultraviolet (UV) rays from the sun and by toxic chemicals, radiation, and unstable molecules called free radicals. Cells are usually able to fix DNA damage before it causes problems. However, in people with Cockayne syndrome, DNA damage is not repaired normally. As more abnormalities build up in DNA, cells malfunction and eventually die. The increased cell death likely contributes to the features of Cockayne syndrome, such as growth failure and premature aging.",Cockayne syndrome,0000194,GHR,https://ghr.nlm.nih.gov/condition/cockayne-syndrome,C0009207,T047,Disorders
Is Cockayne syndrome inherited ?,0000194-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Cockayne syndrome,0000194,GHR,https://ghr.nlm.nih.gov/condition/cockayne-syndrome,C0009207,T047,Disorders
What are the treatments for Cockayne syndrome ?,0000194-5,treatment,"These resources address the diagnosis or management of Cockayne syndrome:  - Gene Review: Gene Review: Cockayne Syndrome  - Genetic Testing Registry: Cockayne syndrome  - Genetic Testing Registry: Cockayne syndrome type A  - Genetic Testing Registry: Cockayne syndrome type C  - Genetic Testing Registry: Cockayne syndrome, type B  - MedlinePlus Encyclopedia: Failure to Thrive   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Cockayne syndrome,0000194,GHR,https://ghr.nlm.nih.gov/condition/cockayne-syndrome,C0009207,T047,Disorders
What is (are) Coffin-Lowry syndrome ?,0000195-1,information,"Coffin-Lowry syndrome is a condition that affects many parts of the body. The signs and symptoms are usually more severe in males than in females, although the features of this disorder range from very mild to severe in affected women.  Males with Coffin-Lowry syndrome typically have severe to profound intellectual disability and delayed development. Affected women may be cognitively normal, or they may have intellectual disability ranging from mild to profound. Beginning in childhood or adolescence, some people with this condition experience brief episodes of collapse when excited or startled by a loud noise. These attacks are called stimulus-induced drop episodes (SIDEs).  Most affected males and some affected females have distinctive facial features including a prominent forehead, widely spaced and downward-slanting eyes, a short nose with a wide tip, and a wide mouth with full lips. These features become more pronounced with age. Soft hands with short, tapered fingers are also characteristic of Coffin-Lowry syndrome. Additional features of this condition include short stature, an unusually small head (microcephaly), progressive abnormal curvature of the spine (kyphoscoliosis), and other skeletal abnormalities.",Coffin-Lowry syndrome,0000195,GHR,https://ghr.nlm.nih.gov/condition/coffin-lowry-syndrome,C0265252,T019,Disorders
How many people are affected by Coffin-Lowry syndrome ?,0000195-2,frequency,"The incidence of this condition is uncertain, but researchers estimate that the disorder affects 1 in 40,000 to 50,000 people.",Coffin-Lowry syndrome,0000195,GHR,https://ghr.nlm.nih.gov/condition/coffin-lowry-syndrome,C0265252,T019,Disorders
What are the genetic changes related to Coffin-Lowry syndrome ?,0000195-3,genetic changes,"Mutations in the RPS6KA3 gene cause Coffin-Lowry syndrome. This gene provides instructions for making a protein that is involved in signaling within cells. Researchers believe that this protein helps control the activity of other genes and plays an important role in the brain. The protein is involved in cell signaling pathways that are required for learning, the formation of long-term memories, and the survival of nerve cells. Gene mutations result in the production of little or no RPS6KA3 protein, but it is unclear how a lack of this protein causes the signs and symptoms of Coffin-Lowry syndrome.  Some people with the features of Coffin-Lowry syndrome do not have identified mutations in the RPS6KA3 gene. In these cases, the cause of the condition is unknown.",Coffin-Lowry syndrome,0000195,GHR,https://ghr.nlm.nih.gov/condition/coffin-lowry-syndrome,C0265252,T019,Disorders
Is Coffin-Lowry syndrome inherited ?,0000195-4,inheritance,"This condition is inherited in an X-linked dominant pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. The inheritance is dominant if one copy of the altered gene in each cell is sufficient to cause the condition. In most cases, males (who have one X chromosome in each cell) experience more severe signs and symptoms of the disorder than females (who have two X chromosomes in each cell). A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  Between 70 percent and 80 percent of people with Coffin-Lowry syndrome have no history of the condition in their families. These cases are caused by new mutations in the RPS6KA3 gene. The remaining 20 percent to 30 percent of affected individuals have other family members with Coffin-Lowry syndrome.",Coffin-Lowry syndrome,0000195,GHR,https://ghr.nlm.nih.gov/condition/coffin-lowry-syndrome,C0265252,T019,Disorders
What are the treatments for Coffin-Lowry syndrome ?,0000195-5,treatment,These resources address the diagnosis or management of Coffin-Lowry syndrome:  - Gene Review: Gene Review: Coffin-Lowry Syndrome  - Genetic Testing Registry: Coffin-Lowry syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Coffin-Lowry syndrome,0000195,GHR,https://ghr.nlm.nih.gov/condition/coffin-lowry-syndrome,C0265252,T019,Disorders
What is (are) Coffin-Siris syndrome ?,0000196-1,information,"Coffin-Siris syndrome is a condition that affects several body systems. Although there are many variable signs and symptoms, hallmarks of this condition include developmental disability, abnormalities of the fifth (pinky) fingers or toes, and characteristic facial features.  Most affected individuals have mild to severe intellectual disability or delayed development of speech and motor skills such as sitting and walking. Another feature of Coffin-Siris syndrome is underdevelopment (hypoplasia) of the tips of the fingers or toes, or hypoplasia or absence of the nails. These abnormalities are most common on the fifth fingers or toes. In addition, most affected individuals have facial features described as coarse. These typically include a wide nose with a flat nasal bridge, a wide mouth with thick lips, and thick eyebrows and eyelashes. Affected individuals can have excess hair on other parts of the face and body (hirsutism), but scalp hair is often sparse. There is a range of facial features seen in people with Coffin-Siris syndrome, and not all affected individuals have the typical features. In addition, people with this condition may have an abnormally small head (microcephaly).  Additionally, some infants and children with Coffin-Siris syndrome have frequent respiratory infections, difficulty feeding, and an inability to gain weight at the expected rate (failure to thrive). Other signs and symptoms that may occur in people with this condition include short stature, low muscle tone (hypotonia), and abnormally loose (lax) joints. Abnormalities of the eyes, brain, heart, and kidneys may also be present.",Coffin-Siris syndrome,0000196,GHR,https://ghr.nlm.nih.gov/condition/coffin-siris-syndrome,C0265338,T019,Disorders
How many people are affected by Coffin-Siris syndrome ?,0000196-2,frequency,Coffin-Siris syndrome is a rare condition that is diagnosed in females more frequently than in males. Approximately 140 cases have been reported in the medical literature.,Coffin-Siris syndrome,0000196,GHR,https://ghr.nlm.nih.gov/condition/coffin-siris-syndrome,C0265338,T019,Disorders
What are the genetic changes related to Coffin-Siris syndrome ?,0000196-3,genetic changes,"Coffin-Siris syndrome is caused by mutations in the ARID1A, ARID1B, SMARCA4, SMARCB1, or SMARCE1 gene. Each of these genes provides instructions for making one piece (subunit) of several different SWI/SNF protein complexes. SWI/SNF complexes regulate gene activity (expression) by a process known as chromatin remodeling. Chromatin is the network of DNA and protein that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly regions of DNA are packaged. Chromatin remodeling is one way gene expression is regulated during development; when DNA is tightly packed, gene expression is often lower than when DNA is loosely packed.  Through their ability to regulate gene activity, SWI/SNF complexes are involved in many processes, including repairing damaged DNA; copying (replicating) DNA; and controlling the growth, division, and maturation (differentiation) of cells.  Although it is unclear what effect mutations in these genes have on SWI/SNF complexes, researchers suggest that the mutations result in abnormal chromatin remodeling. Disturbance of this process alters the activity of many genes and disrupts several cellular processes, which could explain the diverse signs and symptoms of Coffin-Siris syndrome.",Coffin-Siris syndrome,0000196,GHR,https://ghr.nlm.nih.gov/condition/coffin-siris-syndrome,C0265338,T019,Disorders
Is Coffin-Siris syndrome inherited ?,0000196-4,inheritance,"Coffin-Siris syndrome appears to follow an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder. However, the condition is not usually inherited from an affected parent, but occurs from new (de novo) mutations in the gene that likely occur during early embryonic development.",Coffin-Siris syndrome,0000196,GHR,https://ghr.nlm.nih.gov/condition/coffin-siris-syndrome,C0265338,T019,Disorders
What are the treatments for Coffin-Siris syndrome ?,0000196-5,treatment,These resources address the diagnosis or management of Coffin-Siris syndrome:  - Gene Review: Gene Review: Coffin-Siris Syndrome  - Genetic Testing Registry: Coffin-Siris syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Coffin-Siris syndrome,0000196,GHR,https://ghr.nlm.nih.gov/condition/coffin-siris-syndrome,C0265338,T019,Disorders
What is (are) COG5-congenital disorder of glycosylation ?,0000197-1,information,"COG5-congenital disorder of glycosylation (COG5-CDG, formerly known as congenital disorder of glycosylation type IIi) is an inherited condition that causes neurological problems and other abnormalities. The pattern and severity of this disorder's signs and symptoms vary among affected individuals.  Individuals with COG5-CDG typically develop signs and symptoms of the condition during infancy. These individuals often have weak muscle tone (hypotonia) and delayed development. Other neurological features include moderate to severe intellectual disability, poor coordination, and difficulty walking. Some affected individuals never learn to speak. Other features of COG5-CDG include short stature, an unusually small head size (microcephaly), and distinctive facial features, which can include ears that are set low and rotated backward, a short neck with a low hairline in the back, and a prominent nose. Less commonly, affected individuals can have hearing loss caused by changes in the inner ear (sensorineural hearing loss), vision impairment, damage to the nerves that control bladder function (a condition called neurogenic bladder), liver disease, and joint deformities (contractures).",COG5-congenital disorder of glycosylation,0000197,GHR,https://ghr.nlm.nih.gov/condition/cog5-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
How many people are affected by COG5-congenital disorder of glycosylation ?,0000197-2,frequency,COG5-CDG is a very rare disorder; fewer than 10 cases have been described in the medical literature.,COG5-congenital disorder of glycosylation,0000197,GHR,https://ghr.nlm.nih.gov/condition/cog5-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
What are the genetic changes related to COG5-congenital disorder of glycosylation ?,0000197-3,genetic changes,"COG5-CDG is caused by mutations in the COG5 gene, which provides instructions for making one piece of a group of proteins known as the conserved oligomeric Golgi (COG) complex. This complex functions in the Golgi apparatus, which is a cellular structure in which newly produced proteins are modified. One process that occurs in the Golgi apparatus is glycosylation, by which sugar molecules (oligosaccharides) are attached to proteins and fats. Glycosylation modifies proteins so they can perform a wider variety of functions.  The COG complex takes part in the transport of proteins, including those that perform glycosylation, in the Golgi apparatus. COG5 gene mutations reduce the amount of COG5 protein or eliminate it completely, which disrupts protein transport. This disruption results in abnormal protein glycosylation, which can affect numerous body systems, leading to the signs and symptoms of COG5-CDG. The severity of COG5-CDG is related to the amount of COG5 protein that remains in cells.",COG5-congenital disorder of glycosylation,0000197,GHR,https://ghr.nlm.nih.gov/condition/cog5-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
Is COG5-congenital disorder of glycosylation inherited ?,0000197-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",COG5-congenital disorder of glycosylation,0000197,GHR,https://ghr.nlm.nih.gov/condition/cog5-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
What are the treatments for COG5-congenital disorder of glycosylation ?,0000197-5,treatment,These resources address the diagnosis or management of COG5-CDG:  - Gene Review: Gene Review: Congenital Disorders of N-Linked Glycosylation Pathway Overview  - Genetic Testing Registry: Congenital disorder of glycosylation type 2i   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,COG5-congenital disorder of glycosylation,0000197,GHR,https://ghr.nlm.nih.gov/condition/cog5-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
What is (are) Cohen syndrome ?,0000198-1,information,"Cohen syndrome is an inherited disorder that affects many parts of the body and is characterized by developmental delay, intellectual disability, small head size (microcephaly), and weak muscle tone (hypotonia). Other features include progressive nearsightedness (myopia), degeneration of the light-sensitive tissue at the back of the eye (retinal dystrophy), an unusually large range of joint movement (hypermobility), and distinctive facial features. Characteristic facial features include thick hair and eyebrows, long eyelashes, unusually-shaped eyes (down-slanting and wave-shaped), a bulbous nasal tip, a smooth or shortened area between the nose and the upper lip (philtrum), and prominent upper central teeth. The combination of the last two facial features results in an open-mouth appearance.  The features of Cohen syndrome vary widely among affected individuals. Additional signs and symptoms in some individuals with this disorder include low levels of white blood cells (neutropenia), overly friendly behavior, and obesity that develops in late childhood or adolescence. When obesity is present, it typically develops around the torso, with the arms and legs remaining slender. Individuals with Cohen syndrome may also have narrow hands and feet, and slender fingers.",Cohen syndrome,0000198,GHR,https://ghr.nlm.nih.gov/condition/cohen-syndrome,C0265223,T019,Disorders
How many people are affected by Cohen syndrome ?,0000198-2,frequency,"The exact incidence of Cohen syndrome is unknown. It has been diagnosed in fewer than 1,000 people worldwide. More cases are likely undiagnosed.",Cohen syndrome,0000198,GHR,https://ghr.nlm.nih.gov/condition/cohen-syndrome,C0265223,T019,Disorders
What are the genetic changes related to Cohen syndrome ?,0000198-3,genetic changes,"Mutations in the VPS13B gene (frequently called the COH1 gene) cause Cohen syndrome. The function of the protein produced from the VPS13B gene is unknown; however, researchers suggest it may be involved in sorting and transporting proteins inside the cell. Most mutations in the VPS13B gene are believed to prevent cells from producing a functional VPS13B protein. It is unclear how loss of functional VPS13B protein leads to the signs and symptoms of Cohen syndrome.",Cohen syndrome,0000198,GHR,https://ghr.nlm.nih.gov/condition/cohen-syndrome,C0265223,T019,Disorders
Is Cohen syndrome inherited ?,0000198-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Cohen syndrome,0000198,GHR,https://ghr.nlm.nih.gov/condition/cohen-syndrome,C0265223,T019,Disorders
What are the treatments for Cohen syndrome ?,0000198-5,treatment,These resources address the diagnosis or management of Cohen syndrome:  - Gene Review: Gene Review: Cohen Syndrome  - Genetic Testing Registry: Cohen syndrome  - MedlinePlus Encyclopedia: Hypotonia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Cohen syndrome,0000198,GHR,https://ghr.nlm.nih.gov/condition/cohen-syndrome,C0265223,T019,Disorders
What is (are) COL4A1-related brain small-vessel disease ?,0000199-1,information,"COL4A1-related brain small-vessel disease is part of a group of conditions called the COL4A1-related disorders. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. COL4A1-related brain small-vessel disease is characterized by weakening of the blood vessels in the brain. Stroke is often the first symptom of this condition, typically occurring in mid-adulthood. In affected individuals, stroke is usually caused by bleeding in the brain (hemorrhagic stroke) rather than a lack of blood flow in the brain (ischemic stroke), although either type can occur. Individuals with this condition are at increased risk of having more than one stroke in their lifetime. People with COL4A1-related brain small vessel disease also have leukoencephalopathy, which is a change in a type of brain tissue called white matter that can be seen with magnetic resonance imaging (MRI). Affected individuals may also experience seizures and migraine headaches accompanied by visual sensations known as auras.  Some people with COL4A1-related brain small-vessel disease have an eye abnormality called Axenfeld-Rieger anomaly. Axenfeld-Rieger anomaly involves underdevelopment and eventual tearing of the colored part of the eye (iris) and a pupil that is not in the center of the eye. Other eye problems experienced by people with COL4A1-related brain small-vessel disease include clouding of the lens of the eye (cataract) and the presence of arteries that twist and turn abnormally within the light-sensitive tissue at the back of the eye (arterial retinal tortuosity). Axenfeld-Rieger anomaly and cataract can cause impaired vision. Arterial retinal tortuosity can cause episodes of bleeding within the eye following any minor trauma to the eye, leading to temporary vision loss.  The severity of the condition varies greatly among affected individuals. Some individuals with COL4A1-related brain small-vessel disease do not have any signs or symptoms of the condition.",COL4A1-related brain small-vessel disease,0000199,GHR,https://ghr.nlm.nih.gov/condition/col4a1-related-brain-small-vessel-disease,C3810309,T033,Disorders
How many people are affected by COL4A1-related brain small-vessel disease ?,0000199-2,frequency,"COL4A1-related brain small-vessel disease is a rare condition, although the exact prevalence is unknown. At least 50 individuals with this condition have been described in the scientific literature.",COL4A1-related brain small-vessel disease,0000199,GHR,https://ghr.nlm.nih.gov/condition/col4a1-related-brain-small-vessel-disease,C3810309,T033,Disorders
What are the genetic changes related to COL4A1-related brain small-vessel disease ?,0000199-3,genetic changes,"As the name suggests, mutations in the COL4A1 gene cause COL4A1-related brain small vessel disease. The COL4A1 gene provides instructions for making one component of a protein called type IV collagen. Type IV collagen molecules attach to each other to form complex protein networks. These protein networks are the main components of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. Type IV collagen networks play an important role in the basement membranes in virtually all tissues throughout the body, particularly the basement membranes surrounding the body's blood vessels (vasculature).  The COL4A1 gene mutations that cause COL4A1-related brain small-vessel disease result in the production of a protein that disrupts the structure of type IV collagen. As a result, type IV collagen molecules cannot attach to each other to form the protein networks in basement membranes. Basement membranes without these networks are unstable, leading to weakening of the tissues that they surround. In people with COL4A1-related brain small-vessel disease, the vasculature in the brain weakens, which can lead to blood vessel breakage and stroke. Similar blood vessel weakness and breakage occurs in the eyes of some affected individuals.",COL4A1-related brain small-vessel disease,0000199,GHR,https://ghr.nlm.nih.gov/condition/col4a1-related-brain-small-vessel-disease,C3810309,T033,Disorders
Is COL4A1-related brain small-vessel disease inherited ?,0000199-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition. Rarely, new mutations in the gene occur in people with no history of the disorder in their family.",COL4A1-related brain small-vessel disease,0000199,GHR,https://ghr.nlm.nih.gov/condition/col4a1-related-brain-small-vessel-disease,C3810309,T033,Disorders
What are the treatments for COL4A1-related brain small-vessel disease ?,0000199-5,treatment,These resources address the diagnosis or management of COL4A1-related brain small-vessel disease:  - Gene Review: Gene Review: COL4A1-Related Disorders  - Genetic Testing Registry: Brain small vessel disease with hemorrhage   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,COL4A1-related brain small-vessel disease,0000199,GHR,https://ghr.nlm.nih.gov/condition/col4a1-related-brain-small-vessel-disease,C3810309,T033,Disorders
What is (are) cold-induced sweating syndrome ?,0000200-1,information,"Cold-induced sweating syndrome is characterized by problems with regulating body temperature and other abnormalities affecting many parts of the body. In infancy, the features of this condition are often known as Crisponi syndrome. Researchers originally thought that cold-induced sweating syndrome and Crisponi syndrome were separate disorders, but it is now widely believed that they represent the same condition at different times during life.  Infants with Crisponi syndrome have unusual facial features, including a flat nasal bridge, upturned nostrils, a long space between the nose and upper lip (philtrum), a high arched roof of the mouth (palate), a small chin (micrognathia), and low-set ears. The muscles in the lower part of the face are weak, leading to severe feeding difficulties, excessive drooling, and breathing problems. Other physical abnormalities associated with Crisponi syndrome include a scaly skin rash, an inability to fully extend the elbows, overlapping fingers and tightly fisted hands, and malformations of the feet and toes. Affected infants startle easily and often tense their facial muscles into a grimace-like expression. By six months of age, infants with Crisponi syndrome develop unexplained high fevers that increase the risk of seizures and sudden death.  Many of the health problems associated with Crisponi syndrome improve with time, and affected individuals who survive the newborn period go on to develop other features of cold-induced sweating syndrome in early childhood. Within the first decade of life, affected individuals begin having episodes of profuse sweating (hyperhidrosis) and shivering involving the face, torso, and arms. The excessive sweating is usually triggered by exposure to temperatures below about 65 or 70 degrees Fahrenheit, but it can also be triggered by nervousness or eating sugary foods. Paradoxically, affected individuals tend not to sweat in warmer conditions, instead becoming flushed and overheated in hot environments.  Adolescents with cold-induced sweating syndrome typically develop abnormal side-to-side and front-to-back curvature of the spine (scoliosis and kyphosis, often called kyphoscoliosis when they occur together). Although infants may develop life-threatening fevers, affected individuals who survive infancy have a normal life expectancy.",cold-induced sweating syndrome,0000200,GHR,https://ghr.nlm.nih.gov/condition/cold-induced-sweating-syndrome,C1832409,T047,Disorders
How many people are affected by cold-induced sweating syndrome ?,0000200-2,frequency,"Cold-induced sweating syndrome is a rare condition; its prevalence is unknown. The condition was first identified in the Sardinian population, but it has since been reported in regions worldwide.",cold-induced sweating syndrome,0000200,GHR,https://ghr.nlm.nih.gov/condition/cold-induced-sweating-syndrome,C1832409,T047,Disorders
What are the genetic changes related to cold-induced sweating syndrome ?,0000200-3,genetic changes,"About 90 percent of cases of cold-induced sweating syndrome and Crisponi syndrome result from mutations in the CRLF1 gene. These cases are designated as CISS1. The remaining 10 percent of cases are caused by mutations in the CLCF1 gene and are designated as CISS2.  The proteins produced from the CRLF1 and CLCF1 genes work together as part of a signaling pathway that is involved in the normal development of the nervous system. This pathway appears to be particularly important for the development and maintenance of motor neurons, which are nerve cells that control muscle movement. Studies suggest that this pathway also has a role in a part of the nervous system known as the sympathetic nervous system, specifically in the regulation of sweating in response to temperature changes and other factors. The proteins produced from the CRLF1 and CLCF1 genes appear to be critical for the normal development and maturation of nerve cells that control the activity of sweat glands.  Additionally, the CRLF1 and CLCF1 genes likely have functions outside the nervous system, including roles in the body's inflammatory response and in bone development. However, little is known about their involvement in these processes.  Mutations in either the CRLF1 or CLCF1 gene disrupt the normal development of several body systems, including the nervous system. The role of these genes in sympathetic nervous system development may help explain the abnormal sweating that is characteristic of this condition, including unusual sweating patterns and related problems with body temperature regulation. The involvement of these genes in motor neuron development and bone development provides clues to some of the other signs and symptoms of cold-induced sweating syndrome, including distinctive facial features, facial muscle weakness, and skeletal abnormalities. However, little is known about how CRLF1 or CLCF1 gene mutations underlie these other features of cold-induced sweating syndrome.",cold-induced sweating syndrome,0000200,GHR,https://ghr.nlm.nih.gov/condition/cold-induced-sweating-syndrome,C1832409,T047,Disorders
Is cold-induced sweating syndrome inherited ?,0000200-4,inheritance,"Cold-induced sweating syndrome is inherited in anautosomal recessive pattern, which means both copies of the CRLF1 or CLCF1 gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",cold-induced sweating syndrome,0000200,GHR,https://ghr.nlm.nih.gov/condition/cold-induced-sweating-syndrome,C1832409,T047,Disorders
What are the treatments for cold-induced sweating syndrome ?,0000200-5,treatment,These resources address the diagnosis or management of cold-induced sweating syndrome:  - Gene Review: Gene Review: Cold-Induced Sweating Syndrome including Crisponi Syndrome  - Genetic Testing Registry: Cold-induced sweating syndrome 1  - Genetic Testing Registry: Cold-induced sweating syndrome 2  - Merck Manual Consumer Version: Excessive Sweating   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,cold-induced sweating syndrome,0000200,GHR,https://ghr.nlm.nih.gov/condition/cold-induced-sweating-syndrome,C1832409,T047,Disorders
What is (are) Cole disease ?,0000201-1,information,"Cole disease is a disorder that affects the skin. People with this disorder have areas of unusually light-colored skin (hypopigmentation), typically on the arms and legs, and spots of thickened skin on the palms of the hands and the soles of the feet (punctate palmoplantar keratoderma). These skin features are present at birth or develop in the first year of life.  In some cases, individuals with Cole disease develop abnormal accumulations of the mineral calcium (calcifications) in the tendons, which can cause pain during movement. Calcifications may also occur in the skin or breast tissue.",Cole disease,0000201,GHR,https://ghr.nlm.nih.gov/condition/cole-disease,C3809781,T047,Disorders
How many people are affected by Cole disease ?,0000201-2,frequency,Cole disease is a rare disease; its prevalence is unknown. Only a few affected families have been described in the medical literature.,Cole disease,0000201,GHR,https://ghr.nlm.nih.gov/condition/cole-disease,C3809781,T047,Disorders
What are the genetic changes related to Cole disease ?,0000201-3,genetic changes,"Cole disease is caused by mutations in the ENPP1 gene. This gene provides instructions for making a protein that helps to prevent minerals, including calcium, from being deposited in body tissues where they do not belong. It also plays a role in controlling cell signaling in response to the hormone insulin, through interaction between a part of the ENPP1 protein called the SMB2 domain and the insulin receptor. The insulin receptor is a protein that attaches (binds) to insulin and initiates cell signaling.  Insulin plays many roles in the body, including regulating blood sugar levels by controlling how much sugar (in the form of glucose) is passed from the bloodstream into cells to be used as energy. Cell signaling in response to insulin is also important for the maintenance of the outer layer of skin (the epidermis). It helps control the transport of the pigment melanin from the cells in which it is produced (melanocytes) to epidermal cells called keratinocytes, and it is also involved in the development of keratinocytes.  The mutations that cause Cole disease change the structure of the SMB2 domain, which alters its interaction with the insulin receptor and affects cell signaling. The resulting impairment of ENPP1's role in melanin transport and keratinocyte development leads to the hypopigmentation and keratoderma that occurs in Cole disease. The mutations may also impair ENPP1's control of calcification, which likely accounts for the abnormal calcium deposits that occur in some people with this disorder. For reasons that are unclear, the changes in insulin signaling resulting from these ENPP1 gene mutations do not seem to affect blood sugar control.",Cole disease,0000201,GHR,https://ghr.nlm.nih.gov/condition/cole-disease,C3809781,T047,Disorders
Is Cole disease inherited ?,0000201-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In most cases of this disorder, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",Cole disease,0000201,GHR,https://ghr.nlm.nih.gov/condition/cole-disease,C3809781,T047,Disorders
What are the treatments for Cole disease ?,0000201-5,treatment,These resources address the diagnosis or management of Cole disease:  - Genetic Testing Registry: Cole disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Cole disease,0000201,GHR,https://ghr.nlm.nih.gov/condition/cole-disease,C3809781,T047,Disorders
What is (are) collagen VI-related myopathy ?,0000202-1,information,"Collagen VI-related myopathy is a group of disorders that affect skeletal muscles (which are the muscles used for movement) and connective tissue (which provides strength and flexibility to the skin, joints, and other structures throughout the body). Most affected individuals have muscle weakness and joint deformities called contractures that restrict movement of the affected joints and worsen over time. Researchers have described several forms of collagen VI-related myopathy, which range in severity: Bethlem myopathy is the mildest, an intermediate form is moderate in severity, and Ullrich congenital muscular dystrophy is the most severe.  People with Bethlem myopathy usually have loose joints (joint laxity) and weak muscle tone (hypotonia) in infancy, but they develop contractures during childhood, typically in their fingers, wrists, elbows, and ankles. Muscle weakness can begin at any age but often appears in childhood to early adulthood. The muscle weakness is slowly progressive, with about two-thirds of affected individuals over age 50 needing walking assistance. Older individuals may develop weakness in respiratory muscles, which can cause breathing problems. Some people with this mild form of collagen VI-related myopathy have skin abnormalities, including small bumps called follicular hyperkeratosis on the arms and legs; soft, velvety skin on the palms of the hands and soles of the feet; and abnormal wound healing that creates shallow scars.  The intermediate form of collagen VI-related myopathy is characterized by muscle weakness that begins in infancy. Affected children are able to walk, although walking becomes increasingly difficult starting in early adulthood. They develop contractures in the ankles, elbows, knees, and spine in childhood. In some affected people, the respiratory muscles are weakened, requiring people to use a machine to help them breathe (mechanical ventilation), particularly during sleep.  People with Ullrich congenital muscular dystrophy have severe muscle weakness beginning soon after birth. Some affected individuals are never able to walk and others can walk only with support. Those who can walk often lose the ability, usually in adolescence. Individuals with Ullrich congenital muscular dystrophy develop contractures in their neck, hips, and knees, which further impair movement. There may be joint laxity in the fingers, wrists, toes, ankles, and other joints. Some affected individuals need continuous mechanical ventilation to help them breathe. As in Bethlem myopathy, some people with Ullrich congenital muscular dystrophy have follicular hyperkeratosis; soft, velvety skin on the palms and soles; and abnormal wound healing.  Individuals with collagen VI-related myopathy often have signs and symptoms of multiple forms of this condition, so it can be difficult to assign a specific diagnosis. The overlap in disease features, in addition to their common cause, is why these once separate conditions are now considered part of the same disease spectrum.",collagen VI-related myopathy,0000202,GHR,https://ghr.nlm.nih.gov/condition/collagen-vi-related-myopathy,C0026848,T047,Disorders
How many people are affected by collagen VI-related myopathy ?,0000202-2,frequency,"Collagen VI-related myopathy is rare. Bethlem myopathy is estimated to occur in 0.77 per 100,000 individuals, and Ullrich congenital muscular dystrophy is estimated to occur in 0.13 per 100,000 individuals. Only a few cases of the intermediate form have been described in the scientific literature.",collagen VI-related myopathy,0000202,GHR,https://ghr.nlm.nih.gov/condition/collagen-vi-related-myopathy,C0026848,T047,Disorders
What are the genetic changes related to collagen VI-related myopathy ?,0000202-3,genetic changes,"Mutations in the COL6A1, COL6A2, and COL6A3 genes can cause the various forms of collagen VI-related myopathy. These genes each provide instructions for making one component of a protein called type VI collagen. Type VI collagen makes up part of the extracellular matrix that surrounds muscle cells and connective tissue. This matrix is an intricate lattice that forms in the space between cells and provides structural support. The extracellular matrix is necessary for cell stability and growth. Research suggests that type VI collagen helps secure and organize the extracellular matrix by linking the matrix to the cells it surrounds.  Mutations in the COL6A1, COL6A2, and COL6A3 genes result in a decrease or lack of type VI collagen or the production of abnormal type VI collagen. While it is difficult to predict which type of mutation will lead to which form of collagen VI-related myopathy, in general, lower amounts of type VI collagen lead to more severe signs and symptoms that begin earlier in life.  Changes in type VI collagen structure or production lead to an unstable extracellular matrix that is no longer attached to cells. As a result, the stability of the surrounding muscle cells and connective tissue progressively declines, which leads to the muscle weakness, contractures, and other signs and symptoms of collagen VI-related myopathy.",collagen VI-related myopathy,0000202,GHR,https://ghr.nlm.nih.gov/condition/collagen-vi-related-myopathy,C0026848,T047,Disorders
Is collagen VI-related myopathy inherited ?,0000202-4,inheritance,"Collagen VI-related myopathy can be inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Bethlem myopathy is typically inherited in an autosomal dominant manner, as are some cases of the intermediate form and a few rare instances of Ullrich congenital muscular dystrophy. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family. In other cases, an affected person inherits the mutation from one affected parent.  Collagen VI-related myopathy can be inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Ullrich congenital muscular dystrophy is typically inherited in an autosomal recessive manner, as are some cases of the intermediate form and a few rare instances of Bethlem myopathy. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",collagen VI-related myopathy,0000202,GHR,https://ghr.nlm.nih.gov/condition/collagen-vi-related-myopathy,C0026848,T047,Disorders
What are the treatments for collagen VI-related myopathy ?,0000202-5,treatment,These resources address the diagnosis or management of collagen VI-related myopathy:  - Gene Review: Gene Review: Collagen Type VI-Related Disorders  - Genetic Testing Registry: Bethlem myopathy  - Genetic Testing Registry: Collagen Type VI-Related Autosomal Dominant Limb-girdle Muscular Dystrophy  - Genetic Testing Registry: Collagen VI-related myopathy  - Genetic Testing Registry: Ullrich congenital muscular dystrophy  - Muscular Dystrophy UK: Could Cyclosporine A be used to treat Bethlem myopathy and Ullrich congenital muscular dystrophy?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,collagen VI-related myopathy,0000202,GHR,https://ghr.nlm.nih.gov/condition/collagen-vi-related-myopathy,C0026848,T047,Disorders
What is (are) coloboma ?,0000203-1,information,"Coloboma is an eye abnormality that occurs before birth. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in one of several parts of the eye, including the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or the optic nerves, which carry information from the eyes to the brain.  Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision. Colobomas affecting the iris, which result in a ""keyhole"" appearance of the pupil, generally do not lead to vision loss. Colobomas involving the retina result in vision loss in specific parts of the visual field, generally the upper part. Large retinal colobomas or those affecting the optic nerve can cause low vision, which means vision loss that cannot be completely corrected with glasses or contact lenses.  Some people with coloboma also have a condition called microphthalmia. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.  People with coloboma may also have other eye abnormalities, including clouding of the lens of the eye (cataract), increased pressure inside the eye (glaucoma) that can damage the optic nerve, vision problems such as nearsightedness (myopia), involuntary back-and-forth eye movements (nystagmus), or separation of the retina from the back of the eye (retinal detachment).  Some individuals have coloboma as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When coloboma occurs by itself, it is described as nonsyndromic or isolated.  Colobomas involving the eyeball should be distinguished from gaps that occur in the eyelids. While these eyelid gaps are also called colobomas, they arise from abnormalities in different structures during early development.",coloboma,0000203,GHR,https://ghr.nlm.nih.gov/condition/coloboma,C0009363,T019,Disorders
How many people are affected by coloboma ?,0000203-2,frequency,"Coloboma occurs in approximately 1 in 10,000 people. Because coloboma does not always affect vision or the outward appearance of the eye, some people with this condition are likely undiagnosed.",coloboma,0000203,GHR,https://ghr.nlm.nih.gov/condition/coloboma,C0009363,T019,Disorders
What are the genetic changes related to coloboma ?,0000203-3,genetic changes,"Coloboma arises from abnormal development of the eye. During the second month of development before birth, a seam called the optic fissure (also known as the choroidal fissure or embryonic fissure) closes to form the structures of the eye. When the optic fissure does not close completely, the result is a coloboma. The location of the coloboma depends on the part of the optic fissure that failed to close.  Coloboma may be caused by changes in many genes involved in the early development of the eye, most of which have not been identified. The condition may also result from a chromosomal abnormality affecting one or more genes. Most genetic changes associated with coloboma have been identified only in very small numbers of affected individuals.  The risk of coloboma may also be increased by environmental factors that affect early development, such as exposure to alcohol during pregnancy. In these cases, affected individuals usually have other health problems in addition to coloboma.",coloboma,0000203,GHR,https://ghr.nlm.nih.gov/condition/coloboma,C0009363,T019,Disorders
Is coloboma inherited ?,0000203-4,inheritance,"Most often, isolated coloboma is not inherited, and there is only one affected individual in a family. However, the affected individual is still at risk of passing the coloboma on to his or her own children.  In cases when it is passed down in families, coloboma can have different inheritance patterns. Isolated coloboma is sometimes inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. Isolated coloboma can also be inherited in an autosomal recessive pattern, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of a mutated gene, but they typically do not show signs and symptoms of the condition.  Less commonly, isolated coloboma may have X-linked dominant or X-linked recessive patterns of inheritance. X-linked means that a gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  X-linked dominant means that in females (who have two X chromosomes), a mutation in one of the two copies of a gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of a gene in each cell causes the disorder. In most cases, males experience more severe symptoms of the disorder than females.  X-linked recessive means that in females, a mutation would have to occur in both copies of a gene to cause the disorder. In males, one altered copy of a gene in each cell is sufficient to cause the condition. Because it is unlikely that females will have two altered copies of a particular gene, males are affected by X-linked recessive disorders much more frequently than females.  When coloboma occurs as a feature of a genetic syndrome or chromosomal abnormality, it may cluster in families according to the inheritance pattern for that condition, which may be autosomal dominant, autosomal recessive, or X-linked.",coloboma,0000203,GHR,https://ghr.nlm.nih.gov/condition/coloboma,C0009363,T019,Disorders
What are the treatments for coloboma ?,0000203-5,treatment,"These resources address the diagnosis or management of coloboma:  - Genetic Testing Registry: Congenital ocular coloboma  - Genetic Testing Registry: Microphthalmia, isolated, with coloboma 1  - Genetic Testing Registry: Microphthalmia, isolated, with coloboma 2  - Genetic Testing Registry: Microphthalmia, isolated, with coloboma 3  - Genetic Testing Registry: Microphthalmia, isolated, with coloboma 4  - Genetic Testing Registry: Microphthalmia, isolated, with coloboma 5  - Genetic Testing Registry: Microphthalmia, isolated, with coloboma 6  - National Eye Institute: Facts About Uveal Coloboma   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",coloboma,0000203,GHR,https://ghr.nlm.nih.gov/condition/coloboma,C0009363,T019,Disorders
What is (are) color vision deficiency ?,0000204-1,information,"Color vision deficiency (sometimes called color blindness) represents a group of conditions that affect the perception of color. Red-green color vision defects are the most common form of color vision deficiency. Affected individuals have trouble distinguishing between some shades of red, yellow, and green. Blue-yellow color vision defects (also called tritan defects), which are rarer, cause problems with differentiating shades of blue and green and cause difficulty distinguishing dark blue from black. These two forms of color vision deficiency disrupt color perception but do not affect the sharpness of vision (visual acuity).  A less common and more severe form of color vision deficiency called blue cone monochromacy causes very poor visual acuity and severely reduced color vision. Affected individuals have additional vision problems, which can include increased sensitivity to light (photophobia), involuntary back-and-forth eye movements (nystagmus), and nearsightedness (myopia). Blue cone monochromacy is sometimes considered to be a form of achromatopsia, a disorder characterized by a partial or total lack of color vision with other vision problems.",color vision deficiency,0000204,GHR,https://ghr.nlm.nih.gov/condition/color-vision-deficiency,C0242225,T047,Disorders
How many people are affected by color vision deficiency ?,0000204-2,frequency,"Red-green color vision defects are the most common form of color vision deficiency. This condition affects males much more often than females. Among populations with Northern European ancestry, it occurs in about 1 in 12 males and 1 in 200 females. Red-green color vision defects have a lower incidence in almost all other populations studied.  Blue-yellow color vision defects affect males and females equally. This condition occurs in fewer than 1 in 10,000 people worldwide.  Blue cone monochromacy is rarer than the other forms of color vision deficiency, affecting about 1 in 100,000 people worldwide. Like red-green color vision defects, blue cone monochromacy affects males much more often than females.",color vision deficiency,0000204,GHR,https://ghr.nlm.nih.gov/condition/color-vision-deficiency,C0242225,T047,Disorders
What are the genetic changes related to color vision deficiency ?,0000204-3,genetic changes,"Mutations in the OPN1LW, OPN1MW, and OPN1SW genes cause the forms of color vision deficiency described above. The proteins produced from these genes play essential roles in color vision. They are found in the retina, which is the light-sensitive tissue at the back of the eye. The retina contains two types of light receptor cells, called rods and cones, that transmit visual signals from the eye to the brain. Rods provide vision in low light. Cones provide vision in bright light, including color vision. There are three types of cones, each containing a specific pigment (a photopigment called an opsin) that is most sensitive to particular wavelengths of light. The brain combines input from all three types of cones to produce normal color vision.  The OPN1LW, OPN1MW, and OPN1SW genes provide instructions for making the three opsin pigments in cones. The opsin made from the OPN1LW gene is more sensitive to light in the yellow/orange part of the visible spectrum (long-wavelength light), and cones with this pigment are called long-wavelength-sensitive or L cones. The opsin made from the OPN1MW gene is more sensitive to light in the middle of the visible spectrum (yellow/green light), and cones with this pigment are called middle-wavelength-sensitive or M cones. The opsin made from the OPN1SW gene is more sensitive to light in the blue/violet part of the visible spectrum (short-wavelength light), and cones with this pigment are called short-wavelength-sensitive or S cones.  Genetic changes involving the OPN1LW or OPN1MW gene cause red-green color vision defects. These changes lead to an absence of L or M cones or to the production of abnormal opsin pigments in these cones that affect red-green color vision. Blue-yellow color vision defects result from mutations in the OPN1SW gene. These mutations lead to the premature destruction of S cones or the production of defective S cones. Impaired S cone function alters perception of the color blue, making it difficult or impossible to detect differences between shades of blue and green and causing problems with distinguishing dark blue from black.  Blue cone monochromacy occurs when genetic changes affecting the OPN1LW and OPN1MW genes prevent both L and M cones from functioning normally. In people with this condition, only S cones are functional, which leads to reduced visual acuity and poor color vision. The loss of L and M cone function also underlies the other vision problems in people with blue cone monochromacy.  Some problems with color vision are not caused by gene mutations. These nonhereditary conditions are described as acquired color vision deficiencies. They can be caused by other eye disorders, such as diseases involving the retina, the nerve that carries visual information from the eye to the brain (the optic nerve), or areas of the brain involved in processing visual information. Acquired color vision deficiencies can also be side effects of certain drugs, such as chloroquine (which is used to treat malaria), or result from exposure to particular chemicals, such as organic solvents.",color vision deficiency,0000204,GHR,https://ghr.nlm.nih.gov/condition/color-vision-deficiency,C0242225,T047,Disorders
Is color vision deficiency inherited ?,0000204-4,inheritance,"Red-green color vision defects and blue cone monochromacy are inherited in an X-linked recessive pattern. The OPN1LW and OPN1MW genes are located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one genetic change in each cell is sufficient to cause the condition. Males are affected by X-linked recessive disorders much more frequently than females because in females (who have two X chromosomes), a genetic change would have to occur on both copies of the chromosome to cause the disorder. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  Blue-yellow color vision defects are inherited in an autosomal dominant pattern, which means one copy of the altered OPN1SW gene in each cell is sufficient to cause the condition. In many cases, an affected person inherits the condition from an affected parent.",color vision deficiency,0000204,GHR,https://ghr.nlm.nih.gov/condition/color-vision-deficiency,C0242225,T047,Disorders
What are the treatments for color vision deficiency ?,0000204-5,treatment,"These resources address the diagnosis or management of color vision deficiency:  - Gene Review: Gene Review: Red-Green Color Vision Defects  - Genetic Testing Registry: Colorblindness, partial, deutan series  - Genetic Testing Registry: Cone monochromatism  - Genetic Testing Registry: Protan defect  - Genetic Testing Registry: Red-green color vision defects  - Genetic Testing Registry: Tritanopia  - MedlinePlus Encyclopedia: Color Vision Test  - MedlinePlus Encyclopedia: Colorblind   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",color vision deficiency,0000204,GHR,https://ghr.nlm.nih.gov/condition/color-vision-deficiency,C0242225,T047,Disorders
What is (are) combined malonic and methylmalonic aciduria ?,0000205-1,information,"Combined malonic and methylmalonic aciduria (CMAMMA) is a condition characterized by high levels of certain chemicals, known as malonic acid and methylmalonic acid, in the body. A distinguishing feature of this condition is higher levels of methylmalonic acid than malonic acid in the urine, although both are elevated.  The signs and symptoms of CMAMMA can begin in childhood. In some children, the buildup of acids causes the blood to become too acidic (ketoacidosis), which can damage the body's tissues and organs. Other signs and symptoms may include involuntary muscle tensing (dystonia), weak muscle tone (hypotonia), developmental delay, an inability to grow and gain weight at the expected rate (failure to thrive), low blood sugar (hypoglycemia), and coma. Some affected children have an unusually small head size (microcephaly).  Other people with CMAMMA do not develop signs and symptoms until adulthood. These individuals usually have neurological problems, such as seizures, loss of memory, a decline in thinking ability, or psychiatric diseases.",combined malonic and methylmalonic aciduria,0000205,GHR,https://ghr.nlm.nih.gov/condition/combined-malonic-and-methylmalonic-aciduria,C0268583,T047,Disorders
How many people are affected by combined malonic and methylmalonic aciduria ?,0000205-2,frequency,CMAMMA appears to be a rare disease. Approximately a dozen cases have been reported in the scientific literature.,combined malonic and methylmalonic aciduria,0000205,GHR,https://ghr.nlm.nih.gov/condition/combined-malonic-and-methylmalonic-aciduria,C0268583,T047,Disorders
What are the genetic changes related to combined malonic and methylmalonic aciduria ?,0000205-3,genetic changes,"Mutations in the ACSF3 gene cause CMAMMA. This gene provides instructions for making an enzyme that plays a role in the formation (synthesis) of fatty acids. Fatty acids are building blocks used to make fats (lipids). The ACSF3 enzyme performs a chemical reaction that converts malonic acid to malonyl-CoA, which is the first step of fatty acid synthesis in cellular structures called mitochondria. Based on this activity, the enzyme is classified as a malonyl-CoA synthetase. The ACSF3 enzyme also converts methylmalonic acid to methylmalonyl-CoA, making it a methylmalonyl-CoA synthetase as well.  The effects of ACSF3 gene mutations are unknown. Researchers suspect that the mutations lead to altered enzymes that have little or no function. Because the enzyme cannot convert malonic and methylmalonic acids, they build up in the body. Damage to organs and tissues caused by accumulation of these acids may be responsible for the signs and symptoms of CMAMMA, although the mechanisms are unclear.",combined malonic and methylmalonic aciduria,0000205,GHR,https://ghr.nlm.nih.gov/condition/combined-malonic-and-methylmalonic-aciduria,C0268583,T047,Disorders
Is combined malonic and methylmalonic aciduria inherited ?,0000205-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",combined malonic and methylmalonic aciduria,0000205,GHR,https://ghr.nlm.nih.gov/condition/combined-malonic-and-methylmalonic-aciduria,C0268583,T047,Disorders
What are the treatments for combined malonic and methylmalonic aciduria ?,0000205-5,treatment,These resources address the diagnosis or management of CMAMMA:  - Genetic Testing Registry: Combined malonic and methylmalonic aciduria  - Organic Acidemia Association: What are Organic Acidemias?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,combined malonic and methylmalonic aciduria,0000205,GHR,https://ghr.nlm.nih.gov/condition/combined-malonic-and-methylmalonic-aciduria,C0268583,T047,Disorders
What is (are) combined pituitary hormone deficiency ?,0000206-1,information,"Combined pituitary hormone deficiency is a condition that causes a shortage (deficiency) of several hormones produced by the pituitary gland, which is located at the base of the brain. A lack of these hormones may affect the development of many parts of the body. The first signs of this condition include a failure to grow at the expected rate and short stature that usually becomes apparent in early childhood.  People with combined pituitary hormone deficiency may have hypothyroidism, which is underactivity of the butterfly-shaped thyroid gland in the lower neck. Hypothyroidism can cause many symptoms, including weight gain and fatigue. Other features of combined pituitary hormone deficiency include delayed or absent puberty and lack the ability to have biological children (infertility). The condition can also be associated with a deficiency of the hormone cortisol. Cortisol deficiency can impair the body's immune system, causing individuals to be more susceptible to infection.  Rarely, people with combined pituitary hormone deficiency have intellectual disability; a short, stiff neck; or underdeveloped optic nerves, which carry visual information from the eyes to the brain.",combined pituitary hormone deficiency,0000206,GHR,https://ghr.nlm.nih.gov/condition/combined-pituitary-hormone-deficiency,C0857439,T047,Disorders
How many people are affected by combined pituitary hormone deficiency ?,0000206-2,frequency,"The prevalence of combined pituitary hormone deficiency is estimated to be 1 in 8,000 individuals worldwide.",combined pituitary hormone deficiency,0000206,GHR,https://ghr.nlm.nih.gov/condition/combined-pituitary-hormone-deficiency,C0857439,T047,Disorders
What are the genetic changes related to combined pituitary hormone deficiency ?,0000206-3,genetic changes,"Mutations in at least eight genes have been found to cause combined pituitary hormone deficiency. Mutations in the PROP1 gene are the most common known cause of this disorder, accounting for an estimated 12 to 55 percent of cases. Mutations in other genes have each been identified in a smaller number of affected individuals.  The genes associated with combined pituitary hormone deficiency provide instructions for making proteins called transcription factors, which help control the activity of many other genes. The proteins are involved in the development of the pituitary gland and the specialization (differentiation) of its cell types. The cells of the pituitary gland are responsible for triggering the release of several hormones that direct the development of many parts of the body. Some of the transcription factors are found only in the pituitary gland, and some are also active in other parts of the body.  Mutations in the genes associated with combined pituitary hormone deficiency can result in abnormal differentiation of pituitary gland cells and may prevent the production of several hormones. These hormones can include growth hormone (GH), which is needed for normal growth; follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which both play a role in sexual development and the ability to have children (fertility); thyroid-stimulating hormone (TSH), which helps with thyroid gland function; prolactin, which stimulates the production of breast milk; and adrenocorticotropic hormone (ACTH), which influences energy production in the body and maintains normal blood sugar and blood pressure levels. The degree to which these hormones are deficient is variable, with prolactin and ACTH showing the most variability. In many affected individuals, ACTH deficiency does not occur until late adulthood.  Most people with combined pituitary hormone deficiency do not have identified mutations in any of the genes known to be associated with this condition. The cause of the disorder in these individuals is unknown.",combined pituitary hormone deficiency,0000206,GHR,https://ghr.nlm.nih.gov/condition/combined-pituitary-hormone-deficiency,C0857439,T047,Disorders
Is combined pituitary hormone deficiency inherited ?,0000206-4,inheritance,"Most cases of combined pituitary hormone deficiency are sporadic, which means they occur in people with no history of the disorder in their family. Less commonly, this condition has been found to run in families. When the disorder is familial, it can have an autosomal dominant or an autosomal recessive pattern of inheritance.  Autosomal dominant inheritance means one copy of an altered gene in each cell is sufficient to cause the disorder.  Autosomal recessive inheritance means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of a mutated gene, but they typically do not show signs and symptoms of the condition. Most cases of familial combined pituitary hormone deficiency are inherited in an autosomal recessive pattern.",combined pituitary hormone deficiency,0000206,GHR,https://ghr.nlm.nih.gov/condition/combined-pituitary-hormone-deficiency,C0857439,T047,Disorders
What are the treatments for combined pituitary hormone deficiency ?,0000206-5,treatment,"These resources address the diagnosis or management of combined pituitary hormone deficiency:  - Gene Review: Gene Review: PROP1-Related Combined Pituitary Hormone Deficiency  - Genetic Testing Registry: Pituitary hormone deficiency, combined  - Genetic Testing Registry: Pituitary hormone deficiency, combined 1  - Genetic Testing Registry: Pituitary hormone deficiency, combined 2  - Genetic Testing Registry: Pituitary hormone deficiency, combined 3  - Genetic Testing Registry: Pituitary hormone deficiency, combined 4  - Genetic Testing Registry: Pituitary hormone deficiency, combined 5  - Genetic Testing Registry: Pituitary hormone deficiency, combined 6  - Great Ormond Street Hospital for Children (UK): Growth Hormone Deficiency  - MedlinePlus Encyclopedia: ACTH  - MedlinePlus Encyclopedia: FSH  - MedlinePlus Encyclopedia: Growth Hormone Deficiency  - MedlinePlus Encyclopedia: Prolactin  - MedlinePlus Encyclopedia: TSH Test   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",combined pituitary hormone deficiency,0000206,GHR,https://ghr.nlm.nih.gov/condition/combined-pituitary-hormone-deficiency,C0857439,T047,Disorders
What is (are) common variable immune deficiency ?,0000207-1,information,"Common variable immune deficiency (CVID) is a disorder that impairs the immune system. People with CVID are highly susceptible to infection from foreign invaders such as bacteria, or more rarely, viruses and often develop recurrent infections, particularly in the lungs, sinuses, and ears. Pneumonia is common in people with CVID. Over time, recurrent infections can lead to chronic lung disease. Affected individuals may also experience infection or inflammation of the gastrointestinal tract, which can cause diarrhea and weight loss. Abnormal accumulation of immune cells causes enlarged lymph nodes (lymphadenopathy) or an enlarged spleen (splenomegaly) in some people with CVID. Immune cells can accumulate in other organs, forming small lumps called granulomas.  Approximately 25 percent of people with CVID have an autoimmune disorder, which occurs when the immune system malfunctions and attacks the body's tissues and organs. The blood cells are most frequently affected by autoimmune attacks in CVID; the most commonly occurring autoimmune disorders are immune thrombocytopenia purpura, which is an abnormal bleeding disorder caused by a decrease in platelets, and autoimmune hemolytic anemia, which results in premature destruction of red blood cells. Other autoimmune disorders such as rheumatoid arthritis can occur. Individuals with CVID also have a greater than normal risk of developing certain types of cancer, including a cancer of immune system cells called non-Hodgkin lymphoma and less frequently, stomach (gastric) cancer.  People with CVID may start experiencing signs and symptoms of the disorder anytime between childhood and adulthood. The life expectancy of individuals with CVID varies depending on the severity and frequency of illnesses they experience. Most people with CVID live into adulthood.",common variable immune deficiency,0000207,GHR,https://ghr.nlm.nih.gov/condition/common-variable-immune-deficiency,C0009447,T047,Disorders
How many people are affected by common variable immune deficiency ?,0000207-2,frequency,"CVID is estimated to affect 1 in 25,000 to 1 in 50,000 people worldwide, although the prevalence can vary across different populations.",common variable immune deficiency,0000207,GHR,https://ghr.nlm.nih.gov/condition/common-variable-immune-deficiency,C0009447,T047,Disorders
What are the genetic changes related to common variable immune deficiency ?,0000207-3,genetic changes,"CVID is believed to result from mutations in genes that are involved in the development and function of immune system cells called B cells. B cells are specialized white blood cells that help protect the body against infection. When B cells mature, they produce special proteins called antibodies (also known as immunoglobulins). These proteins attach to foreign particles, marking them for destruction. Mutations in the genes associated with CVID result in dysfunctional B cells that cannot make sufficient amounts of antibodies.  People with CVID have a shortage (deficiency) of specific antibodies called immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM). Some have a deficiency of all three antibodies, while others are lacking only IgG and IgA. A shortage of these antibodies makes it difficult for people with this disorder to fight off infections. Abnormal and deficient immune responses over time likely contribute to the increased cancer risk. In addition, vaccines for diseases such as measles and influenza do not provide protection for people with CVID because they cannot produce an antibody response.  Mutations in at least 10 genes have been associated with CVID. Approximately 10 percent of affected individuals have mutations in the TNFRSF13B gene. The protein produced from this gene plays a role in the survival and maturation of B cells and in the production of antibodies. TNFRSF13B gene mutations disrupt B cell function and antibody production, leading to immune dysfunction. Other genes associated with CVID are also involved in the function and maturation of immune system cells, particularly of B cells; mutations in these genes account for only a small percentage of cases.  In most cases of CVID, the cause is unknown, but it is likely a combination of genetic and environmental factors.",common variable immune deficiency,0000207,GHR,https://ghr.nlm.nih.gov/condition/common-variable-immune-deficiency,C0009447,T047,Disorders
Is common variable immune deficiency inherited ?,0000207-4,inheritance,"Most cases of CVID are sporadic and occur in people with no apparent history of the disorder in their family. These cases probably result from a complex interaction of environmental and genetic factors.  In some families, CVID is inherited in an autosomal recessive pattern, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  In very rare cases, this condition is inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder.  When CVID is caused by mutations in the TNFRSF13B gene, it is often sporadic. When TNFRSF13B gene mutations are inherited, they can cause either autosomal dominant CVID or autosomal recessive CVID.  Not all individuals who inherit a gene mutation associated with CVID will develop the disease. In many cases, affected children have an unaffected parent who shares the same mutation. Additional genetic or environmental factors are probably needed for the disorder to occur.",common variable immune deficiency,0000207,GHR,https://ghr.nlm.nih.gov/condition/common-variable-immune-deficiency,C0009447,T047,Disorders
What are the treatments for common variable immune deficiency ?,0000207-5,treatment,"These resources address the diagnosis or management of common variable immune deficiency:  - Genetic Testing Registry: Common variable immunodeficiency 10  - Genetic Testing Registry: Common variable immunodeficiency 11  - Genetic Testing Registry: Common variable immunodeficiency 2  - Genetic Testing Registry: Common variable immunodeficiency 5  - Genetic Testing Registry: Common variable immunodeficiency 6  - Genetic Testing Registry: Common variable immunodeficiency 7  - Genetic Testing Registry: Common variable immunodeficiency 8, with autoimmunity  - Genetic Testing Registry: Common variable immunodeficiency 9  - KidsHealth from Nemours: Blood Test: Immunoglobulins  - MedlinePlus Encyclopedia: Immunodeficiency Disorders  - National Marrow Donor Program  - Primary Immune Deficiency Treatment Consortium  - United States Immunodeficiency Network   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",common variable immune deficiency,0000207,GHR,https://ghr.nlm.nih.gov/condition/common-variable-immune-deficiency,C0009447,T047,Disorders
What is (are) complement component 2 deficiency ?,0000208-1,information,"Complement component 2 deficiency is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. Immunodeficiencies are conditions in which the immune system is not able to protect the body effectively from foreign invaders such as bacteria and viruses. People with complement component 2 deficiency have a significantly increased risk of recurrent bacterial infections, specifically of the lungs (pneumonia), the membrane covering the brain and spinal cord (meningitis), and the blood (sepsis), which may be life-threatening. These infections most commonly occur in infancy and childhood and become less frequent in adolescence and adulthood.  Complement component 2 deficiency is also associated with an increased risk of developing autoimmune disorders such as systemic lupus erythematosus (SLE) or vasculitis. Autoimmune disorders occur when the immune system malfunctions and attacks the body's tissues and organs. Between 10 and 20 percent of individuals with complement component 2 deficiency develop SLE. Females with complement component 2 deficiency are more likely to have SLE than affected males, but this is also true of SLE in the general population.  The severity of complement component 2 deficiency varies widely. While some affected individuals experience recurrent infections and other immune system difficulties, others do not have any health problems related to the disorder.",complement component 2 deficiency,0000208,GHR,https://ghr.nlm.nih.gov/condition/complement-component-2-deficiency,C3150275,T033,Disorders
How many people are affected by complement component 2 deficiency ?,0000208-2,frequency,"In Western countries, complement component 2 deficiency is estimated to affect 1 in 20,000 individuals; its prevalence in other areas of the world is unknown.",complement component 2 deficiency,0000208,GHR,https://ghr.nlm.nih.gov/condition/complement-component-2-deficiency,C3150275,T033,Disorders
What are the genetic changes related to complement component 2 deficiency ?,0000208-3,genetic changes,"Complement component 2 deficiency is caused by mutations in the C2 gene. This gene provides instructions for making the complement component 2 protein, which helps regulate a part of the body's immune response known as the complement system. The complement system is a group of proteins that work together to destroy foreign invaders, trigger inflammation, and remove debris from cells and tissues. The complement component 2 protein is involved in the pathway that turns on (activates) the complement system when foreign invaders, such as bacteria, are detected.  The most common C2 gene mutation, which is found in more than 90 percent of people with complement component 2 deficiency, prevents the production of complement component 2 protein. A lack of this protein impairs activation of the complement pathway. As a result, the complement system's ability to fight infections is diminished. It is unclear how complement component 2 deficiency leads to an increase in autoimmune disorders. Researchers speculate that the dysfunctional complement system is unable to distinguish what it should attack, and it sometimes attacks normal tissues, leading to autoimmunity. Alternatively, the dysfunctional complement system may perform partial attacks on invading molecules, which leaves behind foreign fragments that are difficult to distinguish from the body's tissues, so the complement system sometimes attacks the body's own cells. It is likely that other factors, both genetic and environmental, play a role in the variability of the signs and symptoms of complement component 2 deficiency.",complement component 2 deficiency,0000208,GHR,https://ghr.nlm.nih.gov/condition/complement-component-2-deficiency,C3150275,T033,Disorders
Is complement component 2 deficiency inherited ?,0000208-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",complement component 2 deficiency,0000208,GHR,https://ghr.nlm.nih.gov/condition/complement-component-2-deficiency,C3150275,T033,Disorders
What are the treatments for complement component 2 deficiency ?,0000208-5,treatment,These resources address the diagnosis or management of complement component 2 deficiency:  - Genetic Testing Registry: Complement component 2 deficiency  - MedlinePlus Encyclopedia: Complement  - MedlinePlus Encyclopedia: Immunodeficiency Disorders  - Primary Immune Deficiency Treatment Consortium   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,complement component 2 deficiency,0000208,GHR,https://ghr.nlm.nih.gov/condition/complement-component-2-deficiency,C3150275,T033,Disorders
What is (are) complement factor I deficiency ?,0000210-1,information,"Complement factor I deficiency is a disorder that affects the immune system. People with this condition are prone to recurrent infections, including infections of the upper respiratory tract, ears, skin, and urinary tract. They may also contract more serious infections such as pneumonia, meningitis, and sepsis, which may be life-threatening.  Some people with complement factor I deficiency have a kidney disorder called glomerulonephritis with isolated C3 deposits. Complement factor I deficiency can also be associated with autoimmune disorders such as rheumatoid arthritis or systemic lupus erythematosus (SLE). Autoimmune disorders occur when the immune system malfunctions and attacks the body's tissues and organs.",complement factor I deficiency,0000210,GHR,https://ghr.nlm.nih.gov/condition/complement-factor-i-deficiency,C3463916,T047,Disorders
How many people are affected by complement factor I deficiency ?,0000210-2,frequency,Complement factor I deficiency is a rare disorder; its exact prevalence is unknown. At least 38 cases have been reported in the medical literature.,complement factor I deficiency,0000210,GHR,https://ghr.nlm.nih.gov/condition/complement-factor-i-deficiency,C3463916,T047,Disorders
What are the genetic changes related to complement factor I deficiency ?,0000210-3,genetic changes,"Complement factor I deficiency is caused by mutations in the CFI gene. This gene provides instructions for making a protein called complement factor I. This protein helps regulate a part of the body's immune response known as the complement system. The complement system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. This system must be carefully regulated so it targets only unwanted materials and does not attack the body's healthy cells. Complement factor I and several related proteins protect healthy cells by preventing activation of the complement system when it is not needed.  Mutations in the CFI gene that cause complement factor I deficiency result in abnormal, nonfunctional, or absent complement factor I. The lack (deficiency) of functional complement factor I protein allows uncontrolled activation of the complement system. The unregulated activity of the complement system decreases blood levels of another complement protein called C3, reducing the immune system's ability to fight infections. In addition, the immune system may malfunction and attack its own tissues, resulting in autoimmune disorders.",complement factor I deficiency,0000210,GHR,https://ghr.nlm.nih.gov/condition/complement-factor-i-deficiency,C3463916,T047,Disorders
Is complement factor I deficiency inherited ?,0000210-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",complement factor I deficiency,0000210,GHR,https://ghr.nlm.nih.gov/condition/complement-factor-i-deficiency,C3463916,T047,Disorders
What are the treatments for complement factor I deficiency ?,0000210-5,treatment,These resources address the diagnosis or management of complement factor I deficiency:  - MedlinePlus Encyclopedia: Complement   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,complement factor I deficiency,0000210,GHR,https://ghr.nlm.nih.gov/condition/complement-factor-i-deficiency,C3463916,T047,Disorders
What is (are) complete LCAT deficiency ?,0000211-1,information,"Complete LCAT deficiency is a disorder that primarily affects the eyes and kidneys.  In complete LCAT deficiency, the clear front surface of the eyes (the corneas) gradually becomes cloudy. The cloudiness, which generally first appears in early childhood, consists of small grayish dots of cholesterol (opacities) distributed across the corneas. Cholesterol is a waxy, fat-like substance that is produced in the body and obtained from foods that come from animals; it aids in many functions of the body but can become harmful in excessive amounts. As complete LCAT deficiency progresses, the corneal cloudiness worsens and can lead to severely impaired vision.  People with complete LCAT deficiency often have kidney disease that begins in adolescence or early adulthood. The kidney problems get worse over time and may eventually lead to kidney failure. Individuals with this disorder also usually have a condition known as hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely, resulting in a shortage of red blood cells (anemia). Anemia can cause pale skin, weakness, fatigue, and more serious complications.  Other features of complete LCAT deficiency that occur in some affected individuals include enlargement of the liver (hepatomegaly), spleen (splenomegaly), or lymph nodes (lymphadenopathy) or an accumulation of fatty deposits on the artery walls (atherosclerosis).",complete LCAT deficiency,0000211,GHR,https://ghr.nlm.nih.gov/condition/complete-lcat-deficiency,C0023195,T047,Disorders
How many people are affected by complete LCAT deficiency ?,0000211-2,frequency,Complete LCAT deficiency is a rare disorder. Approximately 70 cases have been reported in the medical literature.,complete LCAT deficiency,0000211,GHR,https://ghr.nlm.nih.gov/condition/complete-lcat-deficiency,C0023195,T047,Disorders
What are the genetic changes related to complete LCAT deficiency ?,0000211-3,genetic changes,"Complete LCAT deficiency is caused by mutations in the LCAT gene. This gene provides instructions for making an enzyme called lecithin-cholesterol acyltransferase (LCAT).  The LCAT enzyme plays a role in removing cholesterol from the blood and tissues by helping it attach to molecules called lipoproteins, which carry it to the liver. Once in the liver, the cholesterol is redistributed to other tissues or removed from the body. The enzyme has two major functions, called alpha- and beta-LCAT activity. Alpha-LCAT activity helps attach cholesterol to a lipoprotein called high-density lipoprotein (HDL). Beta-LCAT activity helps attach cholesterol to other lipoproteins called very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL).  LCAT gene mutations that cause complete LCAT deficiency either prevent the production of LCAT or impair both alpha-LCAT and beta-LCAT activity, reducing the enzyme's ability to attach cholesterol to lipoproteins. Impairment of this mechanism for reducing cholesterol in the body leads to cholesterol deposits in the corneas, kidneys, and other tissues and organs. LCAT gene mutations that affect only alpha-LCAT activity cause a related disorder called fish-eye disease that affects only the corneas.",complete LCAT deficiency,0000211,GHR,https://ghr.nlm.nih.gov/condition/complete-lcat-deficiency,C0023195,T047,Disorders
Is complete LCAT deficiency inherited ?,0000211-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",complete LCAT deficiency,0000211,GHR,https://ghr.nlm.nih.gov/condition/complete-lcat-deficiency,C0023195,T047,Disorders
What are the treatments for complete LCAT deficiency ?,0000211-5,treatment,"These resources address the diagnosis or management of complete LCAT deficiency:  - Genetic Testing Registry: Norum disease  - MedlinePlus Encyclopedia: Corneal Transplant  - National Heart, Lung, and Blood Institute: How is Hemolytic Anemia Treated?  - National Institutes of Diabetes and Digestive and Kidney Diseases: Kidney Failure -- Choosing a Treatment That's Right for You  - Oregon Health and Science University: Corneal Dystrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",complete LCAT deficiency,0000211,GHR,https://ghr.nlm.nih.gov/condition/complete-lcat-deficiency,C0023195,T047,Disorders
What is (are) cone-rod dystrophy ?,0000212-1,information,"Cone-rod dystrophy is a group of related eye disorders that causes vision loss, which becomes more severe over time. These disorders affect the retina, which is the layer of light-sensitive tissue at the back of the eye. In people with cone-rod dystrophy, vision loss occurs as the light-sensing cells of the retina gradually deteriorate.  The first signs and symptoms of cone-rod dystrophy, which often occur in childhood, are usually decreased sharpness of vision (visual acuity) and increased sensitivity to light (photophobia). These features are typically followed by impaired color vision (dyschromatopsia), blind spots (scotomas) in the center of the visual field, and partial side (peripheral) vision loss. Over time, affected individuals develop night blindness and a worsening of their peripheral vision, which can limit independent mobility. Decreasing visual acuity makes reading increasingly difficult and most affected individuals are legally blind by mid-adulthood. As the condition progresses, individuals may develop involuntary eye movements (nystagmus).  There are more than 30 types of cone-rod dystrophy, which are distinguished by their genetic cause and their pattern of inheritance: autosomal recessive, autosomal dominant, or X-linked (each of which is described below). Additionally, cone-rod dystrophy can occur alone without any other signs and symptoms or it can occur as part of a syndrome that affects multiple parts of the body.",cone-rod dystrophy,0000212,GHR,https://ghr.nlm.nih.gov/condition/cone-rod-dystrophy,C0035334,T047,Disorders
How many people are affected by cone-rod dystrophy ?,0000212-2,frequency,"Cone-rod dystrophy is estimated to affect 1 in 30,000 to 40,000 individuals.",cone-rod dystrophy,0000212,GHR,https://ghr.nlm.nih.gov/condition/cone-rod-dystrophy,C0035334,T047,Disorders
What are the genetic changes related to cone-rod dystrophy ?,0000212-3,genetic changes,"Mutations in approximately 30 genes are known to cause cone-rod dystrophy. Approximately 20 of these genes are associated with the form of cone-rod dystrophy that is inherited in an autosomal recessive pattern. Mutations in the ABCA4 gene are the most common cause of autosomal recessive cone-rod dystrophy, accounting for 30 to 60 percent of cases. At least 10 genes have been associated with cone-rod dystrophy that is inherited in an autosomal dominant pattern. Mutations in the GUCY2D and CRX genes account for about half of these cases. Changes in at least two genes cause the X-linked form of the disorder, which is rare.  The genes associated with cone-rod dystrophy play essential roles in the structure and function of specialized light receptor cells (photoreceptors) in the retina. The retina contains two types of photoreceptors, rods and cones. Rods are needed for vision in low light, while cones provide vision in bright light, including color vision.  Mutations in any of the genes associated with cone-rod dystrophy lead to a gradual loss of rods and cones in the retina. The progressive degeneration of these cells causes the characteristic pattern of vision loss that occurs in people with cone-rod dystrophy. Cones typically break down before rods, which is why sensitivity to light and impaired color vision are usually the first signs of the disorder. (The order of cell breakdown is also reflected in the condition name.) Night vision is disrupted later, as rods are lost.  Some of the genes associated with cone-rod dystrophy are also associated with other eye diseases, including a group of related eye disorders called rod-cone dystrophy. Rod-cone dystrophy has signs and symptoms similar to those of cone-rod dystrophy. However, rod-cone dystrophy is characterized by deterioration of the rods first, followed by the cones, so night vision is affected before daylight and color vision. The most common form of rod-cone dystrophy is a condition called retinitis pigmentosa.",cone-rod dystrophy,0000212,GHR,https://ghr.nlm.nih.gov/condition/cone-rod-dystrophy,C0035334,T047,Disorders
Is cone-rod dystrophy inherited ?,0000212-4,inheritance,"Cone-rod dystrophy is usually inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Less frequently, this condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most of these cases, an affected person has one parent with the condition.  Rarely, cone-rod dystrophy is inherited in an X-linked recessive pattern. The genes associated with this form of the condition are located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. Females with one copy of the altered gene have mild vision problems, such as decreased visual acuity. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",cone-rod dystrophy,0000212,GHR,https://ghr.nlm.nih.gov/condition/cone-rod-dystrophy,C0035334,T047,Disorders
What are the treatments for cone-rod dystrophy ?,0000212-5,treatment,"These resources address the diagnosis or management of cone-rod dystrophy:  - Cleveland Clinic: Eye Examinations: What to Expect  - Genetic Testing Registry: CONE-ROD DYSTROPHY, AIPL1-RELATED  - Genetic Testing Registry: Cone-rod dystrophy  - Genetic Testing Registry: Cone-rod dystrophy 1  - Genetic Testing Registry: Cone-rod dystrophy 10  - Genetic Testing Registry: Cone-rod dystrophy 11  - Genetic Testing Registry: Cone-rod dystrophy 12  - Genetic Testing Registry: Cone-rod dystrophy 13  - Genetic Testing Registry: Cone-rod dystrophy 15  - Genetic Testing Registry: Cone-rod dystrophy 16  - Genetic Testing Registry: Cone-rod dystrophy 17  - Genetic Testing Registry: Cone-rod dystrophy 18  - Genetic Testing Registry: Cone-rod dystrophy 19  - Genetic Testing Registry: Cone-rod dystrophy 2  - Genetic Testing Registry: Cone-rod dystrophy 20  - Genetic Testing Registry: Cone-rod dystrophy 21  - Genetic Testing Registry: Cone-rod dystrophy 3  - Genetic Testing Registry: Cone-rod dystrophy 5  - Genetic Testing Registry: Cone-rod dystrophy 6  - Genetic Testing Registry: Cone-rod dystrophy 7  - Genetic Testing Registry: Cone-rod dystrophy 8  - Genetic Testing Registry: Cone-rod dystrophy 9  - Genetic Testing Registry: Cone-rod dystrophy X-linked 3  - Genetic Testing Registry: Cone-rod dystrophy, X-linked 1  - MedlinePlus Encyclopedia: Color Vision Test  - MedlinePlus Encyclopedia: Visual Acuity Test  - MedlinePlus Encyclopedia: Visual Field Test   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",cone-rod dystrophy,0000212,GHR,https://ghr.nlm.nih.gov/condition/cone-rod-dystrophy,C0035334,T047,Disorders
What is (are) congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency ?,0000213-1,information,"Congenital adrenal hyperplasia (CAH) due to 11-beta-hydroxylase deficiency is one of a group of disorders (collectively called congenital adrenal hyperplasia) that affect the adrenal glands. The adrenal glands are located on top of the kidneys and produce a variety of hormones that regulate many essential functions in the body. In people with CAH due to 11-beta-hydroxylase deficiency, the adrenal glands produce excess androgens, which are male sex hormones.  There are two types of CAH due to 11-beta-hydroxylase deficiency, the classic form and the non-classic form. The classic form is the more severe of the two types.  Females with the classic form of CAH due to 11-beta-hydroxylase deficiency have external genitalia that do not look clearly male or female (ambiguous genitalia). However, the internal reproductive organs develop normally. Males and females with the classic form of this condition have early development of their secondary sexual characteristics such as growth of facial and pubic hair, deepening of the voice, appearance of acne, and onset of a growth spurt. The early growth spurt can prevent growth later in adolescence and lead to short stature in adulthood. In addition, approximately two-thirds of individuals with the classic form of CAH due to 11-beta-hydroxylase deficiency have high blood pressure (hypertension). Hypertension typically develops within the first year of life.  Females with the non-classic form of CAH due to 11-beta-hydroxylase deficiency have normal female genitalia. As affected females get older, they may develop excessive body hair growth (hirsutism) and irregular menstruation. Males with the non-classic form of this condition do not typically have any signs or symptoms except for short stature. Hypertension is not a feature of the non-classic form of CAH due to 11-beta-hydroxylase deficiency.",congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency,0000213,GHR,https://ghr.nlm.nih.gov/condition/congenital-adrenal-hyperplasia-due-to-11-beta-hydroxylase-deficiency,C1291314,T019,Disorders
How many people are affected by congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency ?,0000213-2,frequency,"CAH due to 11-beta-hydroxylase deficiency accounts for 5 to 8 percent of all cases of congenital adrenal hyperplasia. It is estimated that CAH due to 11-beta-hydroxylase deficiency occurs in 1 in 100,000 to 200,000 newborns. This condition is more common in Moroccan Jews living in Israel, occurring in approximately 1 in 5,000 to 7,000 newborns. The classic form of CAH due to 11-beta-hydroxylase deficiency appears to be much more common than the non-classic form.",congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency,0000213,GHR,https://ghr.nlm.nih.gov/condition/congenital-adrenal-hyperplasia-due-to-11-beta-hydroxylase-deficiency,C1291314,T019,Disorders
What are the genetic changes related to congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency ?,0000213-3,genetic changes,"Mutations in the CYP11B1 gene cause CAH due to 11-beta-hydroxylase deficiency. The CYP11B1 gene provides instructions for making an enzyme called 11-beta-hydroxylase. This enzyme is found in the adrenal glands, where it helps produce hormones called cortisol and corticosterone. Cortisol has numerous functions, such as maintaining blood sugar levels, protecting the body from stress, and suppressing inflammation. Corticosterone gets converted to the hormone aldosterone, which helps control blood pressure by maintaining proper salt and fluid levels in the body.  CAH due to 11-beta-hydroxylase deficiency is caused by a shortage (deficiency) of the 11-beta-hydroxylase enzyme. When 11-beta-hydroxylase is lacking, precursors that are used to form cortisol and corticosterone build up in the adrenal glands and are converted to androgens. The excess production of androgens leads to abnormalities of sexual development, particularly in females with CAH due to 11-beta-hydroxylase deficiency. A buildup in the precursors used to form corticosterone increases salt retention, leading to hypertension in individuals with the classic form of CAH due to 11-beta-hydroxylase deficiency.  The amount of functional 11-beta-hydroxylase enzyme that an individual produces typically determines the extent of abnormal sexual development. Individuals with the classic form of the condition usually have CYP11B1 gene mutations that result in the production of an enzyme with low levels of function or no function at all. Individuals with the non-classic form of the condition typically have CYP11B1 gene mutations that lead to the production of an enzyme with moderately reduced function. The severity of the signs and symptoms of sexual development do not appear to be related to the severity of the hypertension.",congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency,0000213,GHR,https://ghr.nlm.nih.gov/condition/congenital-adrenal-hyperplasia-due-to-11-beta-hydroxylase-deficiency,C1291314,T019,Disorders
Is congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency inherited ?,0000213-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency,0000213,GHR,https://ghr.nlm.nih.gov/condition/congenital-adrenal-hyperplasia-due-to-11-beta-hydroxylase-deficiency,C1291314,T019,Disorders
What are the treatments for congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency ?,0000213-5,treatment,These resources address the diagnosis or management of congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency:  - Genetic Testing Registry: Deficiency of steroid 11-beta-monooxygenase  - MedlinePlus Encyclopedia: Congenital Adrenal Hyperplasia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency,0000213,GHR,https://ghr.nlm.nih.gov/condition/congenital-adrenal-hyperplasia-due-to-11-beta-hydroxylase-deficiency,C1291314,T019,Disorders
What is (are) congenital afibrinogenemia ?,0000214-1,information,"Congenital afibrinogenemia is a bleeding disorder caused by impairment of the blood clotting process. Normally, blood clots protect the body after an injury by sealing off damaged blood vessels and preventing further blood loss. However, bleeding is uncontrolled in people with congenital afibrinogenemia. Newborns with this condition often experience prolonged bleeding from the umbilical cord stump after birth. Nosebleeds (epistaxis) and bleeding from the gums or tongue are common and can occur after minor trauma or in the absence of injury (spontaneous bleeding). Some affected individuals experience bleeding into the spaces between joints (hemarthrosis) or the muscles (hematoma). Rarely, bleeding in the brain or other internal organs occurs, which can be fatal. Women with congenital afibrinogenemia can have abnormally heavy menstrual bleeding (menorrhagia). Without proper treatment, women with this disorder may have difficulty carrying a pregnancy to term, resulting in repeated miscarriages.",congenital afibrinogenemia,0000214,GHR,https://ghr.nlm.nih.gov/condition/congenital-afibrinogenemia,C0019250,T019,Disorders
How many people are affected by congenital afibrinogenemia ?,0000214-2,frequency,Congenital afibrinogenemia is a rare condition that occurs in approximately 1 in 1 million newborns.,congenital afibrinogenemia,0000214,GHR,https://ghr.nlm.nih.gov/condition/congenital-afibrinogenemia,C0019250,T019,Disorders
What are the genetic changes related to congenital afibrinogenemia ?,0000214-3,genetic changes,"Congenital afibrinogenemia results from mutations in one of three genes, FGA, FGB, or FGG. Each of these genes provides instructions for making one part (subunit) of a protein called fibrinogen. This protein is important for blood clot formation (coagulation), which is needed to stop excessive bleeding after injury. In response to injury, fibrinogen is converted to fibrin, the main protein in blood clots. Fibrin proteins attach to each other, forming a stable network that makes up the blood clot.  Congenital afibrinogenemia is caused by a complete absence of fibrinogen protein. Most FGA, FGB, and FGG gene mutations that cause this condition result in a premature stop signal in the instructions for making the respective protein. If any protein is made, it is nonfunctional. When any one subunit is missing, the fibrinogen protein is not assembled, which results in the absence of fibrin. Consequently, blood clots do not form in response to injury, leading to the excessive bleeding seen in people with congenital afibrinogenemia.",congenital afibrinogenemia,0000214,GHR,https://ghr.nlm.nih.gov/condition/congenital-afibrinogenemia,C0019250,T019,Disorders
Is congenital afibrinogenemia inherited ?,0000214-4,inheritance,"Congenital afibrinogenemia is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene. The parents have about half the normal level of fibrinogen in their blood but typically do not show signs and symptoms of the condition.",congenital afibrinogenemia,0000214,GHR,https://ghr.nlm.nih.gov/condition/congenital-afibrinogenemia,C0019250,T019,Disorders
What are the treatments for congenital afibrinogenemia ?,0000214-5,treatment,These resources address the diagnosis or management of congenital afibrinogenemia:  - Genetic Testing Registry: Hereditary factor I deficiency disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,congenital afibrinogenemia,0000214,GHR,https://ghr.nlm.nih.gov/condition/congenital-afibrinogenemia,C0019250,T019,Disorders
What is (are) congenital bilateral absence of the vas deferens ?,0000215-1,information,"Congenital bilateral absence of the vas deferens occurs in males when the tubes that carry sperm out of the testes (the vas deferens) fail to develop properly. Although the testes usually develop and function normally, sperm cannot be transported through the vas deferens to become part of semen. As a result, men with this condition are unable to father children (infertile) unless they use assisted reproductive technologies. This condition has not been reported to affect sex drive or sexual performance.  This condition can occur alone or as a sign of cystic fibrosis, an inherited disease of the mucus glands. Cystic fibrosis causes progressive damage to the respiratory system and chronic digestive system problems. Many men with congenital bilateral absence of the vas deferens do not have the other characteristic features of cystic fibrosis; however, some men with this condition may experience mild respiratory or digestive problems.",congenital bilateral absence of the vas deferens,0000215,GHR,https://ghr.nlm.nih.gov/condition/congenital-bilateral-absence-of-the-vas-deferens,C0403814,T019,Disorders
How many people are affected by congenital bilateral absence of the vas deferens ?,0000215-2,frequency,This condition is responsible for 1 percent to 2 percent of all infertility in men.,congenital bilateral absence of the vas deferens,0000215,GHR,https://ghr.nlm.nih.gov/condition/congenital-bilateral-absence-of-the-vas-deferens,C0403814,T019,Disorders
What are the genetic changes related to congenital bilateral absence of the vas deferens ?,0000215-3,genetic changes,"Mutations in the CFTR gene cause congenital bilateral absence of the vas deferens.  More than half of all men with this condition have mutations in the CFTR gene. Mutations in this gene also cause cystic fibrosis. When congenital bilateral absence of the vas deferens occurs with CFTR mutations, it is considered a form of atypical cystic fibrosis.  The protein made from the CFTR gene forms a channel that transports negatively charged particles called chloride ions into and out of cells. The flow of chloride ions helps control the movement of water in tissues, which is necessary for the production of thin, freely flowing mucus. Mucus is a slippery substance that lubricates and protects the linings of the airways, digestive system, reproductive system, and other organs and tissues.  Mutations in the CFTR gene disrupt the function of the chloride channels, preventing them from regulating the flow of chloride ions and water across cell membranes. As a result, cells in the male genital tract produce mucus that is abnormally thick and sticky. This mucus clogs the vas deferens as they are forming, causing them to deteriorate before birth.  In instances of congenital bilateral absence of the vas deferens without a mutation in the CFTR gene, the cause of this condition is often unknown. Some cases are associated with other structural problems of the urinary tract.",congenital bilateral absence of the vas deferens,0000215,GHR,https://ghr.nlm.nih.gov/condition/congenital-bilateral-absence-of-the-vas-deferens,C0403814,T019,Disorders
Is congenital bilateral absence of the vas deferens inherited ?,0000215-4,inheritance,"When this condition is caused by mutations in the CFTR gene, it is inherited in an autosomal recessive pattern. This pattern of inheritance means that both copies of the gene in each cell have a mutation. Men with this condition who choose to father children through assisted reproduction have an increased risk of having a child with cystic fibrosis. If congenital absence of the vas deferens is not caused by mutations in CFTR, the risk of having children with cystic fibrosis is not increased.",congenital bilateral absence of the vas deferens,0000215,GHR,https://ghr.nlm.nih.gov/condition/congenital-bilateral-absence-of-the-vas-deferens,C0403814,T019,Disorders
What are the treatments for congenital bilateral absence of the vas deferens ?,0000215-5,treatment,These resources address the diagnosis or management of congenital bilateral absence of the vas deferens:  - Gene Review: Gene Review: CFTR-Related Disorders  - Genetic Testing Registry: Congenital bilateral absence of the vas deferens  - MedlinePlus Encyclopedia: Infertility  - MedlinePlus Encyclopedia: Pathway of sperm (image)  - MedlinePlus Health Topic: Assisted Reproductive Technology   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,congenital bilateral absence of the vas deferens,0000215,GHR,https://ghr.nlm.nih.gov/condition/congenital-bilateral-absence-of-the-vas-deferens,C0403814,T019,Disorders
"What is (are) congenital cataracts, facial dysmorphism, and neuropathy ?",0000218-1,information,"Congenital cataracts, facial dysmorphism, and neuropathy (CCFDN) is a rare disorder that affects several parts of the body. It is characterized by a clouding of the lens of the eyes at birth (congenital cataracts) and other eye abnormalities, such as small or poorly developed eyes (microphthalmia) and abnormal eye movements (nystagmus). Affected individuals, particularly males, often have distinctive facial features that become more apparent as they reach adulthood. These features include a prominent midface, a large nose, protruding teeth, and a small lower jaw.  CCFDN causes progressive damage to the peripheral nerves, which connect the brain and spinal cord to muscles and sensory cells. This nerve damage is known as peripheral neuropathy. Weakness in the legs, followed by the arms, begins in the first few years of life, and as a result children with CCFDN have delayed development of motor skills such as standing and walking. In adolescence, affected individuals develop sensory abnormalities such as numbness and tingling, mainly in the legs. By adulthood they typically have significant difficulties with mobility. Muscle weakness can also lead to skeletal abnormalities such as hand and foot deformities and abnormal curvature of the spine.  People with CCFDN may have problems with balance and coordination (ataxia), tremors, and difficulty with movements that involve judging distance or scale (dysmetria). Some have mild intellectual disability. Individuals with CCFDN have short stature, are typically underweight, and have reduced bone density.  A complication called rhabdomyolysis occurs in some people with CCFDN, typically following a viral infection or, in rare cases, during or after surgery. Rhabdomyolysis is a breakdown of muscle tissue that results in severe muscle weakness. The destruction of muscle tissue releases a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria). The presence of myoglobin causes the urine to be red or brown. The muscles may take up to a year to recover, and the episodes may worsen the muscle weakness caused by the neuropathy.","congenital cataracts, facial dysmorphism, and neuropathy",0000218,GHR,https://ghr.nlm.nih.gov/condition/congenital-cataracts-facial-dysmorphism-and-neuropathy,C0086543,T190,Disorders
"How many people are affected by congenital cataracts, facial dysmorphism, and neuropathy ?",0000218-2,frequency,"The prevalence of CCFDN is unknown. The disorder has been identified in about 150 individuals of Romani ethnicity. Thus far, no affected individuals have been observed outside this community.","congenital cataracts, facial dysmorphism, and neuropathy",0000218,GHR,https://ghr.nlm.nih.gov/condition/congenital-cataracts-facial-dysmorphism-and-neuropathy,C0086543,T190,Disorders
"What are the genetic changes related to congenital cataracts, facial dysmorphism, and neuropathy ?",0000218-3,genetic changes,"A mutation in the CTDP1 gene causes CCFDN. The CTDP1 gene provides instructions for making a protein called carboxy-terminal domain phosphatase 1. This protein helps regulate the process of transcription, which is a key step in using the information carried by genes to direct the production (synthesis) of proteins.  All known individuals with CCFDN have the same mutation in both copies of the CTDP1 gene in each cell. This mutation alters the way the gene's instructions are pieced together to produce the carboxy-terminal domain phosphatase 1 protein. The altered instructions introduce a premature stop signal, resulting in an abnormally short, nonfunctional protein that cannot regulate transcription. Defective regulation of the transcription process affects the development and function of many parts of the body. It is not known how nonfunctional carboxy-terminal domain phosphatase 1 protein results in the specific signs and symptoms of CCFDN.","congenital cataracts, facial dysmorphism, and neuropathy",0000218,GHR,https://ghr.nlm.nih.gov/condition/congenital-cataracts-facial-dysmorphism-and-neuropathy,C0086543,T190,Disorders
"Is congenital cataracts, facial dysmorphism, and neuropathy inherited ?",0000218-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.","congenital cataracts, facial dysmorphism, and neuropathy",0000218,GHR,https://ghr.nlm.nih.gov/condition/congenital-cataracts-facial-dysmorphism-and-neuropathy,C0086543,T190,Disorders
"What are the treatments for congenital cataracts, facial dysmorphism, and neuropathy ?",0000218-5,treatment,"These resources address the diagnosis or management of CCFDN:  - Gene Review: Gene Review: Congenital Cataracts, Facial Dysmorphism, and Neuropathy  - Genetic Testing Registry: Congenital Cataracts, Facial Dysmorphism, and Neuropathy  - MedlinePlus Encyclopedia: Congenital Cataract  - MedlinePlus Encyclopedia: Peripheral Neuropathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","congenital cataracts, facial dysmorphism, and neuropathy",0000218,GHR,https://ghr.nlm.nih.gov/condition/congenital-cataracts-facial-dysmorphism-and-neuropathy,C0086543,T190,Disorders
What is (are) congenital central hypoventilation syndrome ?,0000219-1,information,"Congenital central hypoventilation syndrome (CCHS) is a disorder that affects breathing. People with this disorder take shallow breaths (hypoventilate), especially during sleep, resulting in a shortage of oxygen and a buildup of carbon dioxide in the blood. Ordinarily, the part of the nervous system that controls involuntary body processes (autonomic nervous system) would react to such an imbalance by stimulating the individual to breathe more deeply or wake up. This reaction is impaired in people with CCHS, and they must be supported with a machine to help them breathe (mechanical ventilation) or a device that stimulates a normal breathing pattern (diaphragm pacemaker). Some affected individuals need this support 24 hours a day, while others need it only at night.  Symptoms of CCHS usually become apparent shortly after birth. Affected infants hypoventilate upon falling asleep and exhibit a bluish appearance of the skin or lips (cyanosis). Cyanosis is caused by lack of oxygen in the blood. In some milder cases, CCHS may be diagnosed later in life. In addition to the breathing problem, people with this disorder may have difficulty regulating their heart rate and blood pressure, for example in response to exercise or changes in body position. They may have abnormalities in the nerves that control the digestive tract (Hirschsprung disease), resulting in severe constipation, intestinal blockage, and enlargement of the colon. They are also at increased risk of developing certain tumors of the nervous system called neuroblastomas, ganglioneuromas, and ganglioneuroblastomas. Some affected individuals develop learning difficulties or other neurological problems, which may be worsened by oxygen deprivation if treatment to support their breathing is not completely effective.  Individuals with CCHS usually have eye abnormalities, including a decreased response of the pupils to light. They also have decreased perception of pain, low body temperature, and occasional episodes of profuse sweating.  People with CCHS, especially children, may have a characteristic appearance with a short, wide, somewhat flattened face often described as ""box-shaped."" Life expectancy and the extent of any cognitive disabilities depend on the severity of the disorder, timing of the diagnosis, and the success of treatment.",congenital central hypoventilation syndrome,0000219,GHR,https://ghr.nlm.nih.gov/condition/congenital-central-hypoventilation-syndrome,C1275808,T047,Disorders
How many people are affected by congenital central hypoventilation syndrome ?,0000219-2,frequency,"CCHS is a relatively rare disorder. Approximately 1,000 individuals with this condition have been identified. Researchers believe that some cases of sudden infant death syndrome (SIDS) or sudden unexplained death in children may be caused by undiagnosed CCHS.",congenital central hypoventilation syndrome,0000219,GHR,https://ghr.nlm.nih.gov/condition/congenital-central-hypoventilation-syndrome,C1275808,T047,Disorders
What are the genetic changes related to congenital central hypoventilation syndrome ?,0000219-3,genetic changes,"Mutations in the PHOX2B gene cause CCHS. The PHOX2B gene provides instructions for making a protein that acts early in development to help promote the formation of nerve cells (neurons) and regulate the process by which the neurons mature to carry out specific functions (differentiation). The protein is active in the neural crest, which is a group of cells in the early embryo that give rise to many tissues and organs. Neural crest cells migrate to form parts of the autonomic nervous system, many tissues in the face and skull, and other tissue and cell types.  Mutations are believed to interfere with the PHOX2B protein's role in promoting neuron formation and differentiation, especially in the autonomic nervous system, resulting in the problems regulating breathing and other body functions that occur in CCHS.",congenital central hypoventilation syndrome,0000219,GHR,https://ghr.nlm.nih.gov/condition/congenital-central-hypoventilation-syndrome,C1275808,T047,Disorders
Is congenital central hypoventilation syndrome inherited ?,0000219-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  More than 90 percent of cases of CCHS result from new mutations in the PHOX2B gene. These cases occur in people with no history of the disorder in their family. Occasionally an affected person inherits the mutation from one affected parent. The number of such cases has been increasing as better treatment has allowed more affected individuals to live into adulthood.  About 5 to 10 percent of affected individuals inherit the mutation from a seemingly unaffected parent with somatic mosaicism. Somatic mosaicism means that some of the body's cells have a PHOX2B gene mutation, and others do not. A parent with mosaicism for a PHOX2B gene mutation may not show any signs or symptoms of CCHS.",congenital central hypoventilation syndrome,0000219,GHR,https://ghr.nlm.nih.gov/condition/congenital-central-hypoventilation-syndrome,C1275808,T047,Disorders
What are the treatments for congenital central hypoventilation syndrome ?,0000219-5,treatment,These resources address the diagnosis or management of CCHS:  - Gene Review: Gene Review: Congenital Central Hypoventilation Syndrome  - Genetic Testing Registry: Congenital central hypoventilation  - MedlinePlus Encyclopedia: Hirschsprung's Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,congenital central hypoventilation syndrome,0000219,GHR,https://ghr.nlm.nih.gov/condition/congenital-central-hypoventilation-syndrome,C1275808,T047,Disorders
What is (are) congenital contractural arachnodactyly ?,0000220-1,information,"Congenital contractural arachnodactyly is a disorder that affects many parts of the body. People with this condition typically are tall with long limbs (dolichostenomelia) and long, slender fingers and toes (arachnodactyly). They often have permanently bent joints (contractures) that can restrict movement in their hips, knees, ankles, or elbows. Additional features of congenital contractural arachnodactyly include underdeveloped muscles, a rounded upper back that also curves to the side (kyphoscoliosis), permanently bent fingers and toes (camptodactyly), ears that look ""crumpled,"" and a protruding chest (pectus carinatum). Rarely, people with congenital contractural arachnodactyly have heart defects such as an enlargement of the blood vessel that distributes blood from the heart to the rest of the body (aortic root dilatation) or a leak in one of the valves that control blood flow through the heart (mitral valve prolapse). The life expectancy of individuals with congenital contractural arachnodactyly varies depending on the severity of symptoms but is typically not shortened.  A rare, severe form of congenital contractural arachnodactyly involves both heart and digestive system abnormalities in addition to the skeletal features described above; individuals with this severe form of the condition usually do not live past infancy.",congenital contractural arachnodactyly,0000220,GHR,https://ghr.nlm.nih.gov/condition/congenital-contractural-arachnodactyly,C0220668,T019,Disorders
How many people are affected by congenital contractural arachnodactyly ?,0000220-2,frequency,"The prevalence of congenital contractural arachnodactyly is estimated to be less than 1 in 10,000 worldwide.",congenital contractural arachnodactyly,0000220,GHR,https://ghr.nlm.nih.gov/condition/congenital-contractural-arachnodactyly,C0220668,T019,Disorders
What are the genetic changes related to congenital contractural arachnodactyly ?,0000220-3,genetic changes,"Mutations in the FBN2 gene cause congenital contractural arachnodactyly. The FBN2 gene provides instructions for producing the fibrillin-2 protein. Fibrillin-2 binds to other proteins and molecules to form threadlike filaments called microfibrils. Microfibrils become part of the fibers that provide strength and flexibility to connective tissue that supports the body's joints and organs. Additionally, microfibrils regulate the activity of molecules called growth factors. Growth factors enable the growth and repair of tissues throughout the body.  Mutations in the FBN2 gene can decrease fibrillin-2 production or result in the production of a protein with impaired function. As a result, microfibril formation is reduced, which probably weakens the structure of connective tissue and disrupts regulation of growth factor activity. The resulting abnormalities of connective tissue underlie the signs and symptoms of congenital contractural arachnodactyly.",congenital contractural arachnodactyly,0000220,GHR,https://ghr.nlm.nih.gov/condition/congenital-contractural-arachnodactyly,C0220668,T019,Disorders
Is congenital contractural arachnodactyly inherited ?,0000220-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",congenital contractural arachnodactyly,0000220,GHR,https://ghr.nlm.nih.gov/condition/congenital-contractural-arachnodactyly,C0220668,T019,Disorders
What are the treatments for congenital contractural arachnodactyly ?,0000220-5,treatment,These resources address the diagnosis or management of congenital contractural arachnodactyly:  - Gene Review: Gene Review: Congenital Contractural Arachnodactyly  - Genetic Testing Registry: Congenital contractural arachnodactyly  - MedlinePlus Encyclopedia: Arachnodactyly  - MedlinePlus Encyclopedia: Contracture Deformity  - MedlinePlus Encyclopedia: Skeletal Limb Abnormalities   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,congenital contractural arachnodactyly,0000220,GHR,https://ghr.nlm.nih.gov/condition/congenital-contractural-arachnodactyly,C0220668,T019,Disorders
"What is (are) congenital deafness with labyrinthine aplasia, microtia, and microdontia ?",0000221-1,information,"Congenital deafness with labyrinthine aplasia, microtia, and microdontia (also called LAMM syndrome) is a condition that affects development of the ears and teeth. In people with this condition, the structures that form the inner ear are usually completely absent (labyrinthine aplasia). Rarely, affected individuals have some underdeveloped inner ear structures in one or both ears. The abnormalities of the inner ear cause a form of hearing loss called sensorineural deafness that is present from birth (congenital). Because the inner ear is important for balance as well as hearing, development of motor skills, such as sitting and crawling, may be delayed in affected infants. In addition, people with LAMM syndrome often have abnormally small outer ears (microtia) with narrow ear canals. They can also have unusually small, widely spaced teeth (microdontia).","congenital deafness with labyrinthine aplasia, microtia, and microdontia",0000221,GHR,https://ghr.nlm.nih.gov/condition/congenital-deafness-with-labyrinthine-aplasia-microtia-and-microdontia,C0240340,T019,Disorders
"How many people are affected by congenital deafness with labyrinthine aplasia, microtia, and microdontia ?",0000221-2,frequency,"LAMM syndrome is a rare condition, although its prevalence is unknown. Approximately a dozen affected families have been identified.","congenital deafness with labyrinthine aplasia, microtia, and microdontia",0000221,GHR,https://ghr.nlm.nih.gov/condition/congenital-deafness-with-labyrinthine-aplasia-microtia-and-microdontia,C0240340,T019,Disorders
"What are the genetic changes related to congenital deafness with labyrinthine aplasia, microtia, and microdontia ?",0000221-3,genetic changes,"LAMM syndrome is caused by mutations in the FGF3 gene, which provides instructions for making a protein called fibroblast growth factor 3 (FGF3). By attaching to another protein known as a receptor, the FGF3 protein triggers a cascade of chemical reactions inside the cell that signal the cell to undergo certain changes, such as dividing or maturing to take on specialized functions. During development before birth, the signals triggered by the FGF3 protein stimulate cells to form the structures that make up the inner ears. The FGF3 protein is also involved in the development of many other organs and structures, including the outer ears and teeth.  FGF3 gene mutations involved in LAMM syndrome alter the FGF3 protein. The altered protein likely has reduced or absent function and is unable to stimulate signaling. The loss of FGF3 function impairs development of the ears and teeth, which leads to the characteristic features of LAMM syndrome.","congenital deafness with labyrinthine aplasia, microtia, and microdontia",0000221,GHR,https://ghr.nlm.nih.gov/condition/congenital-deafness-with-labyrinthine-aplasia-microtia-and-microdontia,C0240340,T019,Disorders
"Is congenital deafness with labyrinthine aplasia, microtia, and microdontia inherited ?",0000221-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.","congenital deafness with labyrinthine aplasia, microtia, and microdontia",0000221,GHR,https://ghr.nlm.nih.gov/condition/congenital-deafness-with-labyrinthine-aplasia-microtia-and-microdontia,C0240340,T019,Disorders
"What are the treatments for congenital deafness with labyrinthine aplasia, microtia, and microdontia ?",0000221-5,treatment,"These resources address the diagnosis or management of LAMM syndrome:  - Gene Review: Gene Review: Congenital Deafness with Labyrinthine Aplasia, Microtia, and Microdontia  - Genetic Testing Registry: Deafness with labyrinthine aplasia microtia and microdontia (LAMM)   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","congenital deafness with labyrinthine aplasia, microtia, and microdontia",0000221,GHR,https://ghr.nlm.nih.gov/condition/congenital-deafness-with-labyrinthine-aplasia-microtia-and-microdontia,C0240340,T019,Disorders
What is (are) congenital diaphragmatic hernia ?,0000222-1,information,"Congenital diaphragmatic hernia is a defect in the diaphragm. The diaphragm, which is composed of muscle and other fibrous tissue, separates the organs in the abdomen from those in the chest. Abnormal development of the diaphragm before birth leads to defects ranging from a thinned area in the diaphragm to its complete absence. An absent or partially formed diaphragm results in an abnormal opening (hernia) that allows the stomach and intestines to move into the chest cavity and crowd the heart and lungs. This crowding can lead to underdevelopment of the lungs (pulmonary hypoplasia), potentially resulting in life-threatening breathing difficulties that are apparent from birth.  In 5 to 10 percent of affected individuals, signs and symptoms of congenital diaphragmatic hernia appear later in life and may include breathing problems or abdominal pain from protrusion of the intestine into the chest cavity. In about 1 percent of cases, congenital diaphragmatic hernia has no symptoms; it may be detected incidentally when medical imaging is done for other reasons.  Congenital diaphragmatic hernias are often classified by their position. A Bochdalek hernia is a defect in the side or back of the diaphragm. Between 80 and 90 percent of congenital diaphragmatic hernias are of this type. A Morgnani hernia is a defect involving the front part of the diaphragm. This type of congenital diaphragmatic hernia, which accounts for approximately 2 percent of cases, is less likely to cause severe symptoms at birth. Other types of congenital diaphragmatic hernia, such as those affecting the central region of the diaphragm, or those in which the diaphragm muscle is absent with only a thin membrane in its place, are rare.",congenital diaphragmatic hernia,0000222,GHR,https://ghr.nlm.nih.gov/condition/congenital-diaphragmatic-hernia,C0235833,T019,Disorders
How many people are affected by congenital diaphragmatic hernia ?,0000222-2,frequency,"Congenital diaphragmatic hernia affects approximately 1 in 2,500 newborns.",congenital diaphragmatic hernia,0000222,GHR,https://ghr.nlm.nih.gov/condition/congenital-diaphragmatic-hernia,C0235833,T019,Disorders
What are the genetic changes related to congenital diaphragmatic hernia ?,0000222-3,genetic changes,"Congenital diaphragmatic hernia has many different causes. In 10 to 15 percent of affected individuals, the condition appears as a feature of a disorder that affects many body systems, called a syndrome. Donnai-Barrow syndrome, Fryns syndrome, and Pallister-Killian mosaic syndrome are among several syndromes in which congenital diaphragmatic hernia may occur. Some of these syndromes are caused by changes in single genes, and others are caused by chromosomal abnormalities that affect several genes.  About 25 percent of individuals with congenital diaphragmatic hernia that is not associated with a known syndrome also have abnormalities of one or more major body systems. Affected body systems can include the heart, brain, skeleton, intestines, genitals, kidneys, or eyes. In these individuals, the multiple abnormalities likely result from a common underlying disruption in development that affects more than one area of the body, but the specific mechanism responsible for this disruption is not clear.  Approximately 50 to 60 percent of congenital diaphragmatic hernia cases are isolated, which means that affected individuals have no other major malformations.  More than 80 percent of individuals with congenital diaphragmatic hernia have no known genetic syndrome or chromosomal abnormality. In these cases, the cause of the condition is unknown. Researchers are studying changes in several genes involved in the development of the diaphragm as possible causes of congenital diaphragmatic hernia. Some of these genes are transcription factors, which provide instructions for making proteins that help control the activity of particular genes (gene expression). Others provide instructions for making proteins involved in cell structure or the movement (migration) of cells in the embryo. Environmental factors that influence development before birth may also increase the risk of congenital diaphragmatic hernia, but these environmental factors have not been identified.",congenital diaphragmatic hernia,0000222,GHR,https://ghr.nlm.nih.gov/condition/congenital-diaphragmatic-hernia,C0235833,T019,Disorders
Is congenital diaphragmatic hernia inherited ?,0000222-4,inheritance,"Isolated congenital diaphragmatic hernia is rarely inherited. In almost all cases, there is only one affected individual in a family.  When congenital diaphragmatic hernia occurs as a feature of a genetic syndrome or chromosomal abnormality, it may cluster in families according to the inheritance pattern for that condition.",congenital diaphragmatic hernia,0000222,GHR,https://ghr.nlm.nih.gov/condition/congenital-diaphragmatic-hernia,C0235833,T019,Disorders
What are the treatments for congenital diaphragmatic hernia ?,0000222-5,treatment,"These resources address the diagnosis or management of congenital diaphragmatic hernia:  - Boston Children's Hospital  - Children's Hospital of Philadelphia  - Columbia University Medical Center: DHREAMS  - Columbia University Medical Center: Hernia Repair  - Gene Review: Gene Review: Congenital Diaphragmatic Hernia Overview  - Genetic Testing Registry: Congenital diaphragmatic hernia  - Genetic Testing Registry: Diaphragmatic hernia 2  - Genetic Testing Registry: Diaphragmatic hernia 3  - MedlinePlus Encyclopedia: Diaphragmatic Hernia Repair  - Seattle Children's Hospital: Treatment of Congenital Diaphragmatic Hernia  - University of California, San Francisco Fetal Treatment Center: Congenital Diaphragmatic Hernia  - University of Michigan Health System   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",congenital diaphragmatic hernia,0000222,GHR,https://ghr.nlm.nih.gov/condition/congenital-diaphragmatic-hernia,C0235833,T019,Disorders
What is (are) congenital dyserythropoietic anemia ?,0000223-1,information,"Congenital dyserythropoietic anemia (CDA) is an inherited blood disorder that affects the development of red blood cells. This disorder is one of many types of anemia, which is a condition characterized by a shortage of red blood cells. This shortage prevents the blood from carrying an adequate supply of oxygen to the body's tissues. The resulting symptoms can include tiredness (fatigue), weakness, pale skin, and other complications.  Researchers have identified three major types of CDA: type I, type II, and type III. The types have different genetic causes and different but overlapping patterns of signs and symptoms.  CDA type I is characterized by moderate to severe anemia. It is usually diagnosed in childhood or adolescence, although in some cases, the condition can be detected before birth. Many affected individuals have yellowing of the skin and eyes (jaundice) and an enlarged liver and spleen (hepatosplenomegaly). This condition also causes the body to absorb too much iron, which builds up and can damage tissues and organs. In particular, iron overload can lead to an abnormal heart rhythm (arrhythmia), congestive heart failure, diabetes, and chronic liver disease (cirrhosis). Rarely, people with CDA type I are born with skeletal abnormalities, most often involving the fingers and/or toes.  The anemia associated with CDA type II can range from mild to severe, and most affected individuals have jaundice, hepatosplenomegaly, and the formation of hard deposits in the gallbladder called gallstones. This form of the disorder is usually diagnosed in adolescence or early adulthood. An abnormal buildup of iron typically occurs after age 20, leading to complications including heart disease, diabetes, and cirrhosis.  The signs and symptoms of CDA type III tend to be milder than those of the other types. Most affected individuals do not have hepatosplenomegaly, and iron does not build up in tissues and organs. In adulthood, abnormalities of a specialized tissue at the back of the eye (the retina) can cause vision impairment. Some people with CDA type III also have a blood disorder known as monoclonal gammopathy, which can lead to a cancer of white blood cells (multiple myeloma).  Several other variants of CDA have been described, although they appear to be rare and not much is known about them. Once researchers discover the genetic causes of these variants, some of them may be grouped with the three major types of CDA.",congenital dyserythropoietic anemia,0000223,GHR,https://ghr.nlm.nih.gov/condition/congenital-dyserythropoietic-anemia,C0002876,T047,Disorders
How many people are affected by congenital dyserythropoietic anemia ?,0000223-2,frequency,"Several hundred cases of CDA have been reported worldwide. CDA type II is the most common form of the disorder, with more than 300 reported cases. CDA type III is the rarest form; it has been described in only a few families from Sweden, Argentina, and the United States. The incidence of CDA type I is unknown. Because CDA is so rare and its signs and symptoms overlap with those of other disorders, many cases likely remain undiagnosed or are incorrectly diagnosed as other disorders.",congenital dyserythropoietic anemia,0000223,GHR,https://ghr.nlm.nih.gov/condition/congenital-dyserythropoietic-anemia,C0002876,T047,Disorders
What are the genetic changes related to congenital dyserythropoietic anemia ?,0000223-3,genetic changes,"CDA type I usually results from mutations in the CDAN1 gene. Little is known about the function of this gene, and it is unclear how mutations cause the characteristic features of CDA type I. Some people with this condition do not have identified mutations in the CDAN1 gene, leading researchers to believe that mutations in at least one other gene can also cause this form of the disorder.  CDA type II is caused by mutations in the SEC23B gene. This gene provides instructions for making a protein that is involved in the transport of other proteins within cells. During the development of red blood cells, this protein may help ensure that proteins are transported to the areas where they are needed. Researchers are working to determine how mutations in the SEC23B gene lead to the signs and symptoms of CDA type II.  The genetic cause of CDA type III has not been identified. It likely results from mutations in a gene located on the long arm of chromosome 15 at a position designated 15q22. Researchers continue to search for the specific gene associated with this form of the condition.  The genetic changes responsible for CDA disrupt the normal development of red blood cells, a process called erythropoiesis. The term ""dyserythropoietic"" in the name of this condition means abnormal red blood cell formation. In people with CDA, immature red blood cells called erythroblasts are unusually shaped and have other abnormalities (such as extra nuclei). These abnormal erythroblasts cannot develop into functional mature red blood cells. The resulting shortage of healthy red blood cells leads to the characteristic signs and symptoms of anemia, as well as complications including hepatosplenomegaly and an abnormal buildup of iron.",congenital dyserythropoietic anemia,0000223,GHR,https://ghr.nlm.nih.gov/condition/congenital-dyserythropoietic-anemia,C0002876,T047,Disorders
Is congenital dyserythropoietic anemia inherited ?,0000223-4,inheritance,"The inheritance pattern of CDA depends on the type of the disorder. CDA types I and II are inherited in an autosomal recessive pattern, which means both copies of the associated gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  In several families, CDA type III appears to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder. In these families, affected individuals often have a parent and other relatives with the condition.",congenital dyserythropoietic anemia,0000223,GHR,https://ghr.nlm.nih.gov/condition/congenital-dyserythropoietic-anemia,C0002876,T047,Disorders
What are the treatments for congenital dyserythropoietic anemia ?,0000223-5,treatment,"These resources address the diagnosis or management of CDA:  - Gene Review: Gene Review: Congenital Dyserythropoietic Anemia Type I  - Genetic Testing Registry: Congenital dyserythropoietic anemia, type I  - Genetic Testing Registry: Congenital dyserythropoietic anemia, type II  - Genetic Testing Registry: Congenital dyserythropoietic anemia, type III  - MedlinePlus Encyclopedia: Ham Test  - MedlinePlus Encyclopedia: Hepatomegaly  - MedlinePlus Encyclopedia: Jaundice  - MedlinePlus Encyclopedia: Splenomegaly   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",congenital dyserythropoietic anemia,0000223,GHR,https://ghr.nlm.nih.gov/condition/congenital-dyserythropoietic-anemia,C0002876,T047,Disorders
What is (are) congenital fiber-type disproportion ?,0000224-1,information,"Congenital fiber-type disproportion is a condition that primarily affects skeletal muscles, which are muscles used for movement. People with this condition typically experience muscle weakness (myopathy), particularly in the muscles of the shoulders, upper arms, hips, and thighs. Weakness can also affect the muscles of the face and muscles that control eye movement (ophthalmoplegia), sometimes causing droopy eyelids (ptosis). Individuals with congenital fiber-type disproportion generally have a long face, a high arch in the roof of the mouth (high-arched palate), and crowded teeth. Affected individuals may have joint deformities (contractures) and an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). Approximately 30 percent of people with this disorder experience mild to severe breathing problems related to weakness of muscles needed for breathing. Some people who experience these breathing problems require use of a machine to help regulate their breathing at night (noninvasive mechanical ventilation), and occasionally during the day as well. About 30 percent of affected individuals have difficulty swallowing due to muscle weakness in the throat. Rarely, people with this condition have a weakened and enlarged heart muscle (dilated cardiomyopathy).  The severity of congenital fiber-type disproportion varies widely. It is estimated that up to 25 percent of affected individuals experience severe muscle weakness at birth and die in infancy or childhood. Others have only mild muscle weakness that becomes apparent in adulthood. Most often, the signs and symptoms of this condition appear by age 1. The first signs of this condition are usually decreased muscle tone (hypotonia) and muscle weakness. In most cases, muscle weakness does not worsen over time, and in some instances it may improve. Although motor skills such as standing and walking may be delayed, many affected children eventually learn to walk. These individuals often have less stamina than their peers, but they remain active. Rarely, people with this condition have a progressive decline in muscle strength over time. These individuals may lose the ability to walk and require wheelchair assistance.",congenital fiber-type disproportion,0000224,GHR,https://ghr.nlm.nih.gov/condition/congenital-fiber-type-disproportion,C0546264,T019,Disorders
How many people are affected by congenital fiber-type disproportion ?,0000224-2,frequency,"Congenital fiber-type disproportion is thought to be a rare condition, although its prevalence is unknown.",congenital fiber-type disproportion,0000224,GHR,https://ghr.nlm.nih.gov/condition/congenital-fiber-type-disproportion,C0546264,T019,Disorders
What are the genetic changes related to congenital fiber-type disproportion ?,0000224-3,genetic changes,"Mutations in multiple genes can cause congenital fiber-type disproportion. Mutations in the TPM3, RYR1 and ACTA1 genes cause 35 to 50 percent of cases, while mutations in other genes, some known and some unidentified, are responsible for the remaining cases.  The genes that cause congenital fiber-type disproportion provide instructions for making proteins that are involved in the tensing of muscle fibers (muscle contraction). Changes in these proteins lead to impaired muscle contraction, resulting in muscle weakness.  Skeletal muscle is made up of two types of muscle fibers: type I (slow twitch fibers) and type II (fast twitch fibers). Normally, type I and type II fibers are the same size. In people with congenital fiber-type disproportion, type I skeletal muscle fibers are significantly smaller than type II skeletal muscle fibers. It is unclear whether the small type I skeletal muscle fibers lead to muscle weakness or are caused by muscle weakness in people with congenital fiber-type disproportion.",congenital fiber-type disproportion,0000224,GHR,https://ghr.nlm.nih.gov/condition/congenital-fiber-type-disproportion,C0546264,T019,Disorders
Is congenital fiber-type disproportion inherited ?,0000224-4,inheritance,"Congenital fiber-type disproportion can have multiple inheritance patterns.  When this condition is caused by mutations in the ACTA1 gene, it usually occurs in an autosomal dominant pattern. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder.  Most other cases of congenital fiber-type disproportion, including those caused by mutations in the RYR1 gene, have an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  When this condition is caused by mutations in the TPM3 gene, it can occur in either an autosomal dominant or autosomal recessive pattern.  In rare cases, this condition can be inherited in an X-linked pattern, although the gene or genes associated with X-linked congenital fiber-type disproportion have not been identified. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. Because females have two copies of the X chromosome, one altered copy of the gene in each cell usually leads to less severe symptoms in females than in males or may cause no symptoms at all. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  It is estimated that 40 percent of individuals with congenital fiber-type disproportion have an affected relative.",congenital fiber-type disproportion,0000224,GHR,https://ghr.nlm.nih.gov/condition/congenital-fiber-type-disproportion,C0546264,T019,Disorders
What are the treatments for congenital fiber-type disproportion ?,0000224-5,treatment,These resources address the diagnosis or management of congenital fiber-type disproportion:  - Gene Review: Gene Review: Congenital Fiber-Type Disproportion  - Genetic Testing Registry: Congenital myopathy with fiber type disproportion  - MedlinePlus Encyclopedia: Contracture Deformity  - MedlinePlus Encyclopedia: Hypotonia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,congenital fiber-type disproportion,0000224,GHR,https://ghr.nlm.nih.gov/condition/congenital-fiber-type-disproportion,C0546264,T019,Disorders
What is (are) congenital fibrosis of the extraocular muscles ?,0000225-1,information,"Congenital fibrosis of the extraocular muscles is a disorder that affects the muscles that surround the eyes. These muscles control eye movement and the position of the eyes (for example, looking straight ahead). Congenital fibrosis of the extraocular muscles prevents the normal development and function of these muscles. As a result, affected individuals are unable to move their eyes normally. Most people with this condition have difficulty looking upward, and their side-to-side eye movement may also be limited. The eyes may be misaligned such that they look in different directions (strabismus). Instead of moving their eyes, affected individuals may need to turn their head to track moving objects. Additionally, many people with congenital fibrosis of the extraocular muscles have droopy eyelids (ptosis), which further limits their vision.  Researchers have identified at least four forms of congenital fibrosis of the extraocular muscles, designated CFEOM1, CFEOM2, CFEOM3, and Tukel syndrome. The specific problems with eye movement vary among the types. Tukel syndrome is characterized by missing fingers (oligodactyly) and other hand abnormalities in addition to problems with eye movement.",congenital fibrosis of the extraocular muscles,0000225,GHR,https://ghr.nlm.nih.gov/condition/congenital-fibrosis-of-the-extraocular-muscles,C0016059,T046,Disorders
How many people are affected by congenital fibrosis of the extraocular muscles ?,0000225-2,frequency,"CFEOM1 is the most common form of congenital fibrosis of the extraocular muscles, affecting at least 1 in 230,000 people. CFEOM1 and CFEOM3 have been reported worldwide, whereas CFEOM2 has been seen in only a few families of Turkish, Saudi Arabian, and Iranian descent. Tukel syndrome appears to be very rare; it has been diagnosed in only one large Turkish family.",congenital fibrosis of the extraocular muscles,0000225,GHR,https://ghr.nlm.nih.gov/condition/congenital-fibrosis-of-the-extraocular-muscles,C0016059,T046,Disorders
What are the genetic changes related to congenital fibrosis of the extraocular muscles ?,0000225-3,genetic changes,"CFEOM1 and rare cases of CFEOM3 result from mutations in the KIF21A gene. This gene provides instructions for making a protein called a kinesin, which is essential for the transport of materials within cells. Researchers believe that this protein plays an important role in the normal development and function of nerves in the head and face. In particular, this protein plays a critical role in the development of a particular branch of cranial nerve III, which emerges from the brain and controls muscles that raise the eyes and eyelids. Mutations in the KIF21A gene likely alter the protein's ability to transport materials within nerve cells, preventing the normal development of these cranial nerves and the extraocular muscles they control. Abnormal function of the extraocular muscles leads to restricted eye movement and related problems with vision.  Mutations in the PHOX2A gene cause CFEOM2. This gene provides instructions for making a protein that is found in the developing nervous system. Studies suggest that the PHOX2A protein plays a critical role in the development of cranial nerves III and IV, which are necessary for normal eye movement. Mutations likely eliminate the function of the PHOX2A protein, which prevents the normal development of these cranial nerves and the extraocular muscles they control.  In most cases of CFEOM3, the genetic cause of the condition is unknown. Studies suggest that a gene associated with CFEOM3 may be located near one end of chromosome 16. The gene associated with Tukel syndrome has not been identified either, although researchers think that it may be located near one end of chromosome 21.",congenital fibrosis of the extraocular muscles,0000225,GHR,https://ghr.nlm.nih.gov/condition/congenital-fibrosis-of-the-extraocular-muscles,C0016059,T046,Disorders
Is congenital fibrosis of the extraocular muscles inherited ?,0000225-4,inheritance,"The different types of congenital fibrosis of the extraocular muscles have different patterns of inheritance. CFEOM1 and CFEOM3 are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  CFEOM2 is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Tukel syndrome also appears to have an autosomal recessive pattern of inheritance, although the genetic change responsible for this disorder is unknown.",congenital fibrosis of the extraocular muscles,0000225,GHR,https://ghr.nlm.nih.gov/condition/congenital-fibrosis-of-the-extraocular-muscles,C0016059,T046,Disorders
What are the treatments for congenital fibrosis of the extraocular muscles ?,0000225-5,treatment,"These resources address the diagnosis or management of congenital fibrosis of the extraocular muscles:  - Gene Review: Gene Review: Congenital Fibrosis of the Extraocular Muscles  - Genetic Testing Registry: Fibrosis of extraocular muscles, congenital, 1  - Genetic Testing Registry: Fibrosis of extraocular muscles, congenital, 2  - Genetic Testing Registry: Fibrosis of extraocular muscles, congenital, 3a, with or without extraocular involvement  - Genetic Testing Registry: Tukel syndrome  - MedlinePlus Encyclopedia: Extraocular Muscle Function Testing  - MedlinePlus Encyclopedia: Strabismus   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",congenital fibrosis of the extraocular muscles,0000225,GHR,https://ghr.nlm.nih.gov/condition/congenital-fibrosis-of-the-extraocular-muscles,C0016059,T046,Disorders
What is (are) congenital generalized lipodystrophy ?,0000226-1,information,"Congenital generalized lipodystrophy (also called Berardinelli-Seip congenital lipodystrophy) is a rare condition characterized by an almost total lack of fatty (adipose) tissue in the body and a very muscular appearance. Adipose tissue is found in many parts of the body, including beneath the skin and surrounding the internal organs. It stores fat for energy and also provides cushioning. Congenital generalized lipodystrophy is part of a group of related disorders known as lipodystrophies, which are all characterized by a loss of adipose tissue. A shortage of adipose tissue leads to the storage of fat elsewhere in the body, such as in the liver and muscles, which causes serious health problems.  The signs and symptoms of congenital generalized lipodystrophy are usually apparent from birth or early childhood. One of the most common features is insulin resistance, a condition in which the body's tissues are unable to recognize insulin, a hormone that normally helps to regulate blood sugar levels. Insulin resistance may develop into a more serious disease called diabetes mellitus. Most affected individuals also have high levels of fats called triglycerides circulating in the bloodstream (hypertriglyceridemia), which can lead to the development of small yellow deposits of fat under the skin called eruptive xanthomas and inflammation of the pancreas (pancreatitis). Additionally, congenital generalized lipodystrophy causes an abnormal buildup of fats in the liver (hepatic steatosis), which can result in an enlarged liver (hepatomegaly) and liver failure. Some affected individuals develop a form of heart disease called hypertrophic cardiomyopathy, which can lead to heart failure and an abnormal heart rhythm (arrhythmia) that can cause sudden death.  People with congenital generalized lipodystrophy have a distinctive physical appearance. They appear very muscular because they have an almost complete absence of adipose tissue and an overgrowth of muscle tissue. A lack of adipose tissue under the skin also makes the veins appear prominent. Affected individuals tend to have a large chin, prominent bones above the eyes (orbital ridges), large hands and feet, and a prominent belly button (umbilicus). Affected females may have an enlarged clitoris (clitoromegaly), an increased amount of body hair (hirsutism), irregular menstrual periods, and multiple cysts on the ovaries, which may be related to hormonal changes. Many people with this disorder develop acanthosis nigricans, a skin condition related to high levels of insulin in the bloodstream. Acanthosis nigricans causes the skin in body folds and creases to become thick, dark, and velvety.  Researchers have described four types of congenital generalized lipodystrophy, which are distinguished by their genetic cause. The types also have some differences in their typical signs and symptoms. For example, in addition to the features described above, some people with congenital generalized lipodystrophy type 1 develop cysts in the long bones of the arms and legs after puberty. Type 2 can be associated with intellectual disability, which is usually mild to moderate. Type 3 appears to cause poor growth and short stature, along with other health problems. Type 4 is associated with muscle weakness, delayed development, joint abnormalities, a narrowing of the lower part of the stomach (pyloric stenosis), and severe arrhythmia that can lead to sudden death.",congenital generalized lipodystrophy,0000226,GHR,https://ghr.nlm.nih.gov/condition/congenital-generalized-lipodystrophy,C0221032,T019,Disorders
How many people are affected by congenital generalized lipodystrophy ?,0000226-2,frequency,"Congenital generalized lipodystrophy has an estimated prevalence of 1 in 10 million people worldwide. Between 300 and 500 people with the condition have been described in the medical literature. Although this condition has been reported in populations around the world, it appears to be more common in certain regions of Lebanon and Brazil.",congenital generalized lipodystrophy,0000226,GHR,https://ghr.nlm.nih.gov/condition/congenital-generalized-lipodystrophy,C0221032,T019,Disorders
What are the genetic changes related to congenital generalized lipodystrophy ?,0000226-3,genetic changes,"Mutations in the AGPAT2, BSCL2, CAV1, and PTRF genes cause congenital generalized lipodystrophy types 1 through 4, respectively. The proteins produced from these genes play important roles in the development and function of adipocytes, which are the fat-storing cells in adipose tissue. Mutations in any of these genes reduce or eliminate the function of their respective proteins, which impairs the development, structure, or function of adipocytes and makes the body unable to store and use fats properly. These abnormalities of adipose tissue disrupt hormones and affect many of the body's organs, resulting in the varied signs and symptoms of congenital generalized lipodystrophy.  Some of the genes associated with congenital generalized lipodystrophy also play roles in other cells and tissues. For example, the protein produced from the BSCL2 gene is also present in the brain, although its function is unknown. A loss of this protein in the brain may help explain why congenital generalized lipodystrophy type 2 is sometimes associated with intellectual disability.  In some people with congenital generalized lipodystrophy, no mutations have been found in any of the genes listed above. Researchers are looking for additional genetic changes associated with this disorder.",congenital generalized lipodystrophy,0000226,GHR,https://ghr.nlm.nih.gov/condition/congenital-generalized-lipodystrophy,C0221032,T019,Disorders
Is congenital generalized lipodystrophy inherited ?,0000226-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",congenital generalized lipodystrophy,0000226,GHR,https://ghr.nlm.nih.gov/condition/congenital-generalized-lipodystrophy,C0221032,T019,Disorders
What are the treatments for congenital generalized lipodystrophy ?,0000226-5,treatment,These resources address the diagnosis or management of congenital generalized lipodystrophy:  - Gene Review: Gene Review: Berardinelli-Seip Congenital Lipodystrophy  - Genetic Testing Registry: Berardinelli-Seip congenital lipodystrophy  - MedlinePlus Encyclopedia: Hypertrophic Cardiomypathy  - University of Texas Southwestern Medical Center: Lipodystrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,congenital generalized lipodystrophy,0000226,GHR,https://ghr.nlm.nih.gov/condition/congenital-generalized-lipodystrophy,C0221032,T019,Disorders
What is (are) congenital hemidysplasia with ichthyosiform erythroderma and limb defects ?,0000227-1,information,"Congenital hemidysplasia with ichthyosiform erythroderma and limb defects, more commonly known by the acronym CHILD syndrome, is a condition that affects the development of several parts of the body. The signs and symptoms of this disorder are typically limited to either the right side or the left side of the body. (""Hemi-"" means ""half,"" and ""dysplasia"" refers to abnormal growth.) The right side is affected about twice as often as the left side.  People with CHILD syndrome have a skin condition characterized by large patches of skin that are red and inflamed (erythroderma) and covered with flaky scales (ichthyosis). This condition is most likely to occur in skin folds and creases and usually does not affect the face. The skin abnormalities are present at birth and persist throughout life.  CHILD syndrome also disrupts the formation of the arms and legs during early development. Children with this disorder may be born with one or more limbs that are shortened or missing. The limb abnormalities occur on the same side of the body as the skin abnormalities.  Additionally, CHILD syndrome may affect the development of the brain, heart, lungs, and kidneys.",congenital hemidysplasia with ichthyosiform erythroderma and limb defects,0000227,GHR,https://ghr.nlm.nih.gov/condition/congenital-hemidysplasia-with-ichthyosiform-erythroderma-and-limb-defects,C0265267,T047,Disorders
How many people are affected by congenital hemidysplasia with ichthyosiform erythroderma and limb defects ?,0000227-2,frequency,CHILD syndrome is a rare disorder; it has been reported in about 60 people worldwide. This condition occurs almost exclusively in females.,congenital hemidysplasia with ichthyosiform erythroderma and limb defects,0000227,GHR,https://ghr.nlm.nih.gov/condition/congenital-hemidysplasia-with-ichthyosiform-erythroderma-and-limb-defects,C0265267,T047,Disorders
What are the genetic changes related to congenital hemidysplasia with ichthyosiform erythroderma and limb defects ?,0000227-3,genetic changes,"Mutations in the NSDHL gene cause CHILD syndrome. This gene provides instructions for making an enzyme that is involved in the production of cholesterol. Cholesterol is a type of fat that is produced in the body and obtained from foods that come from animals, particularly egg yolks, meat, fish, and dairy products. Although high cholesterol levels are a well-known risk factor for heart disease, the body needs some cholesterol to develop and function normally both before and after birth. Cholesterol is an important component of cell membranes and the protective substance covering nerve cells (myelin). Additionally, cholesterol plays a role in the production of certain hormones and digestive acids.  The mutations that underlie CHILD syndrome eliminate the activity of the NSDHL enzyme, which disrupts the normal production of cholesterol within cells. A shortage of this enzyme may also allow potentially toxic byproducts of cholesterol production to build up in the body's tissues. Researchers suspect that low cholesterol levels and/or an accumulation of other substances disrupt the growth and development of many parts of the body. It is not known, however, how a disturbance in cholesterol production leads to the specific features of CHILD syndrome.",congenital hemidysplasia with ichthyosiform erythroderma and limb defects,0000227,GHR,https://ghr.nlm.nih.gov/condition/congenital-hemidysplasia-with-ichthyosiform-erythroderma-and-limb-defects,C0265267,T047,Disorders
Is congenital hemidysplasia with ichthyosiform erythroderma and limb defects inherited ?,0000227-4,inheritance,"This condition has an X-linked dominant pattern of inheritance. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. The inheritance is dominant if one copy of the altered gene in each cell is sufficient to cause the condition.  Most cases of CHILD syndrome occur sporadically, which means only one member of a family is affected. Rarely, the condition can run in families and is passed from mother to daughter. Researchers believe that CHILD syndrome occurs almost exclusively in females because affected males die before birth. Only one male with CHILD syndrome has been reported.",congenital hemidysplasia with ichthyosiform erythroderma and limb defects,0000227,GHR,https://ghr.nlm.nih.gov/condition/congenital-hemidysplasia-with-ichthyosiform-erythroderma-and-limb-defects,C0265267,T047,Disorders
What are the treatments for congenital hemidysplasia with ichthyosiform erythroderma and limb defects ?,0000227-5,treatment,These resources address the diagnosis or management of CHILD syndrome:  - Gene Review: Gene Review: NSDHL-Related Disorders  - Genetic Testing Registry: Child syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,congenital hemidysplasia with ichthyosiform erythroderma and limb defects,0000227,GHR,https://ghr.nlm.nih.gov/condition/congenital-hemidysplasia-with-ichthyosiform-erythroderma-and-limb-defects,C0265267,T047,Disorders
What is (are) congenital hepatic fibrosis ?,0000228-1,information,"Congenital hepatic fibrosis is a disease of the liver that is present from birth. The liver has many important functions, including producing various molecules needed by the body and breaking down other molecules so that their components can be used or eliminated.  Congenital hepatic fibrosis is characterized by malformation of the bile ducts and of the blood vessels of the hepatic portal system. Bile ducts carry bile (a fluid that helps to digest fats) from the liver to the gallbladder and small intestine. The hepatic portal system is a branching network of veins (portal veins) that carry blood from the gastrointestinal tract to the liver for processing.  A buildup of scar tissue (fibrosis) in the portal tracts also occurs in this disorder. Portal tracts are structures in the liver that bundle the vessels through which blood, lymph, and bile flow, and fibrosis in the portal tracts can restrict the normal movement of fluids in these vessels. Lymph is a fluid that helps exchange immune cells, proteins, and other substances between the blood and tissues.  Constriction of the portal veins due to malformation and portal tract fibrosis results in high blood pressure in the hepatic portal system (portal hypertension). Portal hypertension impairs the flow of blood from the gastrointestinal tract, causing an increase in pressure in the veins of the esophagus, stomach, and intestines. These veins may stretch and their walls may become thin, leading to a risk of abnormal bleeding.  People with congenital hepatic fibrosis have an enlarged liver and spleen (hepatosplenomegaly). The liver is abnormally shaped. Affected individuals also have an increased risk of infection of the bile ducts (cholangitis), hard deposits in the gallbladder or bile ducts (gallstones), and cancer of the liver or gallbladder.  Congenital hepatic fibrosis may occur alone, in which case it is called isolated congenital hepatic fibrosis. More frequently, it occurs as a feature of genetic syndromes that also affect the kidneys (the renal system), such as polycystic kidney disease (PKD).",congenital hepatic fibrosis,0000228,GHR,https://ghr.nlm.nih.gov/condition/congenital-hepatic-fibrosis,C0009714,T019,Disorders
How many people are affected by congenital hepatic fibrosis ?,0000228-2,frequency,"Isolated congenital hepatic fibrosis is rare. Its prevalence is unknown. The total prevalence of syndromes that include congenital hepatic fibrosis as a feature is estimated to be 1 in 10,000 to 20,000 individuals.",congenital hepatic fibrosis,0000228,GHR,https://ghr.nlm.nih.gov/condition/congenital-hepatic-fibrosis,C0009714,T019,Disorders
What are the genetic changes related to congenital hepatic fibrosis ?,0000228-3,genetic changes,"Syndromes of which congenital hepatic fibrosis is a feature may be caused by changes in many different genes. The gene changes that cause isolated congenital hepatic fibrosis are unknown.  Congenital hepatic fibrosis is caused by problems in the development of the portal veins and bile ducts. These problems include malformation of embryonic structures called ductal plates. Each ductal plate is a cylinder of cells surrounding branches of the portal veins. During development before birth, the ductal plates normally develop into the network of bile ducts. In congenital hepatic fibrosis, the development of the ductal plates does not proceed normally, resulting in the persistence of immature bile ducts. Branching of the portal vein network also proceeds abnormally, and excess fibrous tissue develops in the portal tracts.  The malformation of the portal veins and bile ducts disrupts the normal flow of blood and bile, which leads to the progressive signs and symptoms of congenital hepatic fibrosis.",congenital hepatic fibrosis,0000228,GHR,https://ghr.nlm.nih.gov/condition/congenital-hepatic-fibrosis,C0009714,T019,Disorders
Is congenital hepatic fibrosis inherited ?,0000228-4,inheritance,"The various syndromes of which congenital hepatic fibrosis is often a feature can have different inheritance patterns. Most of these disorders are inherited in an autosomal recessive pattern, which means both copies of the associated gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Rare syndromes involving congenital hepatic fibrosis may be inherited in an X-linked recessive pattern, in which the gene associated with the syndrome is located on the X chromosome, which is one of the two sex chromosomes.  In isolated congenital hepatic fibrosis, the inheritance pattern is unknown.",congenital hepatic fibrosis,0000228,GHR,https://ghr.nlm.nih.gov/condition/congenital-hepatic-fibrosis,C0009714,T019,Disorders
What are the treatments for congenital hepatic fibrosis ?,0000228-5,treatment,These resources address the diagnosis or management of congenital hepatic fibrosis:  - Gene Review: Gene Review: Congenital Hepatic Fibrosis Overview  - Genetic Testing Registry: Congenital hepatic fibrosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,congenital hepatic fibrosis,0000228,GHR,https://ghr.nlm.nih.gov/condition/congenital-hepatic-fibrosis,C0009714,T019,Disorders
What is (are) congenital hyperinsulinism ?,0000229-1,information,"Congenital hyperinsulinism is a condition that causes individuals to have abnormally high levels of insulin, which is a hormone that helps control blood sugar levels. People with this condition have frequent episodes of low blood sugar (hypoglycemia). In infants and young children, these episodes are characterized by a lack of energy (lethargy), irritability, or difficulty feeding. Repeated episodes of low blood sugar increase the risk for serious complications such as breathing difficulties, seizures, intellectual disability, vision loss, brain damage, and coma.  The severity of congenital hyperinsulinism varies widely among affected individuals, even among members of the same family. About 60 percent of infants with this condition experience a hypoglycemic episode within the first month of life. Other affected children develop hypoglycemia by early childhood. Unlike typical episodes of hypoglycemia, which occur most often after periods without food (fasting) or after exercising, episodes of hypoglycemia in people with congenital hyperinsulinism can also occur after eating.",congenital hyperinsulinism,0000229,GHR,https://ghr.nlm.nih.gov/condition/congenital-hyperinsulinism,C2931834,,Disorders
How many people are affected by congenital hyperinsulinism ?,0000229-2,frequency,"Congenital hyperinsulinism affects approximately 1 in 50,000 newborns. This condition is more common in certain populations, affecting up to 1 in 2,500 newborns.",congenital hyperinsulinism,0000229,GHR,https://ghr.nlm.nih.gov/condition/congenital-hyperinsulinism,C2931834,,Disorders
What are the genetic changes related to congenital hyperinsulinism ?,0000229-3,genetic changes,"Congenital hyperinsulinism is caused by mutations in genes that regulate the release (secretion) of insulin, which is produced by beta cells in the pancreas. Insulin clears excess sugar (in the form of glucose) from the bloodstream by passing glucose into cells to be used as energy.  Gene mutations that cause congenital hyperinsulinism lead to over-secretion of insulin from beta cells. Normally, insulin is secreted in response to the amount of glucose in the bloodstream: when glucose levels rise, so does insulin secretion. However, in people with congenital hyperinsulinism, insulin is secreted from beta cells regardless of the amount of glucose present in the blood. This excessive secretion of insulin results in glucose being rapidly removed from the bloodstream and passed into tissues such as muscle, liver, and fat. A lack of glucose in the blood results in frequent states of hypoglycemia in people with congenital hyperinsulinism. Insufficient blood glucose also deprives the brain of its primary source of fuel.  Mutations in at least nine genes have been found to cause congenital hyperinsulinism. Mutations in the ABCC8 gene are the most common known cause of the disorder. They account for this condition in approximately 40 percent of affected individuals. Less frequently, mutations in the KCNJ11 gene have been found in people with congenital hyperinsulinism. Mutations in each of the other genes associated with this condition account for only a small percentage of cases.  In approximately half of people with congenital hyperinsulinism, the cause is unknown.",congenital hyperinsulinism,0000229,GHR,https://ghr.nlm.nih.gov/condition/congenital-hyperinsulinism,C2931834,,Disorders
Is congenital hyperinsulinism inherited ?,0000229-4,inheritance,"Congenital hyperinsulinism can have different inheritance patterns, usually depending on the form of the condition. At least two forms of the condition have been identified. The most common form is the diffuse form, which occurs when all of the beta cells in the pancreas secrete too much insulin. The focal form of congenital hyperinsulinism occurs when only some of the beta cells over-secrete insulin.  Most often, the diffuse form of congenital hyperinsulinism is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Less frequently, the diffuse form is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  The inheritance of the focal form of congenital hyperinsulinism is more complex. For most genes, both copies are turned on (active) in all cells, but for a small subset of genes, one of the two copies is turned off (inactive). Most people with the focal form of this condition inherit one copy of the mutated, inactive gene from their unaffected father. During embryonic development, a mutation occurs in the other, active copy of the gene. This second mutation is found within only some cells in the pancreas. As a result, some pancreatic beta cells have abnormal insulin secretion, while other beta cells function normally.",congenital hyperinsulinism,0000229,GHR,https://ghr.nlm.nih.gov/condition/congenital-hyperinsulinism,C2931834,,Disorders
What are the treatments for congenital hyperinsulinism ?,0000229-5,treatment,"These resources address the diagnosis or management of congenital hyperinsulinism:  - Gene Review: Gene Review: Familial Hyperinsulinism  - Genetic Testing Registry: Exercise-induced hyperinsulinemic hypoglycemia  - Genetic Testing Registry: Familial hyperinsulinism  - Genetic Testing Registry: Hyperinsulinemic hypoglycemia familial 3  - Genetic Testing Registry: Hyperinsulinemic hypoglycemia familial 5  - Genetic Testing Registry: Hyperinsulinemic hypoglycemia, familial, 4  - Genetic Testing Registry: Hyperinsulinism-hyperammonemia syndrome  - Genetic Testing Registry: Islet cell hyperplasia  - Genetic Testing Registry: Persistent hyperinsulinemic hypoglycemia of infancy  - MedlinePlus Encyclopedia: Neonatal Hypoglycemia  - The Children's Hospital of Philadelphia: Congenital Hyperinsulinism Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",congenital hyperinsulinism,0000229,GHR,https://ghr.nlm.nih.gov/condition/congenital-hyperinsulinism,C2931834,,Disorders
What is (are) congenital hypothyroidism ?,0000230-1,information,"Congenital hypothyroidism is a partial or complete loss of function of the thyroid gland (hypothyroidism) that affects infants from birth (congenital). The thyroid gland is a butterfly-shaped tissue in the lower neck. It makes iodine-containing hormones that play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism). People with congenital hypothyroidism have lower-than-normal levels of these important hormones.  Congenital hypothyroidism occurs when the thyroid gland fails to develop or function properly. In 80 to 85 percent of cases, the thyroid gland is absent, severely reduced in size (hypoplastic), or abnormally located. These cases are classified as thyroid dysgenesis. In the remainder of cases, a normal-sized or enlarged thyroid gland (goiter) is present, but production of thyroid hormones is decreased or absent. Most of these cases occur when one of several steps in the hormone synthesis process is impaired; these cases are classified as thyroid dyshormonogenesis. Less commonly, reduction or absence of thyroid hormone production is caused by impaired stimulation of the production process (which is normally done by a structure at the base of the brain called the pituitary gland), even though the process itself is unimpaired. These cases are classified as central (or pituitary) hypothyroidism.  Signs and symptoms of congenital hypothyroidism result from the shortage of thyroid hormones. Affected babies may show no features of the condition, although some babies with congenital hypothyroidism are less active and sleep more than normal. They may have difficulty feeding and experience constipation. If untreated, congenital hypothyroidism can lead to intellectual disability and slow growth. In the United States and many other countries, all hospitals test newborns for congenital hypothyroidism. If treatment begins in the first two weeks after birth, infants usually develop normally.  Congenital hypothyroidism can also occur as part of syndromes that affect other organs and tissues in the body. These forms of the condition are described as syndromic. Some common forms of syndromic hypothyroidism include Pendred syndrome, Bamforth-Lazarus syndrome, and brain-lung-thyroid syndrome.",congenital hypothyroidism,0000230,GHR,https://ghr.nlm.nih.gov/condition/congenital-hypothyroidism,C0010308,T019,Disorders
How many people are affected by congenital hypothyroidism ?,0000230-2,frequency,"Congenital hypothyroidism affects an estimated 1 in 2,000 to 4,000 newborns. For reasons that remain unclear, congenital hypothyroidism affects more than twice as many females as males.",congenital hypothyroidism,0000230,GHR,https://ghr.nlm.nih.gov/condition/congenital-hypothyroidism,C0010308,T019,Disorders
What are the genetic changes related to congenital hypothyroidism ?,0000230-3,genetic changes,"Congenital hypothyroidism can be caused by a variety of factors, only some of which are genetic. The most common cause worldwide is a shortage of iodine in the diet of the mother and the affected infant. Iodine is essential for the production of thyroid hormones. Genetic causes account for about 15 to 20 percent of cases of congenital hypothyroidism.  The cause of the most common type of congenital hypothyroidism, thyroid dysgenesis, is usually unknown. Studies suggest that 2 to 5 percent of cases are inherited. Two of the genes involved in this form of the condition are PAX8 and TSHR. These genes play roles in the proper growth and development of the thyroid gland. Mutations in these genes prevent or disrupt normal development of the gland. The abnormal or missing gland cannot produce normal amounts of thyroid hormones.  Thyroid dyshormonogenesis results from mutations in one of several genes involved in the production of thyroid hormones. These genes include DUOX2, SLC5A5, TG, and TPO. Mutations in each of these genes disrupt a step in thyroid hormone synthesis, leading to abnormally low levels of these hormones. Mutations in the TSHB gene disrupt the synthesis of thyroid hormones by impairing the stimulation of hormone production. Changes in this gene are the primary cause of central hypothyroidism. The resulting shortage of thyroid hormones disrupts normal growth, brain development, and metabolism, leading to the features of congenital hypothyroidism.  Mutations in other genes that have not been as well characterized can also cause congenital hypothyroidism. Still other genes are involved in syndromic forms of the disorder.",congenital hypothyroidism,0000230,GHR,https://ghr.nlm.nih.gov/condition/congenital-hypothyroidism,C0010308,T019,Disorders
Is congenital hypothyroidism inherited ?,0000230-4,inheritance,"Most cases of congenital hypothyroidism are sporadic, which means they occur in people with no history of the disorder in their family.  When inherited, the condition usually has an autosomal recessive inheritance pattern, which means both copies of the gene in each cell have mutations. Typically, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they do not show signs and symptoms of the condition.  When congenital hypothyroidism results from mutations in the PAX8 gene or from certain mutations in the TSHR or DUOX2 gene, the condition has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some of these cases, an affected person inherits the mutation from one affected parent. Other cases result from new (de novo) mutations in the gene that occur during the formation of reproductive cells (eggs or sperm) or in early embryonic development. These cases occur in people with no history of the disorder in their family.",congenital hypothyroidism,0000230,GHR,https://ghr.nlm.nih.gov/condition/congenital-hypothyroidism,C0010308,T019,Disorders
What are the treatments for congenital hypothyroidism ?,0000230-5,treatment,"These resources address the diagnosis or management of congenital hypothyroidism:  - Baby's First Test  - Genetic Testing Registry: Congenital hypothyroidism  - Genetic Testing Registry: Hypothyroidism, congenital, nongoitrous, 1  - MedlinePlus Encyclopedia: Congenital Hypothyroidism   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",congenital hypothyroidism,0000230,GHR,https://ghr.nlm.nih.gov/condition/congenital-hypothyroidism,C0010308,T019,Disorders
What is (are) congenital insensitivity to pain ?,0000231-1,information,"Congenital insensitivity to pain is a condition that inhibits the ability to perceive physical pain. From birth, affected individuals never feel pain in any part of their body when injured. People with this condition can feel the difference between sharp and dull and hot and cold, but cannot sense, for example, that a hot beverage is burning their tongue. This lack of pain awareness often leads to an accumulation of wounds, bruises, broken bones, and other health issues that may go undetected. Young children with congenital insensitivity to pain may have mouth or finger wounds due to repeated self-biting and may also experience multiple burn-related injuries. These repeated injuries often lead to a reduced life expectancy in people with congenital insensitivity to pain. Many people with congenital insensitivity to pain also have a complete loss of the sense of smell (anosmia).  Congenital insensitivity to pain is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and pain.",congenital insensitivity to pain,0000231,GHR,https://ghr.nlm.nih.gov/condition/congenital-insensitivity-to-pain,C0002768,T019,Disorders
How many people are affected by congenital insensitivity to pain ?,0000231-2,frequency,Congenital insensitivity to pain is a rare condition; about 20 cases have been reported in the scientific literature.,congenital insensitivity to pain,0000231,GHR,https://ghr.nlm.nih.gov/condition/congenital-insensitivity-to-pain,C0002768,T019,Disorders
What are the genetic changes related to congenital insensitivity to pain ?,0000231-3,genetic changes,"Mutations in the SCN9A gene cause congenital insensitivity to pain. The SCN9A gene provides instructions for making one part (the alpha subunit) of a sodium channel called NaV1.7. Sodium channels transport positively charged sodium atoms (sodium ions) into cells and play a key role in a cell's ability to generate and transmit electrical signals. NaV1.7 sodium channels are found in nerve cells called nociceptors that transmit pain signals to the spinal cord and brain. The NaV1.7 channel is also found in olfactory sensory neurons, which are nerve cells in the nasal cavity that transmit smell-related signals to the brain.  The SCN9A gene mutations that cause congenital insensitivity to pain result in the production of nonfunctional alpha subunits that cannot be incorporated into NaV1.7 channels. As a result, the channels cannot be formed. The absence of NaV1.7 channels impairs the transmission of pain signals from the site of injury to the brain, causing those affected to be insensitive to pain. Loss of this channel in olfactory sensory neurons likely impairs the transmission of smell-related signals to the brain, leading to anosmia.",congenital insensitivity to pain,0000231,GHR,https://ghr.nlm.nih.gov/condition/congenital-insensitivity-to-pain,C0002768,T019,Disorders
Is congenital insensitivity to pain inherited ?,0000231-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",congenital insensitivity to pain,0000231,GHR,https://ghr.nlm.nih.gov/condition/congenital-insensitivity-to-pain,C0002768,T019,Disorders
What are the treatments for congenital insensitivity to pain ?,0000231-5,treatment,"These resources address the diagnosis or management of congenital insensitivity to pain:  - Genetic Testing Registry: Indifference to pain, congenital, autosomal recessive   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",congenital insensitivity to pain,0000231,GHR,https://ghr.nlm.nih.gov/condition/congenital-insensitivity-to-pain,C0002768,T019,Disorders
What is (are) congenital insensitivity to pain with anhidrosis ?,0000232-1,information,"Congenital insensitivity to pain with anhidrosis (CIPA) has two characteristic features: the inability to feel pain and temperature, and decreased or absent sweating (anhidrosis). This condition is also known as hereditary sensory and autonomic neuropathy type IV. The signs and symptoms of CIPA appear early, usually at birth or during infancy, but with careful medical attention, affected individuals can live into adulthood.  An inability to feel pain and temperature often leads to repeated severe injuries. Unintentional self-injury is common in people with CIPA, typically by biting the tongue, lips, or fingers, which may lead to spontaneous amputation of the affected area. In addition, people with CIPA heal slowly from skin and bone injuries. Repeated trauma can lead to chronic bone infections (osteomyelitis) or a condition called Charcot joints, in which the bones and tissue surrounding joints are destroyed.  Normally, sweating helps cool the body temperature. However, in people with CIPA, anhidrosis often causes recurrent, extremely high fevers (hyperpyrexia) and seizures brought on by high temperature (febrile seizures).  In addition to the characteristic features, there are other signs and symptoms of CIPA. Many affected individuals have thick, leathery skin (lichenification) on the palms of their hands or misshapen fingernails or toenails. They can also have patches on their scalp where hair does not grow (hypotrichosis). About half of people with CIPA show signs of hyperactivity or emotional instability, and many affected individuals have intellectual disability. Some people with CIPA have weak muscle tone (hypotonia) when they are young, but muscle strength and tone become more normal as they get older.",congenital insensitivity to pain with anhidrosis,0000232,GHR,https://ghr.nlm.nih.gov/condition/congenital-insensitivity-to-pain-with-anhidrosis,C0002768,T019,Disorders
How many people are affected by congenital insensitivity to pain with anhidrosis ?,0000232-2,frequency,"CIPA is a rare condition; however, the prevalence is unknown.",congenital insensitivity to pain with anhidrosis,0000232,GHR,https://ghr.nlm.nih.gov/condition/congenital-insensitivity-to-pain-with-anhidrosis,C0002768,T019,Disorders
What are the genetic changes related to congenital insensitivity to pain with anhidrosis ?,0000232-3,genetic changes,"Mutations in the NTRK1 gene cause CIPA. The NTRK1 gene provides instructions for making a receptor protein that attaches (binds) to another protein called NGF. The NTRK1 receptor is important for the survival of nerve cells (neurons).  The NTRK1 receptor is found on the surface of cells, particularly neurons that transmit pain, temperature, and touch sensations (sensory neurons). When the NGF protein binds to the NTRK1 receptor, signals are transmitted inside the cell that tell the cell to grow and divide, and that help it survive. Mutations in the NTRK1 gene lead to a protein that cannot transmit signals. Without the proper signaling, neurons die by a process of self-destruction called apoptosis. Loss of sensory neurons leads to the inability to feel pain in people with CIPA. In addition, people with CIPA lose the nerves leading to their sweat glands, which causes the anhidrosis seen in affected individuals.",congenital insensitivity to pain with anhidrosis,0000232,GHR,https://ghr.nlm.nih.gov/condition/congenital-insensitivity-to-pain-with-anhidrosis,C0002768,T019,Disorders
Is congenital insensitivity to pain with anhidrosis inherited ?,0000232-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",congenital insensitivity to pain with anhidrosis,0000232,GHR,https://ghr.nlm.nih.gov/condition/congenital-insensitivity-to-pain-with-anhidrosis,C0002768,T019,Disorders
What are the treatments for congenital insensitivity to pain with anhidrosis ?,0000232-5,treatment,These resources address the diagnosis or management of CIPA:  - Gene Review: Gene Review: Congenital Insensitivity to Pain with Anhidrosis  - Genetic Testing Registry: Hereditary insensitivity to pain with anhidrosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,congenital insensitivity to pain with anhidrosis,0000232,GHR,https://ghr.nlm.nih.gov/condition/congenital-insensitivity-to-pain-with-anhidrosis,C0002768,T019,Disorders
What is (are) congenital leptin deficiency ?,0000233-1,information,"Congenital leptin deficiency is a condition that causes severe obesity beginning in the first few months of life. Affected individuals are of normal weight at birth, but they are constantly hungry and quickly gain weight. Without treatment, the extreme hunger continues and leads to chronic excessive eating (hyperphagia) and obesity. Beginning in early childhood, affected individuals develop abnormal eating behaviors such as fighting with other children over food, hoarding food, and eating in secret.  People with congenital leptin deficiency also have hypogonadotropic hypogonadism, which is a condition caused by reduced production of hormones that direct sexual development. Without treatment, affected individuals experience delayed puberty or do not go through puberty, and may be unable to conceive children (infertile).",congenital leptin deficiency,0000233,GHR,https://ghr.nlm.nih.gov/condition/congenital-leptin-deficiency,C3838754,T019,Disorders
How many people are affected by congenital leptin deficiency ?,0000233-2,frequency,Congenital leptin deficiency is a rare disorder. Only a few dozen cases have been reported in the medical literature.,congenital leptin deficiency,0000233,GHR,https://ghr.nlm.nih.gov/condition/congenital-leptin-deficiency,C3838754,T019,Disorders
What are the genetic changes related to congenital leptin deficiency ?,0000233-3,genetic changes,"Congenital leptin deficiency is caused by mutations in the LEP gene. This gene provides instructions for making a hormone called leptin, which is involved in the regulation of body weight. Normally, the body's fat cells release leptin in proportion to their size. As fat accumulates in cells, more leptin is produced. This rise in leptin indicates that fat stores are increasing.  Leptin attaches (binds) to and activates a protein called the leptin receptor, fitting into the receptor like a key into a lock. The leptin receptor protein is found on the surface of cells in many organs and tissues of the body including a part of the brain called the hypothalamus. The hypothalamus controls hunger and thirst as well as other functions such as sleep, moods, and body temperature. It also regulates the release of many hormones that have functions throughout the body. In the hypothalamus, the binding of leptin to its receptor triggers a series of chemical signals that affect hunger and help produce a feeling of fullness (satiety).  LEP gene mutations that cause congenital leptin deficiency lead to an absence of leptin. As a result, the signaling that triggers feelings of satiety does not occur, leading to the excessive hunger and weight gain associated with this disorder. Because hypogonadotropic hypogonadism occurs in congenital leptin deficiency, researchers suggest that leptin signaling is also involved in regulating the hormones that control sexual development. However, the specifics of this involvement and how it may be altered in congenital leptin deficiency are unknown.  Congenital leptin deficiency is a rare cause of obesity. Researchers are studying the factors involved in more common forms of obesity.",congenital leptin deficiency,0000233,GHR,https://ghr.nlm.nih.gov/condition/congenital-leptin-deficiency,C3838754,T019,Disorders
Is congenital leptin deficiency inherited ?,0000233-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",congenital leptin deficiency,0000233,GHR,https://ghr.nlm.nih.gov/condition/congenital-leptin-deficiency,C3838754,T019,Disorders
What are the treatments for congenital leptin deficiency ?,0000233-5,treatment,"These resources address the diagnosis or management of congenital leptin deficiency:  - Eunice Kennedy Shriver National Institute of Child Health and Human Development: How Are Obesity and Overweight Diagnosed?  - Genetic Testing Registry: Obesity, severe, due to leptin deficiency  - Genetics of Obesity Study  - National Heart, Lung, and Blood Institute: How Are Overweight and Obesity Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",congenital leptin deficiency,0000233,GHR,https://ghr.nlm.nih.gov/condition/congenital-leptin-deficiency,C3838754,T019,Disorders
What is (are) congenital mirror movement disorder ?,0000234-1,information,"Congenital mirror movement disorder is a condition in which intentional movements of one side of the body are mirrored by involuntary movements of the other side. For example, when an affected individual makes a fist with the right hand, the left hand makes a similar movement. The mirror movements in this disorder primarily involve the upper limbs, especially the hands and fingers. This pattern of movements is present from infancy or early childhood and usually persists throughout life, without other associated signs and symptoms. Intelligence and lifespan are not affected.  People with congenital mirror movement disorder can have some difficulty with certain activities of daily living, particularly with those requiring different movements in each hand, such as typing on a keyboard. They may experience discomfort or pain in the upper limbs during prolonged use of the hands.  The extent of the mirror movements in this disorder can vary, even within the same family. In most cases, the involuntary movements are noticeable but less pronounced than the corresponding voluntary movements. The extent of the movements typically stay the same throughout the lifetime of an affected individual.  Mirror movements can also occur in people who do not have congenital mirror movement disorder. Mild mirror movements are common during the normal development of young children and typically disappear before age 7. They can also develop later in life in people with neurodegenerative disorders such as Parkinson disease. Mirror movements may also be present in certain other conditions with a wider range of signs and symptoms (syndromes).",congenital mirror movement disorder,0000234,GHR,https://ghr.nlm.nih.gov/condition/congenital-mirror-movement-disorder,C0026650,T047,Disorders
How many people are affected by congenital mirror movement disorder ?,0000234-2,frequency,Congenital mirror movement disorder is a very rare disorder. Its prevalence is thought to be less than 1 in 1 million. Researchers suggest that some mildly affected individuals may never be diagnosed.,congenital mirror movement disorder,0000234,GHR,https://ghr.nlm.nih.gov/condition/congenital-mirror-movement-disorder,C0026650,T047,Disorders
What are the genetic changes related to congenital mirror movement disorder ?,0000234-3,genetic changes,"Congenital mirror movement disorder can be caused by mutations in the DCC or RAD51 gene; mutations in these genes account for a total of about 35 percent of cases. Mutations in other genes that have not been identified likely account for other cases of this disorder.  The DCC gene provides instructions for making a protein called the netrin-1 receptor, which is involved in the development of the nervous system. This receptor attaches (binds) to a substance called netrin-1, fitting together like a lock and its key. The binding of netrin-1 to its receptor triggers signaling that helps direct the growth of specialized nerve cell extensions called axons, which transmit nerve impulses that signal muscle movement. Normally, signals from each half of the brain control movements on the opposite side of the body. Binding of netrin-1 to its receptor inhibits axons from developing in ways that would carry movement signals from each half of the brain to the same side of the body.  Mutations in the DCC gene result in an impaired or missing netrin-1 receptor protein. A shortage of functional netrin-1 receptor protein impairs control of axon growth during nervous system development. As a result, movement signals from each half of the brain are abnormally transmitted to both sides of the body, leading to mirror movements.  The RAD51 gene provides instructions for making a protein that is also thought to be involved in the development of nervous system functions that control movement, but its role in this development is unclear. Mutations in the RAD51 gene result in a missing or impaired RAD51 protein, but it is unknown how a shortage of functional RAD51 protein affects nervous system development and leads to the signs and symptoms of congenital mirror movement disorder.",congenital mirror movement disorder,0000234,GHR,https://ghr.nlm.nih.gov/condition/congenital-mirror-movement-disorder,C0026650,T047,Disorders
Is congenital mirror movement disorder inherited ?,0000234-4,inheritance,"In most cases, including those caused by mutations in the DCC or RAD51 gene, this condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the altered gene. Some people who have the altered gene never develop the condition, a situation known as reduced penetrance.  Research suggests that in rare cases, this condition may be inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",congenital mirror movement disorder,0000234,GHR,https://ghr.nlm.nih.gov/condition/congenital-mirror-movement-disorder,C0026650,T047,Disorders
What are the treatments for congenital mirror movement disorder ?,0000234-5,treatment,"These resources address the diagnosis or management of congenital mirror movement disorder:  - Gene Review: Gene Review: Congenital Mirror Movements  - Genetic Testing Registry: Mirror movements 2  - Genetic Testing Registry: Mirror movements, congenital  - KidsHealth: Occupational Therapy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",congenital mirror movement disorder,0000234,GHR,https://ghr.nlm.nih.gov/condition/congenital-mirror-movement-disorder,C0026650,T047,Disorders
What is (are) congenital myasthenic syndrome ?,0000235-1,information,"Congenital myasthenic syndrome is a group of conditions characterized by muscle weakness (myasthenia) that worsens with physical exertion. The muscle weakness typically begins in early childhood but can also appear in adolescence or adulthood. Facial muscles, including muscles that control the eyelids, muscles that move the eyes, and muscles used for chewing and swallowing, are most commonly affected. However, any of the muscles used for movement (skeletal muscles) can be affected in this condition. Due to muscle weakness, affected infants may have feeding difficulties. Development of motor skills such as crawling or walking may be delayed. The severity of the myasthenia varies greatly, with some people experiencing minor weakness and others having such severe weakness that they are unable to walk.  Some individuals have episodes of breathing problems that may be triggered by fevers or infection. Severely affected individuals may also experience short pauses in breathing (apnea) that can lead to a bluish appearance of the skin or lips (cyanosis).",congenital myasthenic syndrome,0000235,GHR,https://ghr.nlm.nih.gov/condition/congenital-myasthenic-syndrome,C0751882,T047,Disorders
How many people are affected by congenital myasthenic syndrome ?,0000235-2,frequency,The prevalence of congenital myasthenic syndrome is unknown. At least 600 families with affected individuals have been described in the scientific literature.,congenital myasthenic syndrome,0000235,GHR,https://ghr.nlm.nih.gov/condition/congenital-myasthenic-syndrome,C0751882,T047,Disorders
What are the genetic changes related to congenital myasthenic syndrome ?,0000235-3,genetic changes,"Mutations in many genes can cause congenital myasthenic syndrome. Mutations in the CHRNE gene are responsible for more than half of all cases. A large number of cases are also caused by mutations in the RAPSN, CHAT, COLQ, and DOK7 genes. All of these genes provide instructions for producing proteins that are involved in the normal function of the neuromuscular junction. The neuromuscular junction is the area between the ends of nerve cells and muscle cells where signals are relayed to trigger muscle movement.  Gene mutations lead to changes in proteins that play a role in the function of the neuromuscular junction and disrupt signaling between the ends of nerve cells and muscle cells. Disrupted signaling between these cells results in an impaired ability to move skeletal muscles, muscle weakness, and delayed development of motor skills. The respiratory problems in congenital myasthenic syndrome result from impaired movement of the muscles of the chest wall and the muscle that separates the abdomen from the chest cavity (the diaphragm).  Mutations in other genes that provide instructions for proteins involved in neuromuscular signaling have been found to cause some cases of congenital myasthenic syndrome, although these mutations account for only a small number of cases. Some people with congenital myasthenic syndrome do not have an identified mutation in any of the genes known to be associated with this condition.",congenital myasthenic syndrome,0000235,GHR,https://ghr.nlm.nih.gov/condition/congenital-myasthenic-syndrome,C0751882,T047,Disorders
Is congenital myasthenic syndrome inherited ?,0000235-4,inheritance,"This condition is most commonly inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Rarely, this condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",congenital myasthenic syndrome,0000235,GHR,https://ghr.nlm.nih.gov/condition/congenital-myasthenic-syndrome,C0751882,T047,Disorders
What are the treatments for congenital myasthenic syndrome ?,0000235-5,treatment,"These resources address the diagnosis or management of congenital myasthenic syndrome:  - Gene Review: Gene Review: Congenital Myasthenic Syndromes  - Genetic Testing Registry: CHRNA1-Related Congenital Myasthenic Syndrome  - Genetic Testing Registry: Congenital myasthenic syndrome  - Genetic Testing Registry: Congenital myasthenic syndrome 1B, fast-channel  - Genetic Testing Registry: Congenital myasthenic syndrome with tubular aggregates 1  - Genetic Testing Registry: Congenital myasthenic syndrome, acetazolamide-responsive  - Genetic Testing Registry: Endplate acetylcholinesterase deficiency  - Genetic Testing Registry: Familial infantile myasthenia  - Genetic Testing Registry: Myasthenia, limb-girdle, familial  - Genetic Testing Registry: Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency  - Genetic Testing Registry: Myasthenic syndrome, slow-channel congenital   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",congenital myasthenic syndrome,0000235,GHR,https://ghr.nlm.nih.gov/condition/congenital-myasthenic-syndrome,C0751882,T047,Disorders
What is (are) congenital neuronal ceroid lipofuscinosis ?,0000236-1,information,"Congenital neuronal ceroid lipofuscinosis (NCL) is an inherited disorder that primarily affects the nervous system. Soon after birth, affected infants develop muscle rigidity, respiratory failure, and prolonged episodes of seizure activity that last several minutes (status epilepticus). It is likely that some affected individuals have seizure activity before birth. Infants with congenital NCL have unusually small heads (microcephaly) with brains that may be less than half the normal size. There is a loss of brain cells in areas that coordinate movement and control thinking and emotions (the cerebellum and the cerebral cortex). Affected individuals also lack a fatty substance called myelin, which protects nerve cells and promotes efficient transmission of nerve impulses. Infants with congenital NCL often die hours to weeks after birth.  Congenital NCL is the most severe form of a group of NCLs (collectively called Batten disease) that affect the nervous system and typically cause progressive problems with vision, movement, and thinking ability. The different types of NCLs are distinguished by the age at which signs and symptoms first appear.",congenital neuronal ceroid lipofuscinosis,0000236,GHR,https://ghr.nlm.nih.gov/condition/congenital-neuronal-ceroid-lipofuscinosis,C0027877,T047,Disorders
How many people are affected by congenital neuronal ceroid lipofuscinosis ?,0000236-2,frequency,Congenital NCL is the rarest type of NCL; approximately 10 cases have been described.,congenital neuronal ceroid lipofuscinosis,0000236,GHR,https://ghr.nlm.nih.gov/condition/congenital-neuronal-ceroid-lipofuscinosis,C0027877,T047,Disorders
What are the genetic changes related to congenital neuronal ceroid lipofuscinosis ?,0000236-3,genetic changes,"Mutations in the CTSD gene cause congenital NCL. The CTSD gene provides instructions for making an enzyme called cathepsin D. Cathepsin D is one of a family of cathepsin proteins that act as proteases, which modify proteins by cutting them apart. Cathepsin D is found in many types of cells and is active in lysosomes, which are compartments within cells that digest and recycle different types of molecules. By cutting proteins apart, cathepsin D can break proteins down, turn on (activate) proteins, and regulate self-destruction of the cell (apoptosis).  CTSD gene mutations that cause congenital NCL lead to a complete lack of cathepsin D enzyme activity. As a result, proteins and other materials are not broken down properly. In the lysosomes, these materials accumulate into fatty substances called lipopigments. These accumulations occur in cells throughout the body, but neurons are likely particularly vulnerable to damage caused by the abnormal cell materials and the loss of cathepsin D function. Early and widespread cell death in congenital NCL leads to severe signs and symptoms and death in infancy.",congenital neuronal ceroid lipofuscinosis,0000236,GHR,https://ghr.nlm.nih.gov/condition/congenital-neuronal-ceroid-lipofuscinosis,C0027877,T047,Disorders
Is congenital neuronal ceroid lipofuscinosis inherited ?,0000236-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",congenital neuronal ceroid lipofuscinosis,0000236,GHR,https://ghr.nlm.nih.gov/condition/congenital-neuronal-ceroid-lipofuscinosis,C0027877,T047,Disorders
What are the treatments for congenital neuronal ceroid lipofuscinosis ?,0000236-5,treatment,"These resources address the diagnosis or management of congenital neuronal ceroid lipofuscinosis:  - Genetic Testing Registry: Neuronal ceroid lipofuscinosis, congenital   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",congenital neuronal ceroid lipofuscinosis,0000236,GHR,https://ghr.nlm.nih.gov/condition/congenital-neuronal-ceroid-lipofuscinosis,C0027877,T047,Disorders
What is (are) congenital plasminogen deficiency ?,0000237-1,information,"Congenital plasminogen deficiency is a disorder that results in inflamed growths on the mucous membranes, which are the moist tissues that line body openings such as the eyelids and the inside of the mouth. Development of the growths are usually triggered by infections or injury, but they may also occur spontaneously in the absence of known triggers. The growths may recur after being removed.  Congenital plasminogen deficiency most often affects the conjunctiva, which are the mucous membranes that protect the white part of the eye (the sclera) and line the eyelids. A characteristic feature of this disorder is ligneous conjunctivitis, in which a buildup of a protein called fibrin causes inflammation of the conjunctiva (conjunctivitis) and leads to thick, woody (ligneous), inflamed growths that are yellow, white, or red. Ligneous conjunctivitis most often occurs on the inside of the eyelids. However, in about one-third of cases, ligneous conjunctivitis over the sclera grows onto the cornea, which is the clear covering that protects the colored part of the eye (the iris) and pupil. Such growths can tear the cornea or cause scarring. These corneal problems as well as obstruction by growths inside the eyelid can lead to vision loss.  People with congenital plasminogen deficiency may also develop ligneous growths on other mucous membranes, including the inside of the mouth and the gums; the lining of the nasal cavity; and in females, the vagina. Growths on the mucous membranes that line the gastrointestinal tract may result in ulcers. The growths may also develop in the windpipe, which can cause life-threatening airway obstruction, especially in children. In a small number of cases, affected individuals are born with impaired drainage of the fluid that surrounds and protects the brain and spinal cord (the cerebrospinal fluid or CSF), resulting in a buildup of this fluid in the skull (occlusive hydrocephalus). It is unclear how this feature is related to the other signs and symptoms of congenital plasminogen deficiency.",congenital plasminogen deficiency,0000237,GHR,https://ghr.nlm.nih.gov/condition/congenital-plasminogen-deficiency,C0398621,T047,Disorders
How many people are affected by congenital plasminogen deficiency ?,0000237-2,frequency,"The prevalence of congenital plasminogen deficiency has been estimated at 1.6 per one million people. This condition is believed to be underdiagnosed, because growths in one area are often not recognized as being a feature of a disorder that affects many body systems. Mild cases likely never come to medical attention.",congenital plasminogen deficiency,0000237,GHR,https://ghr.nlm.nih.gov/condition/congenital-plasminogen-deficiency,C0398621,T047,Disorders
What are the genetic changes related to congenital plasminogen deficiency ?,0000237-3,genetic changes,"Congenital plasminogen deficiency is caused by mutations in the PLG gene. This gene provides instructions for making a protein called plasminogen. Enzymes called plasminogen activators convert plasminogen into the protein plasmin, which breaks down another protein called fibrin. Fibrin is the main protein involved in blood clots and is important for wound healing, creating the framework for normal tissue to grow back. Excess fibrin is broken down when no longer needed, and the new, more flexible normal tissue takes its place.  PLG gene mutations can decrease the amount of plasminogen that is produced, its function, or both. When the mutations affect plasminogen levels as well as the activity of the protein, affected individuals may be said to have type I congenital plasminogen deficiency, characterized by the ligneous growths previously described. People with mutations that result in normal levels of plasminogen with reduced activity are said to have type II congenital plasminogen deficiency or dysplasminogenemia. This form of the condition often has no symptoms.  A reduction in functional plasminogen results in less plasmin to break down fibrin, leading to a buildup of fibrin. The excess fibrin and the resulting inflammation of the tissue result in the inflamed woody growths characteristic of congenital plasminogen deficiency.  It is unclear why the excess fibrin builds up in the mucous membranes but does not usually result in abnormal clots in the blood vessels (thromboses). Researchers suggest that other enzymes in the blood may also break down fibrin, helping to compensate for the reduced plasminogen levels.",congenital plasminogen deficiency,0000237,GHR,https://ghr.nlm.nih.gov/condition/congenital-plasminogen-deficiency,C0398621,T047,Disorders
Is congenital plasminogen deficiency inherited ?,0000237-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",congenital plasminogen deficiency,0000237,GHR,https://ghr.nlm.nih.gov/condition/congenital-plasminogen-deficiency,C0398621,T047,Disorders
What are the treatments for congenital plasminogen deficiency ?,0000237-5,treatment,"These resources address the diagnosis or management of congenital plasminogen deficiency:  - Genetic Testing Registry: Plasminogen deficiency, type I  - Indiana Hemophilia and Thrombosis Center  - Plasminogen Deficiency Registry   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",congenital plasminogen deficiency,0000237,GHR,https://ghr.nlm.nih.gov/condition/congenital-plasminogen-deficiency,C0398621,T047,Disorders
What is (are) congenital stromal corneal dystrophy ?,0000238-1,information,"Congenital stromal corneal dystrophy is an inherited eye disorder. This condition primarily affects the cornea, which is the clear outer covering of the eye. In people with this condition, the cornea appears cloudy and may have an irregular surface. These corneal changes lead to visual impairment, including blurring, glare, and a loss of sharp vision (reduced visual acuity). Visual impairment is often associated with additional eye abnormalities, including ""lazy eye"" (amblyopia), eyes that do not look in the same direction (strabismus), involuntary eye movements (nystagmus), and increased sensitivity to light (photophobia).",congenital stromal corneal dystrophy,0000238,GHR,https://ghr.nlm.nih.gov/condition/congenital-stromal-corneal-dystrophy,C1864738,T047,Disorders
How many people are affected by congenital stromal corneal dystrophy ?,0000238-2,frequency,Congenital stromal corneal dystrophy is probably very rare; only a few affected families have been reported in the medical literature.,congenital stromal corneal dystrophy,0000238,GHR,https://ghr.nlm.nih.gov/condition/congenital-stromal-corneal-dystrophy,C1864738,T047,Disorders
What are the genetic changes related to congenital stromal corneal dystrophy ?,0000238-3,genetic changes,"Congenital stromal corneal dystrophy is caused by mutations in the DCN gene. This gene provides instructions for making a protein called decorin, which is involved in the organization of collagens. Collagens are proteins that strengthen and support connective tissues such as skin, bone, tendons, and ligaments. In the cornea, well-organized bundles of collagen make the cornea transparent. Decorin ensures that collagen fibrils in the cornea are uniformly sized and regularly spaced.  Mutations in the DCN gene lead to the production of a defective version of decorin. This abnormal protein interferes with the organization of collagen fibrils in the cornea. As poorly arranged collagen fibrils accumulate, the cornea becomes cloudy. These corneal changes lead to reduced visual acuity and related eye abnormalities.",congenital stromal corneal dystrophy,0000238,GHR,https://ghr.nlm.nih.gov/condition/congenital-stromal-corneal-dystrophy,C1864738,T047,Disorders
Is congenital stromal corneal dystrophy inherited ?,0000238-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",congenital stromal corneal dystrophy,0000238,GHR,https://ghr.nlm.nih.gov/condition/congenital-stromal-corneal-dystrophy,C1864738,T047,Disorders
What are the treatments for congenital stromal corneal dystrophy ?,0000238-5,treatment,These resources address the diagnosis or management of congenital stromal corneal dystrophy:  - Gene Review: Gene Review: Congenital Stromal Corneal Dystrophy  - Genetic Testing Registry: Congenital Stromal Corneal Dystrophy  - MedlinePlus Encyclopedia: Cloudy Cornea   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,congenital stromal corneal dystrophy,0000238,GHR,https://ghr.nlm.nih.gov/condition/congenital-stromal-corneal-dystrophy,C1864738,T047,Disorders
What is (are) congenital sucrase-isomaltase deficiency ?,0000239-1,information,"Congenital sucrase-isomaltase deficiency is a disorder that affects a person's ability to digest certain sugars. People with this condition cannot break down the sugars sucrose and maltose. Sucrose (a sugar found in fruits, and also known as table sugar) and maltose (the sugar found in grains) are called disaccharides because they are made of two simple sugars. Disaccharides are broken down into simple sugars during digestion. Sucrose is broken down into glucose and another simple sugar called fructose, and maltose is broken down into two glucose molecules. People with congenital sucrase-isomaltase deficiency cannot break down the sugars sucrose and maltose, and other compounds made from these sugar molecules (carbohydrates).  Congenital sucrase-isomaltase deficiency usually becomes apparent after an infant is weaned and starts to consume fruits, juices, and grains. After ingestion of sucrose or maltose, an affected child will typically experience stomach cramps, bloating, excess gas production, and diarrhea. These digestive problems can lead to failure to gain weight and grow at the expected rate (failure to thrive) and malnutrition. Most affected children are better able to tolerate sucrose and maltose as they get older.",congenital sucrase-isomaltase deficiency,0000239,GHR,https://ghr.nlm.nih.gov/condition/congenital-sucrase-isomaltase-deficiency,C1283620,T047,Disorders
How many people are affected by congenital sucrase-isomaltase deficiency ?,0000239-2,frequency,"The prevalence of congenital sucrase-isomaltase deficiency is estimated to be 1 in 5,000 people of European descent. This condition is much more prevalent in the native populations of Greenland, Alaska, and Canada, where as many as 1 in 20 people may be affected.",congenital sucrase-isomaltase deficiency,0000239,GHR,https://ghr.nlm.nih.gov/condition/congenital-sucrase-isomaltase-deficiency,C1283620,T047,Disorders
What are the genetic changes related to congenital sucrase-isomaltase deficiency ?,0000239-3,genetic changes,"Mutations in the SI gene cause congenital sucrase-isomaltase deficiency. The SI gene provides instructions for producing the enzyme sucrase-isomaltase. This enzyme is found in the small intestine and is responsible for breaking down sucrose and maltose into their simple sugar components. These simple sugars are then absorbed by the small intestine. Mutations that cause this condition alter the structure, disrupt the production, or impair the function of sucrase-isomaltase. These changes prevent the enzyme from breaking down sucrose and maltose, causing the intestinal discomfort seen in individuals with congenital sucrase-isomaltase deficiency.",congenital sucrase-isomaltase deficiency,0000239,GHR,https://ghr.nlm.nih.gov/condition/congenital-sucrase-isomaltase-deficiency,C1283620,T047,Disorders
Is congenital sucrase-isomaltase deficiency inherited ?,0000239-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",congenital sucrase-isomaltase deficiency,0000239,GHR,https://ghr.nlm.nih.gov/condition/congenital-sucrase-isomaltase-deficiency,C1283620,T047,Disorders
What are the treatments for congenital sucrase-isomaltase deficiency ?,0000239-5,treatment,These resources address the diagnosis or management of congenital sucrase-isomaltase deficiency:  - Genetic Testing Registry: Sucrase-isomaltase deficiency  - MedlinePlus Encyclopedia: Abdominal bloating  - MedlinePlus Encyclopedia: Inborn errors of metabolism  - MedlinePlus Encyclopedia: Malabsorption   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,congenital sucrase-isomaltase deficiency,0000239,GHR,https://ghr.nlm.nih.gov/condition/congenital-sucrase-isomaltase-deficiency,C1283620,T047,Disorders
What is (are) core binding factor acute myeloid leukemia ?,0000240-1,information,"Core binding factor acute myeloid leukemia (CBF-AML) is one form of a cancer of the blood-forming tissue (bone marrow) called acute myeloid leukemia. In normal bone marrow, early blood cells called hematopoietic stem cells develop into several types of blood cells: white blood cells (leukocytes) that protect the body from infection, red blood cells (erythrocytes) that carry oxygen, and platelets (thrombocytes) that are involved in blood clotting. In acute myeloid leukemia, the bone marrow makes large numbers of abnormal, immature white blood cells called myeloid blasts. Instead of developing into normal white blood cells, the myeloid blasts develop into cancerous leukemia cells. The large number of abnormal cells in the bone marrow interferes with the production of functional white blood cells, red blood cells, and platelets.  People with CBF-AML have a shortage of all types of mature blood cells: a shortage of white blood cells (leukopenia) leads to increased susceptibility to infections, a low number of red blood cells (anemia) causes fatigue and weakness, and a reduction in the amount of platelets (thrombocytopenia) can result in easy bruising and abnormal bleeding. Other symptoms of CBF-AML may include fever and weight loss.  While acute myeloid leukemia is generally a disease of older adults, CBF-AML often begins in young adulthood and can occur in childhood. Compared to other forms of acute myeloid leukemia, CBF-AML has a relatively good prognosis: about 90 percent of individuals with CBF-AML recover from their disease following treatment, compared with 25 to 40 percent of those with other forms of acute myeloid leukemia. However, the disease recurs in approximately half of them after successful treatment of the initial occurrence.",core binding factor acute myeloid leukemia,0000240,GHR,https://ghr.nlm.nih.gov/condition/core-binding-factor-acute-myeloid-leukemia,C3839741,T191,Disorders
How many people are affected by core binding factor acute myeloid leukemia ?,0000240-2,frequency,"Acute myeloid leukemia occurs in approximately 3.5 per 100,000 individuals each year. CBF-AML accounts for 12 to 15 percent of acute myeloid leukemia cases in adults.",core binding factor acute myeloid leukemia,0000240,GHR,https://ghr.nlm.nih.gov/condition/core-binding-factor-acute-myeloid-leukemia,C3839741,T191,Disorders
What are the genetic changes related to core binding factor acute myeloid leukemia ?,0000240-3,genetic changes,"CBF-AML is associated with chromosomal rearrangements between chromosomes 8 and 21 and within chromosome 16. The rearrangements involve the RUNX1, RUNX1T1, CBFB, and MYH11 genes. Two of these genes, RUNX1 and CBFB, provide instructions for making the two pieces of a protein complex known as core binding factor (CBF). CBF attaches to certain regions of DNA and turns on genes that help control the development of blood cells (hematopoiesis). In particular, it plays an important role in development of hematopoietic stem cells. Chromosomal rearrangements involving the RUNX1 or CBFB gene alter CBF, leading to leukemia.  In CBF-AML, the RUNX1 gene is affected by a type of genetic rearrangement known as a translocation; in this type of change, pieces of DNA from two chromosomes break off and are interchanged. The most common translocation in this condition, called t(8;21), fuses a part of the RUNX1 gene on chromosome 21 with part of the RUNX1T1 gene (also known as ETO) on chromosome 8. The combination of these genes leads to production of the RUNX1-ETO fusion protein. This fusion protein is able to form CBF and attach to DNA, like the normal RUNX1 protein. However, because the function of the protein produced from the normal RUNX1T1 gene is to block gene activity, the abnormal CBF turns genes off instead of turning them on.  Other genetic rearrangements associated with CBF-AML alter the CBFB gene. One such rearrangement, called an inversion, involves breakage of a chromosome in two places; the resulting piece of DNA is reversed and reinserted into the chromosome. The inversion involved in CBF-AML (written as inv(16)) leads to the fusion of two genes on chromosome 16, CBFB and MYH11. Less commonly, a translocation involving chromosome 16, written as t(16;16), leads to the fusion of the same two genes. The protein produced from these genetic rearrangements is called CBF-MYH11. The fusion protein can form CBF, but it is thought that the presence of the MYH11 portion of the fusion protein prevents CBF from binding to DNA, impairing its ability to control gene activity. Alternatively, the MYH11 portion may interact with other proteins that prevent CBF from controlling gene activity.  The change in gene activity caused by alteration of CBF blocks the maturation (differentiation) of blood cells and leads to the production of abnormal myeloid blasts. However, a chromosomal rearrangement alone is usually not enough to cause leukemia; one or more additional genetic changes are needed for cancer to develop. The additional changes likely cause the immature cells to grow and divide uncontrollably, leading to the excess of myeloid blasts characteristic of CBF-AML.",core binding factor acute myeloid leukemia,0000240,GHR,https://ghr.nlm.nih.gov/condition/core-binding-factor-acute-myeloid-leukemia,C3839741,T191,Disorders
Is core binding factor acute myeloid leukemia inherited ?,0000240-4,inheritance,CBF-AML is not inherited but arises from genetic rearrangements in the body's cells that occur after conception.,core binding factor acute myeloid leukemia,0000240,GHR,https://ghr.nlm.nih.gov/condition/core-binding-factor-acute-myeloid-leukemia,C3839741,T191,Disorders
What are the treatments for core binding factor acute myeloid leukemia ?,0000240-5,treatment,These resources address the diagnosis or management of core binding factor acute myeloid leukemia:  - Fred Hutchinson Cancer Research Center  - Genetic Testing Registry: Acute myeloid leukemia  - National Cancer Institute: Acute Myeloid Leukemia Treatment  - St. Jude Children's Research Hospital   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,core binding factor acute myeloid leukemia,0000240,GHR,https://ghr.nlm.nih.gov/condition/core-binding-factor-acute-myeloid-leukemia,C3839741,T191,Disorders
What is (are) Cornelia de Lange syndrome ?,0000241-1,information,"Cornelia de Lange syndrome is a developmental disorder that affects many parts of the body. The features of this disorder vary widely among affected individuals and range from relatively mild to severe.  Cornelia de Lange syndrome is characterized by slow growth before and after birth leading to short stature; intellectual disability that is usually moderate to severe; and abnormalities of bones in the arms, hands, and fingers. Most people with Cornelia de Lange syndrome also have distinctive facial features, including arched eyebrows that often meet in the middle (synophrys), long eyelashes, low-set ears, small and widely spaced teeth, and a small and upturned nose. Many affected individuals also have behavior problems similar to autism, a developmental condition that affects communication and social interaction.  Additional signs and symptoms of Cornelia de Lange syndrome can include excessive body hair (hypertrichosis), an unusually small head (microcephaly), hearing loss, and problems with the digestive tract. Some people with this condition are born with an opening in the roof of the mouth called a cleft palate. Seizures, heart defects, and eye problems have also been reported in people with this condition.",Cornelia de Lange syndrome,0000241,GHR,https://ghr.nlm.nih.gov/condition/cornelia-de-lange-syndrome,C0039082,T019,Disorders
How many people are affected by Cornelia de Lange syndrome ?,0000241-2,frequency,"Although the exact incidence is unknown, Cornelia de Lange syndrome likely affects 1 in 10,000 to 30,000 newborns. The condition is probably underdiagnosed because affected individuals with mild or uncommon features may never be recognized as having Cornelia de Lange syndrome.",Cornelia de Lange syndrome,0000241,GHR,https://ghr.nlm.nih.gov/condition/cornelia-de-lange-syndrome,C0039082,T019,Disorders
What are the genetic changes related to Cornelia de Lange syndrome ?,0000241-3,genetic changes,"Cornelia de Lange syndrome can result from mutations in at least five genes: NIPBL, SMC1A, HDAC8, RAD21, and SMC3. Mutations in the NIPBL gene have been identified in more than half of all people with this condition; mutations in the other genes are much less common.  The proteins produced from all five genes contribute to the structure or function of the cohesin complex, a group of proteins with an important role in directing development before birth. Within cells, the cohesin complex helps regulate the structure and organization of chromosomes, stabilize cells' genetic information, and repair damaged DNA. The cohesin complex also regulates the activity of certain genes that guide the development of limbs, face, and other parts of the body.  Mutations in the NIPBL, SMC1A, HDAC8, RAD21, and SMC3 genes cause Cornelia de Lange syndrome by impairing the function of the cohesin complex, which disrupts gene regulation during critical stages of early development.  The features of Cornelia de Lange syndrome vary widely, and the severity of the disorder can differ even in individuals with the same gene mutation. Researchers suspect that additional genetic or environmental factors may be important for determining the specific signs and symptoms in each individual. In general, SMC1A, RAD21, and SMC3 gene mutations cause milder signs and symptoms than NIPBL gene mutations. Mutations in the HDAC8 gene cause a somewhat different set of features, including delayed closure of the ""soft spot"" on the head (the anterior fontanelle) in infancy, widely spaced eyes, and dental abnormalities. Like affected individuals with NIPBL gene mutations, those with HDAC8 gene mutations may have significant intellectual disability.  In about 30 percent of cases, the cause of Cornelia de Lange syndrome is unknown. Researchers are looking for additional changes in the five known genes, as well as mutations in other genes, that may cause this condition.",Cornelia de Lange syndrome,0000241,GHR,https://ghr.nlm.nih.gov/condition/cornelia-de-lange-syndrome,C0039082,T019,Disorders
Is Cornelia de Lange syndrome inherited ?,0000241-4,inheritance,"When Cornelia de Lange syndrome is caused by mutations in the NIPBL, RAD21, or SMC3 gene, the condition is considered to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new gene mutations and occur in people with no history of the condition in their family.  When Cornelia de Lange syndrome is caused by mutations in the HDAC8 or SMC1A gene, the condition has an X-linked dominant pattern of inheritance. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. Studies of X-linked Cornelia de Lange syndrome indicate that one copy of the altered gene in each cell may be sufficient to cause the condition. Unlike X-linked recessive conditions, in which males are more frequently affected or experience more severe symptoms than females, X-linked dominant Cornelia de Lange syndrome appears to affect males and females similarly. Most cases result from new mutations in the HDAC8 or SMC1A gene and occur in people with no history of the condition in their family.",Cornelia de Lange syndrome,0000241,GHR,https://ghr.nlm.nih.gov/condition/cornelia-de-lange-syndrome,C0039082,T019,Disorders
What are the treatments for Cornelia de Lange syndrome ?,0000241-5,treatment,These resources address the diagnosis or management of Cornelia de Lange syndrome:  - Gene Review: Gene Review: Cornelia de Lange Syndrome  - Genetic Testing Registry: De Lange syndrome  - MedlinePlus Encyclopedia: Autism  - MedlinePlus Encyclopedia: Microcephaly   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Cornelia de Lange syndrome,0000241,GHR,https://ghr.nlm.nih.gov/condition/cornelia-de-lange-syndrome,C0039082,T019,Disorders
What is (are) corticosteroid-binding globulin deficiency ?,0000242-1,information,"Corticosteroid-binding globulin deficiency is a condition with subtle signs and symptoms, the most frequent being extreme tiredness (fatigue), especially after physical exertion. Many people with this condition have unusually low blood pressure (hypotension). Some affected individuals have a fatty liver or experience chronic pain, particularly in their muscles. These features vary among affected individuals, even those within the same family.  Many people with corticosteroid-binding globulin deficiency have only one or two of these features; others have no signs and symptoms of the disorder and are only diagnosed after a relative is found to be affected.  Some people with corticosteroid-binding globulin deficiency also have a condition called chronic fatigue syndrome. The features of chronic fatigue syndrome are prolonged fatigue that interferes with daily activities, as well as general symptoms, such as sore throat or headaches.",corticosteroid-binding globulin deficiency,0000242,GHR,https://ghr.nlm.nih.gov/condition/corticosteroid-binding-globulin-deficiency,C1852529,T047,Disorders
How many people are affected by corticosteroid-binding globulin deficiency ?,0000242-2,frequency,"The prevalence of corticosteroid-binding globulin deficiency is unknown, but it is thought to be a rare disorder. However, because some people with the disorder have mild or no symptoms, it is likely that corticosteroid-binding globulin deficiency is underdiagnosed.",corticosteroid-binding globulin deficiency,0000242,GHR,https://ghr.nlm.nih.gov/condition/corticosteroid-binding-globulin-deficiency,C1852529,T047,Disorders
What are the genetic changes related to corticosteroid-binding globulin deficiency ?,0000242-3,genetic changes,"Mutations in the SERPINA6 gene cause corticosteroid-binding globulin deficiency. The SERPINA6 gene provides instructions for making a protein called corticosteroid-binding globulin (CBG), which is primarily produced in the liver. The CBG protein attaches (binds) to a hormone called cortisol. This hormone has numerous functions, such as maintaining blood sugar levels, protecting the body from stress, and suppressing inflammation. When cortisol is bound to CBG, the hormone is turned off (inactive). Normally, around 80 to 90 percent of the body's cortisol is bound to CBG. When cortisol is needed in the body, CBG delivers the cortisol where it is needed and releases it, causing cortisol to become active. In this manner, CBG regulates the amount of cortisol that is available for use in the body. The amount of total cortisol in the body consists of both bound (inactive) and unbound (active) cortisol.  SERPINA6 gene mutations often decrease the CBG protein's ability to bind to cortisol; some severe mutations prevent the production of any CBG protein. With less functional CBG to bind cortisol, people with corticosteroid-binding globulin deficiency usually have increased unbound cortisol levels. Typically, the body decreases cortisol production to compensate, resulting in a reduction in total cortisol.  It is unclear how a decrease in CBG protein and total cortisol leads to the signs and symptoms of corticosteroid-binding globulin deficiency. Since the CBG protein is needed to transport cortisol to specific tissues at certain times, it may be that while cortisol is available in the body, the cortisol is not getting to the tissues that require it. A decrease in cortisol may influence widening or narrowing of the blood vessels, contributing to abnormal blood pressure. Some researchers think the features of the disorder may influence each other and that fatigue could be a result of chronic pain rather than a symptom of the disorder itself. There may also be other genetic or environmental factors that influence whether an affected individual is more likely to develop pain or fatigue.",corticosteroid-binding globulin deficiency,0000242,GHR,https://ghr.nlm.nih.gov/condition/corticosteroid-binding-globulin-deficiency,C1852529,T047,Disorders
Is corticosteroid-binding globulin deficiency inherited ?,0000242-4,inheritance,"This condition is reported to have an autosomal recessive pattern of inheritance, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. However, some people with only one SERPINA6 gene mutation may have symptoms such as fatigue or chronic pain. Alternatively, individuals with two SERPINA6 gene mutations may not have any features of the disorder. It is unclear why some people with mutations have features of the disorder and others do not.",corticosteroid-binding globulin deficiency,0000242,GHR,https://ghr.nlm.nih.gov/condition/corticosteroid-binding-globulin-deficiency,C1852529,T047,Disorders
What are the treatments for corticosteroid-binding globulin deficiency ?,0000242-5,treatment,These resources address the diagnosis or management of corticosteroid-binding globulin deficiency:  - American Heart Association: Understanding Blood Pressure Readings  - Genetic Testing Registry: Corticosteroid-binding globulin deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,corticosteroid-binding globulin deficiency,0000242,GHR,https://ghr.nlm.nih.gov/condition/corticosteroid-binding-globulin-deficiency,C1852529,T047,Disorders
What is (are) Costeff syndrome ?,0000244-1,information,"Costeff syndrome is a condition characterized by vision loss, movement problems, and intellectual disability. People with Costeff syndrome have degeneration (atrophy) of the optic nerves, which carry information from the eyes to the brain. This optic nerve atrophy often begins in infancy or early childhood and results in vision loss that worsens over time. Some affected individuals have rapid and involuntary eye movements (nystagmus) or eyes that do not look in the same direction (strabismus).  Movement problems in people with Costeff syndrome develop in late childhood and include muscle stiffness (spasticity), impaired muscle coordination (ataxia), and involuntary jerking movements (choreiform movements). As a result of these movement difficulties, individuals with Costeff syndrome may require wheelchair assistance.  While some people with Costeff syndrome have intellectual disability that ranges from mild to moderate, many people with this condition have normal intelligence.  Costeff syndrome is associated with increased levels of a substance called 3-methylglutaconic acid in the urine. The amount of the acid does not appear to influence the signs and symptoms of the condition. Costeff syndrome is one of a group of metabolic disorders that can be diagnosed by the presence of increased levels of 3-methylglutaconic acid in urine (3-methylglutaconic aciduria). People with Costeff syndrome also have high urine levels of another acid called 3-methylglutaric acid.",Costeff syndrome,0000244,GHR,https://ghr.nlm.nih.gov/condition/costeff-syndrome,C0574084,T047,Disorders
How many people are affected by Costeff syndrome ?,0000244-2,frequency,"Costeff syndrome affects an estimated 1 in 10,000 individuals in the Iraqi Jewish population, in which at least 40 cases have been described. Outside this population, only a few affected individuals have been identified.",Costeff syndrome,0000244,GHR,https://ghr.nlm.nih.gov/condition/costeff-syndrome,C0574084,T047,Disorders
What are the genetic changes related to Costeff syndrome ?,0000244-3,genetic changes,"Mutations in the OPA3 gene cause Costeff syndrome. The OPA3 gene provides instructions for making a protein whose exact function is unknown. The OPA3 protein is found in structures called mitochondria, which are the energy-producing centers of cells. Researchers speculate that the OPA3 protein is involved in regulating the shape of mitochondria.  OPA3 gene mutations that result in Costeff syndrome lead to a loss of OPA3 protein function. Cells without any functional OPA3 protein have abnormally shaped mitochondria. These cells likely have reduced energy production and die sooner than normal, decreasing energy availability in the body's tissues. It is unclear why the optic nerves and the parts of the brain that control movement are particularly affected.",Costeff syndrome,0000244,GHR,https://ghr.nlm.nih.gov/condition/costeff-syndrome,C0574084,T047,Disorders
Is Costeff syndrome inherited ?,0000244-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Costeff syndrome,0000244,GHR,https://ghr.nlm.nih.gov/condition/costeff-syndrome,C0574084,T047,Disorders
What are the treatments for Costeff syndrome ?,0000244-5,treatment,These resources address the diagnosis or management of Costeff syndrome:  - Baby's First Test  - Gene Review: Gene Review: OPA3-Related 3-Methylglutaconic Aciduria  - Genetic Testing Registry: 3-Methylglutaconic aciduria type 3  - MedlinePlus Encyclopedia: Optic Nerve Atrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Costeff syndrome,0000244,GHR,https://ghr.nlm.nih.gov/condition/costeff-syndrome,C0574084,T047,Disorders
What is (are) Costello syndrome ?,0000245-1,information,"Costello syndrome is a disorder that affects many parts of the body. This condition is characterized by delayed development and intellectual disability, loose folds of skin (which are especially noticeable on the hands and feet), unusually flexible joints, and distinctive facial features including a large mouth. Heart problems are common, including an abnormal heartbeat (arrhythmia), structural heart defects, and a type of heart disease that enlarges and weakens the heart muscle (hypertrophic cardiomyopathy). Infants with Costello syndrome may be larger than average at birth, but most have difficulty feeding and grow more slowly than other children. People with this condition have relatively short stature and may have reduced growth hormone levels. Other signs and symptoms of Costello syndrome can include tight Achilles tendons (which connect the calf muscles to the heel), weak muscle tone (hypotonia), a structural abnormality of the brain called a Chiari I malformation, skeletal abnormalities, dental problems, and problems with vision.  Beginning in early childhood, people with Costello syndrome are at an increased risk of developing certain cancerous and noncancerous tumors. The most common noncancerous tumors associated with this condition are papillomas, which are small, wart-like growths that usually develop around the nose and mouth or near the anus. The most common cancerous tumor associated with Costello syndrome is a childhood cancer called rhabdomyosarcoma, which begins in muscle tissue. Neuroblastoma, a tumor that arises in developing nerve cells, also has been reported in children and adolescents with this syndrome. In addition, some teenagers with Costello syndrome have developed transitional cell carcinoma, a form of bladder cancer that is usually seen in older adults.  The signs and symptoms of Costello syndrome overlap significantly with those of two other genetic conditions, cardiofaciocutaneous syndrome (CFC syndrome) and Noonan syndrome. In affected infants, it can be difficult to tell the three conditions apart based on their physical features. However, the conditions can be distinguished by their genetic cause and by specific patterns of signs and symptoms that develop later in childhood.",Costello syndrome,0000245,GHR,https://ghr.nlm.nih.gov/condition/costello-syndrome,C0587248,T047,Disorders
How many people are affected by Costello syndrome ?,0000245-2,frequency,"This condition is very rare; it probably affects 200 to 300 people worldwide. Reported estimates of Costello syndrome prevalence range from 1 in 300,000 to 1 in 1.25 million people.",Costello syndrome,0000245,GHR,https://ghr.nlm.nih.gov/condition/costello-syndrome,C0587248,T047,Disorders
What are the genetic changes related to Costello syndrome ?,0000245-3,genetic changes,"Mutations in the HRAS gene cause Costello syndrome. This gene provides instructions for making a protein called H-Ras, which is part of a pathway that helps control cell growth and division. Mutations that cause Costello syndrome lead to the production of an H-Ras protein that is abnormally turned on (active). The overactive protein directs cells to grow and divide constantly, which can lead to the development of cancerous and noncancerous tumors. It is unclear how mutations in the HRAS gene cause the other features of Costello syndrome, but many of the signs and symptoms probably result from cell overgrowth and abnormal cell division.  Some people with signs and symptoms of Costello syndrome do not have an identified mutation in the HRAS gene. These individuals may actually have CFC syndrome or Noonan syndrome, which are caused by mutations in related genes. The proteins produced from these genes interact with one another and with the H-Ras protein as part of the same cell growth and division pathway. These interactions help explain why mutations in different genes can cause conditions with overlapping signs and symptoms.",Costello syndrome,0000245,GHR,https://ghr.nlm.nih.gov/condition/costello-syndrome,C0587248,T047,Disorders
Is Costello syndrome inherited ?,0000245-4,inheritance,"Costello syndrome is considered to be an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Almost all reported cases have resulted from new gene mutations and have occurred in people with no history of the disorder in their family.",Costello syndrome,0000245,GHR,https://ghr.nlm.nih.gov/condition/costello-syndrome,C0587248,T047,Disorders
What are the treatments for Costello syndrome ?,0000245-5,treatment,These resources address the diagnosis or management of Costello syndrome:  - Gene Review: Gene Review: Costello Syndrome  - Genetic Testing Registry: Costello syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Costello syndrome,0000245,GHR,https://ghr.nlm.nih.gov/condition/costello-syndrome,C0587248,T047,Disorders
What is (are) Cowden syndrome ?,0000246-1,information,"Cowden syndrome is a disorder characterized by multiple noncancerous, tumor-like growths called hamartomas and an increased risk of developing certain cancers.  Almost everyone with Cowden syndrome develops hamartomas. These growths are most commonly found on the skin and mucous membranes (such as the lining of the mouth and nose), but they can also occur in the intestine and other parts of the body. The growth of hamartomas on the skin and mucous membranes typically becomes apparent by a person's late twenties.  Cowden syndrome is associated with an increased risk of developing several types of cancer, particularly cancers of the breast, a gland in the lower neck called the thyroid, and the lining of the uterus (the endometrium). Other cancers that have been identified in people with Cowden syndrome include colorectal cancer, kidney cancer, and a form of skin cancer called melanoma. Compared with the general population, people with Cowden syndrome develop these cancers at younger ages, often beginning in their thirties or forties. Other diseases of the breast, thyroid, and endometrium are also common in Cowden syndrome. Additional signs and symptoms can include an enlarged head (macrocephaly) and a rare, noncancerous brain tumor called Lhermitte-Duclos disease. A small percentage of affected individuals have delayed development or intellectual disability.  The features of Cowden syndrome overlap with those of another disorder called Bannayan-Riley-Ruvalcaba syndrome. People with Bannayan-Riley-Ruvalcaba syndrome also develop hamartomas and other noncancerous tumors. Both conditions can be caused by mutations in the PTEN gene. Some people with Cowden syndrome have had relatives diagnosed with Bannayan-Riley-Ruvalcaba syndrome, and other individuals have had the characteristic features of both conditions. Based on these similarities, researchers have proposed that Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome represent a spectrum of overlapping features known as PTEN hamartoma tumor syndrome instead of two distinct conditions.  Some people have some of the characteristic features of Cowden syndrome, particularly the cancers associated with this condition, but do not meet the strict criteria for a diagnosis of Cowden syndrome. These individuals are often described as having Cowden-like syndrome.",Cowden syndrome,0000246,GHR,https://ghr.nlm.nih.gov/condition/cowden-syndrome,C0018553,T191,Disorders
How many people are affected by Cowden syndrome ?,0000246-2,frequency,"Although the exact prevalence of Cowden syndrome is unknown, researchers estimate that it affects about 1 in 200,000 people.",Cowden syndrome,0000246,GHR,https://ghr.nlm.nih.gov/condition/cowden-syndrome,C0018553,T191,Disorders
What are the genetic changes related to Cowden syndrome ?,0000246-3,genetic changes,"Changes involving at least four genes, PTEN, SDHB, SDHD, and KLLN, have been identified in people with Cowden syndrome or Cowden-like syndrome.  Most cases of Cowden syndrome and a small percentage of cases of Cowden-like syndrome result from mutations in the PTEN gene. The protein produced from the PTEN gene is a tumor suppressor, which means that it normally prevents cells from growing and dividing (proliferating) too rapidly or in an uncontrolled way. Mutations in the PTEN gene prevent the protein from regulating cell proliferation effectively, leading to uncontrolled cell division and the formation of hamartomas and cancerous tumors. The PTEN gene likely has other important functions within cells; however, it is unclear how mutations in this gene cause the other features of Cowden syndrome, such as macrocephaly and intellectual disability.  Other cases of Cowden syndrome and Cowden-like syndrome result from changes involving the KLLN gene. This gene provides instructions for making a protein called killin. Like the protein produced from the PTEN gene, killin probably acts as a tumor suppressor. The genetic change that causes Cowden syndrome and Cowden-like syndrome is known as promoter hypermethylation. The promoter is a region of DNA near the gene that controls gene activity (expression). Hypermethylation occurs when too many small molecules called methyl groups are attached to the promoter region. The extra methyl groups reduce the expression of the KLLN gene, which means that less killin is produced. A reduced amount of killin may allow abnormal cells to survive and proliferate inappropriately, which can lead to the formation of tumors.  A small percentage of people with Cowden syndrome or Cowden-like syndrome have variations in the SDHB or SDHD gene. These genes provide instructions for making parts of an enzyme called succinate dehydrogenase (SDH), which is important for energy production in the cell. This enzyme also plays a role in signaling pathways that regulate cell survival and proliferation. Variations in the SDHB or SDHD gene alter the function of the SDH enzyme. Studies suggest that the defective enzyme may allow cells to grow and divide unchecked, leading to the formation of hamartomas and cancerous tumors. However, researchers are uncertain whether the identified SDHB and SDHD gene variants are directly associated with Cowden syndrome and Cowden-like syndrome. Some of the variants described above have also been identified in people without the features of these conditions.  When Cowden syndrome and Cowden-like syndrome are not related to changes in the PTEN, SDHB, SDHD, or KLLN genes, the cause of the conditions is unknown.",Cowden syndrome,0000246,GHR,https://ghr.nlm.nih.gov/condition/cowden-syndrome,C0018553,T191,Disorders
Is Cowden syndrome inherited ?,0000246-4,inheritance,"Cowden syndrome and Cowden-like syndrome are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the condition and increase the risk of developing cancer. In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.",Cowden syndrome,0000246,GHR,https://ghr.nlm.nih.gov/condition/cowden-syndrome,C0018553,T191,Disorders
What are the treatments for Cowden syndrome ?,0000246-5,treatment,These resources address the diagnosis or management of Cowden syndrome:  - Gene Review: Gene Review: PTEN Hamartoma Tumor Syndrome (PHTS)  - Genetic Testing Registry: Cowden syndrome  - Genetic Testing Registry: Cowden syndrome 1  - Genetic Testing Registry: Cowden syndrome 2  - National Cancer Institute: Genetic Testing for Hereditary Cancer Syndromes  - University of Iowa: Are Tests for Cowden Syndrome Available?  - University of Iowa: How is Cowden Syndrome Diagnosed?  - University of Iowa: What Should I Be Doing About This Condition?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Cowden syndrome,0000246,GHR,https://ghr.nlm.nih.gov/condition/cowden-syndrome,C0018553,T191,Disorders
What is (are) cranioectodermal dysplasia ?,0000247-1,information,"Cranioectodermal dysplasia is a disorder that affects many parts of the body. The most common features involve bone abnormalities and abnormal development of certain tissues known as ectodermal tissues, which include the skin, hair, nails, and teeth. The signs and symptoms of this condition vary among affected individuals, even among members of the same family.  Distinctive abnormalities of the skull and face are common in people with cranioectodermal dysplasia. Most affected individuals have a prominent forehead (frontal bossing) and an elongated head (dolichocephaly) due to abnormal fusion of certain skull bones (sagittal craniosynostosis). A variety of facial abnormalities can occur in people with this condition; these include low-set ears that may also be rotated backward, an increased distance between the inner corners of the eyes (telecanthus), and outside corners of the eyes that point upward or downward (upslanting or downslanting palpebral fissures) among others.  Development of bones in the rest of the skeleton is also affected in this condition. Abnormalities in the long bones of the arms and legs (metaphyseal dysplasia) lead to short limbs and short stature. In addition, affected individuals often have short fingers (brachydactyly). Some people with this condition have short rib bones and a narrow rib cage, which can cause breathing problems, especially in affected newborns.  Abnormal development of ectodermal tissues in people with cranioectodermal dysplasia can lead to sparse hair, small or missing teeth, short fingernails and toenails, and loose skin.  Cranioectodermal dysplasia can affect additional organs and tissues in the body. A kidney disorder known as nephronophthisis occurs in many people with this condition, and it can lead to a life-threatening failure of kidney function known as end-stage renal disease. Abnormalities of the liver, heart, or eyes also occur in people with cranioectodermal dysplasia.",cranioectodermal dysplasia,0000247,GHR,https://ghr.nlm.nih.gov/condition/cranioectodermal-dysplasia,C0432235,T019,Disorders
How many people are affected by cranioectodermal dysplasia ?,0000247-2,frequency,Cranioectodermal dysplasia is a rare condition with an unknown prevalence. Approximately 40 cases of this condition have been described in the medical literature.,cranioectodermal dysplasia,0000247,GHR,https://ghr.nlm.nih.gov/condition/cranioectodermal-dysplasia,C0432235,T019,Disorders
What are the genetic changes related to cranioectodermal dysplasia ?,0000247-3,genetic changes,"Cranioectodermal dysplasia is caused by mutations in one of at least four genes: the WDR35, IFT122, WDR19, or IFT43 gene. The protein produced from each of these genes is one piece (subunit) of a protein complex called IFT complex A (IFT-A). This complex is found in finger-like structures called cilia that stick out from the surface of cells. These structures are important for the development and function of many types of cells and tissues. The IFT-A complex is involved in a process called intraflagellar transport, which moves substances within cilia. This movement is essential for the assembly and maintenance of these structures. The IFT-A complex carries materials from the tip to the base of cilia.  Mutations in any of the four mentioned genes reduce the amount or function of one of the IFT-A subunits. Shortage or abnormal function of a single component of the IFT-A complex impairs the function of the entire complex, disrupting the assembly and maintenance of cilia. These mutations lead to a smaller number of cilia and to abnormalities in their shape and structure. Although the mechanism is unclear, a loss of normal cilia impedes proper development of bone, ectodermal tissues, and other tissues and organs, leading to the features of cranioectodermal dysplasia.  About 40 percent of people with cranioectodermal dysplasia have mutations in one of the four known genes. The cause of the condition in people without mutations in one of these genes is unknown.",cranioectodermal dysplasia,0000247,GHR,https://ghr.nlm.nih.gov/condition/cranioectodermal-dysplasia,C0432235,T019,Disorders
Is cranioectodermal dysplasia inherited ?,0000247-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",cranioectodermal dysplasia,0000247,GHR,https://ghr.nlm.nih.gov/condition/cranioectodermal-dysplasia,C0432235,T019,Disorders
What are the treatments for cranioectodermal dysplasia ?,0000247-5,treatment,These resources address the diagnosis or management of cranioectodermal dysplasia:  - Gene Review: Gene Review: Cranioectodermal Dysplasia  - Genetic Testing Registry: Cranioectodermal dysplasia 1  - Genetic Testing Registry: Cranioectodermal dysplasia 2  - Genetic Testing Registry: Cranioectodermal dysplasia 3  - Genetic Testing Registry: Cranioectodermal dysplasia 4   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,cranioectodermal dysplasia,0000247,GHR,https://ghr.nlm.nih.gov/condition/cranioectodermal-dysplasia,C0432235,T019,Disorders
What is (are) craniofacial microsomia ?,0000248-1,information,"Craniofacial microsomia is a term used to describe a spectrum of abnormalities that primarily affect the development of the skull (cranium) and face before birth. Microsomia means abnormal smallness of body structures. Most people with craniofacial microsomia have differences in the size and shape of facial structures between the right and left sides of the face (facial asymmetry). In about two-thirds of cases, both sides of the face have abnormalities, which usually differ from one side to the other. Other individuals with craniofacial microsomia are affected on only one side of the face. The facial characteristics in craniofacial microsomia typically include underdevelopment of one side of the upper or lower jaw (maxillary or mandibular hypoplasia), which can cause dental problems and difficulties with feeding and speech. In cases of severe mandibular hypoplasia, breathing may also be affected.  People with craniofacial microsomia usually have ear abnormalities affecting one or both ears, typically to different degrees. They may have growths of skin (skin tags) in front of the ear (preauricular tags), an underdeveloped or absent external ear (microtia or anotia), or a closed or absent ear canal; these abnormalities may lead to hearing loss. Eye problems are less common in craniofacial microsomia, but some affected individuals have an unusually small eyeball (microphthalmia) or other eye abnormalities that result in vision loss.  Abnormalities in other parts of the body, such as malformed bones of the spine (vertebrae), abnormally shaped kidneys, and heart defects, may also occur in people with craniofacial microsomia.  Many other terms have been used for craniofacial microsomia. These other names generally refer to forms of craniofacial microsomia with specific combinations of signs and symptoms, although sometimes they are used interchangeably. Hemifacial microsomia often refers to craniofacial microsomia with maxillary or mandibular hypoplasia. People with hemifacial microsomia and noncancerous (benign) growths in the eye called epibulbar dermoids may be said to have Goldenhar syndrome or oculoauricular dysplasia.",craniofacial microsomia,0000248,GHR,https://ghr.nlm.nih.gov/condition/craniofacial-microsomia,C0265240,T019,Disorders
How many people are affected by craniofacial microsomia ?,0000248-2,frequency,"Craniofacial microsomia has been estimated to occur in between 1 in 5,600 and 1 in 26,550 newborns. However, this range may be an underestimate because not all medical professionals agree on the criteria for diagnosis of this condition, and because mild cases may never come to medical attention. For reasons that are unclear, the disorder occurs about 50 percent more often in males than in females.",craniofacial microsomia,0000248,GHR,https://ghr.nlm.nih.gov/condition/craniofacial-microsomia,C0265240,T019,Disorders
What are the genetic changes related to craniofacial microsomia ?,0000248-3,genetic changes,"It is unclear what genes are involved in craniofacial microsomia. This condition results from problems in the development of structures in the embryo called the first and second pharyngeal arches (also called branchial or visceral arches). Tissue layers in the six pairs of pharyngeal arches give rise to the muscles, arteries, nerves, and cartilage of the face and neck. Specifically, the first and second pharyngeal arches develop into the lower jaw, the nerves and muscles used for chewing and facial expression, the external ear, and the bones of the middle ear. Interference with the normal development of these structures can result in the abnormalities characteristic of craniofacial microsomia.  There are several factors that can disrupt the normal development of the first and second pharyngeal arches and lead to craniofacial microsomia. Some individuals with this condition have chromosomal abnormalities such as deletions or duplications of genetic material; these individuals often have additional developmental problems or malformations. Occasionally, craniofacial microsomia occurs in multiple members of a family in a pattern that suggests inheritance of a causative gene mutation, but the gene or genes involved are unknown. In other families, individuals seem to inherit a predisposition to the disorder. The risk of craniofacial microsomia can also be increased by environmental factors, such as certain drugs taken by the mother during pregnancy. In most affected individuals, the cause of the disorder is unknown.  It is not well understood why certain disruptions to development affect the first and second pharyngeal arches in particular. Researchers suggest that these structures may develop together in such a way that they respond as a unit to these disruptions.",craniofacial microsomia,0000248,GHR,https://ghr.nlm.nih.gov/condition/craniofacial-microsomia,C0265240,T019,Disorders
Is craniofacial microsomia inherited ?,0000248-4,inheritance,"Craniofacial microsomia most often occurs in a single individual in a family and is not inherited. If the condition is caused by a chromosomal abnormality, it may be inherited from one affected parent or it may result from a new abnormality in the chromosome and occur in people with no history of the disorder in their family.  In 1 to 2 percent of cases, craniofacial microsomia is inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. In rare cases, the condition is inherited in an autosomal recessive pattern, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. The gene or genes involved in craniofacial microsomia are unknown.  In some affected families, people seem to inherit an increased risk of developing craniofacial microsomia, not the condition itself. In these cases, some combination of genetic changes and environmental factors may be involved.",craniofacial microsomia,0000248,GHR,https://ghr.nlm.nih.gov/condition/craniofacial-microsomia,C0265240,T019,Disorders
What are the treatments for craniofacial microsomia ?,0000248-5,treatment,These resources address the diagnosis or management of craniofacial microsomia:  - Children's Hospital and Medical Center of the University of Nebraska  - Gene Review: Gene Review: Craniofacial Microsomia Overview  - Genetic Testing Registry: Goldenhar syndrome  - Seattle Children's Hospital  - Virginia Commonwealth University   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,craniofacial microsomia,0000248,GHR,https://ghr.nlm.nih.gov/condition/craniofacial-microsomia,C0265240,T019,Disorders
What is (are) craniofacial-deafness-hand syndrome ?,0000249-1,information,"Craniofacial-deafness-hand syndrome is characterized by distinctive facial features, profound hearing loss, and hand abnormalities.  The distinctive facial features of people with craniofacial-deafness-hand syndrome result from a variety of developmental abnormalities involving the skull (cranium) and face. Affected individuals often have underdeveloped or absent nasal bones resulting in a small nose, thin nostrils, and a flattened mid-face with a flat nasal bridge. Individuals with this condition typically also have widely spaced eyes (ocular hypertelorism), narrowed openings of the eyes (narrowed palpebral fissures), a small upper jaw (hypoplastic maxilla), and a small mouth with pursed lips.  People with this condition also have profound hearing loss that is caused by abnormalities in the inner ear (sensorineural deafness). Hearing loss in these individuals is present from birth.  In affected individuals, a common abnormality of the muscles in the hand is a malformation in which all of the fingers are angled outward toward the fifth finger (ulnar deviation). People with craniofacial-deafness-hand syndrome may also have permanently bent third, fourth, and fifth fingers (camptodactyly), which can limit finger movement and lead to joint deformities called contractures. Contractures in the wrist can further impair hand movements.",craniofacial-deafness-hand syndrome,0000249,GHR,https://ghr.nlm.nih.gov/condition/craniofacial-deafness-hand-syndrome,C0011053,T047,Disorders
How many people are affected by craniofacial-deafness-hand syndrome ?,0000249-2,frequency,Craniofacial-deafness-hand syndrome is an extremely rare condition. Only a few cases have been reported in the scientific literature.,craniofacial-deafness-hand syndrome,0000249,GHR,https://ghr.nlm.nih.gov/condition/craniofacial-deafness-hand-syndrome,C0011053,T047,Disorders
What are the genetic changes related to craniofacial-deafness-hand syndrome ?,0000249-3,genetic changes,"Craniofacial-deafness-hand syndrome is caused by mutations in the PAX3 gene. The PAX3 gene plays a critical role in the formation of tissues and organs during embryonic development. To perform this function, the gene provides instructions for making a protein that attaches (binds) to specific areas of DNA to help control the activity of particular genes. During embryonic development, the PAX3 gene is active in cells called neural crest cells. These cells migrate from the developing spinal cord to specific regions in the embryo. The protein produced from the PAX3 gene directs the activity of other genes that signal neural crest cells to form specialized tissues or cell types. These include some nerve tissues, bones in the face and skull (craniofacial bones), and muscle tissue.  At least one PAX3 gene mutation has been identified in individuals with craniofacial-deafness-hand syndrome. This mutation appears to affect the ability of the PAX3 protein to bind to DNA. As a result, the PAX3 protein cannot control the activity of other genes and cannot regulate the differentiation of neural crest cells. A lack of specialization of neural crest cells leads to the impaired growth of craniofacial bones, nerve tissue, and muscles seen in craniofacial-deafness-hand syndrome.",craniofacial-deafness-hand syndrome,0000249,GHR,https://ghr.nlm.nih.gov/condition/craniofacial-deafness-hand-syndrome,C0011053,T047,Disorders
Is craniofacial-deafness-hand syndrome inherited ?,0000249-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",craniofacial-deafness-hand syndrome,0000249,GHR,https://ghr.nlm.nih.gov/condition/craniofacial-deafness-hand-syndrome,C0011053,T047,Disorders
What are the treatments for craniofacial-deafness-hand syndrome ?,0000249-5,treatment,These resources address the diagnosis or management of craniofacial-deafness-hand syndrome:  - Genetic Testing Registry: Craniofacial deafness hand syndrome  - Johns Hopkins Children's Center: Hearing Loss   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,craniofacial-deafness-hand syndrome,0000249,GHR,https://ghr.nlm.nih.gov/condition/craniofacial-deafness-hand-syndrome,C0011053,T047,Disorders
What is (are) craniometaphyseal dysplasia ?,0000250-1,information,"Craniometaphyseal dysplasia is a rare condition characterized by progressive thickening of bones in the skull (cranium) and abnormalities at the ends of long bones in the limbs (metaphyseal dysplasia). Except in the most severe cases, the lifespan of people with craniometaphyseal dysplasia is normal.  Bone overgrowth in the head causes many of the signs and symptoms of craniometaphyseal dysplasia. Affected individuals typically have distinctive facial features such as a wide nasal bridge, a prominent forehead, wide-set eyes (hypertelorism), and a prominent jaw. Excessive new bone formation (hyperostosis) in the jaw can delay teething (dentition) or result in absent (non-erupting) teeth. Infants with this condition may have breathing or feeding problems caused by narrow nasal passages. In severe cases, abnormal bone growth can compress the nerves that emerge from the brain and extend to various areas of the head and neck (cranial nerves). Compression of the cranial nerves can lead to paralyzed facial muscles (facial nerve palsy), blindness, or deafness.  The x-rays of individuals with craniometaphyseal dysplasia show unusually shaped long bones, particularly the large bones in the legs. The ends of these bones (metaphyses) are wider and appear less dense in people with this condition.  There are two types of craniometaphyseal dysplasia, which are distinguished by their pattern of inheritance. They are known as the autosomal dominant and autosomal recessive types. Autosomal recessive craniometaphyseal dysplasia is typically more severe than the autosomal dominant form.",craniometaphyseal dysplasia,0000250,GHR,https://ghr.nlm.nih.gov/condition/craniometaphyseal-dysplasia,C0265292,T019,Disorders
How many people are affected by craniometaphyseal dysplasia ?,0000250-2,frequency,Craniometaphyseal dysplasia is a very rare disorder; its incidence is unknown.,craniometaphyseal dysplasia,0000250,GHR,https://ghr.nlm.nih.gov/condition/craniometaphyseal-dysplasia,C0265292,T019,Disorders
What are the genetic changes related to craniometaphyseal dysplasia ?,0000250-3,genetic changes,"Mutations in the ANKH gene cause autosomal dominant craniometaphyseal dysplasia. The ANKH gene provides instructions for making a protein that is present in bone and transports a molecule called pyrophosphate out of cells. Pyrophosphate helps regulate bone formation by preventing mineralization, the process by which minerals such as calcium and phosphorus are deposited in developing bones. The ANKH protein may have other, unknown functions.  Mutations in the ANKH gene that cause autosomal dominant craniometaphyseal dysplasia may decrease the ANKH protein's ability to transport pyrophosphate out of cells. Reduced levels of pyrophosphate can increase bone mineralization, contributing to the bone overgrowth seen in craniometaphyseal dysplasia. Why long bones are shaped differently and only the skull bones become thicker in people with this condition remains unclear.  The genetic cause of autosomal recessive craniometaphyseal dysplasia is unknown. Researchers believe that mutations in an unidentified gene on chromosome 6 may be responsible for the autosomal recessive form of this condition.",craniometaphyseal dysplasia,0000250,GHR,https://ghr.nlm.nih.gov/condition/craniometaphyseal-dysplasia,C0265292,T019,Disorders
Is craniometaphyseal dysplasia inherited ?,0000250-4,inheritance,"Craniometaphyseal dysplasia can have different inheritance patterns. In most cases this condition is inherited in an autosomal dominant pattern, which means one altered copy of the ANKH gene in each cell is sufficient to cause the disorder. Individuals with autosomal dominant craniometaphyseal dysplasia typically have one parent who also has the condition. Less often, cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  Rarely, craniometaphyseal dysplasia is suspected to have autosomal recessive inheritance when unaffected parents have more than one child with the condition. Autosomal recessive disorders are caused by mutations in both copies of a gene in each cell. The parents of an individual with an autosomal recessive condition each carry one copy of a mutated gene, but they typically do not show signs and symptoms of the disorder.",craniometaphyseal dysplasia,0000250,GHR,https://ghr.nlm.nih.gov/condition/craniometaphyseal-dysplasia,C0265292,T019,Disorders
What are the treatments for craniometaphyseal dysplasia ?,0000250-5,treatment,"These resources address the diagnosis or management of craniometaphyseal dysplasia:  - Gene Review: Gene Review: Craniometaphyseal Dysplasia, Autosomal Dominant  - Genetic Testing Registry: Craniometaphyseal dysplasia, autosomal dominant  - Genetic Testing Registry: Craniometaphyseal dysplasia, autosomal recessive type  - MedlinePlus Encyclopedia: Facial Paralysis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",craniometaphyseal dysplasia,0000250,GHR,https://ghr.nlm.nih.gov/condition/craniometaphyseal-dysplasia,C0265292,T019,Disorders
What is (are) cri-du-chat syndrome ?,0000251-1,information,"Cri-du-chat (cat's cry) syndrome, also known as 5p- (5p minus) syndrome, is a chromosomal condition that results when a piece of chromosome 5 is missing. Infants with this condition often have a high-pitched cry that sounds like that of a cat. The disorder is characterized by intellectual disability and delayed development, small head size (microcephaly), low birth weight, and weak muscle tone (hypotonia) in infancy. Affected individuals also have distinctive facial features, including widely set eyes (hypertelorism), low-set ears, a small jaw, and a rounded face. Some children with cri-du-chat syndrome are born with a heart defect.",cri-du-chat syndrome,0000251,GHR,https://ghr.nlm.nih.gov/condition/cri-du-chat-syndrome,C0010314,T019,Disorders
How many people are affected by cri-du-chat syndrome ?,0000251-2,frequency,"Cri-du-chat syndrome occurs in an estimated 1 in 20,000 to 50,000 newborns. This condition is found in people of all ethnic backgrounds.",cri-du-chat syndrome,0000251,GHR,https://ghr.nlm.nih.gov/condition/cri-du-chat-syndrome,C0010314,T019,Disorders
What are the genetic changes related to cri-du-chat syndrome ?,0000251-3,genetic changes,"Cri-du-chat syndrome is caused by a deletion of the end of the short (p) arm of chromosome 5. This chromosomal change is written as 5p-. The size of the deletion varies among affected individuals; studies suggest that larger deletions tend to result in more severe intellectual disability and developmental delay than smaller deletions.  The signs and symptoms of cri-du-chat syndrome are probably related to the loss of multiple genes on the short arm of chromosome 5. Researchers believe that the loss of a specific gene, CTNND2, is associated with severe intellectual disability in some people with this condition. They are working to determine how the loss of other genes in this region contributes to the characteristic features of cri-du-chat syndrome.",cri-du-chat syndrome,0000251,GHR,https://ghr.nlm.nih.gov/condition/cri-du-chat-syndrome,C0010314,T019,Disorders
Is cri-du-chat syndrome inherited ?,0000251-4,inheritance,"Most cases of cri-du-chat syndrome are not inherited. The deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family.  About 10 percent of people with cri-du-chat syndrome inherit the chromosome abnormality from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which no genetic material is gained or lost. Balanced translocations usually do not cause any health problems; however, they can become unbalanced as they are passed to the next generation. Children who inherit an unbalanced translocation can have a chromosomal rearrangement with extra or missing genetic material. Individuals with cri-du-chat syndrome who inherit an unbalanced translocation are missing genetic material from the short arm of chromosome 5, which results in the intellectual disability and health problems characteristic of this disorder.",cri-du-chat syndrome,0000251,GHR,https://ghr.nlm.nih.gov/condition/cri-du-chat-syndrome,C0010314,T019,Disorders
What are the treatments for cri-du-chat syndrome ?,0000251-5,treatment,These resources address the diagnosis or management of cri-du-chat syndrome:  - Cri du Chat Syndrome Support Group (UK): Diagnosis  - Cri du Chat Syndrome Support Group (UK): Therapies  - Genetic Testing Registry: 5p partial monosomy syndrome  - MedlinePlus Encyclopedia: Cri du Chat Syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,cri-du-chat syndrome,0000251,GHR,https://ghr.nlm.nih.gov/condition/cri-du-chat-syndrome,C0010314,T019,Disorders
What is (are) Crigler-Najjar syndrome ?,0000252-1,information,"Crigler-Najjar syndrome is a severe condition characterized by high levels of a toxic substance called bilirubin in the blood (hyperbilirubinemia). Bilirubin is produced when red blood cells are broken down. This substance is removed from the body only after it undergoes a chemical reaction in the liver, which converts the toxic form of bilirubin (called unconjugated bilirubin) to a nontoxic form called conjugated bilirubin. People with Crigler-Najjar syndrome have a buildup of unconjugated bilirubin in their blood (unconjugated hyperbilirubinemia).  Bilirubin has an orange-yellow tint, and hyperbilirubinemia causes yellowing of the skin and whites of the eyes (jaundice). In Crigler-Najjar syndrome, jaundice is apparent at birth or in infancy. Severe unconjugated hyperbilirubinemia can lead to a condition called kernicterus, which is a form of brain damage caused by the accumulation of unconjugated bilirubin in the brain and nerve tissues. Babies with kernicterus are often extremely tired (lethargic) and may have weak muscle tone (hypotonia). These babies may experience episodes of increased muscle tone (hypertonia) and arching of their backs. Kernicterus can lead to other neurological problems, including involuntary writhing movements of the body (choreoathetosis), hearing problems, or intellectual disability.  Crigler-Najjar syndrome is divided into two types. Type 1 (CN1) is very severe, and affected individuals can die in childhood due to kernicterus, although with proper treatment, they may survive longer. Type 2 (CN2) is less severe. People with CN2 are less likely to develop kernicterus, and most affected individuals survive into adulthood.",Crigler-Najjar syndrome,0000252,GHR,https://ghr.nlm.nih.gov/condition/crigler-najjar-syndrome,C0010324,T047,Disorders
How many people are affected by Crigler-Najjar syndrome ?,0000252-2,frequency,Crigler-Najjar syndrome is estimated to affect fewer than 1 in 1 million newborns worldwide.,Crigler-Najjar syndrome,0000252,GHR,https://ghr.nlm.nih.gov/condition/crigler-najjar-syndrome,C0010324,T047,Disorders
What are the genetic changes related to Crigler-Najjar syndrome ?,0000252-3,genetic changes,"Mutations in the UGT1A1 gene cause Crigler-Najjar syndrome. This gene provides instructions for making the bilirubin uridine diphosphate glucuronosyl transferase (bilirubin-UGT) enzyme, which is found primarily in liver cells and is necessary for the removal of bilirubin from the body.  The bilirubin-UGT enzyme performs a chemical reaction called glucuronidation. During this reaction, the enzyme transfers a compound called glucuronic acid to unconjugated bilirubin, converting it to conjugated bilirubin. Glucuronidation makes bilirubin dissolvable in water so that it can be removed from the body.  Mutations in the UGT1A1 gene that cause Crigler-Najjar syndrome result in reduced or absent function of the bilirubin-UGT enzyme. People with CN1 have no enzyme function, while people with CN2 have less than 20 percent of normal function. The loss of bilirubin-UGT function decreases glucuronidation of unconjugated bilirubin. This toxic substance then builds up in the body, causing unconjugated hyperbilirubinemia and jaundice.",Crigler-Najjar syndrome,0000252,GHR,https://ghr.nlm.nih.gov/condition/crigler-najjar-syndrome,C0010324,T047,Disorders
Is Crigler-Najjar syndrome inherited ?,0000252-4,inheritance,"Crigler-Najjar syndrome is inherited in an autosomal recessive pattern, which means both copies of the UGT1A1 gene in each cell have mutations. A less severe condition called Gilbert syndrome can occur when one copy of the UGT1A1 gene has a mutation.",Crigler-Najjar syndrome,0000252,GHR,https://ghr.nlm.nih.gov/condition/crigler-najjar-syndrome,C0010324,T047,Disorders
What are the treatments for Crigler-Najjar syndrome ?,0000252-5,treatment,"These resources address the diagnosis or management of Crigler-Najjar syndrome:  - Centers for Disease Control and Prevention: Facts About Jaundice and Kernicterus  - Genetic Testing Registry: Crigler Najjar syndrome, type 1  - Genetic Testing Registry: Crigler-Najjar syndrome  - Genetic Testing Registry: Crigler-Najjar syndrome, type II   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Crigler-Najjar syndrome,0000252,GHR,https://ghr.nlm.nih.gov/condition/crigler-najjar-syndrome,C0010324,T047,Disorders
What is (are) critical congenital heart disease ?,0000253-1,information,"Critical congenital heart disease (CCHD) is a term that refers to a group of serious heart defects that are present from birth. These abnormalities result from problems with the formation of one or more parts of the heart during the early stages of embryonic development. CCHD prevents the heart from pumping blood effectively or reduces the amount of oxygen in the blood. As a result, organs and tissues throughout the body do not receive enough oxygen, which can lead to organ damage and life-threatening complications. Individuals with CCHD usually require surgery soon after birth.  Although babies with CCHD may appear healthy for the first few hours or days of life, signs and symptoms soon become apparent. These can include an abnormal heart sound during a heartbeat (heart murmur), rapid breathing (tachypnea), low blood pressure (hypotension), low levels of oxygen in the blood (hypoxemia), and a blue or purple tint to the skin caused by a shortage of oxygen (cyanosis). If untreated, CCHD can lead to shock, coma, and death. However, most people with CCHD now survive past infancy due to improvements in early detection, diagnosis, and treatment.  Some people with treated CCHD have few related health problems later in life. However, long-term effects of CCHD can include delayed development and reduced stamina during exercise. Adults with these heart defects have an increased risk of abnormal heart rhythms, heart failure, sudden cardiac arrest, stroke, and premature death.  Each of the heart defects associated with CCHD affects the flow of blood into, out of, or through the heart. Some of the heart defects involve structures within the heart itself, such as the two lower chambers of the heart (the ventricles) or the valves that control blood flow through the heart. Others affect the structure of the large blood vessels leading into and out of the heart (including the aorta and pulmonary artery). Still others involve a combination of these structural abnormalities.  People with CCHD have one or more specific heart defects. The heart defects classified as CCHD include coarctation of the aorta, double-outlet right ventricle, D-transposition of the great arteries, Ebstein anomaly, hypoplastic left heart syndrome, interrupted aortic arch, pulmonary atresia with intact septum, single ventricle, total anomalous pulmonary venous connection, tetralogy of Fallot, tricuspid atresia, and truncus arteriosus.",critical congenital heart disease,0000253,GHR,https://ghr.nlm.nih.gov/condition/critical-congenital-heart-disease,C0455683,T019,Disorders
How many people are affected by critical congenital heart disease ?,0000253-2,frequency,"Heart defects are the most common type of birth defect, accounting for more than 30 percent of all infant deaths due to birth defects. CCHD represents some of the most serious types of heart defects. About 7,200 newborns, or 18 per 10,000, in the United States are diagnosed with CCHD each year.",critical congenital heart disease,0000253,GHR,https://ghr.nlm.nih.gov/condition/critical-congenital-heart-disease,C0455683,T019,Disorders
What are the genetic changes related to critical congenital heart disease ?,0000253-3,genetic changes,"In most cases, the cause of CCHD is unknown. A variety of genetic and environmental factors likely contribute to this complex condition.  Changes in single genes have been associated with CCHD. Studies suggest that these genes are involved in normal heart development before birth. Most of the identified mutations reduce the amount or function of the protein that is produced from a specific gene, which likely impairs the normal formation of structures in the heart. Studies have also suggested that having more or fewer copies of particular genes compared with other people, a phenomenon known as copy number variation, may play a role in CCHD. However, it is unclear whether genes affected by copy number variation are involved in heart development and how having missing or extra copies of those genes could lead to heart defects. Researchers believe that single-gene mutations and copy number variation account for a relatively small percentage of all CCHD.  CCHD is usually isolated, which means it occurs alone (without signs and symptoms affecting other parts of the body). However, the heart defects associated with CCHD can also occur as part of genetic syndromes that have additional features. Some of these genetic conditions, such as Down syndrome, Turner syndrome, and 22q11.2 deletion syndrome, result from changes in the number or structure of particular chromosomes. Other conditions, including Noonan syndrome and Alagille syndrome, result from mutations in single genes.  Environmental factors may also contribute to the development of CCHD. Potential risk factors that have been studied include exposure to certain chemicals or drugs before birth, viral infections (such as rubella and influenza) that occur during pregnancy, and other maternal illnesses including diabetes and phenylketonuria. Although researchers are examining risk factors that may be associated with this complex condition, many of these factors remain unknown.",critical congenital heart disease,0000253,GHR,https://ghr.nlm.nih.gov/condition/critical-congenital-heart-disease,C0455683,T019,Disorders
Is critical congenital heart disease inherited ?,0000253-4,inheritance,"Most cases of CCHD are sporadic, which means they occur in people with no history of the disorder in their family. However, close relatives (such as siblings) of people with CCHD may have an increased risk of being born with a heart defect compared with people in the general population.",critical congenital heart disease,0000253,GHR,https://ghr.nlm.nih.gov/condition/critical-congenital-heart-disease,C0455683,T019,Disorders
What are the treatments for critical congenital heart disease ?,0000253-5,treatment,"These resources address the diagnosis or management of critical congenital heart disease:  - Baby's First Test: Critical Congenital Heart Disease  - Boston Children's Hospital  - Centers for Disease Control and Prevention: Screening for Critical Congenital Heart Defects  - Children's Hospital of Philadelphia  - Cincinnati Children's Hospital Medical Center  - Cleveland Clinic  - Genetic Testing Registry: Congenital heart disease  - Genetic Testing Registry: Ebstein's anomaly  - Genetic Testing Registry: Hypoplastic left heart syndrome  - Genetic Testing Registry: Hypoplastic left heart syndrome 2  - Genetic Testing Registry: Persistent truncus arteriosus  - Genetic Testing Registry: Pulmonary atresia with intact ventricular septum  - Genetic Testing Registry: Pulmonary atresia with ventricular septal defect  - Genetic Testing Registry: Tetralogy of Fallot  - Genetic Testing Registry: Transposition of the great arteries  - Genetic Testing Registry: Transposition of the great arteries, dextro-looped 2  - Genetic Testing Registry: Transposition of the great arteries, dextro-looped 3  - Genetic Testing Registry: Tricuspid atresia  - Screening, Technology, and Research in Genetics (STAR-G)  - University of California, San Francisco Fetal Treatment Center: Congenital Heart Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",critical congenital heart disease,0000253,GHR,https://ghr.nlm.nih.gov/condition/critical-congenital-heart-disease,C0455683,T019,Disorders
What is (are) Crohn disease ?,0000254-1,information,"Crohn disease is a complex, chronic disorder that primarily affects the digestive system. This condition typically involves abnormal inflammation of the intestinal walls, particularly in the lower part of the small intestine (the ileum) and portions of the large intestine (the colon). Inflammation can occur in any part of the digestive system, however. The inflamed tissues become thick and swollen, and the inner surface of the intestine may develop open sores (ulcers).  Crohn disease most commonly appears in a person's late teens or twenties, although the disease can appear at any age. Signs and symptoms tend to flare up multiple times throughout life. The most common features of this condition are persistent diarrhea, abdominal pain and cramping, loss of appetite, weight loss, and fever. Some people with Crohn disease have chronic bleeding from inflamed tissues in the intestine; over time, this bleeding can lead to a low number of red blood cells (anemia). In some cases, Crohn disease can also cause medical problems affecting the joints, eyes, or skin.  Intestinal blockage is a common complication of Crohn disease. Blockages are caused by swelling or a buildup of scar tissue in the intestinal walls. Some affected individuals also develop fistulae, which are abnormal connections between the intestine and other tissues. Fistulae occur when ulcers break through the intestinal wall to form passages between loops of the intestine or between the intestine and nearby structures (such as the bladder, vagina, or skin).  Crohn disease is one common form of inflammatory bowel disease (IBD). Another type of IBD, ulcerative colitis, also causes chronic inflammation of the intestinal lining. Unlike Crohn disease, which can affect any part of the digestive system, ulcerative colitis typically causes inflammation only in the colon. In addition, the two disorders involve different patterns of inflammation.",Crohn disease,0000254,GHR,https://ghr.nlm.nih.gov/condition/crohn-disease,C0010346,T047,Disorders
How many people are affected by Crohn disease ?,0000254-2,frequency,"Crohn disease is most common in western Europe and North America, where it affects 100 to 150 in 100,000 people. About one million Americans are currently affected by this disorder. Crohn disease occurs more often in whites and people of eastern and central European (Ashkenazi) Jewish descent than among people of other ethnic backgrounds.",Crohn disease,0000254,GHR,https://ghr.nlm.nih.gov/condition/crohn-disease,C0010346,T047,Disorders
What are the genetic changes related to Crohn disease ?,0000254-3,genetic changes,"Crohn disease is related to chromosomes 5 and 10.  Variations of the ATG16L1, IRGM, and NOD2 genes increase the risk of developing Crohn disease.  The IL23R gene is associated with Crohn disease.  A variety of genetic and environmental factors likely play a role in causing Crohn disease. Although researchers are studying risk factors that may contribute to this complex disorder, many of these factors remain unknown. Cigarette smoking is thought to increase the risk of developing this disease, and it may also play a role in periodic flare-ups of signs and symptoms.  Studies suggest that Crohn disease may result from a combination of certain genetic variations, changes in the immune system, and the presence of bacteria in the digestive tract. Recent studies have identified variations in specific genes, including ATG16L1, IL23R, IRGM, and NOD2, that influence the risk of developing Crohn disease. These genes provide instructions for making proteins that are involved in immune system function. Variations in any of these genes may disrupt the ability of cells in the intestine to respond normally to bacteria. An abnormal immune response to bacteria in the intestinal walls may lead to chronic inflammation and the digestive problems characteristic of Crohn disease.  Researchers have also discovered genetic variations in certain regions of chromosome 5 and chromosome 10 that appear to contribute to Crohn disease risk. One area of chromosome 5, known as the IBD5 locus, contains several genetic changes that may increase the risk of developing this condition. Other regions of chromosome 5 and chromosome 10 identified in studies of Crohn disease risk are known as ""gene deserts"" because they include no known genes. Instead, these regions may contain stretches of DNA that regulate nearby genes. Additional research is needed to determine how genetic variations in these chromosomal regions are related to a person's chance of developing Crohn disease.",Crohn disease,0000254,GHR,https://ghr.nlm.nih.gov/condition/crohn-disease,C0010346,T047,Disorders
Is Crohn disease inherited ?,0000254-4,inheritance,"The inheritance pattern of Crohn disease is unclear because many genetic and environmental factors are likely to be involved. This condition tends to cluster in families, however, and having an affected family member is a significant risk factor for the disease.",Crohn disease,0000254,GHR,https://ghr.nlm.nih.gov/condition/crohn-disease,C0010346,T047,Disorders
What are the treatments for Crohn disease ?,0000254-5,treatment,These resources address the diagnosis or management of Crohn disease:  - Genetic Testing Registry: Inflammatory bowel disease 1  - MedlinePlus Encyclopedia: Crohn's disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Crohn disease,0000254,GHR,https://ghr.nlm.nih.gov/condition/crohn-disease,C0010346,T047,Disorders
What is (are) Crouzon syndrome ?,0000255-1,information,"Crouzon syndrome is a genetic disorder characterized by the premature fusion of certain skull bones (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face.  Many features of Crouzon syndrome result from the premature fusion of the skull bones. Abnormal growth of these bones leads to wide-set, bulging eyes and vision problems caused by shallow eye sockets; eyes that do not point in the same direction (strabismus); a beaked nose; and an underdeveloped upper jaw. In addition, people with Crouzon syndrome may have dental problems and hearing loss, which is sometimes accompanied by narrow ear canals. A few people with Crouzon syndrome have an opening in the lip and the roof of the mouth (cleft lip and palate). The severity of these signs and symptoms varies among affected people. People with Crouzon syndrome are usually of normal intelligence.",Crouzon syndrome,0000255,GHR,https://ghr.nlm.nih.gov/condition/crouzon-syndrome,C0010273,T019,Disorders
How many people are affected by Crouzon syndrome ?,0000255-2,frequency,Crouzon syndrome is seen in about 16 per million newborns. It is the most common craniosynostosis syndrome.,Crouzon syndrome,0000255,GHR,https://ghr.nlm.nih.gov/condition/crouzon-syndrome,C0010273,T019,Disorders
What are the genetic changes related to Crouzon syndrome ?,0000255-3,genetic changes,"Mutations in the FGFR2 gene cause Crouzon syndrome. This gene provides instructions for making a protein called fibroblast growth factor receptor 2. Among its multiple functions, this protein signals immature cells to become bone cells during embryonic development. Mutations in the FGFR2 gene probably overstimulate signaling by the FGFR2 protein, which causes the bones of the skull to fuse prematurely.",Crouzon syndrome,0000255,GHR,https://ghr.nlm.nih.gov/condition/crouzon-syndrome,C0010273,T019,Disorders
Is Crouzon syndrome inherited ?,0000255-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Crouzon syndrome,0000255,GHR,https://ghr.nlm.nih.gov/condition/crouzon-syndrome,C0010273,T019,Disorders
What are the treatments for Crouzon syndrome ?,0000255-5,treatment,These resources address the diagnosis or management of Crouzon syndrome:  - Gene Review: Gene Review: FGFR-Related Craniosynostosis Syndromes  - Genetic Testing Registry: Crouzon syndrome  - MedlinePlus Encyclopedia: Craniosynostosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Crouzon syndrome,0000255,GHR,https://ghr.nlm.nih.gov/condition/crouzon-syndrome,C0010273,T019,Disorders
What is (are) Crouzonodermoskeletal syndrome ?,0000256-1,information,"Crouzonodermoskeletal syndrome is a disorder characterized by the premature joining of certain bones of the skull (craniosynostosis) during development and a skin condition called acanthosis nigricans.  The signs and symptoms of Crouzonodermoskeletal syndrome overlap with those of a similar condition called Crouzon syndrome. Common features include premature fusion of the skull bones, which affects the shape of the head and face; wide-set, bulging eyes due to shallow eye sockets; eyes that do not point in the same direction (strabismus); a small, beaked nose; and an underdeveloped upper jaw. People with Crouzon syndrome or Crouzonodermoskeletal syndrome usually have normal intelligence.  Several features distinguish Crouzonodermoskeletal syndrome from Crouzon syndrome. People with Crouzonodermoskeletal syndrome have acanthosis nigricans, a skin condition characterized by thick, dark, velvety skin in body folds and creases, including the neck and underarms. In addition, subtle changes may be seen in the bones of the spine (vertebrae) on x-rays. Noncancerous growths called cementomas may develop in the jaw during young adulthood.",Crouzonodermoskeletal syndrome,0000256,GHR,https://ghr.nlm.nih.gov/condition/crouzonodermoskeletal-syndrome,C2677099,T019,Disorders
How many people are affected by Crouzonodermoskeletal syndrome ?,0000256-2,frequency,Crouzonodermoskeletal syndrome is rare; this condition is seen in about 1 person per million.,Crouzonodermoskeletal syndrome,0000256,GHR,https://ghr.nlm.nih.gov/condition/crouzonodermoskeletal-syndrome,C2677099,T019,Disorders
What are the genetic changes related to Crouzonodermoskeletal syndrome ?,0000256-3,genetic changes,Mutations in the FGFR3 gene cause Crouzonodermoskeletal syndrome.  The FGFR3 gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. It remains unclear how a mutation in the FGFR3 gene leads to the characteristic features of Crouzonodermoskeletal syndrome. This genetic change appears to disrupt the normal growth of skull bones and affect skin pigmentation.,Crouzonodermoskeletal syndrome,0000256,GHR,https://ghr.nlm.nih.gov/condition/crouzonodermoskeletal-syndrome,C2677099,T019,Disorders
Is Crouzonodermoskeletal syndrome inherited ?,0000256-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In some cases, an affected person inherits the mutation from one affected parent. More commonly, this condition results from new mutations in the gene. These cases occur in people with no history of the disorder in their family.",Crouzonodermoskeletal syndrome,0000256,GHR,https://ghr.nlm.nih.gov/condition/crouzonodermoskeletal-syndrome,C2677099,T019,Disorders
What are the treatments for Crouzonodermoskeletal syndrome ?,0000256-5,treatment,These resources address the diagnosis or management of Crouzonodermoskeletal syndrome:  - Gene Review: Gene Review: FGFR-Related Craniosynostosis Syndromes  - Genetic Testing Registry: Crouzon syndrome with acanthosis nigricans  - MedlinePlus Encyclopedia: Acanthosis Nigricans  - MedlinePlus Encyclopedia: Craniosynostosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Crouzonodermoskeletal syndrome,0000256,GHR,https://ghr.nlm.nih.gov/condition/crouzonodermoskeletal-syndrome,C2677099,T019,Disorders
What is (are) cryptogenic cirrhosis ?,0000257-1,information,"Cryptogenic cirrhosis is a condition that impairs liver function. People with this condition develop irreversible liver disease caused by scarring of the liver (cirrhosis), typically in mid- to late adulthood.  The liver is a part of the digestive system that helps break down food, store energy, and remove waste products, including toxins. Minor damage to the liver can be repaired by the body. However, severe or long-term damage can lead to the replacement of normal liver tissue with scar tissue.  In the early stages of cryptogenic cirrhosis, people often have no symptoms because the liver has enough normal tissue to function. Signs and symptoms become apparent as more of the liver is replaced by scar tissue. Affected individuals can experience fatigue, weakness, loss of appetite, weight loss, nausea, swelling (edema), enlarged blood vessels, and yellowing of the skin and whites of the eyes (jaundice).  People with cryptogenic cirrhosis may develop high blood pressure in the vein that supplies blood to the liver (portal hypertension). Cryptogenic cirrhosis can lead to type 2 diabetes, although the mechanism is unclear. Some people with cryptogenic cirrhosis develop cancer of the liver (hepatocellular cancer).",cryptogenic cirrhosis,0000257,GHR,https://ghr.nlm.nih.gov/condition/cryptogenic-cirrhosis,C0267809,T047,Disorders
How many people are affected by cryptogenic cirrhosis ?,0000257-2,frequency,"Cirrhosis affects more than 600,000 people in the United States; cryptogenic cirrhosis likely accounts for 5 to 30 percent of these cases.",cryptogenic cirrhosis,0000257,GHR,https://ghr.nlm.nih.gov/condition/cryptogenic-cirrhosis,C0267809,T047,Disorders
What are the genetic changes related to cryptogenic cirrhosis ?,0000257-3,genetic changes,"Unlike most cases of cirrhosis, cryptogenic cirrhosis is not caused by the hepatitis C or B virus or chronic alcohol use. A diagnosis of cryptogenic cirrhosis is typically given when all other causes of cirrhosis have been ruled out. When a disorder occurs without an apparent underlying reason, it is described as cryptogenic.  Research has shown that many cases of cryptogenic cirrhosis likely result from a condition called non-alcoholic fatty liver disease (NAFLD). In NAFLD, fat accumulates in the liver, impairing its function. If the fat buildup leads to inflammation and damage to liver tissue, NAFLD progresses to a condition called non-alcoholic steatohepatitis (NASH). Long term inflammation in people with NASH can cause the formation of scar tissue and a decrease in fat buildup. As a result, individuals progress from NASH to cirrhosis.  Cryptogenic cirrhosis may also develop from autoimmune hepatitis, which is a condition that occurs when the body's immune system malfunctions and attacks the liver, causing inflammation and liver damage.  In very rare cases, cryptogenic cirrhosis has been associated with mutations in genes that provide instructions for making certain keratin proteins. Keratins are a group of tough, fibrous proteins that form the structural framework of certain cells, particularly cells that make up the skin, hair, nails, and similar tissues. People with these keratin gene mutations are more likely to have fibrous deposits in their livers than individuals without the mutations. These deposits impair liver function, leading to cirrhosis. Mutations in these genes have also been found in people with other liver disorders.  In many cases, the cause of cryptogenic cirrhosis is unknown. Many people with predisposing conditions do not develop cirrhosis. Researchers are working to discover the causes of cryptogenic cirrhosis as well as to find out why some people seem to be protected from developing cirrhosis and others seem to be susceptible.",cryptogenic cirrhosis,0000257,GHR,https://ghr.nlm.nih.gov/condition/cryptogenic-cirrhosis,C0267809,T047,Disorders
Is cryptogenic cirrhosis inherited ?,0000257-4,inheritance,"Most cases of cryptogenic cirrhosis are not inherited. However, people with a family history of liver disease or autoimmune disease are at an increased risk of developing these diseases themselves, and possibly cirrhosis.  In individuals with an associated keratin gene mutation, the risk of developing cryptogenic cirrhosis appears to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of an altered gene in each cell is sufficient to increase the risk of developing cryptogenic cirrhosis. In these families, people inherit an increased risk of cryptogenic cirrhosis, not the disease itself.",cryptogenic cirrhosis,0000257,GHR,https://ghr.nlm.nih.gov/condition/cryptogenic-cirrhosis,C0267809,T047,Disorders
What are the treatments for cryptogenic cirrhosis ?,0000257-5,treatment,"These resources address the diagnosis or management of cryptogenic cirrhosis:  - Children's Hospital of Pittsburgh: Cirrhosis  - Cleveland Clinic: Cirrhosis of the Liver  - Genetic Testing Registry: Cirrhosis, cryptogenic  - Genetic Testing Registry: Familial cirrhosis  - MedlinePlus Encyclopedia: Cirrhosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",cryptogenic cirrhosis,0000257,GHR,https://ghr.nlm.nih.gov/condition/cryptogenic-cirrhosis,C0267809,T047,Disorders
What is (are) Cushing disease ?,0000258-1,information,"Cushing disease is caused by elevated levels of a hormone called cortisol, which leads to a wide variety of signs and symptoms. This condition usually occurs in adults between the ages of 20 and 50; however, children may also be affected. The first sign of this condition is usually weight gain around the trunk and in the face. Affected individuals may get stretch marks (striae) on their thighs and abdomen and bruise easily. Individuals with Cushing disease can develop a hump on their upper back caused by abnormal deposits of fat. People with this condition can have muscle weakness, severe tiredness, and progressively thin and brittle bones that are prone to fracture (osteoporosis). They also have a weakened immune system and are at an increased risk of infections. Cushing disease can cause mood disorders such as anxiety, irritability, and depression. This condition can also affect a person's concentration and memory. People with Cushing disease have an increased chance of developing high blood pressure (hypertension) and diabetes. Women with Cushing disease may experience irregular menstruation and have excessive hair growth (hirsutism) on their face, abdomen, and legs. Men with Cushing disease may have erectile dysfunction. Children with Cushing disease typically experience slow growth.",Cushing disease,0000258,GHR,https://ghr.nlm.nih.gov/condition/cushing-disease,C0221406,T047,Disorders
How many people are affected by Cushing disease ?,0000258-2,frequency,"Cushing disease is estimated to occur in 10 to 15 per million people worldwide. For reasons that are unclear, Cushing disease affects females more often than males.",Cushing disease,0000258,GHR,https://ghr.nlm.nih.gov/condition/cushing-disease,C0221406,T047,Disorders
What are the genetic changes related to Cushing disease ?,0000258-3,genetic changes,"The genetic cause of Cushing disease is often unknown. In only a few instances, mutations in certain genes have been found to lead to Cushing disease. These genetic changes are called somatic mutations. They are acquired during a person's lifetime and are present only in certain cells. The genes involved often play a role in regulating the activity of hormones.  Cushing disease is caused by an increase in the hormone cortisol, which helps maintain blood sugar levels, protects the body from stress, and stops (suppresses) inflammation. Cortisol is produced by the adrenal glands, which are small glands located at the top of each kidney. The production of cortisol is triggered by the release of a hormone called adrenocorticotropic hormone (ACTH) from the pituitary gland, located at the base of the brain. The adrenal and pituitary glands are part of the hormone-producing (endocrine) system in the body that regulates development, metabolism, mood, and many other processes.  Cushing disease occurs when a noncancerous (benign) tumor called an adenoma forms in the pituitary gland, causing excessive release of ACTH and, subsequently, elevated production of cortisol. Prolonged exposure to increased cortisol levels results in the signs and symptoms of Cushing disease: changes to the amount and distribution of body fat, decreased muscle mass leading to weakness and reduced stamina, thinning skin causing stretch marks and easy bruising, thinning of the bones resulting in osteoporosis, increased blood pressure, impaired regulation of blood sugar leading to diabetes, a weakened immune system, neurological problems, irregular menstruation in women, and slow growth in children. The overactive adrenal glands that produce cortisol may also produce increased amounts of male sex hormones (androgens), leading to hirsutism in females. The effect of the excess androgens on males is unclear.  Most often, Cushing disease occurs alone, but rarely, it appears as a symptom of genetic syndromes that have pituitary adenomas as a feature, such as multiple endocrine neoplasia type 1 (MEN1) or familial isolated pituitary adenoma (FIPA).  Cushing disease is a subset of a larger condition called Cushing syndrome, which results when cortisol levels are increased by one of a number of possible causes. Sometimes adenomas that occur in organs or tissues other than the pituitary gland, such as adrenal gland adenomas, can also increase cortisol production, causing Cushing syndrome. Certain prescription drugs can result in an increase in cortisol production and lead to Cushing syndrome. Sometimes prolonged periods of stress or depression can cause an increase in cortisol levels; when this occurs, the condition is known as pseudo-Cushing syndrome. Not accounting for increases in cortisol due to prescription drugs, pituitary adenomas cause the vast majority of Cushing syndrome in adults and children.",Cushing disease,0000258,GHR,https://ghr.nlm.nih.gov/condition/cushing-disease,C0221406,T047,Disorders
Is Cushing disease inherited ?,0000258-4,inheritance,"Most cases of Cushing disease are sporadic, which means they occur in people with no history of the disorder in their family. Rarely, the condition has been reported to run in families; however, it does not have a clear pattern of inheritance.  The various syndromes that have Cushing disease as a feature can have different inheritance patterns. Most of these disorders are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Cushing disease,0000258,GHR,https://ghr.nlm.nih.gov/condition/cushing-disease,C0221406,T047,Disorders
What are the treatments for Cushing disease ?,0000258-5,treatment,These resources address the diagnosis or management of Cushing disease:  - Genetic Testing Registry: Pituitary dependent hypercortisolism  - MedlinePlus Encyclopedia: Cortisol Level  - MedlinePlus Encyclopedia: Cushing Disease  - The Endocrine Society's Clinical Guidelines: The Diagnosis of Cushing's Syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Cushing disease,0000258,GHR,https://ghr.nlm.nih.gov/condition/cushing-disease,C0221406,T047,Disorders
What is (are) cutis laxa ?,0000259-1,information,"Cutis laxa is a disorder of connective tissue, which is the tissue that forms the body's supportive framework. Connective tissue provides structure and strength to the muscles, joints, organs, and skin.  The term ""cutis laxa"" is Latin for loose or lax skin, and this condition is characterized by skin that is sagging and not stretchy (inelastic). The skin often hangs in loose folds, causing the face and other parts of the body to have a droopy appearance. Extremely wrinkled skin may be particularly noticeable on the neck and in the armpits and groin.  Cutis laxa can also affect connective tissue in other parts of the body, including the heart, blood vessels, joints, intestines, and lungs. The disorder can cause heart problems and abnormal narrowing, bulging, or tearing of critical arteries. Affected individuals may have soft out-pouchings in the lower abdomen (inguinal hernia) or around the belly button (umbilical hernia). Pouches called diverticula can also develop in the walls of certain organs, such as the bladder and intestines. During childhood, some people with cutis laxa develop a lung disease called emphysema, which can make it difficult to breathe. Depending on which organs and tissues are affected, the signs and symptoms of cutis laxa can range from mild to life-threatening.  Researchers have described several different forms of cutis laxa. The forms are often distinguished by their pattern of inheritance: autosomal dominant, autosomal recessive, or X-linked. In general, the autosomal recessive forms of cutis laxa tend to be more severe than the autosomal dominant form. In addition to the features described above, some people with autosomal recessive cutis laxa have delayed development, intellectual disability, seizures, and problems with movement that can worsen over time.  The X-linked form of cutis laxa is often called occipital horn syndrome. This form of the disorder is considered a mild type of Menkes syndrome, which is a condition that affects copper levels in the body. In addition to sagging and inelastic skin, occipital horn syndrome is characterized by wedge-shaped calcium deposits in a bone at the base of the skull (the occipital bone), coarse hair, and loose joints.",cutis laxa,0000259,GHR,https://ghr.nlm.nih.gov/condition/cutis-laxa,C0010495,T047,Disorders
How many people are affected by cutis laxa ?,0000259-2,frequency,Cutis laxa is a rare disorder. About 200 affected families worldwide have been reported.,cutis laxa,0000259,GHR,https://ghr.nlm.nih.gov/condition/cutis-laxa,C0010495,T047,Disorders
What are the genetic changes related to cutis laxa ?,0000259-3,genetic changes,"Cutis laxa can be caused by mutations in the ATP6V0A2, ATP7A, EFEMP2, ELN, or FBLN5 gene. Most of these genes are involved in the formation and function of elastic fibers, which are slender bundles of proteins that provide strength and flexibility to connective tissue throughout the body. Elastic fibers allow the skin to stretch, the lungs to expand and contract, and arteries to handle blood flowing through them at high pressure.  The major component of elastic fibers, a protein called elastin, is produced from the ELN gene. Other proteins that appear to have critical roles in the assembly of elastic fibers are produced from the EFEMP2, FBLN5, and ATP6V0A2 genes. Mutations in any of these genes disrupt the formation, assembly, or function of elastic fibers. A shortage of these fibers weakens connective tissue in the skin, arteries, lungs, and other organs. These defects in connective tissue underlie the major features of cutis laxa.  Occipital horn syndrome is caused by mutations in the ATP7A gene. This gene provides instructions for making a protein that is important for regulating copper levels in the body. Mutations in the ATP7A gene result in poor distribution of copper to the body's cells. A reduced supply of copper can decrease the activity of numerous copper-containing enzymes that are necessary for the structure and function of bone, skin, hair, blood vessels, and the nervous system. The signs and symptoms of occipital horn syndrome are caused by the reduced activity of these copper-containing enzymes.  Mutations in the genes described above account for only a small percentage of all cases of cutis laxa. Researchers suspect that mutations in other genes, which have not been identified, can also be responsible for the condition.  Rare cases of cutis laxa are acquired, which means they are probably not caused by inherited gene mutations. Acquired cutis laxa appears later in life and is related to the destruction of normal elastic fibers. The causes of acquired cutis laxa are unclear, although it may occur as a side effect of treatment with medications that remove copper from the body (copper chelating drugs).",cutis laxa,0000259,GHR,https://ghr.nlm.nih.gov/condition/cutis-laxa,C0010495,T047,Disorders
Is cutis laxa inherited ?,0000259-4,inheritance,"Cutis laxa can have an autosomal dominant, autosomal recessive, or X-linked recessive pattern of inheritance.  When cutis laxa is caused by ELN mutations, it has an autosomal dominant inheritance pattern. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. Rarely, cases of cutis laxa resulting from FBLN5 mutations can also have an autosomal dominant pattern of inheritance.  Researchers have described at least two forms of autosomal recessive cutis laxa. Type I results from mutations in the EFEMP2 or FBLN5 gene, while type II is caused by mutations in the ATP6V02 gene. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Occipital horn syndrome has an X-linked recessive pattern of inheritance. It results from mutations in the ATP7A gene, which is located on the X chromosome. The X chromosome is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",cutis laxa,0000259,GHR,https://ghr.nlm.nih.gov/condition/cutis-laxa,C0010495,T047,Disorders
What are the treatments for cutis laxa ?,0000259-5,treatment,"These resources address the diagnosis or management of cutis laxa:  - Gene Review: Gene Review: ATP6V0A2-Related Cutis Laxa  - Gene Review: Gene Review: ATP7A-Related Copper Transport Disorders  - Gene Review: Gene Review: EFEMP2-Related Cutis Laxa  - Gene Review: Gene Review: FBLN5-Related Cutis Laxa  - Genetic Testing Registry: Autosomal recessive cutis laxa type IA  - Genetic Testing Registry: Cutis laxa with osteodystrophy  - Genetic Testing Registry: Cutis laxa, X-linked  - Genetic Testing Registry: Cutis laxa, autosomal dominant  - MedlinePlus Encyclopedia: Colon Diverticula (image)  - MedlinePlus Encyclopedia: Emphysema (image)  - MedlinePlus Encyclopedia: Hernia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",cutis laxa,0000259,GHR,https://ghr.nlm.nih.gov/condition/cutis-laxa,C0010495,T047,Disorders
What is (are) cyclic neutropenia ?,0000260-1,information,"Cyclic neutropenia is a disorder that causes frequent infections and other health problems in affected individuals. People with this condition have recurrent episodes of neutropenia during which there is a shortage (deficiency) of neutrophils. Neutrophils are a type of white blood cell that plays a role in inflammation and in fighting infection. The episodes of neutropenia are apparent at birth or soon afterward. For most affected individuals, neutropenia recurs every 21 days and lasts about 3 to 5 days.  Neutropenia makes it more difficult for the body to fight off pathogens such as bacteria and viruses, so people with cyclic neutropenia typically develop recurrent infections of the sinuses, respiratory tract, and skin. Additionally, people with this condition often develop open sores (ulcers) in the mouth and colon, inflammation of the throat (pharyngitis) and gums (gingivitis), recurrent fever, or abdominal pain. People with cyclic neutropenia have these health problems only during episodes of neutropenia. At times when their neutrophil levels are normal, they are not at an increased risk of infection and inflammation.",cyclic neutropenia,0000260,GHR,https://ghr.nlm.nih.gov/condition/cyclic-neutropenia,C0221023,T047,Disorders
How many people are affected by cyclic neutropenia ?,0000260-2,frequency,Cyclic neutropenia is a rare condition and is estimated to occur in 1 in 1 million individuals worldwide.,cyclic neutropenia,0000260,GHR,https://ghr.nlm.nih.gov/condition/cyclic-neutropenia,C0221023,T047,Disorders
What are the genetic changes related to cyclic neutropenia ?,0000260-3,genetic changes,"Mutations in the ELANE gene cause cyclic neutropenia. The ELANE gene provides instructions for making a protein called neutrophil elastase, which is found in neutrophils. When the body starts an immune response to fight an infection, neutrophils release neutrophil elastase. This protein then modifies the function of certain cells and proteins to help fight the infection.  ELANE gene mutations that cause cyclic neutropenia lead to an abnormal neutrophil elastase protein that seems to retain some of its function. However, neutrophils that produce abnormal neutrophil elastase protein appear to have a shorter lifespan than normal neutrophils. The shorter neutrophil lifespan is thought to be responsible for the cyclic nature of this condition. When the affected neutrophils die early, there is a period in which there is a shortage of neutrophils because it takes time for the body to replenish its supply.",cyclic neutropenia,0000260,GHR,https://ghr.nlm.nih.gov/condition/cyclic-neutropenia,C0221023,T047,Disorders
Is cyclic neutropenia inherited ?,0000260-4,inheritance,"Cyclic neutropenia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",cyclic neutropenia,0000260,GHR,https://ghr.nlm.nih.gov/condition/cyclic-neutropenia,C0221023,T047,Disorders
What are the treatments for cyclic neutropenia ?,0000260-5,treatment,These resources address the diagnosis or management of cyclic neutropenia:  - Gene Review: Gene Review: ELANE-Related Neutropenia  - Genetic Testing Registry: Cyclical neutropenia  - Seattle Children's Hospital   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,cyclic neutropenia,0000260,GHR,https://ghr.nlm.nih.gov/condition/cyclic-neutropenia,C0221023,T047,Disorders
What is (are) cyclic vomiting syndrome ?,0000261-1,information,"Cyclic vomiting syndrome is a disorder that causes recurrent episodes of nausea, vomiting, and tiredness (lethargy). This condition is diagnosed most often in young children, but it can affect people of any age.  The episodes of nausea, vomiting, and lethargy last anywhere from an hour to 10 days. An affected person may vomit several times per hour, potentially leading to a dangerous loss of fluids (dehydration). Additional symptoms can include unusually pale skin (pallor), abdominal pain, diarrhea, headache, fever, and an increased sensitivity to light (photophobia) or to sound (phonophobia). In most affected people, the signs and symptoms of each attack are quite similar. These attacks can be debilitating, making it difficult for an affected person to go to work or school.  Episodes of nausea, vomiting, and lethargy can occur regularly or apparently at random, or can be triggered by a variety of factors. The most common triggers are emotional excitement and infections. Other triggers can include periods without eating (fasting), temperature extremes, lack of sleep, overexertion, allergies, ingesting certain foods or alcohol, and menstruation.  If the condition is not treated, episodes usually occur four to 12 times per year. Between attacks, vomiting is absent, and nausea is either absent or much reduced. However, many affected people experience other symptoms during and between episodes, including pain, lethargy, digestive disorders such as gastroesophageal reflux and irritable bowel syndrome, and fainting spells (syncope). People with cyclic vomiting syndrome are also more likely than people without the disorder to experience depression, anxiety, and panic disorder. It is unclear whether these health conditions are directly related to nausea and vomiting.  Cyclic vomiting syndrome is often considered to be a variant of migraines, which are severe headaches often associated with pain, nausea, vomiting, and extreme sensitivity to light and sound. Cyclic vomiting syndrome is likely the same as or closely related to a condition called abdominal migraine, which is characterized by attacks of stomach pain and cramping. Attacks of nausea, vomiting, or abdominal pain in childhood may be replaced by migraine headaches as an affected person gets older. Many people with cyclic vomiting syndrome or abdominal migraine have a family history of migraines.  Most people with cyclic vomiting syndrome have normal intelligence, although some affected people have developmental delay or intellectual disability. Autism spectrum disorders, which affect communication and social interaction, have also been associated with cyclic vomiting syndrome. Additionally, muscle weakness (myopathy) and seizures are possible. People with any of these additional features are said to have cyclic vomiting syndrome plus.",cyclic vomiting syndrome,0000261,GHR,https://ghr.nlm.nih.gov/condition/cyclic-vomiting-syndrome,C0152164,T047,Disorders
How many people are affected by cyclic vomiting syndrome ?,0000261-2,frequency,"The exact prevalence of cyclic vomiting syndrome is unknown; estimates range from 4 to 2,000 per 100,000 children. The condition is diagnosed less frequently in adults, although recent studies suggest that the condition may begin in adulthood as commonly as it begins in childhood.",cyclic vomiting syndrome,0000261,GHR,https://ghr.nlm.nih.gov/condition/cyclic-vomiting-syndrome,C0152164,T047,Disorders
What are the genetic changes related to cyclic vomiting syndrome ?,0000261-3,genetic changes,"Although the causes of cyclic vomiting syndrome have yet to be determined, researchers have proposed several factors that may contribute to the disorder. These factors include changes in brain function, hormonal abnormalities, and gastrointestinal problems. Many researchers believe that cyclic vomiting syndrome is a migraine-like condition, which suggests that it is related to changes in signaling between nerve cells (neurons) in certain areas of the brain. Many affected individuals have abnormalities of the autonomic nervous system, which controls involuntary body functions such as heart rate, blood pressure, and digestion. Based on these abnormalities, cystic vomiting syndrome is often classified as a type of dysautonomia.  Some cases of cyclic vomiting syndrome, particularly those that begin in childhood, may be related to changes in mitochondrial DNA. Mitochondria are structures within cells that convert the energy from food into a form that cells can use. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA (known as mitochondrial DNA or mtDNA).  Several changes in mitochondrial DNA have been associated with cyclic vomiting syndrome. Some of these changes alter single DNA building blocks (nucleotides), whereas others rearrange larger segments of mitochondrial DNA. These changes likely impair the ability of mitochondria to produce energy. Researchers speculate that the impaired mitochondria may cause certain cells of the autonomic nervous system to malfunction, which could affect the digestive system. However, it remains unclear how changes in mitochondrial function could cause episodes of nausea, vomiting, and lethargy; abdominal pain; or migraines in people with this condition.",cyclic vomiting syndrome,0000261,GHR,https://ghr.nlm.nih.gov/condition/cyclic-vomiting-syndrome,C0152164,T047,Disorders
Is cyclic vomiting syndrome inherited ?,0000261-4,inheritance,"In most cases of cyclic vomiting syndrome, affected people have no known history of the disorder in their family. However, many affected individuals have a family history of related conditions, such as migraines, irritable bowel syndrome, or depression, in their mothers and other maternal relatives. This family history suggests an inheritance pattern known as maternal inheritance or mitochondrial inheritance, which applies to genes contained in mtDNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children.  Occasionally, people with cyclic vomiting syndrome have a family history of the disorder that does not follow maternal inheritance. In these cases, the inheritance pattern is unknown.",cyclic vomiting syndrome,0000261,GHR,https://ghr.nlm.nih.gov/condition/cyclic-vomiting-syndrome,C0152164,T047,Disorders
What are the treatments for cyclic vomiting syndrome ?,0000261-5,treatment,These resources address the diagnosis or management of cyclic vomiting syndrome:  - Children's Hospital of Wisconsin  - Genetic Testing Registry: Cyclical vomiting syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,cyclic vomiting syndrome,0000261,GHR,https://ghr.nlm.nih.gov/condition/cyclic-vomiting-syndrome,C0152164,T047,Disorders
What is (are) cystic fibrosis ?,0000262-1,information,"Cystic fibrosis is an inherited disease characterized by the buildup of thick, sticky mucus that can damage many of the body's organs. The disorder's most common signs and symptoms include progressive damage to the respiratory system and chronic digestive system problems. The features of the disorder and their severity varies among affected individuals.  Mucus is a slippery substance that lubricates and protects the linings of the airways, digestive system, reproductive system, and other organs and tissues. In people with cystic fibrosis, the body produces mucus that is abnormally thick and sticky. This abnormal mucus can clog the airways, leading to severe problems with breathing and bacterial infections in the lungs. These infections cause chronic coughing, wheezing, and inflammation. Over time, mucus buildup and infections result in permanent lung damage, including the formation of scar tissue (fibrosis) and cysts in the lungs.  Most people with cystic fibrosis also have digestive problems. Some affected babies have meconium ileus, a blockage of the intestine that occurs shortly after birth. Other digestive problems result from a buildup of thick, sticky mucus in the pancreas. The pancreas is an organ that produces insulin (a hormone that helps control blood sugar levels). It also makes enzymes that help digest food. In people with cystic fibrosis, mucus blocks the ducts of the pancreas, reducing the production of insulin and preventing digestive enzymes from reaching the intestines to aid digestion. Problems with digestion can lead to diarrhea, malnutrition, poor growth, and weight loss. In adolescence or adulthood, a shortage of insulin can cause a form of diabetes known as cystic fibrosis-related diabetes mellitus (CFRDM).  Cystic fibrosis used to be considered a fatal disease of childhood. With improved treatments and better ways to manage the disease, many people with cystic fibrosis now live well into adulthood. Adults with cystic fibrosis experience health problems affecting the respiratory, digestive, and reproductive systems. Most men with cystic fibrosis have congenital bilateral absence of the vas deferens (CBAVD), a condition in which the tubes that carry sperm (the vas deferens) are blocked by mucus and do not develop properly. Men with CBAVD are unable to father children (infertile) unless they undergo fertility treatment. Women with cystic fibrosis may experience complications in pregnancy.",cystic fibrosis,0000262,GHR,https://ghr.nlm.nih.gov/condition/cystic-fibrosis,C0010674,T047,Disorders
How many people are affected by cystic fibrosis ?,0000262-2,frequency,"Cystic fibrosis is a common genetic disease within the white population in the United States. The disease occurs in 1 in 2,500 to 3,500 white newborns. Cystic fibrosis is less common in other ethnic groups, affecting about 1 in 17,000 African Americans and 1 in 31,000 Asian Americans.",cystic fibrosis,0000262,GHR,https://ghr.nlm.nih.gov/condition/cystic-fibrosis,C0010674,T047,Disorders
What are the genetic changes related to cystic fibrosis ?,0000262-3,genetic changes,"Mutations in the CFTR gene cause cystic fibrosis. The CFTR gene provides instructions for making a channel that transports negatively charged particles called chloride ions into and out of cells. Chloride is a component of sodium chloride, a common salt found in sweat. Chloride also has important functions in cells; for example, the flow of chloride ions helps control the movement of water in tissues, which is necessary for the production of thin, freely flowing mucus.  Mutations in the CFTR gene disrupt the function of the chloride channels, preventing them from regulating the flow of chloride ions and water across cell membranes. As a result, cells that line the passageways of the lungs, pancreas, and other organs produce mucus that is unusually thick and sticky. This mucus clogs the airways and various ducts, causing the characteristic signs and symptoms of cystic fibrosis.  Other genetic and environmental factors likely influence the severity of the condition. For example, mutations in genes other than CFTR might help explain why some people with cystic fibrosis are more severely affected than others. Most of these genetic changes have not been identified, however.",cystic fibrosis,0000262,GHR,https://ghr.nlm.nih.gov/condition/cystic-fibrosis,C0010674,T047,Disorders
Is cystic fibrosis inherited ?,0000262-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",cystic fibrosis,0000262,GHR,https://ghr.nlm.nih.gov/condition/cystic-fibrosis,C0010674,T047,Disorders
What are the treatments for cystic fibrosis ?,0000262-5,treatment,These resources address the diagnosis or management of cystic fibrosis:  - American Society for Reproductive Medicine: Male Infertility  - Baby's First Test  - Gene Review: Gene Review: CFTR-Related Disorders  - Genetic Testing Registry: Cystic fibrosis  - Genomics Education Programme (UK)  - MedlinePlus Encyclopedia: Cystic Fibrosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,cystic fibrosis,0000262,GHR,https://ghr.nlm.nih.gov/condition/cystic-fibrosis,C0010674,T047,Disorders
What is (are) cystinosis ?,0000263-1,information,"Cystinosis is a condition characterized by accumulation of the amino acid cystine (a building block of proteins) within cells. Excess cystine damages cells and often forms crystals that can build up and cause problems in many organs and tissues. The kidneys and eyes are especially vulnerable to damage; the muscles, thyroid, pancreas, and testes may also be affected.  There are three distinct types of cystinosis. In order of decreasing severity, they are nephropathic cystinosis, intermediate cystinosis, and non-nephropathic or ocular cystinosis.  Nephropathic cystinosis begins in infancy, causing poor growth and a particular type of kidney damage (renal Fanconi syndrome) in which certain molecules that should be reabsorbed into the bloodstream are instead eliminated in the urine. The kidney problems lead to the loss of important minerals, salts, fluids, and many other nutrients. The loss of nutrients impairs growth and may result in soft, bowed bones (hypophosphatemic rickets), especially in the legs. The nutrient imbalances in the body lead to increased urination, thirst, dehydration, and abnormally acidic blood (acidosis). By about the age of 2, cystine crystals may be present in the clear covering of the eye (cornea). The buildup of these crystals in the eye causes pain and an increased sensitivity to light (photophobia). Untreated children will experience complete kidney failure by about the age of 10. Other signs and symptoms that may occur in untreated people, especially after adolescence, include muscle deterioration, blindness, inability to swallow, diabetes, thyroid and nervous system problems, and an inability to father children (infertility) in affected men.  The signs and symptoms of intermediate cystinosis are the same as nephropathic cystinosis, but they occur at a later age. Intermediate cystinosis typically becomes apparent in affected individuals in adolescence. Malfunctioning kidneys and corneal crystals are the main initial features of this disorder. If intermediate cystinosis is left untreated, complete kidney failure will occur, but usually not until the late teens to mid-twenties.  People with non-nephropathic or ocular cystinosis typically experience photophobia due to cystine crystals in the cornea, but usually do not develop kidney malfunction or most of the other signs and symptoms of cystinosis. Due to the absence of severe symptoms, the age at which this form of cystinosis is diagnosed varies widely.",cystinosis,0000263,GHR,https://ghr.nlm.nih.gov/condition/cystinosis,C2931187,T047,Disorders
How many people are affected by cystinosis ?,0000263-2,frequency,"Cystinosis affects approximately 1 in 100,000 to 200,000 newborns worldwide. The incidence is higher in the province of Brittany, France, where the disorder affects 1 in 26,000 individuals.",cystinosis,0000263,GHR,https://ghr.nlm.nih.gov/condition/cystinosis,C2931187,T047,Disorders
What are the genetic changes related to cystinosis ?,0000263-3,genetic changes,"All three types of cystinosis are caused by mutations in the CTNS gene. Mutations in this gene lead to a deficiency of a transporter protein called cystinosin. Within cells, this protein normally moves cystine out of the lysosomes, which are compartments in the cell that digest and recycle materials. When cystinosin is defective or missing, cystine accumulates and forms crystals in the lysosomes. The buildup of cystine damages cells in the kidneys and eyes and may also affect other organs.",cystinosis,0000263,GHR,https://ghr.nlm.nih.gov/condition/cystinosis,C2931187,T047,Disorders
Is cystinosis inherited ?,0000263-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",cystinosis,0000263,GHR,https://ghr.nlm.nih.gov/condition/cystinosis,C2931187,T047,Disorders
What are the treatments for cystinosis ?,0000263-5,treatment,"These resources address the diagnosis or management of cystinosis:  - Cystinosis Research Foundation: Treatment  - Cystinosis Research Network: Symptoms and Treatment  - Gene Review: Gene Review: Cystinosis  - Genetic Testing Registry: Cystinosis  - Genetic Testing Registry: Cystinosis, ocular nonnephropathic  - Genetic Testing Registry: Juvenile nephropathic cystinosis  - MedlinePlus Encyclopedia: Fanconi Syndrome  - MedlinePlus Encyclopedia: Photophobia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",cystinosis,0000263,GHR,https://ghr.nlm.nih.gov/condition/cystinosis,C2931187,T047,Disorders
What is (are) cystinuria ?,0000264-1,information,"Cystinuria is a condition characterized by the buildup of the amino acid cystine, a building block of most proteins, in the kidneys and bladder. As the kidneys filter blood to create urine, cystine is normally absorbed back into the bloodstream. People with cystinuria cannot properly reabsorb cystine into their bloodstream, so the amino acid accumulates in their urine.  As urine becomes more concentrated in the kidneys, the excess cystine forms crystals. Larger crystals become stones that may lodge in the kidneys or in the bladder. Sometimes cystine crystals combine with calcium molecules in the kidneys to form large stones. These crystals and stones can create blockages in the urinary tract and reduce the ability of the kidneys to eliminate waste through urine. The stones also provide sites where bacteria may cause infections.",cystinuria,0000264,GHR,https://ghr.nlm.nih.gov/condition/cystinuria,C0010691,T047,Disorders
How many people are affected by cystinuria ?,0000264-2,frequency,"Cystinuria affects approximately 1 in 10,000 people.",cystinuria,0000264,GHR,https://ghr.nlm.nih.gov/condition/cystinuria,C0010691,T047,Disorders
What are the genetic changes related to cystinuria ?,0000264-3,genetic changes,"Mutations in the SLC3A1 or SLC7A9 gene cause cystinuria. The SLC3A1 and SLC7A9 genes provide instructions for making the two parts (subunits) of a protein complex that is primarily found in the kidneys. Normally this protein complex controls the reabsorption of certain amino acids, including cystine, into the blood from the filtered fluid that will become urine. Mutations in either the SLC3A1 gene or SLC7A9 gene disrupt the ability of the protein complex to reabsorb amino acids, which causes the amino acids to become concentrated in the urine. As the levels of cystine in the urine increase, the crystals typical of cystinuria form. The other amino acids that are reabsorbed by the protein complex do not create crystals when they accumulate in the urine.",cystinuria,0000264,GHR,https://ghr.nlm.nih.gov/condition/cystinuria,C0010691,T047,Disorders
Is cystinuria inherited ?,0000264-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",cystinuria,0000264,GHR,https://ghr.nlm.nih.gov/condition/cystinuria,C0010691,T047,Disorders
What are the treatments for cystinuria ?,0000264-5,treatment,These resources address the diagnosis or management of cystinuria:  - Genetic Testing Registry: Cystinuria  - MedlinePlus Encyclopedia: Cystinuria  - MedlinePlus Encyclopedia: Cystinuria (image)   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,cystinuria,0000264,GHR,https://ghr.nlm.nih.gov/condition/cystinuria,C0010691,T047,Disorders
What is (are) cytochrome c oxidase deficiency ?,0000265-1,information,"Cytochrome c oxidase deficiency is a genetic condition that can affect several parts of the body, including the muscles used for movement (skeletal muscles), the heart, the brain, or the liver. Signs and symptoms of cytochrome c oxidase deficiency usually begin before age 2 but can appear later in mildly affected individuals.  The severity of cytochrome c oxidase deficiency varies widely among affected individuals, even among those in the same family. People who are mildly affected tend to have muscle weakness (myopathy) and poor muscle tone (hypotonia) with no other health problems. More severely affected people have myopathy along with severe brain dysfunction (encephalomyopathy). Approximately one quarter of individuals with cytochrome c oxidase deficiency have a type of heart disease that enlarges and weakens the heart muscle (hypertrophic cardiomyopathy). Another possible feature of this condition is an enlarged liver, which may lead to liver failure. Most individuals with cytochrome c oxidase deficiency have a buildup of a chemical called lactic acid in the body (lactic acidosis), which can cause nausea and an irregular heart rate, and can be life-threatening.  Many people with cytochrome c oxidase deficiency have a specific group of features known as Leigh syndrome. The signs and symptoms of Leigh syndrome include loss of mental function, movement problems, hypertrophic cardiomyopathy, eating difficulties, and brain abnormalities. Cytochrome c oxidase deficiency is one of the many causes of Leigh syndrome.  Cytochrome c oxidase deficiency is frequently fatal in childhood, although some individuals with mild signs and symptoms survive into adolescence or adulthood.",cytochrome c oxidase deficiency,0000265,GHR,https://ghr.nlm.nih.gov/condition/cytochrome-c-oxidase-deficiency,C0268237,T019,Disorders
How many people are affected by cytochrome c oxidase deficiency ?,0000265-2,frequency,"In Eastern Europe, cytochrome c oxidase deficiency is estimated to occur in 1 in 35,000 individuals. The prevalence of this condition outside this region is unknown.",cytochrome c oxidase deficiency,0000265,GHR,https://ghr.nlm.nih.gov/condition/cytochrome-c-oxidase-deficiency,C0268237,T019,Disorders
What are the genetic changes related to cytochrome c oxidase deficiency ?,0000265-3,genetic changes,"Cytochrome c oxidase deficiency is caused by mutations in one of at least 14 genes. In humans, most genes are found in DNA in the cell's nucleus (nuclear DNA). However, some genes are found in DNA in specialized structures in the cell called mitochondria. This type of DNA is known as mitochondrial DNA (mtDNA). Most cases of cytochrome c oxidase deficiency are caused by mutations in genes found within nuclear DNA; however, in some rare instances, mutations in genes located within mtDNA cause this condition.  The genes associated with cytochrome c oxidase deficiency are involved in energy production in mitochondria through a process called oxidative phosphorylation. The gene mutations that cause cytochrome c oxidase deficiency affect an enzyme complex called cytochrome c oxidase, which is responsible for one of the final steps in oxidative phosphorylation. Cytochrome c oxidase is made up of two large enzyme complexes called holoenzymes, which are each composed of multiple protein subunits. Three of these subunits are produced from mitochondrial genes; the rest are produced from nuclear genes. Many other proteins, all produced from nuclear genes, are involved in assembling these subunits into holoenzymes.  Most mutations that cause cytochrome c oxidase alter proteins that assemble the holoenzymes. As a result, the holoenzymes are either partially assembled or not assembled at all. Without complete holoenzymes, cytochrome c oxidase cannot form. Mutations in the three mitochondrial genes and a few nuclear genes that provide instructions for making the holoenzyme subunits can also cause cytochrome c oxidase deficiency. Altered subunit proteins reduce the function of the holoenzymes, resulting in a nonfunctional version of cytochrome c oxidase. A lack of functional cytochrome c oxidase disrupts the last step of oxidative phosphorylation, causing a decrease in energy production.  Researchers believe that impaired oxidative phosphorylation can lead to cell death by reducing the amount of energy available in the cell. Certain tissues that require large amounts of energy, such as the brain, muscles, and heart, seem especially sensitive to decreases in cellular energy. Cell death in other sensitive tissues may also contribute to the features of cytochrome c oxidase deficiency.",cytochrome c oxidase deficiency,0000265,GHR,https://ghr.nlm.nih.gov/condition/cytochrome-c-oxidase-deficiency,C0268237,T019,Disorders
Is cytochrome c oxidase deficiency inherited ?,0000265-4,inheritance,"Cytochrome c oxidase deficiency can have different inheritance patterns depending on the gene involved.  When this condition is caused by mutations in genes within nuclear DNA, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  When this condition is caused by mutations in genes within mtDNA, it is inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mtDNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children.",cytochrome c oxidase deficiency,0000265,GHR,https://ghr.nlm.nih.gov/condition/cytochrome-c-oxidase-deficiency,C0268237,T019,Disorders
What are the treatments for cytochrome c oxidase deficiency ?,0000265-5,treatment,"These resources address the diagnosis or management of cytochrome c oxidase deficiency:  - Cincinnati Children's Hospital: Acute Liver Failure  - Cincinnati Children's Hospital: Cardiomyopathies  - Genetic Testing Registry: Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency  - Genetic Testing Registry: Cytochrome-c oxidase deficiency  - The United Mitochondrial Disease Foundation: Treatments and Therapies   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",cytochrome c oxidase deficiency,0000265,GHR,https://ghr.nlm.nih.gov/condition/cytochrome-c-oxidase-deficiency,C0268237,T019,Disorders
What is (are) cytochrome P450 oxidoreductase deficiency ?,0000266-1,information,"Cytochrome P450 oxidoreductase deficiency is a disorder of hormone production. This condition specifically affects steroid hormones, which are needed for normal development and reproduction. The hormonal changes associated with cytochrome P450 oxidoreductase deficiency can affect the development of the reproductive system, skeleton, and other parts of the body. These signs and symptoms are usually present at birth or become apparent in early childhood.  The signs and symptoms of cytochrome P450 oxidoreductase deficiency vary from mild to severe. Signs and symptoms of mild cases can include a failure to begin menstruation by age 16 (primary amenorrhea), an inability to have biological children (infertility) in both men and women, and a condition called polycystic ovarian syndrome (PCOS). PCOS is characterized by a hormonal imbalance in women that can lead to irregular menstruation, acne, excess body hair (hirsutism), and weight gain.  People with moderate cases of cytochrome P450 oxidoreductase deficiency may have external genitalia that do not look clearly male or female (ambiguous genitalia), and they may have infertility. People with moderate cytochrome P450 oxidoreductase deficiency usually do not have skeletal abnormalities.  The severe form of cytochrome P450 oxidoreductase deficiency is sometimes called Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis. Hormonal changes in affected males and females lead to the development of ambiguous genitalia or other genital abnormalities, as well as infertility. Severe cases are also characterized by skeletal abnormalities, particularly involving bones of the head and face. These include premature fusion of the skull bones (craniosynostosis), a flattened mid-face, a prominent forehead, and low-set ears. Other skeletal abnormalities can include joint deformities (contractures) that limit movement; unusually long, slender fingers (arachnodactyly); bowing of the thigh bones; and radiohumeral synostosis, which is a bone abnormality that locks the elbows in a bent position. A blockage of the nasal passages (choanal atresia), intellectual disability, and delayed development are also associated with the severe form of the disorder.  Some women who are pregnant with fetuses affected by cytochrome P450 oxidoreductase deficiency experience mild symptoms of the disorder even though they themselves do not have the disorder. They may develop excessive body hair growth (hirsutism), acne, and a deep voice. These changes go away soon after delivery.",cytochrome P450 oxidoreductase deficiency,0000266,GHR,https://ghr.nlm.nih.gov/condition/cytochrome-p450-oxidoreductase-deficiency,C1860042,T047,Disorders
How many people are affected by cytochrome P450 oxidoreductase deficiency ?,0000266-2,frequency,"The prevalence of cytochrome P450 oxidoreductase deficiency is unknown. About 65 cases have been reported worldwide.  Researchers suspect that cytochrome P450 oxidoreductase deficiency is underdiagnosed and that mild cases of this disorder may be relatively common. Because the signs and symptoms can be difficult to detect, people with mild cytochrome P450 oxidoreductase deficiency may never come to medical attention.",cytochrome P450 oxidoreductase deficiency,0000266,GHR,https://ghr.nlm.nih.gov/condition/cytochrome-p450-oxidoreductase-deficiency,C1860042,T047,Disorders
What are the genetic changes related to cytochrome P450 oxidoreductase deficiency ?,0000266-3,genetic changes,"Cytochrome P450 oxidoreductase deficiency is caused by mutations in the POR gene. This gene provides instructions for making the enzyme cytochrome P450 oxidoreductase, which plays a critical role in the formation of steroid hormones. This group of hormones includes testosterone and estrogen, which are essential for normal sexual development and reproduction; corticosteroids, which are involved in the body's response to stress; and aldosterone, which helps regulate the body's salt and water balance.  Mutations in the POR gene reduce the activity of cytochrome P450 oxidoreductase, which disrupts the production of steroid hormones. Changes in sex hormones such as testosterone and estrogen lead to problems with sexual development before birth and at puberty. In a woman who is pregnant with an affected fetus, abnormal levels of sex hormones in the fetus may cause her to have mild, temporary signs and symptoms of cytochrome P450 oxidoreductase deficiency.  Cytochrome P450 oxidoreductase is also needed for the production of cholesterol. This substance has many essential functions both before and after birth, including roles in the production of steroid hormones and in the formation and growth of bones. Mutations in the POR gene can disrupt the production of cholesterol, which likely impairs normal bone formation in the severe form of cytochrome P450 oxidoreductase deficiency. Studies suggest that a molecule called retinoic acid also plays a role in the skeletal abnormalities found in severe cases. The breakdown of retinoic acid requires cytochrome P450 oxidoreductase; if a shortage of cytochrome P450 oxidoreductase prevents retinoic acid from being broken down, the resulting excess of that molecule can stimulate the abnormal growth and fusion of bones.  The skeletal abnormalities found in the severe form of this disorder can also result from mutations in another gene, FGFR2. Some researchers use the name Antley-Bixler syndrome to describe these features, whether they are caused by mutations in the POR gene or in the FGFR2 gene. Others use the name Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis for cases caused by POR gene mutations, reserving the name Antley-Bixler syndrome for cases caused by FGFR2 gene mutations.",cytochrome P450 oxidoreductase deficiency,0000266,GHR,https://ghr.nlm.nih.gov/condition/cytochrome-p450-oxidoreductase-deficiency,C1860042,T047,Disorders
Is cytochrome P450 oxidoreductase deficiency inherited ?,0000266-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",cytochrome P450 oxidoreductase deficiency,0000266,GHR,https://ghr.nlm.nih.gov/condition/cytochrome-p450-oxidoreductase-deficiency,C1860042,T047,Disorders
What are the treatments for cytochrome P450 oxidoreductase deficiency ?,0000266-5,treatment,These resources address the diagnosis or management of cytochrome P450 oxidoreductase deficiency:  - Gene Review: Gene Review: Cytochrome P450 Oxidoreductase Deficiency  - Genetic Testing Registry: Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis  - MedlinePlus Encyclopedia: Ambiguous Genitalia  - MedlinePlus Encyclopedia: Craniosynostosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,cytochrome P450 oxidoreductase deficiency,0000266,GHR,https://ghr.nlm.nih.gov/condition/cytochrome-p450-oxidoreductase-deficiency,C1860042,T047,Disorders
What is (are) cytogenetically normal acute myeloid leukemia ?,0000267-1,information,"Cytogenetically normal acute myeloid leukemia (CN-AML) is one form of a cancer of the blood-forming tissue (bone marrow) called acute myeloid leukemia. In normal bone marrow, early blood cells called hematopoietic stem cells develop into several types of blood cells: white blood cells (leukocytes) that protect the body from infection, red blood cells (erythrocytes) that carry oxygen, and platelets (thrombocytes) that are involved in blood clotting. In acute myeloid leukemia, the bone marrow makes large numbers of abnormal, immature white blood cells called myeloid blasts. Instead of developing into normal white blood cells, the myeloid blasts develop into cancerous leukemia cells. The large number of abnormal cells in the bone marrow interferes with the production of functional white blood cells, red blood cells, and platelets.  People with CN-AML have a shortage of all types of mature blood cells: a shortage of white blood cells (leukopenia) leads to increased susceptibility to infections, a low number of red blood cells (anemia) causes fatigue and weakness, and a reduction in the amount of platelets (thrombocytopenia) can result in easy bruising and abnormal bleeding. Other symptoms of CN-AML may include fever and weight loss.  The age at which CN-AML begins ranges from childhood to late adulthood. CN-AML is said to be an intermediate-risk cancer because the prognosis varies: some affected individuals respond well to normal treatment while others may require stronger treatments. The age at which the condition begins and the prognosis are affected by the specific genetic factors involved in the condition.",cytogenetically normal acute myeloid leukemia,0000267,GHR,https://ghr.nlm.nih.gov/condition/cytogenetically-normal-acute-myeloid-leukemia,C3839868,T191,Disorders
How many people are affected by cytogenetically normal acute myeloid leukemia ?,0000267-2,frequency,"Acute myeloid leukemia occurs in approximately 3.5 per 100,000 individuals each year. Forty to 50 percent of people with acute myeloid leukemia have CN-AML.",cytogenetically normal acute myeloid leukemia,0000267,GHR,https://ghr.nlm.nih.gov/condition/cytogenetically-normal-acute-myeloid-leukemia,C3839868,T191,Disorders
What are the genetic changes related to cytogenetically normal acute myeloid leukemia ?,0000267-3,genetic changes,"CN-AML is classified as ""cytogenetically normal"" based on the type of genetic changes involved in its development. Cytogenetically normal refers to the fact that this form of acute myeloid leukemia is not associated with large chromosomal abnormalities. About half of people with acute myeloid leukemia have this form of the condition; the other half have genetic changes that alter large regions of certain chromosomes. These changes can be identified by a test known as cytogenetic analysis. CN-AML is associated with smaller genetic changes that cannot be seen by cytogenetic analysis.  Mutations in a large number of genes have been found in people with CN-AML; the most commonly affected genes are NPM1, FLT3, DNMT3A, CEBPA, IDH1, and IDH2. The proteins produced from these genes have different functions in the cell. Most are involved in regulating processes such as the growth and division (proliferation), maturation (differentiation), or survival of cells. For example, the protein produced from the FLT3 gene stimulates the proliferation and survival of cells. The proteins produced from the CEBPA and DNMT3A genes regulate gene activity and help to control when cells divide and how they mature. The NPM1 gene provides instructions for a protein that is likely involved in the regulation of cell growth and division. Mutations in any of these genes can disrupt one or more of these processes in hematopoietic stem cells and lead to overproduction of abnormal, immature white blood cells, which is characteristic of CN-AML. Although the proteins produced from two other genes involved in CN-AML, IDH1 and IDH2, are not normally involved in proliferation, differentiation, or survival of cells, mutations in these genes lead to the production of proteins with a new function. These changes result in impaired differentiation of hematopoietic stem cells, which leads to CN-AML.  CN-AML is a complex condition influenced by several genetic and environmental factors. Typically, mutations in more than one gene are involved. For example, people with an NPM1 gene mutation frequently also have a mutation in the FLT3 gene, both of which are likely involved in the cancer's development. In addition, environmental factors such as smoking or exposure to radiation increase an individual's risk of developing acute myeloid leukemia.",cytogenetically normal acute myeloid leukemia,0000267,GHR,https://ghr.nlm.nih.gov/condition/cytogenetically-normal-acute-myeloid-leukemia,C3839868,T191,Disorders
Is cytogenetically normal acute myeloid leukemia inherited ?,0000267-4,inheritance,"CN-AML is not usually inherited but arises from genetic changes in the body's cells that occur after conception. Rarely, an inherited mutation in the CEBPA gene causes acute myeloid leukemia. In these cases, the condition follows an autosomal dominant pattern of inheritance, which means that one copy of the altered CEBPA gene in each cell is sufficient to cause the disorder. These cases of CN-AML are referred to as familial acute myeloid leukemia with mutated CEBPA.",cytogenetically normal acute myeloid leukemia,0000267,GHR,https://ghr.nlm.nih.gov/condition/cytogenetically-normal-acute-myeloid-leukemia,C3839868,T191,Disorders
What are the treatments for cytogenetically normal acute myeloid leukemia ?,0000267-5,treatment,These resources address the diagnosis or management of cytogenetically normal acute myeloid leukemia:  - Fred Hutchinson Cancer Research Center  - National Cancer Institute: Acute Myeloid Leukemia Treatment  - St. Jude Children's Research Hospital   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,cytogenetically normal acute myeloid leukemia,0000267,GHR,https://ghr.nlm.nih.gov/condition/cytogenetically-normal-acute-myeloid-leukemia,C3839868,T191,Disorders
What is (are) Czech dysplasia ?,0000268-1,information,"Czech dysplasia is an inherited condition that affects joint function and bone development. People with this condition have joint pain (osteoarthritis) that begins in adolescence or early adulthood. The joint pain mainly affects the hips, knees, shoulders, and spine and may impair mobility. People with Czech dysplasia often have shortened bones in their third and fourth toes, which make their first two toes appear unusually long. Affected individuals may have flattened bones of the spine (platyspondyly) or an abnormal spinal curvature, such as a rounded upper back that also curves to the side (kyphoscoliosis). Some people with Czech dysplasia have progressive hearing loss.",Czech dysplasia,0000268,GHR,https://ghr.nlm.nih.gov/condition/czech-dysplasia,C1836683,T047,Disorders
How many people are affected by Czech dysplasia ?,0000268-2,frequency,The prevalence of Czech dysplasia is unknown; at least 11 families have been affected. Most of these families reside in the Czech Republic.,Czech dysplasia,0000268,GHR,https://ghr.nlm.nih.gov/condition/czech-dysplasia,C1836683,T047,Disorders
What are the genetic changes related to Czech dysplasia ?,0000268-3,genetic changes,"Czech dysplasia is caused by a particular mutation in the COL2A1 gene. The COL2A1 gene provides instructions for making a protein that forms type II collagen. This type of collagen is found mostly in the clear gel that fills the eyeball (the vitreous) and in cartilage. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Type II collagen is essential for the normal development of bones and other connective tissues that form the body's supportive framework. Mutations in the COL2A1 gene interfere with the assembly of type II collagen molecules, which prevents bones and other connective tissues from developing properly.",Czech dysplasia,0000268,GHR,https://ghr.nlm.nih.gov/condition/czech-dysplasia,C1836683,T047,Disorders
Is Czech dysplasia inherited ?,0000268-4,inheritance,"Czech dysplasia is inherited in an autosomal dominant pattern, which means one copy of the altered COL2A1 gene in each cell is sufficient to cause the disorder.  All known individuals with Czech dysplasia inherited the mutation from a parent with the condition.",Czech dysplasia,0000268,GHR,https://ghr.nlm.nih.gov/condition/czech-dysplasia,C1836683,T047,Disorders
What are the treatments for Czech dysplasia ?,0000268-5,treatment,These resources address the diagnosis or management of Czech dysplasia:  - Genetic Testing Registry: Czech dysplasia metatarsal type   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Czech dysplasia,0000268,GHR,https://ghr.nlm.nih.gov/condition/czech-dysplasia,C1836683,T047,Disorders
What is (are) D-bifunctional protein deficiency ?,0000269-1,information,"D-bifunctional protein deficiency is a disorder that causes deterioration of nervous system functions (neurodegeneration) beginning in infancy. Newborns with D-bifunctional protein deficiency have weak muscle tone (hypotonia) and seizures. Most babies with this condition never acquire any developmental skills. Some may reach very early developmental milestones such as the ability to follow movement with their eyes or control their head movement, but they experience a gradual loss of these skills (developmental regression) within a few months. As the condition gets worse, affected children develop exaggerated reflexes (hyperreflexia), increased muscle tone (hypertonia), more severe and recurrent seizures (epilepsy), and loss of vision and hearing. Most children with D-bifunctional protein deficiency do not survive past the age of 2. A small number of individuals with this disorder are somewhat less severely affected. They may acquire additional basic skills, such as voluntary hand movements or unsupported sitting, before experiencing developmental regression, and they may survive longer into childhood than more severely affected individuals.  Individuals with D-bifunctional protein deficiency may have unusual facial features, including a high forehead, widely spaced eyes (hypertelorism), a lengthened area between the nose and mouth (philtrum), and a high arch of the hard palate at the roof of the mouth. Affected infants may also have an unusually large space between the bones of the skull (fontanel). An enlarged liver (hepatomegaly) occurs in about half of affected individuals. Because these features are similar to those of another disorder called Zellweger syndrome (part of a group of disorders called the Zellweger spectrum), D-bifunctional protein deficiency is sometimes called pseudo-Zellweger syndrome.",D-bifunctional protein deficiency,0000269,GHR,https://ghr.nlm.nih.gov/condition/d-bifunctional-protein-deficiency,C0342870,T046,Disorders
How many people are affected by D-bifunctional protein deficiency ?,0000269-2,frequency,"D-bifunctional protein deficiency is estimated to affect 1 in 100,000 newborns.",D-bifunctional protein deficiency,0000269,GHR,https://ghr.nlm.nih.gov/condition/d-bifunctional-protein-deficiency,C0342870,T046,Disorders
What are the genetic changes related to D-bifunctional protein deficiency ?,0000269-3,genetic changes,"D-bifunctional protein deficiency is caused by mutations in the HSD17B4 gene. The protein produced from this gene (D-bifunctional protein) is an enzyme, which means that it helps specific biochemical reactions to take place. The D-bifunctional protein is found in sac-like cell structures (organelles) called peroxisomes, which contain a variety of enzymes that break down many different substances. The D-bifunctional protein is involved in the breakdown of certain molecules called fatty acids. The protein has two separate regions (domains) with enzyme activity, called the hydratase and dehydrogenase domains. These domains help carry out the second and third steps, respectively, of a process called the peroxisomal fatty acid beta-oxidation pathway. This process shortens the fatty acid molecules by two carbon atoms at a time until the fatty acids are converted to a molecule called acetyl-CoA, which is transported out of the peroxisomes for reuse by the cell.  HSD17B4 gene mutations that cause D-bifunctional protein deficiency can affect one or both of the protein's functions; however, this distinction does not seem to affect the severity or features of the disorder. Impairment of one or both of the protein's enzymatic activities prevents the D-bifunctional protein from breaking down fatty acids efficiently. As a result, these fatty acids accumulate in the body. It is unclear how fatty acid accumulation leads to the specific neurological and non-neurological features of D-bifunctional protein deficiency. However, the accumulation may result in abnormal development of the brain and the breakdown of myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. Destruction of myelin leads to a loss of myelin-containing tissue (white matter) in the brain and spinal cord; loss of white matter is described as leukodystrophy. Abnormal brain development and leukodystrophy likely underlie the neurological abnormalities that occur in D-bifunctional protein deficiency.",D-bifunctional protein deficiency,0000269,GHR,https://ghr.nlm.nih.gov/condition/d-bifunctional-protein-deficiency,C0342870,T046,Disorders
Is D-bifunctional protein deficiency inherited ?,0000269-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",D-bifunctional protein deficiency,0000269,GHR,https://ghr.nlm.nih.gov/condition/d-bifunctional-protein-deficiency,C0342870,T046,Disorders
What are the treatments for D-bifunctional protein deficiency ?,0000269-5,treatment,These resources address the diagnosis or management of D-bifunctional protein deficiency:  - Gene Review: Gene Review: Leukodystrophy Overview  - Genetic Testing Registry: Bifunctional peroxisomal enzyme deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,D-bifunctional protein deficiency,0000269,GHR,https://ghr.nlm.nih.gov/condition/d-bifunctional-protein-deficiency,C0342870,T046,Disorders
What is (are) Dandy-Walker malformation ?,0000270-1,information,"Dandy-Walker malformation affects brain development, primarily development of the cerebellum, which is the part of the brain that coordinates movement. In individuals with this condition, various parts of the cerebellum develop abnormally, resulting in malformations that can be observed with medical imaging. The central part of the cerebellum (the vermis) is absent or very small and may be abnormally positioned. The right and left sides of the cerebellum may be small as well. In affected individuals, a fluid-filled cavity between the brainstem and the cerebellum (the fourth ventricle) and the part of the skull that contains the cerebellum and the brainstem (the posterior fossa) are abnormally large. These abnormalities often result in problems with movement, coordination, intellect, mood, and other neurological functions.  In the majority of individuals with Dandy-Walker malformation, signs and symptoms caused by abnormal brain development are present at birth or develop within the first year of life. Some children have a buildup of fluid in the brain (hydrocephalus) that may cause increased head size (macrocephaly). Up to half of affected individuals have intellectual disability that ranges from mild to severe, and those with normal intelligence may have learning disabilities. Children with Dandy-Walker malformation often have delayed development, particularly a delay in motor skills such as crawling, walking, and coordinating movements. People with Dandy-Walker malformation may experience muscle stiffness and partial paralysis of the lower limbs (spastic paraplegia), and they may also have seizures. While rare, hearing and vision problems can be features of this condition.  Less commonly, other brain abnormalities have been reported in people with Dandy-Walker malformation. These abnormalities include an underdeveloped or absent tissue connecting the left and right halves of the brain (agenesis of the corpus callosum), a sac-like protrusion of the brain through an opening at the back of the skull (occipital encephalocele), or a failure of some nerve cells (neurons) to migrate to their proper location in the brain during development. These additional brain malformations are associated with more severe signs and symptoms.  Dandy-Walker malformation typically affects only the brain, but problems in other systems can include heart defects, malformations of the urogenital tract, extra fingers or toes (polydactyly) or fused fingers or toes (syndactyly), or abnormal facial features.  In 10 to 20 percent of people with Dandy-Walker malformation, signs and symptoms of the condition do not appear until late childhood or into adulthood. These individuals typically have a different range of features than those affected in infancy, including headaches, an unsteady walking gait, paralysis of facial muscles (facial palsy), increased muscle tone, muscle spasms, and mental and behavioral changes. Rarely, people with Dandy-Walker malformation have no health problems related to the condition.  Problems related to hydrocephalus or complications of its treatment are the most common cause of death in people with Dandy-Walker malformation.",Dandy-Walker malformation,0000270,GHR,https://ghr.nlm.nih.gov/condition/dandy-walker-malformation,C0010964,T047,Disorders
How many people are affected by Dandy-Walker malformation ?,0000270-2,frequency,"Dandy-Walker malformation is estimated to affect 1 in 10,000 to 30,000 newborns.",Dandy-Walker malformation,0000270,GHR,https://ghr.nlm.nih.gov/condition/dandy-walker-malformation,C0010964,T047,Disorders
What are the genetic changes related to Dandy-Walker malformation ?,0000270-3,genetic changes,"Researchers have found mutations in a few genes that are thought to cause Dandy-Walker malformation, but these mutations account for only a small number of cases. Dandy-Walker malformation has also been associated with many chromosomal abnormalities. This condition can be a feature of some conditions in which there is an extra copy of one chromosome in each cell (trisomy). Dandy-Walker malformation most often occurs in people with trisomy 18 (an extra copy of chromosome 18), but can also occur in people with trisomy 13, trisomy 21, or trisomy 9. This condition can also be associated with missing (deletions) or copied (duplications) pieces of certain chromosomes. Dandy-Walker malformation can also be a feature of genetic syndromes that are caused by mutations in specific genes. However, the brain malformations associated with Dandy-Walker malformation often occur as an isolated feature (not associated with other health problems), and in these cases the cause is frequently unknown.  Research suggests that Dandy-Walker malformation could be caused by environmental factors that affect early development before birth. For example, exposure of the fetus to substances that cause birth defects (teratogens) may be involved in the development of this condition. In addition, a mother with diabetes is more likely than a healthy mother to have a child with Dandy-Walker malformation.",Dandy-Walker malformation,0000270,GHR,https://ghr.nlm.nih.gov/condition/dandy-walker-malformation,C0010964,T047,Disorders
Is Dandy-Walker malformation inherited ?,0000270-4,inheritance,"Most cases of Dandy-Walker malformation are sporadic, which means they occur in people with no history of the disorder in their family. A small percentage of cases seem to run in families; however, Dandy-Walker malformation does not have a clear pattern of inheritance. Multiple genetic and environmental factors likely play a part in determining the risk of developing this disorder. First-degree relatives (such as siblings and children) of people with Dandy-Walker malformation have an increased risk of developing the condition compared with people in the general population.  When Dandy-Walker malformation is a feature of a genetic condition, it is inherited in the pattern of that condition.",Dandy-Walker malformation,0000270,GHR,https://ghr.nlm.nih.gov/condition/dandy-walker-malformation,C0010964,T047,Disorders
What are the treatments for Dandy-Walker malformation ?,0000270-5,treatment,These resources address the diagnosis or management of Dandy-Walker malformation:  - Genetic Testing Registry: Dandy-Walker syndrome  - National Hydrocephalus Foundation: Treatment of Hydrocephalus   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Dandy-Walker malformation,0000270,GHR,https://ghr.nlm.nih.gov/condition/dandy-walker-malformation,C0010964,T047,Disorders
What is (are) Danon disease ?,0000271-1,information,"Danon disease is a condition characterized by weakening of the heart muscle (cardiomyopathy); weakening of the muscles used for movement, called skeletal muscles, (myopathy); and intellectual disability. Males with Danon disease usually develop the condition earlier than females and are more severely affected. Signs and symptoms begin in childhood or adolescence in most affected males and in early adulthood in most affected females. Affected males, on average, live to age 19, while affected females live to an average age of 34.  Cardiomyopathy is the most common symptom of Danon disease and occurs in all males with the condition. Most affected men have hypertrophic cardiomyopathy, which is a thickening of the heart muscle that may make it harder for the heart to pump blood. Other affected males have dilated cardiomyopathy, which is a condition that weakens and enlarges the heart, preventing it from pumping blood efficiently. Some affected men with hypertrophic cardiomyopathy later develop dilated cardiomyopathy. Either type of cardiomyopathy can lead to heart failure and premature death. Most women with Danon disease also develop cardiomyopathy; of the women who have this feature, about half have hypertrophic cardiomyopathy, and the other half have dilated cardiomyopathy.  Affected individuals can have other heart-related signs and symptoms, including a sensation of fluttering or pounding in the chest (palpitations), an abnormal heartbeat (arrhythmia), or chest pain. Many affected individuals have abnormalities of the electrical signals that control the heartbeat (conduction abnormalities). People with Danon disease are often affected by a specific conduction abnormality known as cardiac preexcitation. The type of cardiac preexcitation most often seen in people with Danon disease is called the Wolff-Parkinson-White syndrome pattern.  Skeletal myopathy occurs in most men with Danon disease and about half of affected women. The weakness typically occurs in the muscles of the upper arms, shoulders, neck, and upper thighs. Many males with Danon disease have elevated levels of an enzyme called creatine kinase in their blood, which often indicates muscle disease.  Most men with Danon disease, but only a small percentage of affected women, have intellectual disability. If present, the disability is usually mild.  There can be other signs and symptoms of the condition in addition to the three characteristic features. Several affected individuals have had gastrointestinal disease, breathing problems, or visual abnormalities.",Danon disease,0000271,GHR,https://ghr.nlm.nih.gov/condition/danon-disease,C0878677,T047,Disorders
How many people are affected by Danon disease ?,0000271-2,frequency,"Danon disease is a rare condition, but the exact prevalence is unknown.",Danon disease,0000271,GHR,https://ghr.nlm.nih.gov/condition/danon-disease,C0878677,T047,Disorders
What are the genetic changes related to Danon disease ?,0000271-3,genetic changes,"Danon disease is caused by mutations in the LAMP2 gene. The LAMP2 gene provides instructions for making a protein called lysosomal associated membrane protein-2 (LAMP-2), which, as its name suggests, is found in the membrane of cellular structures called lysosomes. Lysosomes are compartments in the cell that digest and recycle materials. The role the LAMP-2 protein plays in the lysosome is unclear. Some researchers think the LAMP-2 protein may help transport cellular materials or digestive enzymes into the lysosome. The transport of cellular materials into lysosomes requires the formation of cellular structures called autophagic vacuoles (or autophagosomes), which then attach (fuse) to lysosomes. The LAMP-2 protein may be involved in the fusion between autophagic vacuoles and lysosomes.  Mutations in the LAMP2 gene lead to the production of very little or no LAMP-2 protein, which may impair the process of transporting cellular material into the lysosome. Some studies have shown that in cells without the LAMP-2 protein, fusion between autophagic vacuoles and lysosomes occurs more slowly, which may lead to the accumulation of autophagic vacuoles. People with Danon disease have an abnormally large number of autophagic vacuoles in their muscle cells. It is possible that this accumulation leads to breakdown of the muscle cells, causing the muscle weakness seen in Danon disease.",Danon disease,0000271,GHR,https://ghr.nlm.nih.gov/condition/danon-disease,C0878677,T047,Disorders
Is Danon disease inherited ?,0000271-4,inheritance,"This condition is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In most cases, males experience more severe symptoms of the disorder than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",Danon disease,0000271,GHR,https://ghr.nlm.nih.gov/condition/danon-disease,C0878677,T047,Disorders
What are the treatments for Danon disease ?,0000271-5,treatment,These resources address the diagnosis or management of Danon disease:  - American Heart Association: Dilated Cardiomyopathy  - Genetic Testing Registry: Danon disease  - KidsHealth from Nemours: Getting an EKG  - Swedish Information Centre for Rare Diseases   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Danon disease,0000271,GHR,https://ghr.nlm.nih.gov/condition/danon-disease,C0878677,T047,Disorders
What is (are) Darier disease ?,0000272-1,information,"Darier disease is a skin condition characterized by wart-like blemishes on the body. The blemishes are usually yellowish in color, hard to the touch, mildly greasy, and can emit a strong odor. The most common sites for blemishes are the scalp, forehead, upper arms, chest, back, knees, elbows, and behind the ear. The mucous membranes can also be affected, with blemishes on the roof of the mouth (palate), tongue, inside of the cheek, gums, and throat. Other features of Darier disease include nail abnormalities, such as red and white streaks in the nails with an irregular texture, and small pits in the palms of the hands and soles of the feet.  The wart-like blemishes characteristic of Darier disease usually appear in late childhood to early adulthood. The severity of the disease varies over time; affected people experience flare-ups alternating with periods when they have fewer blemishes. The appearance of the blemishes is influenced by environmental factors. Most people with Darier disease will develop more blemishes during the summertime when they are exposed to heat and humidity. UV light; minor injury or friction, such as rubbing or scratching; and ingestion of certain medications can also cause an increase in blemishes.  On occasion, people with Darier disease may have neurological disorders such as mild intellectual disability, epilepsy, and depression. Learning and behavior difficulties have also been reported in people with Darier disease. Researchers do not know if these conditions, which are common in the general population, are associated with the genetic changes that cause Darier disease, or if they are coincidental. Some researchers believe that behavioral problems might be linked to the social stigma experienced by people with numerous skin blemishes.  A form of Darier disease known as the linear or segmental form is characterized by blemishes on localized areas of the skin. The blemishes are not as widespread as they are in typical Darier disease. Some people with the linear form of this condition have the nail abnormalities that are seen in people with classic Darier disease, but these abnormalities occur only on one side of the body.",Darier disease,0000272,GHR,https://ghr.nlm.nih.gov/condition/darier-disease,C0022595,T047,Disorders
How many people are affected by Darier disease ?,0000272-2,frequency,"The worldwide prevalence of Darier disease is unknown. The prevalence of Darier disease is estimated to be 1 in 30,000 people in Scotland, 1 in 36,000 people in northern England, and 1 in 100,000 people in Denmark.",Darier disease,0000272,GHR,https://ghr.nlm.nih.gov/condition/darier-disease,C0022595,T047,Disorders
What are the genetic changes related to Darier disease ?,0000272-3,genetic changes,"Mutations in the ATP2A2 gene cause Darier disease. The ATP2A2 gene provides instructions for producing an enzyme abbreviated as SERCA2. This enzyme acts as a pump that helps control the level of positively charged calcium atoms (calcium ions) inside cells, particularly in the endoplasmic reticulum and the sarcoplasmic reticulum. The endoplasmic reticulum is a structure inside the cell that is involved in protein processing and transport. The sarcoplasmic reticulum is a structure in muscle cells that assists with muscle contraction and relaxation by releasing and storing calcium ions. Calcium ions act as signals for a large number of activities that are important for the normal development and function of cells. SERCA2 allows calcium ions to pass into and out of the cell in response to cell signals.  Mutations in the ATP2A2 gene result in insufficient amounts of functional SERCA2 enzyme. A lack of SERCA2 enzyme reduces calcium levels in the endoplasmic reticulum, causing it to become dysfunctional. SERCA2 is expressed throughout the body; it is not clear why changes in this enzyme affect only the skin. Some researchers note that skin cells are the only cell types expressing SERCA2 that do not have a ""back-up"" enzyme for calcium transport. This dependence on the SERCA2 enzyme may make skin cells particularly vulnerable to changes in this enzyme.  The linear form of Darier disease is caused by ATP2A2 gene mutations that are acquired during a person's lifetime and are present only in certain cells. These changes are called somatic mutations and are not inherited. There have been no known cases of people with the linear form of Darier disease passing it on to their children.",Darier disease,0000272,GHR,https://ghr.nlm.nih.gov/condition/darier-disease,C0022595,T047,Disorders
Is Darier disease inherited ?,0000272-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.  The linear form of Darier disease is generally not inherited but arises from mutations in the body's cells that occur after conception. These alterations are called somatic mutations.",Darier disease,0000272,GHR,https://ghr.nlm.nih.gov/condition/darier-disease,C0022595,T047,Disorders
What are the treatments for Darier disease ?,0000272-5,treatment,These resources address the diagnosis or management of Darier disease:  - Genetic Testing Registry: Keratosis follicularis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Darier disease,0000272,GHR,https://ghr.nlm.nih.gov/condition/darier-disease,C0022595,T047,Disorders
What is (are) deafness and myopia syndrome ?,0000273-1,information,"Deafness and myopia syndrome is a disorder that causes problems with both hearing and vision. People with this disorder have moderate to profound hearing loss in both ears that may worsen over time. The hearing loss may be described as sensorineural, meaning that it is related to changes in the inner ear, or it may be caused by auditory neuropathy, which is a problem with the transmission of sound (auditory) signals from the inner ear to the brain. The hearing loss is either present at birth (congenital) or begins in infancy, before the child learns to speak (prelingual).  Affected individuals also have severe nearsightedness (high myopia). These individuals are able to see nearby objects clearly, but objects that are farther away appear blurry. The myopia is usually diagnosed by early childhood.",deafness and myopia syndrome,0000273,GHR,https://ghr.nlm.nih.gov/condition/deafness-and-myopia-syndrome,C0039082,T047,Disorders
How many people are affected by deafness and myopia syndrome ?,0000273-2,frequency,The prevalence of deafness and myopia syndrome is unknown. Only a few affected families have been described in the medical literature.,deafness and myopia syndrome,0000273,GHR,https://ghr.nlm.nih.gov/condition/deafness-and-myopia-syndrome,C0039082,T047,Disorders
What are the genetic changes related to deafness and myopia syndrome ?,0000273-3,genetic changes,"Deafness and myopia syndrome is caused by mutations in the SLITRK6 gene. The protein produced from this gene is found primarily in the inner ear and the eye. This protein promotes growth and survival of nerve cells (neurons) in the inner ear that transmit auditory signals. It also controls (regulates) the growth of the eye after birth. In particular, the SLITRK6 protein influences the length of the eyeball (axial length), which affects whether a person will be nearsighted or farsighted, or will have normal vision. The SLITRK6 protein spans the cell membrane, where it is anchored in the proper position to perform its function.  SLITRK6 gene mutations that cause deafness and myopia syndrome result in an abnormally short SLITRK6 protein that is not anchored properly to the cell membrane. As a result, the protein is unable to function normally. Impaired SLITRK6 protein function leads to abnormal nerve development in the inner ear and improperly controlled eyeball growth, resulting in the hearing loss and nearsightedness that occur in deafness and myopia syndrome.",deafness and myopia syndrome,0000273,GHR,https://ghr.nlm.nih.gov/condition/deafness-and-myopia-syndrome,C0039082,T047,Disorders
Is deafness and myopia syndrome inherited ?,0000273-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",deafness and myopia syndrome,0000273,GHR,https://ghr.nlm.nih.gov/condition/deafness-and-myopia-syndrome,C0039082,T047,Disorders
What are the treatments for deafness and myopia syndrome ?,0000273-5,treatment,These resources address the diagnosis or management of deafness and myopia syndrome:  - Baby's First Test: Hearing Loss  - EyeSmart: Eyeglasses for Vision Correction  - Gene Review: Gene Review: Deafness and Myopia Syndrome  - Harvard Medical School Center for Hereditary Deafness  - KidsHealth: Hearing Evaluation in Children  - MedlinePlus Encyclopedia: Cochlear Implant  - MedlinePlus Health Topic: Cochlear Implants  - MedlinePlus Health Topic: Hearing Aids  - MedlinePlus Health Topic: Newborn Screening   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,deafness and myopia syndrome,0000273,GHR,https://ghr.nlm.nih.gov/condition/deafness-and-myopia-syndrome,C0039082,T047,Disorders
What is (are) deafness-dystonia-optic neuronopathy syndrome ?,0000274-1,information,"Deafness-dystonia-optic neuronopathy (DDON) syndrome, also known as Mohr-Tranebjrg syndrome, is characterized by hearing loss that begins early in life, problems with movement, impaired vision, and behavior problems. This condition occurs almost exclusively in males.  The first symptom of DDON syndrome is hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss), which begins in early childhood. The hearing impairment worsens over time, and most affected individuals have profound hearing loss by age 10.  People with DDON syndrome typically begin to develop problems with movement during their teens, although the onset of these symptoms varies among affected individuals. Some people experience involuntary tensing of the muscles (dystonia), while others have difficulty coordinating movements (ataxia). The problems with movement usually worsen over time.  Individuals with DDON syndrome have normal vision during childhood, but they may begin to develop an increased sensitivity to light (photophobia) or other vision problems during their teens. These people often have a slowly progressive reduction in the sharpness of vision (visual acuity) and become legally blind in mid-adulthood.  People with this condition may also have behavior problems, including changes in personality and aggressive or paranoid behaviors. They also usually develop a gradual decline in thinking and reasoning abilities (dementia) in their forties. The lifespan of individuals with DDON syndrome depends on the severity of the disorder. People with severe cases have survived into their teenage years, while those with milder cases have lived into their sixties.",deafness-dystonia-optic neuronopathy syndrome,0000274,GHR,https://ghr.nlm.nih.gov/condition/deafness-dystonia-optic-neuronopathy-syndrome,C0796074,T047,Disorders
How many people are affected by deafness-dystonia-optic neuronopathy syndrome ?,0000274-2,frequency,DDON syndrome is a rare disorder; it has been reported in fewer than 70 people worldwide.,deafness-dystonia-optic neuronopathy syndrome,0000274,GHR,https://ghr.nlm.nih.gov/condition/deafness-dystonia-optic-neuronopathy-syndrome,C0796074,T047,Disorders
What are the genetic changes related to deafness-dystonia-optic neuronopathy syndrome ?,0000274-3,genetic changes,"Mutations in the TIMM8A gene cause DDON syndrome. The protein produced from this gene is found inside the energy-producing centers of cells (mitochondria). The TIMM8A protein forms a complex (a group of proteins that work together) with a very similar protein called TIMM13. This complex functions by transporting other proteins within the mitochondria.  Most mutations in the TIMM8A gene result in the absence of functional TIMM8A protein inside the mitochondria, which prevents the formation of the TIMM8A/TIMM13 complex. Researchers believe that the lack of this complex leads to abnormal protein transport, although it is unclear how abnormal protein transport affects the function of the mitochondria and causes the signs and symptoms of DDON syndrome.",deafness-dystonia-optic neuronopathy syndrome,0000274,GHR,https://ghr.nlm.nih.gov/condition/deafness-dystonia-optic-neuronopathy-syndrome,C0796074,T047,Disorders
Is deafness-dystonia-optic neuronopathy syndrome inherited ?,0000274-4,inheritance,"DDON syndrome is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause DDON syndrome. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. Females who carry one altered copy of the TIMM8A gene are typically unaffected; however, they may develop mild hearing loss and dystonia. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",deafness-dystonia-optic neuronopathy syndrome,0000274,GHR,https://ghr.nlm.nih.gov/condition/deafness-dystonia-optic-neuronopathy-syndrome,C0796074,T047,Disorders
What are the treatments for deafness-dystonia-optic neuronopathy syndrome ?,0000274-5,treatment,These resources address the diagnosis or management of deafness-dystonia-optic neuronopathy syndrome:  - Gene Review: Gene Review: Deafness-Dystonia-Optic Neuronopathy Syndrome  - Genetic Testing Registry: Mohr-Tranebjaerg syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,deafness-dystonia-optic neuronopathy syndrome,0000274,GHR,https://ghr.nlm.nih.gov/condition/deafness-dystonia-optic-neuronopathy-syndrome,C0796074,T047,Disorders
What is (are) dentatorubral-pallidoluysian atrophy ?,0000276-1,information,"Dentatorubral-pallidoluysian atrophy, commonly known as DRPLA, is a progressive brain disorder that causes involuntary movements, mental and emotional problems, and a decline in thinking ability. The average age of onset of DRPLA is 30 years, but this condition can appear anytime from infancy to mid-adulthood.  The signs and symptoms of DRPLA differ somewhat between affected children and adults. When DRPLA appears before age 20, it most often involves episodes of involuntary muscle jerking or twitching (myoclonus), seizures, behavioral changes, intellectual disability, and problems with balance and coordination (ataxia). When DRPLA begins after age 20, the most frequent signs and symptoms are ataxia, uncontrollable movements of the limbs (choreoathetosis), psychiatric symptoms such as delusions, and deterioration of intellectual function (dementia).",dentatorubral-pallidoluysian atrophy,0000276,GHR,https://ghr.nlm.nih.gov/condition/dentatorubral-pallidoluysian-atrophy,C0751781,T047,Disorders
How many people are affected by dentatorubral-pallidoluysian atrophy ?,0000276-2,frequency,"DRPLA is most common in the Japanese population, where it has an estimated incidence of 2 to 7 per million people. This condition has also been seen in families from North America and Europe.  Although DRPLA is rare in the United States, it has been studied in a large African American family from the Haw River area of North Carolina. When the family was first identified, researchers named the disorder Haw River syndrome. Later, researchers determined that Haw River syndrome and DRPLA are the same condition.",dentatorubral-pallidoluysian atrophy,0000276,GHR,https://ghr.nlm.nih.gov/condition/dentatorubral-pallidoluysian-atrophy,C0751781,T047,Disorders
What are the genetic changes related to dentatorubral-pallidoluysian atrophy ?,0000276-3,genetic changes,"DRPLA is caused by a mutation in the ATN1 gene. This gene provides instructions for making a protein called atrophin 1. Although the function of atrophin 1 is unclear, it likely plays an important role in nerve cells (neurons) in many areas of the brain.  The ATN1 mutation that underlies DRPLA involves a DNA segment known as a CAG trinucleotide repeat. This segment is made up of a series of three DNA building blocks (cytosine, adenine, and guanine) that appear multiple times in a row. Normally, this segment is repeated 6 to 35 times within the ATN1 gene. In people with DRPLA, the CAG segment is repeated at least 48 times, and the repeat region may be two or three times its usual length. The abnormally long CAG trinucleotide repeat changes the structure of atrophin 1. This altered protein accumulates in neurons and interferes with normal cell functions. The dysfunction and eventual death of these neurons lead to uncontrolled movements, intellectual decline, and the other characteristic features of DRPLA.",dentatorubral-pallidoluysian atrophy,0000276,GHR,https://ghr.nlm.nih.gov/condition/dentatorubral-pallidoluysian-atrophy,C0751781,T047,Disorders
Is dentatorubral-pallidoluysian atrophy inherited ?,0000276-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.  As the altered ATN1 gene is passed from one generation to the next, the size of the CAG trinucleotide repeat often increases in size. Larger repeat expansions are usually associated with an earlier onset of the disorder and more severe signs and symptoms. This phenomenon is called anticipation. Anticipation tends to be more prominent when the ATN1 gene is inherited from a person's father (paternal inheritance) than when it is inherited from a person's mother (maternal inheritance).",dentatorubral-pallidoluysian atrophy,0000276,GHR,https://ghr.nlm.nih.gov/condition/dentatorubral-pallidoluysian-atrophy,C0751781,T047,Disorders
What are the treatments for dentatorubral-pallidoluysian atrophy ?,0000276-5,treatment,These resources address the diagnosis or management of DRPLA:  - Gene Review: Gene Review: DRPLA  - Genetic Testing Registry: Dentatorubral pallidoluysian atrophy  - MedlinePlus Encyclopedia: Dementia  - MedlinePlus Encyclopedia: Epilepsy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,dentatorubral-pallidoluysian atrophy,0000276,GHR,https://ghr.nlm.nih.gov/condition/dentatorubral-pallidoluysian-atrophy,C0751781,T047,Disorders
What is (are) dentinogenesis imperfecta ?,0000277-1,information,"Dentinogenesis imperfecta is a disorder of tooth development. This condition causes the teeth to be discolored (most often a blue-gray or yellow-brown color) and translucent. Teeth are also weaker than normal, making them prone to rapid wear, breakage, and loss. These problems can affect both primary (baby) teeth and permanent teeth.  Researchers have described three types of dentinogenesis imperfecta with similar dental abnormalities. Type I occurs in people who have osteogenesis imperfecta, a genetic condition in which bones are brittle and easily broken. Dentinogenesis imperfecta type II and type III usually occur in people without other inherited disorders. A few older individuals with type II have had progressive high-frequency hearing loss in addition to dental abnormalities, but it is not known whether this hearing loss is related to dentinogenesis imperfecta.  Some researchers believe that dentinogenesis imperfecta type II and type III, along with a condition called dentin dysplasia type II, are actually forms of a single disorder. The signs and symptoms of dentin dysplasia type II are very similar to those of dentinogenesis imperfecta. However, dentin dysplasia type II affects the primary teeth much more than the permanent teeth.",dentinogenesis imperfecta,0000277,GHR,https://ghr.nlm.nih.gov/condition/dentinogenesis-imperfecta,C0011436,T019,Disorders
How many people are affected by dentinogenesis imperfecta ?,0000277-2,frequency,"Dentinogenesis imperfecta affects an estimated 1 in 6,000 to 8,000 people.",dentinogenesis imperfecta,0000277,GHR,https://ghr.nlm.nih.gov/condition/dentinogenesis-imperfecta,C0011436,T019,Disorders
What are the genetic changes related to dentinogenesis imperfecta ?,0000277-3,genetic changes,"Mutations in the DSPP gene have been identified in people with dentinogenesis imperfecta type II and type III. Mutations in this gene are also responsible for dentin dysplasia type II. Dentinogenesis imperfecta type I occurs as part of osteogenesis imperfecta, which is caused by mutations in one of several other genes (most often the COL1A1 or COL1A2 genes).  The DSPP gene provides instructions for making two proteins that are essential for normal tooth development. These proteins are involved in the formation of dentin, which is a bone-like substance that makes up the protective middle layer of each tooth. DSPP gene mutations alter the proteins made from the gene, leading to the production of abnormally soft dentin. Teeth with defective dentin are discolored, weak, and more likely to decay and break. It is unclear whether DSPP gene mutations are related to the hearing loss found in a few older individuals with dentinogenesis imperfecta type II.",dentinogenesis imperfecta,0000277,GHR,https://ghr.nlm.nih.gov/condition/dentinogenesis-imperfecta,C0011436,T019,Disorders
Is dentinogenesis imperfecta inherited ?,0000277-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In most cases, an affected person has one parent with the condition.",dentinogenesis imperfecta,0000277,GHR,https://ghr.nlm.nih.gov/condition/dentinogenesis-imperfecta,C0011436,T019,Disorders
What are the treatments for dentinogenesis imperfecta ?,0000277-5,treatment,These resources address the diagnosis or management of dentinogenesis imperfecta:  - Genetic Testing Registry: Dentinogenesis imperfecta - Shield's type II  - Genetic Testing Registry: Dentinogenesis imperfecta - Shield's type III  - MedlinePlus Encyclopedia: Tooth - abnormal colors   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,dentinogenesis imperfecta,0000277,GHR,https://ghr.nlm.nih.gov/condition/dentinogenesis-imperfecta,C0011436,T019,Disorders
What is (are) Denys-Drash syndrome ?,0000278-1,information,"Denys-Drash syndrome is a condition that affects the kidneys and genitalia.  Denys-Drash syndrome is characterized by kidney disease that begins within the first few months of life. Affected individuals have a condition called diffuse glomerulosclerosis, in which scar tissue forms throughout glomeruli, which are the tiny blood vessels in the kidneys that filter waste from blood. In people with Denys-Drash syndrome, this condition often leads to kidney failure in childhood. People with Denys-Drash syndrome have an estimated 90 percent chance of developing a rare form of kidney cancer known as Wilms tumor. Affected individuals may develop multiple tumors in one or both kidneys.  Although males with Denys-Drash syndrome have the typical male chromosome pattern (46,XY), they have gonadal dysgenesis, in which external genitalia do not look clearly male or clearly female (ambiguous genitalia) or the genitalia appear completely female. The testes of affected males are undescended, which means they are abnormally located in the pelvis, abdomen, or groin. As a result, males with Denys-Drash are typically unable to have biological children (infertile).  Affected females usually have normal genitalia and have only the kidney features of the condition. Because they do not have all the features of the condition, females are usually given the diagnosis of isolated nephrotic syndrome.",Denys-Drash syndrome,0000278,GHR,https://ghr.nlm.nih.gov/condition/denys-drash-syndrome,C0950121,T047,Disorders
How many people are affected by Denys-Drash syndrome ?,0000278-2,frequency,The prevalence of Denys-Drash syndrome is unknown; at least 150 affected individuals have been reported in the scientific literature.,Denys-Drash syndrome,0000278,GHR,https://ghr.nlm.nih.gov/condition/denys-drash-syndrome,C0950121,T047,Disorders
What are the genetic changes related to Denys-Drash syndrome ?,0000278-3,genetic changes,"Mutations in the WT1 gene cause Denys-Drash syndrome. The WT1 gene provides instructions for making a protein that regulates the activity of other genes by attaching (binding) to specific regions of DNA. On the basis of this action, the WT1 protein is called a transcription factor. The WT1 protein plays a role in the development of the kidneys and kidneys and gonads (ovaries in females and testes in males) before birth.  WT1 gene mutations that cause Denys-Drash syndrome lead to the production of an abnormal protein that cannot bind to DNA. As a result, the activity of certain genes is unregulated, which impairs the development of the kidneys and reproductive organs. Abnormal development of these organs leads to diffuse glomerulosclerosis and gonadal dysgenesis, which are characteristic of Denys-Drash syndrome. Abnormal gene activity caused by the loss of normal WT1 protein increases the risk of developing Wilms tumor in affected individuals.  Denys-Drash syndrome has features similar to another condition called Frasier syndrome, which is also caused by mutations in the WT1 gene. Because these two conditions share a genetic cause and have overlapping features, some researchers have suggested that they are part of a spectrum and not two distinct conditions.",Denys-Drash syndrome,0000278,GHR,https://ghr.nlm.nih.gov/condition/denys-drash-syndrome,C0950121,T047,Disorders
Is Denys-Drash syndrome inherited ?,0000278-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Denys-Drash syndrome,0000278,GHR,https://ghr.nlm.nih.gov/condition/denys-drash-syndrome,C0950121,T047,Disorders
What are the treatments for Denys-Drash syndrome ?,0000278-5,treatment,These resources address the diagnosis or management of Denys-Drash syndrome:  - Gene Review: Gene Review: Wilms Tumor Overview  - Genetic Testing Registry: Drash syndrome  - MedlinePlus Encyclopedia: Nephrotic Syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Denys-Drash syndrome,0000278,GHR,https://ghr.nlm.nih.gov/condition/denys-drash-syndrome,C0950121,T047,Disorders
What is (are) deoxyguanosine kinase deficiency ?,0000279-1,information,"Deoxyguanosine kinase deficiency is an inherited disorder that can cause liver disease and neurological problems. Researchers have described two forms of this disorder. The majority of affected individuals have the more severe form, which is called hepatocerebral because of the serious problems it causes in the liver and brain.  Newborns with the hepatocerebral form of deoxyguanosine kinase deficiency may have a buildup of lactic acid in the body (lactic acidosis) within the first few days after birth. They may also have weakness, behavior changes such as poor feeding and decreased activity, and vomiting. Affected newborns sometimes have low blood sugar (hypoglycemia) as a result of liver dysfunction. During the first few weeks of life they begin showing other signs of liver disease which may result in liver failure. They also develop progressive neurological problems including very weak muscle tone (severe hypotonia), abnormal eye movements (nystagmus) and the loss of skills they had previously acquired (developmental regression). Children with this form of the disorder usually do not survive past the age of 2 years.  Some individuals with deoxyguanosine kinase deficiency have a milder form of the disorder without severe neurological problems. Liver disease is the primary symptom of this form of the disorder, generally becoming evident during infancy or childhood. Occasionally it first appears after an illness such as a viral infection. Affected individuals may also develop kidney problems. Mild hypotonia is the only neurological effect associated with this form of the disorder.",deoxyguanosine kinase deficiency,0000279,GHR,https://ghr.nlm.nih.gov/condition/deoxyguanosine-kinase-deficiency,C3711385,T047,Disorders
How many people are affected by deoxyguanosine kinase deficiency ?,0000279-2,frequency,The prevalence of deoxyguanosine kinase deficiency is unknown. Approximately 100 affected individuals have been identified.,deoxyguanosine kinase deficiency,0000279,GHR,https://ghr.nlm.nih.gov/condition/deoxyguanosine-kinase-deficiency,C3711385,T047,Disorders
What are the genetic changes related to deoxyguanosine kinase deficiency ?,0000279-3,genetic changes,"The DGUOK gene provides instructions for making the enzyme deoxyguanosine kinase. This enzyme plays a critical role in mitochondria, which are structures within cells that convert the energy from food into a form that cells can use. Mitochondria each contain a small amount of DNA, known as mitochondrial DNA or mtDNA, which is essential for the normal function of these structures. Deoxyguanosine kinase is involved in producing and maintaining the building blocks of mitochondrial DNA.  Mutations in the DGUOK gene reduce or eliminate the activity of the deoxyguanosine kinase enzyme. Reduced enzyme activity leads to problems with the production and maintenance of mitochondrial DNA. A reduction in the amount of mitochondrial DNA (known as mitochondrial DNA depletion) impairs mitochondrial function in many of the body's cells and tissues. These problems lead to the neurological and liver dysfunction associated with deoxyguanosine kinase deficiency.",deoxyguanosine kinase deficiency,0000279,GHR,https://ghr.nlm.nih.gov/condition/deoxyguanosine-kinase-deficiency,C3711385,T047,Disorders
Is deoxyguanosine kinase deficiency inherited ?,0000279-4,inheritance,"Deoxyguanosine kinase deficiency is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. In most cases, the parents of an individual with this condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",deoxyguanosine kinase deficiency,0000279,GHR,https://ghr.nlm.nih.gov/condition/deoxyguanosine-kinase-deficiency,C3711385,T047,Disorders
What are the treatments for deoxyguanosine kinase deficiency ?,0000279-5,treatment,"These resources address the diagnosis or management of deoxyguanosine kinase deficiency:  - Gene Review: Gene Review: DGUOK-Related Mitochondrial DNA Depletion Syndrome, Hepatocerebral Form  - Genetic Testing Registry: Mitochondrial DNA-depletion syndrome 3, hepatocerebral  - MedlinePlus Encyclopedia: Hypotonia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",deoxyguanosine kinase deficiency,0000279,GHR,https://ghr.nlm.nih.gov/condition/deoxyguanosine-kinase-deficiency,C3711385,T047,Disorders
What is (are) dermatofibrosarcoma protuberans ?,0000280-1,information,"Dermatofibrosarcoma protuberans is a rare type of cancer that causes a tumor in the deep layers of skin. This condition is a type of soft tissue sarcoma, which are cancers that affect skin, fat, muscle, and similar tissues.  In dermatofibrosarcoma protuberans, the tumor most often starts as a small, firm patch of skin, usually 1 to 5 centimeters in diameter, that is usually purplish, reddish, or flesh-colored. The tumor typically grows slowly and can become a raised nodule. Occasionally, the tumor begins as a flat or depressed patch of skin (plaque). Tumors are most commonly found on the torso and can also be found on the arms, legs, head, or neck. Affected individuals usually first show signs of this condition in their thirties, but the age at which a tumor appears varies widely.  In dermatofibrosarcoma protuberans, the tumor has a tendency to return after being removed. However, it does not often spread to other parts of the body (metastasize).  There are several variants of dermatofibrosarcoma protuberans in which different cell types are involved in the tumor. Bednar tumors, often called pigmented dermatofibrosarcoma protuberans, contain dark-colored (pigmented) cells called melanin-containing dendritic cells. Myxoid dermatofibrosarcoma protuberans tumors contain an abnormal type of connective tissue known as myxoid stroma. Giant cell fibroblastoma, which is sometimes referred to as juvenile dermatofibrosarcoma protuberans because it typically affects children and adolescents, is characterized by giant cells in the tumor.  Rarely, the tumors involved in the different types of dermatofibrosarcoma protuberans can have regions that look similar to fibrosarcoma, a more aggressive type of soft tissue sarcoma. In these cases, the condition is called fibrosarcomatous dermatofibrosarcoma protuberans or FS-DFSP. FS-DFSP tumors are more likely to metastasize than tumors in the other types of dermatofibrosarcoma protuberans.",dermatofibrosarcoma protuberans,0000280,GHR,https://ghr.nlm.nih.gov/condition/dermatofibrosarcoma-protuberans,C0392784,T191,Disorders
How many people are affected by dermatofibrosarcoma protuberans ?,0000280-2,frequency,"Dermatofibrosarcoma protuberans is estimated to occur in 1 in 100,000 to 1 in 1 million people per year.",dermatofibrosarcoma protuberans,0000280,GHR,https://ghr.nlm.nih.gov/condition/dermatofibrosarcoma-protuberans,C0392784,T191,Disorders
What are the genetic changes related to dermatofibrosarcoma protuberans ?,0000280-3,genetic changes,"Dermatofibrosarcoma protuberans is associated with a rearrangement (translocation) of genetic material between chromosomes 17 and 22. This translocation, written as t(17;22), fuses part of the COL1A1 gene from chromosome 17 with part of the PDGFB gene from chromosome 22. The translocation is found on one or more extra chromosomes that can be either the normal linear shape or circular. When circular, the extra chromosomes are known as supernumerary ring chromosomes. Ring chromosomes occur when a chromosome breaks in two places and the ends of the chromosome arms fuse together to form a circular structure. Other genes from chromosomes 17 and 22 can be found on the extra chromosomes, but the role these genes play in development of the condition is unclear. The translocation is acquired during a person's lifetime and the chromosomes containing the translocation are present only in the tumor cells. This type of genetic change is called a somatic mutation.  In normal cells, the COL1A1 gene provides instructions for making part of a large molecule called type I collagen, which strengthens and supports many tissues in the body. The PDGFB gene provides instructions for making one version (isoform) of the platelet derived growth factor (PDGF) protein. By attaching to its receptor, the active PDGFB protein stimulates many cellular processes, including cell growth and division (proliferation) and maturation (differentiation).  The abnormally fused COL1A1-PDGFB gene provides instructions for making an abnormal combined (fusion) protein that researchers believe ultimately functions like the PDGFB protein. The gene fusion leads to the production of an excessive amount of protein that functions like the PDGFB protein. In excess, this fusion protein stimulates cells to proliferate and differentiate abnormally, leading to the tumor formation seen in dermatofibrosarcoma protuberans.  The COL1A1-PDGFB fusion gene is found in more than 90 percent of dermatofibrosarcoma protuberans cases. In the remaining cases, changes in other genes may be associated with this condition. These genes have not been identified.",dermatofibrosarcoma protuberans,0000280,GHR,https://ghr.nlm.nih.gov/condition/dermatofibrosarcoma-protuberans,C0392784,T191,Disorders
Is dermatofibrosarcoma protuberans inherited ?,0000280-4,inheritance,Dermatofibrosarcoma protuberans results from a new mutation that occurs in the body's cells after conception and is found only in the tumor cells. This type of genetic change is called a somatic mutation and is generally not inherited.,dermatofibrosarcoma protuberans,0000280,GHR,https://ghr.nlm.nih.gov/condition/dermatofibrosarcoma-protuberans,C0392784,T191,Disorders
What are the treatments for dermatofibrosarcoma protuberans ?,0000280-5,treatment,These resources address the diagnosis or management of dermatofibrosarcoma protuberans:  - American Cancer Society: How are Soft Tissue Sarcomas Diagnosed?  - American Cancer Society: Treatment of Soft Tissue Sarcomas  - Genetic Testing Registry: Dermatofibrosarcoma protuberans  - National Cancer Institute: Adult Soft Tissue Sarcoma  - National Cancer Institute: Targeted Cancer Therapies   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,dermatofibrosarcoma protuberans,0000280,GHR,https://ghr.nlm.nih.gov/condition/dermatofibrosarcoma-protuberans,C0392784,T191,Disorders
What is (are) desmoid tumor ?,0000281-1,information,"A desmoid tumor is an abnormal growth that arises from connective tissue, which is the tissue that provides strength and flexibility to structures such as bones, ligaments, and muscles. Typically, a single tumor develops, although some people have multiple tumors. The tumors can occur anywhere in the body. Tumors that form in the abdominal wall are called abdominal desmoid tumors; those that arise from the tissue that connects the abdominal organs are called intra-abdominal desmoid tumors; and tumors found in other regions of the body are called extra-abdominal desmoid tumors. Extra-abdominal tumors occur most often in the shoulders, upper arms, and upper legs.  Desmoid tumors are fibrous, much like scar tissue. They are generally not considered cancerous (malignant) because they do not spread to other parts of the body (metastasize); however, they can aggressively invade the surrounding tissue and can be very difficult to remove surgically. These tumors often recur, even after apparently complete removal.  The most common symptom of desmoid tumors is pain. Other signs and symptoms, which are often caused by growth of the tumor into surrounding tissue, vary based on the size and location of the tumor. Intra-abdominal desmoid tumors can block the bowel, causing constipation. Extra-abdominal desmoid tumors can restrict the movement of affected joints and cause limping or difficulty moving the arms or legs.  Desmoid tumors occur frequently in people with an inherited form of colon cancer called familial adenomatous polyposis (FAP). These individuals typically develop intra-abdominal desmoid tumors in addition to abnormal growths (called polyps) and cancerous tumors in the colon. Desmoid tumors that are not part of an inherited condition are described as sporadic.",desmoid tumor,0000281,GHR,https://ghr.nlm.nih.gov/condition/desmoid-tumor,C0079218,T191,Disorders
How many people are affected by desmoid tumor ?,0000281-2,frequency,"Desmoid tumors are rare, affecting an estimated 1 to 2 per 500,000 people worldwide. In the United States, 900 to 1,500 new cases are diagnosed per year. Sporadic desmoid tumors are more common than those associated with familial adenomatous polyposis.",desmoid tumor,0000281,GHR,https://ghr.nlm.nih.gov/condition/desmoid-tumor,C0079218,T191,Disorders
What are the genetic changes related to desmoid tumor ?,0000281-3,genetic changes,"Mutations in the CTNNB1 gene or the APC gene cause desmoid tumors. CTNNB1 gene mutations account for around 85 percent of sporadic desmoid tumors. APC gene mutations cause desmoid tumors associated with familial adenomatous polyposis as well as 10 to 15 percent of sporadic desmoid tumors. Both genes are involved in an important cell signaling pathway that controls the growth and division (proliferation) of cells and the process by which cells mature to carry out specific functions (differentiation).  The CTNNB1 gene provides instructions for making a protein called beta-catenin. As part of the cell-signaling pathway, beta-catenin interacts with other proteins to control the activity (expression) of particular genes, which helps promote cell proliferation and differentiation. CTNNB1 gene mutations lead to an abnormally stable beta-catenin protein that is not broken down when it is no longer needed. The protein accumulates in cells, where it continues to function in an uncontrolled way.  The protein produced from the APC gene helps regulate levels of beta-catenin in the cell. When beta-catenin is no longer needed, the APC protein attaches (binds) to it, which signals for it to be broken down. Mutations in the APC gene that cause desmoid tumors lead to a short APC protein that is unable to interact with beta-catenin. As a result, beta-catenin is not broken down and, instead, accumulates in cells. Excess beta-catenin, whether caused by CTNNB1 or APC gene mutations, promotes uncontrolled growth and division of cells, allowing the formation of desmoid tumors.",desmoid tumor,0000281,GHR,https://ghr.nlm.nih.gov/condition/desmoid-tumor,C0079218,T191,Disorders
Is desmoid tumor inherited ?,0000281-4,inheritance,"Most desmoid tumors are sporadic and are not inherited. Sporadic tumors result from gene mutations that occur during a person's lifetime, called somatic mutations. A somatic mutation in one copy of the gene is sufficient to cause the disorder. Somatic mutations in either the CTNNB1 or the APC gene can cause sporadic desmoid tumors.  An inherited mutation in one copy of the APC gene causes familial adenomatous polyposis and predisposes affected individuals to develop desmoid tumors. The desmoid tumors occur when a somatic mutation occurs in the second copy of the APC gene. In these cases, the condition is sometimes called hereditary desmoid disease.",desmoid tumor,0000281,GHR,https://ghr.nlm.nih.gov/condition/desmoid-tumor,C0079218,T191,Disorders
What are the treatments for desmoid tumor ?,0000281-5,treatment,"These resources address the diagnosis or management of desmoid tumor:  - Dana-Farber Cancer Institute  - Desmoid Tumor Research Foundation: About Desmoid Tumors  - Genetic Testing Registry: Desmoid disease, hereditary   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",desmoid tumor,0000281,GHR,https://ghr.nlm.nih.gov/condition/desmoid-tumor,C0079218,T191,Disorders
What is (are) desmosterolosis ?,0000282-1,information,"Desmosterolosis is a condition that is characterized by neurological problems, such as brain abnormalities and developmental delay, and can also include other signs and symptoms.  Children with desmosterolosis have delayed speech and motor skills (such as sitting and walking). Later in childhood, some affected individuals are able to walk with support; verbal communication is often limited to a few words or phrases. Common brain abnormalities in desmosterolosis include malformation of the tissue that connects the left and right halves of the brain (the corpus callosum) and loss of white matter, which consists of nerve fibers covered by a fatty substance called myelin.  People with desmosterolosis commonly have muscle stiffness (spasticity) and stiff, rigid joints (arthrogryposis) affecting their hands and feet. Other features seen in some affected individuals include short stature, abnormal head size (either larger or smaller than normal), a small lower jaw (micrognathia), an opening in the roof of the mouth (cleft palate), involuntary eye movements (nystagmus) or eyes that do not look in the same direction (strabismus), heart defects, and seizures.",desmosterolosis,0000282,GHR,https://ghr.nlm.nih.gov/condition/desmosterolosis,C1865596,T047,Disorders
How many people are affected by desmosterolosis ?,0000282-2,frequency,The prevalence of desmosterolosis is unknown; at least 10 affected individuals have been described in the scientific literature.,desmosterolosis,0000282,GHR,https://ghr.nlm.nih.gov/condition/desmosterolosis,C1865596,T047,Disorders
What are the genetic changes related to desmosterolosis ?,0000282-3,genetic changes,"Desmosterolosis is caused by mutations in the DHCR24 gene. This gene provides instructions for making an enzyme called 24-dehydrocholesterol reductase, which is involved in the production (synthesis) of cholesterol. Cholesterol is a waxy, fat-like substance that can be obtained from foods that come from animals (particularly egg yolks, meat, poultry, fish, and dairy products). It can also be produced in various tissues in the body. For example, the brain cannot access the cholesterol that comes from food, so brain cells must produce their own. Cholesterol is necessary for normal embryonic development and has important functions both before and after birth.  DHCR24 gene mutations lead to the production of 24-dehydrocholesterol reductase with reduced activity. As a result, there is a decrease in cholesterol production. Because the brain relies solely on cellular production for cholesterol, it is most severely affected. Without adequate cholesterol, cell membranes are not formed properly and nerve cells are not protected by myelin, leading to the death of these cells. In addition, a decrease in cholesterol production has more severe effects before birth than during other periods of development because of the rapid increase in cell number that takes place. Disruption of normal cell formation before birth likely accounts for the additional developmental abnormalities of desmosterolosis.",desmosterolosis,0000282,GHR,https://ghr.nlm.nih.gov/condition/desmosterolosis,C1865596,T047,Disorders
Is desmosterolosis inherited ?,0000282-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",desmosterolosis,0000282,GHR,https://ghr.nlm.nih.gov/condition/desmosterolosis,C1865596,T047,Disorders
What are the treatments for desmosterolosis ?,0000282-5,treatment,These resources address the diagnosis or management of desmosterolosis:  - Genetic Testing Registry: Desmosterolosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,desmosterolosis,0000282,GHR,https://ghr.nlm.nih.gov/condition/desmosterolosis,C1865596,T047,Disorders
What is (are) Diamond-Blackfan anemia ?,0000283-1,information,"Diamond-Blackfan anemia is a disorder of the bone marrow. The major function of bone marrow is to produce new blood cells. In Diamond-Blackfan anemia, the bone marrow malfunctions and fails to make enough red blood cells, which carry oxygen to the body's tissues. The resulting shortage of red blood cells (anemia) usually becomes apparent during the first year of life. Symptoms of anemia include fatigue, weakness, and an abnormally pale appearance (pallor).  People with Diamond-Blackfan anemia have an increased risk of several serious complications related to their malfunctioning bone marrow. Specifically, they have a higher-than-average chance of developing myelodysplastic syndrome (MDS), which is a disorder in which immature blood cells fail to develop normally. Affected individuals also have an increased risk of developing certain cancers, including a cancer of blood-forming tissue known as acute myeloid leukemia (AML) and a type of bone cancer called osteosarcoma.  Approximately half of individuals with Diamond-Blackfan anemia have physical abnormalities. They may have an unusually small head size (microcephaly) and a low frontal hairline, along with distinctive facial features such as wide-set eyes (hypertelorism); droopy eyelids (ptosis); a broad, flat bridge of the nose; small, low-set ears; and a small lower jaw (micrognathia). Affected individuals may also have an opening in the roof of the mouth (cleft palate) with or without a split in the upper lip (cleft lip). They may have a short, webbed neck; shoulder blades which are smaller and higher than usual; and abnormalities of their hands, most commonly malformed or absent thumbs. About one-third of affected individuals have slow growth leading to short stature.  Other features of Diamond-Blackfan anemia may include eye problems such as clouding of the lens of the eyes (cataracts), increased pressure in the eyes (glaucoma), or eyes that do not look in the same direction (strabismus). Affected individuals may also have kidney abnormalities; structural defects of the heart; and, in males, the opening of the urethra on the underside of the penis (hypospadias).  The severity of Diamond-Blackfan anemia may vary, even within the same family. Increasingly, individuals with ""non-classical"" Diamond-Blackfan anemia have been identified. This form of the disorder typically has less severe symptoms that may include mild anemia beginning in adulthood.",Diamond-Blackfan anemia,0000283,GHR,https://ghr.nlm.nih.gov/condition/diamond-blackfan-anemia,C1260899,T019,Disorders
How many people are affected by Diamond-Blackfan anemia ?,0000283-2,frequency,Diamond-Blackfan anemia affects approximately 5 to 7 per million liveborn infants worldwide.,Diamond-Blackfan anemia,0000283,GHR,https://ghr.nlm.nih.gov/condition/diamond-blackfan-anemia,C1260899,T019,Disorders
What are the genetic changes related to Diamond-Blackfan anemia ?,0000283-3,genetic changes,"Diamond-Blackfan anemia can be caused by mutations in the RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS19, RPS24, and RPS26 genes. These genes provide instructions for making several of the approximately 80 different ribosomal proteins, which are components of cellular structures called ribosomes. Ribosomes process the cell's genetic instructions to create proteins.  Each ribosome is made up of two parts (subunits) called the large and small subunits. The RPL5, RPL11, and RPL35A genes provide instructions for making ribosomal proteins that are among those found in the large subunit. The ribosomal proteins produced from the RPS7, RPS10, RPS17, RPS19, RPS24, and RPS26 genes are among those found in the small subunit.  The specific functions of each ribosomal protein within these subunits are unclear. Some ribosomal proteins are involved in the assembly or stability of ribosomes. Others help carry out the ribosome's main function of building new proteins. Studies suggest that some ribosomal proteins may have other functions, such as participating in chemical signaling pathways within the cell, regulating cell division, and controlling the self-destruction of cells (apoptosis).  Mutations in any of the genes listed above are believed to affect the stability or function of the ribosomal proteins. Studies indicate that a shortage of functioning ribosomal proteins may increase the self-destruction of blood-forming cells in the bone marrow, resulting in anemia. Abnormal regulation of cell division or inappropriate triggering of apoptosis may contribute to the other health problems that affect some people with Diamond-Blackfan anemia.  Approximately 25 percent of individuals with Diamond-Blackfan anemia have identified mutations in the RPS19 gene. About another 25 to 35 percent of individuals with this disorder have identified mutations in the RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS24, or RPS26 genes. In the remaining 40 to 50 percent of cases, the cause of the condition is unknown. Researchers suspect that other genes may also be associated with Diamond-Blackfan anemia.",Diamond-Blackfan anemia,0000283,GHR,https://ghr.nlm.nih.gov/condition/diamond-blackfan-anemia,C1260899,T019,Disorders
Is Diamond-Blackfan anemia inherited ?,0000283-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In approximately 45 percent of cases, an affected person inherits the mutation from one affected parent. The remaining cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",Diamond-Blackfan anemia,0000283,GHR,https://ghr.nlm.nih.gov/condition/diamond-blackfan-anemia,C1260899,T019,Disorders
What are the treatments for Diamond-Blackfan anemia ?,0000283-5,treatment,These resources address the diagnosis or management of Diamond-Blackfan anemia:  - Gene Review: Gene Review: Diamond-Blackfan Anemia  - Genetic Testing Registry: Aase syndrome  - Genetic Testing Registry: Diamond-Blackfan anemia  - Genetic Testing Registry: Diamond-Blackfan anemia 10  - Genetic Testing Registry: Diamond-Blackfan anemia 2  - Genetic Testing Registry: Diamond-Blackfan anemia 3  - Genetic Testing Registry: Diamond-Blackfan anemia 4  - Genetic Testing Registry: Diamond-Blackfan anemia 5  - Genetic Testing Registry: Diamond-Blackfan anemia 7  - Genetic Testing Registry: Diamond-Blackfan anemia 8  - Genetic Testing Registry: Diamond-Blackfan anemia 9   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Diamond-Blackfan anemia,0000283,GHR,https://ghr.nlm.nih.gov/condition/diamond-blackfan-anemia,C1260899,T019,Disorders
What is (are) diastrophic dysplasia ?,0000284-1,information,"Diastrophic dysplasia is a disorder of cartilage and bone development. Affected individuals have short stature with very short arms and legs. Most also have early-onset joint pain (osteoarthritis) and joint deformities called contractures, which restrict movement. These joint problems often make it difficult to walk and tend to worsen with age. Additional features of diastrophic dysplasia include an inward- and upward-turning foot (clubfoot), progressive abnormal curvature of the spine, and unusually positioned thumbs (hitchhiker thumbs). About half of infants with diastrophic dysplasia are born with an opening in the roof of the mouth (a cleft palate). Swelling of the external ears is also common in newborns and can lead to thickened, deformed ears.  The signs and symptoms of diastrophic dysplasia are similar to those of another skeletal disorder called atelosteogenesis type 2; however, diastrophic dysplasia tends to be less severe. Although some affected infants have breathing problems, most people with diastrophic dysplasia live into adulthood.",diastrophic dysplasia,0000284,GHR,https://ghr.nlm.nih.gov/condition/diastrophic-dysplasia,C0220726,T019,Disorders
How many people are affected by diastrophic dysplasia ?,0000284-2,frequency,"Although the exact incidence of this condition is unknown, researchers estimate that it affects about 1 in 100,000 newborns. Diastrophic dysplasia occurs in all populations but appears to be particularly common in Finland.",diastrophic dysplasia,0000284,GHR,https://ghr.nlm.nih.gov/condition/diastrophic-dysplasia,C0220726,T019,Disorders
What are the genetic changes related to diastrophic dysplasia ?,0000284-3,genetic changes,"Diastrophic dysplasia is one of several skeletal disorders caused by mutations in the SLC26A2 gene. This gene provides instructions for making a protein that is essential for the normal development of cartilage and for its conversion to bone. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Mutations in the SLC26A2 gene alter the structure of developing cartilage, preventing bones from forming properly and resulting in the skeletal problems characteristic of diastrophic dysplasia.",diastrophic dysplasia,0000284,GHR,https://ghr.nlm.nih.gov/condition/diastrophic-dysplasia,C0220726,T019,Disorders
Is diastrophic dysplasia inherited ?,0000284-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",diastrophic dysplasia,0000284,GHR,https://ghr.nlm.nih.gov/condition/diastrophic-dysplasia,C0220726,T019,Disorders
What are the treatments for diastrophic dysplasia ?,0000284-5,treatment,These resources address the diagnosis or management of diastrophic dysplasia:  - Gene Review: Gene Review: Diastrophic Dysplasia  - Genetic Testing Registry: Diastrophic dysplasia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,diastrophic dysplasia,0000284,GHR,https://ghr.nlm.nih.gov/condition/diastrophic-dysplasia,C0220726,T019,Disorders
What is (are) DICER1 syndrome ?,0000285-1,information,"DICER1 syndrome is an inherited disorder that increases the risk of a variety of cancerous and noncancerous (benign) tumors, most commonly certain types of tumors that occur in the lungs, kidneys, ovaries, and thyroid (a butterfly-shaped gland in the lower neck). Affected individuals can develop one or more types of tumors, and members of the same family can have different types. However, the risk of tumor formation in individuals with DICER1 syndrome is only moderately increased compared with tumor risk in the general population; most individuals with genetic changes associated with this condition never develop tumors.  People with DICER1 syndrome who develop tumors most commonly develop pleuropulmonary blastoma, which is characterized by tumors that grow in lung tissue or in the outer covering of the lungs (the pleura). These tumors occur in infants and young children and are rare in adults. Pleuropulmonary blastoma is classified as one of three types on the basis of tumor characteristics: in type I, the growths are composed of air-filled pockets called cysts; in type II, the growths contain both cysts and solid tumors (or nodules); and in type III, the growth is a solid tumor that can fill a large portion of the chest. Pleuropulmonary blastoma is considered cancerous, and types II and III can spread (metastasize), often to the brain, liver, or bones. Individuals with pleuropulmonary blastoma may also develop an abnormal accumulation of air in the chest cavity that can lead to the collapse of a lung (pneumothorax).  Cystic nephroma, which involves multiple benign fluid-filled cysts in the kidneys, can also occur; in people with DICER1 syndrome, the cysts develop early in childhood.  DICER1 syndrome is also associated with tumors in the ovaries known as Sertoli-Leydig cell tumors, which typically develop in affected women in their teens or twenties. Some Sertoli-Leydig cell tumors release the male sex hormone testosterone; in these cases, affected women may develop facial hair, a deep voice, and other male characteristics. Some affected women have irregular menstrual cycles. Sertoli-Leydig cell tumors usually do not metastasize.  People with DICER1 syndrome are also at risk of multinodular goiter, which is enlargement of the thyroid gland caused by the growth of multiple fluid-filled or solid tumors (both referred to as nodules). The nodules are generally slow-growing and benign. Despite the growths, the thyroid's function is often normal. Rarely, individuals with DICER1 syndrome develop thyroid cancer (thyroid carcinoma).",DICER1 syndrome,0000285,GHR,https://ghr.nlm.nih.gov/condition/dicer1-syndrome,C3839822,T191,Disorders
How many people are affected by DICER1 syndrome ?,0000285-2,frequency,DICER1 syndrome is a rare condition; its prevalence is unknown.,DICER1 syndrome,0000285,GHR,https://ghr.nlm.nih.gov/condition/dicer1-syndrome,C3839822,T191,Disorders
What are the genetic changes related to DICER1 syndrome ?,0000285-3,genetic changes,"DICER1 syndrome is caused by mutations in the DICER1 gene. This gene provides instructions for making a protein that is involved in the production of molecules called microRNA (miRNA). MicroRNA is a type of RNA, a chemical cousin of DNA, that attaches to a protein's blueprint (a molecule called messenger RNA) and blocks the production of proteins from it. Through this role in regulating the activity (expression) of genes, the Dicer protein is involved in many processes, including cell growth and division (proliferation) and the maturation of cells to take on specialized functions (differentiation).  Most of the gene mutations involved in DICER1 syndrome lead to an abnormally short Dicer protein that is unable to aid in the production of miRNA. Without appropriate regulation by miRNA, genes are likely expressed abnormally, which could cause cells to grow and divide uncontrollably and lead to tumor formation.",DICER1 syndrome,0000285,GHR,https://ghr.nlm.nih.gov/condition/dicer1-syndrome,C3839822,T191,Disorders
Is DICER1 syndrome inherited ?,0000285-4,inheritance,"DICER1 syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to cause the disorder. It is important to note that people inherit an increased risk of tumors; many people who have mutations in the DICER1 gene do not develop abnormal growths.",DICER1 syndrome,0000285,GHR,https://ghr.nlm.nih.gov/condition/dicer1-syndrome,C3839822,T191,Disorders
What are the treatments for DICER1 syndrome ?,0000285-5,treatment,These resources address the diagnosis or management of DICER1 syndrome:  - Cancer.Net from the American Society of Clinical Oncology: Pleuropulmonary Blastoma--Childhood Treatment  - Gene Review: Gene Review: DICER1-Related Disorders  - Genetic Testing Registry: Pleuropulmonary blastoma   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,DICER1 syndrome,0000285,GHR,https://ghr.nlm.nih.gov/condition/dicer1-syndrome,C3839822,T191,Disorders
What is (are) dihydrolipoamide dehydrogenase deficiency ?,0000286-1,information,"Dihydrolipoamide dehydrogenase deficiency is a severe condition that can affect several body systems. Signs and symptoms of this condition usually appear shortly after birth, and they can vary widely among affected individuals.  A common feature of dihydrolipoamide dehydrogenase deficiency is a potentially life-threatening buildup of lactic acid in tissues (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. Neurological problems are also common in this condition; the first symptoms in affected infants are often decreased muscle tone (hypotonia) and extreme tiredness (lethargy). As the problems worsen, affected infants can have difficulty feeding, decreased alertness, and seizures. Liver problems can also occur in dihydrolipoamide dehydrogenase deficiency, ranging from an enlarged liver (hepatomegaly) to life-threatening liver failure. In some affected people, liver disease, which can begin anytime from infancy to adulthood, is the primary symptom. The liver problems are usually associated with recurrent vomiting and abdominal pain. Rarely, people with dihydrolipoamide dehydrogenase deficiency experience weakness of the muscles used for movement (skeletal muscles), particularly during exercise; droopy eyelids; or a weakened heart muscle (cardiomyopathy). Other features of this condition include excess ammonia in the blood (hyperammonemia), a buildup of molecules called ketones in the body (ketoacidosis), or low blood sugar levels (hypoglycemia).  Typically, the signs and symptoms of dihydrolipoamide dehydrogenase deficiency occur in episodes that may be triggered by fever, injury, or other stresses on the body. Affected individuals are usually symptom-free between episodes. Many infants with this condition do not survive the first few years of life because of the severity of these episodes. Affected individuals who survive past early childhood often have delayed growth and neurological problems, including intellectual disability, muscle stiffness (spasticity), difficulty coordinating movements (ataxia), and seizures.",dihydrolipoamide dehydrogenase deficiency,0000286,GHR,https://ghr.nlm.nih.gov/condition/dihydrolipoamide-dehydrogenase-deficiency,C3492932,T047,Disorders
How many people are affected by dihydrolipoamide dehydrogenase deficiency ?,0000286-2,frequency,"Dihydrolipoamide dehydrogenase deficiency occurs in an estimated 1 in 35,000 to 48,000 individuals of Ashkenazi Jewish descent. This population typically has liver disease as the primary symptom. In other populations, the prevalence of dihydrolipoamide dehydrogenase deficiency is unknown, but the condition is likely rare.",dihydrolipoamide dehydrogenase deficiency,0000286,GHR,https://ghr.nlm.nih.gov/condition/dihydrolipoamide-dehydrogenase-deficiency,C3492932,T047,Disorders
What are the genetic changes related to dihydrolipoamide dehydrogenase deficiency ?,0000286-3,genetic changes,"Mutations in the DLD gene cause dihydrolipoamide dehydrogenase deficiency. This gene provides instructions for making an enzyme called dihydrolipoamide dehydrogenase (DLD). DLD is one component of three different groups of enzymes that work together (enzyme complexes): branched-chain alpha-keto acid dehydrogenase (BCKD), pyruvate dehydrogenase (PDH), and alpha ()-ketoglutarate dehydrogenase (KGDH). The BCKD enzyme complex is involved in the breakdown of three protein building blocks (amino acids) commonly found in protein-rich foods: leucine, isoleucine, and valine. Breakdown of these amino acids produces molecules that can be used for energy. The PDH and KGDH enzyme complexes are involved in other reactions in the pathways that convert the energy from food into a form that cells can use.  Mutations in the DLD gene impair the function of the DLD enzyme, which prevents the three enzyme complexes from functioning properly. As a result, molecules that are normally broken down and their byproducts build up in the body, damaging tissues and leading to lactic acidosis and other chemical imbalances. In addition, the production of cellular energy is diminished. The brain is especially affected by the buildup of molecules and the lack of cellular energy, resulting in the neurological problems associated with dihydrolipoamide dehydrogenase deficiency. Liver problems are likely also related to decreased energy production in cells. The degree of impairment of each complex contributes to the variability in the features of this condition.",dihydrolipoamide dehydrogenase deficiency,0000286,GHR,https://ghr.nlm.nih.gov/condition/dihydrolipoamide-dehydrogenase-deficiency,C3492932,T047,Disorders
Is dihydrolipoamide dehydrogenase deficiency inherited ?,0000286-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",dihydrolipoamide dehydrogenase deficiency,0000286,GHR,https://ghr.nlm.nih.gov/condition/dihydrolipoamide-dehydrogenase-deficiency,C3492932,T047,Disorders
What are the treatments for dihydrolipoamide dehydrogenase deficiency ?,0000286-5,treatment,"These resources address the diagnosis or management of dihydrolipoamide dehydrogenase deficiency:  - Gene Review: Gene Review: Dihydrolipoamide Dehydrogenase Deficiency  - Genetic Testing Registry: Maple syrup urine disease, type 3   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",dihydrolipoamide dehydrogenase deficiency,0000286,GHR,https://ghr.nlm.nih.gov/condition/dihydrolipoamide-dehydrogenase-deficiency,C3492932,T047,Disorders
What is (are) dihydropyrimidinase deficiency ?,0000287-1,information,"Dihydropyrimidinase deficiency is a disorder that can cause neurological and gastrointestinal problems in some affected individuals. Other people with dihydropyrimidinase deficiency have no signs or symptoms related to the disorder, and in these individuals the condition can be diagnosed only by laboratory testing.  The neurological abnormalities that occur most often in people with dihydropyrimidinase deficiency are intellectual disability, seizures, and weak muscle tone (hypotonia). An abnormally small head size (microcephaly) and autistic behaviors that affect communication and social interaction also occur in some individuals with this condition.  Gastrointestinal problems that occur in dihydropyrimidinase deficiency include backflow of acidic stomach contents into the esophagus (gastroesophageal reflux) and recurrent episodes of vomiting (cyclic vomiting). Affected individuals can also have deterioration (atrophy) of the small, finger-like projections (villi) that line the small intestine and provide a large surface area with which to absorb nutrients. This condition, called villous atrophy, can lead to difficulty absorbing nutrients from foods (malabsorption), resulting in a failure to grow and gain weight at the expected rate (failure to thrive).  People with dihydropyrimidinase deficiency, including those who otherwise exhibit no symptoms, may be vulnerable to severe, potentially life-threatening toxic reactions to certain drugs called fluoropyrimidines that are used to treat cancer. Common examples of these drugs are 5-fluorouracil and capecitabine. These drugs may not be broken down efficiently and can build up to toxic levels in the body (fluoropyrimidine toxicity), leading to drug reactions including gastrointestinal problems, blood abnormalities, and other signs and symptoms.",dihydropyrimidinase deficiency,0000287,GHR,https://ghr.nlm.nih.gov/condition/dihydropyrimidinase-deficiency,C0342803,T047,Disorders
How many people are affected by dihydropyrimidinase deficiency ?,0000287-2,frequency,Dihydropyrimidinase deficiency is thought to be a rare disorder. Only a few dozen affected individuals have been described in the medical literature.,dihydropyrimidinase deficiency,0000287,GHR,https://ghr.nlm.nih.gov/condition/dihydropyrimidinase-deficiency,C0342803,T047,Disorders
What are the genetic changes related to dihydropyrimidinase deficiency ?,0000287-3,genetic changes,"Dihydropyrimidinase deficiency is caused by mutations in the DPYS gene, which provides instructions for making an enzyme called dihydropyrimidinase. This enzyme is involved in the breakdown of molecules called pyrimidines, which are building blocks of DNA and its chemical cousin RNA. The dihydropyrimidinase enzyme is involved in the second step of the three-step process that breaks down pyrimidines. This step opens the ring-like structures of molecules called 5,6-dihydrothymine and 5,6-dihydrouracil so that these molecules can be further broken down.  The DPYS gene mutations that cause dihydropyrimidinase deficiency greatly reduce or eliminate dihydropyrimidinase enzyme function. As a result, the enzyme is unable to begin the breakdown of 5,6-dihydrothymine and 5,6-dihydrouracil. Excessive amounts of these molecules accumulate in the blood and in the fluid that surrounds and protects the brain and spinal cord (the cerebrospinal fluid or CSF) and are released in the urine.  The relationship between the inability to break down 5,6-dihydrothymine and 5,6-dihydrouracil and the specific features of dihydropyrimidinase deficiency is unclear. Failure to complete this step in the breakdown of pyrimidines also impedes the final step of the process, which produces molecules called beta-aminoisobutyric acid and beta-alanine. Both of these molecules are thought to protect the nervous system and help it function properly. Reduced production of beta-aminoisobutyric acid and beta-alanine may impair the function of these molecules in the nervous system, leading to neurological problems in some people with dihydropyrimidinase deficiency. Because fluoropyrimidine drugs are broken down by the same three-step process as pyrimidines, deficiency of the dihydropyrimidinase enzyme could lead to the drug buildup that causes fluoropyrimidine toxicity.  It is unknown why some people with dihydropyrimidinase deficiency do not develop health problems related to the condition; other genetic and environmental factors likely help determine the effects of this disorder.",dihydropyrimidinase deficiency,0000287,GHR,https://ghr.nlm.nih.gov/condition/dihydropyrimidinase-deficiency,C0342803,T047,Disorders
Is dihydropyrimidinase deficiency inherited ?,0000287-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",dihydropyrimidinase deficiency,0000287,GHR,https://ghr.nlm.nih.gov/condition/dihydropyrimidinase-deficiency,C0342803,T047,Disorders
What are the treatments for dihydropyrimidinase deficiency ?,0000287-5,treatment,These resources address the diagnosis or management of dihydropyrimidinase deficiency:  - Genetic Testing Registry: Dihydropyrimidinase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,dihydropyrimidinase deficiency,0000287,GHR,https://ghr.nlm.nih.gov/condition/dihydropyrimidinase-deficiency,C0342803,T047,Disorders
What is (are) dihydropyrimidine dehydrogenase deficiency ?,0000288-1,information,"Dihydropyrimidine dehydrogenase deficiency is a disorder characterized by a wide range of severity, with neurological problems in some individuals and no signs or symptoms in others.  In people with severe dihydropyrimidine dehydrogenase deficiency, the disorder becomes apparent in infancy. These affected individuals have neurological problems such as recurrent seizures (epilepsy), intellectual disability, a small head size (microcephaly), increased muscle tone (hypertonia), delayed development of motor skills such as walking, and autistic behaviors that affect communication and social interaction. Other affected individuals are asymptomatic, which means they do not have any signs or symptoms of the condition. Individuals with asymptomatic dihydropyrimidine dehydrogenase deficiency may be identified only by laboratory testing.  People with dihydropyrimidine dehydrogenase deficiency, including those who otherwise exhibit no symptoms, are vulnerable to severe, potentially life-threatening toxic reactions to certain drugs called fluoropyrimidines that are used to treat cancer. Common examples of these drugs are 5-fluorouracil and capecitabine. These drugs are not broken down efficiently by people with dihydropyrimidine dehydrogenase deficiency and build up to toxic levels in the body (fluoropyrimidine toxicity). Severe inflammation and ulceration of the lining of the gastrointestinal tract (mucositis) may occur, which can lead to signs and symptoms including mouth sores, abdominal pain, bleeding, nausea, vomiting, and diarrhea. Fluoropyrimidine toxicity may also lead to low numbers of white blood cells (neutropenia), which increases the risk of infections. It can also be associated with low numbers of platelets in the blood (thrombocytopenia), which impairs blood clotting and may lead to abnormal bleeding (hemorrhage). Redness, swelling, numbness, and peeling of the skin on the palms and soles (hand-foot syndrome); shortness of breath; and hair loss may also occur.",dihydropyrimidine dehydrogenase deficiency,0000288,GHR,https://ghr.nlm.nih.gov/condition/dihydropyrimidine-dehydrogenase-deficiency,C1959620,T047,Disorders
How many people are affected by dihydropyrimidine dehydrogenase deficiency ?,0000288-2,frequency,"Severe dihydropyrimidine dehydrogenase deficiency, with its early-onset neurological symptoms, is a rare disorder. Its prevalence is unknown. However, between 2 and 8 percent of the general population may be vulnerable to toxic reactions to fluoropyrimidine drugs caused by otherwise asymptomatic dihydropyrimidine dehydrogenase deficiency.",dihydropyrimidine dehydrogenase deficiency,0000288,GHR,https://ghr.nlm.nih.gov/condition/dihydropyrimidine-dehydrogenase-deficiency,C1959620,T047,Disorders
What are the genetic changes related to dihydropyrimidine dehydrogenase deficiency ?,0000288-3,genetic changes,"Dihydropyrimidine dehydrogenase deficiency is caused by mutations in the DPYD gene. This gene provides instructions for making an enzyme called dihydropyrimidine dehydrogenase, which is involved in the breakdown of molecules called uracil and thymine. Uracil and thymine are pyrimidines, which are one type of nucleotide. Nucleotides are building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in the cell.  Mutations in the DPYD gene result in a lack (deficiency) of functional dihydropyrimidine dehydrogenase. Dihydropyrimidine dehydrogenase deficiency interferes with the breakdown of uracil and thymine, and results in excess quantities of these molecules in the blood, urine, and the fluid that surrounds the brain and spinal cord (cerebrospinal fluid). It is unclear how the excess uracil and thymine are related to the specific signs and symptoms of dihydropyrimidine dehydrogenase deficiency. Mutations that result in the absence (complete deficiency) of dihydropyrimidine dehydrogenase generally lead to more severe signs and symptoms than do mutations that lead to a partial deficiency of this enzyme.  Because fluoropyrimidine drugs are also broken down by the dihydropyrimidine dehydrogenase enzyme, deficiency of this enzyme leads to the drug buildup that causes fluoropyrimidine toxicity.",dihydropyrimidine dehydrogenase deficiency,0000288,GHR,https://ghr.nlm.nih.gov/condition/dihydropyrimidine-dehydrogenase-deficiency,C1959620,T047,Disorders
Is dihydropyrimidine dehydrogenase deficiency inherited ?,0000288-4,inheritance,"Dihydropyrimidine dehydrogenase deficiency is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Depending on the severity of these mutations, people with two mutated copies of the DPYD gene in each cell may exhibit the signs and symptoms of this disorder, or they may be generally asymptomatic but at risk for toxic reactions to fluoropyrimidine drugs.  The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. However, people with one mutated copy of the DPYD gene in each cell may still experience toxic reactions to fluoropyrimidine drugs.",dihydropyrimidine dehydrogenase deficiency,0000288,GHR,https://ghr.nlm.nih.gov/condition/dihydropyrimidine-dehydrogenase-deficiency,C1959620,T047,Disorders
What are the treatments for dihydropyrimidine dehydrogenase deficiency ?,0000288-5,treatment,These resources address the diagnosis or management of dihydropyrimidine dehydrogenase deficiency:  - Genetic Testing Registry: Dihydropyrimidine dehydrogenase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,dihydropyrimidine dehydrogenase deficiency,0000288,GHR,https://ghr.nlm.nih.gov/condition/dihydropyrimidine-dehydrogenase-deficiency,C1959620,T047,Disorders
What is (are) dilated cardiomyopathy with ataxia syndrome ?,0000289-1,information,"Dilated cardiomyopathy with ataxia (DCMA) syndrome is an inherited condition characterized by heart problems, movement difficulties, and other features affecting multiple body systems.  Beginning in infancy to early childhood, most people with DCMA syndrome develop dilated cardiomyopathy, which is a condition that weakens and enlarges the heart, preventing it from pumping blood efficiently. Some affected individuals also have long QT syndrome, which is a heart condition that causes the cardiac muscle to take longer than usual to recharge between beats. The irregular heartbeats (arrhythmia) can lead to fainting (syncope) or cardiac arrest and sudden death. Rarely, heart problems improve over time; however, in most cases of DCMA syndrome, affected individuals do not survive past childhood due to heart failure. A small percentage of people with DCMA syndrome have no heart problems at all.  By age 2, children with DCMA syndrome have problems with coordination and balance (ataxia). These movement problems can result in delay of motor skills such as standing and walking, but most older children with DCMA syndrome can walk without support.  In addition to heart problems and movement difficulties, most individuals with DCMA syndrome grow slowly before and after birth, which leads to short stature. Additionally, many affected individuals have mild intellectual disability. Many males with DCMA syndrome have genital abnormalities such as undescended testes (cryptorchidism) or the urethra opening on the underside of the penis (hypospadias). Other common features of DCMA syndrome include unusually small red blood cells (microcytic anemia), which can cause pale skin; an abnormal buildup of fats in the liver (hepatic steatosis), which can damage the liver; and the degeneration of nerve cells that carry visual information from the eyes to the brain (optic nerve atrophy), which can lead to vision loss.  DCMA syndrome is associated with increased levels of a substance called 3-methylglutaconic acid in the urine. The amount of acid does not appear to influence the signs and symptoms of the condition. DCMA syndrome is one of a group of metabolic disorders that can be diagnosed by the presence of increased levels of 3-methylglutaconic acid in urine (3-methylglutaconic aciduria). People with DCMA syndrome also have high urine levels of another acid called 3-methylglutaric acid.",dilated cardiomyopathy with ataxia syndrome,0000289,GHR,https://ghr.nlm.nih.gov/condition/dilated-cardiomyopathy-with-ataxia-syndrome,C0878544,T047,Disorders
How many people are affected by dilated cardiomyopathy with ataxia syndrome ?,0000289-2,frequency,DCMA syndrome is a very rare disorder. Approximately 30 cases have been identified in the Dariusleut Hutterite population of the Great Plains region of Canada. Only a few affected individuals have been identified outside this population.,dilated cardiomyopathy with ataxia syndrome,0000289,GHR,https://ghr.nlm.nih.gov/condition/dilated-cardiomyopathy-with-ataxia-syndrome,C0878544,T047,Disorders
What are the genetic changes related to dilated cardiomyopathy with ataxia syndrome ?,0000289-3,genetic changes,"Mutations in the DNAJC19 gene cause DCMA syndrome. The DNAJC19 gene provides instructions for making a protein found in structures called mitochondria, which are the energy-producing centers of cells. While the exact function of the DNAJC19 protein is unclear, it may regulate the transport of other proteins into and out of mitochondria.  The DNAJC19 gene mutations that cause DCMA syndrome lead to the production of an abnormally shortened protein that likely has impaired function. Researchers speculate that a lack of functional DNAJC19 protein alters the transport of other proteins into and out of the mitochondria. When too many or too few proteins move in and out of the mitochondria, energy production and mitochondrial survival can be reduced. Tissues that have high energy demands, such as the heart and the brain, are especially susceptible to decreases in cellular energy production. It is likely that this loss of cellular energy damages these and other tissues, leading to heart problems, movement difficulties, and other features of DCMA syndrome.",dilated cardiomyopathy with ataxia syndrome,0000289,GHR,https://ghr.nlm.nih.gov/condition/dilated-cardiomyopathy-with-ataxia-syndrome,C0878544,T047,Disorders
Is dilated cardiomyopathy with ataxia syndrome inherited ?,0000289-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",dilated cardiomyopathy with ataxia syndrome,0000289,GHR,https://ghr.nlm.nih.gov/condition/dilated-cardiomyopathy-with-ataxia-syndrome,C0878544,T047,Disorders
What are the treatments for dilated cardiomyopathy with ataxia syndrome ?,0000289-5,treatment,"These resources address the diagnosis or management of dilated cardiomyopathy with ataxia syndrome:  - Ann & Robert H. Lurie Children's Hospital of Chicago: Cardiomyopathy  - Baby's First Test  - Genetic Testing Registry: 3-methylglutaconic aciduria type V  - MedlinePlus Encyclopedia: Dilated Cardiomyopathy  - National Heart, Lung, and Blood Institute: How is Cardiomyopathy Diagnosed?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",dilated cardiomyopathy with ataxia syndrome,0000289,GHR,https://ghr.nlm.nih.gov/condition/dilated-cardiomyopathy-with-ataxia-syndrome,C0878544,T047,Disorders
What is (are) distal arthrogryposis type 1 ?,0000290-1,information,"Distal arthrogryposis type 1 is a disorder characterized by joint deformities (contractures) that restrict movement in the hands and feet. The term ""arthrogryposis"" comes from the Greek words for joint (arthro-) and crooked or hooked (gryposis). The characteristic features of this condition include permanently bent fingers and toes (camptodactyly), overlapping fingers, and a hand deformity in which all of the fingers are angled outward toward the fifth finger (ulnar deviation). Clubfoot, which is an inward- and upward-turning foot, is also commonly seen with distal arthrogryposis type 1. The specific hand and foot abnormalities vary among affected individuals. However, this condition typically does not cause any signs and symptoms affecting other parts of the body.",distal arthrogryposis type 1,0000290,GHR,https://ghr.nlm.nih.gov/condition/distal-arthrogryposis-type-1,C0220662,T019,Disorders
How many people are affected by distal arthrogryposis type 1 ?,0000290-2,frequency,"Distal arthrogryposis type 1 affects an estimated 1 in 10,000 people worldwide.",distal arthrogryposis type 1,0000290,GHR,https://ghr.nlm.nih.gov/condition/distal-arthrogryposis-type-1,C0220662,T019,Disorders
What are the genetic changes related to distal arthrogryposis type 1 ?,0000290-3,genetic changes,"Distal arthrogryposis type 1 can be caused by mutations in at least two genes: TPM2 and MYBPC1. These genes are active (expressed) in muscle cells, where they interact with other muscle proteins to help regulate the tensing of muscle fibers (muscle contraction). It is unclear how mutations in the TPM2 and MYBPC1 genes lead to the joint abnormalities characteristic of distal arthrogryposis type 1. However, researchers speculate that contractures may be related to problems with muscle contraction that limit the movement of joints before birth.  In some cases, the genetic cause of distal arthrogryposis type 1 is unknown. Researchers are looking for additional genetic changes that may be responsible for this condition.",distal arthrogryposis type 1,0000290,GHR,https://ghr.nlm.nih.gov/condition/distal-arthrogryposis-type-1,C0220662,T019,Disorders
Is distal arthrogryposis type 1 inherited ?,0000290-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. In many cases, a person with distal arthrogryposis type 1 has a parent and other close family members with the condition.",distal arthrogryposis type 1,0000290,GHR,https://ghr.nlm.nih.gov/condition/distal-arthrogryposis-type-1,C0220662,T019,Disorders
What are the treatments for distal arthrogryposis type 1 ?,0000290-5,treatment,These resources address the diagnosis or management of distal arthrogryposis type 1:  - Genetic Testing Registry: Arthrogryposis multiplex congenita distal type 1  - Merck Manual for Health Care Professionals  - New York University Langone Medical Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,distal arthrogryposis type 1,0000290,GHR,https://ghr.nlm.nih.gov/condition/distal-arthrogryposis-type-1,C0220662,T019,Disorders
"What is (are) distal hereditary motor neuropathy, type II ?",0000291-1,information,"Distal hereditary motor neuropathy, type II is a progressive disorder that affects nerve cells in the spinal cord. It results in muscle weakness and affects movement, primarily in the legs.  Onset of distal hereditary motor neuropathy, type II ranges from the teenage years through mid-adulthood. The initial symptoms of the disorder are cramps or weakness in the muscles of the big toe and later, the entire foot. Over a period of approximately 5 to 10 years, affected individuals experience a gradual loss of muscle tissue (atrophy) in the lower legs. They begin to have trouble walking and running, and eventually may have complete paralysis of the lower legs. The thigh muscles may also be affected, although generally this occurs later and is less severe.  Some individuals with distal hereditary motor neuropathy, type II have weakening of the muscles in the hands and forearms. This weakening is less pronounced than in the lower limbs and does not usually result in paralysis.","distal hereditary motor neuropathy, type II",0000291,GHR,https://ghr.nlm.nih.gov/condition/distal-hereditary-motor-neuropathy-type-ii,C3711384,T047,Disorders
"How many people are affected by distal hereditary motor neuropathy, type II ?",0000291-2,frequency,"The prevalence of distal hereditary motor neuropathy, type II is unknown. At least 25 affected families have been identified worldwide.","distal hereditary motor neuropathy, type II",0000291,GHR,https://ghr.nlm.nih.gov/condition/distal-hereditary-motor-neuropathy-type-ii,C3711384,T047,Disorders
"What are the genetic changes related to distal hereditary motor neuropathy, type II ?",0000291-3,genetic changes,"Mutations in the HSPB1 and HSPB8 genes cause distal hereditary motor neuropathy, type II. These genes provide instructions for making proteins called heat shock protein beta-1 and heat shock protein beta-8. Heat shock proteins help protect cells under adverse conditions such as infection, inflammation, exposure to toxins, elevated temperature, injury, and disease. They block signals that lead to programmed cell death. In addition, they appear to be involved in activities such as cell movement (motility), stabilizing the cell's structural framework (the cytoskeleton), folding and stabilizing newly produced proteins, and repairing damaged proteins. Heat shock proteins also appear to play a role in the tensing of muscle fibers (muscle contraction).  Heat shock protein beta-1 and heat shock protein beta-8 are found in cells throughout the body and are abundant in nerve cells. In nerve cells, heat shock protein beta-1 helps to organize a network of molecular threads called neurofilaments that maintain the diameter of specialized extensions called axons. Maintaining proper axon diameter is essential for the efficient transmission of nerve impulses. The function of heat shock protein beta-8 is not well understood, but studies have shown that it interacts with heat shock protein beta-1.  The HSPB1 and HSPB8 gene mutations that cause distal hereditary motor neuropathy, type II change single protein building blocks (amino acids) in the protein sequence. If either protein is altered, they may be more likely to cluster together and form clumps (aggregates). Aggregates of heat shock proteins may block the transport of substances that are essential for the proper function of nerve axons. The disruption of other cell functions in which these proteins are involved may also contribute to the signs and symptoms of distal hereditary motor neuropathy, type II.","distal hereditary motor neuropathy, type II",0000291,GHR,https://ghr.nlm.nih.gov/condition/distal-hereditary-motor-neuropathy-type-ii,C3711384,T047,Disorders
"Is distal hereditary motor neuropathy, type II inherited ?",0000291-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.","distal hereditary motor neuropathy, type II",0000291,GHR,https://ghr.nlm.nih.gov/condition/distal-hereditary-motor-neuropathy-type-ii,C3711384,T047,Disorders
"What are the treatments for distal hereditary motor neuropathy, type II ?",0000291-5,treatment,"These resources address the diagnosis or management of distal hereditary motor neuropathy, type II:  - Genetic Testing Registry: Distal hereditary motor neuronopathy type 2A  - Genetic Testing Registry: Distal hereditary motor neuronopathy type 2B  - MedlinePlus Encyclopedia: Weakness   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","distal hereditary motor neuropathy, type II",0000291,GHR,https://ghr.nlm.nih.gov/condition/distal-hereditary-motor-neuropathy-type-ii,C3711384,T047,Disorders
"What is (are) distal hereditary motor neuropathy, type V ?",0000292-1,information,"Distal hereditary motor neuropathy, type V is a progressive disorder that affects nerve cells in the spinal cord. It results in muscle weakness and affects movement of the hands and feet.  Symptoms of distal hereditary motor neuropathy, type V usually begin during adolescence, but onset varies from infancy to the mid-thirties. Cramps in the hand brought on by exposure to cold temperatures are often the initial symptom.  The characteristic features of distal hereditary motor neuropathy, type V are weakness and wasting (atrophy) of muscles of the hand, specifically on the thumb side of the index finger and in the palm at the base of the thumb. Foot abnormalities, such as a high arch (pes cavus), are also common, and some affected individuals eventually develop problems with walking (gait disturbance). People with this disorder have normal life expectancies.","distal hereditary motor neuropathy, type V",0000292,GHR,https://ghr.nlm.nih.gov/condition/distal-hereditary-motor-neuropathy-type-v,C1833308,T047,Disorders
"How many people are affected by distal hereditary motor neuropathy, type V ?",0000292-2,frequency,"The incidence of distal hereditary motor neuropathy, type V is unknown. Only a small number of cases have been reported.","distal hereditary motor neuropathy, type V",0000292,GHR,https://ghr.nlm.nih.gov/condition/distal-hereditary-motor-neuropathy-type-v,C1833308,T047,Disorders
"What are the genetic changes related to distal hereditary motor neuropathy, type V ?",0000292-3,genetic changes,"Mutations in the BSCL2 and GARS genes cause distal hereditary motor neuropathy, type V.  The BSCL2 gene provides instructions for making a protein called seipin, whose function is unknown. Mutations in the BSCL2 gene likely alter the structure of seipin, causing it to fold into an incorrect 3-dimensional shape. Research findings indicate that misfolded seipin proteins accumulate in the endoplasmic reticulum, which is a structure inside the cell that is involved in protein processing and transport. This accumulation likely damages and kills motor neurons (specialized nerve cells in the brain and spinal cord that control muscle movement), leading to muscle weakness in the hands and feet.  The GARS gene provides instructions for making an enzyme called glycyl-tRNA synthetase, which is involved in the production (synthesis) of proteins. It is unclear how GARS gene mutations lead to distal hereditary motor neuropathy, type V. The mutations probably reduce the activity of glycyl-tRNA synthetase. A reduction in the activity of this enzyme may impair transmission of nerve impulses. As a result, nerve cells slowly lose the ability to communicate with muscles in the hands and feet.  Mutations in other genes may also cause distal hereditary motor neuropathy, type V.","distal hereditary motor neuropathy, type V",0000292,GHR,https://ghr.nlm.nih.gov/condition/distal-hereditary-motor-neuropathy-type-v,C1833308,T047,Disorders
"Is distal hereditary motor neuropathy, type V inherited ?",0000292-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  Some people who have the altered gene never develop the condition, a situation known as reduced penetrance.","distal hereditary motor neuropathy, type V",0000292,GHR,https://ghr.nlm.nih.gov/condition/distal-hereditary-motor-neuropathy-type-v,C1833308,T047,Disorders
"What are the treatments for distal hereditary motor neuropathy, type V ?",0000292-5,treatment,"These resources address the diagnosis or management of distal hereditary motor neuropathy, type V:  - Gene Review: Gene Review: BSCL2-Related Neurologic Disorders/Seipinopathy  - Gene Review: Gene Review: GARS-Associated Axonal Neuropathy  - Genetic Testing Registry: Distal hereditary motor neuronopathy type 5  - Genetic Testing Registry: Distal hereditary motor neuronopathy type 5B  - MedlinePlus Encyclopedia: High-Arched Foot   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","distal hereditary motor neuropathy, type V",0000292,GHR,https://ghr.nlm.nih.gov/condition/distal-hereditary-motor-neuropathy-type-v,C1833308,T047,Disorders
What is (are) distal myopathy 2 ?,0000293-1,information,"Distal myopathy 2 is a condition characterized by weakness of specific muscles that begins in adulthood. It is a form of muscular dystrophy that specifically involves muscles in the throat, lower legs, and forearms. Muscles farther from the center of the body, like the muscles of the lower legs and forearms, are known as distal muscles.  Muscle weakness in the ankles is usually the first symptom of distal myopathy 2. The weakness can also affect muscles in the hands, wrists, and shoulders. At first, the muscle weakness may be on only one side of the body, but both sides are eventually involved. This muscle weakness can slowly worsen and make actions like walking and lifting the fingers difficult.  Another characteristic feature of distal myopathy 2 is weakness of the vocal cords and throat. This weakness initially causes the voice to sound weak or breathy (hypophonic). Eventually, the voice becomes gurgling, hoarse, and nasal. The weakness can also cause difficulty swallowing (dysphagia).",distal myopathy 2,0000293,GHR,https://ghr.nlm.nih.gov/condition/distal-myopathy-2,C1853723,T047,Disorders
How many people are affected by distal myopathy 2 ?,0000293-2,frequency,The prevalence of distal myopathy 2 is unknown. At least two families with the condition have been described in the scientific literature.,distal myopathy 2,0000293,GHR,https://ghr.nlm.nih.gov/condition/distal-myopathy-2,C1853723,T047,Disorders
What are the genetic changes related to distal myopathy 2 ?,0000293-3,genetic changes,"A mutation in the MATR3 gene has been identified in people with distal myopathy 2. This gene provides instructions for making a protein called matrin 3, which is found in the nucleus of the cell as part of the nuclear matrix. The nuclear matrix is a network of proteins that provides structural support for the nucleus and aids in several important nuclear functions.  The function of the matrin 3 protein is unknown. This protein can attach to (bind) RNA, which is a chemical cousin of DNA. Some studies indicate that matrin 3 binds and stabilizes a type of RNA called messenger RNA (mRNA), which provides the genetic blueprint for proteins. Matrin 3 may also bind certain abnormal RNAs that might lead to nonfunctional or harmful proteins, thereby blocking the formation of such proteins. Other studies suggest that the matrin 3 protein may be involved in cell survival.  The MATR3 gene mutation identified in people with distal myopathy 2 changes a single protein building block (amino acid) in the matrin 3 protein. The effect of this mutation on the function of the protein is unknown, although one study suggests that the mutation may change the location of the protein in the nucleus. Researchers are working to determine how this gene mutation leads to the signs and symptoms of distal myopathy 2.",distal myopathy 2,0000293,GHR,https://ghr.nlm.nih.gov/condition/distal-myopathy-2,C1853723,T047,Disorders
Is distal myopathy 2 inherited ?,0000293-4,inheritance,"Distal myopathy 2 is inherited in an autosomal dominant pattern, which means one copy of the altered MATR3 gene in each cell is sufficient to cause the disorder.",distal myopathy 2,0000293,GHR,https://ghr.nlm.nih.gov/condition/distal-myopathy-2,C1853723,T047,Disorders
What are the treatments for distal myopathy 2 ?,0000293-5,treatment,"These resources address the diagnosis or management of distal myopathy 2:  - Genetic Testing Registry: Myopathy, distal, 2  - MedlinePlus Encyclopedia: Muscular Dystrophy  - National Institute of Neurological Disorders and Stroke: Muscular Dystrophy: Hope Through Research   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",distal myopathy 2,0000293,GHR,https://ghr.nlm.nih.gov/condition/distal-myopathy-2,C1853723,T047,Disorders
What is (are) DMD-associated dilated cardiomyopathy ?,0000294-1,information,"DMD-associated dilated cardiomyopathy is a form of heart disease that is caused by mutations in the DMD gene. Dilated cardiomyopathy enlarges and weakens the heart (cardiac) muscle, preventing the heart from pumping blood efficiently. Signs and symptoms of this condition can include an irregular heartbeat (arrhythmia), shortness of breath, extreme tiredness (fatigue), and swelling of the legs and feet. In males with DMD-associated dilated cardiomyopathy, heart problems usually develop early in life and worsen quickly, leading to heart failure in adolescence or early adulthood. In affected females, the condition appears later in life and worsens more slowly.  Dilated cardiomyopathy is a feature of two related conditions that are also caused by mutations in the DMD gene: Duchenne and Becker muscular dystrophy. In addition to heart disease, these conditions are characterized by progressive weakness and wasting of muscles used for movement (skeletal muscles). People with DMD-associated dilated cardiomyopathy typically do not have any skeletal muscle weakness or wasting, although they may have subtle changes in their skeletal muscle cells that are detectable through laboratory testing. Based on these skeletal muscle changes, DMD-associated dilated cardiomyopathy is sometimes classified as subclinical Becker muscular dystrophy.",DMD-associated dilated cardiomyopathy,0000294,GHR,https://ghr.nlm.nih.gov/condition/dmd-associated-dilated-cardiomyopathy,C0878544,T047,Disorders
How many people are affected by DMD-associated dilated cardiomyopathy ?,0000294-2,frequency,"DMD-associated dilated cardiomyopathy appears to be an uncommon condition, although its prevalence is unknown.",DMD-associated dilated cardiomyopathy,0000294,GHR,https://ghr.nlm.nih.gov/condition/dmd-associated-dilated-cardiomyopathy,C0878544,T047,Disorders
What are the genetic changes related to DMD-associated dilated cardiomyopathy ?,0000294-3,genetic changes,"DMD-associated dilated cardiomyopathy results from mutations in the DMD gene. This gene provides instructions for making a protein called dystrophin, which helps stabilize and protect muscle fibers and may play a role in chemical signaling within cells. The mutations responsible for DMD-associated dilated cardiomyopathy preferentially affect the activity of dystrophin in cardiac muscle cells. As a result of these mutations, affected individuals typically have little or no functional dystrophin in the heart. Without enough of this protein, cardiac muscle cells become damaged as the heart muscle repeatedly contracts and relaxes. The damaged muscle cells weaken and die over time, leading to the heart problems characteristic of DMD-associated dilated cardiomyopathy.  The mutations that cause DMD-associated dilated cardiomyopathy often lead to reduced amounts of dystrophin in skeletal muscle cells. However, enough of this protein is present to prevent weakness and wasting of the skeletal muscles.  Because DMD-associated dilated cardiomyopathy results from a shortage of dystrophin, it is classified as a dystrophinopathy.",DMD-associated dilated cardiomyopathy,0000294,GHR,https://ghr.nlm.nih.gov/condition/dmd-associated-dilated-cardiomyopathy,C0878544,T047,Disorders
Is DMD-associated dilated cardiomyopathy inherited ?,0000294-4,inheritance,"DMD-associated dilated cardiomyopathy has an X-linked pattern of inheritance. The DMD gene is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell usually leads to relatively mild heart disease that appears later in life. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes more severe signs and symptoms that occur earlier in life. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",DMD-associated dilated cardiomyopathy,0000294,GHR,https://ghr.nlm.nih.gov/condition/dmd-associated-dilated-cardiomyopathy,C0878544,T047,Disorders
What are the treatments for DMD-associated dilated cardiomyopathy ?,0000294-5,treatment,"These resources address the diagnosis or management of DMD-associated dilated cardiomyopathy:  - Gene Review: Gene Review: Dilated Cardiomyopathy Overview  - Gene Review: Gene Review: Dystrophinopathies  - Genetic Testing Registry: Dilated cardiomyopathy 3B  - Genetic Testing Registry: Duchenne muscular dystrophy  - National Heart, Lung, and Blood Institute: How Is Cardiomyopathy Diagnosed?  - National Heart, Lung, and Blood Institute: How Is Cardiomyopathy Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",DMD-associated dilated cardiomyopathy,0000294,GHR,https://ghr.nlm.nih.gov/condition/dmd-associated-dilated-cardiomyopathy,C0878544,T047,Disorders
What is (are) DOLK-congenital disorder of glycosylation ?,0000295-1,information,"DOLK-congenital disorder of glycosylation (DOLK-CDG, formerly known as congenital disorder of glycosylation type Im) is an inherited condition that often affects the heart but can also involve other body systems. The pattern and severity of this disorder's signs and symptoms vary among affected individuals.  Individuals with DOLK-CDG typically develop signs and symptoms of the condition during infancy or early childhood. Nearly all individuals with DOLK-CDG develop a weakened and enlarged heart (dilated cardiomyopathy). Other frequent signs and symptoms include recurrent seizures; developmental delay; poor muscle tone (hypotonia); and dry, scaly skin (ichthyosis). Less commonly, affected individuals can have distinctive facial features, kidney disease, hormonal abnormalities, or eye problems.  Individuals with DOLK-CDG typically do not survive into adulthood, often because of complications related to dilated cardiomyopathy, and some do not survive past infancy.",DOLK-congenital disorder of glycosylation,0000295,GHR,https://ghr.nlm.nih.gov/condition/dolk-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
How many people are affected by DOLK-congenital disorder of glycosylation ?,0000295-2,frequency,DOLK-CDG is likely a rare condition; at least 18 cases have been reported in the scientific literature.,DOLK-congenital disorder of glycosylation,0000295,GHR,https://ghr.nlm.nih.gov/condition/dolk-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
What are the genetic changes related to DOLK-congenital disorder of glycosylation ?,0000295-3,genetic changes,"DOLK-CDG is caused by mutations in the DOLK gene. This gene provides instructions for making the enzyme dolichol kinase, which facilitates the final step of the production of a compound called dolichol phosphate. This compound is critical for a process called glycosylation, which attaches groups of sugar molecules (oligosaccharides) to proteins. Glycosylation changes proteins in ways that are important for their functions. During glycosylation, sugars are added to dolichol phosphate in order to build the oligosaccharide chain. Once the chain is formed, dolichol phosphate transports the oligosaccharide to the protein that needs to be glycosylated and attaches it to a specific site on the protein.  Mutations in the DOLK gene lead to the production of abnormal dolichol kinase with reduced or absent activity. Without properly functioning dolichol kinase, dolichol phosphate is not produced and glycosylation cannot proceed normally. In particular, a protein known to stabilize heart muscle fibers, called alpha-dystroglycan, has been shown to have reduced glycosylation in people with DOLK-CDG. Impaired glycosylation of alpha-dystroglycan disrupts its normal function, which damages heart muscle fibers as they repeatedly contract and relax. Over time, the fibers weaken and break down, leading to dilated cardiomyopathy. The other signs and symptoms of DOLK-CDG are likely due to the abnormal glycosylation of additional proteins in other organs and tissues.",DOLK-congenital disorder of glycosylation,0000295,GHR,https://ghr.nlm.nih.gov/condition/dolk-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
Is DOLK-congenital disorder of glycosylation inherited ?,0000295-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",DOLK-congenital disorder of glycosylation,0000295,GHR,https://ghr.nlm.nih.gov/condition/dolk-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
What are the treatments for DOLK-congenital disorder of glycosylation ?,0000295-5,treatment,These resources address the diagnosis or management of DOLK-CDG:  - Gene Review: Gene Review: Congenital Disorders of N-Linked Glycosylation Pathway Overview  - Genetic Testing Registry: Congenital disorder of glycosylation type 1M  - MedlinePlus Encyclopedia: Dilated Cardiomyopathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,DOLK-congenital disorder of glycosylation,0000295,GHR,https://ghr.nlm.nih.gov/condition/dolk-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
What is (are) Donnai-Barrow syndrome ?,0000296-1,information,"Donnai-Barrow syndrome is an inherited disorder that affects many parts of the body. This disorder is characterized by unusual facial features, including prominent, wide-set eyes with outer corners that point downward; a short bulbous nose with a flat nasal bridge; ears that are rotated backward; and a widow's peak hairline.  Individuals with Donnai-Barrow syndrome have severe hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss). In addition, they often experience vision problems, including extreme nearsightedness (high myopia), detachment or deterioration of the light-sensitive tissue in the back of the eye (the retina), and progressive vision loss. Some have a gap or split in the colored part of the eye (iris coloboma).  In almost all people with Donnai-Barrow syndrome, the tissue connecting the left and right halves of the brain (corpus callosum) is underdeveloped or absent. Affected individuals may also have other structural abnormalities of the brain. They generally have mild to moderate intellectual disability and developmental delay.  People with Donnai-Barrow syndrome may also have a hole in the muscle that separates the abdomen from the chest cavity (the diaphragm), which is called a congenital diaphragmatic hernia. This potentially serious birth defect allows the stomach and intestines to move into the chest and possibly crowd the developing heart and lungs. An opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the navel may also occur in affected individuals. Occasionally people with Donnai-Barrow syndrome have abnormalities of the intestine, heart, or other organs.",Donnai-Barrow syndrome,0000296,GHR,https://ghr.nlm.nih.gov/condition/donnai-barrow-syndrome,C1857277,T047,Disorders
How many people are affected by Donnai-Barrow syndrome ?,0000296-2,frequency,"Although its prevalence is unknown, Donnai-Barrow syndrome appears to be a rare disorder. A few dozen affected individuals have been reported in many regions of the world.",Donnai-Barrow syndrome,0000296,GHR,https://ghr.nlm.nih.gov/condition/donnai-barrow-syndrome,C1857277,T047,Disorders
What are the genetic changes related to Donnai-Barrow syndrome ?,0000296-3,genetic changes,"Mutations in the LRP2 gene cause Donnai-Barrow syndrome. The LRP2 gene provides instructions for making a protein called megalin, which functions as a receptor. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. Together, ligands and their receptors trigger signals that affect cell development and function. Megalin has many ligands involved in various body processes, including the absorption of vitamins A and D, immune functioning, stress response, and the transport of fats in the bloodstream.  Megalin is embedded in the membrane of cells that line the surfaces and cavities of the body (epithelial cells). The receptor helps move its ligands from the cell surface into the cell (endocytosis). It is active in the development and function of many parts of the body, including the brain and spinal cord (central nervous system), eyes, ears, lungs, intestine, reproductive system, and the small tubes in the kidneys where urine is formed (renal tubules).  LRP2 gene mutations that cause Donnai-Barrow syndrome are believed to result in the absence of functional megalin protein. The lack of functional megalin in the renal tubules causes megalin's various ligands to be excreted in the urine rather than being absorbed back into the bloodstream. The features of Donnai-Barrow syndrome are probably caused by the inability of megalin to help absorb these ligands, disruption of biochemical signaling pathways, or other effects of the nonfunctional megalin protein. However, it is unclear how these abnormalities result in the specific signs and symptoms of the disorder.  A condition previously classified as a separate disorder called facio-oculo-acoustico-renal (FOAR) syndrome has also been found to be caused by LRP2 mutations. FOAR syndrome is now considered to be the same disorder as Donnai-Barrow syndrome.",Donnai-Barrow syndrome,0000296,GHR,https://ghr.nlm.nih.gov/condition/donnai-barrow-syndrome,C1857277,T047,Disorders
Is Donnai-Barrow syndrome inherited ?,0000296-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. In almost all cases, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene but typically do not show signs and symptoms of the condition.  One individual with Donnai-Barrow syndrome was found to have inherited both copies of the mutated gene from his father as a result of a genetic change called uniparental disomy (UPD). UPD occurs when a person receives two copies of a chromosome, or part of a chromosome, from one parent and no copies from the other parent. UPD can occur as a random event during the formation of egg or sperm cells or may happen in early fetal development.",Donnai-Barrow syndrome,0000296,GHR,https://ghr.nlm.nih.gov/condition/donnai-barrow-syndrome,C1857277,T047,Disorders
What are the treatments for Donnai-Barrow syndrome ?,0000296-5,treatment,These resources address the diagnosis or management of Donnai-Barrow syndrome:  - Gene Review: Gene Review: Donnai-Barrow Syndrome  - Genetic Testing Registry: Donnai Barrow syndrome  - MedlinePlus Encyclopedia: Diaphragmatic Hernia  - MedlinePlus Encyclopedia: Hearing Loss - Infants  - MedlinePlus Encyclopedia: Omphalocele  - Nemours Foundation: Hearing Evaluation in Children   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Donnai-Barrow syndrome,0000296,GHR,https://ghr.nlm.nih.gov/condition/donnai-barrow-syndrome,C1857277,T047,Disorders
What is (are) Donohue syndrome ?,0000297-1,information,"Donohue syndrome is a rare disorder characterized by severe insulin resistance, a condition in which the body's tissues and organs do not respond properly to the hormone insulin. Insulin normally helps regulate blood sugar levels by controlling how much sugar (in the form of glucose) is passed from the bloodstream into cells to be used as energy. Severe insulin resistance leads to problems with regulating blood sugar levels and affects the development and function of organs and tissues throughout the body.  Severe insulin resistance underlies the varied signs and symptoms of Donohue syndrome. Individuals with Donohue syndrome are unusually small starting before birth, and affected infants experience failure to thrive, which means they do not grow and gain weight at the expected rate. Additional features that become apparent soon after birth include a lack of fatty tissue under the skin (subcutaneous fat); wasting (atrophy) of muscles; excessive body hair growth (hirsutism); multiple cysts on the ovaries in females; and enlargement of the nipples, genitalia, kidneys, heart, and other organs. Most affected individuals also have a skin condition called acanthosis nigricans, in which the skin in body folds and creases becomes thick, dark, and velvety. Distinctive facial features in people with Donohue syndrome include bulging eyes, thick lips, upturned nostrils, and low-set ears. Affected individuals develop recurrent, life-threatening infections beginning in infancy.  Donohue syndrome is one of a group of related conditions described as inherited severe insulin resistance syndromes. These disorders, which also include Rabson-Mendenhall syndrome and type A insulin resistance syndrome, are considered part of a spectrum. Donohue syndrome represents the most severe end of the spectrum; most children with this condition do not survive beyond age 2.",Donohue syndrome,0000297,GHR,https://ghr.nlm.nih.gov/condition/donohue-syndrome,C0265344,T047,Disorders
How many people are affected by Donohue syndrome ?,0000297-2,frequency,Donohue syndrome is estimated to affect less than 1 per million people worldwide. Several dozen cases have been reported in the medical literature.,Donohue syndrome,0000297,GHR,https://ghr.nlm.nih.gov/condition/donohue-syndrome,C0265344,T047,Disorders
What are the genetic changes related to Donohue syndrome ?,0000297-3,genetic changes,"Donohue syndrome results from mutations in the INSR gene. This gene provides instructions for making a protein called an insulin receptor, which is found in many types of cells. Insulin receptors are embedded in the outer membrane surrounding the cell, where they attach (bind) to insulin circulating in the bloodstream. This binding triggers signaling pathways that influence many cell functions.  The INSR gene mutations that cause Donohue syndrome greatly reduce the number of insulin receptors that reach the cell membrane or disrupt the function of these receptors. Although insulin is present in the bloodstream, without functional receptors it cannot exert its effects on cells and tissues. This severe resistance to the effects of insulin impairs blood sugar regulation and affects many aspects of development in people with Donohue syndrome.",Donohue syndrome,0000297,GHR,https://ghr.nlm.nih.gov/condition/donohue-syndrome,C0265344,T047,Disorders
Is Donohue syndrome inherited ?,0000297-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Donohue syndrome,0000297,GHR,https://ghr.nlm.nih.gov/condition/donohue-syndrome,C0265344,T047,Disorders
What are the treatments for Donohue syndrome ?,0000297-5,treatment,These resources address the diagnosis or management of Donohue syndrome:  - Genetic Testing Registry: Leprechaunism syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Donohue syndrome,0000297,GHR,https://ghr.nlm.nih.gov/condition/donohue-syndrome,C0265344,T047,Disorders
What is (are) DOORS syndrome ?,0000298-1,information,"DOORS syndrome is a disorder involving multiple abnormalities that are present from birth (congenital). ""DOORS"" is an abbreviation for the major features of the disorder including deafness; short or absent nails (onychodystrophy); short fingers and toes (osteodystrophy); developmental delay and intellectual disability (previously called mental retardation); and seizures. Some people with DOORS syndrome do not have all of these features.  Most people with DOORS syndrome have profound hearing loss caused by changes in the inner ears (sensorineural deafness). Developmental delay and intellectual disability are also often severe in this disorder.  The nail abnormalities affect both the hands and the feet in DOORS syndrome. Impaired growth of the bones at the tips of the fingers and toes (hypoplastic terminal phalanges) account for the short fingers and toes characteristic of this disorder. Some affected individuals also have an extra bone and joint in their thumbs, causing the thumbs to look more like the other fingers (triphalangeal thumbs).  The seizures that occur in people with DOORS syndrome usually start in infancy. The most common seizures in people with this condition are generalized tonic-clonic seizures (also known as grand mal seizures), which cause muscle rigidity, convulsions, and loss of consciousness. Affected individuals may also have other types of seizures, including partial seizures, which affect only one area of the brain and do not cause a loss of consciousness; absence seizures, which cause loss of consciousness for a short period that appears as a staring spell; or myoclonic seizures, which cause rapid, uncontrolled muscle jerks. In some affected individuals the seizures increase in frequency and become more severe and difficult to control, and a potentially life-threatening prolonged seizure (status epilepticus) can occur.  Other features that can occur in people with DOORS syndrome include an unusually small head size (microcephaly) and facial differences, most commonly a wide, bulbous nose. A narrow or high arched roof of the mouth (palate), broadening of the ridges in the upper and lower jaw that contain the sockets of the teeth (alveolar ridges), or shortening of the membrane between the floor of the mouth and the tongue (frenulum) have also been observed in some affected individuals. People with DOORS syndrome may also have dental abnormalities, structural abnormalities of the heart or urinary tract, and abnormally low levels of thyroid hormones (hypothyroidism). Most affected individuals also have higher-than-normal levels of a substance called 2-oxoglutaric acid in their urine; these levels can fluctuate between normal and elevated.",DOORS syndrome,0000298,GHR,https://ghr.nlm.nih.gov/condition/doors-syndrome,C0795934,T047,Disorders
How many people are affected by DOORS syndrome ?,0000298-2,frequency,DOORS syndrome is a rare disorder; its prevalence is unknown. Approximately 50 affected individuals have been described in the medical literature.,DOORS syndrome,0000298,GHR,https://ghr.nlm.nih.gov/condition/doors-syndrome,C0795934,T047,Disorders
What are the genetic changes related to DOORS syndrome ?,0000298-3,genetic changes,"DOORS syndrome can be caused by mutations in the TBC1D24 gene. This gene provides instructions for making a protein whose specific function in the cell is unclear. Studies suggest the protein may have several roles in cells. The TBC1D24 protein belongs to a group of proteins that are involved in the movement (transport) of vesicles, which are small sac-like structures that transport proteins and other materials within cells. Research suggests that the TBC1D24 protein may also help cells respond to oxidative stress. Oxidative stress occurs when unstable molecules called free radicals accumulate to levels that can damage or kill cells. Studies indicate that the TBC1D24 protein is active in a variety of organs and tissues; it is particularly active in the brain and likely plays an important role in normal brain development. The TBC1D24 protein is also active in specialized structures called stereocilia. In the inner ear, stereocilia project from certain cells called hair cells. The stereocilia bend in response to sound waves, which is critical for converting sound waves to nerve impulses.  TBC1D24 gene mutations that cause DOORS syndrome are thought to reduce or eliminate the function of the TBC1D24 protein, but the specific mechanism by which loss of TBC1D24 function leads to the signs and symptoms of DOORS syndrome is not well understood.  In about half of affected individuals, no TBC1D24 gene mutation has been identified. The cause of DOORS syndrome in these individuals is unknown.",DOORS syndrome,0000298,GHR,https://ghr.nlm.nih.gov/condition/doors-syndrome,C0795934,T047,Disorders
Is DOORS syndrome inherited ?,0000298-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",DOORS syndrome,0000298,GHR,https://ghr.nlm.nih.gov/condition/doors-syndrome,C0795934,T047,Disorders
What are the treatments for DOORS syndrome ?,0000298-5,treatment,These resources address the diagnosis or management of DOORS syndrome:  - Gene Review: Gene Review: TBC1D24-Related Disorders   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,DOORS syndrome,0000298,GHR,https://ghr.nlm.nih.gov/condition/doors-syndrome,C0795934,T047,Disorders
What is (are) dopa-responsive dystonia ?,0000299-1,information,"Dopa-responsive dystonia is a disorder that involves involuntary muscle contractions, tremors, and other uncontrolled movements (dystonia). The features of this condition range from mild to severe. This form of dystonia is called dopa-responsive dystonia because the signs and symptoms typically improve with sustained use of a medication known as L-Dopa.  Signs and symptoms of dopa-responsive dystonia usually appear during childhood, most commonly around age 6. The first signs of the condition are typically the development of inward- and upward-turning feet (clubfeet) and dystonia in the lower limbs. The dystonia spreads to the upper limbs over time; beginning in adolescence, the whole body is typically involved. Affected individuals may have unusual limb positioning and a lack of coordination when walking or running. Some people with this condition have sleep problems or episodes of depression more frequently than would normally be expected.  Over time, affected individuals often develop a group of movement abnormalities called parkinsonism. These abnormalities include unusually slow movement (bradykinesia), muscle rigidity, tremors, and an inability to hold the body upright and balanced (postural instability).  The movement difficulties associated with dopa-responsive dystonia usually worsen with age but stabilize around age 30. A characteristic feature of dopa-responsive dystonia is worsening of movement problems later in the day and an improvement of symptoms in the morning, after sleep (diurnal fluctuation).  Rarely, the movement problems associated with dopa-responsive dystonia do not appear until adulthood. In these adult-onset cases, parkinsonism usually develops before dystonia, and movement problems are slow to worsen and do not show diurnal fluctuations.",dopa-responsive dystonia,0000299,GHR,https://ghr.nlm.nih.gov/condition/dopa-responsive-dystonia,C1851920,T047,Disorders
How many people are affected by dopa-responsive dystonia ?,0000299-2,frequency,"Dopa-responsive dystonia is estimated to affect 1 per million people worldwide. However, the disorder is likely underdiagnosed because the condition may not be identified in people with mild symptoms, or it may be misdiagnosed in people who have symptoms similar to other movement disorders.",dopa-responsive dystonia,0000299,GHR,https://ghr.nlm.nih.gov/condition/dopa-responsive-dystonia,C1851920,T047,Disorders
What are the genetic changes related to dopa-responsive dystonia ?,0000299-3,genetic changes,"Mutations in the GCH1 gene are the most common cause of dopa-responsive dystonia. Less often, mutations in the TH or SPR gene cause this condition.  The GCH1 gene provides instructions for making an enzyme called GTP cyclohydrolase. This enzyme is involved in the first of three steps in the production of a molecule called tetrahydrobiopterin (BH4). The SPR gene, which provides instructions for making the sepiapterin reductase enzyme, is involved in the last step of tetrahydrobiopterin production. Tetrahydrobiopterin helps process several protein building blocks (amino acids), and is involved in the production of chemicals called neurotransmitters, which transmit signals between nerve cells in the brain. Specifically, tetrahydrobiopterin is involved in the production of two neurotransmitters called dopamine and serotonin. Among their many functions, dopamine transmits signals within the brain to produce smooth physical movements, and serotonin regulates mood, emotion, sleep, and appetite.  The protein produced from the TH gene is also involved in dopamine production. The TH gene provides instructions for making the enzyme tyrosine hydroxylase, which helps convert the amino acid tyrosine to dopamine.  Mutations in the GCH1 or SPR gene impair the production of tetrahydrobiopterin, which leads to a decrease in the amount of available dopamine. TH gene mutations result in the production of a tyrosine hydroxylase enzyme with reduced function, which leads to a decrease in dopamine production. A reduction in the amount of dopamine interferes with the brain's ability to produce smooth physical movements, resulting in the dystonia, tremor, and other movement problems associated with dopa-responsive dystonia. Sleep and mood disorders also occur in some individuals with GCH1 or SPR gene mutations; these disorders likely result from a disruption in the production of serotonin. Problems with sleep and episodes of depression are not seen in people with dopa-responsive dystonia caused by TH gene mutations, which is sometimes referred to as Segawa syndrome.  Some people with dopa-responsive dystonia do not have an identified mutation in the GCH1, TH, or SPR gene. The cause of the condition in these individuals is unknown.",dopa-responsive dystonia,0000299,GHR,https://ghr.nlm.nih.gov/condition/dopa-responsive-dystonia,C1851920,T047,Disorders
Is dopa-responsive dystonia inherited ?,0000299-4,inheritance,"When dopa-responsive dystonia is caused by mutations in the GCH1 gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  Some people who inherit the altered GCH1 gene never develop features of dopa-responsive dystonia. (This situation is known as reduced penetrance.) It is unclear why some people with a mutated gene develop the disease and other people with a mutated gene do not. For unknown reasons, dopa-responsive dystonia caused by mutations in the GCH1 gene affects females two to four times more often than males.  When TH gene mutations are responsible for causing dopa-responsive dystonia, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  When dopa-responsive dystonia is caused by mutations in the SPR gene, it can have either an autosomal recessive or, less commonly, an autosomal dominant pattern of inheritance.",dopa-responsive dystonia,0000299,GHR,https://ghr.nlm.nih.gov/condition/dopa-responsive-dystonia,C1851920,T047,Disorders
What are the treatments for dopa-responsive dystonia ?,0000299-5,treatment,"These resources address the diagnosis or management of dopa-responsive dystonia:  - Dartmouth-Hitchcock Children's Hospital at Dartmouth  - Gene Review: Gene Review: Dystonia Overview  - Gene Review: Gene Review: GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia  - Genetic Testing Registry: Dystonia 5, Dopa-responsive type  - Genetic Testing Registry: Segawa syndrome, autosomal recessive  - Genetic Testing Registry: Sepiapterin reductase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",dopa-responsive dystonia,0000299,GHR,https://ghr.nlm.nih.gov/condition/dopa-responsive-dystonia,C1851920,T047,Disorders
What is (are) dopamine beta-hydroxylase deficiency ?,0000300-1,information,"Dopamine beta ()-hydroxylase deficiency is a condition that affects the autonomic nervous system, which controls involuntary body processes such as the regulation of blood pressure and body temperature. Problems related to this disorder can first appear during infancy. Early signs and symptoms may include episodes of vomiting, dehydration, decreased blood pressure (hypotension), difficulty maintaining body temperature, and low blood sugar (hypoglycemia).  Individuals with dopamine -hydroxylase deficiency typically experience a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting. This sudden drop in blood pressure is usually more severe when getting out of bed in the morning, during hot weather, and as a person gets older. People with dopamine -hydroxylase deficiency experience extreme fatigue during exercise (exercise intolerance) due to their problems maintaining a normal blood pressure.  Other features of dopamine -hydroxylase deficiency include droopy eyelids (ptosis), nasal congestion, and an inability to stand for a prolonged period of time. Affected males may also experience retrograde ejaculation, a discharge of semen backwards into the bladder. Less common features include an unusually large range of joint movement (hypermobility) and muscle weakness.",dopamine beta-hydroxylase deficiency,0000300,GHR,https://ghr.nlm.nih.gov/condition/dopamine-beta-hydroxylase-deficiency,C0342687,T047,Disorders
How many people are affected by dopamine beta-hydroxylase deficiency ?,0000300-2,frequency,"Dopamine -hydroxylase deficiency is a very rare disorder. Fewer than 20 affected individuals, all of Western European descent, have been described in the scientific literature.",dopamine beta-hydroxylase deficiency,0000300,GHR,https://ghr.nlm.nih.gov/condition/dopamine-beta-hydroxylase-deficiency,C0342687,T047,Disorders
What are the genetic changes related to dopamine beta-hydroxylase deficiency ?,0000300-3,genetic changes,"Mutations in the DBH gene cause dopamine -hydroxylase deficiency. The DBH gene provides instructions for producing the enzyme dopamine -hydroxylase. This enzyme converts dopamine to norepinephrine, both of which are chemical messengers (neurotransmitters) that transmit signals between nerve cells.  DBH gene mutations result in the production of a nonfunctional dopamine -hydroxylase enzyme. People who lack functional dopamine -hydroxylase cannot convert dopamine to norepinephrine, which leads to a shortage of norepinephrine in the body. The lack of norepinephrine causes difficulty with regulating blood pressure and other autonomic nervous system problems seen in dopamine -hydroxylase deficiency.",dopamine beta-hydroxylase deficiency,0000300,GHR,https://ghr.nlm.nih.gov/condition/dopamine-beta-hydroxylase-deficiency,C0342687,T047,Disorders
Is dopamine beta-hydroxylase deficiency inherited ?,0000300-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",dopamine beta-hydroxylase deficiency,0000300,GHR,https://ghr.nlm.nih.gov/condition/dopamine-beta-hydroxylase-deficiency,C0342687,T047,Disorders
What are the treatments for dopamine beta-hydroxylase deficiency ?,0000300-5,treatment,These resources address the diagnosis or management of dopamine beta-hydroxylase deficiency:  - Gene Review: Gene Review: Dopamine Beta-Hydroxylase Deficiency  - Genetic Testing Registry: Dopamine beta hydroxylase deficiency  - Vanderbilt Autonomic Dysfunction Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,dopamine beta-hydroxylase deficiency,0000300,GHR,https://ghr.nlm.nih.gov/condition/dopamine-beta-hydroxylase-deficiency,C0342687,T047,Disorders
What is (are) dopamine transporter deficiency syndrome ?,0000301-1,information,"Dopamine transporter deficiency syndrome is a rare movement disorder. The condition is also known as infantile parkinsonism-dystonia because the problems with movement (dystonia and parkinsonism, described below) usually start in infancy and worsen over time. However, the features of the condition sometimes do not appear until childhood or later.  People with dopamine transporter deficiency syndrome develop a pattern of involuntary, sustained muscle contractions known as dystonia. The dystonia is widespread (generalized), affecting many different muscles. The continuous muscle cramping and spasms cause difficulty with basic activities, including speaking, eating, drinking, picking up objects, and walking.  As the condition worsens, affected individuals develop parkinsonism, which is a group of movement abnormalities including tremors, unusually slow movement (bradykinesia), rigidity, and an inability to hold the body upright and balanced (postural instability). Other signs and symptoms that can develop include abnormal eye movements; reduced facial expression (hypomimia); disturbed sleep; frequent episodes of pneumonia; and problems with the digestive system, including a backflow of acidic stomach contents into the esophagus (gastroesophageal reflux) and constipation.  People with dopamine transporter deficiency syndrome may have a shortened lifespan, although the long-term effects of this condition are not fully understood. Children with this condition have died from pneumonia and breathing problems. When the first signs and symptoms appear later in life, affected individuals may survive into adulthood.",dopamine transporter deficiency syndrome,0000301,GHR,https://ghr.nlm.nih.gov/condition/dopamine-transporter-deficiency-syndrome,C2751067,T047,Disorders
How many people are affected by dopamine transporter deficiency syndrome ?,0000301-2,frequency,Dopamine transporter deficiency syndrome appears to be a rare disease; only about 20 affected individuals have been described in the medical literature. Researchers believe that the condition is probably underdiagnosed because its signs and symptoms overlap with cerebral palsy and other movement disorders.,dopamine transporter deficiency syndrome,0000301,GHR,https://ghr.nlm.nih.gov/condition/dopamine-transporter-deficiency-syndrome,C2751067,T047,Disorders
What are the genetic changes related to dopamine transporter deficiency syndrome ?,0000301-3,genetic changes,"Dopamine transporter deficiency syndrome is caused by mutations in the SLC6A3 gene. This gene provides instructions for making a protein called the dopamine transporter. This protein is embedded in the membrane of certain nerve cells (neurons) in the brain, where it transports a molecule called dopamine into the cell. Dopamine is a chemical messenger (neurotransmitter) that relays signals from one neuron to another. Dopamine has many important functions, including playing complex roles in thought (cognition), motivation, behavior, and control of movement.  Mutations in the SLC6A3 gene impair or eliminate the function of the dopamine transporter. The resulting shortage (deficiency) of functional transporter disrupts dopamine signaling in the brain. Although dopamine has a critical role in controlling movement, it is unclear how altered dopamine signaling causes the specific movement abnormalities found in people with dopamine transporter deficiency syndrome.  Studies suggest that the age at which signs and symptoms appear is related to how severely the function of the dopamine transporter is affected. Affected individuals who develop movement problems starting in infancy most often have transporter activity that is less than 5 percent of normal. Those whose movement problems appear in childhood or later tend to have somewhat higher levels of transporter activity, although they are still lower than normal. Researchers speculate that higher levels of transporter activity may delay the onset of the disease in these individuals.",dopamine transporter deficiency syndrome,0000301,GHR,https://ghr.nlm.nih.gov/condition/dopamine-transporter-deficiency-syndrome,C2751067,T047,Disorders
Is dopamine transporter deficiency syndrome inherited ?,0000301-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",dopamine transporter deficiency syndrome,0000301,GHR,https://ghr.nlm.nih.gov/condition/dopamine-transporter-deficiency-syndrome,C2751067,T047,Disorders
What are the treatments for dopamine transporter deficiency syndrome ?,0000301-5,treatment,These resources address the diagnosis or management of dopamine transporter deficiency syndrome:  - Gene Review: Gene Review: Parkinson Disease Overview  - Genetic Testing Registry: Infantile Parkinsonism-dystonia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,dopamine transporter deficiency syndrome,0000301,GHR,https://ghr.nlm.nih.gov/condition/dopamine-transporter-deficiency-syndrome,C2751067,T047,Disorders
What is (are) Dowling-Degos disease ?,0000302-1,information,"Dowling-Degos disease is a skin condition characterized by a lacy or net-like (reticulate) pattern of abnormally dark skin coloring (hyperpigmentation), particularly in the body's folds and creases. These skin changes typically first appear in the armpits and groin area and can later spread to other skin folds such as the crook of the elbow and back of the knee. Less commonly, pigmentation changes can also occur on the wrist, back of the hand, face, scalp, scrotum (in males), and vulva (in females). These areas of hyperpigmentation do not darken with exposure to sunlight and cause no health problems.  Individuals with Dowling-Degos disease may also have dark lesions on the face and back that resemble blackheads, red bumps around the mouth that resemble acne, or depressed or pitted scars on the face similar to acne scars but with no history of acne. Cysts within the hair follicle (pilar cysts) may develop, most commonly on the scalp. Rarely, affected individuals have patches of skin that are unusually light in color (hypopigmented).  The pigmentation changes characteristic of Dowling-Degos disease typically begin in late childhood or in adolescence, although in some individuals, features of the condition do not appear until adulthood. New areas of hyperpigmentation tend to develop over time, and the other skin lesions tend to increase in number as well. While the skin changes caused by Dowling-Degos disease can be bothersome, they typically cause no health problems.  A condition called Galli-Galli disease has signs and symptoms similar to those of Dowling-Degos disease. In addition to pigmentation changes, individuals with Galli-Galli disease also have a breakdown of cells in the outer layer of skin (acantholysis). Acantholysis can cause skin irritation and itchiness. These conditions used to be considered two separate disorders, but Galli-Galli disease and Dowling-Degos disease are now regarded as the same condition.",Dowling-Degos disease,0000302,GHR,https://ghr.nlm.nih.gov/condition/dowling-degos-disease,C3714534,T019,Disorders
How many people are affected by Dowling-Degos disease ?,0000302-2,frequency,"Dowling-Degos disease appears to be a rare condition, although its prevalence is unknown.",Dowling-Degos disease,0000302,GHR,https://ghr.nlm.nih.gov/condition/dowling-degos-disease,C3714534,T019,Disorders
What are the genetic changes related to Dowling-Degos disease ?,0000302-3,genetic changes,"Mutations in the KRT5 gene cause Dowling-Degos disease. The KRT5 gene provides instructions for making a protein called keratin 5. Keratins are a family of proteins that form the structural framework of certain cells, particularly cells that make up the skin, hair, and nails. Keratin 5 is produced in cells called keratinocytes found in the outer layer of the skin (the epidermis). Keratin 5 is one component of molecules called keratin intermediate filaments. These filaments assemble into strong networks that help attach keratinocytes together and anchor the epidermis to underlying layers of skin. Researchers believe that keratin 5 may also play a role in transporting melanosomes, which are cellular structures that produce a pigment called melanin. The transport of these structures into keratinocytes is important for normal skin coloration (pigmentation).  KRT5 gene mutations that cause Dowling-Degos disease lead to a decrease in the amount of functional keratin 5 protein that is produced. A reduction in keratin 5 can impair the formation of keratin intermediate filaments. As a result, the normal organization of the epidermis is altered, leading to the development of different types of skin lesions. Additionally, a decrease in keratin 5 may disrupt the movement of pigment-carrying melanosomes into keratinocytes, where they are needed for normal skin pigmentation. This disruption of melanosome transport is thought to cause the pigmentation abnormalities seen in individuals with Dowling-Degos disease.  Some people with Dowling-Degos disease do not have an identified mutation in the KRT5 gene. In these cases, the cause of the condition is unknown.",Dowling-Degos disease,0000302,GHR,https://ghr.nlm.nih.gov/condition/dowling-degos-disease,C3714534,T019,Disorders
Is Dowling-Degos disease inherited ?,0000302-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Dowling-Degos disease,0000302,GHR,https://ghr.nlm.nih.gov/condition/dowling-degos-disease,C3714534,T019,Disorders
What are the treatments for Dowling-Degos disease ?,0000302-5,treatment,These resources address the diagnosis or management of Dowling-Degos disease:  - Cleveland Clinic: Skin Care Concerns  - Genetic Testing Registry: Reticulate acropigmentation of Kitamura   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Dowling-Degos disease,0000302,GHR,https://ghr.nlm.nih.gov/condition/dowling-degos-disease,C3714534,T019,Disorders
What is (are) Down syndrome ?,0000303-1,information,"Down syndrome is a chromosomal condition that is associated with intellectual disability, a characteristic facial appearance, and weak muscle tone (hypotonia) in infancy. All affected individuals experience cognitive delays, but the intellectual disability is usually mild to moderate.  People with Down syndrome may have a variety of birth defects. About half of all affected children are born with a heart defect. Digestive abnormalities, such as a blockage of the intestine, are less common.  Individuals with Down syndrome have an increased risk of developing several medical conditions. These include gastroesophageal reflux, which is a backflow of acidic stomach contents into the esophagus, and celiac disease, which is an intolerance of a wheat protein called gluten. About 15 percent of people with Down syndrome have an underactive thyroid gland (hypothyroidism). The thyroid gland is a butterfly-shaped organ in the lower neck that produces hormones. Individuals with Down syndrome also have an increased risk of hearing and vision problems. Additionally, a small percentage of children with Down syndrome develop cancer of blood-forming cells (leukemia).  Delayed development and behavioral problems are often reported in children with Down syndrome. Affected individuals' speech and language develop later and more slowly than in children without Down syndrome, and affected individuals' speech may be more difficult to understand. Behavioral issues can include attention problems, obsessive/compulsive behavior, and stubbornness or tantrums. A small percentage of people with Down syndrome are also diagnosed with developmental conditions called autism spectrum disorders, which affect communication and social interaction.  People with Down syndrome often experience a gradual decline in thinking ability (cognition) as they age, usually starting around age 50. Down syndrome is also associated with an increased risk of developing Alzheimer disease, a brain disorder that results in a gradual loss of memory, judgment, and ability to function. Approximately half of adults with Down syndrome develop Alzheimer disease. Although Alzheimer disease is usually a disorder that occurs in older adults, people with Down syndrome usually develop this condition in their fifties or sixties.",Down syndrome,0000303,GHR,https://ghr.nlm.nih.gov/condition/down-syndrome,C0039082,T019,Disorders
How many people are affected by Down syndrome ?,0000303-2,frequency,"Down syndrome occurs in about 1 in 800 newborns. About 5,300 babies with Down syndrome are born in the United States each year, and an estimated 250,000 people in this country have the condition. Although women of any age can have a child with Down syndrome, the chance of having a child with this condition increases as a woman gets older.",Down syndrome,0000303,GHR,https://ghr.nlm.nih.gov/condition/down-syndrome,C0039082,T019,Disorders
What are the genetic changes related to Down syndrome ?,0000303-3,genetic changes,"Most cases of Down syndrome result from trisomy 21, which means each cell in the body has three copies of chromosome 21 instead of the usual two copies.  Less commonly, Down syndrome occurs when part of chromosome 21 becomes attached (translocated) to another chromosome during the formation of reproductive cells (eggs and sperm) in a parent or very early in fetal development. Affected people have two normal copies of chromosome 21 plus extra material from chromosome 21 attached to another chromosome, resulting in three copies of genetic material from chromosome 21. Affected individuals with this genetic change are said to have translocation Down syndrome.  A very small percentage of people with Down syndrome have an extra copy of chromosome 21 in only some of the body's cells. In these people, the condition is called mosaic Down syndrome.  Researchers believe that having extra copies of genes on chromosome 21 disrupts the course of normal development, causing the characteristic features of Down syndrome and the increased risk of health problems associated with this condition.",Down syndrome,0000303,GHR,https://ghr.nlm.nih.gov/condition/down-syndrome,C0039082,T019,Disorders
Is Down syndrome inherited ?,0000303-4,inheritance,"Most cases of Down syndrome are not inherited. When the condition is caused by trisomy 21, the chromosomal abnormality occurs as a random event during the formation of reproductive cells in a parent. The abnormality usually occurs in egg cells, but it occasionally occurs in sperm cells. An error in cell division called nondisjunction results in a reproductive cell with an abnormal number of chromosomes. For example, an egg or sperm cell may gain an extra copy of chromosome 21. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have an extra chromosome 21 in each of the body's cells.  People with translocation Down syndrome can inherit the condition from an unaffected parent. The parent carries a rearrangement of genetic material between chromosome 21 and another chromosome. This rearrangement is called a balanced translocation. No genetic material is gained or lost in a balanced translocation, so these chromosomal changes usually do not cause any health problems. However, as this translocation is passed to the next generation, it can become unbalanced. People who inherit an unbalanced translocation involving chromosome 21 may have extra genetic material from chromosome 21, which causes Down syndrome.  Like trisomy 21, mosaic Down syndrome is not inherited. It occurs as a random event during cell division early in fetal development. As a result, some of the body's cells have the usual two copies of chromosome 21, and other cells have three copies of this chromosome.",Down syndrome,0000303,GHR,https://ghr.nlm.nih.gov/condition/down-syndrome,C0039082,T019,Disorders
What are the treatments for Down syndrome ?,0000303-5,treatment,These resources address the diagnosis or management of Down syndrome:  - GeneFacts: Down Syndrome: Diagnosis  - GeneFacts: Down Syndrome: Management  - Genetic Testing Registry: Complete trisomy 21 syndrome  - National Down Syndrome Congress: Health Care  - National Down Syndrome Congress: Speech and Language  - National Down Syndrome Society: Health Care  - National Down Syndrome Society: Therapies and Development   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Down syndrome,0000303,GHR,https://ghr.nlm.nih.gov/condition/down-syndrome,C0039082,T019,Disorders
What is (are) Duane-radial ray syndrome ?,0000304-1,information,"Duane-radial ray syndrome is a disorder that affects the eyes and causes abnormalities of bones in the arms and hands. This condition is characterized by a particular problem with eye movement called Duane anomaly (also known as Duane syndrome). This abnormality results from the improper development of certain nerves that control eye movement. Duane anomaly limits outward eye movement (toward the ear), and in some cases may limit inward eye movement (toward the nose). Also, as the eye moves inward, the eye opening becomes narrower and the eyeball may pull back (retract) into its socket.  Bone abnormalities in the hands include malformed or absent thumbs, an extra thumb, or a long thumb that looks like a finger. Partial or complete absence of bones in the forearm is also common. Together, these hand and arm abnormalities are known as radial ray malformations.  People with the combination of Duane anomaly and radial ray malformations may have a variety of other signs and symptoms. These features include unusually shaped ears, hearing loss, heart and kidney defects, a distinctive facial appearance, an inward- and upward-turning foot (clubfoot), and fused spinal bones (vertebrae).  The varied signs and symptoms of Duane-radial ray syndrome often overlap with features of other disorders. For example, acro-renal-ocular syndrome is characterized by Duane anomaly and other eye abnormalities, radial ray malformations, and kidney defects. Both conditions are caused by mutations in the same gene. Based on these similarities, researchers suspect that Duane-radial ray syndrome and acro-renal-ocular syndrome are part of an overlapping set of syndromes with many possible signs and symptoms. The features of Duane-radial ray syndrome are also similar to those of a condition called Holt-Oram syndrome; however, these two disorders are caused by mutations in different genes.",Duane-radial ray syndrome,0000304,GHR,https://ghr.nlm.nih.gov/condition/duane-radial-ray-syndrome,C1623209,T047,Disorders
How many people are affected by Duane-radial ray syndrome ?,0000304-2,frequency,Duane-radial ray syndrome is a rare condition whose prevalence is unknown. Only a few affected families have been reported worldwide.,Duane-radial ray syndrome,0000304,GHR,https://ghr.nlm.nih.gov/condition/duane-radial-ray-syndrome,C1623209,T047,Disorders
What are the genetic changes related to Duane-radial ray syndrome ?,0000304-3,genetic changes,"Duane-radial ray syndrome results from mutations in the SALL4 gene. This gene is part of a group of genes called the SALL family. SALL genes provide instructions for making proteins that are involved in the formation of tissues and organs before birth. The proteins produced from these genes act as transcription factors, which means they attach (bind) to specific regions of DNA and help control the activity of particular genes. The exact function of the SALL4 protein is unclear, although it appears to be important for the normal development of the eyes, heart, and limbs.  Mutations in the SALL4 gene prevent cells from making any functional protein from one copy of the gene. It is unclear how a reduction in the amount of the SALL4 protein leads to Duane anomaly, radial ray malformations, and the other features of Duane-radial ray syndrome and similar conditions.",Duane-radial ray syndrome,0000304,GHR,https://ghr.nlm.nih.gov/condition/duane-radial-ray-syndrome,C1623209,T047,Disorders
Is Duane-radial ray syndrome inherited ?,0000304-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered SALL4 gene in each cell is sufficient to cause the disorder. In many cases, an affected person inherits a mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",Duane-radial ray syndrome,0000304,GHR,https://ghr.nlm.nih.gov/condition/duane-radial-ray-syndrome,C1623209,T047,Disorders
What are the treatments for Duane-radial ray syndrome ?,0000304-5,treatment,These resources address the diagnosis or management of Duane-radial ray syndrome:  - Gene Review: Gene Review: SALL4-Related Disorders  - Genetic Testing Registry: Duane-radial ray syndrome  - MedlinePlus Encyclopedia: Skeletal Limb Abnormalities   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Duane-radial ray syndrome,0000304,GHR,https://ghr.nlm.nih.gov/condition/duane-radial-ray-syndrome,C1623209,T047,Disorders
What is (are) Dubin-Johnson syndrome ?,0000305-1,information,"Dubin-Johnson syndrome is a condition characterized by jaundice, which is a yellowing of the skin and whites of the eyes. In most affected people jaundice appears during adolescence or early adulthood, although a few individuals have been diagnosed soon after birth. Jaundice is typically the only symptom of Dubin-Johnson syndrome, but some people also experience weakness, mild upper abdominal pain, nausea, and/or vomiting.",Dubin-Johnson syndrome,0000305,GHR,https://ghr.nlm.nih.gov/condition/dubin-johnson-syndrome,C0022350,T047,Disorders
How many people are affected by Dubin-Johnson syndrome ?,0000305-2,frequency,"Although Dubin-Johnson syndrome occurs in people of all ethnic backgrounds, it is more common among Iranian and Moroccan Jews living in Israel. Studies suggest that this disorder affects 1 in 1,300 Iranian Jews in Israel. Additionally, several people in the Japanese population have been diagnosed with Dubin-Johnson syndrome. This condition appears to be less common in other countries.",Dubin-Johnson syndrome,0000305,GHR,https://ghr.nlm.nih.gov/condition/dubin-johnson-syndrome,C0022350,T047,Disorders
What are the genetic changes related to Dubin-Johnson syndrome ?,0000305-3,genetic changes,"Dubin-Johnson syndrome is caused by mutations in the ABCC2 gene. The ABCC2 gene provides instructions for making a protein called multidrug resistance protein 2 (MRP2). This protein acts as a pump to transport substances out of the liver, kidneys, intestine, or placenta so they can be excreted from the body. For example, MRP2 transports a substance called bilirubin out of liver cells and into bile (a digestive fluid produced by the liver). Bilirubin is produced during the breakdown of old red blood cells and has an orange-yellow tint.  ABCC2 gene mutations lead to a version of MRP2 that cannot effectively pump substances out of cells. These mutations particularly affect the transport of bilirubin into bile. As a result, bilirubin accumulates in the body, causing a condition called hyperbilirubinemia. The buildup of bilirubin in the body causes the yellowing of the skin and whites of the eyes seen in people with Dubin-Johnson syndrome.",Dubin-Johnson syndrome,0000305,GHR,https://ghr.nlm.nih.gov/condition/dubin-johnson-syndrome,C0022350,T047,Disorders
Is Dubin-Johnson syndrome inherited ?,0000305-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Dubin-Johnson syndrome,0000305,GHR,https://ghr.nlm.nih.gov/condition/dubin-johnson-syndrome,C0022350,T047,Disorders
What are the treatments for Dubin-Johnson syndrome ?,0000305-5,treatment,These resources address the diagnosis or management of Dubin-Johnson syndrome:  - Genetic Testing Registry: Dubin-Johnson syndrome  - MedlinePlus Encyclopedia: Bilirubin  - MedlinePlus Encyclopedia: Dubin-Johnson syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Dubin-Johnson syndrome,0000305,GHR,https://ghr.nlm.nih.gov/condition/dubin-johnson-syndrome,C0022350,T047,Disorders
What is (are) Duchenne and Becker muscular dystrophy ?,0000306-1,information,"Muscular dystrophies are a group of genetic conditions characterized by progressive muscle weakness and wasting (atrophy). The Duchenne and Becker types of muscular dystrophy are two related conditions that primarily affect skeletal muscles, which are used for movement, and heart (cardiac) muscle. These forms of muscular dystrophy occur almost exclusively in males.  Duchenne and Becker muscular dystrophies have similar signs and symptoms and are caused by different mutations in the same gene. The two conditions differ in their severity, age of onset, and rate of progression. In boys with Duchenne muscular dystrophy, muscle weakness tends to appear in early childhood and worsen rapidly. Affected children may have delayed motor skills, such as sitting, standing, and walking. They are usually wheelchair-dependent by adolescence. The signs and symptoms of Becker muscular dystrophy are usually milder and more varied. In most cases, muscle weakness becomes apparent later in childhood or in adolescence and worsens at a much slower rate.  Both the Duchenne and Becker forms of muscular dystrophy are associated with a heart condition called cardiomyopathy. This form of heart disease weakens the cardiac muscle, preventing the heart from pumping blood efficiently. In both Duchenne and Becker muscular dystrophy, cardiomyopathy typically begins in adolescence. Later, the heart muscle becomes enlarged, and the heart problems develop into a condition known as dilated cardiomyopathy. Signs and symptoms of dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath, extreme tiredness (fatigue), and swelling of the legs and feet. These heart problems worsen rapidly and become life-threatening in many cases. Males with Duchenne muscular dystrophy typically live into their twenties, while males with Becker muscular dystrophy can survive into their forties or beyond.  A related condition called DMD-associated dilated cardiomyopathy is a form of heart disease caused by mutations in the same gene as Duchenne and Becker muscular dystrophy, and it is sometimes classified as subclinical Becker muscular dystrophy. People with DMD-associated dilated cardiomyopathy typically do not have any skeletal muscle weakness or wasting, although they may have subtle changes in their skeletal muscle cells that are detectable through laboratory testing.",Duchenne and Becker muscular dystrophy,0000306,GHR,https://ghr.nlm.nih.gov/condition/duchenne-and-becker-muscular-dystrophy,C3542021,T047,Disorders
How many people are affected by Duchenne and Becker muscular dystrophy ?,0000306-2,frequency,"Duchenne and Becker muscular dystrophies together affect 1 in 3,500 to 5,000 newborn males worldwide. Between 400 and 600 boys in the United States are born with these conditions each year.",Duchenne and Becker muscular dystrophy,0000306,GHR,https://ghr.nlm.nih.gov/condition/duchenne-and-becker-muscular-dystrophy,C3542021,T047,Disorders
What are the genetic changes related to Duchenne and Becker muscular dystrophy ?,0000306-3,genetic changes,"Mutations in the DMD gene cause the Duchenne and Becker forms of muscular dystrophy. The DMD gene provides instructions for making a protein called dystrophin. This protein is located primarily in skeletal and cardiac muscle, where it helps stabilize and protect muscle fibers. Dystrophin may also play a role in chemical signaling within cells.  Mutations in the DMD gene alter the structure or function of dystrophin or prevent any functional dystrophin from being produced. Muscle cells without enough of this protein become damaged as muscles repeatedly contract and relax with use. The damaged fibers weaken and die over time, leading to the muscle weakness and heart problems characteristic of Duchenne and Becker muscular dystrophies. Mutations that lead to an abnormal version of dystrophin that retains some function usually cause Becker muscular dystrophy, while mutations that prevent the production of any functional dystrophin tend to cause Duchenne muscular dystrophy.  Because Duchenne and Becker muscular dystrophies result from faulty or missing dystrophin, these conditions are classified as dystrophinopathies.",Duchenne and Becker muscular dystrophy,0000306,GHR,https://ghr.nlm.nih.gov/condition/duchenne-and-becker-muscular-dystrophy,C3542021,T047,Disorders
Is Duchenne and Becker muscular dystrophy inherited ?,0000306-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In about two-thirds of cases, an affected male inherits the mutation from his mother, who carries one altered copy of the DMD gene. The other one-third of cases probably result from new mutations in the gene in affected males and are not inherited.  In X-linked recessive inheritance, a female with one mutated copy of the gene in each cell is called a carrier. She can pass on the altered gene but usually does not experience signs and symptoms of the disorder. Occasionally, however, females who carry a DMD gene mutation may have muscle weakness and cramping. These symptoms are typically milder than the severe muscle weakness and atrophy seen in affected males. Females who carry a DMD gene mutation also have an increased risk of developing heart abnormalities including cardiomyopathy.",Duchenne and Becker muscular dystrophy,0000306,GHR,https://ghr.nlm.nih.gov/condition/duchenne-and-becker-muscular-dystrophy,C3542021,T047,Disorders
What are the treatments for Duchenne and Becker muscular dystrophy ?,0000306-5,treatment,These resources address the diagnosis or management of Duchenne and Becker muscular dystrophy:  - Gene Review: Gene Review: Dilated Cardiomyopathy Overview  - Gene Review: Gene Review: Dystrophinopathies  - Genetic Testing Registry: Becker muscular dystrophy  - Genetic Testing Registry: Duchenne muscular dystrophy  - Genomics Education Programme (UK)  - MedlinePlus Encyclopedia: Becker Muscular Dystrophy  - MedlinePlus Encyclopedia: Dilated Cardiomyopathy  - MedlinePlus Encyclopedia: Duchenne Muscular Dystrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Duchenne and Becker muscular dystrophy,0000306,GHR,https://ghr.nlm.nih.gov/condition/duchenne-and-becker-muscular-dystrophy,C3542021,T047,Disorders
What is (are) dyserythropoietic anemia and thrombocytopenia ?,0000307-1,information,"Dyserythropoietic anemia and thrombocytopenia is a condition that affects blood cells and primarily occurs in males. A main feature of this condition is a type of anemia called dyserythropoietic anemia, which is characterized by a shortage of red blood cells. The term ""dyserythropoietic"" refers to the abnormal red blood cell formation that occurs in this condition. In affected individuals, immature red blood cells are unusually shaped and cannot develop into functional mature cells, leading to a shortage of healthy red blood cells. People with dyserythropoietic anemia and thrombocytopenia can have another blood disorder characterized by a reduced level of circulating platelets (thrombocytopenia). Platelets are cell fragments that normally assist with blood clotting. Thrombocytopenia can cause easy bruising and abnormal bleeding. While people with dyserythropoietic anemia and thrombocytopenia can have signs and symptoms of both blood disorders, some are primarily affected by anemia, while others are more affected by thrombocytopenia.  The most severe cases of dyserythropoietic anemia and thrombocytopenia are characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. For many others, the signs and symptoms of dyserythropoietic anemia and thrombocytopenia begin in infancy. People with this condition experience prolonged bleeding or bruising after minor trauma or even in the absence of injury (spontaneous bleeding). Anemia can cause pale skin, weakness, and fatigue. Severe anemia may create a need for frequent blood transfusions to replenish the supply of red blood cells; however, repeated blood transfusions over many years can cause health problems such as excess iron in the blood. People with dyserythropoietic anemia and thrombocytopenia may also have a shortage of white blood cells (neutropenia), which can make them prone to recurrent infections. Additionally, they may have an enlarged spleen (splenomegaly). The severity of these abnormalities varies among affected individuals.  Some people with dyserythropoietic anemia and thrombocytopenia have additional blood disorders such as beta thalassemia or congenital erythropoietic porphyria. Beta thalassemia is a condition that reduces the production of hemoglobin, which is the iron-containing protein in red blood cells that carries oxygen. A decrease in hemoglobin can lead to a shortage of oxygen in cells and tissues throughout the body. Congenital erythropoietic porphyria is another disorder that impairs hemoglobin production. People with congenital erythropoietic porphyria are also very sensitive to sunlight, and areas of skin exposed to the sun can become fragile and blistered.",dyserythropoietic anemia and thrombocytopenia,0000307,GHR,https://ghr.nlm.nih.gov/condition/dyserythropoietic-anemia-and-thrombocytopenia,C0678199,T047,Disorders
How many people are affected by dyserythropoietic anemia and thrombocytopenia ?,0000307-2,frequency,"Dyserythropoietic anemia and thrombocytopenia is a rare condition; its prevalence is unknown. Occasionally, individuals with this disorder are mistakenly diagnosed as having more common blood disorders, making it even more difficult to determine how many people have dyserythropoietic anemia and thrombocytopenia.",dyserythropoietic anemia and thrombocytopenia,0000307,GHR,https://ghr.nlm.nih.gov/condition/dyserythropoietic-anemia-and-thrombocytopenia,C0678199,T047,Disorders
What are the genetic changes related to dyserythropoietic anemia and thrombocytopenia ?,0000307-3,genetic changes,"Mutations in the GATA1 gene cause dyserythropoietic anemia and thrombocytopenia. The GATA1 gene provides instructions for making a protein that attaches (binds) to specific regions of DNA and helps control the activity of many other genes. On the basis of this action, the GATA1 protein is known as a transcription factor. The GATA1 protein is involved in the specialization (differentiation) of immature blood cells. To function properly, these immature cells must differentiate into specific types of mature blood cells. Through its activity as a transcription factor and its interactions with other proteins, the GATA1 protein regulates the growth and division (proliferation) of immature red blood cells and platelet-precursor cells (megakaryocytes) and helps with their differentiation.  GATA1 gene mutations disrupt the protein's ability to bind with DNA or interact with other proteins. These impairments in the GATA1 protein's normal function result in an increased proliferation of megakaryocytes and a decrease in mature platelets, leading to abnormal bleeding. An abnormal GATA1 protein causes immature red blood cells to undergo a form of programmed cell death called apoptosis. A lack of immature red blood cells results in decreased amounts of specialized, mature red blood cells, leading to anemia. The severity of dyserythropoietic anemia and thrombocytopenia can usually be predicted by the type of GATA1 gene mutation.  When the two blood disorders dyserythropoietic anemia and thrombocytopenia occur separately, each of the conditions can result from many different factors. The occurrence of these disorders together is characteristic of mutations in the GATA1 gene.",dyserythropoietic anemia and thrombocytopenia,0000307,GHR,https://ghr.nlm.nih.gov/condition/dyserythropoietic-anemia-and-thrombocytopenia,C0678199,T047,Disorders
Is dyserythropoietic anemia and thrombocytopenia inherited ?,0000307-4,inheritance,"This condition is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. Because females have two copies of the X chromosome, one altered copy of the gene in each cell usually leads to less severe symptoms in females than in males or may cause no symptoms in females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",dyserythropoietic anemia and thrombocytopenia,0000307,GHR,https://ghr.nlm.nih.gov/condition/dyserythropoietic-anemia-and-thrombocytopenia,C0678199,T047,Disorders
What are the treatments for dyserythropoietic anemia and thrombocytopenia ?,0000307-5,treatment,These resources address the diagnosis or management of dyserythropoietic anemia and thrombocytopenia:  - Gene Review: Gene Review: GATA1-Related X-Linked Cytopenia  - Genetic Testing Registry: GATA-1-related thrombocytopenia with dyserythropoiesis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,dyserythropoietic anemia and thrombocytopenia,0000307,GHR,https://ghr.nlm.nih.gov/condition/dyserythropoietic-anemia-and-thrombocytopenia,C0678199,T047,Disorders
What is (are) dyskeratosis congenita ?,0000308-1,information,"Dyskeratosis congenita is a disorder that can affect many parts of the body. There are three features that are characteristic of this disorder: fingernails and toenails that grow poorly or are abnormally shaped (nail dystrophy); changes in skin coloring (pigmentation), especially on the neck and chest, in a pattern often described as ""lacy""; and white patches inside the mouth (oral leukoplakia).  People with dyskeratosis congenita have an increased risk of developing several life-threatening conditions. They are especially vulnerable to disorders that impair bone marrow function. These disorders disrupt the ability of the bone marrow to produce new blood cells. Affected individuals may develop aplastic anemia, also known as bone marrow failure, which occurs when the bone marrow does not produce enough new blood cells. They are also at higher than average risk for myelodysplastic syndrome, a condition in which immature blood cells fail to develop normally; this condition may progress to a form of blood cancer called leukemia. People with dyskeratosis congenita are also at increased risk of developing leukemia even if they never develop myelodysplastic syndrome. In addition, they have a higher than average risk of developing other cancers, especially cancers of the head, neck, anus, or genitals.  People with dyskeratosis congenita may also develop pulmonary fibrosis, a condition that causes scar tissue (fibrosis) to build up in the lungs, decreasing the transport of oxygen into the bloodstream. Additional signs and symptoms that occur in some people with dyskeratosis congenita include eye abnormalities such as narrow tear ducts that may become blocked, preventing drainage of tears and leading to eyelid irritation; dental problems; hair loss or prematurely grey hair; low bone mineral density (osteoporosis); degeneration (avascular necrosis) of the hip and shoulder joints; or liver disease. Some affected males may have narrowing (stenosis) of the urethra, which is the tube that carries urine out of the body from the bladder. Urethral stenosis may lead to difficult or painful urination and urinary tract infections.  The severity of dyskeratosis congenita varies widely among affected individuals. The least severely affected individuals have only a few mild physical features of the disorder and normal bone marrow function. More severely affected individuals have many of the characteristic physical features and experience bone marrow failure, cancer, or pulmonary fibrosis by early adulthood.  While most people with dyskeratosis congenita have normal intelligence and development of motor skills such as standing and walking, developmental delay may occur in some severely affected individuals. In one severe form of the disorder called Hoyeraal Hreidaarsson syndrome, affected individuals have an unusually small and underdeveloped cerebellum, which is the part of the brain that coordinates movement. Another severe variant called Revesz syndrome involves abnormalities in the light-sensitive tissue at the back of the eye (retina) in addition to the other symptoms of dyskeratosis congenita.",dyskeratosis congenita,0000308,GHR,https://ghr.nlm.nih.gov/condition/dyskeratosis-congenita,C0265965,T019,Disorders
How many people are affected by dyskeratosis congenita ?,0000308-2,frequency,The exact prevalence of dyskeratosis congenita is unknown. It is estimated to occur in approximately 1 in 1 million people.,dyskeratosis congenita,0000308,GHR,https://ghr.nlm.nih.gov/condition/dyskeratosis-congenita,C0265965,T019,Disorders
What are the genetic changes related to dyskeratosis congenita ?,0000308-3,genetic changes,"In about half of people with dyskeratosis congenita, the disorder is caused by mutations in the TERT, TERC, DKC1, or TINF2 gene. These genes provide instructions for making proteins that help maintain structures known as telomeres, which are found at the ends of chromosomes. In a small number of individuals with dyskeratosis congenita, mutations in other genes involved with telomere maintenance have been identified. Other affected individuals have no mutations in any of the genes currently associated with dyskeratosis congenita. In these cases, the cause of the disorder is unknown, but other unidentified genes related to telomere maintenance are likely involved.  Telomeres help protect chromosomes from abnormally sticking together or breaking down (degrading). In most cells, telomeres become progressively shorter as the cell divides. After a certain number of cell divisions, the telomeres become so short that they trigger the cell to stop dividing or to self-destruct (undergo apoptosis).  Telomeres are maintained by two important protein complexes called telomerase and shelterin. Telomerase helps maintain normal telomere length by adding small repeated segments of DNA to the ends of chromosomes each time the cell divides. The main components of telomerase, called hTR and hTERT, are produced from the TERC and TERT genes, respectively. The hTR component is an RNA molecule, a chemical cousin of DNA. It provides a template for creating the repeated sequence of DNA that telomerase adds to the ends of chromosomes. The function of the hTERT component is to add the new DNA segment to chromosome ends. The DKC1 gene provides instructions for making another protein that is important in telomerase function. This protein, called dyskerin, attaches (binds) to hTR and helps stabilize the telomerase complex.  The shelterin complex helps protect telomeres from the cell's DNA repair process. Without the protection of shelterin, the repair mechanism would sense the chromosome ends as abnormal breaks in the DNA sequence and either attempt to join the ends together or initiate apoptosis. The TINF2 gene provides instructions for making a protein that is part of the shelterin complex.  TERT, TERC, DKC1, or TINF2 gene mutations result in dysfunction of the telomerase or shelterin complexes, leading to impaired maintenance of telomeres and reduced telomere length. Cells that divide rapidly are especially vulnerable to the effects of shortened telomeres. As a result, people with dyskeratosis congenita may experience a variety of problems affecting quickly dividing cells in the body such as cells of the nail beds, hair follicles, skin, lining of the mouth (oral mucosa), and bone marrow.  Breakage and instability of chromosomes resulting from inadequate telomere maintenance may lead to genetic changes that allow cells to divide in an uncontrolled way, resulting in the development of cancer in people with dyskeratosis congenita.",dyskeratosis congenita,0000308,GHR,https://ghr.nlm.nih.gov/condition/dyskeratosis-congenita,C0265965,T019,Disorders
Is dyskeratosis congenita inherited ?,0000308-4,inheritance,"Dyskeratosis congenita can have different inheritance patterns.  When dyskeratosis congenita is caused by DKC1 gene mutations, it is inherited in an X-linked recessive pattern. The DKC1 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  When dyskeratosis congenita is caused by mutations in other genes, it can be inherited in an autosomal dominant or autosomal recessive pattern. Autosomal dominant means one copy of the altered gene in each cell is sufficient to cause the disorder. Autosomal recessive means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",dyskeratosis congenita,0000308,GHR,https://ghr.nlm.nih.gov/condition/dyskeratosis-congenita,C0265965,T019,Disorders
What are the treatments for dyskeratosis congenita ?,0000308-5,treatment,These resources address the diagnosis or management of dyskeratosis congenita:  - Gene Review: Gene Review: Dyskeratosis Congenita  - Genetic Testing Registry: Dyskeratosis congenita  - Genetic Testing Registry: Dyskeratosis congenita X-linked  - Genetic Testing Registry: Dyskeratosis congenita autosomal dominant  - Genetic Testing Registry: Dyskeratosis congenita autosomal recessive 1  - Seattle Children's Hospital   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,dyskeratosis congenita,0000308,GHR,https://ghr.nlm.nih.gov/condition/dyskeratosis-congenita,C0265965,T019,Disorders
What is (are) dystonia 6 ?,0000309-1,information,"Dystonia 6 is one of many forms of dystonia, which is a group of conditions characterized by involuntary movements, twisting (torsion) and tensing of various muscles, and unusual positioning of affected body parts. Dystonia 6 can appear at any age from childhood through adulthood; the average age of onset is 18.  The signs and symptoms of dystonia 6 vary among affected individuals. The disorder usually first impacts muscles of the head and neck, causing problems with speaking (dysarthria) and eating (dysphagia). Eyelid twitching (blepharospasm) may also occur. Involvement of one or more limbs is common, and in some cases occurs before the head and neck problems. Dystonia 6 gradually gets worse, and it may eventually involve most of the body.",dystonia 6,0000309,GHR,https://ghr.nlm.nih.gov/condition/dystonia-6,C1414216,T047,Disorders
How many people are affected by dystonia 6 ?,0000309-2,frequency,"The prevalence of dystonia 6 is unknown. Studies indicate that it likely accounts for between 1 and 3 percent of all cases of dystonia. For reasons that are unclear, the disorder appears to be slightly more prevalent in females than in males.",dystonia 6,0000309,GHR,https://ghr.nlm.nih.gov/condition/dystonia-6,C1414216,T047,Disorders
What are the genetic changes related to dystonia 6 ?,0000309-3,genetic changes,"Dystonia 6 is caused by mutations in the THAP1 gene. This gene provides instructions for making a protein that is a transcription factor, which means that it attaches (binds) to specific regions of DNA and regulates the activity of other genes. Through this function, it is thought to help control several processes in the body, including the growth and division (proliferation) of endothelial cells, which line the inside surface of blood vessels and other circulatory system structures called lymphatic vessels. The THAP1 protein also plays a role in the self-destruction of cells that are no longer needed (apoptosis).  Studies indicate that most of the THAP1 gene mutations that cause dystonia 6 affect the stability of the THAP1 protein, reducing the amount of functional THAP1 protein available for DNA binding. Other mutations may impair the protein's ability to bind with the correct regions of DNA. Problems with DNA binding likely disrupt the proper regulation of gene activity, leading to the signs and symptoms of dystonia 6.  A particular THAP1 gene mutation is specific to a Mennonite population in the Midwestern United States in which dystonia 6 was first described. This mutation changes the DNA sequence in a region of the gene known as exon 2. Some researchers use the term DYT6 dystonia to refer to dystonia caused by this particular mutation, and the broader term THAP1 dystonia to refer to dystonia caused by any THAP1 gene mutation. In general, mutations affecting the region of the THAP1 protein that binds to DNA, including the mutation found in the Mennonite population, tend to result in more severe signs and symptoms than mutations affecting other regions of the protein.",dystonia 6,0000309,GHR,https://ghr.nlm.nih.gov/condition/dystonia-6,C1414216,T047,Disorders
Is dystonia 6 inherited ?,0000309-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell can be sufficient to cause the disorder. Some people who inherit the altered gene never develop the condition, a situation known as reduced penetrance.",dystonia 6,0000309,GHR,https://ghr.nlm.nih.gov/condition/dystonia-6,C1414216,T047,Disorders
What are the treatments for dystonia 6 ?,0000309-5,treatment,"These resources address the diagnosis or management of dystonia 6:  - Gene Review: Gene Review: Dystonia Overview  - Genetic Testing Registry: Dystonia 6, torsion   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",dystonia 6,0000309,GHR,https://ghr.nlm.nih.gov/condition/dystonia-6,C1414216,T047,Disorders
What is (are) dystrophic epidermolysis bullosa ?,0000310-1,information,"Epidermolysis bullosa is a group of genetic conditions that cause the skin to be very fragile and to blister easily. Blisters and skin erosions form in response to minor injury or friction, such as rubbing or scratching. Dystrophic epidermolysis bullosa (DEB) is one of the major forms of epidermolysis bullosa. The signs and symptoms of this condition vary widely among affected individuals. In mild cases, blistering may primarily affect the hands, feet, knees, and elbows. Severe cases of this condition involve widespread blistering that can lead to vision loss, disfigurement, and other serious medical problems.  Researchers classify dystrophic epidermolysis bullosa into three major types. Although the types differ in severity, their features overlap significantly and they are caused by mutations in the same gene.  Autosomal recessive dystrophic epidermolysis bullosa, Hallopeau-Siemens type (RDEB-HS) is the most severe, classic form of the condition. Affected infants are typically born with widespread blistering and areas of missing skin, often caused by trauma during birth. Most often, blisters are present over the whole body and affect mucous membranes such as the moist lining of the mouth and digestive tract. As the blisters heal, they result in severe scarring. Scarring in the mouth and esophagus can make it difficult to chew and swallow food, leading to chronic malnutrition and slow growth. Additional complications of progressive scarring can include fusion of the fingers and toes, loss of fingernails and toenails, joint deformities (contractures) that restrict movement, and eye inflammation leading to vision loss. Additionally, young adults with the classic form of dystrophic epidermolysis bullosa have a very high risk of developing a form of skin cancer called squamous cell carcinoma, which tends to be unusually aggressive and is often life-threatening.  A second type of autosomal recessive dystrophic epidermolysis bullosa is known as the non-Hallopeau-Siemens type (non-HS RDEB). This form of the condition is somewhat less severe than the classic type and includes a range of subtypes. Blistering is limited to the hands, feet, knees, and elbows in mild cases, but may be widespread in more severe cases. Affected people often have malformed fingernails and toenails. Non-HS RDEB involves scarring in the areas where blisters occur, but this form of the condition does not cause the severe scarring characteristic of the classic type.  The third major type of dystrophic epidermolysis bullosa is known as the autosomal dominant type (DDEB). The signs and symptoms of this condition tend to be milder than those of the autosomal recessive forms, with blistering often limited to the hands, feet, knees, and elbows. The blisters heal with scarring, but it is less severe. Most affected people have malformed fingernails and toenails, and the nails may be lost over time. In the mildest cases, abnormal nails are the only sign of the condition.",dystrophic epidermolysis bullosa,0000310,GHR,https://ghr.nlm.nih.gov/condition/dystrophic-epidermolysis-bullosa,C0079294,T047,Disorders
How many people are affected by dystrophic epidermolysis bullosa ?,0000310-2,frequency,"Considered together, the incidence of all types of dystrophic epidermolysis bullosa is estimated to be 6.5 per million newborns in the United States. The severe autosomal recessive forms of this disorder affect fewer than 1 per million newborns.",dystrophic epidermolysis bullosa,0000310,GHR,https://ghr.nlm.nih.gov/condition/dystrophic-epidermolysis-bullosa,C0079294,T047,Disorders
What are the genetic changes related to dystrophic epidermolysis bullosa ?,0000310-3,genetic changes,"Mutations in the COL7A1 gene cause all three major forms of dystrophic epidermolysis bullosa. This gene provides instructions for making a protein that is used to assemble type VII collagen. Collagens are molecules that give structure and strength to connective tissues, such as skin, tendons, and ligaments, throughout the body. Type VII collagen plays an important role in strengthening and stabilizing the skin. It is the main component of structures called anchoring fibrils, which anchor the top layer of skin, called the epidermis, to an underlying layer called the dermis.  COL7A1 mutations alter the structure or disrupt the production of type VII collagen, which impairs its ability to help connect the epidermis to the dermis. When type VII collagen is abnormal or missing, friction or other minor trauma can cause the two skin layers to separate. This separation leads to the formation of blisters, which can cause extensive scarring as they heal. Researchers are working to determine how abnormalities of type VII collagen also underlie the increased risk of skin cancer seen in the severe form of dystrophic epidermolysis bullosa.",dystrophic epidermolysis bullosa,0000310,GHR,https://ghr.nlm.nih.gov/condition/dystrophic-epidermolysis-bullosa,C0079294,T047,Disorders
Is dystrophic epidermolysis bullosa inherited ?,0000310-4,inheritance,"The most severe types of dystrophic epidermolysis bullosa are inherited in an autosomal recessive pattern. Autosomal recessive inheritance means that both copies of the COL7A1 gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.  A milder form of dystrophic epidermolysis bullosa has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder. About 70 percent of all people with autosomal dominant dystrophic epidermolysis bullosa have inherited an altered COL7A1 gene from an affected parent. The remaining 30 percent of affected people have the condition as a result of a new mutation in the COL7A1 gene. These cases occur in people with no history of the disorder in their family.",dystrophic epidermolysis bullosa,0000310,GHR,https://ghr.nlm.nih.gov/condition/dystrophic-epidermolysis-bullosa,C0079294,T047,Disorders
What are the treatments for dystrophic epidermolysis bullosa ?,0000310-5,treatment,These resources address the diagnosis or management of dystrophic epidermolysis bullosa:  - Gene Review: Gene Review: Dystrophic Epidermolysis Bullosa  - Genetic Testing Registry: Dystrophic epidermolysis bullosa  - Genetic Testing Registry: Generalized dominant dystrophic epidermolysis bullosa  - Genetic Testing Registry: Recessive dystrophic epidermolysis bullosa  - MedlinePlus Encyclopedia: Epidermolysis bullosa  - MedlinePlus Encyclopedia: Squamous Cell Skin Cancer   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,dystrophic epidermolysis bullosa,0000310,GHR,https://ghr.nlm.nih.gov/condition/dystrophic-epidermolysis-bullosa,C0079294,T047,Disorders
What is (are) early-onset glaucoma ?,0000311-1,information,"Glaucoma is a group of eye disorders in which the optic nerves connecting the eyes and the brain are progressively damaged. This damage can lead to reduction in side (peripheral) vision and eventual blindness. Other signs and symptoms may include bulging eyes, excessive tearing, and abnormal sensitivity to light (photophobia). The term ""early-onset glaucoma"" may be used when the disorder appears before the age of 40.  In most people with glaucoma, the damage to the optic nerves is caused by increased pressure within the eyes (intraocular pressure). Intraocular pressure depends on a balance between fluid entering and leaving the eyes.  Usually glaucoma develops in older adults, in whom the risk of developing the disorder may be affected by a variety of medical conditions including high blood pressure (hypertension) and diabetes mellitus, as well as family history. The risk of early-onset glaucoma depends mainly on heredity.  Structural abnormalities that impede fluid drainage in the eye may be present at birth and usually become apparent during the first year of life. Such abnormalities may be part of a genetic disorder that affects many body systems, called a syndrome. If glaucoma appears before the age of 5 without other associated abnormalities, it is called primary congenital glaucoma.  Other individuals experience early onset of primary open-angle glaucoma, the most common adult form of glaucoma. If primary open-angle glaucoma develops during childhood or early adulthood, it is called juvenile open-angle glaucoma.",early-onset glaucoma,0000311,GHR,https://ghr.nlm.nih.gov/condition/early-onset-glaucoma,C3711383,T047,Disorders
How many people are affected by early-onset glaucoma ?,0000311-2,frequency,"Primary congenital glaucoma affects approximately 1 in 10,000 people. Its frequency is higher in the Middle East. Juvenile open-angle glaucoma affects about 1 in 50,000 people. Primary open-angle glaucoma is much more common after the age of 40, affecting about 1 percent of the population worldwide.",early-onset glaucoma,0000311,GHR,https://ghr.nlm.nih.gov/condition/early-onset-glaucoma,C3711383,T047,Disorders
What are the genetic changes related to early-onset glaucoma ?,0000311-3,genetic changes,"Approximately 10 percent to 33 percent of people with juvenile open-angle glaucoma have mutations in the MYOC gene. MYOC gene mutations have also been detected in some people with primary congenital glaucoma. The MYOC gene provides instructions for producing a protein called myocilin. Myocilin is found in certain structures of the eye, called the trabecular meshwork and the ciliary body, that regulate the intraocular pressure.  Researchers believe that myocilin functions together with other proteins as part of a protein complex. Mutations may alter the protein in such a way that the complex cannot be formed. Defective myocilin that is not incorporated into functional complexes may accumulate in the trabecular meshwork and ciliary body. The excess protein may prevent sufficient flow of fluid from the eye, resulting in increased intraocular pressure and causing the signs and symptoms of early-onset glaucoma.  Between 20 percent and 40 percent of people with primary congenital glaucoma have mutations in the CYP1B1 gene. CYP1B1 gene mutations have also been detected in some people with juvenile open-angle glaucoma. The CYP1B1 gene provides instructions for producing a form of the cytochrome P450 protein. Like myocilin, this protein is found in the trabecular meshwork, ciliary body, and other structures of the eye.  It is not well understood how defects in the CYP1B1 protein cause signs and symptoms of glaucoma. Recent studies suggest that the defects may interfere with the early development of the trabecular meshwork. In the clear covering of the eye (the cornea), the CYP1B1 protein may also be involved in a process that regulates the secretion of fluid inside the eye. If this fluid is produced in excess, the high intraocular pressure characteristic of glaucoma may develop.  The CYP1B1 protein may interact with myocilin. Individuals with mutations in both the MYOC and CYP1B1 genes may develop glaucoma at an earlier age and have more severe symptoms than do those with mutations in only one of the genes. Mutations in other genes may also be involved in early-onset glaucoma.",early-onset glaucoma,0000311,GHR,https://ghr.nlm.nih.gov/condition/early-onset-glaucoma,C3711383,T047,Disorders
Is early-onset glaucoma inherited ?,0000311-4,inheritance,"Early-onset glaucoma can have different inheritance patterns. Primary congenital glaucoma is usually inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.  Juvenile open-angle glaucoma is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some families, primary congenital glaucoma may also be inherited in an autosomal dominant pattern.",early-onset glaucoma,0000311,GHR,https://ghr.nlm.nih.gov/condition/early-onset-glaucoma,C3711383,T047,Disorders
What are the treatments for early-onset glaucoma ?,0000311-5,treatment,"These resources address the diagnosis or management of early-onset glaucoma:  - Gene Review: Gene Review: Primary Congenital Glaucoma  - Genetic Testing Registry: Glaucoma, congenital  - Genetic Testing Registry: Primary open angle glaucoma juvenile onset 1  - MedlinePlus Encyclopedia: Glaucoma   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",early-onset glaucoma,0000311,GHR,https://ghr.nlm.nih.gov/condition/early-onset-glaucoma,C3711383,T047,Disorders
What is (are) early-onset primary dystonia ?,0000312-1,information,"Early-onset primary dystonia is a condition characterized by progressive problems with movement, typically beginning in childhood. Dystonia is a movement disorder that involves involuntary tensing of the muscles (muscle contractions), twisting of specific body parts such as an arm or a leg, rhythmic shaking (tremors), and other uncontrolled movements. A primary dystonia is one that occurs without other neurological symptoms, such as seizures or a loss of intellectual function (dementia). Early-onset primary dystonia does not affect a person's intelligence.  On average, the signs and symptoms of early-onset primary dystonia appear around age 12. Abnormal muscle spasms in an arm or a leg are usually the first sign. These unusual movements initially occur while a person is doing a specific action, such as writing or walking. In some affected people, dystonia later spreads to other parts of the body and may occur at rest. The abnormal movements persist throughout life, but they do not usually cause pain.  The signs and symptoms of early-onset primary dystonia vary from person to person, even among affected members of the same family. The mildest cases affect only a single part of the body, causing isolated problems such as a writer's cramp in the hand. Severe cases involve abnormal movements affecting many regions of the body.",early-onset primary dystonia,0000312,GHR,https://ghr.nlm.nih.gov/condition/early-onset-primary-dystonia,C1851945,T047,Disorders
How many people are affected by early-onset primary dystonia ?,0000312-2,frequency,"Early-onset primary dystonia is among the most common forms of childhood dystonia. This disorder occurs most frequently in people of Ashkenazi (central and eastern European) Jewish heritage, affecting 1 in 3,000 to 9,000 people in this population. The condition is less common among people with other backgrounds; it is estimated to affect 1 in 10,000 to 30,000 non-Jewish people worldwide.",early-onset primary dystonia,0000312,GHR,https://ghr.nlm.nih.gov/condition/early-onset-primary-dystonia,C1851945,T047,Disorders
What are the genetic changes related to early-onset primary dystonia ?,0000312-3,genetic changes,"A particular mutation in the TOR1A gene (also known as DYT1) is responsible for most cases of early-onset primary dystonia. The TOR1A gene provides instructions for making a protein called torsinA. Although little is known about its function, this protein may help process and transport other proteins within cells. It appears to be critical for the normal development and function of nerve cells in the brain.  A mutation in the TOR1A gene alters the structure of torsinA. The altered protein's effect on the function of nerve cells in the brain is unclear. People with early-onset primary dystonia do not have a loss of nerve cells or obvious changes in the structure of the brain that would explain the abnormal muscle contractions. Instead, the altered torsinA protein may have subtle effects on the connections between nerve cells and likely disrupts chemical signaling between nerve cells that control movement. Researchers are working to determine how a change in this protein leads to the characteristic features of this disorder.",early-onset primary dystonia,0000312,GHR,https://ghr.nlm.nih.gov/condition/early-onset-primary-dystonia,C1851945,T047,Disorders
Is early-onset primary dystonia inherited ?,0000312-4,inheritance,"Mutations in the TOR1A gene are inherited in an autosomal dominant pattern, which means one of the two copies of the gene is altered in each cell. Many people who have a mutation in this gene are not affected by the disorder and may never know they have the mutation. Only 30 to 40 percent of people who inherit a TOR1A mutation will ever develop signs and symptoms of early-onset primary dystonia.  Everyone who has been diagnosed with early-onset primary dystonia has inherited a TOR1A mutation from one parent. The parent may or may not have signs and symptoms of the condition, and other family members may or may not be affected.",early-onset primary dystonia,0000312,GHR,https://ghr.nlm.nih.gov/condition/early-onset-primary-dystonia,C1851945,T047,Disorders
What are the treatments for early-onset primary dystonia ?,0000312-5,treatment,These resources address the diagnosis or management of early-onset primary dystonia:  - Gene Review: Gene Review: DYT1 Early-Onset Primary Dystonia  - Genetic Testing Registry: Dystonia 1  - MedlinePlus Encyclopedia: Movement - uncontrolled or slow   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,early-onset primary dystonia,0000312,GHR,https://ghr.nlm.nih.gov/condition/early-onset-primary-dystonia,C1851945,T047,Disorders
What is (are) Ehlers-Danlos syndrome ?,0000313-1,information,"Ehlers-Danlos syndrome is a group of disorders that affect the connective tissues that support the skin, bones, blood vessels, and many other organs and tissues. Defects in connective tissues cause the signs and symptoms of Ehlers-Danlos syndrome, which vary from mildly loose joints to life-threatening complications.  Previously, there were more than 10 recognized types of Ehlers-Danlos syndrome, differentiated by Roman numerals. In 1997, researchers proposed a simpler classification that reduced the number of major types to six and gave them descriptive names: the classical type (formerly types I and II), the hypermobility type (formerly type III), the vascular type (formerly type IV), the kyphoscoliosis type (formerly type VIA), the arthrochalasia type (formerly types VIIA and VIIB), and the dermatosparaxis type (formerly type VIIC). This six-type classification, known as the Villefranche nomenclature, is still commonly used. The types are distinguished by their signs and symptoms, their underlying genetic causes, and their patterns of inheritance. Since 1997, several additional forms of the condition have been described. These additional forms appear to be rare, affecting a small number of families, and most have not been well characterized.  Although all types of Ehlers-Danlos syndrome affect the joints and skin, additional features vary by type. An unusually large range of joint movement (hypermobility) occurs with most forms of Ehlers-Danlos syndrome, particularly the hypermobility type. Infants with hypermobile joints often have weak muscle tone, which can delay the development of motor skills such as sitting, standing, and walking. The loose joints are unstable and prone to dislocation and chronic pain. Hypermobility and dislocations of both hips at birth are characteristic features in infants with the arthrochalasia type of Ehlers-Danlos syndrome.  Many people with Ehlers-Danlos syndrome have soft, velvety skin that is highly stretchy (elastic) and fragile. Affected individuals tend to bruise easily, and some types of the condition also cause abnormal scarring. People with the classical form of Ehlers-Danlos syndrome experience wounds that split open with little bleeding and leave scars that widen over time to create characteristic ""cigarette paper"" scars. The dermatosparaxis type of the disorder is characterized by skin that sags and wrinkles. Extra (redundant) folds of skin may be present as affected children get older.  Some forms of Ehlers-Danlos syndrome, notably the vascular type and to a lesser extent the kyphoscoliosis and classical types, can involve serious and potentially life-threatening complications due to unpredictable tearing (rupture) of blood vessels. This rupture can cause internal bleeding, stroke, and shock. The vascular type of Ehlers-Danlos syndrome is also associated with an increased risk of organ rupture, including tearing of the intestine and rupture of the uterus (womb) during pregnancy. People with the kyphoscoliosis form of Ehlers-Danlos syndrome experience severe, progressive curvature of the spine that can interfere with breathing.",Ehlers-Danlos syndrome,0000313,GHR,https://ghr.nlm.nih.gov/condition/ehlers-danlos-syndrome,C0013720,T019,Disorders
How many people are affected by Ehlers-Danlos syndrome ?,0000313-2,frequency,"Although it is difficult to estimate the overall frequency of Ehlers-Danlos syndrome, the combined prevalence of all types of this condition may be about 1 in 5,000 individuals worldwide. The hypermobility and classical forms are most common; the hypermobility type may affect as many as 1 in 10,000 to 15,000 people, while the classical type probably occurs in 1 in 20,000 to 40,000 people.  Other forms of Ehlers-Danlos syndrome are very rare. About 30 cases of the arthrochalasia type and about 60 cases of the kyphoscoliosis type have been reported worldwide. About a dozen infants and children with the dermatosparaxis type have been described. The vascular type is also rare; estimates vary widely, but the condition may affect about 1 in 250,000 people.",Ehlers-Danlos syndrome,0000313,GHR,https://ghr.nlm.nih.gov/condition/ehlers-danlos-syndrome,C0013720,T019,Disorders
What are the genetic changes related to Ehlers-Danlos syndrome ?,0000313-3,genetic changes,"Mutations in more than a dozen genes have been found to cause Ehlers-Danlos syndrome. The classical type results most often from mutations in either the COL5A1 gene or the COL5A2 gene. Mutations in the TNXB gene have been found in a very small percentage of cases of the hypermobility type (although in most cases, the cause of this type is unknown). The vascular type results from mutations in the COL3A1 gene. PLOD1 gene mutations cause the kyphoscoliosis type. Mutations in the COL1A1 gene or the COL1A2 gene result in the arthrochalasia type. The dermatosparaxis type is caused by mutations in the ADAMTS2 gene. The other, less well-characterized forms of Ehlers-Danlos syndrome result from mutations in other genes, some of which have not been identified.  Some of the genes associated with Ehlers-Danlos syndrome, including COL1A1, COL1A2, COL3A1, COL5A1, and COL5A2, provide instructions for making pieces of several different types of collagen. These pieces assemble to form mature collagen molecules that give structure and strength to connective tissues throughout the body. Other genes, including ADAMTS2, PLOD1, and TNXB, provide instructions for making proteins that process or interact with collagen. Mutations that cause the different forms of Ehlers-Danlos syndrome disrupt the production or processing of collagen, preventing these molecules from being assembled properly. These defects weaken connective tissues in the skin, bones, and other parts of the body, resulting in the characteristic features of this condition.",Ehlers-Danlos syndrome,0000313,GHR,https://ghr.nlm.nih.gov/condition/ehlers-danlos-syndrome,C0013720,T019,Disorders
Is Ehlers-Danlos syndrome inherited ?,0000313-4,inheritance,"The inheritance pattern of Ehlers-Danlos syndrome varies by type. The arthrochalasia, classical, hypermobility, and vascular forms of the disorder have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new (sporadic) gene mutations and occur in people with no history of the disorder in their family.  The dermatosparaxis and kyphoscoliosis types of Ehlers-Danlos syndrome, as well as some of the rare, less well-characterized types of the disorder, are inherited in an autosomal recessive pattern. In autosomal recessive inheritance, two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.",Ehlers-Danlos syndrome,0000313,GHR,https://ghr.nlm.nih.gov/condition/ehlers-danlos-syndrome,C0013720,T019,Disorders
What are the treatments for Ehlers-Danlos syndrome ?,0000313-5,treatment,"These resources address the diagnosis or management of Ehlers-Danlos syndrome:  - Gene Review: Gene Review: Ehlers-Danlos Syndrome, Classic Type  - Gene Review: Gene Review: Ehlers-Danlos Syndrome, Hypermobility Type  - Gene Review: Gene Review: Ehlers-Danlos Syndrome, Kyphoscoliotic Form  - Gene Review: Gene Review: Vascular Ehlers-Danlos Syndrome  - Genetic Testing Registry: Ehlers-Danlos syndrome  - Genetic Testing Registry: Ehlers-Danlos syndrome, musculocontractural type 2  - Genetic Testing Registry: Ehlers-Danlos syndrome, progeroid type, 2  - Genetic Testing Registry: Ehlers-Danlos syndrome, type 7A  - MedlinePlus Encyclopedia: Ehlers-Danlos Syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Ehlers-Danlos syndrome,0000313,GHR,https://ghr.nlm.nih.gov/condition/ehlers-danlos-syndrome,C0013720,T019,Disorders
What is (are) Ellis-van Creveld syndrome ?,0000314-1,information,"Ellis-van Creveld syndrome is an inherited disorder of bone growth that results in very short stature (dwarfism). People with this condition have particularly short forearms and lower legs and a narrow chest with short ribs. Ellis-van Creveld syndrome is also characterized by the presence of extra fingers and toes (polydactyly), malformed fingernails and toenails, and dental abnormalities. More than half of affected individuals are born with a heart defect, which can cause serious or life-threatening health problems.  The features of Ellis-van Creveld syndrome overlap with those of another, milder condition called Weyers acrofacial dysostosis. Like Ellis-van Creveld syndrome, Weyers acrofacial dysostosis involves tooth and nail abnormalities, although affected individuals have less pronounced short stature and typically do not have heart defects. The two conditions are caused by mutations in the same genes.",Ellis-van Creveld syndrome,0000314,GHR,https://ghr.nlm.nih.gov/condition/ellis-van-creveld-syndrome,C0013903,T047,Disorders
How many people are affected by Ellis-van Creveld syndrome ?,0000314-2,frequency,"In most parts of the world, Ellis-van Creveld syndrome occurs in 1 in 60,000 to 200,000 newborns. It is difficult to estimate the exact prevalence because the disorder is very rare in the general population. This condition is much more common in the Old Order Amish population of Lancaster County, Pennsylvania, and in the indigenous (native) population of Western Australia.",Ellis-van Creveld syndrome,0000314,GHR,https://ghr.nlm.nih.gov/condition/ellis-van-creveld-syndrome,C0013903,T047,Disorders
What are the genetic changes related to Ellis-van Creveld syndrome ?,0000314-3,genetic changes,"Ellis-van Creveld syndrome can be caused by mutations in the EVC or EVC2 gene. Little is known about the function of these genes, although they appear to play important roles in cell-to-cell signaling during development. In particular, the proteins produced from the EVC and EVC2 genes are thought to help regulate the Sonic Hedgehog signaling pathway. This pathway plays roles in cell growth, cell specialization, and the normal shaping (patterning) of many parts of the body.  The mutations that cause Ellis-van Creveld syndrome result in the production of an abnormally small, nonfunctional version of the EVC or EVC2 protein. It is unclear how the defective proteins lead to the specific signs and symptoms of this condition. Studies suggest that they prevent normal Sonic Hedgehog signaling in the developing embryo, disrupting the formation and growth of the bones, teeth, and other parts of the body.  Together, mutations in the EVC and EVC2 genes account for more than half of all cases of Ellis-van Creveld syndrome. The cause of the remaining cases is unknown.",Ellis-van Creveld syndrome,0000314,GHR,https://ghr.nlm.nih.gov/condition/ellis-van-creveld-syndrome,C0013903,T047,Disorders
Is Ellis-van Creveld syndrome inherited ?,0000314-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Ellis-van Creveld syndrome,0000314,GHR,https://ghr.nlm.nih.gov/condition/ellis-van-creveld-syndrome,C0013903,T047,Disorders
What are the treatments for Ellis-van Creveld syndrome ?,0000314-5,treatment,These resources address the diagnosis or management of Ellis-van Creveld syndrome:  - Genetic Testing Registry: Chondroectodermal dysplasia  - MedlinePlus Encyclopedia: Congenital Heart Disease  - MedlinePlus Encyclopedia: Ellis-van Creveld Syndrome  - MedlinePlus Encyclopedia: Polydactyly   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Ellis-van Creveld syndrome,0000314,GHR,https://ghr.nlm.nih.gov/condition/ellis-van-creveld-syndrome,C0013903,T047,Disorders
What is (are) Emanuel syndrome ?,0000315-1,information,"Emanuel syndrome is a chromosomal disorder that disrupts normal development and affects many parts of the body. Infants with Emanuel syndrome have weak muscle tone (hypotonia) and fail to gain weight and grow at the expected rate (failure to thrive). Their development is significantly delayed, and most affected individuals have severe to profound intellectual disability.  Other features of Emanuel syndrome include an unusually small head (microcephaly), distinctive facial features, and a small lower jaw (micrognathia). Ear abnormalities are common, including small holes in the skin just in front of the ears (preauricular pits or sinuses). About half of all affected infants are born with an opening in the roof of the mouth (cleft palate) or a high arched palate. Males with Emanuel syndrome often have genital abnormalities. Additional signs of this condition can include heart defects and absent or unusually small (hypoplastic) kidneys; these problems can be life-threatening in infancy or childhood.",Emanuel syndrome,0000315,GHR,https://ghr.nlm.nih.gov/condition/emanuel-syndrome,C1836929,T047,Disorders
How many people are affected by Emanuel syndrome ?,0000315-2,frequency,Emanuel syndrome is a rare disorder; its prevalence is unknown. More than 100 individuals with this condition have been reported.,Emanuel syndrome,0000315,GHR,https://ghr.nlm.nih.gov/condition/emanuel-syndrome,C1836929,T047,Disorders
What are the genetic changes related to Emanuel syndrome ?,0000315-3,genetic changes,"Emanuel syndrome is caused by the presence of extra genetic material from chromosome 11 and chromosome 22 in each cell. In addition to the usual 46 chromosomes, people with Emanuel syndrome have an extra (supernumerary) chromosome consisting of a piece of chromosome 11 attached to a piece of chromosome 22. The extra chromosome is known as a derivative 22 or der(22) chromosome.  As a result of the extra chromosome, people with Emanuel syndrome have three copies of some genes in each cell instead of the usual two copies. The excess genetic material disrupts the normal course of development, leading to the characteristic signs and symptoms of this disorder. Researchers are working to determine which genes are included on the der(22) chromosome and what role these genes play in development.",Emanuel syndrome,0000315,GHR,https://ghr.nlm.nih.gov/condition/emanuel-syndrome,C1836929,T047,Disorders
Is Emanuel syndrome inherited ?,0000315-4,inheritance,"Almost everyone with Emanuel syndrome inherits the der(22) chromosome from an unaffected parent. The parent carries a chromosomal rearrangement between chromosomes 11 and 22 called a balanced translocation. No genetic material is gained or lost in a balanced translocation, so these chromosomal changes usually do not cause any health problems. However, translocations can become unbalanced as they are passed to the next generation. Individuals with Emanuel syndrome inherit an unbalanced translocation between chromosomes 11 and 22 that introduces extra genetic material in the form of the der(22) chromosome. This extra genetic material causes birth defects and the other health problems characteristic of this disorder.",Emanuel syndrome,0000315,GHR,https://ghr.nlm.nih.gov/condition/emanuel-syndrome,C1836929,T047,Disorders
What are the treatments for Emanuel syndrome ?,0000315-5,treatment,These resources address the diagnosis or management of Emanuel syndrome:  - Gene Review: Gene Review: Emanuel Syndrome  - Genetic Testing Registry: Emanuel syndrome  - MedlinePlus Encyclopedia: Cleft Lip and Palate  - MedlinePlus Encyclopedia: Microcephaly  - MedlinePlus Encyclopedia: Preauricular Tag or Pit   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Emanuel syndrome,0000315,GHR,https://ghr.nlm.nih.gov/condition/emanuel-syndrome,C1836929,T047,Disorders
What is (are) Emery-Dreifuss muscular dystrophy ?,0000316-1,information,"Emery-Dreifuss muscular dystrophy is a condition that chiefly affects muscles used for movement (skeletal muscles) and heart (cardiac) muscle. Among the earliest features of this disorder are joint deformities called contractures, which restrict the movement of certain joints. Contractures become noticeable in early childhood and most often involve the elbows, ankles, and neck. Most affected individuals also experience slowly progressive muscle weakness and wasting, beginning in muscles of the upper arms and lower legs and progressing to muscles in the shoulders and hips.  Almost all people with Emery-Dreifuss muscular dystrophy have heart problems by adulthood. In many cases, these heart problems stem from abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects) and abnormal heart rhythms (arrhythmias). If untreated, these abnormalities can lead to an unusually slow heartbeat (bradycardia), fainting (syncope), and an increased risk of stroke and sudden death.  The types of Emery-Dreifuss muscular dystrophy are distinguished by their pattern of inheritance: X-linked, autosomal dominant, and autosomal recessive. Although the three types have similar signs and symptoms, researchers believe that the features of autosomal dominant Emery-Dreifuss muscular dystrophy are more variable than the other types. A small percentage of people with the autosomal dominant form experience heart problems without any weakness or wasting of skeletal muscles.",Emery-Dreifuss muscular dystrophy,0000316,GHR,https://ghr.nlm.nih.gov/condition/emery-dreifuss-muscular-dystrophy,C0410189,T047,Disorders
How many people are affected by Emery-Dreifuss muscular dystrophy ?,0000316-2,frequency,"X-linked Emery-Dreifuss muscular dystrophy is the most common form of this condition, affecting an estimated 1 in 100,000 people. The autosomal recessive type of this disorder appears to be very rare; only a few cases have been reported worldwide. The incidence of the autosomal dominant form is unknown.",Emery-Dreifuss muscular dystrophy,0000316,GHR,https://ghr.nlm.nih.gov/condition/emery-dreifuss-muscular-dystrophy,C0410189,T047,Disorders
What are the genetic changes related to Emery-Dreifuss muscular dystrophy ?,0000316-3,genetic changes,"Mutations in the EMD and LMNA genes cause Emery-Dreifuss muscular dystrophy.  The EMD and LMNA genes provide instructions for making proteins that are components of the nuclear envelope, which surrounds the nucleus in cells. The nuclear envelope regulates the movement of molecules into and out of the nucleus, and researchers believe it may play a role in regulating the activity of certain genes.  Most cases of Emery-Dreifuss muscular dystrophy are caused by mutations in the EMD gene. This gene provides instructions for making a protein called emerin, which appears to be essential for the normal function of skeletal and cardiac muscle. Most EMD gene mutations prevent the production of any functional emerin. It remains unclear how a lack of this protein results in the signs and symptoms of Emery-Dreifuss muscular dystrophy.  Less commonly, Emery-Dreifuss muscular dystrophy results from mutations in the LMNA gene. This gene provides instructions for making two very similar proteins, lamin A and lamin C. Most of the LMNA mutations that cause this condition result in the production of an altered version of these proteins. Researchers are investigating how the altered versions of lamins A and C lead to muscle wasting and heart problems in people with Emery-Dreifuss muscular dystrophy.",Emery-Dreifuss muscular dystrophy,0000316,GHR,https://ghr.nlm.nih.gov/condition/emery-dreifuss-muscular-dystrophy,C0410189,T047,Disorders
Is Emery-Dreifuss muscular dystrophy inherited ?,0000316-4,inheritance,"Emery-Dreifuss muscular dystrophy can have several different patterns of inheritance. When this condition is caused by mutations in the EMD gene, it is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. Males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In females (who have two X chromosomes), a mutation typically must be present in both copies of the EMD gene to cause X-linked Emery-Dreifuss muscular dystrophy. Females who carry one altered copy of the EMD gene usually do not experience the muscle weakness and wasting that are characteristic of this condition. In some cases, however, they may experience heart problems associated with this disorder.  Other cases of Emery-Dreifuss muscular dystrophy result from mutations in the LMNA gene and are considered to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. About 75 percent of autosomal dominant Emery-Dreifuss muscular dystrophy cases are caused by new mutations in the LMNA gene and occur in people with no history of the disorder in their family. In the remaining cases, people with this form of the condition inherit the altered LMNA gene from an affected parent.  Rarely, LMNA gene mutations can cause a form of Emery-Dreifuss muscular dystrophy that is inherited in an autosomal recessive pattern. Autosomal recessive inheritance means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.",Emery-Dreifuss muscular dystrophy,0000316,GHR,https://ghr.nlm.nih.gov/condition/emery-dreifuss-muscular-dystrophy,C0410189,T047,Disorders
What are the treatments for Emery-Dreifuss muscular dystrophy ?,0000316-5,treatment,"These resources address the diagnosis or management of Emery-Dreifuss muscular dystrophy:  - Gene Review: Gene Review: Emery-Dreifuss Muscular Dystrophy  - Genetic Testing Registry: Emery-Dreifuss muscular dystrophy  - Genetic Testing Registry: Emery-Dreifuss muscular dystrophy 1, X-linked  - MedlinePlus Encyclopedia: Arrhythmias  - MedlinePlus Encyclopedia: Contracture deformity  - MedlinePlus Encyclopedia: Muscular dystrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Emery-Dreifuss muscular dystrophy,0000316,GHR,https://ghr.nlm.nih.gov/condition/emery-dreifuss-muscular-dystrophy,C0410189,T047,Disorders
What is (are) enlarged parietal foramina ?,0000317-1,information,"Enlarged parietal foramina is an inherited condition of impaired skull development. It is characterized by enlarged openings (foramina) in the parietal bones, which are the two bones that form the top and sides of the skull. This condition is due to incomplete bone formation (ossification) within the parietal bones. The openings are symmetrical and circular in shape, ranging in size from a few millimeters to several centimeters wide. Parietal foramina are a normal feature of fetal development, but typically they close before the baby is born, usually by the fifth month of pregnancy. However, in people with this condition, the parietal foramina remain open throughout life.  The enlarged parietal foramina are soft to the touch due to the lack of bone at those areas of the skull. People with enlarged parietal foramina usually do not have any related health problems; however, scalp defects, seizures, and structural brain abnormalities have been noted in a small percentage of affected people. Pressure applied to the openings can lead to severe headaches, and individuals with this condition have an increased risk of brain damage or skull fractures if any trauma is experienced in the area of the openings.  There are two forms of enlarged parietal foramina, called type 1 and type 2, which differ in their genetic cause.",enlarged parietal foramina,0000317,GHR,https://ghr.nlm.nih.gov/condition/enlarged-parietal-foramina,C1868598,T047,Disorders
How many people are affected by enlarged parietal foramina ?,0000317-2,frequency,"The prevalence of enlarged parietal foramina is estimated to be 1 in 15,000 to 50,000 individuals.",enlarged parietal foramina,0000317,GHR,https://ghr.nlm.nih.gov/condition/enlarged-parietal-foramina,C1868598,T047,Disorders
What are the genetic changes related to enlarged parietal foramina ?,0000317-3,genetic changes,"Mutations in the ALX4 gene account for 60 percent of cases of enlarged parietal foramina and mutations in the MSX2 gene account for 40 percent of cases. These genes provide instructions for producing proteins called transcription factors, which are required for proper development throughout the body. Transcription factors attach (bind) to specific regions of DNA and help control the activity of particular genes. The ALX4 and MSX2 transcription factor proteins are involved in regulating genes that are needed in various cell processes in early development.  Mutations in either the ALX4 or MSX2 gene likely impair the ability of their respective transcription factors to bind to DNA. As a result, the regulation of multiple genes is altered, which disrupts a number of necessary cell functions. The processes that guide skull development seem to be particularly sensitive to changes in the activity of these transcription factors.  If the condition is caused by a mutation in the MSX2 gene, it is called enlarged parietal foramina type 1. Mutations in the ALX4 gene cause enlarged parietal foramina type 2. There appears to be no difference in the size of the openings between enlarged parietal foramina types 1 and 2.",enlarged parietal foramina,0000317,GHR,https://ghr.nlm.nih.gov/condition/enlarged-parietal-foramina,C1868598,T047,Disorders
Is enlarged parietal foramina inherited ?,0000317-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.  However, in rare cases, people who inherit an altered gene do not have enlarged parietal foramina. (This situation is known as reduced penetrance.)",enlarged parietal foramina,0000317,GHR,https://ghr.nlm.nih.gov/condition/enlarged-parietal-foramina,C1868598,T047,Disorders
What are the treatments for enlarged parietal foramina ?,0000317-5,treatment,These resources address the diagnosis or management of enlarged parietal foramina:  - Gene Review: Gene Review: Enlarged Parietal Foramina  - Genetic Testing Registry: Parietal foramina  - Genetic Testing Registry: Parietal foramina 1  - Genetic Testing Registry: Parietal foramina 2  - MedlinePlus Encyclopedia: Skull of a Newborn   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,enlarged parietal foramina,0000317,GHR,https://ghr.nlm.nih.gov/condition/enlarged-parietal-foramina,C1868598,T047,Disorders
What is (are) eosinophil peroxidase deficiency ?,0000318-1,information,"Eosinophil peroxidase deficiency is a condition that affects certain white blood cells called eosinophils but causes no health problems in affected individuals. Eosinophils aid in the body's immune response. During a normal immune response, these cells are turned on (activated), and they travel to the area of injury or inflammation. The cells then release proteins and other compounds that have a toxic effect on severely damaged cells or invading organisms. One of these proteins is called eosinophil peroxidase. In eosinophil peroxidase deficiency, eosinophils have little or no eosinophil peroxidase. A lack of this protein does not seem to affect the eosinophils' ability to carry out an immune response.  Because eosinophil peroxidase deficiency does not cause any health problems, this condition is often diagnosed when blood tests are done for other reasons or when a family member has been diagnosed with the condition.",eosinophil peroxidase deficiency,0000318,GHR,https://ghr.nlm.nih.gov/condition/eosinophil-peroxidase-deficiency,C1850000,T047,Disorders
How many people are affected by eosinophil peroxidase deficiency ?,0000318-2,frequency,"Approximately 100 individuals with eosinophil peroxidase deficiency have been described in the scientific literature. Based on blood test data, varying estimates of the prevalence of the condition have been reported in specific populations. Eosinophil peroxidase deficiency is estimated to occur in 8.6 in 1,000 Yemenite Jews, in 3 in 1,000 North-African Jews, and in 1 in 1,000 Iraqi Jews. In northeastern Italy, the condition occurs in approximately 1 in 14,000 individuals; in Japan it occurs in 1 in 36,000 people; and in Luxembourg, eosinophil peroxidase deficiency is thought to occur in 1 in 100,000 people.",eosinophil peroxidase deficiency,0000318,GHR,https://ghr.nlm.nih.gov/condition/eosinophil-peroxidase-deficiency,C1850000,T047,Disorders
What are the genetic changes related to eosinophil peroxidase deficiency ?,0000318-3,genetic changes,"Mutations in the EPX gene cause eosinophil peroxidase deficiency. The EPX gene provides instructions for making the eosinophil peroxidase protein. During an immune response, activated eosinophils release eosinophil peroxidase at the site of injury. This protein helps form molecules that are highly toxic to bacteria and parasites. These toxic molecules also play a role in regulating inflammation by fighting microbial invaders.  EPX gene mutations reduce or prevent eosinophil peroxidase production or result in a protein that is unstable and nonfunctional. As a result, eosinophils have severely reduced amounts of eosinophil peroxidase or none at all. Other proteins within affected eosinophils are normal, and while the cells lacking eosinophil peroxidase are smaller and may have structural changes, the loss of eosinophil peroxidase does not appear to impair the function of eosinophils.",eosinophil peroxidase deficiency,0000318,GHR,https://ghr.nlm.nih.gov/condition/eosinophil-peroxidase-deficiency,C1850000,T047,Disorders
Is eosinophil peroxidase deficiency inherited ?,0000318-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",eosinophil peroxidase deficiency,0000318,GHR,https://ghr.nlm.nih.gov/condition/eosinophil-peroxidase-deficiency,C1850000,T047,Disorders
What are the treatments for eosinophil peroxidase deficiency ?,0000318-5,treatment,These resources address the diagnosis or management of eosinophil peroxidase deficiency:  - Genetic Testing Registry: Eosinophil peroxidase deficiency  - Tulane University Eosinophilic Disorder Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,eosinophil peroxidase deficiency,0000318,GHR,https://ghr.nlm.nih.gov/condition/eosinophil-peroxidase-deficiency,C1850000,T047,Disorders
What is (are) epidermal nevus ?,0000319-1,information,"An epidermal nevus (plural: nevi) is an abnormal, noncancerous (benign) patch of skin caused by an overgrowth of skin cells. Epidermal nevi are typically seen at birth or develop in early childhood. They can be flat, tan patches of skin or raised, velvety patches. As the affected individual ages, the nevus can become thicker and darker and develop a wart-like (verrucous) appearance. Often, epidermal nevi follow a pattern on the skin known as the lines of Blaschko. The lines of Blaschko, which are invisible on skin, are thought to follow the paths along which cells migrate as the skin develops before birth.  There are several types of epidermal nevi that are defined in part by the type of skin cell involved. The epidermis is the outermost layer of skin and is composed primarily of a specific cell type called a keratinocyte. One group of epidermal nevi, called keratinocytic or nonorganoid epidermal nevi, includes nevi that involve only keratinocytes. Other types of epidermal nevi involve additional types of epidermal cells, such as the cells that make up the hair follicles or the sebaceous glands (glands in the skin that produce a substance that protects the skin and hair). These nevi comprise a group called organoid epidermal nevi.  Some affected individuals have only an epidermal nevus and no other abnormalities. However, sometimes people with an epidermal nevus also have problems in other body systems, such as the brain, eyes, or bones. In these cases, the affected individual has a condition called an epidermal nevus syndrome. There are several different epidermal nevus syndromes characterized by the type of epidermal nevus involved.",epidermal nevus,0000319,GHR,https://ghr.nlm.nih.gov/condition/epidermal-nevus,C0334082,T047,Disorders
How many people are affected by epidermal nevus ?,0000319-2,frequency,"Epidermal nevi affect approximately 1 in 1,000 people.",epidermal nevus,0000319,GHR,https://ghr.nlm.nih.gov/condition/epidermal-nevus,C0334082,T047,Disorders
What are the genetic changes related to epidermal nevus ?,0000319-3,genetic changes,"Mutations in the FGFR3 gene have been found in approximately 30 percent of people with a type of nevus in the keratinocytic epidermal nevi group. The gene mutations involved in most epidermal nevi are unknown.  Mutations associated with an epidermal nevus are present only in the cells of the nevus, not in the normal skin cells surrounding it. Because the mutation is found in some of the body's cells but not in others, people with an epidermal nevus are said to be mosaic for the mutation.  The FGFR3 gene provides instructions for the fibroblast growth factor receptor 3 (FGFR3) protein. This protein is involved in several important cellular processes, including regulation of growth and division of skin cells. The FGFR3 protein interacts with specific growth factors outside the cell to receive signals that control growth and development. When these growth factors attach to the FGFR3 protein, the protein is turned on (activated), which triggers a cascade of chemical reactions inside the cell that control growth and other cellular functions.  The most common FGFR3 gene mutation in epidermal nevi creates a protein that is turned on without attachment of a growth factor, which means that the FGFR3 protein is constantly active. Cells with a mutated FGFR3 gene grow and divide more than normal cells. In addition, these mutated cells do not undergo a form of self-destruction called apoptosis as readily as normal cells. These effects result in overgrowth of skin cells, leading to epidermal nevi.",epidermal nevus,0000319,GHR,https://ghr.nlm.nih.gov/condition/epidermal-nevus,C0334082,T047,Disorders
Is epidermal nevus inherited ?,0000319-4,inheritance,"This condition is generally not inherited but arises from mutations in the body's cells that occur after conception. This alteration is called a somatic mutation.  Occasionally, the somatic mutation occurs in a person's reproductive cells (sperm or eggs) and is passed to the next generation. An inherited FGFR3 gene mutation is found in every cell in the body, which results in skeletal abnormalities rather than epidermal nevus.",epidermal nevus,0000319,GHR,https://ghr.nlm.nih.gov/condition/epidermal-nevus,C0334082,T047,Disorders
What are the treatments for epidermal nevus ?,0000319-5,treatment,These resources address the diagnosis or management of epidermal nevus:  - Genetic Testing Registry: Epidermal nevus   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,epidermal nevus,0000319,GHR,https://ghr.nlm.nih.gov/condition/epidermal-nevus,C0334082,T047,Disorders
What is (are) epidermolysis bullosa simplex ?,0000320-1,information,"Epidermolysis bullosa simplex is one of a group of genetic conditions called epidermolysis bullosa that cause the skin to be very fragile and to blister easily. Blisters and areas of skin loss (erosions) occur in response to minor injury or friction, such as rubbing or scratching. Epidermolysis bullosa simplex is one of the major forms of epidermolysis bullosa. The signs and symptoms of this condition vary widely among affected individuals. Blistering primarily affects the hands and feet in mild cases, and the blisters usually heal without leaving scars. Severe cases of this condition involve widespread blistering that can lead to infections, dehydration, and other medical problems. Severe cases may be life-threatening in infancy.  Researchers have identified four major types of epidermolysis bullosa simplex. Although the types differ in severity, their features overlap significantly, and they are caused by mutations in the same genes. Most researchers now consider the major forms of this condition to be part of a single disorder with a range of signs and symptoms.  The mildest form of epidermolysis bullosa simplex, known as the localized type (formerly called the Weber-Cockayne type), is characterized by skin blistering that begins anytime between childhood and adulthood and is usually limited to the hands and feet. Later in life, skin on the palms of the hands and soles of the feet may thicken and harden (hyperkeratosis).  The Dowling-Meara type is the most severe form of epidermolysis bullosa simplex. Extensive, severe blistering can occur anywhere on the body, including the inside of the mouth, and blisters may appear in clusters. Blistering is present from birth and tends to improve with age. Affected individuals also experience abnormal nail growth and hyperkeratosis of the palms and soles.  Another form of epidermolysis bullosa simplex, known as the other generalized type (formerly called the Koebner type), is associated with widespread blisters that appear at birth or in early infancy. The blistering tends to be less severe than in the Dowling-Meara type.  Epidermolysis bullosa simplex with mottled pigmentation is characterized by patches of darker skin on the trunk, arms, and legs that fade in adulthood. This form of the disorder also involves skin blistering from early infancy, hyperkeratosis of the palms and soles, and abnormal nail growth.  In addition to the four major types described above, researchers have identified another skin condition related to epidermolysis bullosa simplex, which they call the Ogna type. It is caused by mutations in a gene that is not associated with the other types of epidermolysis bullosa simplex. It is unclear whether the Ogna type is a subtype of epidermolysis bullosa simplex or represents a separate form of epidermolysis bullosa.  Several other variants of epidermolysis bullosa simplex have been proposed, but they appear to be very rare.",epidermolysis bullosa simplex,0000320,GHR,https://ghr.nlm.nih.gov/condition/epidermolysis-bullosa-simplex,C0079298,T047,Disorders
How many people are affected by epidermolysis bullosa simplex ?,0000320-2,frequency,"The exact prevalence of epidermolysis bullosa simplex is unknown, but this condition is estimated to affect 1 in 30,000 to 50,000 people. The localized type is the most common form of the condition.",epidermolysis bullosa simplex,0000320,GHR,https://ghr.nlm.nih.gov/condition/epidermolysis-bullosa-simplex,C0079298,T047,Disorders
What are the genetic changes related to epidermolysis bullosa simplex ?,0000320-3,genetic changes,"The four major types of epidermolysis bullosa simplex can result from mutations in either the KRT5 or KRT14 gene. These genes provide instructions for making proteins called keratin 5 and keratin 14. These tough, fibrous proteins work together to provide strength and resiliency to the outer layer of the skin (the epidermis). Mutations in either the KRT5 or KRT14 gene prevent the keratin proteins from assembling into strong networks, causing cells in the epidermis to become fragile and easily damaged. As a result, the skin is less resistant to friction and minor trauma and blisters easily. In rare cases, no KRT5 or KRT14 gene mutations are identified in people with one of the four major types of epidermolysis bullosa simplex.  Mutations in another gene, PLEC, have been associated with the rare Ogna type of epidermolysis bullosa simplex. The PLEC gene provides instructions for making a protein called plectin, which helps attach the epidermis to underlying layers of skin. Researchers are working to determine how PLEC gene mutations lead to the major features of the condition.",epidermolysis bullosa simplex,0000320,GHR,https://ghr.nlm.nih.gov/condition/epidermolysis-bullosa-simplex,C0079298,T047,Disorders
Is epidermolysis bullosa simplex inherited ?,0000320-4,inheritance,"Epidermolysis bullosa simplex is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Some affected people inherit the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  In rare cases, epidermolysis bullosa simplex is inherited in an autosomal recessive pattern. Autosomal recessive inheritance means the condition results when two copies of the gene in each cell are altered. The parents of an individual with an autosomal recessive disorder typically each carry one copy of the altered gene, but do not show signs and symptoms of the disorder.",epidermolysis bullosa simplex,0000320,GHR,https://ghr.nlm.nih.gov/condition/epidermolysis-bullosa-simplex,C0079298,T047,Disorders
What are the treatments for epidermolysis bullosa simplex ?,0000320-5,treatment,"These resources address the diagnosis or management of epidermolysis bullosa simplex:  - Dystrophic Epidermolysis Bullosa Research Association (DebRA) of America: Wound Care  - Epidermolysis Bullosa Center, Cincinnati Children's Hospital Medical Center  - Gene Review: Gene Review: Epidermolysis Bullosa Simplex  - Genetic Testing Registry: Epidermolysis bullosa simplex  - Genetic Testing Registry: Epidermolysis bullosa simplex with mottled pigmentation  - Genetic Testing Registry: Epidermolysis bullosa simplex, Cockayne-Touraine type  - Genetic Testing Registry: Epidermolysis bullosa simplex, Koebner type  - Genetic Testing Registry: Epidermolysis bullosa simplex, Ogna type  - Genetic Testing Registry: Epidermolysis bullosa simplex, autosomal recessive  - MedlinePlus Encyclopedia: Epidermolysis Bullosa   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",epidermolysis bullosa simplex,0000320,GHR,https://ghr.nlm.nih.gov/condition/epidermolysis-bullosa-simplex,C0079298,T047,Disorders
What is (are) epidermolysis bullosa with pyloric atresia ?,0000321-1,information,"Epidermolysis bullosa with pyloric atresia (EB-PA) is a condition that affects the skin and digestive tract. This condition is one of several forms of epidermolysis bullosa, a group of genetic conditions that cause the skin to be fragile and to blister easily. Affected infants are often born with widespread blistering and areas of missing skin. Blisters continue to appear in response to minor injury or friction, such as rubbing or scratching. Most often, blisters occur over the whole body and affect mucous membranes such as the moist lining of the mouth and digestive tract.  People with EB-PA are also born with pyloric atresia, which is an obstruction of the lower part of the stomach (the pylorus). This obstruction prevents food from emptying out of the stomach into the intestine. Signs of pyloric atresia include vomiting, a swollen (distended) abdomen, and an absence of stool. Pyloric atresia is life-threatening and must be repaired with surgery soon after birth.  Other complications of EB-PA can include fusion of the skin between the fingers and toes, abnormalities of the fingernails and toenails, joint deformities (contractures) that restrict movement, and hair loss (alopecia). Some affected individuals are also born with malformations of the urinary tract, including the kidneys and bladder.  Because the signs and symptoms of EB-PA are so severe, many infants with this condition do not survive beyond the first year of life. In those who survive, the condition may improve with time; some affected individuals have little or no blistering later in life. However, many affected individuals who live past infancy experience severe medical problems, including blistering and the formation of red, bumpy patches called granulation tissue. Granulation tissue most often forms on the skin around the mouth, nose, fingers, and toes. It can also build up in the airway, leading to difficulty breathing.",epidermolysis bullosa with pyloric atresia,0000321,GHR,https://ghr.nlm.nih.gov/condition/epidermolysis-bullosa-with-pyloric-atresia,C1856934,T047,Disorders
How many people are affected by epidermolysis bullosa with pyloric atresia ?,0000321-2,frequency,"EB-PA appears to be a rare condition, although its prevalence is unknown. At least 50 affected individuals have been reported worldwide.",epidermolysis bullosa with pyloric atresia,0000321,GHR,https://ghr.nlm.nih.gov/condition/epidermolysis-bullosa-with-pyloric-atresia,C1856934,T047,Disorders
What are the genetic changes related to epidermolysis bullosa with pyloric atresia ?,0000321-3,genetic changes,"EB-PA can be caused by mutations in the ITGA6, ITGB4, and PLEC genes. These genes provide instructions for making proteins with critical roles in the skin and digestive tract.  ITGB4 gene mutations are the most common cause of EB-PA; these mutations are responsible for about 80 percent of all cases. ITGA6 gene mutations cause about 5 percent of cases. The proteins produced from the ITGA6 and ITGB4 genes join to form a protein known as 64 integrin. This protein plays an important role in strengthening and stabilizing the skin by helping to attach the top layer of skin (the epidermis) to underlying layers. Mutations in either the ITGA6 gene or the ITGB4 gene lead to the production of a defective or nonfunctional version of 64 integrin, or prevent cells from making any of this protein. A shortage of functional 64 integrin causes cells in the epidermis to be fragile and easily damaged. Friction or other minor trauma can cause the skin layers to separate, leading to the formation of blisters.  About 15 percent of all cases of EB-PA result from mutations in the PLEC gene. This gene provides instructions for making a protein called plectin. Like 64 integrin, plectin helps attach the epidermis to underlying layers of skin. Some PLEC gene mutations prevent the cell from making any functional plectin, while other mutations result in an abnormal form of the protein. When plectin is altered or missing, the skin is less resistant to friction and minor trauma and blisters easily.  Researchers are working to determine how mutations in the ITGA6, ITGB4, and PLEC genes lead to pyloric atresia in people with EB-PA. Studies suggest that these genes are important for the normal development of the digestive tract.",epidermolysis bullosa with pyloric atresia,0000321,GHR,https://ghr.nlm.nih.gov/condition/epidermolysis-bullosa-with-pyloric-atresia,C1856934,T047,Disorders
Is epidermolysis bullosa with pyloric atresia inherited ?,0000321-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",epidermolysis bullosa with pyloric atresia,0000321,GHR,https://ghr.nlm.nih.gov/condition/epidermolysis-bullosa-with-pyloric-atresia,C1856934,T047,Disorders
What are the treatments for epidermolysis bullosa with pyloric atresia ?,0000321-5,treatment,"These resources address the diagnosis or management of epidermolysis bullosa with pyloric atresia:  - Epidermolysis Bullosa Center, Cincinnati Children's Hospital Medical Center  - Gene Review: Gene Review: Epidermolysis Bullosa with Pyloric Atresia  - Genetic Testing Registry: Epidermolysis bullosa simplex with pyloric atresia  - Genetic Testing Registry: Epidermolysis bullosa with pyloric atresia  - MedlinePlus Encyclopedia: Epidermolysis Bullosa   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",epidermolysis bullosa with pyloric atresia,0000321,GHR,https://ghr.nlm.nih.gov/condition/epidermolysis-bullosa-with-pyloric-atresia,C1856934,T047,Disorders
What is (are) epidermolytic hyperkeratosis ?,0000322-1,information,"Epidermolytic hyperkeratosis is a skin disorder that is present at birth. Affected babies may have very red skin (erythroderma) and severe blisters. Because newborns with this disorder are missing the protection provided by normal skin, they are at risk of becoming dehydrated and developing infections in the skin or throughout the body (sepsis).  As affected individuals get older, blistering is less frequent, erythroderma becomes less evident, and the skin becomes thick (hyperkeratotic), especially over joints, on areas of skin that come into contact with each other, or on the scalp or neck. This thickened skin is usually darker than normal. Bacteria can grow in the thick skin, often causing a distinct odor.  Epidermolytic hyperkeratosis can be categorized into two types. People with PS-type epidermolytic hyperkeratosis have thick skin on the palms of their hands and soles of their feet (palmoplantar or palm/sole hyperkeratosis) in addition to other areas of the body. People with the other type, NPS-type, do not have extensive palmoplantar hyperkeratosis but do have hyperkeratosis on other areas of the body.  Epidermolytic hyperkeratosis is part of a group of conditions called ichthyoses, which refers to the scaly skin seen in individuals with related disorders. However, in epidermolytic hyperkeratosis, the skin is thick but not scaly as in some of the other conditions in the group.",epidermolytic hyperkeratosis,0000322,GHR,https://ghr.nlm.nih.gov/condition/epidermolytic-hyperkeratosis,C0079153,T019,Disorders
How many people are affected by epidermolytic hyperkeratosis ?,0000322-2,frequency,"Epidermolytic hyperkeratosis affects approximately 1 in 200,000 to 300,000 people worldwide.",epidermolytic hyperkeratosis,0000322,GHR,https://ghr.nlm.nih.gov/condition/epidermolytic-hyperkeratosis,C0079153,T019,Disorders
What are the genetic changes related to epidermolytic hyperkeratosis ?,0000322-3,genetic changes,"Mutations in the KRT1 or KRT10 genes are responsible for epidermolytic hyperkeratosis. These genes provide instructions for making proteins called keratin 1 and keratin 10, which are found in cells called keratinocytes in the outer layer of the skin (the epidermis). The tough, fibrous keratin proteins attach to each other and form fibers called intermediate filaments, which form networks and provide strength and resiliency to the epidermis.  Mutations in the KRT1 or KRT10 genes lead to changes in the keratin proteins, preventing them from forming strong, stable intermediate filament networks within cells. Without a strong network, keratinocytes become fragile and are easily damaged, which can lead to blistering in response to friction or mild trauma. It is unclear how these mutations cause the overgrowth of epidermal cells that results in hyperkeratotic skin.  KRT1 gene mutations are associated with PS-type epidermal hyperkeratosis, and KRT10 gene mutations are usually associated with NPS-type. The keratin 1 protein is present in the keratinocytes of the skin on the palms of the hands and the soles of the feet as well as other parts of the body, so mutations in the KRT1 gene lead to skin problems in these areas. The keratin 10 protein is not found in the skin of the palms and soles, so these areas are unaffected by mutations in the KRT10 gene.",epidermolytic hyperkeratosis,0000322,GHR,https://ghr.nlm.nih.gov/condition/epidermolytic-hyperkeratosis,C0079153,T019,Disorders
Is epidermolytic hyperkeratosis inherited ?,0000322-4,inheritance,"Epidermolytic hyperkeratosis can have different inheritance patterns. About half of the cases of this condition result from new mutations in the KRT1 or KRT10 gene and occur in people with no history of the disorder in their family.  When epidermolytic hyperkeratosis is inherited, it is usually in an autosomal dominant pattern, which means one copy of the altered KRT1 or KRT10 gene in each cell is sufficient to cause the disorder.  Very rarely, epidermolytic hyperkeratosis caused by mutations in the KRT10 gene can be inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",epidermolytic hyperkeratosis,0000322,GHR,https://ghr.nlm.nih.gov/condition/epidermolytic-hyperkeratosis,C0079153,T019,Disorders
What are the treatments for epidermolytic hyperkeratosis ?,0000322-5,treatment,These resources address the diagnosis or management of epidermolytic hyperkeratosis:  - Genetic Testing Registry: Bullous ichthyosiform erythroderma  - The Swedish Information Centre for Rare Diseases: Ichthyosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,epidermolytic hyperkeratosis,0000322,GHR,https://ghr.nlm.nih.gov/condition/epidermolytic-hyperkeratosis,C0079153,T019,Disorders
What is (are) episodic ataxia ?,0000323-1,information,"Episodic ataxia is a group of related conditions that affect the nervous system and cause problems with movement. People with episodic ataxia have recurrent episodes of poor coordination and balance (ataxia). During these episodes, many people also experience dizziness (vertigo), nausea and vomiting, migraine headaches, blurred or double vision, slurred speech, and ringing in the ears (tinnitus). Seizures, muscle weakness, and paralysis affecting one side of the body (hemiplegia) may also occur during attacks. Additionally, some affected individuals have a muscle abnormality called myokymia during or between episodes. This abnormality can cause muscle cramping, stiffness, and continuous, fine muscle twitching that appears as rippling under the skin.  Episodes of ataxia and other symptoms can begin anytime from early childhood to adulthood. They can be triggered by environmental factors such as emotional stress, caffeine, alcohol, certain medications, physical activity, and illness. The frequency of attacks ranges from several per day to one or two per year. Between episodes, some affected individuals continue to experience ataxia, which may worsen over time, as well as involuntary eye movements called nystagmus.  Researchers have identified at least seven types of episodic ataxia, designated type 1 through type 7. The types are distinguished by their pattern of signs and symptoms, age of onset, length of attacks, and, when known, genetic cause.",episodic ataxia,0000323,GHR,https://ghr.nlm.nih.gov/condition/episodic-ataxia,C1720189,T047,Disorders
How many people are affected by episodic ataxia ?,0000323-2,frequency,"Episodic ataxia is uncommon, affecting less than 1 in 100,000 people. Only types 1 and 2 have been identified in more than one family, and type 2 is by far the most common form of the condition.",episodic ataxia,0000323,GHR,https://ghr.nlm.nih.gov/condition/episodic-ataxia,C1720189,T047,Disorders
What are the genetic changes related to episodic ataxia ?,0000323-3,genetic changes,"Episodic ataxia can be caused by mutations in several genes that play important roles in the nervous system. Three of these genes, KCNA1, CACNA1A, and CACNB4, provide instructions for making proteins that are involved in the transport of charged atoms (ions) across cell membranes. The movement of these ions is critical for normal signaling between nerve cells (neurons) in the brain and other parts of the nervous system. Mutations in the KCNA1, CACNA1A, and CACNB4 genes are responsible for episodic ataxia types 1, 2, and 5, respectively.  Mutations in the SLC1A3 gene have been found to cause episodic ataxia type 6. This gene provides instructions for making a protein that transports a brain chemical (neurotransmitter) called glutamate. Neurotransmitters, including glutamate, allow neurons to communicate by relaying chemical signals from one neuron to another.  Researchers believe that mutations in the KCNA1, CACNA1A, CACNB4, and SLC1A3 genes alter the transport of ions and glutamate in the brain, which causes certain neurons to become overexcited and disrupts normal communication between these cells. Although changes in chemical signaling in the brain underlie the recurrent attacks seen in people with episodic ataxia, it is unclear how mutations in these genes cause the specific features of the disorder.  The genetic causes of episodic ataxia types 3, 4, and 7 have not been identified. Researchers are looking for additional genes that can cause episodic ataxia.",episodic ataxia,0000323,GHR,https://ghr.nlm.nih.gov/condition/episodic-ataxia,C1720189,T047,Disorders
Is episodic ataxia inherited ?,0000323-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",episodic ataxia,0000323,GHR,https://ghr.nlm.nih.gov/condition/episodic-ataxia,C1720189,T047,Disorders
What are the treatments for episodic ataxia ?,0000323-5,treatment,"These resources address the diagnosis or management of episodic ataxia:  - Consortium for Clinical Investigations of Neurological Channelopathies (CINCH)  - Gene Review: Gene Review: Episodic Ataxia Type 1  - Gene Review: Gene Review: Episodic Ataxia Type 2  - Genetic Testing Registry: Episodic ataxia type 1  - Genetic Testing Registry: Episodic ataxia type 2  - Genetic Testing Registry: Episodic ataxia, type 3  - Genetic Testing Registry: Episodic ataxia, type 4  - Genetic Testing Registry: Episodic ataxia, type 7  - MedlinePlus Encyclopedia: Movement - uncoordinated  - MedlinePlus Encyclopedia: Vertigo-associated disorders   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",episodic ataxia,0000323,GHR,https://ghr.nlm.nih.gov/condition/episodic-ataxia,C1720189,T047,Disorders
What is (are) Erdheim-Chester disease ?,0000324-1,information,"Erdheim-Chester disease is a rare disorder characterized by histiocytosis, a condition in which the immune system produces excess quantities of cells called histiocytes. Histiocytes normally function to destroy foreign substances and protect the body from infection. Erdheim-Chester disease is classified as a form of non-Langerhans cell histiocytosis to distinguish it from Langerhans cell histiocytosis, which involves accumulation of a specific type of histiocyte called Langerhans cells. In Erdheim-Chester disease, histiocytosis leads to inflammation that can damage organs and tissues throughout the body, causing them to become thickened, dense, and scarred (fibrotic); this tissue damage may lead to organ failure.  People with Erdheim-Chester disease often have bone pain, especially in the lower legs and upper arms, due to an abnormal increase in bone density (osteosclerosis). Damage to the pituitary gland (a structure at the base of the brain that produces several hormones, including a hormone that controls the amount of water released in the urine) may result in hormonal problems such as a condition called diabetes insipidus that leads to excessive urination. Abnormally high pressure of the cerebrospinal fluid within the skull (intracranial hypertension) caused by accumulation of histiocytes in the brain may result in headaches, seizures, cognitive impairment, or problems with movement or sensation. People with this condition can also have shortness of breath, heart or kidney disease, protruding eyes (exophthalmos), skin growths, or inability to conceive a child (infertility). Affected individuals may also experience fever, night sweats, fatigue, weakness, and weight loss.  The signs and symptoms of Erdheim-Chester disease usually appear between the ages of 40 and 60, although the disorder can occur at any age. The severity of the condition varies widely; some affected individuals have few or no associated health problems, while others have severe complications that can be life-threatening.",Erdheim-Chester disease,0000324,GHR,https://ghr.nlm.nih.gov/condition/erdheim-chester-disease,C0878675,T047,Disorders
How many people are affected by Erdheim-Chester disease ?,0000324-2,frequency,"Erdheim-Chester disease is a rare disorder; its exact prevalence is unknown. More than 500 affected individuals worldwide have been described in the medical literature. For unknown reasons, men are slightly more likely to develop the disease, accounting for about 60 percent of cases.",Erdheim-Chester disease,0000324,GHR,https://ghr.nlm.nih.gov/condition/erdheim-chester-disease,C0878675,T047,Disorders
What are the genetic changes related to Erdheim-Chester disease ?,0000324-3,genetic changes,"More than half of people with Erdheim-Chester disease have a specific mutation in the BRAF gene. Mutations in other genes are also thought to be involved in this disorder.  The BRAF gene provides instructions for making a protein that helps transmit chemical signals from outside the cell to the cell's nucleus. This protein is part of a signaling pathway known as the RAS/MAPK pathway, which controls several important cell functions. Specifically, the RAS/MAPK pathway regulates the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement (migration), and the self-destruction of cells (apoptosis).  The BRAF gene mutation that causes Erdheim-Chester disease is somatic, which means that it occurs during a person's lifetime and is present only in certain cells. The mutation occurs in histiocytes or in immature precursor cells that will develop into histiocytes. This mutation leads to production of a BRAF protein that is abnormally active, which disrupts regulation of cell growth and division. The unregulated overproduction of histiocytes results in their accumulation in the body's tissues and organs, leading to the signs and symptoms of Erdheim-Chester disease.  The BRAF gene belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous. Researchers disagree on whether Erdheim-Chester disease should be considered a form of cancer because of the unregulated accumulation of histiocytes.",Erdheim-Chester disease,0000324,GHR,https://ghr.nlm.nih.gov/condition/erdheim-chester-disease,C0878675,T047,Disorders
Is Erdheim-Chester disease inherited ?,0000324-4,inheritance,This condition is not inherited. It arises from a somatic mutation in histiocytes or their precursor cells during an individual's lifetime.,Erdheim-Chester disease,0000324,GHR,https://ghr.nlm.nih.gov/condition/erdheim-chester-disease,C0878675,T047,Disorders
What are the treatments for Erdheim-Chester disease ?,0000324-5,treatment,These resources address the diagnosis or management of Erdheim-Chester disease:  - Histiocytosis Association: Erdheim-Chester Disease Diagnosis and Treatment   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Erdheim-Chester disease,0000324,GHR,https://ghr.nlm.nih.gov/condition/erdheim-chester-disease,C0878675,T047,Disorders
What is (are) erythrokeratodermia variabilis et progressiva ?,0000325-1,information,"Erythrokeratodermia variabilis et progressiva (EKVP) is a skin disorder that is present at birth or becomes apparent in infancy. Although its signs and symptoms vary, the condition is characterized by two major features. The first is areas of hyperkeratosis, which is rough, thickened skin. These thickened patches are usually reddish-brown and can either be widespread over many parts of the body or occur only in a small area. They tend to be fixed, meaning they do not spread or go away. However, the patches can vary in size and shape, and in some affected people they get larger over time. The areas of thickened skin are generally symmetric, which means they occur in the same places on the right and left sides of the body.  The second major feature of EKVP is patches of reddened skin called erythematous areas. Unlike the hyperkeratosis that occurs in this disorder, the erythematous areas are usually transient, which means they come and go. They vary in size, shape, and location, and can occur anywhere on the body. The redness can be triggered by sudden changes in temperature, emotional stress, or trauma or irritation to the area. It usually fades within hours to days.",erythrokeratodermia variabilis et progressiva,0000325,GHR,https://ghr.nlm.nih.gov/condition/erythrokeratodermia-variabilis-et-progressiva,C0265961,T019,Disorders
How many people are affected by erythrokeratodermia variabilis et progressiva ?,0000325-2,frequency,EKVP is a rare disorder; its prevalence is unknown.,erythrokeratodermia variabilis et progressiva,0000325,GHR,https://ghr.nlm.nih.gov/condition/erythrokeratodermia-variabilis-et-progressiva,C0265961,T019,Disorders
What are the genetic changes related to erythrokeratodermia variabilis et progressiva ?,0000325-3,genetic changes,"EKVP can be caused by mutations in the GJB3 or GJB4 gene. These genes provide instructions for making proteins called connexin 31 and connexin 30.3, respectively. These proteins are part of the connexin family, a group of proteins that form channels called gap junctions on the surface of cells. Gap junctions open and close to regulate the flow of nutrients, charged atoms (ions), and other signaling molecules from one cell to another. They are essential for direct communication between neighboring cells. Gap junctions formed with connexin 31 and connexin 30.3 are found in several tissues, including the outermost layer of skin (the epidermis).  The GJB3 and GJB4 gene mutations that cause EKVP alter the structure of the connexins produced from these genes. Studies suggest that the abnormal proteins can build up in a cell structure called the endoplasmic reticulum (ER), triggering a harmful process known as ER stress. Researchers suspect that ER stress damages and leads to the premature death of cells in the epidermis. This cell death leads to skin inflammation, which appears to underlie the development of erythematous areas. The mechanism by which epidermal damage and cell death contributes to hyperkeratosis is poorly understood.  In some cases, affected individuals have no identified mutation in the GJB3 or GJB4 gene. In these individuals, the cause of the disorder is unknown. Researchers suspect that changes in other, unidentified genes may also be associated with EKVP.",erythrokeratodermia variabilis et progressiva,0000325,GHR,https://ghr.nlm.nih.gov/condition/erythrokeratodermia-variabilis-et-progressiva,C0265961,T019,Disorders
Is erythrokeratodermia variabilis et progressiva inherited ?,0000325-4,inheritance,"EKVP is most often inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new gene mutations and occur in people with no history of the disorder in their family.  A few studies have suggested that EKVP can also have an autosomal recessive pattern of inheritance. However, this inheritance pattern has only been reported in a small number of affected families, and not all researchers agree that it is truly autosomal recessive. Autosomal recessive inheritance means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",erythrokeratodermia variabilis et progressiva,0000325,GHR,https://ghr.nlm.nih.gov/condition/erythrokeratodermia-variabilis-et-progressiva,C0265961,T019,Disorders
What are the treatments for erythrokeratodermia variabilis et progressiva ?,0000325-5,treatment,These resources address the diagnosis or management of EKVP:  - Genetic Testing Registry: Erythrokeratodermia variabilis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,erythrokeratodermia variabilis et progressiva,0000325,GHR,https://ghr.nlm.nih.gov/condition/erythrokeratodermia-variabilis-et-progressiva,C0265961,T019,Disorders
What is (are) erythromelalgia ?,0000326-1,information,"Erythromelalgia is a condition characterized by episodes of pain, redness, and swelling in various parts of the body, particularly the hands and feet. These episodes are usually triggered by increased body temperature, which may be caused by exercise or entering a warm room. Ingesting alcohol or spicy foods may also trigger an episode. Wearing warm socks, tight shoes, or gloves can cause a pain episode so debilitating that it can impede everyday activities such as wearing shoes and walking. Pain episodes can prevent an affected person from going to school or work regularly.  The signs and symptoms of erythromelalgia typically begin in childhood, although mildly affected individuals may have their first pain episode later in life. As individuals with erythromelalgia get older and the disease progresses, the hands and feet may be constantly red, and the affected areas can extend from the hands to the arms, shoulders, and face, and from the feet to the entire legs.  Erythromelalgia is often considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and pain.",erythromelalgia,0000326,GHR,https://ghr.nlm.nih.gov/condition/erythromelalgia,C0014804,T047,Disorders
How many people are affected by erythromelalgia ?,0000326-2,frequency,The prevalence of erythromelalgia is unknown.,erythromelalgia,0000326,GHR,https://ghr.nlm.nih.gov/condition/erythromelalgia,C0014804,T047,Disorders
What are the genetic changes related to erythromelalgia ?,0000326-3,genetic changes,"Mutations in the SCN9A gene can cause erythromelalgia. The SCN9A gene provides instructions for making one part (the alpha subunit) of a sodium channel called NaV1.7. Sodium channels transport positively charged sodium atoms (sodium ions) into cells and play a key role in a cell's ability to generate and transmit electrical signals. NaV1.7 sodium channels are found in nerve cells called nociceptors that transmit pain signals to the spinal cord and brain.  The SCN9A gene mutations that cause erythromelalgia result in NaV1.7 sodium channels that open more easily than usual and stays open longer than normal, increasing the flow of sodium ions into nociceptors. This increase in sodium ions enhances transmission of pain signals, leading to the signs and symptoms of erythromelalgia. It is unknown why the pain episodes associated with erythromelalgia mainly occur in the hands and feet.  An estimated 15 percent of cases of erythromelalgia are caused by mutations in the SCN9A gene. Other cases are thought to have a nongenetic cause or may be caused by mutations in one or more as-yet unidentified genes.",erythromelalgia,0000326,GHR,https://ghr.nlm.nih.gov/condition/erythromelalgia,C0014804,T047,Disorders
Is erythromelalgia inherited ?,0000326-4,inheritance,"Some cases of erythromelalgia occur in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some of these instances, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",erythromelalgia,0000326,GHR,https://ghr.nlm.nih.gov/condition/erythromelalgia,C0014804,T047,Disorders
What are the treatments for erythromelalgia ?,0000326-5,treatment,These resources address the diagnosis or management of erythromelalgia:  - Gene Review: Gene Review: SCN9A-Related Inherited Erythromelalgia  - Genetic Testing Registry: Primary erythromelalgia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,erythromelalgia,0000326,GHR,https://ghr.nlm.nih.gov/condition/erythromelalgia,C0014804,T047,Disorders
What is (are) esophageal atresia/tracheoesophageal fistula ?,0000327-1,information,"Esophageal atresia/tracheoesophageal fistula (EA/TEF) is a condition resulting from abnormal development before birth of the tube that carries food from the mouth to the stomach (the esophagus). During early development, the esophagus and windpipe (trachea) begin as a single tube that normally divides into the two adjacent passages between four and eight weeks after conception. If this separation does not occur properly, EA/TEF is the result.  In esophageal atresia (EA), the upper esophagus does not connect (atresia) to the lower esophagus and stomach. Almost 90 percent of babies born with esophageal atresia also have a tracheoesophageal fistula (TEF), in which the esophagus and the trachea are abnormally connected, allowing fluids from the esophagus to get into the airways and interfere with breathing. A small number of infants have only one of these abnormalities.  There are several types of EA/TEF, classified by the location of the malformation and the structures that are affected. In more than 80 percent of cases, the lower section of the malformed esophagus is connected to the trachea (EA with a distal TEF). Other possible configurations include having the upper section of the malformed esophagus connected to the trachea (EA with a proximal TEF), connections to the trachea from both the upper and lower sections of the malformed esophagus (EA with proximal and distal TEF), an esophagus that is malformed but does not connect to the trachea (isolated EA), and a connection to the trachea from an otherwise normal esophagus (H-type TEF with no EA).  While EA/TEF arises during fetal development, it generally becomes apparent shortly after birth. Saliva, liquids fed to the infant, or digestive fluids may enter the windpipe through the tracheoesophageal fistula, leading to coughing, respiratory distress, and a bluish appearance of the skin or lips (cyanosis). Esophageal atresia blocks liquids fed to the infant from entering the stomach, so they are spit back up, sometimes along with fluids from the respiratory tract. EA/TEF is a life-threatening condition; affected babies generally require surgery to correct the malformation in order to allow feeding and prevent lung damage from repeated exposure to esophageal fluids.  EA/TEF occurs alone (isolated EA/TEF) in about 40 percent of affected individuals. In other cases it occurs with other birth defects or as part of a genetic syndrome (non-isolated or syndromic EA/TEF).",esophageal atresia/tracheoesophageal fistula,0000327,GHR,https://ghr.nlm.nih.gov/condition/esophageal-atresia-tracheoesophageal-fistula,C0341154,T019,Disorders
How many people are affected by esophageal atresia/tracheoesophageal fistula ?,0000327-2,frequency,"EA/TEF occurs in 1 in 3,000 to 5,000 newborns.",esophageal atresia/tracheoesophageal fistula,0000327,GHR,https://ghr.nlm.nih.gov/condition/esophageal-atresia-tracheoesophageal-fistula,C0341154,T019,Disorders
What are the genetic changes related to esophageal atresia/tracheoesophageal fistula ?,0000327-3,genetic changes,"Isolated EA/TEF is considered to be a multifactorial condition, which means that multiple gene variations and environmental factors likely contribute to its occurrence. In most cases of isolated EA/TEF, no specific genetic changes or environmental factors have been conclusively determined to be the cause.  Non-isolated or syndromic forms of EA/TEF can be caused by changes in single genes or in chromosomes, or they can be multifactorial. For example, approximately 10 percent of people with CHARGE syndrome, which is usually caused by mutations in the CHD7 gene, have EA/TEF. About 25 percent of individuals with the chromosomal abnormality trisomy 18 are born with EA/TEF. EA/TEF also occurs in VACTERL association, a multifactorial condition. VACTERL is an acronym that stands for vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities. People diagnosed with VACTERL association typically have at least three of these features; between 50 and 80 percent have a tracheoesophageal fistula.",esophageal atresia/tracheoesophageal fistula,0000327,GHR,https://ghr.nlm.nih.gov/condition/esophageal-atresia-tracheoesophageal-fistula,C0341154,T019,Disorders
Is esophageal atresia/tracheoesophageal fistula inherited ?,0000327-4,inheritance,"When EA/TEF occurs as a feature of a genetic syndrome or chromosomal abnormality, it may cluster in families according to the inheritance pattern for that condition. Often EA/TEF is not inherited, and there is only one affected individual in a family.",esophageal atresia/tracheoesophageal fistula,0000327,GHR,https://ghr.nlm.nih.gov/condition/esophageal-atresia-tracheoesophageal-fistula,C0341154,T019,Disorders
What are the treatments for esophageal atresia/tracheoesophageal fistula ?,0000327-5,treatment,"These resources address the diagnosis or management of EA/TEF:  - Boston Children's Hospital: Esophageal Atresia  - Children's Hospital of Wisconsin  - Gene Review: Gene Review: Esophageal Atresia/Tracheoesophageal Fistula Overview  - Genetic Testing Registry: Tracheoesophageal fistula  - MedlinePlus Encyclopedia: Tracheoesophageal Fistula and Esophageal Atresia Repair  - University of California, San Francisco (UCSF) Medical Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",esophageal atresia/tracheoesophageal fistula,0000327,GHR,https://ghr.nlm.nih.gov/condition/esophageal-atresia-tracheoesophageal-fistula,C0341154,T019,Disorders
What is (are) essential pentosuria ?,0000328-1,information,"Essential pentosuria is a condition characterized by high levels of a sugar called L-xylulose in urine. The condition is so named because L-xylulose is a type of sugar called a pentose. Despite the excess sugar, affected individuals have no associated health problems.",essential pentosuria,0000328,GHR,https://ghr.nlm.nih.gov/condition/essential-pentosuria,C0268162,T047,Disorders
How many people are affected by essential pentosuria ?,0000328-2,frequency,"Essential pentosuria occurs almost exclusively in individuals with Ashkenazi Jewish ancestry. Approximately 1 in 3,300 people in this population are affected.",essential pentosuria,0000328,GHR,https://ghr.nlm.nih.gov/condition/essential-pentosuria,C0268162,T047,Disorders
What are the genetic changes related to essential pentosuria ?,0000328-3,genetic changes,"Essential pentosuria is caused by mutations in the DCXR gene. This gene provides instructions for making a protein called dicarbonyl/L-xylulose reductase (DCXR), which plays multiple roles in the body. One of its functions is to perform a chemical reaction that converts a sugar called L-xylulose to a molecule called xylitol. This reaction is one step in a process by which the body can use sugars for energy.  DCXR gene mutations lead to the production of altered DCXR proteins that are quickly broken down. Without this protein, L-xylulose is not converted to xylitol, and the excess sugar is released in the urine.  While essential pentosuria is caused by genetic mutations, some people develop a non-inherited form of pentosuria if they eat excessive amounts of fruits high in L-xylulose or another pentose called L-arabinose. This form of the condition, which disappears if the diet is changed, is referred to as alimentary pentosuria. Studies show that some drugs can also cause a form of temporary pentosuria called drug-induced pentosuria. These non-inherited forms of the condition also do not cause any health problems.",essential pentosuria,0000328,GHR,https://ghr.nlm.nih.gov/condition/essential-pentosuria,C0268162,T047,Disorders
Is essential pentosuria inherited ?,0000328-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",essential pentosuria,0000328,GHR,https://ghr.nlm.nih.gov/condition/essential-pentosuria,C0268162,T047,Disorders
What are the treatments for essential pentosuria ?,0000328-5,treatment,These resources address the diagnosis or management of essential pentosuria:  - Genetic Testing Registry: Essential pentosuria   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,essential pentosuria,0000328,GHR,https://ghr.nlm.nih.gov/condition/essential-pentosuria,C0268162,T047,Disorders
What is (are) essential thrombocythemia ?,0000329-1,information,"Essential thrombocythemia is a condition characterized by an increased number of platelets (thrombocythemia). Platelets (thrombocytes) are blood cell fragments involved in blood clotting. While some people with this condition have no symptoms, others develop problems associated with the excess platelets.  Abnormal blood clotting (thrombosis) is common in people with essential thrombocythemia and causes many signs and symptoms of this condition. Clots that block blood flow to the brain can cause strokes or temporary stroke-like episodes known as transient ischemic attacks. Thrombosis in the legs can cause leg pain, swelling, or both. In addition, clots can travel to the lungs (pulmonary embolism), blocking blood flow in the lungs and causing chest pain and difficulty breathing (dyspnea).  Another problem in essential thrombocythemia is abnormal bleeding, which occurs more often in people with a very high number of platelets. Affected people may have nosebleeds, bleeding gums, or bleeding in the gastrointestinal tract. It is thought that bleeding occurs because a specific protein in the blood that helps with clotting is reduced, although why the protein is reduced is unclear.  Other signs and symptoms of essential thrombocythemia include an enlarged spleen (splenomegaly); weakness; headaches; or a sensation in the skin of burning, tingling, or prickling. Some people with essential thrombocythemia have episodes of severe pain, redness, and swelling (erythromelalgia), which commonly occur in the hands and feet.",essential thrombocythemia,0000329,GHR,https://ghr.nlm.nih.gov/condition/essential-thrombocythemia,C0040028,T047,Disorders
How many people are affected by essential thrombocythemia ?,0000329-2,frequency,Essential thrombocythemia affects an estimated 1 to 24 per 1 million people worldwide.,essential thrombocythemia,0000329,GHR,https://ghr.nlm.nih.gov/condition/essential-thrombocythemia,C0040028,T047,Disorders
What are the genetic changes related to essential thrombocythemia ?,0000329-3,genetic changes,"The JAK2 and CALR genes are the most commonly mutated genes in essential thrombocythemia. The MPL, THPO, and TET2 genes can also be altered in this condition. The JAK2, MPL, and THPO genes provide instructions for making proteins that promote the growth and division (proliferation) of blood cells. The CALR gene provides instructions for making a protein with multiple functions, including ensuring the proper folding of newly formed proteins and maintaining the correct levels of stored calcium in cells. The TET2 gene provides instructions for making a protein whose function is unknown.  The proteins produced from the JAK2, MPL, and THPO genes are part of a signaling pathway called the JAK/STAT pathway, which transmits chemical signals from outside the cell to the cell's nucleus. These proteins work together to turn on (activate) the JAK/STAT pathway, which promotes the proliferation of blood cells, particularly platelets and their precursor cells, megakaryocytes.  Mutations in the JAK2, MPL, and THPO genes that are associated with essential thrombocythemia lead to overactivation of the JAK/STAT pathway. The abnormal activation of JAK/STAT signaling leads to overproduction of megakaryocytes, which results in an increased number of platelets. Excess platelets can cause thrombosis, which leads to many signs and symptoms of essential thrombocythemia.  Although mutations in the CALR and TET2 genes have been found in people with essential thrombocythemia, it is unclear how these gene mutations are involved in development of the condition.  Some people with essential thrombocythemia do not have a mutation in any of the known genes associated with this condition. Researchers are working to identify other genes that may be involved in the condition.",essential thrombocythemia,0000329,GHR,https://ghr.nlm.nih.gov/condition/essential-thrombocythemia,C0040028,T047,Disorders
Is essential thrombocythemia inherited ?,0000329-4,inheritance,"Most cases of essential thrombocythemia are not inherited. Instead, the condition arises from gene mutations that occur in early blood-forming cells after conception. These alterations are called somatic mutations.  Less commonly, essential thrombocythemia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. When it is inherited, the condition is called familial essential thrombocythemia.",essential thrombocythemia,0000329,GHR,https://ghr.nlm.nih.gov/condition/essential-thrombocythemia,C0040028,T047,Disorders
What are the treatments for essential thrombocythemia ?,0000329-5,treatment,These resources address the diagnosis or management of essential thrombocythemia:  - Cleveland Clinic: Thrombocytosis  - Genetic Testing Registry: Essential thrombocythemia  - Merck Manual for Health Care Professionals: Essential Thrombocythemia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,essential thrombocythemia,0000329,GHR,https://ghr.nlm.nih.gov/condition/essential-thrombocythemia,C0040028,T047,Disorders
What is (are) essential tremor ?,0000330-1,information,"Essential tremor is a movement disorder that causes involuntary, rhythmic shaking (tremor), especially in the hands. It is distinguished from tremor that results from other disorders or known causes, such as Parkinson disease or head trauma. Essential tremor usually occurs alone, without other neurological signs or symptoms. However, some experts think that essential tremor can include additional features, such as mild balance problems.  Essential tremor usually occurs with movements and can occur during many different types of activities, such as eating, drinking, or writing. Essential tremor can also occur when the muscles are opposing gravity, such as when the hands are extended. It is usually not evident at rest.  In addition to the hands and arms, muscles of the trunk, face, head, and neck may also exhibit tremor in this disorder; the legs and feet are less often involved. Head tremor may appear as a ""yes-yes"" or ""no-no"" movement while the affected individual is seated or standing. In some people with essential tremor, the tremor may affect the voice (vocal tremor).  Essential tremor does not shorten the lifespan. However, it may interfere with fine motor skills such as using eating utensils, writing, shaving, or applying makeup, and in some cases these and other activities of daily living can be greatly impaired. Symptoms of essential tremor may be aggravated by emotional stress, anxiety, fatigue, hunger, caffeine, cigarette smoking, or temperature extremes.  Essential tremor may appear at any age but is most common in the elderly. Some studies have suggested that people with essential tremor have a higher than average risk of developing neurological conditions including Parkinson disease or sensory problems such as hearing loss, especially in individuals whose tremor appears after age 65.",essential tremor,0000330,GHR,https://ghr.nlm.nih.gov/condition/essential-tremor,C3543433,T047,Disorders
How many people are affected by essential tremor ?,0000330-2,frequency,"Essential tremor is a common disorder, affecting up to 10 million people in the United States. Estimates of its prevalence vary widely because several other disorders, as well as other factors such as certain medications, can result in similar tremors. In addition, mild cases are often not brought to medical attention, or may not be detected in clinical exams that do not include the particular circumstances in which an individual's tremor occurs. Severe cases are often misdiagnosed as Parkinson disease.",essential tremor,0000330,GHR,https://ghr.nlm.nih.gov/condition/essential-tremor,C3543433,T047,Disorders
What are the genetic changes related to essential tremor ?,0000330-3,genetic changes,"The causes of essential tremor are unknown. Researchers are studying several areas (loci) on particular chromosomes that may be linked to essential tremor, but no specific genetic associations have been confirmed. Several genes as well as environmental factors likely help determine an individual's risk of developing this complex condition. The specific changes in the nervous system that account for the signs and symptoms of essential tremor are unknown.",essential tremor,0000330,GHR,https://ghr.nlm.nih.gov/condition/essential-tremor,C3543433,T047,Disorders
Is essential tremor inherited ?,0000330-4,inheritance,"Essential tremor can be passed through generations in families, but the inheritance pattern varies. In most affected families, essential tremor appears to be inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder, although no genes that cause essential tremor have been identified. In other families, the inheritance pattern is unclear. Essential tremor may also appear in people with no history of the disorder in their family.  In some families, some individuals have essential tremor while others have other movement disorders, such as involuntary muscle tensing (dystonia). The potential genetic connection between essential tremor and other movement disorders is an active area of research.",essential tremor,0000330,GHR,https://ghr.nlm.nih.gov/condition/essential-tremor,C3543433,T047,Disorders
What are the treatments for essential tremor ?,0000330-5,treatment,These resources address the diagnosis or management of essential tremor:  - Genetic Testing Registry: Hereditary essential tremor 1  - Johns Hopkins Movement Disorders Center  - MedlinePlus Encyclopedia: Essential Tremor   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,essential tremor,0000330,GHR,https://ghr.nlm.nih.gov/condition/essential-tremor,C3543433,T047,Disorders
What is (are) ethylmalonic encephalopathy ?,0000331-1,information,"Ethylmalonic encephalopathy is an inherited disorder that affects several body systems, particularly the nervous system. Neurologic signs and symptoms include progressively delayed development, weak muscle tone (hypotonia), seizures, and abnormal movements. The body's network of blood vessels (the vascular system) is also affected. Children with this disorder may experience rashes of tiny red spots (petechiae) caused by bleeding under the skin and blue discoloration in the hands and feet due to reduced oxygen in the blood (acrocyanosis). Chronic diarrhea is another common feature of ethylmalonic encephalopathy.  The signs and symptoms of ethylmalonic encephalopathy are apparent at birth or begin in the first few months of life. Problems with the nervous system typically worsen over time, and most affected individuals survive only into early childhood. A few children with a milder, chronic form of this disorder have been reported.",ethylmalonic encephalopathy,0000331,GHR,https://ghr.nlm.nih.gov/condition/ethylmalonic-encephalopathy,C1865349,T047,Disorders
How many people are affected by ethylmalonic encephalopathy ?,0000331-2,frequency,"About 30 individuals with this condition have been identified worldwide, mostly in Mediterranean and Arab populations. Although ethylmalonic encephalopathy appears to be very rare, researchers suggest that some cases have been misdiagnosed as other neurologic disorders.",ethylmalonic encephalopathy,0000331,GHR,https://ghr.nlm.nih.gov/condition/ethylmalonic-encephalopathy,C1865349,T047,Disorders
What are the genetic changes related to ethylmalonic encephalopathy ?,0000331-3,genetic changes,"Mutations in the ETHE1 gene cause ethylmalonic encephalopathy.  The ETHE1 gene provides instructions for making an enzyme that plays an important role in energy production. It is active in mitochondria, which are the energy-producing centers within cells. Little is known about the enzyme's exact function, however.  Mutations in the ETHE1 gene lead to the production of a nonfunctional version of the enzyme or prevent any enzyme from being made. A lack of the ETHE1 enzyme impairs the body's ability to make energy in mitochondria. Additionally, a loss of this enzyme allows potentially toxic compounds, including ethylmalonic acid and lactic acid, to build up in the body. Excess amounts of these compounds can be detected in urine. It remains unclear how a loss of the ETHE1 enzyme leads to progressive brain dysfunction and the other features of ethylmalonic encephalopathy.",ethylmalonic encephalopathy,0000331,GHR,https://ghr.nlm.nih.gov/condition/ethylmalonic-encephalopathy,C1865349,T047,Disorders
Is ethylmalonic encephalopathy inherited ?,0000331-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",ethylmalonic encephalopathy,0000331,GHR,https://ghr.nlm.nih.gov/condition/ethylmalonic-encephalopathy,C1865349,T047,Disorders
What are the treatments for ethylmalonic encephalopathy ?,0000331-5,treatment,These resources address the diagnosis or management of ethylmalonic encephalopathy:  - Baby's First Test  - Genetic Testing Registry: Ethylmalonic encephalopathy  - MedlinePlus Encyclopedia: Skin discoloration - bluish   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,ethylmalonic encephalopathy,0000331,GHR,https://ghr.nlm.nih.gov/condition/ethylmalonic-encephalopathy,C1865349,T047,Disorders
What is (are) Ewing sarcoma ?,0000332-1,information,"Ewing sarcoma is a cancerous tumor that occurs in bones or soft tissues, such as cartilage or nerves. There are several types of Ewing sarcoma, including Ewing sarcoma of bone, extraosseous Ewing sarcoma, peripheral primitive neuroectodermal tumor (pPNET), and Askin tumor. These tumors are considered to be related because they have similar genetic causes. These types of Ewing sarcoma can be distinguished from one another by the tissue in which the tumor develops. Approximately 87 percent of Ewing sarcomas are Ewing sarcoma of bone, which is a bone tumor that usually occurs in the thigh bones (femurs), pelvis, ribs, or shoulder blades. Extraosseous (or extraskeletal) Ewing sarcoma describes tumors in the soft tissues around bones, such as cartilage. pPNETs occur in nerve tissue and can be found in many parts of the body. A type of pPNET found in the chest is called Askin tumor.  Ewing sarcomas most often occur in children and young adults. Affected individuals usually feel stiffness, pain, swelling, or tenderness of the bone or surrounding tissue. Sometimes, there is a lump near the surface of the skin that feels warm and soft to the touch. Often, children have a fever that does not go away. Ewing sarcoma of bone can cause weakening of the involved bone, and affected individuals may have a broken bone with no obvious cause.  It is common for Ewing sarcoma to spread to other parts of the body (metastasize), usually to the lungs, to other bones, or to the bone marrow.",Ewing sarcoma,0000332,GHR,https://ghr.nlm.nih.gov/condition/ewing-sarcoma,C1261473,T191,Disorders
How many people are affected by Ewing sarcoma ?,0000332-2,frequency,"Approximately 3 per 1 million children each year are diagnosed with a Ewing sarcoma. It is estimated that, in the United States, 250 children are diagnosed with one of these types of tumor each year. Ewing sarcoma accounts for about 1.5 percent of all childhood cancers, and it is the second most common type of bone tumor in children (the most common type of bone cancer is called osteosarcoma).",Ewing sarcoma,0000332,GHR,https://ghr.nlm.nih.gov/condition/ewing-sarcoma,C1261473,T191,Disorders
What are the genetic changes related to Ewing sarcoma ?,0000332-3,genetic changes,"The most common mutation that causes Ewing sarcoma involves two genes, the EWSR1 gene on chromosome 22 and the FLI1 gene on chromosome 11. A rearrangement (translocation) of genetic material between chromosomes 22 and 11, written as t(11;22), fuses part of the EWSR1 gene with part of the FLI1 gene, creating the EWSR1/FLI1 fusion gene. This mutation is acquired during a person's lifetime and is present only in tumor cells. This type of genetic change, called a somatic mutation, is not inherited.  The protein produced from the EWSR1/FLI1 fusion gene, called EWS/FLI, has functions of the protein products of both genes. The FLI protein, produced from the FLI1 gene, attaches (binds) to DNA and regulates an activity called transcription, which is the first step in the production of proteins from genes. The FLI protein controls the growth and development of some cell types by regulating the transcription of certain genes. The EWS protein, produced from the EWSR1 gene, also regulates transcription. The EWS/FLI protein has the DNA-binding function of the FLI protein as well as the transcription regulation function of the EWS protein. It is thought that the EWS/FLI protein turns the transcription of a variety of genes on and off abnormally. This dysregulation of transcription leads to uncontrolled growth and division (proliferation) and abnormal maturation and survival of cells, causing tumor development.  The EWSR1/FLI1 fusion gene occurs in approximately 85 percent of Ewing sarcomas. Translocations that fuse the EWSR1 gene with other genes that are related to the FLI1 gene can also cause these types of tumors, although these alternative translocations are relatively uncommon. The fusion proteins produced from the less common gene translocations have the same function as the EWS/FLI protein.",Ewing sarcoma,0000332,GHR,https://ghr.nlm.nih.gov/condition/ewing-sarcoma,C1261473,T191,Disorders
Is Ewing sarcoma inherited ?,0000332-4,inheritance,This condition is generally not inherited but arises from a mutation in the body's cells that occurs after conception. This alteration is called a somatic mutation.,Ewing sarcoma,0000332,GHR,https://ghr.nlm.nih.gov/condition/ewing-sarcoma,C1261473,T191,Disorders
What are the treatments for Ewing sarcoma ?,0000332-5,treatment,These resources address the diagnosis or management of Ewing sarcoma:  - Cancer.Net: Ewing Family of Tumors - Childhood: Diagnosis  - Cancer.Net: Ewing Family of Tumors - Childhood: Treatment  - Genetic Testing Registry: Ewing's sarcoma  - MedlinePlus Encyclopedia: Ewing Sarcoma   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Ewing sarcoma,0000332,GHR,https://ghr.nlm.nih.gov/condition/ewing-sarcoma,C1261473,T191,Disorders
What is (are) Fabry disease ?,0000333-1,information,"Fabry disease is an inherited disorder that results from the buildup of a particular type of fat, called globotriaosylceramide, in the body's cells. Beginning in childhood, this buildup causes signs and symptoms that affect many parts of the body. Characteristic features of Fabry disease include episodes of pain, particularly in the hands and feet (acroparesthesias); clusters of small, dark red spots on the skin called angiokeratomas; a decreased ability to sweat (hypohidrosis); cloudiness of the front part of the eye (corneal opacity); problems with the gastrointestinal system; ringing in the ears (tinnitus); and hearing loss. Fabry disease also involves potentially life-threatening complications such as progressive kidney damage, heart attack, and stroke. Some affected individuals have milder forms of the disorder that appear later in life and affect only the heart or kidneys.",Fabry disease,0000333,GHR,https://ghr.nlm.nih.gov/condition/fabry-disease,C0002986,T047,Disorders
How many people are affected by Fabry disease ?,0000333-2,frequency,"Fabry disease affects an estimated 1 in 40,000 to 60,000 males. This disorder also occurs in females, although the prevalence is unknown. Milder, late-onset forms of the disorder are probably more common than the classic, severe form.",Fabry disease,0000333,GHR,https://ghr.nlm.nih.gov/condition/fabry-disease,C0002986,T047,Disorders
What are the genetic changes related to Fabry disease ?,0000333-3,genetic changes,"Fabry disease is caused by mutations in the GLA gene. This gene provides instructions for making an enzyme called alpha-galactosidase A. This enzyme is active in lysosomes, which are structures that serve as recycling centers within cells. Alpha-galactosidase A normally breaks down a fatty substance called globotriaosylceramide. Mutations in the GLA gene alter the structure and function of the enzyme, preventing it from breaking down this substance effectively. As a result, globotriaosylceramide builds up in cells throughout the body, particularly cells lining blood vessels in the skin and cells in the kidneys, heart, and nervous system. The progressive accumulation of this substance damages cells, leading to the varied signs and symptoms of Fabry disease.  GLA gene mutations that result in an absence of alpha-galactosidase A activity lead to the classic, severe form of Fabry disease. Mutations that decrease but do not eliminate the enzyme's activity usually cause the milder, late-onset forms of Fabry disease that affect only the heart or kidneys.",Fabry disease,0000333,GHR,https://ghr.nlm.nih.gov/condition/fabry-disease,C0002986,T047,Disorders
Is Fabry disease inherited ?,0000333-4,inheritance,"This condition is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), one altered copy of the GLA gene in each cell is sufficient to cause the condition. Because females have two copies of the X chromosome, one altered copy of the gene in each cell usually leads to less severe symptoms in females than in males, or rarely may cause no symptoms at all.  Unlike other X-linked disorders, Fabry disease causes significant medical problems in many females who have one altered copy of the GLA gene. These women may experience many of the classic features of the disorder, including nervous system abnormalities, kidney problems, chronic pain, and fatigue. They also have an increased risk of developing high blood pressure, heart disease, stroke, and kidney failure. The signs and symptoms of Fabry disease usually begin later in life and are milder in females than in their affected male relatives.  A small percentage of females who carry a mutation in one copy of the GLA gene never develop signs and symptoms of Fabry disease.",Fabry disease,0000333,GHR,https://ghr.nlm.nih.gov/condition/fabry-disease,C0002986,T047,Disorders
What are the treatments for Fabry disease ?,0000333-5,treatment,These resources address the diagnosis or management of Fabry disease:  - Baby's First Test  - Gene Review: Gene Review: Fabry Disease  - Genetic Testing Registry: Fabry disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Fabry disease,0000333,GHR,https://ghr.nlm.nih.gov/condition/fabry-disease,C0002986,T047,Disorders
What is (are) facioscapulohumeral muscular dystrophy ?,0000334-1,information,"Facioscapulohumeral muscular dystrophy is a disorder characterized by muscle weakness and wasting (atrophy). This condition gets its name from the muscles that are affected most often: those of the face (facio-), around the shoulder blades (scapulo-), and in the upper arms (humeral). The signs and symptoms of facioscapulohumeral muscular dystrophy usually appear in adolescence. However, the onset and severity of the condition varies widely. Milder cases may not become noticeable until later in life, whereas rare severe cases become apparent in infancy or early childhood.  Weakness involving the facial muscles or shoulders is usually the first symptom of this condition. Facial muscle weakness often makes it difficult to drink from a straw, whistle, or turn up the corners of the mouth when smiling. Weakness in muscles around the eyes can prevent the eyes from closing fully while a person is asleep, which can lead to dry eyes and other eye problems. For reasons that are unclear, weakness may be more severe in one side of the face than the other. Weak shoulder muscles tend to make the shoulder blades (scapulae) protrude from the back, a common sign known as scapular winging. Weakness in muscles of the shoulders and upper arms can make it difficult to raise the arms over the head or throw a ball.  The muscle weakness associated with facioscapulohumeral muscular dystrophy worsens slowly over decades and may spread to other parts of the body. Weakness in muscles of the lower legs can lead to a condition called foot drop, which affects walking and increases the risk of falls. Muscular weakness in the hips and pelvis can make it difficult to climb stairs or walk long distances. Additionally, affected individuals may have an exaggerated curvature of the lower back (lordosis) due to weak abdominal muscles. About 20 percent of affected individuals eventually require the use of a wheelchair.  Additional signs and symptoms of facioscapulohumeral muscular dystrophy can include mild high-tone hearing loss and abnormalities involving the light-sensitive tissue at the back of the eye (the retina). These signs are often not noticeable and may be discovered only during medical testing. Rarely, facioscapulohumeral muscular dystrophy affects the heart (cardiac) muscle or muscles needed for breathing.  Researchers have described two types of facioscapulohumeral muscular dystrophy: type 1 (FSHD1) and type 2 (FSHD2). The two types have the same signs and symptoms and are distinguished by their genetic cause.",facioscapulohumeral muscular dystrophy,0000334,GHR,https://ghr.nlm.nih.gov/condition/facioscapulohumeral-muscular-dystrophy,C0238288,T019,Disorders
How many people are affected by facioscapulohumeral muscular dystrophy ?,0000334-2,frequency,"Facioscapulohumeral muscular dystrophy has an estimated prevalence of 1 in 20,000 people. About 95 percent of all cases are FSHD1; the remaining 5 percent are FSHD2.",facioscapulohumeral muscular dystrophy,0000334,GHR,https://ghr.nlm.nih.gov/condition/facioscapulohumeral-muscular-dystrophy,C0238288,T019,Disorders
What are the genetic changes related to facioscapulohumeral muscular dystrophy ?,0000334-3,genetic changes,"Facioscapulohumeral muscular dystrophy is caused by genetic changes involving the long (q) arm of chromosome 4. Both types of the disease result from changes in a region of DNA near the end of the chromosome known as D4Z4. This region consists of 11 to more than 100 repeated segments, each of which is about 3,300 DNA base pairs (3.3 kb) long. The entire D4Z4 region is normally hypermethylated, which means that it has a large number of methyl groups (consisting of one carbon atom and three hydrogen atoms) attached to the DNA. The addition of methyl groups turns off (silences) genes, so hypermethylated regions of DNA tend to have fewer genes that are turned on (active). Facioscapulohumeral muscular dystrophy results when the D4Z4 region is hypomethylated, with a shortage of attached methyl groups. In FSHD1, hypomethylation occurs because the D4Z4 region is abnormally shortened (contracted), containing between 1 and 10 repeats instead of the usual 11 to 100 repeats. In FSHD2, hypomethylation most often results from mutations in a gene called SMCHD1, which provides instructions for making a protein that normally hypermethylates the D4Z4 region. However, about 20 percent of people with FSHD2 do not have an identified mutation in the SMCHD1 gene, and the cause of the hypomethylation is unknown.  Hypermethylation of the D4Z4 region normally keeps a gene called DUX4 silenced in most adult cells and tissues. The DUX4 gene is located in the segment of the D4Z4 region closest to the end of chromosome 4. In people with facioscapulohumeral muscular dystrophy, hypomethylation of the D4Z4 region prevents the DUX4 gene from being silenced in cells and tissues where it is usually turned off. Although little is known about the function of the DUX4 gene when it is active, researchers believe that it influences the activity of other genes, particularly in muscle cells. It is unknown how abnormal activity of the DUX4 gene damages or destroys these cells, leading to progressive muscle weakness and atrophy.  The DUX4 gene is located next to a regulatory region of DNA on chromosome 4 known as a pLAM sequence, which is necessary for the production of the DUX4 protein. Some copies of chromosome 4 have a functional pLAM sequence, while others do not. Copies of chromosome 4 with a functional pLAM sequence are described as 4qA or ""permissive."" Those without a functional pLAM sequence are described as 4qB or ""non-permissive."" Without a functional pLAM sequence, no DUX4 protein is made. Because there are two copies of chromosome 4 in each cell, individuals may have two ""permissive"" copies of chromosome 4, two ""non-permissive"" copies, or one of each. Facioscapulohumeral muscular dystrophy can only occur in people who have at least one ""permissive"" copy of chromosome 4. Whether an affected individual has a contracted D4Z4 region or a SMCHD1 gene mutation, the disease results only if a functional pLAM sequence is also present to allow DUX4 protein to be produced.  Studies suggest that mutations in the SMCHD1 gene, which cause FSHD2, can also increase the severity of the disease in people with FSHD1. Researchers suspect that the combination of a contracted D4Z4 region and a SMCHD1 gene mutation causes the D4Z4 region to have even fewer methyl groups attached, which allows the DUX4 gene to be highly active. In people with both genetic changes, the overactive gene leads to severe muscle weakness and atrophy.",facioscapulohumeral muscular dystrophy,0000334,GHR,https://ghr.nlm.nih.gov/condition/facioscapulohumeral-muscular-dystrophy,C0238288,T019,Disorders
Is facioscapulohumeral muscular dystrophy inherited ?,0000334-4,inheritance,"FSHD1 is inherited in an autosomal dominant pattern, which means one copy of the shortened D4Z4 region on a ""permissive"" chromosome 4 is sufficient to cause the disorder. In most cases, an affected person inherits the altered chromosome from one affected parent. Other people with FSHD1 have no history of the disorder in their family. These cases are described as sporadic and are caused by a new (de novo) D4Z4 contraction on one copy of a ""permissive"" chromosome 4.  FSHD2 is inherited in a digenic pattern, which means that two independent genetic changes are necessary to cause the disorder. To have FSHD2, an individual must inherit a mutation in the SMCHD1 gene (which is located on chromosome 18) and, separately, they must inherit one copy of a ""permissive"" chromosome 4. Affected individuals typically inherit the SMCHD1 gene mutation from one parent and the ""permissive"" chromosome 4 from the other parent. (Because neither parent has both genetic changes in most cases, they are typically unaffected.)",facioscapulohumeral muscular dystrophy,0000334,GHR,https://ghr.nlm.nih.gov/condition/facioscapulohumeral-muscular-dystrophy,C0238288,T019,Disorders
What are the treatments for facioscapulohumeral muscular dystrophy ?,0000334-5,treatment,These resources address the diagnosis or management of facioscapulohumeral muscular dystrophy:  - Gene Review: Gene Review: Facioscapulohumeral Muscular Dystrophy  - Genetic Testing Registry: Facioscapulohumeral muscular dystrophy  - Genetic Testing Registry: Facioscapulohumeral muscular dystrophy 2  - MedlinePlus Encyclopedia: Facioscapulohumeral Muscular Dystrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,facioscapulohumeral muscular dystrophy,0000334,GHR,https://ghr.nlm.nih.gov/condition/facioscapulohumeral-muscular-dystrophy,C0238288,T019,Disorders
What is (are) factor V deficiency ?,0000335-1,information,"Factor V deficiency is a rare bleeding disorder. The signs and symptoms of this condition can begin at any age, although the most severe cases are apparent in childhood. Factor V deficiency commonly causes nosebleeds; easy bruising; bleeding under the skin; bleeding of the gums; and prolonged or excessive bleeding following surgery, trauma, or childbirth. Women with factor V deficiency can have heavy or prolonged menstrual bleeding (menorrhagia). Bleeding into joint spaces (hemarthrosis) can also occur, although it is rare. Severely affected individuals have an increased risk of bleeding inside the skull (intracranial hemorrhage), in the lungs (pulmonary hemorrhage), or in the gastrointestinal tract, which can be life-threatening.",factor V deficiency,0000335,GHR,https://ghr.nlm.nih.gov/condition/factor-v-deficiency,C0015499,T047,Disorders
How many people are affected by factor V deficiency ?,0000335-2,frequency,"Factor V deficiency affects an estimated 1 in 1 million people. This condition is more common in countries such as Iran and southern India, where it occurs up to ten times more frequently than in western countries.",factor V deficiency,0000335,GHR,https://ghr.nlm.nih.gov/condition/factor-v-deficiency,C0015499,T047,Disorders
What are the genetic changes related to factor V deficiency ?,0000335-3,genetic changes,"Factor V deficiency is usually caused by mutations in the F5 gene, which provides instructions for making a protein called coagulation factor V. This protein plays a critical role in the coagulation system, which is a series of chemical reactions that forms blood clots in response to injury. F5 gene mutations that cause factor V deficiency prevent the production of functional coagulation factor V or severely reduce the amount of the protein in the bloodstream. People with this condition typically have less than 10 percent of normal levels of coagulation factor V in their blood; the most severely affected individuals have less than 1 percent. A reduced amount of functional coagulation factor V prevents blood from clotting normally, causing episodes of abnormal bleeding that can be severe.  Very rarely, a form of factor V deficiency is caused by abnormal antibodies that recognize coagulation factor V. Antibodies normally attach (bind) to specific foreign particles and germs, marking them for destruction, but the antibodies in this form of factor V deficiency attack a normal human protein, leading to its inactivation. These cases are called acquired factor V deficiency and usually occur in individuals who have been treated with substances that stimulate the production of anti-factor V antibodies, such as bovine thrombin used during surgical procedures. There is no known genetic cause for this form of the condition.",factor V deficiency,0000335,GHR,https://ghr.nlm.nih.gov/condition/factor-v-deficiency,C0015499,T047,Disorders
Is factor V deficiency inherited ?,0000335-4,inheritance,"Factor V deficiency is inherited in an autosomal recessive pattern, which means both copies of the F5 gene in each cell have mutations. Individuals with a mutation in a single copy of the F5 gene have a reduced amount of coagulation factor V in their blood and can have mild bleeding problems, although most have no related health effects.",factor V deficiency,0000335,GHR,https://ghr.nlm.nih.gov/condition/factor-v-deficiency,C0015499,T047,Disorders
What are the treatments for factor V deficiency ?,0000335-5,treatment,These resources address the diagnosis or management of factor V deficiency:  - Genetic Testing Registry: Factor V deficiency  - MedlinePlus Encyclopedia: Factor V Deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,factor V deficiency,0000335,GHR,https://ghr.nlm.nih.gov/condition/factor-v-deficiency,C0015499,T047,Disorders
What is (are) factor V Leiden thrombophilia ?,0000336-1,information,"Factor V Leiden thrombophilia is an inherited disorder of blood clotting. Factor V Leiden is the name of a specific gene mutation that results in thrombophilia, which is an increased tendency to form abnormal blood clots that can block blood vessels.  People with factor V Leiden thrombophilia have a higher than average risk of developing a type of blood clot called a deep venous thrombosis (DVT). DVTs occur most often in the legs, although they can also occur in other parts of the body, including the brain, eyes, liver, and kidneys. Factor V Leiden thrombophilia also increases the risk that clots will break away from their original site and travel through the bloodstream. These clots can lodge in the lungs, where they are known as pulmonary emboli. Although factor V Leiden thrombophilia increases the risk of blood clots, only about 10 percent of individuals with the factor V Leiden mutation ever develop abnormal clots.  The factor V Leiden mutation is associated with a slightly increased risk of pregnancy loss (miscarriage). Women with this mutation are two to three times more likely to have multiple (recurrent) miscarriages or a pregnancy loss during the second or third trimester. Some research suggests that the factor V Leiden mutation may also increase the risk of other complications during pregnancy, including pregnancy-induced high blood pressure (preeclampsia), slow fetal growth, and early separation of the placenta from the uterine wall (placental abruption). However, the association between the factor V Leiden mutation and these complications has not been confirmed. Most women with factor V Leiden thrombophilia have normal pregnancies.",factor V Leiden thrombophilia,0000336,GHR,https://ghr.nlm.nih.gov/condition/factor-v-leiden-thrombophilia,C1861171,T047,Disorders
How many people are affected by factor V Leiden thrombophilia ?,0000336-2,frequency,"Factor V Leiden is the most common inherited form of thrombophilia. Between 3 and 8 percent of people with European ancestry carry one copy of the factor V Leiden mutation in each cell, and about 1 in 5,000 people have two copies of the mutation. The mutation is less common in other populations.",factor V Leiden thrombophilia,0000336,GHR,https://ghr.nlm.nih.gov/condition/factor-v-leiden-thrombophilia,C1861171,T047,Disorders
What are the genetic changes related to factor V Leiden thrombophilia ?,0000336-3,genetic changes,"A particular mutation in the F5 gene causes factor V Leiden thrombophilia. The F5 gene provides instructions for making a protein called coagulation factor V. This protein plays a critical role in the coagulation system, which is a series of chemical reactions that forms blood clots in response to injury.  The coagulation system is controlled by several proteins, including a protein called activated protein C (APC). APC normally inactivates coagulation factor V, which slows down the clotting process and prevents clots from growing too large. However, in people with factor V Leiden thrombophilia, coagulation factor V cannot be inactivated normally by APC. As a result, the clotting process remains active longer than usual, increasing the chance of developing abnormal blood clots.  Other factors also increase the risk of developing blood clots in people with factor V Leiden thrombophilia. These factors include increasing age, obesity, injury, surgery, smoking, pregnancy, and the use of oral contraceptives (birth control pills) or hormone replacement therapy. The risk of abnormal clots is also much higher in people who have a combination of the factor V Leiden mutation and another mutation in the F5 gene. Additionally, the risk is increased in people who have the factor V Leiden mutation together with a mutation in another gene involved in the coagulation system.",factor V Leiden thrombophilia,0000336,GHR,https://ghr.nlm.nih.gov/condition/factor-v-leiden-thrombophilia,C1861171,T047,Disorders
Is factor V Leiden thrombophilia inherited ?,0000336-4,inheritance,"The chance of developing an abnormal blood clot depends on whether a person has one or two copies of the factor V Leiden mutation in each cell. People who inherit two copies of the mutation, one from each parent, have a higher risk of developing a clot than people who inherit one copy of the mutation. Considering that about 1 in 1,000 people per year in the general population will develop an abnormal blood clot, the presence of one copy of the factor V Leiden mutation increases that risk to 3 to 8 in 1,000, and having two copies of the mutation may raise the risk to as high as 80 in 1,000.",factor V Leiden thrombophilia,0000336,GHR,https://ghr.nlm.nih.gov/condition/factor-v-leiden-thrombophilia,C1861171,T047,Disorders
What are the treatments for factor V Leiden thrombophilia ?,0000336-5,treatment,These resources address the diagnosis or management of factor V Leiden thrombophilia:  - American College of Medical Genetics Consensus Statement on Factor V Leiden Mutation Testing  - Gene Review: Gene Review: Factor V Leiden Thrombophilia  - GeneFacts: Factor V Leiden-Associated Thrombosis: Diagnosis  - GeneFacts: Factor V Leiden-Associated Thrombosis: Management  - Genetic Testing Registry: Thrombophilia due to activated protein C resistance  - Genetic Testing Registry: Thrombophilia due to factor V Leiden  - MedlinePlus Encyclopedia: Deep Venous Thrombosis  - MedlinePlus Encyclopedia: Pulmonary Embolus   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,factor V Leiden thrombophilia,0000336,GHR,https://ghr.nlm.nih.gov/condition/factor-v-leiden-thrombophilia,C1861171,T047,Disorders
What is (are) factor X deficiency ?,0000337-1,information,"Factor X deficiency is a rare bleeding disorder that varies in severity among affected individuals. The signs and symptoms of this condition can begin at any age, although the most severe cases are apparent in childhood. Factor X deficiency commonly causes nosebleeds, easy bruising, bleeding under the skin, bleeding of the gums, blood in the urine (hematuria), and prolonged or excessive bleeding following surgery or trauma. Women with factor X deficiency can have heavy or prolonged menstrual bleeding (menorrhagia) or excessive bleeding in childbirth, and may be at increased risk of pregnancy loss (miscarriage). Bleeding into joint spaces (hemarthrosis) occasionally occurs. Severely affected individuals have an increased risk of bleeding inside the skull (intracranial hemorrhage), in the lungs (pulmonary hemorrhage), or in the gastrointestinal tract, which can be life-threatening.",factor X deficiency,0000337,GHR,https://ghr.nlm.nih.gov/condition/factor-x-deficiency,C0015519,T047,Disorders
How many people are affected by factor X deficiency ?,0000337-2,frequency,Factor X deficiency occurs in approximately 1 per million individuals worldwide.,factor X deficiency,0000337,GHR,https://ghr.nlm.nih.gov/condition/factor-x-deficiency,C0015519,T047,Disorders
What are the genetic changes related to factor X deficiency ?,0000337-3,genetic changes,"The inherited form of factor X deficiency, known as congenital factor X deficiency, is caused by mutations in the F10 gene, which provides instructions for making a protein called coagulation factor X. This protein plays a critical role in the coagulation system, which is a series of chemical reactions that forms blood clots in response to injury. Some F10 gene mutations that cause factor X deficiency reduce the amount of coagulation factor X in the bloodstream, resulting in a form of the disorder called type I. Other F10 gene mutations result in the production of a coagulation factor X protein with impaired function, leading to type II factor X deficiency. Reduced quantity or function of coagulation factor X prevents blood from clotting normally, causing episodes of abnormal bleeding that can be severe.  A non-inherited form of the disorder, called acquired factor X deficiency, is more common than the congenital form. Acquired factor X deficiency can be caused by other disorders such as severe liver disease or systemic amyloidosis, a condition involving the accumulation of abnormal proteins called amyloids. Acquired factor X deficiency can also be caused by certain drugs such as medicines that prevent clotting, or by a deficiency of vitamin K.",factor X deficiency,0000337,GHR,https://ghr.nlm.nih.gov/condition/factor-x-deficiency,C0015519,T047,Disorders
Is factor X deficiency inherited ?,0000337-4,inheritance,"When this condition is caused by mutations in the F10 gene, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Acquired factor X deficiency is not inherited, and generally occurs in individuals with no history of the disorder in their family.",factor X deficiency,0000337,GHR,https://ghr.nlm.nih.gov/condition/factor-x-deficiency,C0015519,T047,Disorders
What are the treatments for factor X deficiency ?,0000337-5,treatment,These resources address the diagnosis or management of factor X deficiency:  - Genetic Testing Registry: Factor X deficiency  - MedlinePlus Encyclopedia: Factor X Assay   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,factor X deficiency,0000337,GHR,https://ghr.nlm.nih.gov/condition/factor-x-deficiency,C0015519,T047,Disorders
What is (are) factor XIII deficiency ?,0000338-1,information,"Factor XIII deficiency is a rare bleeding disorder. Researchers have identified an inherited form and a less severe form that is acquired during a person's lifetime.  Signs and symptoms of inherited factor XIII deficiency begin soon after birth, usually with abnormal bleeding from the umbilical cord stump. If the condition is not treated, affected individuals may have episodes of excessive and prolonged bleeding that can be life-threatening. Abnormal bleeding can occur after surgery or minor trauma. The condition can also cause spontaneous bleeding into the joints or muscles, leading to pain and disability. Women with inherited factor XIII deficiency tend to have heavy or prolonged menstrual bleeding (menorrhagia) and may experience recurrent pregnancy losses (miscarriages). Other signs and symptoms of inherited factor XIII deficiency include nosebleeds, bleeding of the gums, easy bruising, problems with wound healing, and abnormal scar formation. Inherited factor XIII deficiency also increases the risk of spontaneous bleeding inside the skull (intracranial hemorrhage), which is the leading cause of death in people with this condition.  Acquired factor XIII deficiency becomes apparent later in life. People with the acquired form are less likely to have severe or life-threatening episodes of abnormal bleeding than those with the inherited form.",factor XIII deficiency,0000338,GHR,https://ghr.nlm.nih.gov/condition/factor-xiii-deficiency,C0015530,T047,Disorders
How many people are affected by factor XIII deficiency ?,0000338-2,frequency,"Inherited factor XIII deficiency affects 1 to 3 per million people worldwide. Researchers suspect that mild factor XIII deficiency, including the acquired form of the disorder, is underdiagnosed because many affected people never have a major episode of abnormal bleeding that would lead to a diagnosis.",factor XIII deficiency,0000338,GHR,https://ghr.nlm.nih.gov/condition/factor-xiii-deficiency,C0015530,T047,Disorders
What are the genetic changes related to factor XIII deficiency ?,0000338-3,genetic changes,"Inherited factor XIII deficiency results from mutations in the F13A1 gene or, less commonly, the F13B gene. These genes provide instructions for making the two parts (subunits) of a protein called factor XIII. This protein plays a critical role in the coagulation cascade, which is a series of chemical reactions that forms blood clots in response to injury. After an injury, clots seal off blood vessels to stop bleeding and trigger blood vessel repair. Factor XIII acts at the end of the cascade to strengthen and stabilize newly formed clots, preventing further blood loss.  Mutations in the F13A1 or F13B gene significantly reduce the amount of functional factor XIII available to participate in blood clotting. In most people with the inherited form of the condition, factor XIII levels in the bloodstream are less than 5 percent of normal. A loss of this protein's activity weakens blood clots, preventing the clots from stopping blood loss effectively.  The acquired form of factor XIII deficiency results when the production of factor XIII is reduced or when the body uses factor XIII faster than cells can replace it. Acquired factor XIII deficiency is generally mild because levels of factor XIII in the bloodstream are 20 to 70 percent of normal; levels above 10 percent of normal are usually adequate to prevent spontaneous bleeding episodes.  Acquired factor XIII deficiency can be caused by disorders including an inflammatory disease of the liver called hepatitis, scarring of the liver (cirrhosis), inflammatory bowel disease, overwhelming bacterial infections (sepsis), and several types of cancer. Acquired factor XIII deficiency can also be caused by abnormal activation of the immune system, which produces specialized proteins called autoantibodies that attack and disable the factor XIII protein. The production of autoantibodies against factor XIII is sometimes associated with immune system diseases such as systemic lupus erythematosus and rheumatoid arthritis. In other cases, the trigger for autoantibody production is unknown.",factor XIII deficiency,0000338,GHR,https://ghr.nlm.nih.gov/condition/factor-xiii-deficiency,C0015530,T047,Disorders
Is factor XIII deficiency inherited ?,0000338-4,inheritance,"Inherited factor XIII deficiency is considered to have an autosomal recessive pattern of inheritance, which means that it results when both copies of either the F13A1 gene or the F13B gene in each cell have mutations.  Some people, including parents of individuals with factor XIII deficiency, carry a single mutated copy of the F13A1 or F13B gene in each cell. These mutation carriers have a reduced amount of factor XIII in their bloodstream (20 to 60 percent of normal), and they may experience abnormal bleeding after surgery, dental work, or major trauma. However, most people who carry one mutated copy of the F13A1 or F13B gene do not have abnormal bleeding episodes under normal circumstances, and so they never come to medical attention.  The acquired form of factor XIII deficiency is not inherited and does not run in families.",factor XIII deficiency,0000338,GHR,https://ghr.nlm.nih.gov/condition/factor-xiii-deficiency,C0015530,T047,Disorders
What are the treatments for factor XIII deficiency ?,0000338-5,treatment,"These resources address the diagnosis or management of factor XIII deficiency:  - Genetic Testing Registry: Factor xiii, a subunit, deficiency of  - Genetic Testing Registry: Factor xiii, b subunit, deficiency of   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",factor XIII deficiency,0000338,GHR,https://ghr.nlm.nih.gov/condition/factor-xiii-deficiency,C0015530,T047,Disorders
What is (are) familial acute myeloid leukemia with mutated CEBPA ?,0000339-1,information,"Familial acute myeloid leukemia with mutated CEBPA is one form of a cancer of the blood-forming tissue (bone marrow) called acute myeloid leukemia. In normal bone marrow, early blood cells called hematopoietic stem cells develop into several types of blood cells: white blood cells (leukocytes) that protect the body from infection, red blood cells (erythrocytes) that carry oxygen, and platelets (thrombocytes) that are involved in blood clotting. In acute myeloid leukemia, the bone marrow makes large numbers of abnormal, immature white blood cells called myeloid blasts. Instead of developing into normal white blood cells, the myeloid blasts develop into cancerous leukemia cells. The large number of abnormal cells in the bone marrow interferes with the production of functional white blood cells, red blood cells, and platelets.  People with familial acute myeloid leukemia with mutated CEBPA have a shortage of white blood cells (leukopenia), leading to increased susceptibility to infections. A low number of red blood cells (anemia) also occurs in this disorder, resulting in fatigue and weakness. Affected individuals also have a reduction in the amount of platelets (thrombocytopenia), which can result in easy bruising and abnormal bleeding. Other symptoms of familial acute myeloid leukemia with mutated CEBPA may include fever and weight loss.  While acute myeloid leukemia is generally a disease of older adults, familial acute myeloid leukemia with mutated CEBPA often begins earlier in life, and it has been reported to occur as early as age 4. Between 50 and 65 percent of affected individuals survive their disease, compared with 25 to 40 percent of those with other forms of acute myeloid leukemia. However, people with familial acute myeloid leukemia with mutated CEBPA have a higher risk of having a new primary occurrence of this disorder after successful treatment of the initial occurrence.",familial acute myeloid leukemia with mutated CEBPA,0000339,GHR,https://ghr.nlm.nih.gov/condition/familial-acute-myeloid-leukemia-with-mutated-cebpa,C0023470,T191,Disorders
How many people are affected by familial acute myeloid leukemia with mutated CEBPA ?,0000339-2,frequency,"Acute myeloid leukemia occurs in approximately 3.5 in 100,000 individuals per year. Familial acute myeloid leukemia with mutated CEBPA is a very rare form of acute myeloid leukemia; only a few affected families have been identified.",familial acute myeloid leukemia with mutated CEBPA,0000339,GHR,https://ghr.nlm.nih.gov/condition/familial-acute-myeloid-leukemia-with-mutated-cebpa,C0023470,T191,Disorders
What are the genetic changes related to familial acute myeloid leukemia with mutated CEBPA ?,0000339-3,genetic changes,"As its name suggests, familial acute myeloid leukemia with mutated CEBPA is caused by mutations in the CEBPA gene that are passed down within families. These inherited mutations are present throughout a person's life in virtually every cell in the body.  The CEBPA gene provides instructions for making a protein called CCAAT/enhancer-binding protein alpha. This protein is a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of certain genes. It is believed to act as a tumor suppressor, helping to prevent cells from growing and dividing too rapidly or in an uncontrolled way.  CEBPA gene mutations that cause familial acute myeloid leukemia with mutated CEBPA result in a shorter version of CCAAT/enhancer-binding protein alpha. This shorter version is produced from one copy of the CEBPA gene in each cell, and it is believed to interfere with the tumor suppressor function of the normal protein produced from the second copy of the gene. Absence of the tumor suppressor function of CCAAT/enhancer-binding protein alpha is believed to disrupt the regulation of blood cell production in the bone marrow, leading to the uncontrolled production of abnormal cells that occurs in acute myeloid leukemia.  In addition to the inherited mutation in one copy of the CEBPA gene in each cell, most individuals with familial acute myeloid leukemia with mutated CEBPA also acquire a mutation in the second copy of the CEBPA gene. The additional mutation, which is called a somatic mutation, is found only in the leukemia cells and is not inherited. The somatic CEBPA gene mutations identified in leukemia cells generally decrease the DNA-binding ability of CCAAT/enhancer-binding protein alpha. The effect of this second mutation on the development of acute myeloid leukemia is unclear.",familial acute myeloid leukemia with mutated CEBPA,0000339,GHR,https://ghr.nlm.nih.gov/condition/familial-acute-myeloid-leukemia-with-mutated-cebpa,C0023470,T191,Disorders
Is familial acute myeloid leukemia with mutated CEBPA inherited ?,0000339-4,inheritance,"Familial acute myeloid leukemia with mutated CEBPA is inherited in an autosomal dominant pattern. Autosomal dominant inheritance means that one copy of the altered CEBPA gene in each cell is sufficient to cause the disorder. Most affected individuals also acquire a second, somatic CEBPA gene mutation in their leukemia cells.",familial acute myeloid leukemia with mutated CEBPA,0000339,GHR,https://ghr.nlm.nih.gov/condition/familial-acute-myeloid-leukemia-with-mutated-cebpa,C0023470,T191,Disorders
What are the treatments for familial acute myeloid leukemia with mutated CEBPA ?,0000339-5,treatment,These resources address the diagnosis or management of familial acute myeloid leukemia with mutated CEBPA:  - Fred Hutchison Cancer Research Center  - Gene Review: Gene Review: CEBPA-Associated Familial Acute Myeloid Leukemia (AML)  - Genetic Testing Registry: Acute myeloid leukemia  - MedlinePlus Encyclopedia: Bone Marrow Biopsy  - MedlinePlus Encyclopedia: Bone Marrow Transplant  - National Cancer Institute: Acute Myeloid Leukemia Treatment  - St. Jude Children's Research Hospital   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,familial acute myeloid leukemia with mutated CEBPA,0000339,GHR,https://ghr.nlm.nih.gov/condition/familial-acute-myeloid-leukemia-with-mutated-cebpa,C0023470,T191,Disorders
What is (are) familial adenomatous polyposis ?,0000340-1,information,"Familial adenomatous polyposis (FAP) is an inherited disorder characterized by cancer of the large intestine (colon) and rectum. People with the classic type of familial adenomatous polyposis may begin to develop multiple noncancerous (benign) growths (polyps) in the colon as early as their teenage years. Unless the colon is removed, these polyps will become malignant (cancerous). The average age at which an individual develops colon cancer in classic familial adenomatous polyposis is 39 years. Some people have a variant of the disorder, called attenuated familial adenomatous polyposis, in which polyp growth is delayed. The average age of colorectal cancer onset for attenuated familial adenomatous polyposis is 55 years.  In people with classic familial adenomatous polyposis, the number of polyps increases with age, and hundreds to thousands of polyps can develop in the colon. Also of particular significance are noncancerous growths called desmoid tumors. These fibrous tumors usually occur in the tissue covering the intestines and may be provoked by surgery to remove the colon. Desmoid tumors tend to recur after they are surgically removed. In both classic familial adenomatous polyposis and its attenuated variant, benign and malignant tumors are sometimes found in other places in the body, including the duodenum (a section of the small intestine), stomach, bones, skin, and other tissues. People who have colon polyps as well as growths outside the colon are sometimes described as having Gardner syndrome.  A milder type of familial adenomatous polyposis, called autosomal recessive familial adenomatous polyposis, has also been identified. People with the autosomal recessive type of this disorder have fewer polyps than those with the classic type. Fewer than 100 polyps typically develop, rather than hundreds or thousands. The autosomal recessive type of this disorder is caused by mutations in a different gene than the classic and attenuated types of familial adenomatous polyposis.",familial adenomatous polyposis,0000340,GHR,https://ghr.nlm.nih.gov/condition/familial-adenomatous-polyposis,C0032580,T191,Disorders
How many people are affected by familial adenomatous polyposis ?,0000340-2,frequency,"The reported incidence of familial adenomatous polyposis varies from 1 in 7,000 to 1 in 22,000 individuals.",familial adenomatous polyposis,0000340,GHR,https://ghr.nlm.nih.gov/condition/familial-adenomatous-polyposis,C0032580,T191,Disorders
What are the genetic changes related to familial adenomatous polyposis ?,0000340-3,genetic changes,"Mutations in the APC gene cause both classic and attenuated familial adenomatous polyposis. These mutations affect the ability of the cell to maintain normal growth and function. Cell overgrowth resulting from mutations in the APC gene leads to the colon polyps seen in familial adenomatous polyposis. Although most people with mutations in the APC gene will develop colorectal cancer, the number of polyps and the time frame in which they become malignant depend on the location of the mutation in the gene.  Mutations in the MUTYH gene cause autosomal recessive familial adenomatous polyposis (also called MYH-associated polyposis). Mutations in this gene prevent cells from correcting mistakes that are made when DNA is copied (DNA replication) in preparation for cell division. As these mistakes build up in a person's DNA, the likelihood of cell overgrowth increases, leading to colon polyps and the possibility of colon cancer.",familial adenomatous polyposis,0000340,GHR,https://ghr.nlm.nih.gov/condition/familial-adenomatous-polyposis,C0032580,T191,Disorders
Is familial adenomatous polyposis inherited ?,0000340-4,inheritance,"Familial adenomatous polyposis can have different inheritance patterns.  When familial adenomatous polyposis results from mutations in the APC gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.  When familial adenomatous polyposis results from mutations in the MUTYH gene, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.",familial adenomatous polyposis,0000340,GHR,https://ghr.nlm.nih.gov/condition/familial-adenomatous-polyposis,C0032580,T191,Disorders
What are the treatments for familial adenomatous polyposis ?,0000340-5,treatment,"These resources address the diagnosis or management of familial adenomatous polyposis:  - American Medical Association and National Coalition for Health Professional Education in Genetics: Understand the Basics of Genetic Testing for Hereditary Colorectal Cancer  - Gene Review: Gene Review: APC-Associated Polyposis Conditions  - Gene Review: Gene Review: MUTYH-Associated Polyposis  - GeneFacts: Familial Adenomatous Polyposis: Diagnosis  - GeneFacts: Familial Adenomatous Polyposis: Management  - Genetic Testing Registry: Desmoid disease, hereditary  - Genetic Testing Registry: Familial adenomatous polyposis 1  - Genetic Testing Registry: Familial multiple polyposis syndrome  - Genetic Testing Registry: MYH-associated polyposis  - Genomics Education Programme (UK): Familial Adenomatous Polyposis  - Genomics Education Programme (UK): MYH-Associated Polyposis  - MedlinePlus Encyclopedia: Colon Cancer  - MedlinePlus Encyclopedia: Colorectal polyps  - National Cancer Institute: Genetic Testing for Hereditary Cancer Syndromes   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",familial adenomatous polyposis,0000340,GHR,https://ghr.nlm.nih.gov/condition/familial-adenomatous-polyposis,C0032580,T191,Disorders
What is (are) familial atrial fibrillation ?,0000341-1,information,"Familial atrial fibrillation is an inherited condition that disrupts the heart's normal rhythm. This condition is characterized by uncoordinated electrical activity in the heart's upper chambers (the atria), which causes the heartbeat to become fast and irregular. If untreated, this abnormal heart rhythm can lead to dizziness, chest pain, a sensation of fluttering or pounding in the chest (palpitations), shortness of breath, or fainting (syncope). Atrial fibrillation also increases the risk of stroke and sudden death. Complications of familial atrial fibrillation can occur at any age, although some people with this heart condition never experience any health problems associated with the disorder.",familial atrial fibrillation,0000341,GHR,https://ghr.nlm.nih.gov/condition/familial-atrial-fibrillation,C3468561,T046,Disorders
How many people are affected by familial atrial fibrillation ?,0000341-2,frequency,"Atrial fibrillation is the most common type of sustained abnormal heart rhythm (arrhythmia), affecting more than 3 million people in the United States. The risk of developing this irregular heart rhythm increases with age. The incidence of the familial form of atrial fibrillation is unknown; however, recent studies suggest that up to 30 percent of all people with atrial fibrillation may have a history of the condition in their family.",familial atrial fibrillation,0000341,GHR,https://ghr.nlm.nih.gov/condition/familial-atrial-fibrillation,C3468561,T046,Disorders
What are the genetic changes related to familial atrial fibrillation ?,0000341-3,genetic changes,"A small percentage of all cases of familial atrial fibrillation are associated with changes in the KCNE2, KCNJ2, and KCNQ1 genes. These genes provide instructions for making proteins that act as channels across the cell membrane. These channels transport positively charged atoms (ions) of potassium into and out of cells. In heart (cardiac) muscle, the ion channels produced from the KCNE2, KCNJ2, and KCNQ1 genes play critical roles in maintaining the heart's normal rhythm. Mutations in these genes have been identified in only a few families worldwide. These mutations increase the activity of the channels, which changes the flow of potassium ions between cells. This disruption in ion transport alters the way the heart beats, increasing the risk of syncope, stroke, and sudden death.  Most cases of atrial fibrillation are not caused by mutations in a single gene. This condition is often related to structural abnormalities of the heart or underlying heart disease. Additional risk factors for atrial fibrillation include high blood pressure (hypertension), diabetes mellitus, a previous stroke, or an accumulation of fatty deposits and scar-like tissue in the lining of the arteries (atherosclerosis). Although most cases of atrial fibrillation are not known to run in families, studies suggest that they may arise partly from genetic risk factors. Researchers are working to determine which genetic changes may influence the risk of atrial fibrillation.",familial atrial fibrillation,0000341,GHR,https://ghr.nlm.nih.gov/condition/familial-atrial-fibrillation,C3468561,T046,Disorders
Is familial atrial fibrillation inherited ?,0000341-4,inheritance,"Familial atrial fibrillation appears to be inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",familial atrial fibrillation,0000341,GHR,https://ghr.nlm.nih.gov/condition/familial-atrial-fibrillation,C3468561,T046,Disorders
What are the treatments for familial atrial fibrillation ?,0000341-5,treatment,"These resources address the diagnosis or management of familial atrial fibrillation:  - Genetic Testing Registry: Atrial fibrillation, familial, 1  - Genetic Testing Registry: Atrial fibrillation, familial, 2  - Genetic Testing Registry: Atrial fibrillation, familial, 3  - MedlinePlus Encyclopedia: Arrhythmias  - MedlinePlus Encyclopedia: Atrial fibrillation/flutter   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",familial atrial fibrillation,0000341,GHR,https://ghr.nlm.nih.gov/condition/familial-atrial-fibrillation,C3468561,T046,Disorders
What is (are) familial cold autoinflammatory syndrome ?,0000342-1,information,"Familial cold autoinflammatory syndrome is a condition that causes episodes of fever, skin rash, and joint pain after exposure to cold temperatures. These episodes usually begin in infancy and occur throughout life.  People with this condition usually experience symptoms after cold exposure of an hour or more, although in some individuals only a few minutes of exposure is required. Symptoms may be delayed for up to a few hours after the cold exposure. Episodes last an average of 12 hours, but may continue for up to 3 days.  In people with familial cold autoinflammatory syndrome, the most common symptom that occurs during an episode is an itchy or burning rash. The rash usually begins on the face or extremities and spreads to the rest of the body. Occasionally swelling in the extremities may occur.  In addition to the skin rash, episodes are characterized by fever, chills, and joint pain, most often affecting the hands, knees, and ankles. Redness in the whites of the eye (conjunctivitis), sweating, drowsiness, headache, thirst, and nausea may also occur during an episode of this disorder.",familial cold autoinflammatory syndrome,0000342,GHR,https://ghr.nlm.nih.gov/condition/familial-cold-autoinflammatory-syndrome,C0009443,T047,Disorders
How many people are affected by familial cold autoinflammatory syndrome ?,0000342-2,frequency,"Familial cold autoinflammatory syndrome is a very rare condition, believed to have a prevalence of less than 1 per million people.",familial cold autoinflammatory syndrome,0000342,GHR,https://ghr.nlm.nih.gov/condition/familial-cold-autoinflammatory-syndrome,C0009443,T047,Disorders
What are the genetic changes related to familial cold autoinflammatory syndrome ?,0000342-3,genetic changes,"Mutations in the NLRP3 and NLRP12 genes cause familial cold autoinflammatory syndrome. The NLRP3 gene (also known as CIAS1) provides instructions for making a protein called cryopyrin, and the NLRP12 gene provides instructions for making the protein monarch-1.  Cryopyrin and monarch-1 belong to a family of proteins called nucleotide-binding domain and leucine-rich repeat containing (NLR) proteins. These proteins are involved in the immune system, helping to regulate the process of inflammation. Inflammation occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight microbial invaders and facilitate tissue repair. When this has been accomplished, the body stops (inhibits) the inflammatory response to prevent damage to its own cells and tissues.  Cryopyrin is involved in the assembly of a molecular complex called an inflammasome, which helps start the inflammatory process. Mutations in the NLRP3 gene result in a hyperactive cryopyrin protein that inappropriately triggers an inflammatory response.  Monarch-1 is involved in the inhibition of the inflammatory response. Mutations in the NLRP12 gene appear to reduce the ability of the monarch-1 protein to inhibit inflammation.  Impairment of the body's mechanisms for controlling inflammation results in the episodes of skin rash, fever, and joint pain seen in familial cold autoinflammatory syndrome. It is unclear why episodes are triggered by cold exposure in this disorder.",familial cold autoinflammatory syndrome,0000342,GHR,https://ghr.nlm.nih.gov/condition/familial-cold-autoinflammatory-syndrome,C0009443,T047,Disorders
Is familial cold autoinflammatory syndrome inherited ?,0000342-4,inheritance,This condition is inherited in an autosomal dominant pattern from an affected parent; one copy of the altered gene in each cell is sufficient to cause the disorder.,familial cold autoinflammatory syndrome,0000342,GHR,https://ghr.nlm.nih.gov/condition/familial-cold-autoinflammatory-syndrome,C0009443,T047,Disorders
What are the treatments for familial cold autoinflammatory syndrome ?,0000342-5,treatment,These resources address the diagnosis or management of familial cold autoinflammatory syndrome:  - Genetic Testing Registry: Familial cold autoinflammatory syndrome 2  - Genetic Testing Registry: Familial cold urticaria   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,familial cold autoinflammatory syndrome,0000342,GHR,https://ghr.nlm.nih.gov/condition/familial-cold-autoinflammatory-syndrome,C0009443,T047,Disorders
What is (are) familial cylindromatosis ?,0000343-1,information,"Familial cylindromatosis is a condition involving multiple skin tumors that develop from structures associated with the skin (skin appendages), such as hair follicles and sweat glands. People with familial cylindromatosis typically develop large numbers of tumors called cylindromas. While previously thought to derive from sweat glands, cylindromas are now generally believed to begin in hair follicles.  Individuals with familial cylindromatosis occasionally develop other types of tumors, including growths called spiradenomas and trichoepitheliomas. Spiradenomas begin in sweat glands. Trichoepitheliomas arise from hair follicles. The tumors associated with familial cylindromatosis are generally noncancerous (benign), but occasionally they may become cancerous (malignant). Affected individuals are also at increased risk of developing tumors in tissues other than skin appendages, particularly benign or malignant tumors of the salivary glands.  People with familial cylindromatosis typically begin developing tumors in adolescence or early adulthood. The tumors are most often found in hairy regions of the body, with approximately 90 percent occurring on the head and neck. They grow larger and increase in number over time.  In severely affected individuals, multiple tumors on the scalp may combine into a large, turban-like growth. Large growths frequently develop open sores (ulcers) and are prone to infections. The tumors may also get in the way of the eyes, ears, nose, or mouth and affect vision, hearing, or other functions. The growths can be disfiguring and may contribute to depression or other psychological problems. For reasons that are unclear, females with familial cylindromatosis are often more severely affected than males.",familial cylindromatosis,0000343,GHR,https://ghr.nlm.nih.gov/condition/familial-cylindromatosis,C1305968,T191,Disorders
How many people are affected by familial cylindromatosis ?,0000343-2,frequency,Familial cylindromatosis is a rare disorder; its prevalence is unknown.,familial cylindromatosis,0000343,GHR,https://ghr.nlm.nih.gov/condition/familial-cylindromatosis,C1305968,T191,Disorders
What are the genetic changes related to familial cylindromatosis ?,0000343-3,genetic changes,"Familial cylindromatosis is caused by mutations in the CYLD gene. This gene provides instructions for making a protein that helps regulate nuclear factor-kappa-B. Nuclear factor-kappa-B is a group of related proteins that help protect cells from self-destruction (apoptosis) in response to certain signals. In regulating the action of nuclear factor-kappa-B, the CYLD protein allows cells to respond properly to signals to self-destruct when appropriate, such as when the cells become abnormal. By this mechanism, the CYLD protein acts as a tumor suppressor, which means that it helps prevent cells from growing and dividing too fast or in an uncontrolled way.  People with familial cylindromatosis are born with a mutation in one of the two copies of the CYLD gene in each cell. This mutation prevents the cell from making functional CYLD protein from the altered copy of the gene. However, enough protein is usually produced from the other, normal copy of the gene to regulate cell growth effectively. For tumors to develop, a second mutation or deletion of genetic material involving the other copy of the CYLD gene must occur in certain cells during a person's lifetime.  When both copies of the CYLD gene are mutated in a particular cell, that cell cannot produce any functional CYLD protein. The loss of this protein allows the cell to grow and divide in an uncontrolled way to form a tumor. In people with familial cylindromatosis, a second CYLD mutation typically occurs in multiple cells over an affected person's lifetime. The loss of CYLD protein in these cells leads to the growth of skin appendage tumors.  Some researchers consider familial cylindromatosis and two related conditions called multiple familial trichoepithelioma and Brooke-Spiegler syndrome, which are also caused by CYLD gene mutations, to be different forms of the same disorder. It is unclear why mutations in the CYLD gene cause different patterns of skin appendage tumors in each of these conditions, or why the tumors are generally confined to the skin in these disorders.",familial cylindromatosis,0000343,GHR,https://ghr.nlm.nih.gov/condition/familial-cylindromatosis,C1305968,T191,Disorders
Is familial cylindromatosis inherited ?,0000343-4,inheritance,"Susceptibility to familial cylindromatosis has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell increases the risk of developing this condition. However, a second, non-inherited mutation is required for development of skin appendage tumors in this disorder.",familial cylindromatosis,0000343,GHR,https://ghr.nlm.nih.gov/condition/familial-cylindromatosis,C1305968,T191,Disorders
What are the treatments for familial cylindromatosis ?,0000343-5,treatment,"These resources address the diagnosis or management of familial cylindromatosis:  - Genetic Testing Registry: Cylindromatosis, familial   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",familial cylindromatosis,0000343,GHR,https://ghr.nlm.nih.gov/condition/familial-cylindromatosis,C1305968,T191,Disorders
What is (are) familial dilated cardiomyopathy ?,0000344-1,information,"Familial dilated cardiomyopathy is a genetic form of heart disease. It occurs when heart (cardiac) muscle becomes stretched out in at least one chamber of the heart, causing the open area of the chamber to become enlarged (dilated). As a result, the heart is unable to pump blood as efficiently as usual. Eventually, all four chambers of the heart become dilated as the cardiac muscle tries to increase the amount of blood being pumped through the heart. However, as the cardiac muscle becomes increasingly thin and weakened, it is less able to pump blood. Over time, this condition results in heart failure.  It usually takes many years for symptoms of familial dilated cardiomyopathy to appear. They typically begin in mid-adulthood, but can occur at any time from infancy to late adulthood. Signs and symptoms of familial dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath (dyspnea), extreme tiredness (fatigue), fainting episodes (syncope), and swelling of the legs and feet. In some cases, the first sign of the disorder is sudden cardiac death. The severity of the condition varies among affected individuals, even in members of the same family.",familial dilated cardiomyopathy,0000344,GHR,https://ghr.nlm.nih.gov/condition/familial-dilated-cardiomyopathy,C0340427,T047,Disorders
How many people are affected by familial dilated cardiomyopathy ?,0000344-2,frequency,"It is estimated that 750,000 people in the United States have dilated cardiomyopathy; roughly half of these cases are familial.",familial dilated cardiomyopathy,0000344,GHR,https://ghr.nlm.nih.gov/condition/familial-dilated-cardiomyopathy,C0340427,T047,Disorders
What are the genetic changes related to familial dilated cardiomyopathy ?,0000344-3,genetic changes,"Mutations in more than 30 genes have been found to cause familial dilated cardiomyopathy. These genes provide instructions for making proteins that are found in cardiac muscle cells called cardiomyocytes.  Many of these proteins play important roles in the contraction of the cardiac muscle through their association with cell structures called sarcomeres. Sarcomeres are the basic units of muscle contraction; they are made of proteins that generate the mechanical force needed for muscles to contract. Many other proteins associated with familial dilated cardiomyopathy make up the structural framework (the cytoskeleton) of cardiomyocytes. The remaining proteins play various roles within cardiomyocytes to ensure their proper functioning.  Mutations in one gene, TTN, account for approximately 20 percent of cases of familial dilated cardiomyopathy. The TTN gene provides instructions for making a protein called titin, which is found in the sarcomeres of many types of muscle cells, including cardiomyocytes. Titin has several functions within sarcomeres. One of its most important jobs is to provide structure, flexibility, and stability to these cell structures. Titin also plays a role in chemical signaling and in assembling new sarcomeres. The TTN gene mutations that cause familial dilated cardiomyopathy result in the production of an abnormally short titin protein. It is unclear how the altered protein causes familial dilated cardiomyopathy, but it is likely that it impairs sarcomere function and disrupts chemical signaling.  It is unclear how mutations in the other genes cause familial dilated cardiomyopathy. It is likely that the changes impair cardiomyocyte function and reduce the ability of these cells to contract, weakening and thinning cardiac muscle.  People with familial dilated cardiomyopathy often do not have an identified mutation in any of the known associated genes. The cause of the condition in these individuals is unknown.  Familial dilated cardiomyopathy is described as nonsyndromic or isolated because it typically affects only the heart. However, dilated cardiomyopathy can also occur as part of syndromes that affect other organs and tissues in the body. These forms of the condition are described as syndromic and are caused by mutations in other genes. Additionally, there are many nongenetic causes of dilated cardiomyopathy, including viral infection and chronic alcohol abuse.",familial dilated cardiomyopathy,0000344,GHR,https://ghr.nlm.nih.gov/condition/familial-dilated-cardiomyopathy,C0340427,T047,Disorders
Is familial dilated cardiomyopathy inherited ?,0000344-4,inheritance,"Familial dilated cardiomyopathy has different inheritance patterns depending on the gene involved.  In 80 to 90 percent of cases, familial dilated cardiomyopathy is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent. However, some people who inherit the altered gene never develop features of familial dilated cardiomyopathy. (This situation is known as reduced penetrance.) Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  In rare instances, this condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  In other rare cases, this condition is inherited in an X-linked pattern. In these cases, the gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell increases the risk of developing heart disease, but females with such a mutation may not develop familial dilated cardiomyopathy. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes familial dilated cardiomyopathy. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",familial dilated cardiomyopathy,0000344,GHR,https://ghr.nlm.nih.gov/condition/familial-dilated-cardiomyopathy,C0340427,T047,Disorders
What are the treatments for familial dilated cardiomyopathy ?,0000344-5,treatment,"These resources address the diagnosis or management of familial dilated cardiomyopathy:  - Cincinnati Children's Hospital  - Gene Review: Gene Review: Dilated Cardiomyopathy Overview  - Gene Review: Gene Review: Dystrophinopathies  - Gene Review: Gene Review: LMNA-Related Dilated Cardiomyopathy  - MedlinePlus Encyclopedia: Dilated Cardiomyopathy  - National Heart, Lung, and Blood Institute: How Is Cardiomyopathy Treated?  - Seattle Children's Hospital: Cardiomyopathy Treatment Options  - The Sarcomeric Human Cardiomyopathies Registry (ShaRe)   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",familial dilated cardiomyopathy,0000344,GHR,https://ghr.nlm.nih.gov/condition/familial-dilated-cardiomyopathy,C0340427,T047,Disorders
What is (are) familial dysautonomia ?,0000345-1,information,"Familial dysautonomia is a genetic disorder that affects the development and survival of certain nerve cells. The disorder disturbs cells in the autonomic nervous system, which controls involuntary actions such as digestion, breathing, production of tears, and the regulation of blood pressure and body temperature. It also affects the sensory nervous system, which controls activities related to the senses, such as taste and the perception of pain, heat, and cold. Familial dysautonomia is also called hereditary sensory and autonomic neuropathy, type III.  Problems related to this disorder first appear during infancy. Early signs and symptoms include poor muscle tone (hypotonia), feeding difficulties, poor growth, lack of tears, frequent lung infections, and difficulty maintaining body temperature. Older infants and young children with familial dysautonomia may hold their breath for prolonged periods of time, which may cause a bluish appearance of the skin or lips (cyanosis) or fainting. This breath-holding behavior usually stops by age 6. Developmental milestones, such as walking and speech, are usually delayed, although some affected individuals show no signs of developmental delay.  Additional signs and symptoms in school-age children include bed wetting, episodes of vomiting, reduced sensitivity to temperature changes and pain, poor balance, abnormal curvature of the spine (scoliosis), poor bone quality and increased risk of bone fractures, and kidney and heart problems. Affected individuals also have poor regulation of blood pressure. They may experience a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting. They can also have episodes of high blood pressure when nervous or excited, or during vomiting incidents. About one-third of children with familial dysautonomia have learning disabilities, such as a short attention span, that require special education classes. By adulthood, affected individuals often have increasing difficulties with balance and walking unaided. Other problems that may appear in adolescence or early adulthood include lung damage due to repeated infections, impaired kidney function, and worsening vision due to the shrinking size (atrophy) of optic nerves, which carry information from the eyes to the brain.",familial dysautonomia,0000345,GHR,https://ghr.nlm.nih.gov/condition/familial-dysautonomia,C0013364,T019,Disorders
How many people are affected by familial dysautonomia ?,0000345-2,frequency,"Familial dysautonomia occurs primarily in people of Ashkenazi (central or eastern European) Jewish descent. It affects about 1 in 3,700 individuals in Ashkenazi Jewish populations. Familial dysautonomia is extremely rare in the general population.",familial dysautonomia,0000345,GHR,https://ghr.nlm.nih.gov/condition/familial-dysautonomia,C0013364,T019,Disorders
What are the genetic changes related to familial dysautonomia ?,0000345-3,genetic changes,"Mutations in the IKBKAP gene cause familial dysautonomia.  The IKBKAP gene provides instructions for making a protein called IKK complex-associated protein (IKAP). This protein is found in a variety of cells throughout the body, including brain cells.  Nearly all individuals with familial dysautonomia have two copies of the same IKBKAP gene mutation in each cell. This mutation can disrupt how information in the IKBKAP gene is pieced together to make a blueprint for the production of IKAP protein. As a result of this error, a reduced amount of normal IKAP protein is produced. This mutation behaves inconsistently, however. Some cells produce near normal amounts of the protein, and other cellsparticularly brain cellshave very little of the protein. Critical activities in brain cells are probably disrupted by reduced amounts or the absence of IKAP protein, leading to the signs and symptoms of familial dysautonomia.",familial dysautonomia,0000345,GHR,https://ghr.nlm.nih.gov/condition/familial-dysautonomia,C0013364,T019,Disorders
Is familial dysautonomia inherited ?,0000345-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",familial dysautonomia,0000345,GHR,https://ghr.nlm.nih.gov/condition/familial-dysautonomia,C0013364,T019,Disorders
What are the treatments for familial dysautonomia ?,0000345-5,treatment,These resources address the diagnosis or management of familial dysautonomia:  - Gene Review: Gene Review: Familial Dysautonomia  - Genetic Testing Registry: Familial dysautonomia  - MedlinePlus Encyclopedia: Riley-Day Syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,familial dysautonomia,0000345,GHR,https://ghr.nlm.nih.gov/condition/familial-dysautonomia,C0013364,T019,Disorders
What is (are) familial encephalopathy with neuroserpin inclusion bodies ?,0000346-1,information,"Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a disorder that causes progressive dysfunction of the brain (encephalopathy). It is characterized by a loss of intellectual functioning (dementia) and seizures. At first, affected individuals may have difficulty sustaining attention and concentrating. They may experience repetitive thoughts, speech, or movements. As the condition progresses, their personality changes and judgment, insight, and memory become impaired. Affected people lose the ability to perform the activities of daily living, and most eventually require comprehensive care.  The signs and symptoms of FENIB vary in their severity and age of onset. In severe cases, the condition causes seizures and episodes of sudden, involuntary muscle jerking or twitching (myoclonus) in addition to dementia. These signs can appear as early as a person's teens. Less severe cases are characterized by a progressive decline in intellectual functioning beginning in a person's forties or fifties.",familial encephalopathy with neuroserpin inclusion bodies,0000346,GHR,https://ghr.nlm.nih.gov/condition/familial-encephalopathy-with-neuroserpin-inclusion-bodies,C0085584,T047,Disorders
How many people are affected by familial encephalopathy with neuroserpin inclusion bodies ?,0000346-2,frequency,This condition appears to be rare; only a few affected individuals have been reported worldwide.,familial encephalopathy with neuroserpin inclusion bodies,0000346,GHR,https://ghr.nlm.nih.gov/condition/familial-encephalopathy-with-neuroserpin-inclusion-bodies,C0085584,T047,Disorders
What are the genetic changes related to familial encephalopathy with neuroserpin inclusion bodies ?,0000346-3,genetic changes,"FENIB results from mutations in the SERPINI1 gene. This gene provides instructions for making a protein called neuroserpin, which is found in nerve cells (neurons). Neuroserpin plays a role in the development and function of the nervous system. This protein helps control the growth of neurons and their connections with one another, which suggests that it may be important for learning and memory.  Mutations in the SERPINI1 gene result in the production of an abnormally shaped, unstable form of neuroserpin. Within neurons, defective neuroserpin proteins can attach to one another and form clumps called neuroserpin inclusion bodies or Collins bodies. These clumps disrupt the cells' normal functioning and ultimately lead to cell death. The gradual loss of neurons in certain parts of the brain causes progressive dementia. Researchers believe that a buildup of related, potentially toxic substances in neurons may also contribute to the signs and symptoms of this condition.",familial encephalopathy with neuroserpin inclusion bodies,0000346,GHR,https://ghr.nlm.nih.gov/condition/familial-encephalopathy-with-neuroserpin-inclusion-bodies,C0085584,T047,Disorders
Is familial encephalopathy with neuroserpin inclusion bodies inherited ?,0000346-4,inheritance,"FENIB is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In many cases, an affected person has a parent with the condition.",familial encephalopathy with neuroserpin inclusion bodies,0000346,GHR,https://ghr.nlm.nih.gov/condition/familial-encephalopathy-with-neuroserpin-inclusion-bodies,C0085584,T047,Disorders
What are the treatments for familial encephalopathy with neuroserpin inclusion bodies ?,0000346-5,treatment,These resources address the diagnosis or management of FENIB:  - Genetic Testing Registry: Familial encephalopathy with neuroserpin inclusion bodies  - MedlinePlus Encyclopedia: Dementia  - MedlinePlus Encyclopedia: Seizures   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,familial encephalopathy with neuroserpin inclusion bodies,0000346,GHR,https://ghr.nlm.nih.gov/condition/familial-encephalopathy-with-neuroserpin-inclusion-bodies,C0085584,T047,Disorders
What is (are) familial erythrocytosis ?,0000347-1,information,"Familial erythrocytosis is an inherited condition characterized by an increased number of red blood cells (erythrocytes). The primary function of these cells is to carry oxygen from the lungs to tissues and organs throughout the body. Signs and symptoms of familial erythrocytosis can include headaches, dizziness, nosebleeds, and shortness of breath. The excess red blood cells also increase the risk of developing abnormal blood clots that can block the flow of blood through arteries and veins. If these clots restrict blood flow to essential organs and tissues (particularly the heart, lungs, or brain), they can cause life-threatening complications such as a heart attack or stroke. However, many people with familial erythrocytosis experience only mild signs and symptoms or never have any problems related to their extra red blood cells.",familial erythrocytosis,0000347,GHR,https://ghr.nlm.nih.gov/condition/familial-erythrocytosis,C0152264,T047,Disorders
How many people are affected by familial erythrocytosis ?,0000347-2,frequency,Familial erythrocytosis is a rare condition; its prevalence is unknown.,familial erythrocytosis,0000347,GHR,https://ghr.nlm.nih.gov/condition/familial-erythrocytosis,C0152264,T047,Disorders
What are the genetic changes related to familial erythrocytosis ?,0000347-3,genetic changes,"Familial erythrocytosis can result from mutations in the EPOR, VHL, EGLN1, or EPAS1 gene. Researchers define four types of familial erythrocytosis, ECYT1 through ECYT4, based on which of these genes is altered.  The EPOR gene provides instructions for making a protein known as the erythropoietin receptor, which is found on the surface of certain blood-forming cells in the bone marrow. Erythropoietin is a hormone that directs the production of new red blood cells. Erythropoietin fits into the receptor like a key into a lock, triggering signaling pathways that lead to the formation of red blood cells. Mutations in the EPOR gene cause the erythropoietin receptor to be turned on for an abnormally long time after attaching to erythropoietin. The overactive receptor signals the production of red blood cells even when they are not needed, which results in an excess of these cells in the bloodstream. When familial erythrocytosis is caused by mutations in the EPOR gene, it is known as ECYT1.  The proteins produced from the VHL, EGLN1, and EPAS1 genes are also involved in red blood cell production; they each play a role in regulating erythropoietin. The protein produced from the EPAS1 gene is one component of a protein complex called hypoxia-inducible factor (HIF). When oxygen levels are lower than normal (hypoxia), HIF activates genes that help the body adapt, including the gene that provides instructions for making erythropoietin. Erythropoietin stimulates the production of more red blood cells to carry oxygen to organs and tissues. The proteins produced from the VHL and EGLN1 genes indirectly regulate erythropoietin by controlling the amount of available HIF. Mutations in any of these three genes can disrupt the regulation of red blood cell formation, leading to an overproduction of these cells. When familial erythrocytosis results from VHL gene mutations it is known as ECYT2; when the condition is caused by EGLN1 gene mutations it is called ECYT3; and when the condition results from EPAS1 gene mutations it is known as ECYT4.  Researchers have also described non-familial (acquired) forms of erythrocytosis. Causes of acquired erythrocytosis include long-term exposure to high altitude, chronic lung or heart disease, episodes in which breathing slows or stops for short periods during sleep (sleep apnea), and certain types of tumors. Another form of acquired erythrocytosis, called polycythemia vera, results from somatic (non-inherited) mutations in other genes involved in red blood cell production. In some cases, the cause of erythrocytosis is unknown.",familial erythrocytosis,0000347,GHR,https://ghr.nlm.nih.gov/condition/familial-erythrocytosis,C0152264,T047,Disorders
Is familial erythrocytosis inherited ?,0000347-4,inheritance,"Familial erythrocytosis can have different inheritance patterns depending on the gene involved.  When the condition is caused by mutations in the EPOR, EGLN1, or EPAS1 gene, it has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. Most affected individuals inherit the altered gene from one affected parent.  When familial erythrocytosis is caused by mutations in the VHL gene, it has an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",familial erythrocytosis,0000347,GHR,https://ghr.nlm.nih.gov/condition/familial-erythrocytosis,C0152264,T047,Disorders
What are the treatments for familial erythrocytosis ?,0000347-5,treatment,"These resources address the diagnosis or management of familial erythrocytosis:  - Genetic Testing Registry: Erythrocytosis, familial, 2  - Genetic Testing Registry: Erythrocytosis, familial, 3  - Genetic Testing Registry: Erythrocytosis, familial, 4  - Genetic Testing Registry: Familial erythrocytosis, 1  - MedlinePlus Encyclopedia: Erythropoietin Test   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",familial erythrocytosis,0000347,GHR,https://ghr.nlm.nih.gov/condition/familial-erythrocytosis,C0152264,T047,Disorders
What is (are) familial exudative vitreoretinopathy ?,0000348-1,information,"Familial exudative vitreoretinopathy is a hereditary disorder that can cause progressive vision loss. This condition affects the retina, the specialized light-sensitive tissue that lines the back of the eye. The disorder prevents blood vessels from forming at the edges of the retina, which reduces the blood supply to this tissue.  The signs and symptoms of familial exudative vitreoretinopathy vary widely, even within the same family. In many affected individuals, the retinal abnormalities never cause any vision problems. In others, a reduction in the retina's blood supply causes the retina to fold, tear, or separate from the back of the eye (retinal detachment). This retinal damage can lead to vision loss and blindness. Other eye abnormalities are also possible, including eyes that do not look in the same direction (strabismus) and a visible whiteness (leukocoria) in the normally black pupil.  Some people with familial exudative vitreoretinopathy also have reduced bone mineral density, which weakens bones and increases the risk of fractures.",familial exudative vitreoretinopathy,0000348,GHR,https://ghr.nlm.nih.gov/condition/familial-exudative-vitreoretinopathy,C0339539,T019,Disorders
How many people are affected by familial exudative vitreoretinopathy ?,0000348-2,frequency,"The prevalence of familial exudative vitreoretinopathy is unknown. It appears to be rare, although affected people with normal vision may never come to medical attention.",familial exudative vitreoretinopathy,0000348,GHR,https://ghr.nlm.nih.gov/condition/familial-exudative-vitreoretinopathy,C0339539,T019,Disorders
What are the genetic changes related to familial exudative vitreoretinopathy ?,0000348-3,genetic changes,"Mutations in the FZD4, LRP5, and NDP genes can cause familial exudative vitreoretinopathy. These genes provide instructions for making proteins that participate in a chemical signaling pathway that affects the way cells and tissues develop. In particular, the proteins produced from the FZD4, LRP5, and NDP genes appear to play critical roles in the specialization of retinal cells and the establishment of a blood supply to the retina and the inner ear. The LRP5 protein also helps regulate bone formation.  Mutations in the FZD4, LRP5, or NDP gene disrupt chemical signaling during early development, which interferes with the formation of blood vessels at the edges of the retina. The resulting abnormal blood supply to this tissue leads to retinal damage and vision loss in some people with familial exudative vitreoretinopathy.  The eye abnormalities associated with familial exudative vitreoretinopathy tend to be similar no matter which gene is altered. However, affected individuals with LRP5 gene mutations often have reduced bone mineral density in addition to vision loss. Mutations in the other genes responsible for familial exudative vitreoretinopathy do not appear to affect bone density.  In some cases, the cause of familial exudative vitreoretinopathy is unknown. Researchers believe that mutations in several as-yet-unidentified genes are responsible for the disorder in these cases.",familial exudative vitreoretinopathy,0000348,GHR,https://ghr.nlm.nih.gov/condition/familial-exudative-vitreoretinopathy,C0339539,T019,Disorders
Is familial exudative vitreoretinopathy inherited ?,0000348-4,inheritance,"Familial exudative vitreoretinopathy has different inheritance patterns depending on the gene involved. Most commonly, the condition results from mutations in the FZD4 or LRP5 gene and has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. Most people with autosomal dominant familial exudative vitreoretinopathy inherit the altered gene from a parent, although the parent may not have any signs and symptoms associated with this disorder.  Familial exudative vitreoretinopathy caused by LRP5 gene mutations can also have an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with autosomal recessive familial exudative vitreoretinopathy each carry one copy of the mutated gene, but they do not have the disorder.  When familial exudative vitreoretinopathy is caused by mutations in the NDP gene, it has an X-linked recessive pattern of inheritance. The NDP gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",familial exudative vitreoretinopathy,0000348,GHR,https://ghr.nlm.nih.gov/condition/familial-exudative-vitreoretinopathy,C0339539,T019,Disorders
What are the treatments for familial exudative vitreoretinopathy ?,0000348-5,treatment,"These resources address the diagnosis or management of familial exudative vitreoretinopathy:  - Gene Review: Gene Review: Familial Exudative Vitreoretinopathy, Autosomal Dominant  - Gene Review: Gene Review: NDP-Related Retinopathies  - Genetic Testing Registry: Exudative vitreoretinopathy 1  - Genetic Testing Registry: Exudative vitreoretinopathy 3  - Genetic Testing Registry: Exudative vitreoretinopathy 4  - Genetic Testing Registry: Familial exudative vitreoretinopathy, X-linked   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",familial exudative vitreoretinopathy,0000348,GHR,https://ghr.nlm.nih.gov/condition/familial-exudative-vitreoretinopathy,C0339539,T019,Disorders
What is (are) familial glucocorticoid deficiency ?,0000349-1,information,"Familial glucocorticoid deficiency is a condition that occurs when the adrenal glands, which are hormone-producing glands located on top of each kidney, do not produce certain hormones called glucocorticoids. These hormones, which include cortisol and corticosterone, aid in immune system function, play a role in maintaining normal blood sugar levels, help trigger nerve cell signaling in the brain, and serve many other purposes in the body.  A shortage of adrenal hormones (adrenal insufficiency) causes the signs and symptoms of familial glucocorticoid deficiency. These signs and symptoms often begin in infancy or early childhood. Most affected children first develop low blood sugar (hypoglycemia). These hypoglycemic children can fail to grow and gain weight at the expected rate (failure to thrive). If left untreated, hypoglycemia can lead to seizures, learning difficulties, and other neurological problems. Hypoglycemia that is left untreated for prolonged periods can lead to neurological damage and death. Other features of familial glucocorticoid deficiency can include recurrent infections and skin coloring darker than that of other family members (hyperpigmentation).  There are multiple types of familial glucocorticoid deficiency, which are distinguished by their genetic cause.",familial glucocorticoid deficiency,0000349,GHR,https://ghr.nlm.nih.gov/condition/familial-glucocorticoid-deficiency,C1955741,T047,Disorders
How many people are affected by familial glucocorticoid deficiency ?,0000349-2,frequency,The prevalence of familial glucocorticoid deficiency is unknown.,familial glucocorticoid deficiency,0000349,GHR,https://ghr.nlm.nih.gov/condition/familial-glucocorticoid-deficiency,C1955741,T047,Disorders
What are the genetic changes related to familial glucocorticoid deficiency ?,0000349-3,genetic changes,"Mutations in the MC2R, MRAP, and NNT genes account for the majority of cases of familial glucocorticoid deficiency; mutations in other genes, some known and some unidentified, can also cause this condition.  The MC2R gene provides instructions for making a protein called adrenocorticotropic hormone (ACTH) receptor, which is found primarily in the adrenal glands. The protein produced from the MRAP gene transports the ACTH receptor from the interior of the cell to the cell membrane. When the ACTH receptor is embedded within the cell membrane, it is turned on (activated) by the MRAP protein. Activated ACTH receptor can then attach (bind) to ACTH, and this binding triggers the adrenal glands to produce glucocorticoids. MC2R gene mutations lead to the production of a receptor that cannot be transported to the cell membrane or, if it does get to the cell membrane, cannot bind to ACTH. MRAP gene mutations impair the transport of the ACTH receptor to the cell membrane. Without the binding of the ACTH receptor to its hormone, there is no signal to trigger the adrenal glands to produce glucocorticoids.  The NNT gene provides instructions for making an enzyme called nicotinamide nucleotide transhydrogenase. This enzyme is found embedded in the inner membrane of structures called mitochondria, which are the energy-producing centers of cells. This enzyme helps produce a substance called NADPH, which is involved in removing potentially toxic molecules called reactive oxygen species that can damage DNA, proteins, and cell membranes. NNT gene mutations impair the enzyme's ability to produce NADPH, leading to an increase in reactive oxygen species in adrenal gland tissues. Over time, these toxic molecules can impair the function of adrenal gland cells and lead to their death (apoptosis), diminishing the production of glucocorticoids.",familial glucocorticoid deficiency,0000349,GHR,https://ghr.nlm.nih.gov/condition/familial-glucocorticoid-deficiency,C1955741,T047,Disorders
Is familial glucocorticoid deficiency inherited ?,0000349-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",familial glucocorticoid deficiency,0000349,GHR,https://ghr.nlm.nih.gov/condition/familial-glucocorticoid-deficiency,C1955741,T047,Disorders
What are the treatments for familial glucocorticoid deficiency ?,0000349-5,treatment,"These resources address the diagnosis or management of familial glucocorticoid deficiency:  - Genetic Testing Registry: ACTH resistance  - Genetic Testing Registry: Glucocorticoid deficiency 2  - Genetic Testing Registry: Glucocorticoid deficiency 3  - Genetic Testing Registry: Glucocorticoid deficiency 4  - Genetic Testing Registry: Natural killer cell deficiency, familial isolated   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",familial glucocorticoid deficiency,0000349,GHR,https://ghr.nlm.nih.gov/condition/familial-glucocorticoid-deficiency,C1955741,T047,Disorders
What is (are) familial HDL deficiency ?,0000350-1,information,"Familial HDL deficiency is a condition characterized by low levels of high-density lipoprotein (HDL) in the blood. HDL is a molecule that transports cholesterol and certain fats called phospholipids through the bloodstream from the body's tissues to the liver. Once in the liver, cholesterol and phospholipids are redistributed to other tissues or removed from the body. HDL is often referred to as ""good cholesterol"" because high levels of this substance reduce the chances of developing heart and blood vessel (cardiovascular) disease. People with familial HDL deficiency may develop cardiovascular disease at a relatively young age, often before age 50.  Severely reduced levels of HDL in the blood is a characteristic feature of a related disorder called Tangier disease. People with Tangier disease have additional signs and symptoms, such as disturbances in nerve function; enlarged, orange-colored tonsils; and clouding of the clear covering of the eye (corneal clouding). However, people with familial HDL deficiency do not have these additional features.",familial HDL deficiency,0000350,GHR,https://ghr.nlm.nih.gov/condition/familial-hdl-deficiency,C2931838,T047,Disorders
How many people are affected by familial HDL deficiency ?,0000350-2,frequency,"Familial HDL deficiency is a rare disorder, although the prevalence is unknown.",familial HDL deficiency,0000350,GHR,https://ghr.nlm.nih.gov/condition/familial-hdl-deficiency,C2931838,T047,Disorders
What are the genetic changes related to familial HDL deficiency ?,0000350-3,genetic changes,"Mutations in the ABCA1 gene or the APOA1 gene cause familial HDL deficiency. The proteins produced from these genes work together to remove cholesterol and phospholipids from cells.  The ABCA1 gene provides instructions for making a protein that removes cholesterol and phospholipids from cells by moving them across the cell membrane. The movement of these substances across the membrane is enhanced by another protein called apolipoprotein A-I (apoA-I), which is produced by the APOA1 gene. Once outside the cell, the cholesterol and phospholipids combine with apoA-I to form HDL. ApoA-I also triggers a reaction that converts cholesterol to a form that can be fully integrated into HDL and transported through the bloodstream.  ABCA1 gene mutations and some APOA1 gene mutations prevent the release of cholesterol and phospholipids from cells. Other mutations in the APOA1 gene reduce the protein's ability to stimulate the conversion of cholesterol. These ABCA1 and APOA1 gene mutations decrease the amount of cholesterol or phospholipids available to form HDL, resulting in low levels of HDL in the blood. A shortage (deficiency) of HDL is believed to increase the risk of cardiovascular disease.",familial HDL deficiency,0000350,GHR,https://ghr.nlm.nih.gov/condition/familial-hdl-deficiency,C2931838,T047,Disorders
Is familial HDL deficiency inherited ?,0000350-4,inheritance,"Familial HDL deficiency is inherited in an autosomal dominant pattern, which means an alteration in one copy of either the ABCA1 or the APOA1 gene in each cell is sufficient to cause the disorder. People with alterations in both copies of the ABCA1 gene develop the related disorder Tangier disease.",familial HDL deficiency,0000350,GHR,https://ghr.nlm.nih.gov/condition/familial-hdl-deficiency,C2931838,T047,Disorders
What are the treatments for familial HDL deficiency ?,0000350-5,treatment,These resources address the diagnosis or management of familial HDL deficiency:  - Genetic Testing Registry: Familial hypoalphalipoproteinemia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,familial HDL deficiency,0000350,GHR,https://ghr.nlm.nih.gov/condition/familial-hdl-deficiency,C2931838,T047,Disorders
What is (are) familial hemiplegic migraine ?,0000351-1,information,"Familial hemiplegic migraine is a form of migraine headache that runs in families. Migraines usually cause intense, throbbing pain in one area of the head, often accompanied by nausea, vomiting, and extreme sensitivity to light and sound. These recurrent headaches typically begin in childhood or adolescence and can be triggered by certain foods, emotional stress, and minor head trauma. Each headache may last from a few hours to a few days.  In some types of migraine, including familial hemiplegic migraine, a pattern of neurological symptoms called an aura precedes the headache. The most common symptoms associated with an aura are temporary visual changes such as blind spots (scotomas), flashing lights, zig-zagging lines, and double vision. In people with familial hemiplegic migraine, auras are also characterized by temporary numbness or weakness, often affecting one side of the body (hemiparesis). Additional features of an aura can include difficulty with speech, confusion, and drowsiness. An aura typically develops gradually over a few minutes and lasts about an hour.  Unusually severe migraine episodes have been reported in some people with familial hemiplegic migraine. These episodes have included fever, seizures, prolonged weakness, coma, and, rarely, death. Although most people with familial hemiplegic migraine recover completely between episodes, neurological symptoms such as memory loss and problems with attention can last for weeks or months. About 20 percent of people with this condition develop mild but permanent difficulty coordinating movements (ataxia), which may worsen with time, and rapid, involuntary eye movements called nystagmus.",familial hemiplegic migraine,0000351,GHR,https://ghr.nlm.nih.gov/condition/familial-hemiplegic-migraine,C0338484,T047,Disorders
How many people are affected by familial hemiplegic migraine ?,0000351-2,frequency,"The worldwide prevalence of familial hemiplegic migraine is unknown. Studies suggest that in Denmark about 1 in 10,000 people have hemiplegic migraine and that the condition occurs equally in families with multiple affected individuals (familial hemiplegic migraine) and in individuals with no family history of the condition (sporadic hemiplegic migraine). Like other forms of migraine, familial hemiplegic migraine affects females more often than males.",familial hemiplegic migraine,0000351,GHR,https://ghr.nlm.nih.gov/condition/familial-hemiplegic-migraine,C0338484,T047,Disorders
What are the genetic changes related to familial hemiplegic migraine ?,0000351-3,genetic changes,"Mutations in the CACNA1A, ATP1A2, SCN1A, and PRRT2 genes have been found to cause familial hemiplegic migraine. The first three genes provide instructions for making proteins that are involved in the transport of charged atoms (ions) across cell membranes. The movement of these ions is critical for normal signaling between nerve cells (neurons) in the brain and other parts of the nervous system. The function of the protein produced from the PRRT2 gene is unknown, although studies suggest it interacts with a protein that helps control signaling between neurons.  Communication between neurons depends on chemicals called neurotransmitters, which are released from one neuron and taken up by neighboring neurons. Researchers believe that mutations in the CACNA1A, ATP1A2, and SCN1A genes can upset the balance of ions in neurons, which disrupts the normal release and uptake of certain neurotransmitters in the brain. Although the mechanism is unknown, researchers speculate that mutations in the PRRT2 gene, which reduce the amount of PRRT2 protein, also disrupt normal control of neurotransmitter release. The resulting changes in signaling between neurons lead people with familial hemiplegic migraine to develop these severe headaches.  There is little evidence that mutations in the CACNA1A, ATP1A2, SCN1A, and PRRT2 genes play a role in common migraines, which affect millions of people each year. Researchers are searching for additional genetic changes that may underlie rare types of migraine, such as familial hemiplegic migraine, as well as the more common forms of migraine.",familial hemiplegic migraine,0000351,GHR,https://ghr.nlm.nih.gov/condition/familial-hemiplegic-migraine,C0338484,T047,Disorders
Is familial hemiplegic migraine inherited ?,0000351-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, affected individuals have one affected parent. However, some people who inherit an altered gene never develop features of familial hemiplegic migraine. (This situation is known as reduced penetrance.) A related condition, sporadic hemiplegic migraine, has identical signs and symptoms but occurs in individuals with no history of the disorder in their family.",familial hemiplegic migraine,0000351,GHR,https://ghr.nlm.nih.gov/condition/familial-hemiplegic-migraine,C0338484,T047,Disorders
What are the treatments for familial hemiplegic migraine ?,0000351-5,treatment,These resources address the diagnosis or management of familial hemiplegic migraine:  - Gene Review: Gene Review: Familial Hemiplegic Migraine  - Genetic Testing Registry: Familial hemiplegic migraine  - Genetic Testing Registry: Familial hemiplegic migraine type 1  - Genetic Testing Registry: Familial hemiplegic migraine type 2  - Genetic Testing Registry: Familial hemiplegic migraine type 3   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,familial hemiplegic migraine,0000351,GHR,https://ghr.nlm.nih.gov/condition/familial-hemiplegic-migraine,C0338484,T047,Disorders
What is (are) familial hemophagocytic lymphohistiocytosis ?,0000352-1,information,"Familial hemophagocytic lymphohistiocytosis is a disorder in which the immune system produces too many activated immune cells (lymphocytes) called T cells, natural killer cells, B cells, and macrophages (histiocytes). Excessive amounts of immune system proteins called cytokines are also produced. This overactivation of the immune system causes fever and damages the liver and spleen, resulting in enlargement of these organs.  Familial hemophagocytic lymphohistiocytosis also destroys blood-producing cells in the bone marrow, a process called hemophagocytosis. As a result, affected individuals have low numbers of red blood cells (anemia) and a reduction in the number of blood cells involved in clotting (platelets). A reduction in platelets may cause easy bruising and abnormal bleeding.  The brain may also be affected in familial hemophagocytic lymphohistiocytosis. As a result, affected individuals may experience irritability, delayed closure of the bones of the skull in infants, neck stiffness, abnormal muscle tone, impaired muscle coordination, paralysis, blindness, seizures, and coma. In addition to neurological problems, familial hemophagocytic lymphohistiocytosis can cause abnormalities of the heart, kidneys, and other organs and tissues. Affected individuals also have an increased risk of developing cancers of blood-forming cells (leukemia and lymphoma).  Signs and symptoms of familial hemophagocytic lymphohistiocytosis usually become apparent during infancy, although occasionally they appear later in life. They usually occur when the immune system launches an exaggerated response to an infection, but may also occur in the absence of infection. Without treatment, most people with familial hemophagocytic lymphohistiocytosis survive only a few months.",familial hemophagocytic lymphohistiocytosis,0000352,GHR,https://ghr.nlm.nih.gov/condition/familial-hemophagocytic-lymphohistiocytosis,C0272199,T046,Disorders
How many people are affected by familial hemophagocytic lymphohistiocytosis ?,0000352-2,frequency,"Familial hemophagocytic lymphohistiocytosis occurs in approximately 1 in 50,000 individuals worldwide.",familial hemophagocytic lymphohistiocytosis,0000352,GHR,https://ghr.nlm.nih.gov/condition/familial-hemophagocytic-lymphohistiocytosis,C0272199,T046,Disorders
What are the genetic changes related to familial hemophagocytic lymphohistiocytosis ?,0000352-3,genetic changes,"Familial hemophagocytic lymphohistiocytosis may be caused by mutations in any of several genes. These genes provide instructions for making proteins that help destroy or deactivate lymphocytes that are no longer needed. By controlling the number of activated lymphocytes, these genes help regulate immune system function.  Approximately 40 to 60 percent of cases of familial hemophagocytic lymphohistiocytosis are caused by mutations in the PRF1 or UNC13D genes. Smaller numbers of cases are caused by mutations in other known genes. In some affected individuals, the genetic cause of the disorder is unknown.  The gene mutations that cause familial hemophagocytic lymphohistiocytosis impair the body's ability to regulate the immune system. These changes result in the exaggerated immune response characteristic of this condition.",familial hemophagocytic lymphohistiocytosis,0000352,GHR,https://ghr.nlm.nih.gov/condition/familial-hemophagocytic-lymphohistiocytosis,C0272199,T046,Disorders
Is familial hemophagocytic lymphohistiocytosis inherited ?,0000352-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",familial hemophagocytic lymphohistiocytosis,0000352,GHR,https://ghr.nlm.nih.gov/condition/familial-hemophagocytic-lymphohistiocytosis,C0272199,T046,Disorders
What are the treatments for familial hemophagocytic lymphohistiocytosis ?,0000352-5,treatment,"These resources address the diagnosis or management of familial hemophagocytic lymphohistiocytosis:  - Gene Review: Gene Review: Hemophagocytic Lymphohistiocytosis, Familial  - Genetic Testing Registry: Familial hemophagocytic lymphohistiocytosis  - Genetic Testing Registry: Hemophagocytic lymphohistiocytosis, familial, 2  - Genetic Testing Registry: Hemophagocytic lymphohistiocytosis, familial, 3  - Genetic Testing Registry: Hemophagocytic lymphohistiocytosis, familial, 4  - Genetic Testing Registry: Hemophagocytic lymphohistiocytosis, familial, 5  - The Merck Manual for Healthcare Professionals  - University of Minnesota: Pediatric Blood & Marrow Transplantation Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",familial hemophagocytic lymphohistiocytosis,0000352,GHR,https://ghr.nlm.nih.gov/condition/familial-hemophagocytic-lymphohistiocytosis,C0272199,T046,Disorders
What is (are) familial hyperaldosteronism ?,0000353-1,information,"Familial hyperaldosteronism is a group of inherited conditions in which the adrenal glands, which are small glands located on top of each kidney, produce too much of the hormone aldosterone. Aldosterone helps control the amount of salt retained by the kidneys. Excess aldosterone causes the kidneys to retain more salt than normal, which in turn increases the body's fluid levels and blood pressure. People with familial hyperaldosteronism may develop severe high blood pressure (hypertension), often early in life. Without treatment, hypertension increases the risk of strokes, heart attacks, and kidney failure.  Familial hyperaldosteronism is categorized into three types, distinguished by their clinical features and genetic causes. In familial hyperaldosteronism type I, hypertension generally appears in childhood to early adulthood and can range from mild to severe. This type can be treated with steroid medications called glucocorticoids, so it is also known as glucocorticoid-remediable aldosteronism (GRA). In familial hyperaldosteronism type II, hypertension usually appears in early to middle adulthood and does not improve with glucocorticoid treatment. In most individuals with familial hyperaldosteronism type III, the adrenal glands are enlarged up to six times their normal size. These affected individuals have severe hypertension that starts in childhood. The hypertension is difficult to treat and often results in damage to organs such as the heart and kidneys. Rarely, individuals with type III have milder symptoms with treatable hypertension and no adrenal gland enlargement.  There are other forms of hyperaldosteronism that are not familial. These conditions are caused by various problems in the adrenal glands or kidneys. In some cases, a cause for the increase in aldosterone levels cannot be found.",familial hyperaldosteronism,0000353,GHR,https://ghr.nlm.nih.gov/condition/familial-hyperaldosteronism,C3713420,T047,Disorders
How many people are affected by familial hyperaldosteronism ?,0000353-2,frequency,The prevalence of familial hyperaldosteronism is unknown. Familial hyperaldosteronism type II appears to be the most common variety. All types of familial hyperaldosteronism combined account for fewer than 1 out of 10 cases of hyperaldosteronism.,familial hyperaldosteronism,0000353,GHR,https://ghr.nlm.nih.gov/condition/familial-hyperaldosteronism,C3713420,T047,Disorders
What are the genetic changes related to familial hyperaldosteronism ?,0000353-3,genetic changes,"The various types of familial hyperaldosteronism have different genetic causes. Familial hyperaldosteronism type I is caused by the abnormal joining together (fusion) of two similar genes called CYP11B1 and CYP11B2, which are located close together on chromosome 8. These genes provide instructions for making two enzymes that are found in the adrenal glands.  The CYP11B1 gene provides instructions for making an enzyme called 11-beta-hydroxylase. This enzyme helps produce hormones called cortisol and corticosterone. The CYP11B2 gene provides instructions for making another enzyme called aldosterone synthase, which helps produce aldosterone. When CYP11B1 and CYP11B2 are abnormally fused together, too much aldosterone synthase is produced. This overproduction causes the adrenal glands to make excess aldosterone, which leads to the signs and symptoms of familial hyperaldosteronism type I.  Familial hyperaldosteronism type III is caused by mutations in the KCNJ5 gene. The KCNJ5 gene provides instructions for making a protein that functions as a potassium channel, which means that it transports positively charged atoms (ions) of potassium into and out of cells. In the adrenal glands,the flow of ions through potassium channels produced from the KCNJ5 gene is thought to help regulate the production of aldosterone. Mutations in the KCNJ5 gene likely result in the production of potassium channels that are less selective, allowing other ions (predominantly sodium) to pass as well. The abnormal ion flow results in the activation of biochemical processes (pathways) that lead to increased aldosterone production, causing the hypertension associated with familial hyperaldosteronism type III.  The genetic cause of familial hyperaldosteronism type II is unknown.",familial hyperaldosteronism,0000353,GHR,https://ghr.nlm.nih.gov/condition/familial-hyperaldosteronism,C3713420,T047,Disorders
Is familial hyperaldosteronism inherited ?,0000353-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",familial hyperaldosteronism,0000353,GHR,https://ghr.nlm.nih.gov/condition/familial-hyperaldosteronism,C3713420,T047,Disorders
What are the treatments for familial hyperaldosteronism ?,0000353-5,treatment,These resources address the diagnosis or management of familial hyperaldosteronism:  - Genetic Testing Registry: Familial hyperaldosteronism type 1  - Genetic Testing Registry: Familial hyperaldosteronism type 3  - Hormone Health Network: A Patient's Guide: Primary Hyperaldosteronism  - International Registry for Glucocorticoid-Remediable Aldosteronism  - MedlinePlus Encyclopedia: Aldosterone   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,familial hyperaldosteronism,0000353,GHR,https://ghr.nlm.nih.gov/condition/familial-hyperaldosteronism,C3713420,T047,Disorders
What is (are) familial hypertrophic cardiomyopathy ?,0000354-1,information,"Familial hypertrophic cardiomyopathy is a heart condition characterized by thickening (hypertrophy) of the heart (cardiac) muscle. Thickening usually occurs in the interventricular septum, which is the muscular wall that separates the lower left chamber of the heart (the left ventricle) from the lower right chamber (the right ventricle). In some people, thickening of the interventricular septum impedes the flow of oxygen-rich blood from the heart, which may lead to an abnormal heart sound during a heartbeat (heart murmur) and other signs and symptoms of the condition. Other affected individuals do not have physical obstruction of blood flow, but the pumping of blood is less efficient, which can also lead to symptoms of the condition. Cardiac hypertrophy often begins in adolescence or young adulthood, although it can develop at any time throughout life.  The symptoms of familial hypertrophic cardiomyopathy are variable, even within the same family. Many affected individuals have no symptoms. Other people with familial hypertrophic cardiomyopathy may experience chest pain; shortness of breath, especially with physical exertion; a sensation of fluttering or pounding in the chest (palpitations); lightheadedness; dizziness; and fainting.  While most people with familial hypertrophic cardiomyopathy are symptom-free or have only mild symptoms, this condition can have serious consequences. It can cause abnormal heart rhythms (arrhythmias) that may be life threatening. People with familial hypertrophic cardiomyopathy have an increased risk of sudden death, even if they have no other symptoms of the condition. A small number of affected individuals develop potentially fatal heart failure, which may require heart transplantation.",familial hypertrophic cardiomyopathy,0000354,GHR,https://ghr.nlm.nih.gov/condition/familial-hypertrophic-cardiomyopathy,C0949658,T047,Disorders
How many people are affected by familial hypertrophic cardiomyopathy ?,0000354-2,frequency,Familial hypertrophic cardiomyopathy affects an estimated 1 in 500 people worldwide. It is the most common genetic heart disease in the United States.,familial hypertrophic cardiomyopathy,0000354,GHR,https://ghr.nlm.nih.gov/condition/familial-hypertrophic-cardiomyopathy,C0949658,T047,Disorders
What are the genetic changes related to familial hypertrophic cardiomyopathy ?,0000354-3,genetic changes,"Mutations in one of several genes can cause familial hypertrophic cardiomyopathy; the most commonly involved genes are MYH7, MYBPC3, TNNT2, and TNNI3. Other genes, including some that have not been identified, may also be involved in this condition.  The proteins produced from the genes associated with familial hypertrophic cardiomyopathy play important roles in contraction of the heart muscle by forming muscle cell structures called sarcomeres. Sarcomeres, which are the basic units of muscle contraction, are made up of thick and thin protein filaments. The overlapping thick and thin filaments attach to each other and release, which allows the filaments to move relative to one another so that muscles can contract. In the heart, regular contractions of cardiac muscle pump blood to the rest of the body.  The protein produced from the MYH7 gene, called cardiac beta ()-myosin heavy chain, is the major component of the thick filament in sarcomeres. The protein produced from the MYBPC3 gene, cardiac myosin binding protein C, associates with the thick filament, providing structural support and helping to regulate muscle contractions.  The TNNT2 and TNNI3 genes provide instructions for making cardiac troponin T and cardiac troponin I, respectively, which are two of the three proteins that make up the troponin protein complex found in cardiac muscle cells. The troponin complex associates with the thin filament of sarcomeres. It controls muscle contraction and relaxation by regulating the interaction of the thick and thin filaments.  It is unknown how mutations in sarcomere-related genes lead to hypertrophy of the heart muscle and problems with heart rhythm. The mutations may result in an altered sarcomere protein or reduce the amount of the protein. An abnormality in or shortage of any one of these proteins may impair the function of the sarcomere, disrupting normal cardiac muscle contraction. Research shows that, in affected individuals, contraction and relaxation of the heart muscle is abnormal, even before hypertrophy develops. However, it is not clear how these contraction problems are related to hypertrophy or the symptoms of familial hypertrophic cardiomyopathy.",familial hypertrophic cardiomyopathy,0000354,GHR,https://ghr.nlm.nih.gov/condition/familial-hypertrophic-cardiomyopathy,C0949658,T047,Disorders
Is familial hypertrophic cardiomyopathy inherited ?,0000354-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Rarely, both copies of the gene are altered, leading to more severe signs and symptoms.  In most cases, an affected person has one parent with the condition.",familial hypertrophic cardiomyopathy,0000354,GHR,https://ghr.nlm.nih.gov/condition/familial-hypertrophic-cardiomyopathy,C0949658,T047,Disorders
What are the treatments for familial hypertrophic cardiomyopathy ?,0000354-5,treatment,These resources address the diagnosis or management of familial hypertrophic cardiomyopathy:  - Cleveland Clinic  - Gene Review: Gene Review: Hypertrophic Cardiomyopathy Overview  - Genetic Testing Registry: Familial hypertrophic cardiomyopathy 1  - Genetic Testing Registry: Familial hypertrophic cardiomyopathy 2  - Genetic Testing Registry: Familial hypertrophic cardiomyopathy 4  - Genetic Testing Registry: Familial hypertrophic cardiomyopathy 7  - MedlinePlus Encyclopedia: Hypertrophic Cardiomyopathy  - Stanford University Hospitals and Clinics  - The Sarcomeric Human Cardiomyopathies Registry (ShaRe)   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,familial hypertrophic cardiomyopathy,0000354,GHR,https://ghr.nlm.nih.gov/condition/familial-hypertrophic-cardiomyopathy,C0949658,T047,Disorders
What is (are) familial hypobetalipoproteinemia ?,0000355-1,information,"Familial hypobetalipoproteinemia (FHBL) is a disorder that impairs the body's ability to absorb and transport fats. This condition is characterized by low levels of a fat-like substance called cholesterol in the blood. The severity of signs and symptoms experienced by people with FHBL vary widely. The most mildly affected individuals have few problems with absorbing fats from the diet and no related signs and symptoms. Many individuals with FHBL develop an abnormal buildup of fats in the liver called hepatic steatosis or fatty liver. In more severely affected individuals, fatty liver may progress to chronic liver disease (cirrhosis). Individuals with severe FHBL have greater difficulty absorbing fats as well as fat-soluble vitamins such as vitamin E and vitamin A. This difficulty in fat absorption leads to excess fat in the feces (steatorrhea). In childhood, these digestive problems can result in an inability to grow or gain weight at the expected rate (failure to thrive).",familial hypobetalipoproteinemia,0000355,GHR,https://ghr.nlm.nih.gov/condition/familial-hypobetalipoproteinemia,C1862596,T047,Disorders
How many people are affected by familial hypobetalipoproteinemia ?,0000355-2,frequency,"FHBL is estimated to occur in 1 in 1,000 to 3,000 individuals.",familial hypobetalipoproteinemia,0000355,GHR,https://ghr.nlm.nih.gov/condition/familial-hypobetalipoproteinemia,C1862596,T047,Disorders
What are the genetic changes related to familial hypobetalipoproteinemia ?,0000355-3,genetic changes,"Most cases of FHBL are caused by mutations in the APOB gene. This gene provides instructions for making two versions of the apolipoprotein B protein: a short version called apolipoprotein B-48 and a longer version known as apolipoprotein B-100. Both of these proteins are components of lipoproteins, which transport fats and cholesterol in the blood.  Most APOB gene mutations that lead to FHBL cause both versions of apolipoprotein B to be abnormally short. The severity of the condition largely depends on the length of these two versions of apolipoprotein B. Severely shortened versions cannot partner with lipoproteins and transport fats and cholesterol. Proteins that are only slightly shortened retain some function but partner less effectively with lipoproteins. Generally, the signs and symptoms of FHBL are worse if both versions of apolipoprotein B are severely shortened. Mild or no signs and symptoms result when the proteins are only slightly shortened. All of these protein changes lead to a reduction of functional apolipoprotein B. As a result, the transportation of dietary fats and cholesterol is decreased or absent. A decrease in fat transport reduces the body's ability to absorb fats and fat-soluble vitamins from the diet.  Although APOB gene mutations are responsible for most cases of FHBL, mutations in a few other genes account for a small number of cases. Some people with FHBL do not have identified mutations in any of these genes. Changes in other, unidentified genes are likely involved in this condition.",familial hypobetalipoproteinemia,0000355,GHR,https://ghr.nlm.nih.gov/condition/familial-hypobetalipoproteinemia,C1862596,T047,Disorders
Is familial hypobetalipoproteinemia inherited ?,0000355-4,inheritance,"This condition is inherited in an autosomal codominant pattern. Codominance means that copies of the gene from both parents are active (expressed), and both copies influence the genetic trait. In FHBL, a change in one copy of the APOB gene in each cell can cause the condition, but changes in both copies of the gene cause more severe health problems.",familial hypobetalipoproteinemia,0000355,GHR,https://ghr.nlm.nih.gov/condition/familial-hypobetalipoproteinemia,C1862596,T047,Disorders
What are the treatments for familial hypobetalipoproteinemia ?,0000355-5,treatment,"These resources address the diagnosis or management of familial hypobetalipoproteinemia:  - Genetic Testing Registry: Familial hypobetalipoproteinemia  - Genetic Testing Registry: Hypobetalipoproteinemia, familial, 2   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",familial hypobetalipoproteinemia,0000355,GHR,https://ghr.nlm.nih.gov/condition/familial-hypobetalipoproteinemia,C1862596,T047,Disorders
What is (are) familial idiopathic basal ganglia calcification ?,0000356-1,information,"Familial idiopathic basal ganglia calcification (FIBGC, formerly known as Fahr disease) is a condition characterized by abnormal deposits of calcium (calcification) in the brain. These calcium deposits typically occur in the basal ganglia, which are structures deep within the brain that help start and control movement; however, other brain regions can also be affected.  The signs and symptoms of FIBGC include movement disorders and psychiatric or behavioral difficulties. These problems begin in adulthood, usually in a person's thirties. The movement difficulties experienced by people with FIBGC include involuntary tensing of various muscles (dystonia), problems coordinating movements (ataxia), and uncontrollable movements of the limbs (choreoathetosis). Affected individuals often have seizures as well. The psychiatric and behavioral problems include difficulty concentrating, memory loss, changes in personality, a distorted view of reality (psychosis), and decline in intellectual function (dementia). An estimated 20 to 30 percent of people with FIBGC have one of these psychiatric disorders.  The severity of this condition varies among affected individuals; some people have no symptoms related to the brain calcification, whereas other people have significant movement and psychiatric problems.",familial idiopathic basal ganglia calcification,0000356,GHR,https://ghr.nlm.nih.gov/condition/familial-idiopathic-basal-ganglia-calcification,C0393590,T047,Disorders
How many people are affected by familial idiopathic basal ganglia calcification ?,0000356-2,frequency,"FIBGC is thought to be a rare disorder; about 60 affected families have been described in the medical literature. However, because brain imaging tests are needed to recognize the calcium deposits, this condition is believed to be underdiagnosed.",familial idiopathic basal ganglia calcification,0000356,GHR,https://ghr.nlm.nih.gov/condition/familial-idiopathic-basal-ganglia-calcification,C0393590,T047,Disorders
What are the genetic changes related to familial idiopathic basal ganglia calcification ?,0000356-3,genetic changes,"Mutations in the SLC20A2 gene cause nearly half of all cases of FIBGC. A small percentage of cases are caused by mutations in the PDGFRB gene. Other cases of FIBGC appear to be associated with changes in chromosomes 2, 7, 9, and 14, although specific genes have yet to be identified. These findings suggest that multiple genes are involved in this condition.  The SLC20A2 gene provides instructions for making a protein called sodium-dependent phosphate transporter 2 (PiT-2). This protein plays a major role in regulating phosphate levels within the body (phosphate homeostasis) by transporting phosphate across cell membranes. The SLC20A2 gene mutations that cause FIBGC lead to the production of a PiT-2 protein that cannot effectively transport phosphate into cells. As a result, phosphate levels in the bloodstream rise. In the brain, the excess phosphate combines with calcium and forms deposits.  The PDGFRB gene provides instructions for making a protein that plays a role in turning on (activating) signaling pathways that control many cell processes. It is unclear how PDGFRB gene mutations cause FIBGC. Mutations may alter signaling within cells that line blood vessels in the brain, causing them to take in excess calcium, and leading to calcification of the lining of these blood vessels. Alternatively, changes in the PDGFRB protein could alter phosphate transport signaling pathways, causing an increase in phosphate levels and the formation of calcium deposits.  Researchers suggest that calcium deposits lead to the characteristic features of FIBGC by interrupting signaling pathways in various parts of the brain. Calcium deposits may disrupt the pathways that connect the basal ganglia to other areas of the brain, particularly the frontal lobes. These areas at the front of the brain are involved in reasoning, planning, judgment, and problem-solving. The regions of the brain that regulate social behavior, mood, and motivation may also be affected.  Research has shown that people with significant calcification tend to have more signs and symptoms of FIBGC than people with little or no calcification. However, this association does not apply to all people with FIBGC.",familial idiopathic basal ganglia calcification,0000356,GHR,https://ghr.nlm.nih.gov/condition/familial-idiopathic-basal-ganglia-calcification,C0393590,T047,Disorders
Is familial idiopathic basal ganglia calcification inherited ?,0000356-4,inheritance,"FIBGC is inherited in an autosomal dominant pattern. Autosomal dominant inheritance means one copy of an altered SLC20A2 or PDGFRB gene in each cell is sufficient to cause the disorder. This condition appears to follow an autosomal dominant pattern of inheritance when the genetic cause is not known. In most cases, an affected person has one parent with the condition.",familial idiopathic basal ganglia calcification,0000356,GHR,https://ghr.nlm.nih.gov/condition/familial-idiopathic-basal-ganglia-calcification,C0393590,T047,Disorders
What are the treatments for familial idiopathic basal ganglia calcification ?,0000356-5,treatment,"These resources address the diagnosis or management of FIBGC:  - Dystonia Medical Research Foundation: Treatments  - Gene Review: Gene Review: Primary Familial Brain Calcification  - Genetic Testing Registry: Basal ganglia calcification, idiopathic, 2  - Genetic Testing Registry: Basal ganglia calcification, idiopathic, 4  - Genetic Testing Registry: Idiopathic basal ganglia calcification 1   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",familial idiopathic basal ganglia calcification,0000356,GHR,https://ghr.nlm.nih.gov/condition/familial-idiopathic-basal-ganglia-calcification,C0393590,T047,Disorders
What is (are) familial isolated hyperparathyroidism ?,0000357-1,information,"Familial isolated hyperparathyroidism is an inherited condition characterized by overactivity of the parathyroid glands (hyperparathyroidism). The four parathyroid glands are located in the neck, and they release a hormone called parathyroid hormone that regulates the amount of calcium in the blood. In familial isolated hyperparathyroidism, one or more overactive parathyroid glands release excess parathyroid hormone, which causes the levels of calcium in the blood to rise (hypercalcemia). Parathyroid hormone stimulates the removal of calcium from bone and the absorption of calcium from the diet, and the mineral is then released into the bloodstream.  In people with familial isolated hyperparathyroidism, the production of excess parathyroid hormone is caused by tumors that involve the parathyroid glands. Typically only one of the four parathyroid glands is affected, but in some people, more than one gland develops a tumor. The tumors are usually noncancerous (benign), in which case they are called adenomas. Rarely, people with familial isolated hyperparathyroidism develop a cancerous tumor called parathyroid carcinoma. Because the production of excess parathyroid hormone is caused by abnormalities of the parathyroid glands, familial isolated hyperparathyroidism is considered a form of primary hyperparathyroidism.  Disruption of the normal calcium balance resulting from overactive parathyroid glands causes many of the common signs and symptoms of familial isolated hyperparathyroidism, such as kidney stones, nausea, vomiting, high blood pressure (hypertension), weakness, and fatigue. Because calcium is removed from bones to be released into the bloodstream, hyperparathyroidism often causes thinning of the bones (osteoporosis). The age at which familial isolated hyperparathyroidism is diagnosed varies from childhood to adulthood. Often, the first indication of the condition is elevated calcium levels identified through a routine blood test, even though the affected individual may not yet have signs or symptoms of hyperparathyroidism or hypercalcemia.",familial isolated hyperparathyroidism,0000357,GHR,https://ghr.nlm.nih.gov/condition/familial-isolated-hyperparathyroidism,C1840402,T047,Disorders
How many people are affected by familial isolated hyperparathyroidism ?,0000357-2,frequency,The prevalence of familial isolated hyperparathyroidism is unknown.,familial isolated hyperparathyroidism,0000357,GHR,https://ghr.nlm.nih.gov/condition/familial-isolated-hyperparathyroidism,C1840402,T047,Disorders
What are the genetic changes related to familial isolated hyperparathyroidism ?,0000357-3,genetic changes,"Familial isolated hyperparathyroidism can be caused by mutations in the MEN1, CDC73, or CASR gene.  The MEN1 gene provides instructions for producing a protein called menin. Menin acts as a tumor suppressor, which means it normally keeps cells from growing and dividing (proliferating) too rapidly or in an uncontrolled way. In familial isolated hyperparathyroidism, MEN1 gene mutations result in an altered menin protein that is no longer able to control cell growth and division. The resulting increase in cell proliferation leads to the formation of an adenoma involving one or more parathyroid glands. Overproduction of parathyroid hormone from these abnormal glands stimulates the release of excess calcium into the blood, leading to the signs and symptoms of familial isolated hyperparathyroidism. It is unclear why this condition affects only the parathyroid glands.  The CDC73 gene provides instructions for making the parafibromin protein, which is also thought to act as a tumor suppressor. Parafibromin is likely involved in regulating the activity of other genes (gene transcription) and in cell proliferation. CDC73 gene mutations that cause familial isolated hyperparathyroidism likely result in decreased activity of the parafibromin protein. The loss of parafibromin's tumor suppressor function can lead to the development of parathyroid adenoma or, rarely, parathyroid carcinoma.  The CASR gene provides instructions for producing a protein called the calcium-sensing receptor (CaSR), which helps regulate the amount of calcium in the body, in part by controlling the production of parathyroid hormone. Calcium molecules attach (bind) to CaSR, turning on (activating) the receptor. When calcium binds to the CaSR protein in cells of the parathyroid gland, the activated receptor sends signals that block the production and release of parathyroid hormone. Without parathyroid hormone, calcium is not released into the blood. CASR gene mutations associated with familial isolated hyperparathyroidism lead to the production of a less sensitive CaSR that requires an abnormally high concentration of calcium to trigger signaling. As a result, parathyroid hormone is produced even when the concentration of calcium in the blood is elevated, allowing the calcium levels to continue to rise. A small number of individuals with CASR-related familial isolated hyperparathyroidism have enlarged parathyroid glands, and overproduction of parathyroid hormone from these abnormal glands further contributes to the elevated calcium levels in the bloodstream. The excess calcium causes the characteristic features of this condition.  Mutations in the MEN1 gene and the CDC73 gene are involved in other conditions in which hyperparathyroidism is just one of many features. However, some people with mutations in these genes have only signs and symptoms related to hyperparathyroidism (isolated hyperparathyroidism) without the additional features of these other conditions. While some individuals later develop additional signs and symptoms of the other conditions, others do not. Familial isolated hyperparathyroidism may be a milder variant or early form of the other conditions.  In many individuals with the signs and symptoms of familial isolated hyperparathyroidism, a mutation in the MEN1, CDC73, or CASR gene has not been identified, indicating that other genes may be involved in this condition. The genetic cause of these cases is unknown.",familial isolated hyperparathyroidism,0000357,GHR,https://ghr.nlm.nih.gov/condition/familial-isolated-hyperparathyroidism,C1840402,T047,Disorders
Is familial isolated hyperparathyroidism inherited ?,0000357-4,inheritance,"This condition is typically inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",familial isolated hyperparathyroidism,0000357,GHR,https://ghr.nlm.nih.gov/condition/familial-isolated-hyperparathyroidism,C1840402,T047,Disorders
What are the treatments for familial isolated hyperparathyroidism ?,0000357-5,treatment,These resources address the diagnosis or management of familial isolated hyperparathyroidism:  - Cleveland Clinic: Hyperparathyroidism  - Gene Review: Gene Review: CDC73-Related Disorders  - Genetic Testing Registry: Hyperparathyroidism 1  - MedlinePlus Encyclopedia: Hyperparathyroidism   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,familial isolated hyperparathyroidism,0000357,GHR,https://ghr.nlm.nih.gov/condition/familial-isolated-hyperparathyroidism,C1840402,T047,Disorders
What is (are) familial isolated pituitary adenoma ?,0000358-1,information,"Familial isolated pituitary adenoma (FIPA) is an inherited condition characterized by development of a noncancerous tumor in the pituitary gland (called a pituitary adenoma). The pituitary gland, which is found at the base of the brain, produces hormones that control many important body functions.  Tumors that form in the pituitary gland can release excess levels of one or more hormones, although some tumors do not produce hormones (nonfunctioning pituitary adenomas). Those that do are typically distinguished by the particular hormones they produce. Prolactinomas are the most common tumors in FIPA. These tumors release prolactin, a hormone that stimulates breast milk production in females. Both women and men can develop prolactinomas, although they are more common in women. In women, these tumors may lead to changes in the menstrual cycle or difficulty becoming pregnant. Some affected women may produce breast milk, even though they are not pregnant or nursing. In men, prolactinomas may cause erectile dysfunction or decreased interest in sex. Rarely, affected men produce breast milk. Large prolactinomas can press on nearby tissues such as the nerves that carry information from the eyes to the brain (the optic nerves), causing problems with vision.  Another type of tumor called somatotropinoma is also common in FIPA. These tumors release growth hormone (also called somatotropin), which promotes growth of the body. Somatotropinomas in children or adolescents can lead to increased height (gigantism), because the long bones of their arms and legs are still growing. In adults, growth of the long bones has stopped, but the tumors can cause overgrowth of the hands, feet, and face (acromegaly) as well as other tissues.  Less common tumor types in FIPA include somatolactotropinomas, nonfunctioning pituitary adenomas, adrenocorticotropic hormone-secreting tumors (which cause a condition known as Cushing disease), thyrotropinomas, and gonadotropinomas. In a family with the condition, affected members can develop the same type of tumor (homogenous FIPA) or different types (heterogenous FIPA).  In FIPA, pituitary tumors usually occur at a younger age than sporadic pituitary adenomas, which are not inherited. In general, FIPA tumors are also larger than sporadic pituitary tumors. Often, people with FIPA have macroadenomas, which are tumors larger than 10 millimeters.  Familial pituitary adenomas can occur as one of many features in other inherited conditions such as multiple endocrine neoplasia type 1 and Carney complex; however, in FIPA, the pituitary adenomas are described as isolated because only the pituitary gland is affected.",familial isolated pituitary adenoma,0000358,GHR,https://ghr.nlm.nih.gov/condition/familial-isolated-pituitary-adenoma,C2676191,T191,Disorders
How many people are affected by familial isolated pituitary adenoma ?,0000358-2,frequency,"Pituitary adenomas, including sporadic tumors, are relatively common; they are identified in an estimated 1 in 1,000 people. FIPA, though, is quite rare, accounting for approximately 2 percent of pituitary adenomas. More than 200 families with FIPA have been described in the medical literature.",familial isolated pituitary adenoma,0000358,GHR,https://ghr.nlm.nih.gov/condition/familial-isolated-pituitary-adenoma,C2676191,T191,Disorders
What are the genetic changes related to familial isolated pituitary adenoma ?,0000358-3,genetic changes,"FIPA can be caused by mutations in the AIP gene. The function of the protein produced from this gene is not well understood, but it is thought to act as a tumor suppressor, which means it helps prevent cells from growing and dividing in an uncontrolled way. Mutations in the AIP gene alter the protein or reduce the production of functional protein. These changes likely impair the ability of the AIP protein to control the growth and division of cells, allowing pituitary cells to grow and divide unchecked and form a tumor. It is not known why the pituitary gland is specifically affected or why certain types of pituitary adenomas develop.  AIP gene mutations account for approximately 15 to 25 percent of cases of FIPA. Somatotropinomas are the most common type of tumor in these individuals. The tumors usually occur at a younger age, often in childhood, and are larger than FIPA tumors not caused by AIP gene mutations. The other genetic causes of FIPA are unknown.",familial isolated pituitary adenoma,0000358,GHR,https://ghr.nlm.nih.gov/condition/familial-isolated-pituitary-adenoma,C2676191,T191,Disorders
Is familial isolated pituitary adenoma inherited ?,0000358-4,inheritance,"FIPA is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. However, only 20 to 30 percent of individuals with an AIP gene mutation develop a pituitary adenoma. This phenomenon, in which some individuals with a mutation do not develop the features of a particular disorder, is called incomplete penetrance.",familial isolated pituitary adenoma,0000358,GHR,https://ghr.nlm.nih.gov/condition/familial-isolated-pituitary-adenoma,C2676191,T191,Disorders
What are the treatments for familial isolated pituitary adenoma ?,0000358-5,treatment,These resources address the diagnosis or management of familial isolated pituitary adenoma:  - American Cancer Society: How are Pituitary Tumors Diagnosed?  - Gene Review: Gene Review: AIP-Related Familial Isolated Pituitary Adenomas  - Genetic Testing Registry: AIP-Related Familial Isolated Pituitary Adenomas  - MedlinePlus Encyclopedia: Prolactinoma  - MedlinePlus Health Topic: Pituitary Tumors   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,familial isolated pituitary adenoma,0000358,GHR,https://ghr.nlm.nih.gov/condition/familial-isolated-pituitary-adenoma,C2676191,T191,Disorders
What is (are) familial lipoprotein lipase deficiency ?,0000359-1,information,"Familial lipoprotein lipase deficiency is an inherited condition that disrupts the normal breakdown of fats in the body, resulting in an increase of certain kinds of fats.  People with familial lipoprotein lipase deficiency typically develop signs and symptoms before age 10, with one-quarter showing symptoms by age 1. The first symptom of this condition is usually abdominal pain, which can vary from mild to severe. The abdominal pain is often due to inflammation of the pancreas (pancreatitis). These episodes of pancreatitis begin as sudden (acute) attacks. If left untreated, pancreatitis can develop into a chronic condition that can damage the pancreas and, in rare cases, be life-threatening.  Affected individuals may also have an enlarged liver and spleen (hepatosplenomegaly). The higher the levels of fat in the body, the larger the liver and spleen become. As fat levels rise, certain white blood cells called macrophages take in excess fat in an attempt to rid fat from the bloodstream. After taking in fat, the macrophages travel to the liver and spleen, where the fatty cells accumulate.  Approximately half of individuals with familial lipoprotein lipase deficiency develop small yellow deposits of fat under the skin called eruptive xanthomas. These fat deposits most commonly appear on the trunk, buttocks, knees, and arms. Eruptive xanthomas are small (about 1 millimeter in diameter), but individual xanthomas can cluster together to form larger patches. They are generally not painful unless exposed to repeated friction or abrasion. Eruptive xanthomas begin to appear when fat intake increases and levels rise; the deposits disappear when fat intake slows and levels decrease.  The blood of people with familial lipoprotein lipase deficiency can have a milky appearance due to its high fat content. When fat levels get very high in people with this condition, fats can accumulate in blood vessels in the tissue that lines the back of the eye (the retina). The fat buildup gives this tissue a pale pink appearance when examined (lipemia retinalis). This fat accumulation does not affect vision and will disappear once fats from the diet are reduced and levels in the body decrease.  In people with familial lipoprotein lipase deficiency, increased fat levels can also cause neurological features, such as depression, memory loss, and mild intellectual decline (dementia). These problems are remedied when dietary fat levels normalize.",familial lipoprotein lipase deficiency,0000359,GHR,https://ghr.nlm.nih.gov/condition/familial-lipoprotein-lipase-deficiency,C0023817,T047,Disorders
How many people are affected by familial lipoprotein lipase deficiency ?,0000359-2,frequency,"This condition affects about 1 per million people worldwide. It is much more common in certain areas of the province of Quebec, Canada.",familial lipoprotein lipase deficiency,0000359,GHR,https://ghr.nlm.nih.gov/condition/familial-lipoprotein-lipase-deficiency,C0023817,T047,Disorders
What are the genetic changes related to familial lipoprotein lipase deficiency ?,0000359-3,genetic changes,"Mutations in the LPL gene cause familial lipoprotein lipase deficiency. The LPL gene provides instructions for producing an enzyme called lipoprotein lipase, which is found primarily on the surface of cells that line tiny blood vessels (capillaries) within muscles and fatty (adipose) tissue. This enzyme helps break down fats called triglycerides, which are carried by molecules called lipoproteins.  Mutations that cause familial lipoprotein lipase deficiency lead to a reduction or elimination of lipoprotein lipase activity, which prevents the enzyme from effectively breaking down triglycerides. As a result, triglycerides attached to lipoproteins build up in the blood and tissues, leading to the signs and symptoms of familial lipoprotein lipase deficiency.",familial lipoprotein lipase deficiency,0000359,GHR,https://ghr.nlm.nih.gov/condition/familial-lipoprotein-lipase-deficiency,C0023817,T047,Disorders
Is familial lipoprotein lipase deficiency inherited ?,0000359-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Researchers speculate that if family members of affected individuals have a mutation in one copy of the LPL gene in each cell, they may have a mild increase in fat levels in the blood, which could increase their risk of health problems such as heart disease or diabetes. However, studies have not clearly demonstrated whether these individuals are more prone to develop these health problems than individuals in the general population.",familial lipoprotein lipase deficiency,0000359,GHR,https://ghr.nlm.nih.gov/condition/familial-lipoprotein-lipase-deficiency,C0023817,T047,Disorders
What are the treatments for familial lipoprotein lipase deficiency ?,0000359-5,treatment,"These resources address the diagnosis or management of familial lipoprotein lipase deficiency:  - Gene Review: Gene Review: Familial Lipoprotein Lipase Deficiency  - Genetic Testing Registry: Hyperlipoproteinemia, type I  - MedlinePlus Encyclopedia: Chylomicronemia Syndrome  - MedlinePlus Encyclopedia: Familial Lipoprotein Lipase Deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",familial lipoprotein lipase deficiency,0000359,GHR,https://ghr.nlm.nih.gov/condition/familial-lipoprotein-lipase-deficiency,C0023817,T047,Disorders
What is (are) familial male-limited precocious puberty ?,0000360-1,information,"Familial male-limited precocious puberty is a condition that causes early sexual development in males; females are not affected. Boys with this disorder begin exhibiting the signs of puberty in early childhood, between the ages of 2 and 5. Signs of male puberty include a deepening voice, acne, increased body hair, underarm odor, growth of the penis and testes, and spontaneous erections. Changes in behavior, such as increased aggression and early interest in sex, may also occur. Without treatment, affected boys grow quickly at first, but they stop growing earlier than usual. As a result, they tend to be shorter in adulthood compared with other members of their family.",familial male-limited precocious puberty,0000360,GHR,https://ghr.nlm.nih.gov/condition/familial-male-limited-precocious-puberty,C0034013,T047,Disorders
How many people are affected by familial male-limited precocious puberty ?,0000360-2,frequency,Familial male-limited precocious puberty is a rare disorder; its prevalence is unknown.,familial male-limited precocious puberty,0000360,GHR,https://ghr.nlm.nih.gov/condition/familial-male-limited-precocious-puberty,C0034013,T047,Disorders
What are the genetic changes related to familial male-limited precocious puberty ?,0000360-3,genetic changes,"Familial male-limited precocious puberty can be caused by mutations in the LHCGR gene. This gene provides instructions for making a receptor protein called the luteinizing hormone/chorionic gonadotropin receptor. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. Together, ligands and their receptors trigger signals that affect cell development and function.  The protein produced from the LHCGR gene acts as a receptor for two ligands: luteinizing hormone and a similar hormone called chorionic gonadotropin. The receptor allows the body to respond appropriately to these hormones. In males, chorionic gonadotropin stimulates the development of cells in the testes called Leydig cells, and luteinizing hormone triggers these cells to produce androgens. Androgens, including testosterone, are the hormones that control male sexual development and reproduction. In females, luteinizing hormone triggers the release of egg cells from the ovaries (ovulation); chorionic gonadotropin is produced during pregnancy and helps maintain conditions necessary for the pregnancy to continue.  Certain LHCGR gene mutations result in a receptor protein that is constantly turned on (constitutively activated), even when not attached (bound) to luteinizing hormone or chorionic gonadotropin. In males, the overactive receptor causes excess production of testosterone, which triggers male sexual development and lead to early puberty in affected individuals. The overactive receptor has no apparent effect on females.  Approximately 18 percent of individuals with familial male-limited precocious puberty have no identified LHCGR gene mutation. In these individuals, the cause of the disorder is unknown.",familial male-limited precocious puberty,0000360,GHR,https://ghr.nlm.nih.gov/condition/familial-male-limited-precocious-puberty,C0034013,T047,Disorders
Is familial male-limited precocious puberty inherited ?,0000360-4,inheritance,"This condition is inherited in an autosomal dominant, male-limited pattern, which means one copy of the altered LHCGR gene in each cell is sufficient to cause the disorder in males. Females with mutations associated with familial male-limited precocious puberty appear to be unaffected. In some cases, an affected male inherits the mutation from either his mother or his father. Other cases result from new mutations in the gene and occur in males with no history of the disorder in their family.",familial male-limited precocious puberty,0000360,GHR,https://ghr.nlm.nih.gov/condition/familial-male-limited-precocious-puberty,C0034013,T047,Disorders
What are the treatments for familial male-limited precocious puberty ?,0000360-5,treatment,These resources address the diagnosis or management of familial male-limited precocious puberty:  - Boston Children's Hospital: Precocious Puberty  - Genetic Testing Registry: Gonadotropin-independent familial sexual precocity   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,familial male-limited precocious puberty,0000360,GHR,https://ghr.nlm.nih.gov/condition/familial-male-limited-precocious-puberty,C0034013,T047,Disorders
What is (are) familial Mediterranean fever ?,0000361-1,information,"Familial Mediterranean fever is an inherited condition characterized by recurrent episodes of painful inflammation in the abdomen, chest, or joints. These episodes are often accompanied by fever and sometimes a rash or headache. Occasionally inflammation may occur in other parts of the body, such as the heart; the membrane surrounding the brain and spinal cord; and in males, the testicles. In about half of affected individuals, attacks are preceded by mild signs and symptoms known as a prodrome. Prodromal symptoms include mildly uncomfortable sensations in the area that will later become inflamed, or more general feelings of discomfort.  The first episode of illness in familial Mediterranean fever usually occurs in childhood or the teenage years, but in some cases, the initial attack occurs much later in life. Typically, episodes last 12 to 72 hours and can vary in severity. The length of time between attacks is also variable and can range from days to years. During these periods, affected individuals usually have no signs or symptoms related to the condition. However, without treatment to help prevent attacks and complications, a buildup of protein deposits (amyloidosis) in the body's organs and tissues may occur, especially in the kidneys, which can lead to kidney failure.",familial Mediterranean fever,0000361,GHR,https://ghr.nlm.nih.gov/condition/familial-mediterranean-fever,C0031069,T047,Disorders
How many people are affected by familial Mediterranean fever ?,0000361-2,frequency,"Familial Mediterranean fever primarily affects populations originating in the Mediterranean region, particularly people of Armenian, Arab, Turkish, or Jewish ancestry. The disorder affects 1 in 200 to 1,000 people in these populations. It is less common in other populations.",familial Mediterranean fever,0000361,GHR,https://ghr.nlm.nih.gov/condition/familial-mediterranean-fever,C0031069,T047,Disorders
What are the genetic changes related to familial Mediterranean fever ?,0000361-3,genetic changes,"Mutations in the MEFV gene cause familial Mediterranean fever. The MEFV gene provides instructions for making a protein called pyrin (also known as marenostrin), which is found in white blood cells. This protein is involved in the immune system, helping to regulate the process of inflammation. Inflammation occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight microbial invaders and facilitate tissue repair. When this process is complete, the body stops the inflammatory response to prevent damage to its own cells and tissues.  Mutations in the MEFV gene reduce the activity of the pyrin protein, which disrupts control of the inflammation process. An inappropriate or prolonged inflammatory response can result, leading to fever and pain in the abdomen, chest, or joints.  Normal variations in the SAA1 gene may modify the course of familial Mediterranean fever. Some evidence suggests that a particular version of the SAA1 gene (called the alpha variant) increases the risk of amyloidosis among people with familial Mediterranean fever.",familial Mediterranean fever,0000361,GHR,https://ghr.nlm.nih.gov/condition/familial-mediterranean-fever,C0031069,T047,Disorders
Is familial Mediterranean fever inherited ?,0000361-4,inheritance,"Familial Mediterranean fever is almost always inherited in an autosomal recessive pattern, which means both copies of the MEFV gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  In rare cases, this condition appears to be inherited in an autosomal dominant pattern. An autosomal dominant inheritance pattern describes cases in which one copy of the altered gene in each cell is sufficient to cause the disorder. In autosomal dominant inheritance, affected individuals often inherit the mutation from one affected parent.  However, another mechanism is believed to account for some cases of familial Mediterranean fever that were originally thought to be inherited in an autosomal dominant pattern. A gene mutation that occurs frequently in a population may result in a disorder with autosomal recessive inheritance appearing in multiple generations in a family, a pattern that mimics autosomal dominant inheritance. If one parent has familial Mediterranean fever (with mutations in both copies of the MEFV gene in each cell) and the other parent is an unaffected carrier (with a mutation in one copy of the MEFV gene in each cell), it may appear as if the affected child inherited the disorder only from the affected parent. This appearance of autosomal dominant inheritance when the pattern is actually autosomal recessive is called pseudodominance.",familial Mediterranean fever,0000361,GHR,https://ghr.nlm.nih.gov/condition/familial-mediterranean-fever,C0031069,T047,Disorders
What are the treatments for familial Mediterranean fever ?,0000361-5,treatment,These resources address the diagnosis or management of familial Mediterranean fever:  - Gene Review: Gene Review: Familial Mediterranean Fever  - Genetic Testing Registry: Familial Mediterranean fever   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,familial Mediterranean fever,0000361,GHR,https://ghr.nlm.nih.gov/condition/familial-mediterranean-fever,C0031069,T047,Disorders
What is (are) familial osteochondritis dissecans ?,0000362-1,information,"Familial osteochondritis dissecans is a condition that affects the joints and is associated with abnormal cartilage. Cartilage is a tough but flexible tissue that covers the ends of the bones at joints and is also part of the developing skeleton. A characteristic feature of familial osteochondritis dissecans is areas of bone damage (lesions) caused by detachment of cartilage and a piece of the underlying bone from the end of the bone at a joint. People with this condition develop multiple lesions that affect several joints, primarily the knees, elbows, hips, and ankles. The lesions cause stiffness, pain, and swelling in the joint. Often, the affected joint feels like it catches or locks during movement. Other characteristic features of familial osteochondritis dissecans include short stature and development of a joint disorder called osteoarthritis at an early age. Osteoarthritis is characterized by the breakdown of joint cartilage and the underlying bone. It causes pain and stiffness and restricts the movement of joints.  A similar condition called sporadic osteochondritis dissecans is associated with a single lesion in one joint, most often the knee. These cases may be caused by injury to or repetitive use of the joint (often sports-related). Some people with sporadic osteochondritis dissecans develop osteoarthritis in the affected joint, especially if the lesion occurs later in life after the bone has stopped growing. Short stature is not associated with this form of the condition.",familial osteochondritis dissecans,0000362,GHR,https://ghr.nlm.nih.gov/condition/familial-osteochondritis-dissecans,C3665488,T047,Disorders
How many people are affected by familial osteochondritis dissecans ?,0000362-2,frequency,"Familial osteochondritis dissecans is a rare condition, although the prevalence is unknown. Sporadic osteochondritis dissecans is more common; it is estimated to occur in the knee in 15 to 29 per 100,000 individuals.",familial osteochondritis dissecans,0000362,GHR,https://ghr.nlm.nih.gov/condition/familial-osteochondritis-dissecans,C3665488,T047,Disorders
What are the genetic changes related to familial osteochondritis dissecans ?,0000362-3,genetic changes,"Mutation of the ACAN gene can cause familial osteochondritis dissecans. The ACAN gene provides instructions for making the aggrecan protein, which is a component of cartilage. Aggrecan attaches to the other components of cartilage, organizing the network of molecules that gives cartilage its strength. In addition, aggrecan attracts water molecules and gives cartilage its gel-like structure. This feature enables the cartilage to resist compression, protecting bones and joints.  The ACAN gene mutation associated with familial osteochondritis dissecans results in an abnormal protein that is unable to attach to the other components of cartilage. As a result, the cartilage is disorganized and weak. It is unclear how the abnormal cartilage leads to the lesions and osteoarthritis characteristic of familial osteochondritis dissecans. Researchers suggest that a disorganized cartilage network in growing bones impairs their normal growth, leading to short stature.  Sporadic osteochondritis dissecans is not caused by genetic changes and is not inherited.",familial osteochondritis dissecans,0000362,GHR,https://ghr.nlm.nih.gov/condition/familial-osteochondritis-dissecans,C3665488,T047,Disorders
Is familial osteochondritis dissecans inherited ?,0000362-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In most cases, an affected person has one parent with the condition.",familial osteochondritis dissecans,0000362,GHR,https://ghr.nlm.nih.gov/condition/familial-osteochondritis-dissecans,C3665488,T047,Disorders
What are the treatments for familial osteochondritis dissecans ?,0000362-5,treatment,These resources address the diagnosis or management of familial osteochondritis dissecans:  - Cedars-Sinai  - Genetic Testing Registry: Osteochondritis dissecans  - Seattle Children's: Osteochondritis Dissecans Symptoms and Diagnosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,familial osteochondritis dissecans,0000362,GHR,https://ghr.nlm.nih.gov/condition/familial-osteochondritis-dissecans,C3665488,T047,Disorders
What is (are) familial paroxysmal kinesigenic dyskinesia ?,0000363-1,information,"Familial paroxysmal kinesigenic dyskinesia is a disorder characterized by episodes of abnormal movement that range from mild to severe. In the condition name, the word paroxysmal indicates that the abnormal movements come and go over time, kinesigenic means that episodes are triggered by movement, and dyskinesia refers to involuntary movement of the body.  People with familial paroxysmal kinesigenic dyskinesia experience episodes of irregular jerking or shaking movements that are induced by sudden motion, such as standing up quickly or being startled. An episode may involve slow, prolonged muscle contractions (dystonia); small, fast, ""dance-like"" motions (chorea); writhing movements of the limbs (athetosis); or, rarely, flailing movements of the limbs (ballismus). Familial paroxysmal kinesigenic dyskinesia may affect one or both sides of the body. The type of abnormal movement varies among affected individuals, even among members of the same family. In many people with familial paroxysmal kinesigenic dyskinesia, a pattern of symptoms called an aura immediately precedes the episode. The aura is often described as a crawling or tingling sensation in the affected body part. Individuals with this condition do not lose consciousness during an episode and do not experience any symptoms between episodes.  Individuals with familial paroxysmal kinesigenic dyskinesia usually begin to show signs and symptoms of the disorder during childhood or adolescence. Episodes typically last less than five minutes, and the frequency of episodes ranges from one per month to 100 per day. In most affected individuals, episodes occur less often with age.  In some people with familial paroxysmal kinesigenic dyskinesia the disorder begins in infancy with recurring seizures called benign infantile convulsions. These seizures usually develop in the first year of life and stop by age 3. When benign infantile convulsions are associated with familial paroxysmal kinesigenic dyskinesia, the condition is known as infantile convulsions and choreoathetosis (ICCA). In families with ICCA, some individuals develop only benign infantile convulsions, some have only familial paroxysmal kinesigenic dyskinesia, and others develop both.",familial paroxysmal kinesigenic dyskinesia,0000363,GHR,https://ghr.nlm.nih.gov/condition/familial-paroxysmal-kinesigenic-dyskinesia,C3714094,T047,Disorders
How many people are affected by familial paroxysmal kinesigenic dyskinesia ?,0000363-2,frequency,"Familial paroxysmal kinesigenic dyskinesia is estimated to occur in 1 in 150,000 individuals. For unknown reasons, this condition affects more males than females.",familial paroxysmal kinesigenic dyskinesia,0000363,GHR,https://ghr.nlm.nih.gov/condition/familial-paroxysmal-kinesigenic-dyskinesia,C3714094,T047,Disorders
What are the genetic changes related to familial paroxysmal kinesigenic dyskinesia ?,0000363-3,genetic changes,"Familial paroxysmal kinesigenic dyskinesia can be caused by mutations in the PRRT2 gene. The function of the protein produced from this gene is unknown, although it is thought to be involved in the development and function of the brain. Studies suggest that the PRRT2 protein interacts with a protein that helps control signaling between nerve cells (neurons). It is thought that PRRT2 gene mutations, which reduce the amount of PRRT2 protein, lead to abnormal neuronal signaling. Altered neuronal activity could underlie the movement problems associated with familial paroxysmal kinesigenic dyskinesia.  Not everyone with this condition has a mutation in the PRRT2 gene. When no PRRT2 gene mutations are found, the cause of the condition is unknown.",familial paroxysmal kinesigenic dyskinesia,0000363,GHR,https://ghr.nlm.nih.gov/condition/familial-paroxysmal-kinesigenic-dyskinesia,C3714094,T047,Disorders
Is familial paroxysmal kinesigenic dyskinesia inherited ?,0000363-4,inheritance,"This condition is inherited in an autosomal dominant pattern. Autosomal dominant inheritance means that one copy of an altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.",familial paroxysmal kinesigenic dyskinesia,0000363,GHR,https://ghr.nlm.nih.gov/condition/familial-paroxysmal-kinesigenic-dyskinesia,C3714094,T047,Disorders
What are the treatments for familial paroxysmal kinesigenic dyskinesia ?,0000363-5,treatment,These resources address the diagnosis or management of familial paroxysmal kinesigenic dyskinesia:  - Gene Review: Gene Review: Familial Paroxysmal Kinesigenic Dyskinesia  - Genetic Testing Registry: Dystonia 10   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,familial paroxysmal kinesigenic dyskinesia,0000363,GHR,https://ghr.nlm.nih.gov/condition/familial-paroxysmal-kinesigenic-dyskinesia,C3714094,T047,Disorders
What is (are) familial paroxysmal nonkinesigenic dyskinesia ?,0000364-1,information,"Familial paroxysmal nonkinesigenic dyskinesia is a disorder of the nervous system that causes periods of involuntary movement. Paroxysmal indicates that the abnormal movements come and go over time. Nonkinesigenic means that episodes are not triggered by sudden movement. Dyskinesia broadly refers to involuntary movement of the body.  People with familial paroxysmal nonkinesigenic dyskinesia experience episodes of abnormal movement that develop without a known cause or are brought on by alcohol, caffeine, stress, fatigue, menses, or excitement. Episodes are not induced by exercise or sudden movement and do not occur during sleep. An episode is characterized by irregular, jerking or shaking movements that range from mild to severe. In this disorder, the dyskinesias can include slow, prolonged contraction of muscles (dystonia); small, fast, ""dance-like"" motions (chorea); writhing movements of the limbs (athetosis); and, rarely, flailing movements of the limbs (ballismus). Dyskinesias also affect muscles in the trunk and face. The type of abnormal movement varies among affected individuals, even among members of the same family. Individuals with familial paroxysmal nonkinesigenic dyskinesia do not lose consciousness during an episode. Most people do not experience any other neurological symptoms between episodes.  Individuals with familial paroxysmal nonkinesigenic dyskinesia usually begin to show signs and symptoms of the disorder during childhood or their early teens. Episodes typically last 1-4 hours, and the frequency of episodes ranges from several per day to one per year. In some affected individuals, episodes occur less often with age.",familial paroxysmal nonkinesigenic dyskinesia,0000364,GHR,https://ghr.nlm.nih.gov/condition/familial-paroxysmal-nonkinesigenic-dyskinesia,C1869117,T047,Disorders
How many people are affected by familial paroxysmal nonkinesigenic dyskinesia ?,0000364-2,frequency,Familial paroxysmal nonkinesigenic dyskinesia is a very rare disorder. Its prevalence is estimated to be 1 in 5 million people.,familial paroxysmal nonkinesigenic dyskinesia,0000364,GHR,https://ghr.nlm.nih.gov/condition/familial-paroxysmal-nonkinesigenic-dyskinesia,C1869117,T047,Disorders
What are the genetic changes related to familial paroxysmal nonkinesigenic dyskinesia ?,0000364-3,genetic changes,"Mutations in the PNKD gene cause familial paroxysmal nonkinesigenic dyskinesia. The function of the protein produced from the PNKD gene is unknown; however, it is similar to a protein that helps break down a chemical called methylglyoxal. Methylglyoxal is found in alcoholic beverages, coffee, tea, and cola. Research has demonstrated that this chemical has a toxic effect on nerve cells (neurons). It remains unclear if the PNKD gene is related to the breakdown of methlglyoxal. How mutations in the PNKD gene lead to the signs and symptoms of familial paroxysmal nonkinesigenic dyskinesia is also unknown.",familial paroxysmal nonkinesigenic dyskinesia,0000364,GHR,https://ghr.nlm.nih.gov/condition/familial-paroxysmal-nonkinesigenic-dyskinesia,C1869117,T047,Disorders
Is familial paroxysmal nonkinesigenic dyskinesia inherited ?,0000364-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is typically sufficient to cause the disorder. Almost everyone with a mutation in the PNKD gene will develop familial paroxysmal nonkinesigenic dyskinesia. In all reported cases, an affected person has inherited the mutation from one parent.",familial paroxysmal nonkinesigenic dyskinesia,0000364,GHR,https://ghr.nlm.nih.gov/condition/familial-paroxysmal-nonkinesigenic-dyskinesia,C1869117,T047,Disorders
What are the treatments for familial paroxysmal nonkinesigenic dyskinesia ?,0000364-5,treatment,These resources address the diagnosis or management of familial paroxysmal nonkinesigenic dyskinesia:  - Gene Review: Gene Review: Familial Paroxysmal Nonkinesigenic Dyskinesia  - Genetic Testing Registry: Paroxysmal choreoathetosis  - Genetic Testing Registry: Paroxysmal nonkinesigenic dyskinesia 2   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,familial paroxysmal nonkinesigenic dyskinesia,0000364,GHR,https://ghr.nlm.nih.gov/condition/familial-paroxysmal-nonkinesigenic-dyskinesia,C1869117,T047,Disorders
What is (are) familial pityriasis rubra pilaris ?,0000365-1,information,"Familial pityriasis rubra pilaris is a rare genetic condition that affects the skin. The name of the condition reflects its major features: The term ""pityriasis"" refers to scaling; ""rubra"" means redness; and ""pilaris"" suggests the involvement of hair follicles in this disorder. Affected individuals have a salmon-colored skin rash covered in fine scales. This rash occurs in patches all over the body, with distinct areas of unaffected skin between the patches. Affected individuals also develop bumps called follicular keratoses that occur around hair follicles. The skin on the palms of the hands and soles of the feet often becomes thick, hard, and callused, a condition known as palmoplantar keratoderma.  Researchers have distinguished six types of pityriasis rubra pilaris based on the features of the disorder and the age at which signs and symptoms appear. The familial form is usually considered part of type V, which is also known as the atypical juvenile type. People with familial pityriasis rubra pilaris typically have skin abnormalities from birth or early childhood, and these skin problems persist throughout life.",familial pityriasis rubra pilaris,0000365,GHR,https://ghr.nlm.nih.gov/condition/familial-pityriasis-rubra-pilaris,C2930842,T047,Disorders
How many people are affected by familial pityriasis rubra pilaris ?,0000365-2,frequency,"Familial pityriasis rubra pilaris is a rare condition. Its incidence is unknown, although the familial form appears to be the least common type of pityriasis rubra pilaris.",familial pityriasis rubra pilaris,0000365,GHR,https://ghr.nlm.nih.gov/condition/familial-pityriasis-rubra-pilaris,C2930842,T047,Disorders
What are the genetic changes related to familial pityriasis rubra pilaris ?,0000365-3,genetic changes,"In most cases of pityriasis rubra pilaris, the cause of the condition is unknown. However, mutations in the CARD14 gene have been found to cause the familial form of the disorder in a few affected families. The CARD14 gene provides instructions for making a protein that turns on (activates) a group of interacting proteins known as nuclear factor-kappa-B (NF-B). NF-B regulates the activity of multiple genes, including genes that control the body's immune responses and inflammatory reactions. It also protects cells from certain signals that would otherwise cause them to self-destruct (undergo apoptosis).  The CARD14 protein is found in many of the body's tissues, but it is particularly abundant in the skin. NF-B signaling appears to play an important role in regulating inflammation in the skin. Mutations in the CARD14 gene lead to overactivation of NF-B signaling, which triggers an abnormal inflammatory response. Researchers are working to determine how these changes lead to the specific features of familial pityriasis rubra pilaris.",familial pityriasis rubra pilaris,0000365,GHR,https://ghr.nlm.nih.gov/condition/familial-pityriasis-rubra-pilaris,C2930842,T047,Disorders
Is familial pityriasis rubra pilaris inherited ?,0000365-4,inheritance,"Familial pityriasis rubra pilaris usually has an autosomal dominant inheritance pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Affected individuals usually inherit the condition from one affected parent. However, the condition is said to have incomplete penetrance because not everyone who inherits the altered gene from a parent develops the condition's characteristic skin abnormalities.  The other types of pityriasis rubra pilaris are sporadic, which means they occur in people with no history of the disorder in their family.",familial pityriasis rubra pilaris,0000365,GHR,https://ghr.nlm.nih.gov/condition/familial-pityriasis-rubra-pilaris,C2930842,T047,Disorders
What are the treatments for familial pityriasis rubra pilaris ?,0000365-5,treatment,These resources address the diagnosis or management of familial pityriasis rubra pilaris:  - Genetic Testing Registry: Pityriasis rubra pilaris   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,familial pityriasis rubra pilaris,0000365,GHR,https://ghr.nlm.nih.gov/condition/familial-pityriasis-rubra-pilaris,C2930842,T047,Disorders
What is (are) familial porencephaly ?,0000366-1,information,"Familial porencephaly is part of a group of conditions called the COL4A1-related disorders. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. In familial porencephaly, fluid-filled cysts develop in the brain (porencephaly) during fetal development or soon after birth. These cysts typically occur in only one side of the brain and vary in size. The cysts are thought to be the result of bleeding within the brain (hemorrhagic stroke). People with this condition also have leukoencephalopathy, which is a change in a type of brain tissue called white matter that can be seen with magnetic resonance imaging (MRI).  During infancy, people with familial porencephaly typically have paralysis affecting one side of the body (infantile hemiplegia). Affected individuals may also have recurrent seizures (epilepsy), migraine headaches, speech problems, intellectual disability, and uncontrolled muscle tensing (dystonia). Some people are severely affected, and others may have no symptoms related to the brain cysts.",familial porencephaly,0000366,GHR,https://ghr.nlm.nih.gov/condition/familial-porencephaly,C1867983,T019,Disorders
How many people are affected by familial porencephaly ?,0000366-2,frequency,"Familial porencephaly is a rare condition, although the exact prevalence is unknown. At least eight affected families have been described in the scientific literature.",familial porencephaly,0000366,GHR,https://ghr.nlm.nih.gov/condition/familial-porencephaly,C1867983,T019,Disorders
What are the genetic changes related to familial porencephaly ?,0000366-3,genetic changes,"Mutations in the COL4A1 gene cause familial porencephaly. The COL4A1 gene provides instructions for making one component of a protein called type IV collagen. Type IV collagen molecules attach to each other to form complex protein networks. These protein networks are the main components of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. Type IV collagen networks play an important role in the basement membranes in virtually all tissues throughout the body, particularly the basement membranes surrounding the body's blood vessels (vasculature).  The COL4A1 gene mutations that cause familial porencephaly result in the production of a protein that disrupts the structure of type IV collagen. As a result, type IV collagen molecules cannot attach to each other to form the protein networks in basement membranes. Basement membranes without normal type IV collagen are unstable, leading to weakening of the tissues that they surround. In people with familial porencephaly, the vasculature in the brain weakens, which can lead to blood vessel breakage and hemorrhagic stroke. Bleeding within the brain is followed by the formation of fluid-filled cysts characteristic of this condition. It is thought that the pressure and stress on the head during birth contributes to vessel breakage in people with this condition; however in some individuals, bleeding in the brain can occur before birth.",familial porencephaly,0000366,GHR,https://ghr.nlm.nih.gov/condition/familial-porencephaly,C1867983,T019,Disorders
Is familial porencephaly inherited ?,0000366-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",familial porencephaly,0000366,GHR,https://ghr.nlm.nih.gov/condition/familial-porencephaly,C1867983,T019,Disorders
What are the treatments for familial porencephaly ?,0000366-5,treatment,These resources address the diagnosis or management of familial porencephaly:  - Gene Review: Gene Review: COL4A1-Related Disorders  - Genetic Testing Registry: Familial porencephaly   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,familial porencephaly,0000366,GHR,https://ghr.nlm.nih.gov/condition/familial-porencephaly,C1867983,T019,Disorders
What is (are) familial restrictive cardiomyopathy ?,0000367-1,information,"Familial restrictive cardiomyopathy is a genetic form of heart disease. For the heart to beat normally, the heart (cardiac) muscle must contract and relax in a coordinated way. Oxygen-rich blood from the lungs travels first through the upper chambers of the heart (the atria), and then to the lower chambers of the heart (the ventricles).  In people with familial restrictive cardiomyopathy, the heart muscle is stiff and cannot fully relax after each contraction. Impaired muscle relaxation causes blood to back up in the atria and lungs, which reduces the amount of blood in the ventricles.  Familial restrictive cardiomyopathy can appear anytime from childhood to adulthood. The first signs and symptoms of this condition in children are failure to gain weight and grow at the expected rate (failure to thrive), extreme tiredness (fatigue), and fainting. Children who are severely affected may also have abnormal swelling or puffiness (edema), increased blood pressure, an enlarged liver, an abnormal buildup of fluid in the abdominal cavity (ascites), and lung congestion. Some children with familial restrictive cardiomyopathy do not have any obvious signs or symptoms, but they may die suddenly due to heart failure. Without treatment, the majority of affected children survive only a few years after they are diagnosed.  Adults with familial restrictive cardiomyopathy typically first develop shortness of breath, fatigue, and a reduced ability to exercise. Some individuals have an irregular heart beat (arrhythmia) and may also experience a sensation of fluttering or pounding in the chest (palpitations) and dizziness. Abnormal blood clots are commonly seen in adults with this condition. Without treatment, approximately one-third of adults with familial restrictive cardiomyopathy do not survive more than five years after diagnosis.",familial restrictive cardiomyopathy,0000367,GHR,https://ghr.nlm.nih.gov/condition/familial-restrictive-cardiomyopathy,C0007196,T019,Disorders
How many people are affected by familial restrictive cardiomyopathy ?,0000367-2,frequency,"The prevalence of familial restrictive cardiomyopathy is unknown. Although cardiomyopathy is a relatively common condition, restrictive cardiomyopathy, in which relaxation of the heart muscle is impaired, is the least common type. Some other forms of cardiomyopathy involve a weak or enlarged heart muscle with impaired contraction. In the United States and in Europe, restrictive cardiomyopathy accounts for less than five percent of all cardiomyopathies. The proportion of restrictive cardiomyopathy that runs in families is not known.",familial restrictive cardiomyopathy,0000367,GHR,https://ghr.nlm.nih.gov/condition/familial-restrictive-cardiomyopathy,C0007196,T019,Disorders
What are the genetic changes related to familial restrictive cardiomyopathy ?,0000367-3,genetic changes,"Mutations in several genes have been found to cause familial restrictive cardiomyopathy. Mutations in the TNNI3 gene are one of the major causes of this condition. The TNNI3 gene provides instructions for making a protein called cardiac troponin I, which is found solely in the heart. Cardiac troponin I is one of three proteins that make up the troponin protein complex, which helps regulate tensing (contraction) and relaxation of the heart muscle.  TNNI3 gene mutations associated with familial restrictive cardiomyopathy result in the production of a defective cardiac troponin I protein. The altered protein disrupts the function of the troponin protein complex and does not allow the heart muscle to fully relax. As a result, not enough blood enters the ventricles, leading to a buildup in the atria and lungs. The abnormal heart relaxation and blood flow is responsible for many of the signs and symptoms of familial restrictive cardiomyopathy.  Mutations in other genes associated with familial restrictive cardiomyopathy each account for a small percentage of cases of this condition. Some people with familial restrictive cardiomyopathy do not have an identified mutation in any of the known associated genes. The cause of the disorder in these individuals is unknown.",familial restrictive cardiomyopathy,0000367,GHR,https://ghr.nlm.nih.gov/condition/familial-restrictive-cardiomyopathy,C0007196,T019,Disorders
Is familial restrictive cardiomyopathy inherited ?,0000367-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",familial restrictive cardiomyopathy,0000367,GHR,https://ghr.nlm.nih.gov/condition/familial-restrictive-cardiomyopathy,C0007196,T019,Disorders
What are the treatments for familial restrictive cardiomyopathy ?,0000367-5,treatment,These resources address the diagnosis or management of familial restrictive cardiomyopathy:  - Genetic Testing Registry: Familial restrictive cardiomyopathy  - Genetic Testing Registry: Familial restrictive cardiomyopathy 1  - Genetic Testing Registry: Familial restrictive cardiomyopathy 2  - Genetic Testing Registry: Familial restrictive cardiomyopathy 3  - Johns Hopkins Medicine: Cardiomyopathy/Heart Failure  - MedlinePlus Encyclopedia: Restrictive Cardiomyopathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,familial restrictive cardiomyopathy,0000367,GHR,https://ghr.nlm.nih.gov/condition/familial-restrictive-cardiomyopathy,C0007196,T019,Disorders
What is (are) familial thoracic aortic aneurysm and dissection ?,0000368-1,information,"Familial thoracic aortic aneurysm and dissection (familial TAAD) involves problems with the aorta, which is the large blood vessel that distributes blood from the heart to the rest of the body. Familial TAAD affects the upper part of the aorta, near the heart. This part of the aorta is called the thoracic aorta because it is located in the chest (thorax). Other vessels that carry blood from the heart to the rest of the body (arteries) can also be affected.  In familial TAAD, the aorta can become weakened and stretched (aortic dilatation), which can lead to a bulge in the blood vessel wall (an aneurysm). Aortic dilatation may also lead to a sudden tearing of the layers in the aorta wall (aortic dissection), allowing blood to flow abnormally between the layers. These aortic abnormalities are potentially life-threatening because they can decrease blood flow to other parts of the body such as the brain or other vital organs, or cause the aorta to break open (rupture).  The occurrence and timing of these aortic abnormalities vary, even within the same affected family. They can begin in childhood or not occur until late in life. Aortic dilatation is generally the first feature of familial TAAD to develop, although in some affected individuals dissection occurs with little or no aortic dilatation.  Aortic aneurysms usually have no symptoms. However, depending on the size, growth rate, and location of these abnormalities, they can cause pain in the jaw, neck, chest, or back; swelling in the arms, neck, or head; difficult or painful swallowing; hoarseness; shortness of breath; wheezing; a chronic cough; or coughing up blood. Aortic dissections usually cause severe, sudden chest or back pain, and may also result in unusually pale skin (pallor), a very faint pulse, numbness or tingling (paresthesias) in one or more limbs, or paralysis.  Familial TAAD may not be associated with other signs and symptoms. However, some individuals in affected families show mild features of related conditions called Marfan syndrome or Loeys-Dietz syndrome. These features include tall stature, stretch marks on the skin, an unusually large range of joint movement (joint hypermobility), and either a sunken or protruding chest. Occasionally, people with familial TAAD develop aneurysms in the brain or in the section of the aorta located in the abdomen (abdominal aorta). Some people with familial TAAD have heart abnormalities that are present from birth (congenital). Affected individuals may also have a soft out-pouching in the lower abdomen (inguinal hernia), an abnormal curvature of the spine (scoliosis), or a purplish skin discoloration (livedo reticularis) caused by abnormalities in the tiny blood vessels of the skin (dermal capillaries). However, these conditions are also common in the general population. Depending on the genetic cause of familial TAAD in particular families, they may have an increased risk of developing blockages in smaller arteries, which can lead to heart attack and stroke.",familial thoracic aortic aneurysm and dissection,0000368,GHR,https://ghr.nlm.nih.gov/condition/familial-thoracic-aortic-aneurysm-and-dissection,C0345050,T019,Disorders
How many people are affected by familial thoracic aortic aneurysm and dissection ?,0000368-2,frequency,"Familial TAAD is believed to account for at least 20 percent of thoracic aortic aneurysms and dissections. In the remainder of cases, the abnormalities are thought to be caused by factors that are not inherited, such as damage to the walls of the aorta from aging, tobacco use, injury, or disease.  While aortic aneurysms are common worldwide, it is difficult to determine their exact prevalence because they usually cause no symptoms unless they rupture. Ruptured aortic aneurysms and dissections are estimated to cause almost 30,000 deaths in the United States each year.",familial thoracic aortic aneurysm and dissection,0000368,GHR,https://ghr.nlm.nih.gov/condition/familial-thoracic-aortic-aneurysm-and-dissection,C0345050,T019,Disorders
What are the genetic changes related to familial thoracic aortic aneurysm and dissection ?,0000368-3,genetic changes,"Mutations in any of several genes are associated with familial TAAD. Mutations in the ACTA2 gene have been identified in 14 to 20 percent of people with this disorder, and TGFBR2 gene mutations have been found in 2.5 percent of affected individuals. Mutations in several other genes account for smaller percentages of cases.  The ACTA2 gene provides instructions for making a protein called smooth muscle alpha ()-2 actin, which is found in vascular smooth muscle cells. Layers of these cells are found in the walls of the aorta and other arteries. Within vascular smooth muscle cells, smooth muscle -2 actin forms the core of structures called sarcomeres, which are necessary for muscles to contract. This ability to contract allows the arteries to maintain their shape instead of stretching out as blood is pumped through them.  ACTA2 gene mutations that are associated with familial TAAD change single protein building blocks (amino acids) in the smooth muscle -2 actin protein. These changes likely affect the way the protein functions in smooth muscle contraction, interfering with the sarcomeres' ability to prevent the arteries from stretching. The aorta, where the force of blood pumped directly from the heart is most intense, is particularly vulnerable to this stretching. Abnormal stretching of the aorta results in the aortic dilatation, aneurysms, and dissections that characterize familial TAAD.  TGFBR2 gene mutations are also associated with familial TAAD. The TGFBR2 gene provides instructions for making a protein called transforming growth factor-beta (TGF-) receptor type 2. This receptor transmits signals from the cell surface into the cell through a process called signal transduction. Through this type of signaling, the environment outside the cell affects activities inside the cell. In particular, the TGF- receptor type 2 protein helps control the growth and division (proliferation) of cells and the process by which cells mature to carry out specific functions (differentiation). It is also involved in the formation of the extracellular matrix, an intricate lattice of proteins and other molecules that forms in the spaces between cells.  TGFBR2 gene mutations alter the receptor's structure, which disturbs signal transduction. The disturbed signaling can impair cell growth and development. It is not known how these changes result in the specific aortic abnormalities associated with familial TAAD.  Mutations in other genes, some of which have not been identified, are also associated with familial TAAD.",familial thoracic aortic aneurysm and dissection,0000368,GHR,https://ghr.nlm.nih.gov/condition/familial-thoracic-aortic-aneurysm-and-dissection,C0345050,T019,Disorders
Is familial thoracic aortic aneurysm and dissection inherited ?,0000368-4,inheritance,"Familial TAAD is inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell can be sufficient to cause the condition. In most cases, an affected person has one affected parent. However, some people who inherit an altered gene never develop the aortic abnormalities associated with the condition; this situation is known as reduced penetrance.",familial thoracic aortic aneurysm and dissection,0000368,GHR,https://ghr.nlm.nih.gov/condition/familial-thoracic-aortic-aneurysm-and-dissection,C0345050,T019,Disorders
What are the treatments for familial thoracic aortic aneurysm and dissection ?,0000368-5,treatment,"These resources address the diagnosis or management of familial TAAD:  - Gene Review: Gene Review: Thoracic Aortic Aneurysms and Aortic Dissections  - Genetic Testing Registry: Aortic aneurysm, familial thoracic 2  - Genetic Testing Registry: Aortic aneurysm, familial thoracic 4  - Genetic Testing Registry: Aortic aneurysm, familial thoracic 6  - Genetic Testing Registry: Congenital aneurysm of ascending aorta  - Genetic Testing Registry: Thoracic aortic aneurysm and aortic dissection   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",familial thoracic aortic aneurysm and dissection,0000368,GHR,https://ghr.nlm.nih.gov/condition/familial-thoracic-aortic-aneurysm-and-dissection,C0345050,T019,Disorders
What is (are) Fanconi anemia ?,0000369-1,information,"Fanconi anemia is a condition that affects many parts of the body. People with this condition may have bone marrow failure, physical abnormalities, organ defects, and an increased risk of certain cancers.  The major function of bone marrow is to produce new blood cells. These include red blood cells, which carry oxygen to the body's tissues; white blood cells, which fight infections; and platelets, which are necessary for normal blood clotting. Approximately 90 percent of people with Fanconi anemia have impaired bone marrow function that leads to a decrease in the production of all blood cells (aplastic anemia). Affected individuals experience extreme tiredness (fatigue) due to low numbers of red blood cells (anemia), frequent infections due to low numbers of white blood cells (neutropenia), and clotting problems due to low numbers of platelets (thrombocytopenia). People with Fanconi anemia may also develop myelodysplastic syndrome, a condition in which immature blood cells fail to develop normally.  More than half of people with Fanconi anemia have physical abnormalities. These abnormalities can involve irregular skin coloring such as unusually light-colored skin (hypopigmentation) or caf-au-lait spots, which are flat patches on the skin that are darker than the surrounding area. Other possible symptoms of Fanconi anemia include malformed thumbs or forearms and other skeletal problems including short stature; malformed or absent kidneys and other defects of the urinary tract; gastrointestinal abnormalities; heart defects; eye abnormalities such as small or abnormally shaped eyes; and malformed ears and hearing loss. People with this condition may have abnormal genitalia or malformations of the reproductive system. As a result, most affected males and about half of affected females cannot have biological children (are infertile). Additional signs and symptoms can include abnormalities of the brain and spinal cord (central nervous system), including increased fluid in the center of the brain (hydrocephalus) or an unusually small head size (microcephaly).  Individuals with Fanconi anemia have an increased risk of developing a cancer of blood-forming cells in the bone marrow called acute myeloid leukemia (AML) or tumors of the head, neck, skin, gastrointestinal system, or genital tract. The likelihood of developing one of these cancers in people with Fanconi anemia is between 10 and 30 percent.",Fanconi anemia,0000369,GHR,https://ghr.nlm.nih.gov/condition/fanconi-anemia,C3469521,T047,Disorders
How many people are affected by Fanconi anemia ?,0000369-2,frequency,"Fanconi anemia occurs in 1 in 160,000 individuals worldwide. This condition is more common among people of Ashkenazi Jewish descent, the Roma population of Spain, and black South Africans.",Fanconi anemia,0000369,GHR,https://ghr.nlm.nih.gov/condition/fanconi-anemia,C3469521,T047,Disorders
What are the genetic changes related to Fanconi anemia ?,0000369-3,genetic changes,"Mutations in at least 15 genes can cause Fanconi anemia. Proteins produced from these genes are involved in a cell process known as the FA pathway. The FA pathway is turned on (activated) when the process of making new copies of DNA, called DNA replication, is blocked due to DNA damage. The FA pathway sends certain proteins to the area of damage, which trigger DNA repair so DNA replication can continue.  The FA pathway is particularly responsive to a certain type of DNA damage known as interstrand cross-links (ICLs). ICLs occur when two DNA building blocks (nucleotides) on opposite strands of DNA are abnormally attached or linked together, which stops the process of DNA replication. ICLs can be caused by a buildup of toxic substances produced in the body or by treatment with certain cancer therapy drugs.  Eight proteins associated with Fanconi anemia group together to form a complex known as the FA core complex. The FA core complex activates two proteins, called FANCD2 and FANCI. The activation of these two proteins brings DNA repair proteins to the area of the ICL so the cross-link can be removed and DNA replication can continue.  Eighty to 90 percent of cases of Fanconi anemia are due to mutations in one of three genes, FANCA, FANCC, and FANCG. These genes provide instructions for producing components of the FA core complex. Mutations in any of the many genes associated with the FA core complex will cause the complex to be nonfunctional and disrupt the entire FA pathway. As a result, DNA damage is not repaired efficiently and ICLs build up over time. The ICLs stall DNA replication, ultimately resulting in either abnormal cell death due to an inability make new DNA molecules or uncontrolled cell growth due to a lack of DNA repair processes. Cells that divide quickly, such as bone marrow cells and cells of the developing fetus, are particularly affected. The death of these cells results in the decrease in blood cells and the physical abnormalities characteristic of Fanconi anemia. When the buildup of errors in DNA leads to uncontrolled cell growth, affected individuals can develop acute myeloid leukemia or other cancers.",Fanconi anemia,0000369,GHR,https://ghr.nlm.nih.gov/condition/fanconi-anemia,C3469521,T047,Disorders
Is Fanconi anemia inherited ?,0000369-4,inheritance,"Fanconi anemia is most often inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Very rarely, this condition is inherited in an X-linked recessive pattern. The gene associated with X-linked recessive Fanconi anemia is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",Fanconi anemia,0000369,GHR,https://ghr.nlm.nih.gov/condition/fanconi-anemia,C3469521,T047,Disorders
What are the treatments for Fanconi anemia ?,0000369-5,treatment,"These resources address the diagnosis or management of Fanconi anemia:  - Cincinnati Children's Hospital: Fanconi Anemia Comprehensive Care Center  - Fanconi Anemia Research Fund: Fanconi Anemia Guidelines for Diagnosis and Management  - Gene Review: Gene Review: Fanconi Anemia  - Genetic Testing Registry: Fanconi anemia  - Genetic Testing Registry: Fanconi anemia, complementation group A  - Genetic Testing Registry: Fanconi anemia, complementation group B  - Genetic Testing Registry: Fanconi anemia, complementation group C  - Genetic Testing Registry: Fanconi anemia, complementation group D1  - Genetic Testing Registry: Fanconi anemia, complementation group D2  - Genetic Testing Registry: Fanconi anemia, complementation group E  - Genetic Testing Registry: Fanconi anemia, complementation group F  - Genetic Testing Registry: Fanconi anemia, complementation group G  - Genetic Testing Registry: Fanconi anemia, complementation group I  - Genetic Testing Registry: Fanconi anemia, complementation group J  - Genetic Testing Registry: Fanconi anemia, complementation group L  - Genetic Testing Registry: Fanconi anemia, complementation group M  - Genetic Testing Registry: Fanconi anemia, complementation group N  - Genetic Testing Registry: Fanconi anemia, complementation group O  - Genetic Testing Registry: Fanconi anemia, complementation group P  - MedlinePlus Encyclopedia: Fanconi's Anemia  - National Cancer Institute: Adult Acute Myeloid Leukemia Treatment PDQ  - National Cancer Institute: Myelodysplastic Syndromes Treatment PDQ  - National Heart Lung and Blood Institute: How is Fanconi Anemia Treated?  - The Rockefeller University: International Fanconi Anemia Registry   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Fanconi anemia,0000369,GHR,https://ghr.nlm.nih.gov/condition/fanconi-anemia,C3469521,T047,Disorders
What is (are) Farber lipogranulomatosis ?,0000370-1,information,"Farber lipogranulomatosis is a rare inherited condition involving the breakdown and use of fats in the body (lipid metabolism). In affected individuals, lipids accumulate abnormally in cells and tissues throughout the body, particularly around the joints.  Three classic signs occur in Farber lipogranulomatosis: a hoarse voice or a weak cry, small lumps of fat under the skin and in other tissues (lipogranulomas), and swollen and painful joints. Affected individuals may also have difficulty breathing, an enlarged liver and spleen (hepatosplenomegaly), and developmental delay.  Researchers have described seven types of Farber lipogranulomatosis based on their characteristic features.  Type 1 is the most common, or classical, form of this condition and is associated with the classic signs of voice, skin, and joint problems that begin a few months after birth. Developmental delay and lung disease also commonly occur. Infants born with type 1 Farber lipogranulomatosis usually survive only into early childhood.  Types 2 and 3 generally have less severe signs and symptoms than the other types. Affected individuals have the three classic signs and usually do not have developmental delay. Children with these types of Farber lipogranulomatosis typically live into mid- to late childhood.  Types 4 and 5 are associated with severe neurological problems. Type 4 usually causes life-threatening health problems beginning in infancy due to massive lipid deposits in the liver, spleen, lungs, and immune system tissues. Children with this type typically do not survive past their first year of life. Type 5 is characterized by progressive decline in brain and spinal cord (central nervous system) function, which causes paralysis of the arms and legs (quadriplegia), seizures, loss of speech, involuntary muscle jerks (myoclonus), and developmental delay. Children with type 5 Farber lipogranulomatosis survive into early childhood.  Types 6 and 7 are very rare, and affected individuals have other associated disorders in addition to Farber lipogranulomatosis.",Farber lipogranulomatosis,0000370,GHR,https://ghr.nlm.nih.gov/condition/farber-lipogranulomatosis,C0268255,T047,Disorders
How many people are affected by Farber lipogranulomatosis ?,0000370-2,frequency,Farber lipogranulomatosis is a rare disorder. About 80 cases have been reported worldwide.,Farber lipogranulomatosis,0000370,GHR,https://ghr.nlm.nih.gov/condition/farber-lipogranulomatosis,C0268255,T047,Disorders
What are the genetic changes related to Farber lipogranulomatosis ?,0000370-3,genetic changes,"Mutations in the ASAH1 gene cause Farber lipogranulomatosis. The ASAH1 gene provides instructions for making an enzyme called acid ceramidase. This enzyme is found in cell compartments called lysosomes, which digest and recycle materials. Acid ceramidase breaks down fats called ceramides into a fat called sphingosine and a fatty acid. These two breakdown products are recycled to create new ceramides for the body to use. Ceramides have several roles within cells. For example, they are a component of a fatty substance called myelin that insulates and protects nerve cells.  Mutations in the ASAH1 gene lead to severe reduction in acid ceramidase, typically to below 10 percent of normal. As a result, the enzyme cannot break down ceramides properly and they build up in the lysosomes of various cells, including in the lung, liver, colon, muscles used for movement (skeletal muscles), cartilage, and bone. The buildup of ceramides along with the reduction of its fatty breakdown products in cells likely causes the signs and symptoms of Farber lipogranulomatosis. It is unclear whether the level of acid ceramidase activity is related to the severity of the disorder.",Farber lipogranulomatosis,0000370,GHR,https://ghr.nlm.nih.gov/condition/farber-lipogranulomatosis,C0268255,T047,Disorders
Is Farber lipogranulomatosis inherited ?,0000370-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Farber lipogranulomatosis,0000370,GHR,https://ghr.nlm.nih.gov/condition/farber-lipogranulomatosis,C0268255,T047,Disorders
What are the treatments for Farber lipogranulomatosis ?,0000370-5,treatment,These resources address the diagnosis or management of Farber lipogranulomatosis:  - Genetic Testing Registry: Farber's lipogranulomatosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Farber lipogranulomatosis,0000370,GHR,https://ghr.nlm.nih.gov/condition/farber-lipogranulomatosis,C0268255,T047,Disorders
What is (are) fatty acid hydroxylase-associated neurodegeneration ?,0000371-1,information,"Fatty acid hydroxylase-associated neurodegeneration (FAHN) is a progressive disorder of the nervous system (neurodegeneration) characterized by problems with movement and vision that begin during childhood or adolescence.  Changes in the way a person walks (gait) and frequent falls are usually the first noticeable signs of FAHN. Affected individuals gradually develop extreme muscle stiffness (spasticity) and exaggerated reflexes. They typically have involuntary muscle cramping (dystonia), problems with coordination and balance (ataxia), or both. The movement problems worsen over time, and some people with this condition eventually require wheelchair assistance.  People with FAHN often develop vision problems, which occur due to deterioration (atrophy) of the nerves that carry information from the eyes to the brain (the optic nerves) and difficulties with the muscles that control eye movement. Affected individuals may have a loss of sharp vision (reduced visual acuity), decreased field of vision, impaired color perception, eyes that do not look in the same direction (strabismus), rapid involuntary eye movements (nystagmus), or difficulty moving the eyes intentionally (supranuclear gaze palsy).  Speech impairment (dysarthria) also occurs in FAHN, and severely affected individuals may lose the ability to speak. People with this disorder may also have difficulty chewing or swallowing (dysphagia). In severe cases, they may develop malnutrition and require a feeding tube. The swallowing difficulties can lead to a bacterial lung infection called aspiration pneumonia, which can be life-threatening. As the disorder progresses, some affected individuals experience seizures and a decline in intellectual function.  Magnetic resonance imaging (MRI) of the brain in people with FAHN shows signs of iron accumulation, especially in an area of the brain called the globus pallidus, which is involved in regulating movement. Similar patterns of iron accumulation are seen in certain other neurological disorders such as infantile neuroaxonal dystrophy and pantothenate kinase-associated neurodegeneration. All these conditions belong to a class of disorders called neurodegeneration with brain iron accumulation (NBIA).",fatty acid hydroxylase-associated neurodegeneration,0000371,GHR,https://ghr.nlm.nih.gov/condition/fatty-acid-hydroxylase-associated-neurodegeneration,C3668943,T047,Disorders
How many people are affected by fatty acid hydroxylase-associated neurodegeneration ?,0000371-2,frequency,FAHN is a rare disorder; only a few dozen cases have been reported.,fatty acid hydroxylase-associated neurodegeneration,0000371,GHR,https://ghr.nlm.nih.gov/condition/fatty-acid-hydroxylase-associated-neurodegeneration,C3668943,T047,Disorders
What are the genetic changes related to fatty acid hydroxylase-associated neurodegeneration ?,0000371-3,genetic changes,"Mutations in the FA2H gene cause FAHN. The FA2H gene provides instructions for making an enzyme called fatty acid 2-hydroxylase. This enzyme modifies fatty acids, which are building blocks used to make fats (lipids). Specifically, fatty acid 2-hydroxylase adds a single oxygen atom to a hydrogen atom at a particular point on a fatty acid to create a 2-hydroxylated fatty acid. Certain 2-hydroxylated fatty acids are important in forming normal myelin; myelin is the protective covering that insulates nerves and ensures the rapid transmission of nerve impulses. The part of the brain and spinal cord that contains myelin is called white matter.  The FA2H gene mutations that cause FAHN reduce or eliminate the function of the fatty acid 2-hydroxylase enzyme. Reduction of this enzyme's function may result in abnormal myelin that is prone to deterioration (demyelination), leading to a loss of white matter (leukodystrophy). Leukodystrophy is likely involved in the development of the movement problems and other neurological abnormalities that occur in FAHN. Iron accumulation in the brain is probably also involved, although it is unclear how FA2H gene mutations lead to the buildup of iron.  People with FA2H gene mutations and some of the movement problems seen in FAHN were once classified as having a separate disorder called spastic paraplegia 35. People with mutations in this gene resulting in intellectual decline and optic nerve atrophy were said to have a disorder called FA2H-related leukodystrophy. However, these conditions are now generally considered to be forms of FAHN.",fatty acid hydroxylase-associated neurodegeneration,0000371,GHR,https://ghr.nlm.nih.gov/condition/fatty-acid-hydroxylase-associated-neurodegeneration,C3668943,T047,Disorders
Is fatty acid hydroxylase-associated neurodegeneration inherited ?,0000371-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",fatty acid hydroxylase-associated neurodegeneration,0000371,GHR,https://ghr.nlm.nih.gov/condition/fatty-acid-hydroxylase-associated-neurodegeneration,C3668943,T047,Disorders
What are the treatments for fatty acid hydroxylase-associated neurodegeneration ?,0000371-5,treatment,These resources address the diagnosis or management of fatty acid hydroxylase-associated neurodegeneration:  - Gene Review: Gene Review: Fatty Acid Hydroxylase-Associated Neurodegeneration  - Genetic Testing Registry: Spastic paraplegia 35   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,fatty acid hydroxylase-associated neurodegeneration,0000371,GHR,https://ghr.nlm.nih.gov/condition/fatty-acid-hydroxylase-associated-neurodegeneration,C3668943,T047,Disorders
What is (are) Feingold syndrome ?,0000372-1,information,"Feingold syndrome is a disorder that affects many parts of the body. The signs and symptoms of this condition vary among affected individuals, even among members of the same family.  Individuals with Feingold syndrome have characteristic abnormalities of their fingers and toes. Almost all people with this condition have a specific hand abnormality called brachymesophalangy, which refers to shortening of the second and fifth fingers. Other common abnormalities include fifth fingers that curve inward (clinodactyly), underdeveloped thumbs (thumb hypoplasia), and fusion (syndactyly) of the second and third toes or the fourth and fifth toes.  People with Feingold syndrome are frequently born with a blockage in part of their digestive system called gastrointestinal atresia. In most cases, the blockage occurs in the esophagus (esophageal atresia) or in part of the small intestine (duodenal atresia). Additional common features of Feingold syndrome include an unusually small head size (microcephaly), a small jaw (micrognathia), a narrow opening of the eyelids (short palpebral fissures), and mild to moderate learning disability. Less often, affected individuals have hearing loss, impaired growth, and kidney and heart abnormalities.",Feingold syndrome,0000372,GHR,https://ghr.nlm.nih.gov/condition/feingold-syndrome,C0796068,T047,Disorders
How many people are affected by Feingold syndrome ?,0000372-2,frequency,"Feingold syndrome appears to be a rare condition, although its exact prevalence is unknown.",Feingold syndrome,0000372,GHR,https://ghr.nlm.nih.gov/condition/feingold-syndrome,C0796068,T047,Disorders
What are the genetic changes related to Feingold syndrome ?,0000372-3,genetic changes,"Mutations in the MYCN gene cause Feingold syndrome. This gene provides instructions for making a protein that plays an important role in the formation of tissues and organs during embryonic development. Studies in animals suggest that this protein is necessary for normal development of the limbs, heart, kidneys, nervous system, digestive system, and lungs. The MYCN protein regulates the activity of other genes by attaching (binding) to specific regions of DNA. On the basis of this action, this protein is called a transcription factor.  Mutations in the MYCN gene that cause Feingold syndrome prevent one copy of the gene in each cell from producing any functional MYCN protein. As a result, only half the normal amount of this protein is available to control the activity of specific genes during embryonic development. It remains unclear how a reduced amount of the MYCN protein causes the specific features of Feingold syndrome.",Feingold syndrome,0000372,GHR,https://ghr.nlm.nih.gov/condition/feingold-syndrome,C0796068,T047,Disorders
Is Feingold syndrome inherited ?,0000372-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Feingold syndrome,0000372,GHR,https://ghr.nlm.nih.gov/condition/feingold-syndrome,C0796068,T047,Disorders
What are the treatments for Feingold syndrome ?,0000372-5,treatment,These resources address the diagnosis or management of Feingold syndrome:  - Gene Review: Gene Review: Feingold Syndrome 1  - Genetic Testing Registry: Feingold syndrome 1  - Genetic Testing Registry: Feingold syndrome 2  - MedlinePlus Encyclopedia: Duodenal Atresia  - MedlinePlus Encyclopedia: Esophageal Atresia  - MedlinePlus Encyclopedia: Microcephaly  - MedlinePlus Encyclopedia: Webbing of the Fingers or Toes   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Feingold syndrome,0000372,GHR,https://ghr.nlm.nih.gov/condition/feingold-syndrome,C0796068,T047,Disorders
What is (are) FG syndrome ?,0000373-1,information,"FG syndrome is a genetic condition that affects many parts of the body and occurs almost exclusively in males. ""FG"" represents the surname initials of the first family diagnosed with the disorder.  FG syndrome affects intelligence and behavior. Almost everyone with the condition has intellectual disability, which ranges from mild to severe. Affected individuals tend to be friendly, inquisitive, and hyperactive, with a short attention span. Compared to people with other forms of intellectual disability, their socialization and daily living skills are strong, while verbal communication and language skills tend to be weaker.  The physical features of FG syndrome include weak muscle tone (hypotonia), broad thumbs, and wide first (big) toes. Abnormalities of the tissue connecting the left and right halves of the brain (the corpus callosum) are also common. Most affected individuals have constipation, and many have abnormalities of the anus such as an obstruction of the anal opening (imperforate anus). People with FG syndrome also tend to have a distinctive facial appearance including small, underdeveloped ears; a tall, prominent forehead; and outside corners of the eyes that point downward (down-slanting palpebral fissures).  Additional features seen in some people with FG syndrome include widely set eyes (hypertelorism), an upswept frontal hairline, and a large head compared to body size (relative macrocephaly). Other health problems have also been reported, including heart defects, seizures, undescended testes (cryptorchidism) in males, and a soft out-pouching in the lower abdomen (an inguinal hernia).",FG syndrome,0000373,GHR,https://ghr.nlm.nih.gov/condition/fg-syndrome,C0220769,T019,Disorders
How many people are affected by FG syndrome ?,0000373-2,frequency,"The prevalence of FG syndrome is unknown, although several hundred cases have been reported worldwide. Researchers suspect that FG syndrome may be overdiagnosed because many of its signs and symptoms are also seen with other disorders.",FG syndrome,0000373,GHR,https://ghr.nlm.nih.gov/condition/fg-syndrome,C0220769,T019,Disorders
What are the genetic changes related to FG syndrome ?,0000373-3,genetic changes,"Researchers have identified changes in five regions of the X chromosome that are linked to FG syndrome in affected families. Mutations in a gene called MED12, which is located in one of these regions, appear to be the most common cause of the disorder. Researchers are investigating genes in other regions of the X chromosome that may also be associated with FG syndrome.  The MED12 gene provides instructions for making a protein that helps regulate gene activity. Specifically, the MED12 protein forms part of a large complex (a group of proteins that work together) that turns genes on and off. The MED12 protein is thought to play an essential role in development both before and after birth.  At least two mutations in the MED12 gene have been found to cause FG syndrome. Although the mutations alter the structure of the MED12 protein, it is unclear how they lead to intellectual disability, behavioral changes, and the physical features associated with this condition.",FG syndrome,0000373,GHR,https://ghr.nlm.nih.gov/condition/fg-syndrome,C0220769,T019,Disorders
Is FG syndrome inherited ?,0000373-4,inheritance,"FG syndrome is inherited in an X-linked recessive pattern. The genes likely associated with this disorder, including MED12, are located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation usually must occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of a gene on the X chromosome, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",FG syndrome,0000373,GHR,https://ghr.nlm.nih.gov/condition/fg-syndrome,C0220769,T019,Disorders
What are the treatments for FG syndrome ?,0000373-5,treatment,These resources address the diagnosis or management of FG syndrome:  - Gene Review: Gene Review: MED12-Related Disorders  - Genetic Testing Registry: FG syndrome  - Genetic Testing Registry: FG syndrome 2  - Genetic Testing Registry: FG syndrome 3  - Genetic Testing Registry: FG syndrome 4  - Genetic Testing Registry: FG syndrome 5  - MedlinePlus Encyclopedia: Corpus Callosum of the Brain (image)  - MedlinePlus Encyclopedia: Imperforate Anus   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,FG syndrome,0000373,GHR,https://ghr.nlm.nih.gov/condition/fg-syndrome,C0220769,T019,Disorders
What is (are) fibrochondrogenesis ?,0000374-1,information,"Fibrochondrogenesis is a very severe disorder of bone growth. Affected infants have a very narrow chest, which prevents the lungs from developing normally. Most infants with this condition are stillborn or die shortly after birth from respiratory failure. However, some affected individuals have lived into childhood.  Fibrochondrogenesis is characterized by short stature (dwarfism) and other skeletal abnormalities. Affected individuals have shortened long bones in the arms and legs that are unusually wide at the ends (described as dumbbell-shaped). People with this condition also have a narrow chest with short, wide ribs and a round and prominent abdomen. The bones of the spine (vertebrae) are flattened (platyspondyly) and have a characteristic pinched or pear shape that is noticeable on x-rays. Other skeletal abnormalities associated with fibrochondrogenesis include abnormal curvature of the spine and underdeveloped hip (pelvic) bones.  People with fibrochondrogenesis also have distinctive facial features. These include prominent eyes, low-set ears, a small mouth with a long upper lip, and a small chin (micrognathia). Affected individuals have a relatively flat-appearing midface, particularly a small nose with a flat nasal bridge and nostrils that open to the front rather than downward (anteverted nares). Vision problems, including severe nearsightedness (high myopia) and clouding of the lens of the eye (cataract), are common in those who survive infancy. Most affected individuals also have sensorineural hearing loss, which is caused by abnormalities of the inner ear.",fibrochondrogenesis,0000374,GHR,https://ghr.nlm.nih.gov/condition/fibrochondrogenesis,C0265282,T019,Disorders
How many people are affected by fibrochondrogenesis ?,0000374-2,frequency,Fibrochondrogenesis appears to be a rare disorder. About 20 affected individuals have been described in the medical literature.,fibrochondrogenesis,0000374,GHR,https://ghr.nlm.nih.gov/condition/fibrochondrogenesis,C0265282,T019,Disorders
What are the genetic changes related to fibrochondrogenesis ?,0000374-3,genetic changes,"Fibrochondrogenesis can result from mutations in the COL11A1 or COL11A2 gene. These genes provide instructions for making components of type XI collagen, which is a complex molecule that gives structure and strength to the connective tissues that support the body's joints and organs. Specifically, type XI collagen is found in cartilage, a tough but flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Type XI collagen is also part of the inner ear; the vitreous, which is the clear gel that fills the eyeball; and the nucleus pulposus, which is the center portion of the discs between vertebrae.  Mutations in the COL11A1 or COL11A2 gene impair the assembly of type XI collagen, in most cases leading to the production of abnormal collagen molecules. The defective collagen weakens connective tissues, impairing the formation of bones throughout the skeleton and causing changes in the eye and inner ear that lead to vision and hearing problems.",fibrochondrogenesis,0000374,GHR,https://ghr.nlm.nih.gov/condition/fibrochondrogenesis,C0265282,T019,Disorders
Is fibrochondrogenesis inherited ?,0000374-4,inheritance,"Fibrochondrogenesis is generally inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they usually do not show signs and symptoms of the condition. In a few reported cases, parents of children with fibrochondrogenesis have had mild features that may be related to the condition, including slightly short stature, myopia, cataracts, joint pain, and hearing loss.  In at least one case of fibrochondrogenesis caused by a COL11A2 gene mutation, the condition was inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In this case, the condition resulted from a new (de novo) mutation in the gene that occurred during the formation of reproductive cells (eggs or sperm) in one of the affected individual's parents. There was no history of the disorder in the family.",fibrochondrogenesis,0000374,GHR,https://ghr.nlm.nih.gov/condition/fibrochondrogenesis,C0265282,T019,Disorders
What are the treatments for fibrochondrogenesis ?,0000374-5,treatment,These resources address the diagnosis or management of fibrochondrogenesis:  - Genetic Testing Registry: Fibrochondrogenesis  - Genetic Testing Registry: Fibrochondrogenesis 2   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,fibrochondrogenesis,0000374,GHR,https://ghr.nlm.nih.gov/condition/fibrochondrogenesis,C0265282,T019,Disorders
What is (are) fibrodysplasia ossificans progressiva ?,0000375-1,information,"Fibrodysplasia ossificans progressiva (FOP) is a disorder in which muscle tissue and connective tissue such as tendons and ligaments are gradually replaced by bone (ossified), forming bone outside the skeleton (extra-skeletal or heterotopic bone) that constrains movement. This process generally becomes noticeable in early childhood, starting with the neck and shoulders and proceeding down the body and into the limbs.  Extra-skeletal bone formation causes progressive loss of mobility as the joints become affected. Inability to fully open the mouth may cause difficulty in speaking and eating. Over time, people with this disorder may experience malnutrition due to their eating problems. They may also have breathing difficulties as a result of extra bone formation around the rib cage that restricts expansion of the lungs.  Any trauma to the muscles of an individual with fibrodysplasia ossificans progressiva, such as a fall or invasive medical procedures, may trigger episodes of muscle swelling and inflammation (myositis) followed by more rapid ossification in the injured area. Flare-ups may also be caused by viral illnesses such as influenza.  People with fibrodysplasia ossificans progressiva are generally born with malformed big toes. This abnormality of the big toes is a characteristic feature that helps to distinguish this disorder from other bone and muscle problems. Affected individuals may also have short thumbs and other skeletal abnormalities.",fibrodysplasia ossificans progressiva,0000375,GHR,https://ghr.nlm.nih.gov/condition/fibrodysplasia-ossificans-progressiva,C0016037,T047,Disorders
How many people are affected by fibrodysplasia ossificans progressiva ?,0000375-2,frequency,"Fibrodysplasia ossificans progressiva is a very rare disorder, believed to occur in approximately 1 in 2 million people worldwide. Several hundred cases have been reported.",fibrodysplasia ossificans progressiva,0000375,GHR,https://ghr.nlm.nih.gov/condition/fibrodysplasia-ossificans-progressiva,C0016037,T047,Disorders
What are the genetic changes related to fibrodysplasia ossificans progressiva ?,0000375-3,genetic changes,"Mutations in the ACVR1 gene cause fibrodysplasia ossificans progressiva.  The ACVR1 gene provides instructions for producing a member of a protein family called bone morphogenetic protein (BMP) type I receptors. The ACVR1 protein is found in many tissues of the body including skeletal muscle and cartilage. It helps to control the growth and development of the bones and muscles, including the gradual replacement of cartilage by bone (ossification) that occurs in normal skeletal maturation from birth to young adulthood.  Researchers believe that a mutation in the ACVR1 gene may change the shape of the receptor under certain conditions and disrupt mechanisms that control the receptor's activity. As a result, the receptor may be constantly turned on (constitutive activation). Constitutive activation of the receptor causes overgrowth of bone and cartilage and fusion of joints, resulting in the signs and symptoms of fibrodysplasia ossificans progressiva.",fibrodysplasia ossificans progressiva,0000375,GHR,https://ghr.nlm.nih.gov/condition/fibrodysplasia-ossificans-progressiva,C0016037,T047,Disorders
Is fibrodysplasia ossificans progressiva inherited ?,0000375-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  Most cases of fibrodysplasia ossificans progressiva result from new mutations in the gene. These cases occur in people with no history of the disorder in their family. In a small number of cases, an affected person has inherited the mutation from one affected parent.",fibrodysplasia ossificans progressiva,0000375,GHR,https://ghr.nlm.nih.gov/condition/fibrodysplasia-ossificans-progressiva,C0016037,T047,Disorders
What are the treatments for fibrodysplasia ossificans progressiva ?,0000375-5,treatment,These resources address the diagnosis or management of fibrodysplasia ossificans progressiva:  - Genetic Testing Registry: Progressive myositis ossificans   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,fibrodysplasia ossificans progressiva,0000375,GHR,https://ghr.nlm.nih.gov/condition/fibrodysplasia-ossificans-progressiva,C0016037,T047,Disorders
What is (are) fibronectin glomerulopathy ?,0000376-1,information,"Fibronectin glomerulopathy is a kidney disease that usually develops between early and mid-adulthood but can occur at any age. It eventually leads to irreversible kidney failure (end-stage renal disease).  Individuals with fibronectin glomerulopathy usually have blood and excess protein in their urine (hematuria and proteinuria, respectively). They also have high blood pressure (hypertension). Some affected individuals develop renal tubular acidosis, which occurs when the kidneys are unable to remove enough acid from the body and the blood becomes too acidic.  The kidneys of people with fibronectin glomerulopathy have large deposits of the protein fibronectin-1 in structures called glomeruli. These structures are clusters of tiny blood vessels in the kidneys that filter waste products from blood. The waste products are then released in urine. The fibronectin-1 deposits impair the glomeruli's filtration ability.  Fifteen to 20 years following the appearance of signs and symptoms, individuals with fibronectin glomerulopathy often develop end-stage renal disease. Affected individuals may receive treatment in the form of a kidney transplant; in some cases, fibronectin glomerulopathy comes back (recurs) following transplantation.",fibronectin glomerulopathy,0000376,GHR,https://ghr.nlm.nih.gov/condition/fibronectin-glomerulopathy,C1866075,T047,Disorders
How many people are affected by fibronectin glomerulopathy ?,0000376-2,frequency,"Fibronectin glomerulopathy is likely a rare condition, although its prevalence is unknown. At least 45 cases have been described in the scientific literature.",fibronectin glomerulopathy,0000376,GHR,https://ghr.nlm.nih.gov/condition/fibronectin-glomerulopathy,C1866075,T047,Disorders
What are the genetic changes related to fibronectin glomerulopathy ?,0000376-3,genetic changes,"Fibronectin glomerulopathy can be caused by mutations in the FN1 gene. The FN1 gene provides instructions for making the fibronectin-1 protein. Fibronectin-1 is involved in the continual formation of the extracellular matrix, which is an intricate lattice of proteins and other molecules that forms in the spaces between cells. During extracellular matrix formation, fibronectin-1 helps individual cells expand (spread) and move (migrate) to cover more space, and it also influences cell shape and maturation (differentiation).  FN1 gene mutations lead to production of an abnormal fibronectin-1 protein that gets deposited in the glomeruli of the kidneys, probably as the body attempts to filter it out as waste. Even though there is an abundance of fibronectin-1 in the glomeruli, the extracellular matrix that supports the blood vessels is weak because the altered fibronectin-1 cannot assist in the matrix's continual formation. Without a strong cellular support network, the glomeruli are less able to filter waste. As a result, products that normally are retained by the body, such as protein and blood, get released in the urine, and acids are not properly filtered from the blood. Over time, the kidneys' ability to filter waste decreases until the kidneys can no longer function, resulting in end-stage renal disease.  It is estimated that mutations in the FN1 gene are responsible for 40 percent of cases of fibronectin glomerulopathy. The cause of the remaining cases of this condition is unknown.",fibronectin glomerulopathy,0000376,GHR,https://ghr.nlm.nih.gov/condition/fibronectin-glomerulopathy,C1866075,T047,Disorders
Is fibronectin glomerulopathy inherited ?,0000376-4,inheritance,"When fibronectin glomerulopathy is caused by mutations in the FN1 gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some of these cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family. Some people who have the altered FN1 gene never develop the condition, a situation known as reduced penetrance.",fibronectin glomerulopathy,0000376,GHR,https://ghr.nlm.nih.gov/condition/fibronectin-glomerulopathy,C1866075,T047,Disorders
What are the treatments for fibronectin glomerulopathy ?,0000376-5,treatment,These resources address the diagnosis or management of fibronectin glomerulopathy:  - Genetic Testing Registry: Glomerulopathy with fibronectin deposits 2  - MedlinePlus Encyclopedia: Protein Urine Test   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,fibronectin glomerulopathy,0000376,GHR,https://ghr.nlm.nih.gov/condition/fibronectin-glomerulopathy,C1866075,T047,Disorders
What is (are) fish-eye disease ?,0000377-1,information,"Fish-eye disease, also called partial LCAT deficiency, is a disorder that causes the clear front surface of the eyes (the corneas) to gradually become cloudy. The cloudiness, which generally first appears in adolescence or early adulthood, consists of small grayish dots of cholesterol (opacities) distributed across the corneas. Cholesterol is a waxy, fat-like substance that is produced in the body and obtained from foods that come from animals; it aids in many functions of the body but can become harmful in excessive amounts. As fish-eye disease progresses, the corneal cloudiness worsens and can lead to severely impaired vision.",fish-eye disease,0000377,GHR,https://ghr.nlm.nih.gov/condition/fish-eye-disease,C0342895,T047,Disorders
How many people are affected by fish-eye disease ?,0000377-2,frequency,Fish-eye disease is a rare disorder. Approximately 30 cases have been reported in the medical literature.,fish-eye disease,0000377,GHR,https://ghr.nlm.nih.gov/condition/fish-eye-disease,C0342895,T047,Disorders
What are the genetic changes related to fish-eye disease ?,0000377-3,genetic changes,"Fish-eye disease is caused by mutations in the LCAT gene. This gene provides instructions for making an enzyme called lecithin-cholesterol acyltransferase (LCAT).  The LCAT enzyme plays a role in removing cholesterol from the blood and tissues by helping it attach to molecules called lipoproteins, which carry it to the liver. Once in the liver, the cholesterol is redistributed to other tissues or removed from the body. The enzyme has two major functions, called alpha- and beta-LCAT activity. Alpha-LCAT activity helps attach cholesterol to a lipoprotein called high-density lipoprotein (HDL). Beta-LCAT activity helps attach cholesterol to other lipoproteins called very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL).  LCAT gene mutations that cause fish-eye disease impair alpha-LCAT activity, reducing the enzyme's ability to attach cholesterol to HDL. Impairment of this mechanism for reducing cholesterol in the body leads to cholesterol-containing opacities in the corneas. It is not known why the cholesterol deposits affect only the corneas in this disorder. Mutations that affect both alpha-LCAT activity and beta-LCAT activity lead to a related disorder called complete LCAT deficiency, which involves corneal opacities in combination with features affecting other parts of the body.",fish-eye disease,0000377,GHR,https://ghr.nlm.nih.gov/condition/fish-eye-disease,C0342895,T047,Disorders
Is fish-eye disease inherited ?,0000377-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",fish-eye disease,0000377,GHR,https://ghr.nlm.nih.gov/condition/fish-eye-disease,C0342895,T047,Disorders
What are the treatments for fish-eye disease ?,0000377-5,treatment,These resources address the diagnosis or management of fish-eye disease:  - Genetic Testing Registry: Fish-eye disease  - MedlinePlus Encyclopedia: Corneal Transplant  - Oregon Health and Science University: Corneal Dystrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,fish-eye disease,0000377,GHR,https://ghr.nlm.nih.gov/condition/fish-eye-disease,C0342895,T047,Disorders
What is (are) Floating-Harbor syndrome ?,0000378-1,information,"Floating-Harbor syndrome is a disorder involving short stature, slowing of the mineralization of the bones (delayed bone age), delayed speech development, and characteristic facial features. The condition is named for the hospitals where it was first described, the Boston Floating Hospital and Harbor General Hospital in Torrance, California.  Growth deficiency in people with Floating-Harbor syndrome generally becomes apparent in the first year of life, and affected individuals are usually among the shortest 5 percent of their age group. Bone age is delayed in early childhood; for example, an affected 3-year-old child may have bones more typical of a child of 2. However, bone age is usually normal by age 6 to 12.  Delay in speech development (expressive language delay) may be severe in Floating-Harbor syndrome, and language impairment can lead to problems in verbal communication. Most affected individuals also have mild intellectual disability. Their development of motor skills, such as sitting and crawling, is similar to that of other children their age.  Typical facial features in people with Floating-Harbor syndrome include a triangular face; a low hairline; deep-set eyes; long eyelashes; a large, distinctive nose with a low-hanging separation (overhanging columella) between large nostrils; a shortened distance between the nose and upper lip (a short philtrum); and thin lips. As affected children grow and mature, the nose becomes more prominent.  Additional features that have occurred in some affected individuals include short fingers and toes (brachydactyly); widened and rounded tips of the fingers (clubbing); curved pinky fingers (fifth finger clinodactyly); an unusually high-pitched voice; and, in males, undescended testes (cryptorchidism).",Floating-Harbor syndrome,0000378,GHR,https://ghr.nlm.nih.gov/condition/floating-harbor-syndrome,C0729582,T047,Disorders
How many people are affected by Floating-Harbor syndrome ?,0000378-2,frequency,Floating-Harbor syndrome is a rare disorder; only about 50 cases have been reported in the medical literature.,Floating-Harbor syndrome,0000378,GHR,https://ghr.nlm.nih.gov/condition/floating-harbor-syndrome,C0729582,T047,Disorders
What are the genetic changes related to Floating-Harbor syndrome ?,0000378-3,genetic changes,"Floating-Harbor syndrome is caused by mutations in the SRCAP gene. This gene provides instructions for making a protein called Snf2-related CREBBP activator protein, or SRCAP. SRCAP is one of several proteins that help activate a gene called CREBBP. The protein produced from the CREBBP gene plays a key role in regulating cell growth and division and is important for normal development.  Mutations in the SRCAP gene may result in an altered protein that interferes with normal activation of the CREBBP gene, resulting in problems in development. However, the relationship between SRCAP gene mutations and the specific signs and symptoms of Floating-Harbor syndrome is unknown. Rubinstein-Taybi syndrome, a disorder with similar features, is caused by mutations in the CREBBP gene itself.",Floating-Harbor syndrome,0000378,GHR,https://ghr.nlm.nih.gov/condition/floating-harbor-syndrome,C0729582,T047,Disorders
Is Floating-Harbor syndrome inherited ?,0000378-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  Most cases of Floating-Harbor syndrome result from new mutations in the gene and occur in people with no history of the disorder in their family. However, in some cases an affected person inherits the mutation from one affected parent.",Floating-Harbor syndrome,0000378,GHR,https://ghr.nlm.nih.gov/condition/floating-harbor-syndrome,C0729582,T047,Disorders
What are the treatments for Floating-Harbor syndrome ?,0000378-5,treatment,These resources address the diagnosis or management of Floating-Harbor syndrome:  - Gene Review: Gene Review: Floating-Harbor Syndrome  - Genetic Testing Registry: Floating-Harbor syndrome  - KidsHealth: Bone Age Study   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Floating-Harbor syndrome,0000378,GHR,https://ghr.nlm.nih.gov/condition/floating-harbor-syndrome,C0729582,T047,Disorders
What is (are) focal dermal hypoplasia ?,0000379-1,information,"Focal dermal hypoplasia is a genetic disorder that primarily affects the skin, skeleton, eyes, and face. About 90 percent of affected individuals are female. Males usually have milder signs and symptoms than females. Although intelligence is typically unaffected, some individuals have intellectual disability.  People with focal dermal hypoplasia have skin abnormalities present from birth, such as streaks of very thin skin (dermal hypoplasia), yellowish-pink nodules of fat under the skin, areas where the top layers of skin are absent (cutis aplasia), small clusters of veins on the surface of the skin (telangiectases), and streaks of slightly darker or lighter skin. These skin changes may cause pain, itching, irritation, or lead to skin infections. Wart-like growths called papillomas are usually not present at birth but develop with age. Papillomas typically form around the nostrils, lips, anus, and female genitalia. They may also be present in the throat, specifically in the esophagus or larynx, and can cause problems with swallowing, breathing, or sleeping. Papillomas can usually be surgically removed if necessary. Affected individuals may have small, ridged fingernails and toenails. Hair on the scalp can be sparse and brittle or absent.  Many individuals with focal dermal hypoplasia have hand and foot abnormalities, including missing fingers or toes (oligodactyly), webbed or fused fingers or toes (syndactyly), and a deep split in the hands or feet with missing fingers or toes and fusion of the remaining digits (ectrodactyly). X-rays can show streaks of altered bone density, called osteopathia striata, that do not cause any symptoms in people with focal dermal hypoplasia.  Eye abnormalities are common in individuals with focal dermal hypoplasia, including small eyes (microphthalmia), absent or severely underdeveloped eyes (anophthalmia), and problems with the tear ducts. Affected individuals may also have incomplete development of the light-sensitive tissue at the back of the eye (retina) or the nerve that relays visual information from the eye to the brain (optic nerve). This abnormal development of the retina and optic nerve can result in a gap or split in these structures, which is called a coloboma. Some of these eye abnormalities do not impair vision, while others can lead to low vision or blindness.  People with focal dermal hypoplasia may have distinctive facial features. Affected individuals often have a pointed chin, small ears, notched nostrils, and a slight difference in the size and shape of the right and left sides of the face (facial asymmetry). These facial characteristics are typically very subtle. An opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate) may also be present.  About half of individuals with focal dermal hypoplasia have abnormalities of their teeth, especially the hard, white material that forms the protective outer layer of each tooth (enamel). Less commonly, abnormalities of the kidneys and gastrointestinal system are present. The kidneys may be fused together, which predisposes affected individuals to kidney infections but does not typically cause significant health problems. The main gastrointestinal abnormality that occurs in people with focal dermal hypoplasia is an omphalocele, which is an opening in the wall of the abdomen that allows the abdominal organs to protrude through the navel. The signs and symptoms of focal dermal hypoplasia vary widely, although almost all affected individuals have skin abnormalities.",focal dermal hypoplasia,0000379,GHR,https://ghr.nlm.nih.gov/condition/focal-dermal-hypoplasia,C0016395,T047,Disorders
How many people are affected by focal dermal hypoplasia ?,0000379-2,frequency,"Focal dermal hypoplasia appears to be a rare condition, although its exact prevalence is unknown.",focal dermal hypoplasia,0000379,GHR,https://ghr.nlm.nih.gov/condition/focal-dermal-hypoplasia,C0016395,T047,Disorders
What are the genetic changes related to focal dermal hypoplasia ?,0000379-3,genetic changes,"Mutations in the PORCN gene cause focal dermal hypoplasia. This gene provides instructions for making a protein that is responsible for modifying other proteins, called Wnt proteins. Wnt proteins participate in chemical signaling pathways in the body that regulate development of the skin, bones, and other structures before birth.  Mutations in the PORCN gene appear to prevent the production of any functional PORCN protein. Researchers believe Wnt proteins cannot be released from the cell without the PORCN protein. When Wnt proteins are unable to leave the cell, they cannot participate in the chemical signaling pathways that are critical for normal development. The various signs and symptoms of focal dermal hypoplasia are likely due to abnormal Wnt signaling during early development.",focal dermal hypoplasia,0000379,GHR,https://ghr.nlm.nih.gov/condition/focal-dermal-hypoplasia,C0016395,T047,Disorders
Is focal dermal hypoplasia inherited ?,0000379-4,inheritance,"Focal dermal hypoplasia is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. The X chromosome that contains the mutated PORCN gene may be turned on (active) or turned off (inactive) due to a process called X-inactivation. Early in embryonic development in females, one of the two X chromosomes is permanently inactivated in somatic cells (cells other than egg and sperm cells). X-inactivation ensures that females, like males, have only one active copy of the X chromosome in each body cell. Usually X-inactivation occurs randomly, so that each X chromosome is active in about half the body's cells. Sometimes X-inactivation is not random, and one X chromosome is active in more than half of cells. When X-inactivation does not occur randomly, it is called skewed X-inactivation. Researchers suspect that the distribution of active and inactive X chromosomes may play a role in determining the severity of focal dermal hypoplasia in females.  In males (who have only one X chromosome), a mutation in the only copy of the PORCN gene in each cell appears to be lethal very early in development. A male can be born with focal dermal hypoplasia if he has a PORCN gene mutation in only some of his cells (known as mosaicism). Affected males typically experience milder symptoms of the disorder than females because more of their cells have a functional copy of the PORCN gene. A characteristic of focal dermal hypoplasia is that mildly affected fathers cannot pass this condition to their sons, but they can pass it to their daughters, who are usually more severely affected than they are. Women with focal dermal hypoplasia cannot pass this condition to their sons (because it is lethal early in development) but can pass it to their daughters.  Most cases of focal dermal hypoplasia in females result from new mutations in the PORCN gene and occur in people with no history of the disorder in their family. When focal dermal hypoplasia occurs in males, it always results from a new mutation in this gene that is not inherited. Only about 5 percent of females with this condition inherit a mutation in the PORCN gene from a parent.",focal dermal hypoplasia,0000379,GHR,https://ghr.nlm.nih.gov/condition/focal-dermal-hypoplasia,C0016395,T047,Disorders
What are the treatments for focal dermal hypoplasia ?,0000379-5,treatment,These resources address the diagnosis or management of focal dermal hypoplasia:  - Gene Review: Gene Review: Focal Dermal Hypoplasia  - Genetic Testing Registry: Focal dermal hypoplasia  - MedlinePlus Encyclopedia: Ectodermal dysplasia  - MedlinePlus Encyclopedia: Omphalocele   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,focal dermal hypoplasia,0000379,GHR,https://ghr.nlm.nih.gov/condition/focal-dermal-hypoplasia,C0016395,T047,Disorders
What is (are) FOXG1 syndrome ?,0000380-1,information,"FOXG1 syndrome is a condition characterized by impaired development and structural brain abnormalities. Affected infants are small at birth, and their heads grow more slowly than normal, leading to an unusually small head size (microcephaly) by early childhood. The condition is associated with a particular pattern of brain malformations that includes a thin or underdeveloped connection between the right and left halves of the brain (a structure called the corpus callosum), reduced folds and grooves (gyri) on the surface of the brain, and a smaller than usual amount of brain tissue known as white matter.  FOXG1 syndrome affects most aspects of development, and children with the condition typically have severe intellectual disability. Abnormal or involuntary movements, such as jerking movements of the arms and legs and repeated hand motions, are common, and most affected children do not learn to sit or walk without assistance. Babies and young children with FOXG1 syndrome often have feeding problems, sleep disturbances, seizures, irritability, and excessive crying. The condition is also characterized by limited communication and social interaction, including poor eye contact and a near absence of speech and language skills. Because of these social impairments, FOXG1 syndrome is classified as an autism spectrum disorder.  FOXG1 syndrome was previously described as a congenital variant of Rett syndrome, which is a similar disorder of brain development. Both disorders are characterized by impaired development, intellectual disability, and problems with communication and language. However, Rett syndrome is diagnosed almost exclusively in females, while FOXG1 syndrome affects both males and females. Rett syndrome also involves a period of apparently normal early development that does not occur in FOXG1 syndrome. Because of these differences, physicians and researchers now usually consider FOXG1 syndrome to be distinct from Rett syndrome.",FOXG1 syndrome,0000380,GHR,https://ghr.nlm.nih.gov/condition/foxg1-syndrome,C3150705,T019,Disorders
How many people are affected by FOXG1 syndrome ?,0000380-2,frequency,FOXG1 syndrome appears to be rare. At least 30 affected individuals have been described in the medical literature.,FOXG1 syndrome,0000380,GHR,https://ghr.nlm.nih.gov/condition/foxg1-syndrome,C3150705,T019,Disorders
What are the genetic changes related to FOXG1 syndrome ?,0000380-3,genetic changes,"As its name suggests, FOXG1 syndrome is caused by changes involving the FOXG1 gene. This gene provides instructions for making a protein called forkhead box G1. This protein plays an important role in brain development before birth, particularly in a region of the embryonic brain known as the telencephalon. The telencephalon ultimately develops into several critical structures, including the the largest part of the brain (the cerebrum), which controls most voluntary activity, language, sensory perception, learning, and memory.  In some cases, FOXG1 syndrome is caused by mutations within the FOXG1 gene itself. In others, the condition results from a deletion of genetic material from a region of the long (q) arm of chromosome 14 that includes the FOXG1 gene. All of these genetic changes prevent the production of forkhead box G1 or impair the protein's function. A shortage of functional forkhead box G1 disrupts normal brain development starting before birth, which appears to underlie the structural brain abnormalities and severe developmental problems characteristic of FOXG1 syndrome.",FOXG1 syndrome,0000380,GHR,https://ghr.nlm.nih.gov/condition/foxg1-syndrome,C3150705,T019,Disorders
Is FOXG1 syndrome inherited ?,0000380-4,inheritance,"FOXG1 syndrome is considered an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. All reported cases have resulted from new mutations or deletions involving the FOXG1 gene and have occurred in people with no history of the disorder in their family. Because the condition is so severe, no one with FOXG1 syndrome has been known to have children.",FOXG1 syndrome,0000380,GHR,https://ghr.nlm.nih.gov/condition/foxg1-syndrome,C3150705,T019,Disorders
What are the treatments for FOXG1 syndrome ?,0000380-5,treatment,"These resources address the diagnosis or management of FOXG1 syndrome:  - Genetic Testing Registry: Rett syndrome, congenital variant   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",FOXG1 syndrome,0000380,GHR,https://ghr.nlm.nih.gov/condition/foxg1-syndrome,C3150705,T019,Disorders
What is (are) fragile X syndrome ?,0000381-1,information,"Fragile X syndrome is a genetic condition that causes a range of developmental problems including learning disabilities and cognitive impairment. Usually, males are more severely affected by this disorder than females.  Affected individuals usually have delayed development of speech and language by age 2. Most males with fragile X syndrome have mild to moderate intellectual disability, while about one-third of affected females are intellectually disabled. Children with fragile X syndrome may also have anxiety and hyperactive behavior such as fidgeting or impulsive actions. They may have attention deficit disorder (ADD), which includes an impaired ability to maintain attention and difficulty focusing on specific tasks. About one-third of individuals with fragile X syndrome have features of autism spectrum disorders that affect communication and social interaction. Seizures occur in about 15 percent of males and about 5 percent of females with fragile X syndrome.  Most males and about half of females with fragile X syndrome have characteristic physical features that become more apparent with age. These features include a long and narrow face, large ears, a prominent jaw and forehead, unusually flexible fingers, flat feet, and in males, enlarged testicles (macroorchidism) after puberty.",fragile X syndrome,0000381,GHR,https://ghr.nlm.nih.gov/condition/fragile-x-syndrome,C0016667,T019,Disorders
How many people are affected by fragile X syndrome ?,0000381-2,frequency,"Fragile X syndrome occurs in approximately 1 in 4,000 males and 1 in 8,000 females.",fragile X syndrome,0000381,GHR,https://ghr.nlm.nih.gov/condition/fragile-x-syndrome,C0016667,T019,Disorders
What are the genetic changes related to fragile X syndrome ?,0000381-3,genetic changes,"Mutations in the FMR1 gene cause fragile X syndrome. The FMR1 gene provides instructions for making a protein called FMRP. This protein helps regulate the production of other proteins and plays a role in the development of synapses, which are specialized connections between nerve cells. Synapses are critical for relaying nerve impulses.  Nearly all cases of fragile X syndrome are caused by a mutation in which a DNA segment, known as the CGG triplet repeat, is expanded within the FMR1 gene. Normally, this DNA segment is repeated from 5 to about 40 times. In people with fragile X syndrome, however, the CGG segment is repeated more than 200 times. The abnormally expanded CGG segment turns off (silences) the FMR1 gene, which prevents the gene from producing FMRP. Loss or a shortage (deficiency) of this protein disrupts nervous system functions and leads to the signs and symptoms of fragile X syndrome.  Males and females with 55 to 200 repeats of the CGG segment are said to have an FMR1 gene premutation. Most people with a premutation are intellectually normal. In some cases, however, individuals with a premutation have lower than normal amounts of FMRP. As a result, they may have mild versions of the physical features seen in fragile X syndrome (such as prominent ears) and may experience emotional problems such as anxiety or depression. Some children with a premutation may have learning disabilities or autistic-like behavior. The premutation is also associated with an increased risk of disorders called fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS).",fragile X syndrome,0000381,GHR,https://ghr.nlm.nih.gov/condition/fragile-x-syndrome,C0016667,T019,Disorders
Is fragile X syndrome inherited ?,0000381-4,inheritance,"Fragile X syndrome is inherited in an X-linked dominant pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. (The Y chromosome is the other sex chromosome.) The inheritance is dominant if one copy of the altered gene in each cell is sufficient to cause the condition. X-linked dominant means that in females (who have two X chromosomes), a mutation in one of the two copies of a gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of a gene in each cell causes the disorder. In most cases, males experience more severe symptoms of the disorder than females.  In women, the FMR1 gene premutation on the X chromosome can expand to more than 200 CGG repeats in cells that develop into eggs. This means that women with the premutation have an increased risk of having a child with fragile X syndrome. By contrast, the premutation in men does not expand to more than 200 repeats as it is passed to the next generation. Men pass the premutation only to their daughters. Their sons receive a Y chromosome, which does not include the FMR1 gene.",fragile X syndrome,0000381,GHR,https://ghr.nlm.nih.gov/condition/fragile-x-syndrome,C0016667,T019,Disorders
What are the treatments for fragile X syndrome ?,0000381-5,treatment,These resources address the diagnosis or management of fragile X syndrome:  - Gene Review: Gene Review: FMR1-Related Disorders  - GeneFacts: Fragile X Syndrome: Diagnosis  - GeneFacts: Fragile X Syndrome: Management  - Genetic Testing Registry: Fragile X syndrome  - MedlinePlus Encyclopedia: Fragile X syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,fragile X syndrome,0000381,GHR,https://ghr.nlm.nih.gov/condition/fragile-x-syndrome,C0016667,T019,Disorders
What is (are) fragile X-associated primary ovarian insufficiency ?,0000382-1,information,"Fragile X-associated primary ovarian insufficiency (FXPOI) is a condition that affects women and is characterized by reduced function of the ovaries. The ovaries are the female reproductive organs in which egg cells are produced. As a form of primary ovarian insufficiency, FXPOI can cause irregular menstrual cycles, early menopause, an inability to have children (infertility), and elevated levels of a hormone known as follicle stimulating hormone (FSH). FSH is produced in both males and females and helps regulate the development of reproductive cells (eggs in females and sperm in males). In females, the level of FSH rises and falls, but overall it increases as a woman ages. In younger women, elevated levels may indicate early menopause and fertility problems.  The severity of FXPOI is variable. The most severely affected women have overt POI (formerly called premature ovarian failure). These women have irregular or absent menstrual periods and elevated FSH levels before age 40. Overt POI often causes infertility. Other women have occult POI; they have normal menstrual periods but reduced fertility, and they may have elevated levels of FSH (in which case, it is called biochemical POI). The reduction in ovarian function caused by FXPOI results in low levels of the hormone estrogen, which leads to many of the common signs and symptoms of menopause, such as hot flashes, insomnia, and thinning of the bones (osteoporosis). Women with FXPOI undergo menopause an average of 5 years earlier than women without the condition.",fragile X-associated primary ovarian insufficiency,0000382,GHR,https://ghr.nlm.nih.gov/condition/fragile-x-associated-primary-ovarian-insufficiency,C0085215,T019,Disorders
How many people are affected by fragile X-associated primary ovarian insufficiency ?,0000382-2,frequency,"An estimated 1 in 200 females has the genetic change that leads to FXPOI, although only about a quarter of them develop the condition. FXPOI accounts for about 4 to 6 percent of all cases of primary ovarian insufficiency in women.",fragile X-associated primary ovarian insufficiency,0000382,GHR,https://ghr.nlm.nih.gov/condition/fragile-x-associated-primary-ovarian-insufficiency,C0085215,T019,Disorders
What are the genetic changes related to fragile X-associated primary ovarian insufficiency ?,0000382-3,genetic changes,"Mutations in the FMR1 gene increase a woman's risk of developing FXPOI. The FMR1 gene provides instructions for making a protein called FMRP, which helps regulate the production of other proteins. This protein plays a role in the functioning of nerve cells. It is also important for normal ovarian function, although the role is not fully understood.  Women with FXPOI have a mutation in which a DNA segment, known as a CGG triplet repeat, is expanded within the FMR1 gene. Normally, this DNA segment is repeated from 5 to about 40 times. In women with FXPOI, however, the CGG segment is repeated 55 to 200 times. This mutation is known as an FMR1 gene premutation. Some studies show that women with about 44 to 54 CGG repeats, known as an intermediate (or gray zone) mutation, can also have features of FXPOI. An expansion of more than 200 repeats, a full mutation, causes a more serious disorder called fragile X syndrome, which is characterized by intellectual disability, learning problems, and certain physical features.  For unknown reasons, the premutation leads to the overproduction of abnormal FMR1 mRNA that contains the expanded repeat region. The FMR1 mRNA is the genetic blueprint for FMRP. Researchers believe that the high levels of mRNA cause the signs and symptoms of FXPOI. It is thought that the mRNA attaches to other proteins and keeps them from performing their functions. In addition, the repeats make producing FMRP from the blueprint more difficult, and as a result, people with the FMR1 gene premutation can have less FMRP than normal. A reduction of this protein is not thought to be involved in FXPOI. However, it may cause mild versions of the features seen in fragile X syndrome, such as prominent ears, anxiety, and mood swings.",fragile X-associated primary ovarian insufficiency,0000382,GHR,https://ghr.nlm.nih.gov/condition/fragile-x-associated-primary-ovarian-insufficiency,C0085215,T019,Disorders
Is fragile X-associated primary ovarian insufficiency inherited ?,0000382-4,inheritance,"An increased risk of developing FXPOI is inherited in an X-linked dominant pattern. The FMR1 gene is located on the X chromosome, which is one of the two sex chromosomes. (The Y chromosome is the other sex chromosome.) The inheritance is dominant because one copy of the altered gene in each cell is sufficient to elevate the risk of developing FXPOI. In females (who have two X chromosomes), a mutation in one of the two copies of a gene in each cell can lead to the disorder. However, not all women who inherit an FMR1 premutation will develop FXPOI. Because males do not have ovaries, they are unaffected.",fragile X-associated primary ovarian insufficiency,0000382,GHR,https://ghr.nlm.nih.gov/condition/fragile-x-associated-primary-ovarian-insufficiency,C0085215,T019,Disorders
What are the treatments for fragile X-associated primary ovarian insufficiency ?,0000382-5,treatment,These resources address the diagnosis or management of FXPOI:  - Gene Review: Gene Review: FMR1-Related Disorders  - Genetic Testing Registry: Premature ovarian failure 1   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,fragile X-associated primary ovarian insufficiency,0000382,GHR,https://ghr.nlm.nih.gov/condition/fragile-x-associated-primary-ovarian-insufficiency,C0085215,T019,Disorders
What is (are) fragile X-associated tremor/ataxia syndrome ?,0000383-1,information,"Fragile X-associated tremor/ataxia syndrome (FXTAS) is characterized by problems with movement and thinking ability (cognition). FXTAS is a late-onset disorder, usually occurring after age 50, and its signs and symptoms worsen with age. This condition affects males more frequently and severely than females. Affected individuals have areas of damage in the part of the brain that controls movement (the cerebellum) and in a type of brain tissue known as white matter, which can be seen with magnetic resonance imaging (MRI). This damage leads to the movement problems and other impairments associated with FXTAS.  The characteristic features of FXTAS are intention tremor, which is trembling or shaking of a limb when trying to perform a voluntary movement such as reaching for an object, and problems with coordination and balance (ataxia). Typically intention tremors will develop first, followed a few years later by ataxia, although not everyone with FXTAS has both features. Many affected individuals develop other movement problems, such as a pattern of movement abnormalities known as parkinsonism, which includes tremors when not moving (resting tremor), rigidity, and unusually slow movement (bradykinesia). In addition, affected individuals may have reduced sensation, numbness or tingling, pain, or muscle weakness in the lower limbs. Some people with FXTAS experience problems with the autonomic nervous system, which controls involuntary body functions, leading to the inability to control the bladder or bowel.  People with FXTAS commonly have cognitive disabilities. They may develop short-term memory loss and loss of executive function, which is the ability to plan and implement actions and develop problem-solving strategies. Loss of this function impairs skills such as impulse control, self-monitoring, focusing attention appropriately, and cognitive flexibility. Many people with FXTAS experience anxiety, depression, moodiness, or irritability.  Some women develop immune system disorders, such as hypothyroidism or fibromyalgia, before the signs and symptoms of FXTAS appear.",fragile X-associated tremor/ataxia syndrome,0000383,GHR,https://ghr.nlm.nih.gov/condition/fragile-x-associated-tremor-ataxia-syndrome,C1839780,T047,Disorders
How many people are affected by fragile X-associated tremor/ataxia syndrome ?,0000383-2,frequency,"Studies show that approximately 1 in 450 males has the genetic change that leads to FXTAS, although the condition occurs in only about 40 percent of them. It is estimated that 1 in 3,000 men over age 50 is affected. Similarly, 1 in 200 females has the genetic change, but only an estimated 16 percent of them develop signs and symptoms of FXTAS.",fragile X-associated tremor/ataxia syndrome,0000383,GHR,https://ghr.nlm.nih.gov/condition/fragile-x-associated-tremor-ataxia-syndrome,C1839780,T047,Disorders
What are the genetic changes related to fragile X-associated tremor/ataxia syndrome ?,0000383-3,genetic changes,"Mutations in the FMR1 gene increase the risk of developing FXTAS. The FMR1 gene provides instructions for making a protein called FMRP, which helps regulate the production of other proteins. FMRP plays a role in the development of synapses, which are specialized connections between nerve cells. Synapses are critical for relaying nerve impulses.  Individuals with FXTAS have a mutation in which a DNA segment, known as a CGG triplet repeat, is expanded within the FMR1 gene. Normally, this DNA segment is repeated from 5 to about 40 times. In people with FXTAS, however, the CGG segment is repeated 55 to 200 times. This mutation is known as an FMR1 gene premutation. An expansion of more than 200 repeats, a full mutation, causes a more serious condition called fragile X syndrome, which is characterized by intellectual disability, learning problems, and certain physical features.  For unknown reasons, the premutation leads to the overproduction of abnormal FMR1 mRNA that contains the expanded repeat region. The FMR1mRNA is the genetic blueprint for the production of FMRP. Researchers believe that the high levels of mRNA cause the signs and symptoms of FXTAS. The mRNA has been found in clumps of proteins and mRNA (intranuclear inclusions) in brain and nerve cells in people with FXTAS. It is thought that attaching to FMR1 mRNA and forming clumps keeps the other proteins from performing their functions, although the effect of the intranuclear inclusions is unclear. In addition, the repeat expansion makes producing FMRP from the mRNA blueprint more difficult, and as a result, people with the FMR1 gene premutation can have less FMRP than normal. A reduction in the protein is not thought to be involved in FXTAS. However, it may cause mild versions of the features seen in fragile X syndrome, such as prominent ears, anxiety, and mood swings.",fragile X-associated tremor/ataxia syndrome,0000383,GHR,https://ghr.nlm.nih.gov/condition/fragile-x-associated-tremor-ataxia-syndrome,C1839780,T047,Disorders
Is fragile X-associated tremor/ataxia syndrome inherited ?,0000383-4,inheritance,"An increased risk of developing FXTAS is inherited in an X-linked dominant pattern. The FMR1 gene is located on the X chromosome, one of the two sex chromosomes. (The Y chromosome is the other sex chromosome.) The inheritance is dominant because one copy of the altered gene in each cell is sufficient to elevate the risk of developing FXTAS. In females (who have two X chromosomes), a mutation in one of the two copies of the FMR1 gene in each cell can lead to the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell can result in the disorder. However, not all people who inherit an FMR1 premutation will develop FXTAS. In X-linked dominant disorders, males typically experience more severe symptoms than females.  Fewer females than males develop FXTAS because the X chromosome that contains the premutation may be turned off (inactive) due to a process called X-inactivation. Early in embryonic development in females, one of the two X chromosomes is permanently inactivated in somatic cells (cells other than egg and sperm cells). X-inactivation ensures that females, like males, have only one active copy of the X chromosome in each body cell. Usually X-inactivation occurs randomly, so that each X chromosome is active in about half the body's cells. Sometimes X-inactivation is not random, and one X chromosome is active in more than half of cells. When X-inactivation does not occur randomly, it is called skewed X-inactivation. Researchers suspect that the distribution of active and inactive X chromosomes may help determine the severity of FXTAS in females or whether they develop signs and symptoms of the condition.",fragile X-associated tremor/ataxia syndrome,0000383,GHR,https://ghr.nlm.nih.gov/condition/fragile-x-associated-tremor-ataxia-syndrome,C1839780,T047,Disorders
What are the treatments for fragile X-associated tremor/ataxia syndrome ?,0000383-5,treatment,These resources address the diagnosis or management of FXTAS:  - Fragile X Research Foundation of Canada: FXTAS  - Gene Review: Gene Review: FMR1-Related Disorders  - Genetic Testing Registry: Fragile X tremor/ataxia syndrome  - Merck Manual Consumer Version   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,fragile X-associated tremor/ataxia syndrome,0000383,GHR,https://ghr.nlm.nih.gov/condition/fragile-x-associated-tremor-ataxia-syndrome,C1839780,T047,Disorders
What is (are) fragile XE syndrome ?,0000384-1,information,"Fragile XE syndrome is a genetic disorder that impairs thinking ability and cognitive functioning. Most affected individuals have mild intellectual disability. In some people with this condition, cognitive function is described as borderline, which means that it is below average but not low enough to be classified as an intellectual disability. Females are rarely diagnosed with fragile XE syndrome, likely because the signs and symptoms are so mild that the individuals function normally.  Learning disabilities are the most common sign of impaired cognitive function in people with fragile XE syndrome. The learning disabilities are likely a result of communication and behavioral problems, including delayed speech, poor writing skills, hyperactivity, and a short attention span. Some affected individuals display autistic behaviors, such as hand flapping, repetitive behaviors, and intense interest in a particular subject. Unlike some other forms of intellectual disability, cognitive functioning remains steady and does not decline with age in fragile XE syndrome.",fragile XE syndrome,0000384,GHR,https://ghr.nlm.nih.gov/condition/fragile-xe-syndrome,C0039082,T047,Disorders
How many people are affected by fragile XE syndrome ?,0000384-2,frequency,"Fragile XE syndrome is estimated to affect 1 in 25,000 to 100,000 newborn males. Only a small number of affected females have been described in the medical literature. Because mildly affected individuals may never be diagnosed, it is thought that the condition may be more common than reported.",fragile XE syndrome,0000384,GHR,https://ghr.nlm.nih.gov/condition/fragile-xe-syndrome,C0039082,T047,Disorders
What are the genetic changes related to fragile XE syndrome ?,0000384-3,genetic changes,"Fragile XE syndrome is caused by mutations in the AFF2 gene. This gene provides instructions for making a protein whose function is not well understood. Some studies show that the AFF2 protein can attach (bind) to DNA and help control the activity of other genes. Other studies suggest that the AFF2 protein is involved in the process by which the blueprint for making proteins is cut and rearranged to produce different versions of the protein (alternative splicing). Researchers are working to determine which genes and proteins are affected by AFF2.  Nearly all cases of fragile XE syndrome occur when a region of the AFF2 gene, known as the CCG trinucleotide repeat, is abnormally expanded. Normally, this segment of three DNA building blocks (nucleotides) is repeated approximately 4 to 40 times. However, in people with fragile XE syndrome, the CCG segment is repeated more than 200 times, which makes this region of the gene unstable. (When expanded, this region is known as the FRAXE fragile site.) As a result, the AFF2 gene is turned off (silenced), and no AFF2 protein is produced. It is unclear how a shortage of this protein leads to intellectual disability in people with fragile XE syndrome.  People with 50 to 200 CCG repeats are said to have an AFF2 gene premutation. Current research suggests that people with a premutation do not have associated cognitive problems.",fragile XE syndrome,0000384,GHR,https://ghr.nlm.nih.gov/condition/fragile-xe-syndrome,C0039082,T047,Disorders
Is fragile XE syndrome inherited ?,0000384-4,inheritance,"Fragile XE syndrome is inherited in an X-linked dominant pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In most cases, males experience more severe symptoms of the disorder than females.  In parents with the AFF2 gene premutation, the number of CCG repeats can expand to more than 200 in cells that develop into eggs or sperm. This means that parents with the premutation have an increased risk of having a child with fragile XE syndrome. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons; sons receive a Y chromosome from their father, which does not include the AFF2 gene.",fragile XE syndrome,0000384,GHR,https://ghr.nlm.nih.gov/condition/fragile-xe-syndrome,C0039082,T047,Disorders
What are the treatments for fragile XE syndrome ?,0000384-5,treatment,These resources address the diagnosis or management of fragile XE syndrome:  - Centers for Disease Control and Prevention: Developmental Screening Fact Sheet  - Genetic Testing Registry: FRAXE   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,fragile XE syndrome,0000384,GHR,https://ghr.nlm.nih.gov/condition/fragile-xe-syndrome,C0039082,T047,Disorders
What is (are) Fraser syndrome ?,0000385-1,information,"Fraser syndrome is a rare disorder that affects development starting before birth. Characteristic features of this condition include eyes that are completely covered by skin and usually malformed (cryptophthalmos), fusion of the skin between the fingers and toes (cutaneous syndactyly), and abnormalities of the genitalia and the urinary tract (genitourinary anomalies). Other tissues and organs can also be affected. Depending on the severity of the signs and symptoms, Fraser syndrome can be fatal before or shortly after birth; less severely affected individuals can live into childhood or adulthood.  Cryptophthalmos is the most common abnormality in people with Fraser syndrome. Both eyes are usually completely covered by skin, but in some cases, only one eye is covered or one or both eyes are partially covered. In cryptophthalmos, the eyes can also be malformed; for example, the eyeballs may be fused to the skin covering them, or they may be small (microphthalmia) or missing (anophthalmia). Eye abnormalities typically lead to impairment or loss of vision in people with Fraser syndrome. Affected individuals can have other problems related to abnormal eye development, including missing eyebrows or eyelashes or a patch of hair extending from the side hairline to the eyebrow.  Cutaneous syndactyly typically occurs in both the hands and the feet in Fraser syndrome. In most people with this feature, the skin between the middle three fingers and toes are fused, but the other digits can also be involved. Other abnormalities of the hands and feet can occur in people with Fraser syndrome.  Individuals with Fraser syndrome can have abnormalities of the genitalia, such as an enlarged clitoris in females or undescended testes (cryptorchidism) in males. Some affected individuals have external genitalia that do not appear clearly female or male (ambiguous genitalia).  The most common urinary tract abnormality in Fraser syndrome is the absence of one or both kidneys (renal agenesis). Affected individuals can have other kidney problems or abnormalities of the bladder and other parts of the urinary tract.  A variety of other signs and symptoms can be involved in Fraser syndrome, including heart malformations or abnormalities of the voicebox (larynx) or other parts of the respiratory tract. Some affected individuals have facial abnormalities, including ear or nose abnormalities or an opening in the upper lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate).",Fraser syndrome,0000385,GHR,https://ghr.nlm.nih.gov/condition/fraser-syndrome,C0265233,T019,Disorders
How many people are affected by Fraser syndrome ?,0000385-2,frequency,"Fraser syndrome affects an estimated 1 in 200,000 newborns. The condition occurs in approximately 1 in 10,000 fetuses that do not survive to birth.",Fraser syndrome,0000385,GHR,https://ghr.nlm.nih.gov/condition/fraser-syndrome,C0265233,T019,Disorders
What are the genetic changes related to Fraser syndrome ?,0000385-3,genetic changes,"Mutations in the FRAS1, FREM2, or GRIP1 gene can cause Fraser syndrome. FRAS1 gene mutations are the most common cause, accounting for about half of cases of Fraser syndrome. FREM2 and GRIP1 gene mutations are each found in a small percentage of cases.  The FRAS1 and FREM2 proteins (produced from the FRAS1 and FREM2 genes, respectively) are part of a group of proteins called the FRAS/FREM complex. The GRIP1 protein (produced from the GRIP1 gene) ensures that FRAS1 and FREM2 get to the correct location of the cell to form the FRAS/FREM complex.  The FRAS/FREM complex is found in basement membranes, which are thin, sheet-like structures that separate and support cells in many tissues. This complex is particularly important during development before birth. One of the complex's roles is to anchor the top layer of skin by connecting its basement membrane to the layer of skin below. The FRAS/FREM complex is also involved in the proper development of other organs and tissues, including the kidneys, although the mechanism is unclear.  Mutations in any of these genes prevent formation of the FRAS/FREM complex. Lack of this complex in the basement membrane of the skin leads to detachment of the top layer of skin, causing blisters to form during development. These blisters likely impair the proper formation of certain structures before birth, leading to cryptophthalmos and cutaneous syndactyly. It is unknown how lack of the FRAS/FREM complex leads to kidney and genital abnormalities and other problems in Fraser syndrome.",Fraser syndrome,0000385,GHR,https://ghr.nlm.nih.gov/condition/fraser-syndrome,C0265233,T019,Disorders
Is Fraser syndrome inherited ?,0000385-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Fraser syndrome,0000385,GHR,https://ghr.nlm.nih.gov/condition/fraser-syndrome,C0265233,T019,Disorders
What are the treatments for Fraser syndrome ?,0000385-5,treatment,These resources address the diagnosis or management of Fraser syndrome:  - Genetic Testing Registry: Cryptophthalmos syndrome  - University of Arizona College of Medicine: Cryptophthalmos   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Fraser syndrome,0000385,GHR,https://ghr.nlm.nih.gov/condition/fraser-syndrome,C0265233,T019,Disorders
What is (are) Frasier syndrome ?,0000386-1,information,"Frasier syndrome is a condition that affects the kidneys and genitalia.  Frasier syndrome is characterized by kidney disease that begins in early childhood. Affected individuals have a condition called focal segmental glomerulosclerosis, in which scar tissue forms in some glomeruli, which are the tiny blood vessels in the kidneys that filter waste from blood. In people with Frasier syndrome, this condition often leads to kidney failure by adolescence.  Although males with Frasier syndrome have the typical male chromosome pattern (46,XY), they have gonadal dysgenesis, in which external genitalia do not look clearly male or clearly female (ambiguous genitalia) or the genitalia appear completely female. The internal reproductive organs (gonads) are typically undeveloped and referred to as streak gonads. These abnormal gonads are nonfunctional and often become cancerous, so they are usually removed surgically early in life.  Affected females usually have normal genitalia and gonads and have only the kidney features of the condition. Because they do not have all the features of the condition, females are usually given the diagnosis of isolated nephrotic syndrome.",Frasier syndrome,0000386,GHR,https://ghr.nlm.nih.gov/condition/frasier-syndrome,C0950122,T019,Disorders
How many people are affected by Frasier syndrome ?,0000386-2,frequency,Frasier syndrome is thought to be a rare condition; approximately 50 cases have been described in the scientific literature.,Frasier syndrome,0000386,GHR,https://ghr.nlm.nih.gov/condition/frasier-syndrome,C0950122,T019,Disorders
What are the genetic changes related to Frasier syndrome ?,0000386-3,genetic changes,"Mutations in the WT1 gene cause Frasier syndrome. The WT1 gene provides instructions for making a protein that regulates the activity of other genes by attaching (binding) to specific regions of DNA. On the basis of this action, the WT1 protein is called a transcription factor. The WT1 protein plays a role in the development of the kidneys and gonads (ovaries in females and testes in males) before birth.  The WT1 gene mutations that cause Frasier syndrome lead to the production of a protein with an impaired ability to control gene activity and regulate the development of the kidneys and reproductive organs, resulting in the signs and symptoms of Frasier syndrome.  Frasier syndrome has features similar to another condition called Denys-Drash syndrome, which is also caused by mutations in the WT1 gene. Because these two conditions share a genetic cause and have overlapping features, some researchers have suggested that they are part of a spectrum and not two distinct conditions.",Frasier syndrome,0000386,GHR,https://ghr.nlm.nih.gov/condition/frasier-syndrome,C0950122,T019,Disorders
Is Frasier syndrome inherited ?,0000386-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Frasier syndrome,0000386,GHR,https://ghr.nlm.nih.gov/condition/frasier-syndrome,C0950122,T019,Disorders
What are the treatments for Frasier syndrome ?,0000386-5,treatment,These resources address the diagnosis or management of Frasier syndrome:  - Genetic Testing Registry: Frasier syndrome  - MedlinePlus Encyclopedia: Focal Segmental Glomerulosclerosis  - MedlinePlus Encyclopedia: Nephrotic Syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Frasier syndrome,0000386,GHR,https://ghr.nlm.nih.gov/condition/frasier-syndrome,C0950122,T019,Disorders
What is (are) Freeman-Sheldon syndrome ?,0000387-1,information,"Freeman-Sheldon syndrome is a condition that primarily affects the face, hands, and feet. People with this disorder have a distinctive facial appearance including a small mouth (microstomia) with pursed lips, giving the appearance of a ""whistling face."" For this reason, the condition is sometimes called ""whistling face syndrome.""  People with Freeman-Sheldon syndrome may also have a prominent forehead and brow ridges, a sunken appearance of the middle of the face (midface hypoplasia), a short nose, a long area between the nose and mouth (philtrum), deep folds in the skin between the nose and lips (nasolabial folds), full cheeks, and a chin dimple shaped like an ""H"" or ""V"".  Affected individuals may have a number of abnormalities that affect the eyes. These may include widely spaced eyes (hypertelorism), deep-set eyes, outside corners of the eyes that point downward (down-slanting palpebral fissures), a narrowing of the eye opening (blepharophimosis), droopy eyelids (ptosis), and eyes that do not look in the same direction (strabismus).  Other facial features that may occur in Freeman-Sheldon syndrome include an unusually small tongue (microglossia) and jaw (micrognathia) and a high arch in the roof of the mouth (high-arched palate). People with this disorder may have difficulty swallowing (dysphagia), a failure to gain weight and grow at the expected rate (failure to thrive), and respiratory complications that may be life-threatening. Speech problems are also common in this disorder. Some affected individuals have hearing loss.  Freeman-Sheldon syndrome is also characterized by joint deformities (contractures) that restrict movement. People with this disorder typically have multiple contractures in the hands and feet at birth (distal arthrogryposis). These contractures lead to permanently bent fingers and toes (camptodactyly), a hand deformity in which all of the fingers are angled outward toward the fifth finger (ulnar deviation, also called ""windmill vane hand""), and inward- and downward-turning feet (clubfoot). Affected individuals may also have a spine that curves to the side (scoliosis).  People with Freeman-Sheldon syndrome also have an increased risk of developing a severe reaction to certain drugs used during surgery and other invasive procedures. This reaction is called malignant hyperthermia. Malignant hyperthermia occurs in response to some anesthetic gases, which are used to block the sensation of pain. A particular type of muscle relaxant may also trigger the reaction. If given these drugs, people at risk for malignant hyperthermia may experience muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), a high fever, increased acid levels in the blood and other tissues (acidosis), and a rapid heart rate. The complications of malignant hyperthermia can be life-threatening unless they are treated promptly.  Intelligence is unaffected in most people with Freeman-Sheldon syndrome, but approximately one-third have some degree of intellectual disability.",Freeman-Sheldon syndrome,0000387,GHR,https://ghr.nlm.nih.gov/condition/freeman-sheldon-syndrome,C0265224,T019,Disorders
How many people are affected by Freeman-Sheldon syndrome ?,0000387-2,frequency,Freeman-Sheldon syndrome is a rare disorder; its exact prevalence is unknown.,Freeman-Sheldon syndrome,0000387,GHR,https://ghr.nlm.nih.gov/condition/freeman-sheldon-syndrome,C0265224,T019,Disorders
What are the genetic changes related to Freeman-Sheldon syndrome ?,0000387-3,genetic changes,"Freeman-Sheldon syndrome may be caused by mutations in the MYH3 gene. The MYH3 gene provides instructions for making a protein called embryonic skeletal muscle myosin heavy chain 3. This protein belongs to a group of proteins called myosins, which are involved in cell movement and transport of materials within and between cells. Myosin and another protein called actin are the primary components of muscle fibers and are important for the tensing of muscles (muscle contraction). Embryonic skeletal muscle myosin heavy chain 3 forms part of a myosin protein complex that is active before birth and is important for normal development of the muscles.  MYH3 gene mutations that cause Freeman-Sheldon syndrome likely disrupt the function of the embryonic skeletal muscle myosin heavy chain 3 protein, reducing the ability of fetal muscle cells to contract. This impairment of muscle contraction may interfere with muscle development in the fetus, resulting in the contractures and other muscle and skeletal abnormalities associated with Freeman-Sheldon syndrome. It is unclear how MYH3 gene mutations may cause other features of this disorder.  Some people with Freeman-Sheldon syndrome do not have mutations in the MYH3 gene. In these individuals, the cause of the disorder is unknown.",Freeman-Sheldon syndrome,0000387,GHR,https://ghr.nlm.nih.gov/condition/freeman-sheldon-syndrome,C0265224,T019,Disorders
Is Freeman-Sheldon syndrome inherited ?,0000387-4,inheritance,"Freeman-Sheldon syndrome can have different inheritance patterns. In some cases, the condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. The condition can also have an autosomal recessive inheritance pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  In some cases, the inheritance pattern is unknown.",Freeman-Sheldon syndrome,0000387,GHR,https://ghr.nlm.nih.gov/condition/freeman-sheldon-syndrome,C0265224,T019,Disorders
What are the treatments for Freeman-Sheldon syndrome ?,0000387-5,treatment,These resources address the diagnosis or management of Freeman-Sheldon syndrome:  - Genetic Testing Registry: Freeman-Sheldon syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Freeman-Sheldon syndrome,0000387,GHR,https://ghr.nlm.nih.gov/condition/freeman-sheldon-syndrome,C0265224,T019,Disorders
What is (are) Friedreich ataxia ?,0000388-1,information,"Friedreich ataxia is a genetic condition that affects the nervous system and causes movement problems. People with this condition develop impaired muscle coordination (ataxia) that worsens over time. Other features of this condition include the gradual loss of strength and sensation in the arms and legs, muscle stiffness (spasticity), and impaired speech. Individuals with Friedreich ataxia often have a form of heart disease called hypertrophic cardiomyopathy that enlarges and weakens the heart muscle. Some affected individuals develop diabetes, impaired vision, hearing loss, or an abnormal curvature of the spine (scoliosis).  Most people with Friedreich ataxia begin to experience the signs and symptoms of the disorder around puberty. Poor balance when walking and slurred speech are often the first noticeable features. Affected individuals typically require the use of a wheelchair about 10 years after signs and symptoms appear.  About 25 percent of people with Friedreich ataxia have an atypical form that begins after age 25. Affected individuals who develop Friedreich ataxia between ages 26 and 39 are considered to have late-onset Friedreich ataxia (LOFA). When the signs and symptoms begin after age 40 the condition is called very late-onset Friedreich ataxia (VLOFA). LOFA and VLOFA usually progress more slowly than typical Friedreich ataxia.",Friedreich ataxia,0000388,GHR,https://ghr.nlm.nih.gov/condition/friedreich-ataxia,C0016719,T047,Disorders
How many people are affected by Friedreich ataxia ?,0000388-2,frequency,"Friedreich ataxia is estimated to affect 1 in 40,000 people. This condition is found in people with European, Middle Eastern, or North African ancestry. It is rarely identified in other ethnic groups.",Friedreich ataxia,0000388,GHR,https://ghr.nlm.nih.gov/condition/friedreich-ataxia,C0016719,T047,Disorders
What are the genetic changes related to Friedreich ataxia ?,0000388-3,genetic changes,"Mutations in the FXN gene cause Friedreich ataxia. This gene provides instructions for making a protein called frataxin. Although its role is not fully understood, frataxin appears to be important for the normal function of mitochondria, the energy-producing centers within cells. One region of the FXN gene contains a segment of DNA known as a GAA trinucleotide repeat. This segment is made up of a series of three DNA building blocks (one guanine and two adenines) that appear multiple times in a row. Normally, this segment is repeated 5 to 33 times within the FXN gene.  In people with Friedreich ataxia, the GAA segment is repeated 66 to more than 1,000 times. The length of the GAA trinucleotide repeat appears to be related to the age at which the symptoms of Friedreich ataxia appear. People with GAA segments repeated fewer than 300 times tend to have a later appearance of symptoms (after age 25) than those with larger GAA trinucleotide repeats. The abnormally long GAA trinucleotide repeat disrupts the production of frataxin, which severely reduces the amount of this protein in cells. Certain nerve and muscle cells cannot function properly with a shortage of frataxin, leading to the characteristic signs and symptoms of Friedreich ataxia.",Friedreich ataxia,0000388,GHR,https://ghr.nlm.nih.gov/condition/friedreich-ataxia,C0016719,T047,Disorders
Is Friedreich ataxia inherited ?,0000388-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Friedreich ataxia,0000388,GHR,https://ghr.nlm.nih.gov/condition/friedreich-ataxia,C0016719,T047,Disorders
What are the treatments for Friedreich ataxia ?,0000388-5,treatment,These resources address the diagnosis or management of Friedreich ataxia:  - Friedreich's Ataxia Research Alliance: Clinical Care Guidelines  - Gene Review: Gene Review: Friedreich Ataxia  - Genetic Testing Registry: Friedreich ataxia 1  - MedlinePlus Encyclopedia: Friedreich's Ataxia  - MedlinePlus Encyclopedia: Hypertrophic Cardiomyopathy  - National Institute of Neurological Disorders and Stroke: Friedreich's Ataxia Fact Sheet   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Friedreich ataxia,0000388,GHR,https://ghr.nlm.nih.gov/condition/friedreich-ataxia,C0016719,T047,Disorders
What is (are) frontometaphyseal dysplasia ?,0000389-1,information,"Frontometaphyseal dysplasia is a disorder involving abnormalities in skeletal development and other health problems. It is a member of a group of related conditions called otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 1, otopalatodigital syndrome type 2, and Melnick-Needles syndrome. In general, these disorders involve hearing loss caused by malformations in the tiny bones in the ears (ossicles), problems in the development of the roof of the mouth (palate), and skeletal abnormalities involving the fingers and/or toes (digits).  Frontometaphyseal dysplasia is distinguished from the other otopalatodigital spectrum disorders by the presence of joint deformities called contractures that restrict the movement of certain joints. People with frontometaphyseal dysplasia may also have bowed limbs, an abnormal curvature of the spine (scoliosis), and abnormalities of the fingers and hands.  Characteristic facial features may include prominent brow ridges; wide-set and downward-slanting eyes; a very small lower jaw and chin (micrognathia); and small, missing or misaligned teeth. Some affected individuals have hearing loss.  In addition to skeletal abnormalities, individuals with frontometaphyseal dysplasia may have obstruction of the ducts between the kidneys and bladder (ureters), heart defects, or constrictions in the passages leading from the windpipe to the lungs (the bronchi) that can cause problems with breathing.  Males with frontometaphyseal dysplasia generally have more severe signs and symptoms of the disorder than do females, who may show only the characteristic facial features.",frontometaphyseal dysplasia,0000389,GHR,https://ghr.nlm.nih.gov/condition/frontometaphyseal-dysplasia,C0265293,T019,Disorders
How many people are affected by frontometaphyseal dysplasia ?,0000389-2,frequency,Frontometaphyseal dysplasia is a rare disorder; only a few dozen cases have been reported worldwide.,frontometaphyseal dysplasia,0000389,GHR,https://ghr.nlm.nih.gov/condition/frontometaphyseal-dysplasia,C0265293,T019,Disorders
What are the genetic changes related to frontometaphyseal dysplasia ?,0000389-3,genetic changes,"Mutations in the FLNA gene cause frontometaphyseal dysplasia.  The FLNA gene provides instructions for producing the protein filamin A, which helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. Filamin A binds to another protein called actin, and helps the actin to form the branching network of filaments that make up the cytoskeleton. Filamin A also links actin to many other proteins to perform various functions within the cell.  A small number of mutations in the FLNA gene have been identified in people with frontometaphyseal dysplasia. These mutations are described as ""gain-of-function"" because they appear to enhance the activity of the filamin A protein or give the protein a new, atypical function. Researchers believe that the mutations may change the way the filamin A protein helps regulate processes involved in skeletal development, but it is not known how changes in the protein relate to the specific signs and symptoms of frontometaphyseal dysplasia.",frontometaphyseal dysplasia,0000389,GHR,https://ghr.nlm.nih.gov/condition/frontometaphyseal-dysplasia,C0265293,T019,Disorders
Is frontometaphyseal dysplasia inherited ?,0000389-4,inheritance,"This condition is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In most cases, males experience more severe symptoms of the disorder than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",frontometaphyseal dysplasia,0000389,GHR,https://ghr.nlm.nih.gov/condition/frontometaphyseal-dysplasia,C0265293,T019,Disorders
What are the treatments for frontometaphyseal dysplasia ?,0000389-5,treatment,These resources address the diagnosis or management of frontometaphyseal dysplasia:  - Gene Review: Gene Review: Otopalatodigital Spectrum Disorders  - Genetic Testing Registry: Frontometaphyseal dysplasia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,frontometaphyseal dysplasia,0000389,GHR,https://ghr.nlm.nih.gov/condition/frontometaphyseal-dysplasia,C0265293,T019,Disorders
What is (are) frontonasal dysplasia ?,0000390-1,information,"Frontonasal dysplasia is a condition that results from abnormal development of the head and face before birth. People with frontonasal dysplasia have at least two of the following features: widely spaced eyes (ocular hypertelorism); a broad nose; a slit (cleft) in one or both sides of the nose; no nasal tip; a central cleft involving the nose, upper lip, or roof of the mouth (palate); incomplete formation of the front of the skull with skin covering the head where bone should be (anterior cranium bifidum occultum); or a widow's peak hairline.  Other features of frontonasal dysplasia can include additional facial malformations, absence or malformation of the tissue that connects the left and right halves of the brain (the corpus callosum), and intellectual disability.  There are at least three types of frontonasal dysplasia that are distinguished by their genetic causes and their signs and symptoms. In addition to the features previously described, each type of frontonasal dysplasia is associated with other distinctive features. Individuals with frontonasal dysplasia type 1 typically have abnormalities of the nose, a long area between the nose and upper lip (philtrum), and droopy upper eyelids (ptosis). Individuals with frontonasal dysplasia type 2 can have hair loss (alopecia) and an enlarged opening in the two bones that make up much of the top and sides of the skull (enlarged parietal foramina). Males with this form of the condition often have genital abnormalities. Features of frontonasal dysplasia type 3 include eyes that are missing (anophthalmia) or very small (microphthalmia) and low-set ears that are rotated backward. Frontonasal dysplasia type 3 is typically associated with the most severe facial abnormalities, but the severity of the condition varies widely, even among individuals with the same type.  Life expectancy of affected individuals depends on the severity of the malformations and whether or not surgical intervention can improve associated health problems, such as breathing and feeding problems caused by the facial clefts.",frontonasal dysplasia,0000390,GHR,https://ghr.nlm.nih.gov/condition/frontonasal-dysplasia,C1876203,T019,Disorders
How many people are affected by frontonasal dysplasia ?,0000390-2,frequency,Frontonasal dysplasia is likely a rare condition; at least 100 cases have been reported in the scientific literature.,frontonasal dysplasia,0000390,GHR,https://ghr.nlm.nih.gov/condition/frontonasal-dysplasia,C1876203,T019,Disorders
What are the genetic changes related to frontonasal dysplasia ?,0000390-3,genetic changes,"Mutations in the ALX3 gene cause frontonasal dysplasia type 1, ALX4 gene mutations cause type 2, and ALX1 gene mutations cause type 3. These genes provide instructions for making proteins that are necessary for normal development, particularly of the head and face, before birth. The proteins produced from the ALX3, ALX4, and ALX1 genes are transcription factors, which means they attach (bind) to DNA and control the activity of certain genes. Specifically, the proteins control the activity of genes that regulate cell growth and division (proliferation) and movement (migration), ensuring that cells grow and stop growing at specific times and that they are positioned correctly during development. The ALX3 and ALX4 proteins are primarily involved in the development of the nose and surrounding tissues, while the ALX1 protein is involved in development of the eyes, nose, and mouth.  ALX3, ALX4, or ALX1 gene mutations reduce or eliminate function of the respective protein. As a result, the regulation of cell organization during development of the head and face is disrupted, particularly affecting the middle of the face. Abnormal development of the nose, philtrum, and upper lip leads to the facial clefts that characterize this disorder. This abnormal development also interferes with the proper formation of the skull and other facial structures, leading to anterior cranium bifidum occultum, hypertelorism, and other features of frontonasal dysplasia.",frontonasal dysplasia,0000390,GHR,https://ghr.nlm.nih.gov/condition/frontonasal-dysplasia,C1876203,T019,Disorders
Is frontonasal dysplasia inherited ?,0000390-4,inheritance,"When frontonasal dysplasia is caused by mutations in the ALX1 or ALX3 gene, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  When ALX4 gene mutations cause frontonasal dysplasia, the condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",frontonasal dysplasia,0000390,GHR,https://ghr.nlm.nih.gov/condition/frontonasal-dysplasia,C1876203,T019,Disorders
What are the treatments for frontonasal dysplasia ?,0000390-5,treatment,These resources address the diagnosis or management of frontonasal dysplasia:  - Genetic Testing Registry: Frontonasal dysplasia 1  - Genetic Testing Registry: Frontonasal dysplasia 2  - Genetic Testing Registry: Frontonasal dysplasia 3  - KidsHealth from Nemours: Cleft Lip and Palate  - MedlinePlus Encyclopedia: Head and Face Reconstruction  - Mount Sinai Hospital: Cleft Nasal Deformity  - University of Rochester Medical Center: Nasal Alveolar Molding   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,frontonasal dysplasia,0000390,GHR,https://ghr.nlm.nih.gov/condition/frontonasal-dysplasia,C1876203,T019,Disorders
What is (are) frontotemporal dementia with parkinsonism-17 ?,0000391-1,information,"Frontotemporal dementia with parkinsonism-17 (FTDP-17) is a progressive brain disorder that affects behavior, language, and movement. The symptoms of this disorder usually become noticeable in a person's forties or fifties. Most affected people survive 5 to 10 years after the appearance of symptoms, although a few have survived for two decades or more.  Changes in personality and behavior are often early signs of FTDP-17. These changes include a loss of inhibition, inappropriate emotional responses, restlessness, neglect of personal hygiene, and a general loss of interest in activities and events. The disease also leads to deterioration of cognitive functions (dementia), including problems with judgment, planning, and concentration. Some people with FTDP-17 develop psychiatric symptoms, including obsessive-compulsive behaviors, delusions, and hallucinations. It may become difficult for affected individuals to interact with others in a socially appropriate manner. They increasingly require help with personal care and other activities of daily living.  Many people with FTDP-17 develop problems with speech and language. They may have trouble finding words, confuse one word with another (semantic paraphasias), and repeat words spoken by others (echolalia). Difficulties with speech and language worsen over time, and most affected individuals eventually lose the ability to communicate.  FTDP-17 is also characterized by progressive problems with movement. Many affected individuals develop features of parkinsonism, including tremors, rigidity, and unusually slow movement (bradykinesia). As the disease progresses, most affected individuals become unable to walk. Some people with FTDP-17 also have restricted up-and-down eye movement (vertical gaze palsy) and rapid abnormal movements of both eyes (saccades).",frontotemporal dementia with parkinsonism-17,0000391,GHR,https://ghr.nlm.nih.gov/condition/frontotemporal-dementia-with-parkinsonism-17,C3811924,T047,Disorders
How many people are affected by frontotemporal dementia with parkinsonism-17 ?,0000391-2,frequency,"The worldwide prevalence of FTDP-17 is unknown. In the Netherlands, where the disease prevalence has been studied, it is estimated to affect 1 in 1 million people. However, the disorder is likely underdiagnosed, so it may actually be more common than this.  FTDP-17 probably accounts for a small percentage of all cases of frontotemporal dementia.",frontotemporal dementia with parkinsonism-17,0000391,GHR,https://ghr.nlm.nih.gov/condition/frontotemporal-dementia-with-parkinsonism-17,C3811924,T047,Disorders
What are the genetic changes related to frontotemporal dementia with parkinsonism-17 ?,0000391-3,genetic changes,"FTDP-17 is caused by mutations in the MAPT gene. This gene is located on chromosome 17, which is how the disease got its name.  The MAPT gene provides instructions for making a protein called tau. This protein is found throughout the nervous system, including in nerve cells (neurons) in the brain. It is involved in assembling and stabilizing microtubules, which are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). Microtubules help cells maintain their shape, assist in the process of cell division, and are essential for the transport of materials within cells.  Mutations in the MAPT gene disrupt the normal structure and function of tau. The defective protein assembles into abnormal clumps within neurons and other brain cells. However, it is unclear what effect these clumps have on cell function and survival. FTDP-17 is characterized by the gradual death of cells in areas of the brain called the frontal and temporal lobes. The frontal lobes are involved in reasoning, planning, judgment, and problem-solving, while the temporal lobes help process hearing, speech, memory, and emotion. A loss of cells in these brain regions leads to personality changes, speech difficulties, and the other features of FTDP-17.  FTDP-17 is one of several related diseases known as tauopathies, which are characterized by an abnormal buildup of tau in the brain.",frontotemporal dementia with parkinsonism-17,0000391,GHR,https://ghr.nlm.nih.gov/condition/frontotemporal-dementia-with-parkinsonism-17,C3811924,T047,Disorders
Is frontotemporal dementia with parkinsonism-17 inherited ?,0000391-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",frontotemporal dementia with parkinsonism-17,0000391,GHR,https://ghr.nlm.nih.gov/condition/frontotemporal-dementia-with-parkinsonism-17,C3811924,T047,Disorders
What are the treatments for frontotemporal dementia with parkinsonism-17 ?,0000391-5,treatment,These resources address the diagnosis or management of FTDP-17:  - Gene Review: Gene Review: MAPT-Related Disorders  - Genetic Testing Registry: Frontotemporal dementia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,frontotemporal dementia with parkinsonism-17,0000391,GHR,https://ghr.nlm.nih.gov/condition/frontotemporal-dementia-with-parkinsonism-17,C3811924,T047,Disorders
What is (are) Fryns syndrome ?,0000392-1,information,"Fryns syndrome is a condition that affects the development of many parts of the body. The features of this disorder vary widely among affected individuals and overlap with the signs and symptoms of several other disorders. These factors can make Fryns syndrome difficult to diagnose.  Most people with Fryns syndrome have a defect in the muscle that separates the abdomen from the chest cavity (the diaphragm). The most common defect is a congenital diaphragmatic hernia, which is a hole in the diaphragm that develops before birth. This hole allows the stomach and intestines to move into the chest and crowd the heart and lungs. As a result, the lungs often do not develop properly (pulmonary hypoplasia), which can cause life-threatening breathing difficulties in affected infants.  Other major signs of Fryns syndrome include abnormalities of the fingers and toes and distinctive facial features. The tips of the fingers and toes tend to be underdeveloped, resulting in a short and stubby appearance with small or absent nails. Most affected individuals have several unusual facial features, including widely spaced eyes (hypertelorism), a broad and flat nasal bridge, a thick nasal tip, a wide space between the nose and upper lip (a long philtrum), a large mouth (macrostomia), and a small chin (micrognathia). Many also have low-set and abnormally shaped ears.  Several additional features have been reported in people with Fryns syndrome. These include small eyes (microphthalmia), clouding of the clear outer covering of the eye (the cornea), and an opening in the roof of the mouth (cleft palate) with or without a split in the lip (cleft lip). Fryns syndrome can also affect the development of the brain, cardiovascular system, gastrointestinal system, kidneys, and genitalia.  Most people with Fryns syndrome die before birth or in early infancy from pulmonary hypoplasia caused by a congenital diaphragmatic hernia. However, a few affected individuals have lived into childhood. Many of these children have had severe developmental delay and intellectual disability.",Fryns syndrome,0000392,GHR,https://ghr.nlm.nih.gov/condition/fryns-syndrome,C0220730,T047,Disorders
How many people are affected by Fryns syndrome ?,0000392-2,frequency,The worldwide incidence of Fryns syndrome is unknown. More than 50 affected individuals have been reported in the medical literature. Studies suggest that Fryns syndrome occurs in 1.3 to 10 percent of all cases of congenital diaphragmatic hernia.,Fryns syndrome,0000392,GHR,https://ghr.nlm.nih.gov/condition/fryns-syndrome,C0220730,T047,Disorders
What are the genetic changes related to Fryns syndrome ?,0000392-3,genetic changes,"The cause of Fryns syndrome is unknown. The disorder is thought to be genetic because it tends to run in families and has features similar to those of other genetic disorders. Duplications and deletions in several chromosome regions have been associated with congenital diaphragmatic hernia and some of the other features of Fryns syndrome. However, no specific genetic change has been found to cause all of the signs and symptoms of this disorder.",Fryns syndrome,0000392,GHR,https://ghr.nlm.nih.gov/condition/fryns-syndrome,C0220730,T047,Disorders
Is Fryns syndrome inherited ?,0000392-4,inheritance,"Fryns syndrome appears to be inherited in an autosomal recessive pattern, which means both copies of a gene in each cell have mutations. However, no associated gene has been identified. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.",Fryns syndrome,0000392,GHR,https://ghr.nlm.nih.gov/condition/fryns-syndrome,C0220730,T047,Disorders
What are the treatments for Fryns syndrome ?,0000392-5,treatment,These resources address the diagnosis or management of Fryns syndrome:  - Children's Hospital of Philadelphia: Treatment of Congenital Diaphragmatic Hernia  - Gene Review: Gene Review: Fryns Syndrome  - Genetic Testing Registry: Fryns syndrome  - Seattle Children's Hospital: Treatment of Congenital Diaphragmatic Hernia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Fryns syndrome,0000392,GHR,https://ghr.nlm.nih.gov/condition/fryns-syndrome,C0220730,T047,Disorders
What is (are) Fuchs endothelial dystrophy ?,0000393-1,information,"Fuchs endothelial dystrophy is a condition that causes vision problems. The first symptom of this condition is typically blurred vision in the morning that usually clears during the day. Over time, affected individuals lose the ability to see details (visual acuity). People with Fuchs endothelial dystrophy also become sensitive to bright lights.  Fuchs endothelial dystrophy specifically affects the front surface of the eye called the cornea. Deposits called guttae, which are detectable during an eye exam, form in the middle of the cornea and eventually spread. These guttae contribute to the loss of cells in the cornea, leading to vision problems. Tiny blisters may develop on the cornea, which can burst and cause eye pain.  The signs and symptoms of Fuchs endothelial dystrophy usually begin in a person's forties or fifties. A very rare early-onset variant of this condition starts to affect vision in a person's twenties.",Fuchs endothelial dystrophy,0000393,GHR,https://ghr.nlm.nih.gov/condition/fuchs-endothelial-dystrophy,C0016781,T047,Disorders
How many people are affected by Fuchs endothelial dystrophy ?,0000393-2,frequency,"The late-onset form of Fuchs endothelial dystrophy is a common condition, affecting approximately 4 percent of people over the age of 40. The early-onset variant of Fuchs endothelial dystrophy is rare, although the exact prevalence is unknown.  For reasons that are unclear, women are affected with Fuchs endothelial dystrophy somewhat more frequently than men.",Fuchs endothelial dystrophy,0000393,GHR,https://ghr.nlm.nih.gov/condition/fuchs-endothelial-dystrophy,C0016781,T047,Disorders
What are the genetic changes related to Fuchs endothelial dystrophy ?,0000393-3,genetic changes,"The genetics of Fuchs endothelial dystrophy are unclear. Researchers have identified regions of a few chromosomes and several genes that they think may play a role in the development of Fuchs endothelial dystrophy, but many of these associations need to be further tested.  Fuchs endothelial dystrophy affects a thin layer of cells that line the back of the cornea, called corneal endothelial cells. These cells regulate the amount of fluid inside the cornea. An appropriate fluid balance in the cornea is necessary for clear vision. Fuchs endothelial dystrophy occurs when the endothelial cells die, and the cornea becomes swollen with too much fluid. Corneal endothelial cells continue to die over time, resulting in further vision problems. It is thought that mutations in genes that are active (expressed) primarily in corneal endothelial cells or surrounding tissue may lead to the death of corneal endothelial cells, resulting in Fuchs endothelial dystrophy.  Some cases of the early-onset variant of Fuchs endothelial dystrophy are caused by mutations in the COL8A2 gene. This gene provides instructions for making a protein that is part of type VIII collagen. Type VIII collagen is largely found within the cornea, surrounding the endothelial cells. Specifically, type VIII collagen is a major component of a tissue at the back of the cornea, called Descemet's membrane. This membrane is a thin, sheet-like structure that separates and supports corneal endothelial cells. COL8A2 gene mutations that cause the early-onset variant of Fuchs endothelial dystrophy lead to an abnormal Descemet's membrane, which causes the cells to die and leads to the vision problems in people with this condition.  Mutations in unidentified genes are also likely to cause the early-onset variant of Fuchs endothelial dystrophy. The genetic causes of the late-onset form of the disorder are unknown.",Fuchs endothelial dystrophy,0000393,GHR,https://ghr.nlm.nih.gov/condition/fuchs-endothelial-dystrophy,C0016781,T047,Disorders
Is Fuchs endothelial dystrophy inherited ?,0000393-4,inheritance,"In some cases, Fuchs endothelial dystrophy appears to be inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. When this condition is caused by a mutation in the COL8A2 gene, it is inherited in an autosomal dominant pattern. In addition, an autosomal dominant inheritance pattern is apparent in some situations in which the condition is caused by alterations in an unknown gene.  In many families, the inheritance pattern is unknown.  Some cases result from new mutations in a gene and occur in people with no history of the disorder in their family.",Fuchs endothelial dystrophy,0000393,GHR,https://ghr.nlm.nih.gov/condition/fuchs-endothelial-dystrophy,C0016781,T047,Disorders
What are the treatments for Fuchs endothelial dystrophy ?,0000393-5,treatment,"These resources address the diagnosis or management of Fuchs endothelial dystrophy:  - Duke Eye Center: Corneal Disease  - Genetic Testing Registry: Corneal dystrophy, Fuchs endothelial 1  - Genetic Testing Registry: Corneal dystrophy, Fuchs endothelial, 2  - Genetic Testing Registry: Corneal dystrophy, Fuchs endothelial, 3  - Genetic Testing Registry: Corneal dystrophy, Fuchs endothelial, 4  - Genetic Testing Registry: Corneal dystrophy, Fuchs endothelial, 5  - Genetic Testing Registry: Corneal dystrophy, Fuchs endothelial, 6  - Genetic Testing Registry: Corneal dystrophy, Fuchs endothelial, 7  - MedlinePlus Encyclopedia: Fuchs Dystrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Fuchs endothelial dystrophy,0000393,GHR,https://ghr.nlm.nih.gov/condition/fuchs-endothelial-dystrophy,C0016781,T047,Disorders
What is (are) fucosidosis ?,0000394-1,information,"Fucosidosis is a condition that affects many areas of the body, especially the brain. Affected individuals have intellectual disability that worsens with age, and many develop dementia later in life. People with this condition often have delayed development of motor skills such as walking; the skills they do acquire deteriorate over time. Additional signs and symptoms of fucosidosis include impaired growth; abnormal bone development (dysostosis multiplex); seizures; abnormal muscle stiffness (spasticity); clusters of enlarged blood vessels forming small, dark red spots on the skin (angiokeratomas); distinctive facial features that are often described as ""coarse""; recurrent respiratory infections; and abnormally large abdominal organs (visceromegaly).  In severe cases, symptoms typically appear in infancy, and affected individuals usually live into late childhood. In milder cases, symptoms begin at age 1 or 2, and affected individuals tend to survive into mid-adulthood.  In the past, researchers described two types of this condition based on symptoms and age of onset, but current opinion is that the two types are actually a single disorder with signs and symptoms that range in severity.",fucosidosis,0000394,GHR,https://ghr.nlm.nih.gov/condition/fucosidosis,C0016788,T047,Disorders
How many people are affected by fucosidosis ?,0000394-2,frequency,"Fucosidosis is a rare condition; approximately 100 cases have been reported worldwide. This condition appears to be most prevalent in Italy, Cuba, and the southwestern United States.",fucosidosis,0000394,GHR,https://ghr.nlm.nih.gov/condition/fucosidosis,C0016788,T047,Disorders
What are the genetic changes related to fucosidosis ?,0000394-3,genetic changes,"Mutations in the FUCA1 gene cause fucosidosis. The FUCA1 gene provides instructions for making an enzyme called alpha-L-fucosidase. This enzyme plays a role in the breakdown of complexes of sugar molecules (oligosaccharides) attached to certain proteins (glycoproteins) and fats (glycolipids). Alpha-L-fucosidase is responsible for cutting (cleaving) off a sugar molecule called fucose toward the end of the breakdown process.  FUCA1 gene mutations severely reduce or eliminate the activity of the alpha-L-fucosidase enzyme. A lack of enzyme activity results in an incomplete breakdown of glycolipids and glycoproteins. These partially broken down compounds gradually accumulate within various cells and tissues throughout the body and cause cells to malfunction. Brain cells are particularly sensitive to the buildup of glycolipids and glycoproteins, which can result in cell death. Loss of brain cells is thought to cause the neurological symptoms of fucosidosis. Accumulation of glycolipids and glycoproteins also occurs in other organs such as the liver, spleen, skin, heart, pancreas, and kidneys, contributing to the additional symptoms of fucosidosis.",fucosidosis,0000394,GHR,https://ghr.nlm.nih.gov/condition/fucosidosis,C0016788,T047,Disorders
Is fucosidosis inherited ?,0000394-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",fucosidosis,0000394,GHR,https://ghr.nlm.nih.gov/condition/fucosidosis,C0016788,T047,Disorders
What are the treatments for fucosidosis ?,0000394-5,treatment,These resources address the diagnosis or management of fucosidosis:  - Genetic Testing Registry: Fucosidosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,fucosidosis,0000394,GHR,https://ghr.nlm.nih.gov/condition/fucosidosis,C0016788,T047,Disorders
What is (are) Fukuyama congenital muscular dystrophy ?,0000395-1,information,"Fukuyama congenital muscular dystrophy is an inherited condition that predominantly affects the muscles, brain, and eyes. Congenital muscular dystrophies are a group of genetic conditions that cause muscle weakness and wasting (atrophy) beginning very early in life.  Fukuyama congenital muscular dystrophy affects the skeletal muscles, which are muscles the body uses for movement. The first signs of the disorder appear in early infancy and include a weak cry, poor feeding, and weak muscle tone (hypotonia). Weakness of the facial muscles often leads to a distinctive facial appearance including droopy eyelids (ptosis) and an open mouth. In childhood, muscle weakness and joint deformities (contractures) restrict movement and interfere with the development of motor skills such as sitting, standing, and walking.  Fukuyama congenital muscular dystrophy also impairs brain development. People with this condition have a brain abnormality called cobblestone lissencephaly, in which the surface of the brain develops a bumpy, irregular appearance (like that of cobblestones). These changes in the structure of the brain lead to significantly delayed development of speech and motor skills and moderate to severe intellectual disability. Social skills are less severely impaired. Most children with Fukuyama congenital muscular dystrophy are never able to stand or walk, although some can sit without support and slide across the floor in a seated position. More than half of all affected children also experience seizures.  Other signs and symptoms of Fukuyama congenital muscular dystrophy include impaired vision, other eye abnormalities, and slowly progressive heart problems after age 10. As the disease progresses, affected people may develop swallowing difficulties that can lead to a bacterial lung infection called aspiration pneumonia. Because of the serious medical problems associated with Fukuyama congenital muscular dystrophy, most people with the disorder live only into late childhood or adolescence.",Fukuyama congenital muscular dystrophy,0000395,GHR,https://ghr.nlm.nih.gov/condition/fukuyama-congenital-muscular-dystrophy,C0410174,T047,Disorders
How many people are affected by Fukuyama congenital muscular dystrophy ?,0000395-2,frequency,"Fukuyama congenital muscular dystrophy is seen almost exclusively in Japan, where it is the second most common form of childhood muscular dystrophy (after Duchenne muscular dystrophy). Fukuyama congenital muscular dystrophy has an estimated incidence of 2 to 4 per 100,000 Japanese infants.",Fukuyama congenital muscular dystrophy,0000395,GHR,https://ghr.nlm.nih.gov/condition/fukuyama-congenital-muscular-dystrophy,C0410174,T047,Disorders
What are the genetic changes related to Fukuyama congenital muscular dystrophy ?,0000395-3,genetic changes,"Fukuyama congenital muscular dystrophy is caused by mutations in the FKTN gene. This gene provides instructions for making a protein called fukutin. Although the exact function of fukutin is unclear, researchers predict that it may chemically modify a protein called alpha ()-dystroglycan. This protein anchors cells to the lattice of proteins and other molecules (the extracellular matrix) that surrounds them. In skeletal muscles, -dystroglycan helps stabilize and protect muscle fibers. In the brain, this protein helps direct the movement (migration) of nerve cells (neurons) during early development.  The most common mutation in the FKTN gene reduces the amount of fukutin produced within cells. A shortage of fukutin likely prevents the normal modification of -dystroglycan, which disrupts that protein's normal function. Without functional -dystroglycan to stabilize muscle cells, muscle fibers become damaged as they repeatedly contract and relax with use. The damaged fibers weaken and die over time, leading to progressive weakness and atrophy of the skeletal muscles.  Defective -dystroglycan also affects the migration of neurons during the early development of the brain. Instead of stopping when they reach their intended destinations, some neurons migrate past the surface of the brain into the fluid-filled space that surrounds it. Researchers believe that this problem with neuronal migration causes cobblestone lissencephaly in children with Fukuyama congenital muscular dystrophy. Less is known about the effects of FKTN mutations in other parts of the body.  Because Fukuyama congenital muscular dystrophy involves a malfunction of -dystroglycan, this condition is described as a dystroglycanopathy.",Fukuyama congenital muscular dystrophy,0000395,GHR,https://ghr.nlm.nih.gov/condition/fukuyama-congenital-muscular-dystrophy,C0410174,T047,Disorders
Is Fukuyama congenital muscular dystrophy inherited ?,0000395-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Fukuyama congenital muscular dystrophy,0000395,GHR,https://ghr.nlm.nih.gov/condition/fukuyama-congenital-muscular-dystrophy,C0410174,T047,Disorders
What are the treatments for Fukuyama congenital muscular dystrophy ?,0000395-5,treatment,These resources address the diagnosis or management of Fukuyama congenital muscular dystrophy:  - Gene Review: Gene Review: Congenital Muscular Dystrophy Overview  - Gene Review: Gene Review: Fukuyama Congenital Muscular Dystrophy  - Genetic Testing Registry: Fukuyama congenital muscular dystrophy  - MedlinePlus Encyclopedia: Aspiration Pneumonia  - MedlinePlus Encyclopedia: Muscular Dystrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Fukuyama congenital muscular dystrophy,0000395,GHR,https://ghr.nlm.nih.gov/condition/fukuyama-congenital-muscular-dystrophy,C0410174,T047,Disorders
What is (are) fumarase deficiency ?,0000396-1,information,"Fumarase deficiency is a condition that primarily affects the nervous system, especially the brain. Affected infants may have an abnormally small head size (microcephaly), abnormal brain structure, severe developmental delay, weak muscle tone (hypotonia), and failure to gain weight and grow at the expected rate (failure to thrive). They may also experience seizures. Some people with this disorder have unusual facial features, including a prominent forehead (frontal bossing), low-set ears, a small jaw (micrognathia), widely spaced eyes (ocular hypertelorism), and a depressed nasal bridge. An enlarged liver and spleen (hepatosplenomegaly) may also be associated with this disorder, as well as an excess of red blood cells (polycythemia) or deficiency of white blood cells (leukopenia) in infancy. Affected individuals usually survive only a few months, but a few have lived into early adulthood.",fumarase deficiency,0000396,GHR,https://ghr.nlm.nih.gov/condition/fumarase-deficiency,C0342770,T047,Disorders
How many people are affected by fumarase deficiency ?,0000396-2,frequency,Fumarase deficiency is a very rare disorder. Approximately 100 affected individuals have been reported worldwide. Several were born in an isolated religious community in the southwestern United States.,fumarase deficiency,0000396,GHR,https://ghr.nlm.nih.gov/condition/fumarase-deficiency,C0342770,T047,Disorders
What are the genetic changes related to fumarase deficiency ?,0000396-3,genetic changes,"The FH gene provides instructions for making an enzyme called fumarase (also known as fumarate hydratase). Fumarase participates in an important series of reactions known as the citric acid cycle or Krebs cycle, which allows cells to use oxygen and generate energy. Specifically, fumarase helps convert a molecule called fumarate to a molecule called malate.  Mutations in the FH gene disrupt the enzyme's ability to help convert fumarate to malate, interfering with the function of this reaction in the citric acid cycle. Impairment of the process that generates energy for cells is particularly harmful to cells in the developing brain, and this impairment results in the signs and symptoms of fumarase deficiency.",fumarase deficiency,0000396,GHR,https://ghr.nlm.nih.gov/condition/fumarase-deficiency,C0342770,T047,Disorders
Is fumarase deficiency inherited ?,0000396-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",fumarase deficiency,0000396,GHR,https://ghr.nlm.nih.gov/condition/fumarase-deficiency,C0342770,T047,Disorders
What are the treatments for fumarase deficiency ?,0000396-5,treatment,These resources address the diagnosis or management of fumarase deficiency:  - Gene Review: Gene Review: Fumarate Hydratase Deficiency  - Genetic Testing Registry: Fumarase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,fumarase deficiency,0000396,GHR,https://ghr.nlm.nih.gov/condition/fumarase-deficiency,C0342770,T047,Disorders
What is (are) galactosemia ?,0000397-1,information,"Galactosemia is a disorder that affects how the body processes a simple sugar called galactose. A small amount of galactose is present in many foods. It is primarily part of a larger sugar called lactose, which is found in all dairy products and many baby formulas. The signs and symptoms of galactosemia result from an inability to use galactose to produce energy.  Researchers have identified several types of galactosemia. These conditions are each caused by mutations in a particular gene and affect different enzymes involved in breaking down galactose.  Classic galactosemia, also known as type I, is the most common and most severe form of the condition. If infants with classic galactosemia are not treated promptly with a low-galactose diet, life-threatening complications appear within a few days after birth. Affected infants typically develop feeding difficulties, a lack of energy (lethargy), a failure to gain weight and grow as expected (failure to thrive), yellowing of the skin and whites of the eyes (jaundice), liver damage, and abnormal bleeding. Other serious complications of this condition can include overwhelming bacterial infections (sepsis) and shock. Affected children are also at increased risk of delayed development, clouding of the lens of the eye (cataract), speech difficulties, and intellectual disability. Females with classic galactosemia may develop reproductive problems caused by an early loss of function of the ovaries (premature ovarian insufficiency).  Galactosemia type II (also called galactokinase deficiency) and type III (also called galactose epimerase deficiency) cause different patterns of signs and symptoms. Galactosemia type II causes fewer medical problems than the classic type. Affected infants develop cataracts but otherwise experience few long-term complications. The signs and symptoms of galactosemia type III vary from mild to severe and can include cataracts, delayed growth and development, intellectual disability, liver disease, and kidney problems.",galactosemia,0000397,GHR,https://ghr.nlm.nih.gov/condition/galactosemia,C0016952,T047,Disorders
How many people are affected by galactosemia ?,0000397-2,frequency,"Classic galactosemia occurs in 1 in 30,000 to 60,000 newborns. Galactosemia type II and type III are less common; type II probably affects fewer than 1 in 100,000 newborns and type III appears to be very rare.",galactosemia,0000397,GHR,https://ghr.nlm.nih.gov/condition/galactosemia,C0016952,T047,Disorders
What are the genetic changes related to galactosemia ?,0000397-3,genetic changes,"Mutations in the GALT, GALK1, and GALE genes cause galactosemia. These genes provide instructions for making enzymes that are essential for processing galactose obtained from the diet. These enzymes break down galactose into another simple sugar, glucose, and other molecules that the body can store or use for energy.  Mutations in the GALT gene cause classic galactosemia (type I). Most of these genetic changes almost completely eliminate the activity of the enzyme produced from the GALT gene, preventing the normal processing of galactose and resulting in the life-threatening signs and symptoms of this disorder. Another GALT gene mutation, known as the Duarte variant, reduces but does not eliminate the activity of the enzyme. People with the Duarte variant tend to have much milder features of galactosemia.  Galactosemia type II results from mutations in the GALK1 gene, while mutations in the GALE gene underlie galactosemia type III. Like the enzyme produced from the GALT gene, the enzymes made from the GALK1 and GALE genes play important roles in processing galactose. A shortage of any of these critical enzymes allows galactose and related compounds to build up to toxic levels in the body. The accumulation of these substances damages tissues and organs, leading to the characteristic features of galactosemia.",galactosemia,0000397,GHR,https://ghr.nlm.nih.gov/condition/galactosemia,C0016952,T047,Disorders
Is galactosemia inherited ?,0000397-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",galactosemia,0000397,GHR,https://ghr.nlm.nih.gov/condition/galactosemia,C0016952,T047,Disorders
What are the treatments for galactosemia ?,0000397-5,treatment,These resources address the diagnosis or management of galactosemia:  - Baby's First Test: Classic Galactosemia  - Baby's First Test: Galactoepimerase Deficiency  - Baby's First Test: Galactokinase Deficiency  - Gene Review: Gene Review: Classic Galactosemia and Clinical Variant Galactosemia  - Gene Review: Gene Review: Duarte Variant Galactosemia  - Gene Review: Gene Review: Epimerase Deficiency Galactosemia  - Genetic Testing Registry: Galactosemia  - MedlinePlus Encyclopedia: Galactose-1-phosphate uridyltransferase  - MedlinePlus Encyclopedia: Galactosemia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,galactosemia,0000397,GHR,https://ghr.nlm.nih.gov/condition/galactosemia,C0016952,T047,Disorders
What is (are) galactosialidosis ?,0000398-1,information,"Galactosialidosis is a condition that affects many areas of the body. The three forms of galactosialidosis are distinguished by the age at which symptoms develop and the pattern of features.  The early infantile form of galactosialidosis is associated with extensive swelling caused by fluid accumulation before birth (hydrops fetalis), a soft out-pouching in the lower abdomen (an inguinal hernia), and an enlarged liver and spleen (hepatosplenomegaly). Additional features of this form include abnormal bone development (dysostosis multiplex) and distinctive facial features that are often described as ""coarse."" Some infants have an enlarged heart (cardiomegaly); an eye abnormality called a cherry-red spot, which can be identified with an eye examination; and kidney disease that can progress to kidney failure. Infants with this form usually are diagnosed between birth and 3 months; they typically live into late infancy.  The late infantile form of galactosialidosis shares some features with the early infantile form, although the signs and symptoms are somewhat less severe and begin later in infancy. This form is characterized by short stature, dysostosis multiplex, heart valve problems, hepatosplenomegaly, and ""coarse"" facial features. Other symptoms seen in some individuals with this type include intellectual disability, hearing loss, and a cherry-red spot. Children with this condition typically develop symptoms within the first year of life. The life expectancy of individuals with this type varies depending on the severity of symptoms.  The juvenile/adult form of galactosialidosis has signs and symptoms that are somewhat different than those of the other two types. This form is distinguished by difficulty coordinating movements (ataxia), muscle twitches (myoclonus), seizures, and progressive intellectual disability. People with this form typically also have dark red spots on the skin (angiokeratomas), abnormalities in the bones of the spine, ""coarse"" facial features, a cherry-red spot, vision loss, and hearing loss. The age at which symptoms begin to develop varies widely among affected individuals, but the average age is 16. This form is typically associated with a normal life expectancy.",galactosialidosis,0000398,GHR,https://ghr.nlm.nih.gov/condition/galactosialidosis,C0268233,T047,Disorders
How many people are affected by galactosialidosis ?,0000398-2,frequency,The prevalence of galactosialidosis is unknown; more than 100 cases have been reported. Approximately 60 percent of people with galactosialidosis have the juvenile/adult form. Most people with this type of the condition are of Japanese descent.,galactosialidosis,0000398,GHR,https://ghr.nlm.nih.gov/condition/galactosialidosis,C0268233,T047,Disorders
What are the genetic changes related to galactosialidosis ?,0000398-3,genetic changes,"Mutations in the CTSA gene cause all forms of galactosialidosis. The CTSA gene provides instructions for making a protein called cathepsin A, which is active in cellular compartments called lysosomes. These compartments contain enzymes that digest and recycle materials when they are no longer needed. Cathepsin A works together with two enzymes, neuraminidase 1 and beta-galactosidase, to form a protein complex. This complex breaks down sugar molecules (oligosaccharides) attached to certain proteins (glycoproteins) or fats (glycolipids). Cathepsin A is also found on the cell surface, where it forms a complex with neuraminidase 1 and a protein called elastin binding protein. Elastin binding protein plays a role in the formation of elastic fibers, a component of the connective tissues that form the body's supportive framework.  CTSA mutations interfere with the normal function of cathepsin A. Most mutations disrupt the protein structure of cathepsin A, impairing its ability to form complexes with neuraminidase 1, beta-galactosidase, and elastin binding protein. As a result, these other enzymes are not functional, or they break down prematurely.  Galactosialidosis belongs to a large family of lysosomal storage disorders, each caused by the deficiency of a specific lysosomal enzyme or protein. In galactosialidosis, impaired functioning of cathepsin A and other enzymes causes certain substances to accumulate in the lysosomes.",galactosialidosis,0000398,GHR,https://ghr.nlm.nih.gov/condition/galactosialidosis,C0268233,T047,Disorders
Is galactosialidosis inherited ?,0000398-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",galactosialidosis,0000398,GHR,https://ghr.nlm.nih.gov/condition/galactosialidosis,C0268233,T047,Disorders
What are the treatments for galactosialidosis ?,0000398-5,treatment,These resources address the diagnosis or management of galactosialidosis:  - Genetic Testing Registry: Combined deficiency of sialidase AND beta galactosidase  - MedlinePlus Encyclopedia: Hepatosplenomegaly (image)  - MedlinePlus Encyclopedia: Hydrops fetalis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,galactosialidosis,0000398,GHR,https://ghr.nlm.nih.gov/condition/galactosialidosis,C0268233,T047,Disorders
What is (are) gastrointestinal stromal tumor ?,0000399-1,information,"A gastrointestinal stromal tumor (GIST) is a type of tumor that occurs in the gastrointestinal tract, most commonly in the stomach or small intestine. The tumors are thought to grow from specialized cells found in the gastrointestinal tract called interstitial cells of Cajal (ICCs) or precursors to these cells. GISTs are usually found in adults between ages 40 and 70; rarely, children and young adults develop these tumors. The tumors can be cancerous (malignant) or noncancerous (benign).  Small tumors may cause no signs or symptoms. However, some people with GISTs may experience pain or swelling in the abdomen, nausea, vomiting, loss of appetite, or weight loss. Sometimes, tumors cause bleeding, which may lead to low red blood cell counts (anemia) and, consequently, weakness and tiredness. Bleeding into the intestinal tract may cause black and tarry stools, and bleeding into the throat or stomach may cause vomiting of blood.  Affected individuals with no family history of GIST typically have only one tumor (called a sporadic GIST). People with a family history of GISTs (called familial GISTs) often have multiple tumors and additional signs or symptoms, including noncancerous overgrowth (hyperplasia) of other cells in the gastrointestinal tract and patches of dark skin on various areas of the body. Some affected individuals have a skin condition called urticaria pigmentosa (also known as cutaneous mastocytosis), which is characterized by raised patches of brownish skin that sting or itch when touched.",gastrointestinal stromal tumor,0000399,GHR,https://ghr.nlm.nih.gov/condition/gastrointestinal-stromal-tumor,C0238198,T191,Disorders
How many people are affected by gastrointestinal stromal tumor ?,0000399-2,frequency,"Approximately 5,000 new cases of GIST are diagnosed in the United States each year. However, GISTs may be more common than this estimate because small tumors may remain undiagnosed.",gastrointestinal stromal tumor,0000399,GHR,https://ghr.nlm.nih.gov/condition/gastrointestinal-stromal-tumor,C0238198,T191,Disorders
What are the genetic changes related to gastrointestinal stromal tumor ?,0000399-3,genetic changes,"Genetic changes in one of several genes are involved in the formation of GISTs. About 80 percent of cases are associated with a mutation in the KIT gene, and about 10 percent of cases are associated with a mutation in the PDGFRA gene. Mutations in the KIT and PDGFRA genes are associated with both familial and sporadic GISTs. A small number of affected individuals have mutations in other genes.  The KIT and PDGFRA genes provide instructions for making receptor proteins that are found in the cell membrane of certain cell types and stimulate signaling pathways inside the cell. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. When the ligand attaches (binds), the KIT or PDGFRA receptor protein is turned on (activated), which leads to activation of a series of proteins in multiple signaling pathways. These signaling pathways control many important cellular processes, such as cell growth and division (proliferation) and survival.  Mutations in the KIT and PDGFRA genes lead to proteins that no longer require ligand binding to be activated. As a result, the proteins and the signaling pathways are constantly turned on (constitutively activated), which increases the proliferation and survival of cells. When these mutations occur in ICCs or their precursors, the uncontrolled cell growth leads to GIST formation.",gastrointestinal stromal tumor,0000399,GHR,https://ghr.nlm.nih.gov/condition/gastrointestinal-stromal-tumor,C0238198,T191,Disorders
Is gastrointestinal stromal tumor inherited ?,0000399-4,inheritance,"Most cases of GIST are not inherited. Sporadic GIST is associated with somatic mutations, which are genetic changes that occur only in the tumor cells and occur during a person's lifetime.  In some cases of familial GIST, including those associated with mutations in the KIT and PDGFRA genes, mutations are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase a person's chance of developing tumors.  When familial GIST is associated with mutations in other genes, it can have an autosomal recessive pattern of inheritance, which means alterations in both copies of the gene in each cell increase a person's chance of developing tumors.",gastrointestinal stromal tumor,0000399,GHR,https://ghr.nlm.nih.gov/condition/gastrointestinal-stromal-tumor,C0238198,T191,Disorders
What are the treatments for gastrointestinal stromal tumor ?,0000399-5,treatment,These resources address the diagnosis or management of gastrointestinal stromal tumor:  - American Cancer Society: Treating Gastrointestinal Stromal Tumor (GIST)  - Cancer.Net: Gastrointestinal Stromal Tumor--Diagnosis  - Genetic Testing Registry: Gastrointestinal stromal tumor   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,gastrointestinal stromal tumor,0000399,GHR,https://ghr.nlm.nih.gov/condition/gastrointestinal-stromal-tumor,C0238198,T191,Disorders
What is (are) Gaucher disease ?,0000400-1,information,"Gaucher disease is an inherited disorder that affects many of the body's organs and tissues. The signs and symptoms of this condition vary widely among affected individuals. Researchers have described several types of Gaucher disease based on their characteristic features.  Type 1 Gaucher disease is the most common form of this condition. Type 1 is also called non-neuronopathic Gaucher disease because the brain and spinal cord (the central nervous system) are usually not affected. The features of this condition range from mild to severe and may appear anytime from childhood to adulthood. Major signs and symptoms include enlargement of the liver and spleen (hepatosplenomegaly), a low number of red blood cells (anemia), easy bruising caused by a decrease in blood platelets (thrombocytopenia), lung disease, and bone abnormalities such as bone pain, fractures, and arthritis.  Types 2 and 3 Gaucher disease are known as neuronopathic forms of the disorder because they are characterized by problems that affect the central nervous system. In addition to the signs and symptoms described above, these conditions can cause abnormal eye movements, seizures, and brain damage. Type 2 Gaucher disease usually causes life-threatening medical problems beginning in infancy. Type 3 Gaucher disease also affects the nervous system, but it tends to worsen more slowly than type 2.  The most severe type of Gaucher disease is called the perinatal lethal form. This condition causes severe or life-threatening complications starting before birth or in infancy. Features of the perinatal lethal form can include extensive swelling caused by fluid accumulation before birth (hydrops fetalis); dry, scaly skin (ichthyosis) or other skin abnormalities; hepatosplenomegaly; distinctive facial features; and serious neurological problems. As its name indicates, most infants with the perinatal lethal form of Gaucher disease survive for only a few days after birth.  Another form of Gaucher disease is known as the cardiovascular type because it primarily affects the heart, causing the heart valves to harden (calcify). People with the cardiovascular form of Gaucher disease may also have eye abnormalities, bone disease, and mild enlargement of the spleen (splenomegaly).",Gaucher disease,0000400,GHR,https://ghr.nlm.nih.gov/condition/gaucher-disease,C0017205,T047,Disorders
How many people are affected by Gaucher disease ?,0000400-2,frequency,"Gaucher disease occurs in 1 in 50,000 to 100,000 people in the general population. Type 1 is the most common form of the disorder; it occurs more frequently in people of Ashkenazi (eastern and central European) Jewish heritage than in those with other backgrounds. This form of the condition affects 1 in 500 to 1,000 people of Ashkenazi Jewish heritage. The other forms of Gaucher disease are uncommon and do not occur more frequently in people of Ashkenazi Jewish descent.",Gaucher disease,0000400,GHR,https://ghr.nlm.nih.gov/condition/gaucher-disease,C0017205,T047,Disorders
What are the genetic changes related to Gaucher disease ?,0000400-3,genetic changes,"Mutations in the GBA gene cause Gaucher disease. The GBA gene provides instructions for making an enzyme called beta-glucocerebrosidase. This enzyme breaks down a fatty substance called glucocerebroside into a sugar (glucose) and a simpler fat molecule (ceramide). Mutations in the GBA gene greatly reduce or eliminate the activity of beta-glucocerebrosidase. Without enough of this enzyme, glucocerebroside and related substances can build up to toxic levels within cells. Tissues and organs are damaged by the abnormal accumulation and storage of these substances, causing the characteristic features of Gaucher disease.",Gaucher disease,0000400,GHR,https://ghr.nlm.nih.gov/condition/gaucher-disease,C0017205,T047,Disorders
Is Gaucher disease inherited ?,0000400-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Gaucher disease,0000400,GHR,https://ghr.nlm.nih.gov/condition/gaucher-disease,C0017205,T047,Disorders
What are the treatments for Gaucher disease ?,0000400-5,treatment,These resources address the diagnosis or management of Gaucher disease:  - Baby's First Test  - Gene Review: Gene Review: Gaucher Disease  - Genetic Testing Registry: Gaucher disease  - MedlinePlus Encyclopedia: Gaucher Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Gaucher disease,0000400,GHR,https://ghr.nlm.nih.gov/condition/gaucher-disease,C0017205,T047,Disorders
What is (are) geleophysic dysplasia ?,0000401-1,information,"Geleophysic dysplasia is an inherited condition that affects many parts of the body. It is characterized by abnormalities involving the bones, joints, heart, and skin.  People with geleophysic dysplasia have short stature with very short hands and feet. Most also develop thickened skin and joint deformities called contractures, both of which significantly limit mobility. Affected individuals usually have a limited range of motion in their fingers, toes, wrists, and elbows. Additionally, contractures in the legs and hips cause many affected people to walk on their toes.  The name of this condition, which comes from the Greek words for happy (""gelios"") and nature (""physis""), is derived from the good-natured facial appearance seen in most affected individuals. The distinctive facial features associated with this condition include a round face with full cheeks, a small nose with upturned nostrils, a broad nasal bridge, a thin upper lip, upturned corners of the mouth, and a flat area between the upper lip and the nose (philtrum).  Geleophysic dysplasia is also characterized by heart (cardiac) problems, particularly abnormalities of the cardiac valves. These valves normally control the flow of blood through the heart. In people with geleophysic dysplasia, the cardiac valves thicken, which impedes blood flow and increases blood pressure in the heart. Other heart problems have also been reported in people with geleophysic dysplasia; these include a narrowing of the artery from the heart to the lungs (pulmonary stenosis) and a hole between the two upper chambers of the heart (atrial septal defect).  Other features of geleophysic dysplasia can include an enlarged liver (hepatomegaly) and recurrent respiratory and ear infections. In severe cases, a narrowing of the windpipe (tracheal stenosis) can cause serious breathing problems. As a result of heart and respiratory abnormalities, geleophysic dysplasia is often life-threatening in childhood. However, some affected people have lived into adulthood.",geleophysic dysplasia,0000401,GHR,https://ghr.nlm.nih.gov/condition/geleophysic-dysplasia,C3489726,T019,Disorders
How many people are affected by geleophysic dysplasia ?,0000401-2,frequency,Geleophysic dysplasia is a rare disorder whose prevalence is unknown. More than 30 affected individuals have been reported.,geleophysic dysplasia,0000401,GHR,https://ghr.nlm.nih.gov/condition/geleophysic-dysplasia,C3489726,T019,Disorders
What are the genetic changes related to geleophysic dysplasia ?,0000401-3,genetic changes,"Geleophysic dysplasia results from mutations in the ADAMTSL2 gene. This gene provides instructions for making a protein whose function is unclear. The protein is found in the extracellular matrix, which is the intricate lattice of proteins and other molecules that forms in the spaces between cells. Studies suggest that the ADAMTSL2 protein may play a role in the microfibrillar network, which is an organized clustering of thread-like filaments (called microfibrils) in the extracellular matrix. This network provides strength and flexibility to tissues throughout the body.  Mutations in the ADAMTSL2 protein likely change the protein's 3-dimensional structure. Through a process that is poorly understood, ADAMTSL2 gene mutations alter the microfibrillar network in many different tissues. Impairment of this essential network disrupts the normal functions of cells, which likely contributes to the varied signs and symptoms of geleophysic dysplasia. Researchers are working to determine how mutations in the ADAMTSL2 gene lead to short stature, heart disease, and the other features of this condition.",geleophysic dysplasia,0000401,GHR,https://ghr.nlm.nih.gov/condition/geleophysic-dysplasia,C3489726,T019,Disorders
Is geleophysic dysplasia inherited ?,0000401-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",geleophysic dysplasia,0000401,GHR,https://ghr.nlm.nih.gov/condition/geleophysic-dysplasia,C3489726,T019,Disorders
What are the treatments for geleophysic dysplasia ?,0000401-5,treatment,These resources address the diagnosis or management of geleophysic dysplasia:  - Gene Review: Gene Review: Geleophysic Dysplasia  - Genetic Testing Registry: Geleophysic dysplasia 2  - MedlinePlus Encyclopedia: Short Stature   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,geleophysic dysplasia,0000401,GHR,https://ghr.nlm.nih.gov/condition/geleophysic-dysplasia,C3489726,T019,Disorders
What is (are) generalized arterial calcification of infancy ?,0000402-1,information,"Generalized arterial calcification of infancy (GACI) is a disorder affecting the circulatory system that becomes apparent before birth or within the first few months of life. It is characterized by abnormal accumulation of the mineral calcium (calcification) in the walls of the blood vessels that carry blood from the heart to the rest of the body (the arteries). This calcification often occurs along with thickening of the lining of the arterial walls (the intima). These changes lead to narrowing (stenosis) and stiffness of the arteries, which forces the heart to work harder to pump blood. As a result, heart failure may develop in affected individuals, with signs and symptoms including difficulty breathing, accumulation of fluid (edema) in the extremities, a bluish appearance of the skin or lips (cyanosis), severe high blood pressure (hypertension), and an enlarged heart (cardiomegaly).  People with GACI may also have calcification in other organs and tissues, particularly around the joints. In addition, they may have hearing loss or softening and weakening of the bones (rickets).  Some individuals with GACI also develop features similar to those of another disorder called pseudoxanthoma elasticum (PXE). PXE is characterized by the accumulation of calcium and other minerals (mineralization) in elastic fibers, which are a component of connective tissue. Connective tissue provides strength and flexibility to structures throughout the body. Features characteristic of PXE that also occur in GACI include yellowish bumps called papules on the underarms and other areas of skin that touch when a joint bends (flexor areas); and abnormalities called angioid streaks affecting tissue at the back of the eye, which can be detected during an eye examination.  As a result of the cardiovascular problems associated with GACI, individuals with this condition often do not survive past infancy, with death typically caused by a heart attack or stroke. However, affected individuals who survive their first six months, known as the critical period, can live into adolescence or early adulthood.",generalized arterial calcification of infancy,0000402,GHR,https://ghr.nlm.nih.gov/condition/generalized-arterial-calcification-of-infancy,C1859727,T047,Disorders
How many people are affected by generalized arterial calcification of infancy ?,0000402-2,frequency,"The prevalence of GACI has been estimated to be about 1 in 391,000. At least 200 affected individuals have been described in the medical literature.",generalized arterial calcification of infancy,0000402,GHR,https://ghr.nlm.nih.gov/condition/generalized-arterial-calcification-of-infancy,C1859727,T047,Disorders
What are the genetic changes related to generalized arterial calcification of infancy ?,0000402-3,genetic changes,"In about two-thirds of cases, GACI is caused by mutations in the ENPP1 gene. This gene provides instructions for making a protein that helps break down a molecule called adenosine triphosphate (ATP), specifically when it is found outside the cell (extracellular). Extracellular ATP is quickly broken down into other molecules called adenosine monophosphate (AMP) and pyrophosphate. Pyrophosphate is important in controlling calcification and other mineralization in the body. Mutations in the ENPP1 gene are thought to result in reduced availability of pyrophosphate, leading to excessive calcification in the body and causing the signs and symptoms of GACI.  GACI can also be caused by mutations in the ABCC6 gene. This gene provides instructions for making a protein called MRP6, also known as the ABCC6 protein. This protein is found primarily in the liver and kidneys, with small amounts in other tissues such as the skin, stomach, blood vessels, and eyes.  MRP6 is thought to transport certain substances across the cell membrane; however, the substances have not been identified. Some studies suggest that the MRP6 protein stimulates the release of ATP from cells through an unknown mechanism, allowing it to be broken down into AMP and pyrophosphate and helping to control deposition of calcium and other minerals in the body as described above. Other studies suggest that a substance transported by MRP6 is involved in the breakdown of ATP. This unidentified substance is thought to help prevent mineralization of tissues.  Mutations in the ABCC6 gene lead to an absent or nonfunctional MRP6 protein. It is unclear how a lack of properly functioning MRP6 protein leads to GACI. This shortage may impair the release of ATP from cells. As a result, little pyrophosphate is produced, and calcium accumulates in the blood vessels and other tissues affected by GACI. Alternatively, a lack of functioning MRP6 may impair the transport of a substance that would normally prevent mineralization, leading to the abnormal accumulation of calcium characteristic of GACI.  Some people with GACI do not have mutations in the ENPP1 or ABCC6 gene. In these affected individuals, the cause of the disorder is unknown.",generalized arterial calcification of infancy,0000402,GHR,https://ghr.nlm.nih.gov/condition/generalized-arterial-calcification-of-infancy,C1859727,T047,Disorders
Is generalized arterial calcification of infancy inherited ?,0000402-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",generalized arterial calcification of infancy,0000402,GHR,https://ghr.nlm.nih.gov/condition/generalized-arterial-calcification-of-infancy,C1859727,T047,Disorders
What are the treatments for generalized arterial calcification of infancy ?,0000402-5,treatment,These resources address the diagnosis or management of GACI:  - Gene Review: Gene Review: Generalized Arterial Calcification of Infancy  - Genetic Testing Registry: Generalized arterial calcification of infancy 2   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,generalized arterial calcification of infancy,0000402,GHR,https://ghr.nlm.nih.gov/condition/generalized-arterial-calcification-of-infancy,C1859727,T047,Disorders
What is (are) genitopatellar syndrome ?,0000403-1,information,"Genitopatellar syndrome is a rare condition characterized by genital abnormalities, missing or underdeveloped kneecaps (patellae), intellectual disability, and abnormalities affecting other parts of the body.  The genital abnormalities in affected males typically include undescended testes (cryptorchidism) and underdevelopment of the scrotum. Affected females can have an enlarged clitoris (clitoromegaly) and small labia.  Missing or underdeveloped patellae is the most common skeletal abnormality associated with genitopatellar syndrome. Affected individuals may have additional skeletal problems, including joint deformities (contractures) involving the hips and knees or an inward- and upward-turning foot called a clubfoot. Bone abnormalities of the spine, ribs, collarbone (clavicle), and pelvis have also been reported.  Genitopatellar syndrome is also associated with delayed development and intellectual disability, which are often severe. Affected individuals may have an usually small head (microcephaly) and structural brain abnormalities, including underdeveloped or absent tissue connecting the left and right halves of the brain (agenesis of the corpus callosum).  People with genitopatellar syndrome may have distinctive facial features such as prominent cheeks and eyes, a nose with a rounded tip or a broad bridge, an unusually small chin (micrognathia) or a chin that protrudes (prognathism), and a narrowing of the head at the temples. Many affected infants have weak muscle tone (hypotonia) that leads to breathing and feeding difficulties. The condition can also be associated with abnormalities of the heart, kidneys, and teeth.",genitopatellar syndrome,0000403,GHR,https://ghr.nlm.nih.gov/condition/genitopatellar-syndrome,C3812898,T047,Disorders
How many people are affected by genitopatellar syndrome ?,0000403-2,frequency,Genitopatellar syndrome is estimated to occur in fewer than 1 per million people. At least 18 cases have been reported in the medical literature.,genitopatellar syndrome,0000403,GHR,https://ghr.nlm.nih.gov/condition/genitopatellar-syndrome,C3812898,T047,Disorders
What are the genetic changes related to genitopatellar syndrome ?,0000403-3,genetic changes,"Genitopatellar syndrome is caused by mutations in the KAT6B gene. This gene provides instructions for making a type of enzyme called a histone acetyltransferase. These enzymes modify histones, which are structural proteins that attach (bind) to DNA and give chromosomes their shape. By adding a small molecule called an acetyl group to histones, histone acetyltransferases control the activity of certain genes. Little is known about the function of the histone acetyltransferase produced from the KAT6B gene. It appears to regulate genes that are important for early development, including development of the skeleton and nervous system.  The mutations that cause genitopatellar syndrome occur near the end of the KAT6B gene and lead to the production of a shortened histone acetyltransferase enzyme. Researchers suspect that the shortened enzyme may function differently than the full-length version, altering the regulation of various genes during early development. However, it is unclear how these changes lead to the specific features of genitopatellar syndrome.",genitopatellar syndrome,0000403,GHR,https://ghr.nlm.nih.gov/condition/genitopatellar-syndrome,C3812898,T047,Disorders
Is genitopatellar syndrome inherited ?,0000403-4,inheritance,"This condition has an autosomal dominant inheritance pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. All reported cases have resulted from new mutations in the gene and have occurred in people with no history of the disorder in their family.",genitopatellar syndrome,0000403,GHR,https://ghr.nlm.nih.gov/condition/genitopatellar-syndrome,C3812898,T047,Disorders
What are the treatments for genitopatellar syndrome ?,0000403-5,treatment,These resources address the diagnosis or management of genitopatellar syndrome:  - Gene Review: Gene Review: KAT6B-Related Disorders  - Genetic Testing Registry: Genitopatellar syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,genitopatellar syndrome,0000403,GHR,https://ghr.nlm.nih.gov/condition/genitopatellar-syndrome,C3812898,T047,Disorders
What is (are) Ghosal hematodiaphyseal dysplasia ?,0000404-1,information,"Ghosal hematodiaphyseal dysplasia is a rare inherited condition characterized by abnormally thick bones and a shortage of red blood cells (anemia). Signs and symptoms of the condition become apparent in early childhood.  In affected individuals, the long bones in the arms and legs are unusually dense and wide. The bone changes specifically affect the shafts of the long bones, called diaphyses, and areas near the ends of the bones called metaphyses. The bone abnormalities can lead to bowing of the legs and difficulty walking.  Ghosal hematodiaphyseal dysplasia also causes scarring (fibrosis) of the bone marrow, which is the spongy tissue inside long bones where blood cells are formed. The abnormal bone marrow cannot produce enough red blood cells, which leads to anemia.Signs and symptoms of anemia that have been reported in people with Ghosal hematodiaphyseal dysplasia include extremely pale skin (pallor) and excessive tiredness (fatigue).",Ghosal hematodiaphyseal dysplasia,0000404,GHR,https://ghr.nlm.nih.gov/condition/ghosal-hematodiaphyseal-dysplasia,C1856465,T019,Disorders
How many people are affected by Ghosal hematodiaphyseal dysplasia ?,0000404-2,frequency,Ghosal hematodiaphyseal dysplasia is a rare disorder; only a few cases have been reported in the medical literature. Most affected individuals have been from the Middle East and India.,Ghosal hematodiaphyseal dysplasia,0000404,GHR,https://ghr.nlm.nih.gov/condition/ghosal-hematodiaphyseal-dysplasia,C1856465,T019,Disorders
What are the genetic changes related to Ghosal hematodiaphyseal dysplasia ?,0000404-3,genetic changes,"Ghosal hematodiaphyseal dysplasia results from mutations in the TBXAS1 gene. This gene provides instructions for making an enzyme called thromboxane A synthase 1, which acts as part of a chemical signaling pathway involved in normal blood clotting (hemostasis). Based on its role in Ghosal hematodiaphyseal dysplasia, researchers suspect that thromboxane A synthase 1 may also be important for bone remodeling, which is a normal process in which old bone is removed and new bone is created to replace it, and for the production of red blood cells in bone marrow.  Mutations in the TBXAS1 gene severely reduce the activity of thromboxane A synthase 1. Studies suggest that a lack of this enzyme's activity may lead to abnormal bone remodeling and fibrosis of the bone marrow. However, the mechanism by which a shortage of thromboxane A synthase 1 activity leads to the particular abnormalities characteristic of Ghosal hematodiaphyseal dysplasia is unclear.",Ghosal hematodiaphyseal dysplasia,0000404,GHR,https://ghr.nlm.nih.gov/condition/ghosal-hematodiaphyseal-dysplasia,C1856465,T019,Disorders
Is Ghosal hematodiaphyseal dysplasia inherited ?,0000404-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Ghosal hematodiaphyseal dysplasia,0000404,GHR,https://ghr.nlm.nih.gov/condition/ghosal-hematodiaphyseal-dysplasia,C1856465,T019,Disorders
What are the treatments for Ghosal hematodiaphyseal dysplasia ?,0000404-5,treatment,"These resources address the diagnosis or management of Ghosal hematodiaphyseal dysplasia:  - Genetic Testing Registry: Ghosal syndrome  - National Heart, Lung, and Blood Institute: How is Anemia Diagnosed?  - National Heart, Lung, and Blood Institute: How is Anemia Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Ghosal hematodiaphyseal dysplasia,0000404,GHR,https://ghr.nlm.nih.gov/condition/ghosal-hematodiaphyseal-dysplasia,C1856465,T019,Disorders
What is (are) giant axonal neuropathy ?,0000405-1,information,"Giant axonal neuropathy is an inherited condition involving dysfunction of a specific type of protein in nerve cells (neurons). The protein is essential for normal nerve function because it forms neurofilaments. Neurofilaments make up a structural framework that helps to define the shape and size of the neurons. This condition is characterized by abnormally large and dysfunctional axons, which are the specialized extensions of nerve cells that are required for the transmission of nerve impulses.  Giant axonal neuropathy generally appears in infancy or early childhood. It progresses slowly as neuronal injury becomes more severe. Signs of giant axonal neuropathy usually begin in the peripheral nervous system, which governs movement and sensation in the arms, legs, and other parts of the body. Most individuals with this disorder first have problems with walking. Later they may lose sensation, coordination, strength, and reflexes in their limbs. Hearing and visual problems may also occur. Extremely kinky hair (as compared to others in the family) is characteristic of giant axonal neuropathy, occurring in almost all affected people.  As the disorder progresses, the brain and spinal cord (central nervous system) may become involved, causing a gradual decline in mental function, loss of control of body movement, and seizures.",giant axonal neuropathy,0000405,GHR,https://ghr.nlm.nih.gov/condition/giant-axonal-neuropathy,C1850386,T047,Disorders
How many people are affected by giant axonal neuropathy ?,0000405-2,frequency,Giant axonal neuropathy is a very rare disorder; the incidence is unknown.,giant axonal neuropathy,0000405,GHR,https://ghr.nlm.nih.gov/condition/giant-axonal-neuropathy,C1850386,T047,Disorders
What are the genetic changes related to giant axonal neuropathy ?,0000405-3,genetic changes,"Giant axonal neuropathy is caused by mutations in the GAN gene, which provides instructions for making a protein called gigaxonin. Some GAN gene mutations change the shape of the protein, affecting how it binds to other proteins to form a functional complex. Other mutations prevent cells from producing any gigaxonin protein.  Gigaxonin is involved in a cellular function that destroys and gets rid of excess or damaged proteins using a mechanism called the ubiquitin-proteasome system. Neurons without functional gigaxonin accumulate excess neurofilaments in the axon, causing the axons to become distended. These giant axons do not transmit signals properly and eventually deteriorate, resulting in problems with movement and other nervous system dysfunction.",giant axonal neuropathy,0000405,GHR,https://ghr.nlm.nih.gov/condition/giant-axonal-neuropathy,C1850386,T047,Disorders
Is giant axonal neuropathy inherited ?,0000405-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",giant axonal neuropathy,0000405,GHR,https://ghr.nlm.nih.gov/condition/giant-axonal-neuropathy,C1850386,T047,Disorders
What are the treatments for giant axonal neuropathy ?,0000405-5,treatment,These resources address the diagnosis or management of giant axonal neuropathy:  - Gene Review: Gene Review: Giant Axonal Neuropathy  - Genetic Testing Registry: Giant axonal neuropathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,giant axonal neuropathy,0000405,GHR,https://ghr.nlm.nih.gov/condition/giant-axonal-neuropathy,C1850386,T047,Disorders
What is (are) giant congenital melanocytic nevus ?,0000406-1,information,"Giant congenital melanocytic nevus is a skin condition characterized by an abnormally dark, noncancerous skin patch (nevus) that is composed of pigment-producing cells called melanocytes. It is present from birth (congenital) or is noticeable soon after birth. The nevus may be small in infants, but it will usually grow at the same rate the body grows and will eventually be at least 40 cm (15.75 inches) across. The nevus can appear anywhere on the body, but it is more often found on the trunk or limbs. The color ranges from tan to black and can become darker or lighter over time. The surface of a nevus can be flat, rough, raised, thickened, or bumpy; the surface can vary in different regions of the nevus, and it can change over time. The skin of the nevus is often dry and prone to irritation and itching (dermatitis). Excessive hair growth (hypertrichosis) can occur within the nevus. There is often less fat tissue under the skin of the nevus; the skin may appear thinner there than over other areas of the body.  People with giant congenital melanocytic nevus may have more than one nevus (plural: nevi). The other nevi are often smaller than the giant nevus. Affected individuals may have one or two additional nevi or multiple small nevi that are scattered over the skin; these are known as satellite or disseminated nevi.  Affected individuals may feel anxiety or emotional stress due to the impact the nevus may have on their appearance and their health. Children with giant congenital melanocytic nevus can develop emotional or behavior problems.  Some people with giant congenital melanocytic nevus develop a condition called neurocutaneous melanosis, which is the presence of pigment-producing skin cells (melanocytes) in the tissue that covers the brain and spinal cord. These melanocytes may be spread out or grouped together in clusters. Their growth can cause increased pressure in the brain, leading to headache, vomiting, irritability, seizures, and movement problems. Tumors in the brain may also develop.  Individuals with giant congenital melanocytic nevus have an increased risk of developing an aggressive form of cancer called melanoma, which arises from melanocytes. Estimates vary, but it is generally thought that people with giant congenital melanocytic nevus have a 5 to 10 percent lifetime risk of developing melanoma. Melanoma commonly begins in the nevus, but it can develop when melanocytes that invade other tissues, such as those in the brain and spinal cord, become cancerous. When melanoma occurs in people with giant congenital melanocytic nevus, the survival rate is low.  Other types of tumors can also develop in individuals with giant congenital melanocytic nevus, including soft tissue tumors (sarcomas), fatty tumors (lipomas), and tumors of the nerve cells (schwannomas).",giant congenital melanocytic nevus,0000406,GHR,https://ghr.nlm.nih.gov/condition/giant-congenital-melanocytic-nevus,C0017547,T191,Disorders
How many people are affected by giant congenital melanocytic nevus ?,0000406-2,frequency,"Giant congenital melanocytic nevus occurs in approximately 1 in 20,000 newborns worldwide.",giant congenital melanocytic nevus,0000406,GHR,https://ghr.nlm.nih.gov/condition/giant-congenital-melanocytic-nevus,C0017547,T191,Disorders
What are the genetic changes related to giant congenital melanocytic nevus ?,0000406-3,genetic changes,"NRAS gene mutations cause most cases of giant congenital melanocytic nevus. Rarely, mutations in the BRAF gene are responsible for this condition.  The proteins produced from these genes are involved in a process known as signal transduction by which signals are relayed from outside the cell to the cell's nucleus. Signals relayed by the N-Ras and BRAF proteins instruct the cell to grow and divide (proliferate) or to mature and take on specialized functions (differentiate). To transmit signals, these proteins must be turned on; when the proteins are turned off, they do not relay signals to the cell's nucleus.  The NRAS or BRAF gene mutations responsible for giant congenital melanocytic nevus are somatic, meaning that they are acquired during a person's lifetime and are present only in certain cells. These mutations occur early in embryonic development during the growth and division (proliferation) of cells that develop into melanocytes. Somatic NRAS or BRAF gene mutations cause the altered protein in affected cells to be constantly turned on (constitutively active) and relaying signals. The overactive protein may contribute to the development of giant congenital melanocytic nevus by allowing cells that develop into melanocytes to grow and divide uncontrollably, starting before birth.",giant congenital melanocytic nevus,0000406,GHR,https://ghr.nlm.nih.gov/condition/giant-congenital-melanocytic-nevus,C0017547,T191,Disorders
Is giant congenital melanocytic nevus inherited ?,0000406-4,inheritance,This condition is generally not inherited but arises from a mutation in the body's cells that occurs after conception. This alteration is called a somatic mutation. A somatic mutation in one copy of the NRAS or BRAF gene is sufficient to cause this disorder.,giant congenital melanocytic nevus,0000406,GHR,https://ghr.nlm.nih.gov/condition/giant-congenital-melanocytic-nevus,C0017547,T191,Disorders
What are the treatments for giant congenital melanocytic nevus ?,0000406-5,treatment,These resources address the diagnosis or management of giant congenital melanocytic nevus:  - Cleveland Clinic: The Facts About Melanoma  - Genetic Testing Registry: Giant pigmented hairy nevus  - MedlinePlus Encyclopedia: Giant Congenital Nevus  - Nevus Outreach: Treatment Options  - Primary Care Dermatology Society   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,giant congenital melanocytic nevus,0000406,GHR,https://ghr.nlm.nih.gov/condition/giant-congenital-melanocytic-nevus,C0017547,T191,Disorders
What is (are) Gilbert syndrome ?,0000407-1,information,"Gilbert syndrome is a relatively mild condition characterized by periods of elevated levels of a toxic substance called bilirubin in the blood (hyperbilirubinemia). Bilirubin, which has an orange-yellow tint, is produced when red blood cells are broken down. This substance is removed from the body only after it undergoes a chemical reaction in the liver, which converts the toxic form of bilirubin (unconjugated bilirubin) to a nontoxic form called conjugated bilirubin. People with Gilbert syndrome have a buildup of unconjugated bilirubin in their blood (unconjugated hyperbilirubinemia). In affected individuals, bilirubin levels fluctuate and very rarely increase to levels that cause jaundice, which is yellowing of the skin and whites of the eyes.  Gilbert syndrome is usually recognized in adolescence. If people with this condition have episodes of hyperbilirubinemia, these episodes are generally mild and typically occur when the body is under stress, for instance because of dehydration, prolonged periods without food (fasting), illness, vigorous exercise, or menstruation. Some people with Gilbert syndrome also experience abdominal discomfort or tiredness. However, approximately 30 percent of people with Gilbert syndrome have no signs or symptoms of the condition and are discovered only when routine blood tests reveal elevated unconjugated bilirubin levels.",Gilbert syndrome,0000407,GHR,https://ghr.nlm.nih.gov/condition/gilbert-syndrome,C0017551,T047,Disorders
How many people are affected by Gilbert syndrome ?,0000407-2,frequency,Gilbert syndrome is a common condition that is estimated to affect 3 to 7 percent of Americans.,Gilbert syndrome,0000407,GHR,https://ghr.nlm.nih.gov/condition/gilbert-syndrome,C0017551,T047,Disorders
What are the genetic changes related to Gilbert syndrome ?,0000407-3,genetic changes,"Changes in the UGT1A1 gene cause Gilbert syndrome. This gene provides instructions for making the bilirubin uridine diphosphate glucuronosyltransferase (bilirubin-UGT) enzyme, which is found primarily in liver cells and is necessary for the removal of bilirubin from the body.  The bilirubin-UGT enzyme performs a chemical reaction called glucuronidation. During this reaction, the enzyme transfers a compound called glucuronic acid to unconjugated bilirubin, converting it to conjugated bilirubin. Glucuronidation makes bilirubin dissolvable in water so that it can be removed from the body.  Gilbert syndrome occurs worldwide, but some mutations occur more often in particular populations. In many populations, the most common genetic change that causes Gilbert syndrome (known as UGT1A1*28) occurs in an area near the UGT1A1 gene called the promoter region, which controls the production of the bilirubin-UGT enzyme. This genetic change impairs enzyme production. However, this change is uncommon in Asian populations, and affected Asians often have a mutation that changes a single protein building block (amino acid) in the bilirubin-UGT enzyme. This type of mutation, known as a missense mutation, results in reduced enzyme function.  People with Gilbert syndrome have approximately 30 percent of normal bilirubin-UGT enzyme function. As a result, unconjugated bilirubin is not glucuronidated quickly enough. This toxic substance then builds up in the body, causing mild hyperbilirubinemia.  Not everyone with the genetic changes that cause Gilbert syndrome develops hyperbilirubinemia, indicating that additional factors, such as conditions that further hinder the glucuronidation process, may be necessary for development of the condition. For example, red blood cells may break down too easily, releasing excess amounts of bilirubin that the impaired enzyme cannot keep up with. Alternatively, movement of bilirubin into the liver, where it would be glucuronidated, may be impaired. These other factors may be due to changes in other genes.",Gilbert syndrome,0000407,GHR,https://ghr.nlm.nih.gov/condition/gilbert-syndrome,C0017551,T047,Disorders
Is Gilbert syndrome inherited ?,0000407-4,inheritance,"Gilbert syndrome can have different inheritance patterns. When the condition is caused by the UGT1A1*28 change in the promoter region of the UGT1A1 gene, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have the mutation. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  When the condition is caused by a missense mutation in the UGT1A1 gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. A more severe condition known as Crigler-Najjar syndrome occurs when both copies of the UGT1A1 gene have mutations.",Gilbert syndrome,0000407,GHR,https://ghr.nlm.nih.gov/condition/gilbert-syndrome,C0017551,T047,Disorders
What are the treatments for Gilbert syndrome ?,0000407-5,treatment,These resources address the diagnosis or management of Gilbert syndrome:  - Genetic Testing Registry: Gilbert's syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Gilbert syndrome,0000407,GHR,https://ghr.nlm.nih.gov/condition/gilbert-syndrome,C0017551,T047,Disorders
What is (are) Gillespie syndrome ?,0000408-1,information,"Gillespie syndrome is a disorder that involves eye abnormalities, problems with balance and coordinating movements (ataxia), and mild to moderate intellectual disability.  Gillespie syndrome is characterized by aniridia, which is the absence of the colored part of the eye (the iris). In most affected individuals, only part of the iris is missing (partial aniridia) in both eyes, but in some affected individuals, partial aniridia affects only one eye, or the entire iris is missing (complete aniridia) in one or both eyes. The absence of all or part of the iris can cause blurry vision (reduced visual acuity) and increased sensitivity to light (photophobia). Rapid, involuntary eye movements (nystagmus) can also occur in Gillespie syndrome.  The balance and movement problems in Gillespie syndrome result from underdevelopment (hypoplasia) of a part of the brain called the cerebellum. This abnormality can cause delayed development of motor skills such as walking. In addition, difficulty controlling the muscles in the mouth can lead to delayed speech development. The difficulties with coordination generally become noticeable in early childhood when the individual is learning these skills. People with Gillespie syndrome usually continue to have an unsteady gait and speech problems. However, the problems do not get worse over time, and in some cases they improve slightly.  Other features of Gillespie syndrome can include abnormalities in the bones of the spine (vertebrae) and malformations of the heart.",Gillespie syndrome,0000408,GHR,https://ghr.nlm.nih.gov/condition/gillespie-syndrome,C0431401,T019,Disorders
How many people are affected by Gillespie syndrome ?,0000408-2,frequency,The prevalence of Gillespie syndrome is unknown. Only a few dozen affected individuals have been described in the medical literature. It has been estimated that Gillespie syndrome accounts for about 2 percent of cases of aniridia.,Gillespie syndrome,0000408,GHR,https://ghr.nlm.nih.gov/condition/gillespie-syndrome,C0431401,T019,Disorders
What are the genetic changes related to Gillespie syndrome ?,0000408-3,genetic changes,"Gillespie syndrome can be caused by mutations in the PAX6 gene. The PAX6 gene provides instructions for making a protein that is involved in early development, including the development of the eyes and brain. The PAX6 protein attaches (binds) to specific regions of DNA and regulates the activity of other genes. On the basis of this role, the PAX6 protein is called a transcription factor.  Mutations in the PAX6 gene result in the absence of the PAX6 protein or production of a nonfunctional PAX6 protein that is unable to bind to DNA and regulate the activity of other genes. This lack of functional protein disrupts embryonic development, especially the development of the eyes and brain, leading to the signs and symptoms of Gillespie syndrome.  Most people with Gillespie syndrome do not have mutations in the PAX6 gene. In these affected individuals, the cause of the disorder is unknown.",Gillespie syndrome,0000408,GHR,https://ghr.nlm.nih.gov/condition/gillespie-syndrome,C0431401,T019,Disorders
Is Gillespie syndrome inherited ?,0000408-4,inheritance,"In some cases, including those in which Gillespie syndrome is caused by PAX6 gene mutations, the condition occurs in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Some affected individuals inherit the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  Gillespie syndrome can also be inherited in an autosomal recessive pattern, which means both copies of a gene in each cell have mutations. The gene or genes involved in these cases are unknown. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Gillespie syndrome,0000408,GHR,https://ghr.nlm.nih.gov/condition/gillespie-syndrome,C0431401,T019,Disorders
What are the treatments for Gillespie syndrome ?,0000408-5,treatment,"These resources address the diagnosis or management of Gillespie syndrome:  - Eunice Kennedy Shriver National Institute of Child Health and Human Development: How Do Health Care Providers Diagnose Intellectual and Developmental Disabilities?  - Eunice Kennedy Shriver National Institute of Child Health and Human Development: What Are Treatments for Intellectual and Developmental Disabilities?  - Genetic Testing Registry: Aniridia, cerebellar ataxia, and mental retardation   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Gillespie syndrome,0000408,GHR,https://ghr.nlm.nih.gov/condition/gillespie-syndrome,C0431401,T019,Disorders
What is (are) Gitelman syndrome ?,0000409-1,information,"Gitelman syndrome is a kidney disorder that causes an imbalance of charged atoms (ions) in the body, including ions of potassium, magnesium, and calcium.  The signs and symptoms of Gitelman syndrome usually appear in late childhood or adolescence. Common features of this condition include painful muscle spasms (tetany), muscle weakness or cramping, dizziness, and salt craving. Also common is a tingling or prickly sensation in the skin (paresthesias), most often affecting the face. Some individuals with Gitelman syndrome experience excessive tiredness (fatigue), low blood pressure, and a painful joint condition called chondrocalcinosis. Studies suggest that Gitelman syndrome may also increase the risk of a potentially dangerous abnormal heart rhythm called ventricular arrhythmia.  The signs and symptoms of Gitelman syndrome vary widely, even among affected members of the same family. Most people with this condition have relatively mild symptoms, although affected individuals with severe muscle cramping, paralysis, and slow growth have been reported.",Gitelman syndrome,0000409,GHR,https://ghr.nlm.nih.gov/condition/gitelman-syndrome,C0268450,T047,Disorders
How many people are affected by Gitelman syndrome ?,0000409-2,frequency,"Gitelman syndrome affects an estimated 1 in 40,000 people worldwide.",Gitelman syndrome,0000409,GHR,https://ghr.nlm.nih.gov/condition/gitelman-syndrome,C0268450,T047,Disorders
What are the genetic changes related to Gitelman syndrome ?,0000409-3,genetic changes,"Gitelman syndrome is usually caused by mutations in the SLC12A3 gene. Less often, the condition results from mutations in the CLCNKB gene. The proteins produced from these genes are involved in the kidneys' reabsorption of salt (sodium chloride or NaCl) from urine back into the bloodstream. Mutations in either gene impair the kidneys' ability to reabsorb salt, leading to the loss of excess salt in the urine (salt wasting). Abnormalities of salt transport also affect the reabsorption of other ions, including ions of potassium, magnesium, and calcium. The resulting imbalance of ions in the body underlies the major features of Gitelman syndrome.",Gitelman syndrome,0000409,GHR,https://ghr.nlm.nih.gov/condition/gitelman-syndrome,C0268450,T047,Disorders
Is Gitelman syndrome inherited ?,0000409-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Gitelman syndrome,0000409,GHR,https://ghr.nlm.nih.gov/condition/gitelman-syndrome,C0268450,T047,Disorders
What are the treatments for Gitelman syndrome ?,0000409-5,treatment,These resources address the diagnosis or management of Gitelman syndrome:  - Genetic Testing Registry: Familial hypokalemia-hypomagnesemia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Gitelman syndrome,0000409,GHR,https://ghr.nlm.nih.gov/condition/gitelman-syndrome,C0268450,T047,Disorders
What is (are) Glanzmann thrombasthenia ?,0000410-1,information,"Glanzmann thrombasthenia is a bleeding disorder that is characterized by prolonged or spontaneous bleeding starting from birth. People with Glanzmann thrombasthenia tend to bruise easily, have frequent nosebleeds (epistaxis), and may bleed from the gums. They may also develop red or purple spots on the skin caused by bleeding underneath the skin (petechiae) or swelling caused by bleeding within tissues (hematoma). Glanzmann thrombasthenia can also cause prolonged bleeding following injury, trauma, or surgery (including dental work). Women with this condition can have prolonged and sometimes abnormally heavy menstrual bleeding. Affected women also have an increased risk of excessive blood loss during pregnancy and childbirth.  About a quarter of individuals with Glanzmann thrombasthenia have bleeding in the gastrointestinal tract, which often occurs later in life. Rarely, affected individuals have bleeding inside the skull (intracranial hemorrhage) or joints (hemarthrosis).  The severity and frequency of the bleeding episodes in Glanzmann thrombasthenia can vary greatly among affected individuals, even in the same family. Spontaneous bleeding tends to become less frequent with age.",Glanzmann thrombasthenia,0000410,GHR,https://ghr.nlm.nih.gov/condition/glanzmann-thrombasthenia,C0040015,T047,Disorders
How many people are affected by Glanzmann thrombasthenia ?,0000410-2,frequency,"Glanzmann thrombasthenia is estimated to affect 1 in one million individuals worldwide, but may be more common in certain groups, including those of Romani ethnicity, particularly people within the French Manouche community.",Glanzmann thrombasthenia,0000410,GHR,https://ghr.nlm.nih.gov/condition/glanzmann-thrombasthenia,C0040015,T047,Disorders
What are the genetic changes related to Glanzmann thrombasthenia ?,0000410-3,genetic changes,"Mutations in the ITGA2B or ITGB3 gene cause Glanzmann thrombasthenia. These genes provide instructions for making the two parts (subunits) of a receptor protein called integrin alphaIIb/beta3 (IIb3). This protein is abundant on the surface of platelets. Platelets are small cell fragments that circulate in blood and are an essential component of blood clots. During clot formation, integrin IIb3 helps platelets bind together. Blood clots protect the body after injury by sealing off damaged blood vessels and preventing further blood loss.  ITGA2B or ITGB3 gene mutations result in a shortage (deficiency) of functional integrin IIb3. As a result, platelets cannot clump together to form a blood clot, leading to prolonged bleeding.  Three types of Glanzmann thrombasthenia have been classified according to the amount of integrin IIb3 that is available. People with type I (the most common type) have less than 5 percent of normal integrin IIb3 levels, people with type II have between 5 and 20 percent of normal integrin IIb3 levels, and people with the variant type have adequate integrin IIb3 levels but produce only nonfunctional integrin.  Some people with Glanzmann thrombasthenia do not have an identified mutation in either the ITGA2B or ITGB3 gene; the cause of the disorder in these individuals is unknown.",Glanzmann thrombasthenia,0000410,GHR,https://ghr.nlm.nih.gov/condition/glanzmann-thrombasthenia,C0040015,T047,Disorders
Is Glanzmann thrombasthenia inherited ?,0000410-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Glanzmann thrombasthenia,0000410,GHR,https://ghr.nlm.nih.gov/condition/glanzmann-thrombasthenia,C0040015,T047,Disorders
What are the treatments for Glanzmann thrombasthenia ?,0000410-5,treatment,These resources address the diagnosis or management of Glanzmann thrombasthenia:  - CLIMB Glanzmann Thrombasthenia Info Sheet  - Canadian Hemophilia Society: Glanzmann Thrombasthenia Information Booklet  - Genetic Testing Registry: Glanzmann's thrombasthenia  - MedlinePlus Encyclopedia: Glanzmann's Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Glanzmann thrombasthenia,0000410,GHR,https://ghr.nlm.nih.gov/condition/glanzmann-thrombasthenia,C0040015,T047,Disorders
What is (are) globozoospermia ?,0000411-1,information,"Globozoospermia is a condition that affects only males. It is characterized by abnormal sperm and leads to an inability to father biological children (infertility).  Normal sperm cells have an oval-shaped head with a cap-like covering called the acrosome. The acrosome contains enzymes that break down the outer membrane of an egg cell, allowing the sperm to fertilize the egg. The sperm cells of males with globozoospermia, however, have a round head and no acrosome. The abnormal sperm are unable to fertilize an egg cell, leading to infertility.",globozoospermia,0000411,GHR,https://ghr.nlm.nih.gov/condition/globozoospermia,C0403825,T033,Disorders
How many people are affected by globozoospermia ?,0000411-2,frequency,"Globozoospermia is a rare condition that is estimated to affect 1 in 65,000 men. It is most common in North Africa, where it accounts for approximately 1 in 100 cases of male infertility.",globozoospermia,0000411,GHR,https://ghr.nlm.nih.gov/condition/globozoospermia,C0403825,T033,Disorders
What are the genetic changes related to globozoospermia ?,0000411-3,genetic changes,"Globozoospermia is most commonly caused by mutations in the DPY19L2 gene, which are found in about 70 percent of men with this condition. Mutations in other genes likely also cause globozoospermia.  The DPY19L2 gene provides instructions for making a protein that is found in developing sperm cells. The DPY19L2 protein is involved in the development of the acrosome and elongation of the sperm head, which are integral steps in sperm cell maturation. Mutations in the DPY19L2 gene result in a loss of functional DPY19L2 protein. As a result, sperm cells have no acrosome and do not elongate properly. Without an acrosome, the abnormal sperm are unable to get through the outer membrane of an egg cell to fertilize it, leading to infertility in affected men. Researchers have described other characteristics of the abnormal sperm cells that make fertilization of an egg cell difficult, although it is not clear how changes in the DPY19L2 gene are involved in development of these characteristics.",globozoospermia,0000411,GHR,https://ghr.nlm.nih.gov/condition/globozoospermia,C0403825,T033,Disorders
Is globozoospermia inherited ?,0000411-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",globozoospermia,0000411,GHR,https://ghr.nlm.nih.gov/condition/globozoospermia,C0403825,T033,Disorders
What are the treatments for globozoospermia ?,0000411-5,treatment,These resources address the diagnosis or management of globozoospermia:  - Association for Reproductive Medicine: Semen Analysis  - Centers for Disease Control: Assisted Reproductive Technology (ART)  - Genetic Testing Registry: Globozoospermia  - MedlinePlus Encyclopedia: Semen Analysis  - MedlinePlus Health Topic: Assisted Reproductive Technology   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,globozoospermia,0000411,GHR,https://ghr.nlm.nih.gov/condition/globozoospermia,C0403825,T033,Disorders
What is (are) glucose phosphate isomerase deficiency ?,0000412-1,information,"Glucose phosphate isomerase (GPI) deficiency is an inherited disorder that affects red blood cells, which carry oxygen to the body's tissues. People with this disorder have a condition known as chronic hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely, resulting in a shortage of red blood cells (anemia). Chronic hemolytic anemia can lead to unusually pale skin (pallor), yellowing of the eyes and skin (jaundice), extreme tiredness (fatigue), shortness of breath (dyspnea), and a rapid heart rate (tachycardia). An enlarged spleen (splenomegaly), an excess of iron in the blood, and small pebble-like deposits in the gallbladder or bile ducts (gallstones) may also occur in this disorder.  Hemolytic anemia in GPI deficiency can range from mild to severe. In the most severe cases, affected individuals do not survive to birth. Individuals with milder disease can survive into adulthood. People with any level of severity of the disorder can have episodes of more severe hemolysis, called hemolytic crises, which can be triggered by bacterial or viral infections.  A small percentage of individuals with GPI deficiency also have neurological problems, including intellectual disability and difficulty with coordinating movements (ataxia).",glucose phosphate isomerase deficiency,0000412,GHR,https://ghr.nlm.nih.gov/condition/glucose-phosphate-isomerase-deficiency,C3469598,T047,Disorders
How many people are affected by glucose phosphate isomerase deficiency ?,0000412-2,frequency,GPI deficiency is a rare cause of hemolytic anemia; its prevalence is unknown. About 50 cases have been described in the medical literature.,glucose phosphate isomerase deficiency,0000412,GHR,https://ghr.nlm.nih.gov/condition/glucose-phosphate-isomerase-deficiency,C3469598,T047,Disorders
What are the genetic changes related to glucose phosphate isomerase deficiency ?,0000412-3,genetic changes,"GPI deficiency is caused by mutations in the GPI gene, which provides instructions for making an enzyme called glucose phosphate isomerase (GPI). This enzyme has two distinct functions based on its structure. When two GPI molecules form a complex (a homodimer), the enzyme plays a role in a critical energy-producing process known as glycolysis, also called the glycolytic pathway. During glycolysis, the simple sugar glucose is broken down to produce energy. Specifically, GPI is involved in the second step of the glycolytic pathway; in this step, a molecule called glucose-6-phosphate is converted to another molecule called fructose-6-phosphate.  When GPI remains a single molecule (a monomer) it is involved in the development and maintenance of nerve cells (neurons). In this context, it is often known as neuroleukin (NLK).  Some GPI gene mutations may result in a less stable homodimer, impairing the activity of the enzyme in the glycolytic pathway. The resulting imbalance of molecules involved in the glycolytic pathway eventually impairs the ability of red blood cells to maintain their structure, leading to hemolysis.  Other GPI gene mutations may cause the monomer to break down more easily, thereby interfering with its function in nerve cells. In addition, the shortage of monomers hinders homodimer formation, which impairs the glycolytic pathway. These mutations have been identified in individuals with GPI deficiency who have both hemolytic anemia and neurological problems.",glucose phosphate isomerase deficiency,0000412,GHR,https://ghr.nlm.nih.gov/condition/glucose-phosphate-isomerase-deficiency,C3469598,T047,Disorders
Is glucose phosphate isomerase deficiency inherited ?,0000412-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",glucose phosphate isomerase deficiency,0000412,GHR,https://ghr.nlm.nih.gov/condition/glucose-phosphate-isomerase-deficiency,C3469598,T047,Disorders
What are the treatments for glucose phosphate isomerase deficiency ?,0000412-5,treatment,"These resources address the diagnosis or management of GPI deficiency:  - Genetic Testing Registry: Glucosephosphate isomerase deficiency  - Genetic Testing Registry: Hemolytic anemia, nonspherocytic, due to glucose phosphate isomerase deficiency  - National Heart, Lung, and Blood Institute: How is Hemolytic Anemia Diagnosed?  - National Heart, Lung, and Blood Institute: How is Hemolytic Anemia Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",glucose phosphate isomerase deficiency,0000412,GHR,https://ghr.nlm.nih.gov/condition/glucose-phosphate-isomerase-deficiency,C3469598,T047,Disorders
What is (are) glucose-6-phosphate dehydrogenase deficiency ?,0000413-1,information,"Glucose-6-phosphate dehydrogenase deficiency is a genetic disorder that occurs most often in males. This condition mainly affects red blood cells, which carry oxygen from the lungs to tissues throughout the body. In affected individuals, a defect in an enzyme called glucose-6-phosphate dehydrogenase causes red blood cells to break down prematurely. This destruction of red blood cells is called hemolysis.  The most common medical problem associated with glucose-6-phosphate dehydrogenase deficiency is hemolytic anemia, which occurs when red blood cells are destroyed faster than the body can replace them. This type of anemia leads to paleness, yellowing of the skin and whites of the eyes (jaundice), dark urine, fatigue, shortness of breath, and a rapid heart rate. In people with glucose-6-dehydrogenase deficiency, hemolytic anemia is most often triggered by bacterial or viral infections or by certain drugs (such as some antibiotics and medications used to treat malaria). Hemolytic anemia can also occur after eating fava beans or inhaling pollen from fava plants (a reaction called favism).  Glucose-6-dehydrogenase deficiency is also a significant cause of mild to severe jaundice in newborns. Many people with this disorder, however, never experience any signs or symptoms.",glucose-6-phosphate dehydrogenase deficiency,0000413,GHR,https://ghr.nlm.nih.gov/condition/glucose-6-phosphate-dehydrogenase-deficiency,C2939465,T047,Disorders
How many people are affected by glucose-6-phosphate dehydrogenase deficiency ?,0000413-2,frequency,"An estimated 400 million people worldwide have glucose-6-phosphate dehydrogenase deficiency. This condition occurs most frequently in certain parts of Africa, Asia, and the Mediterranean. It affects about 1 in 10 African American males in the United States.",glucose-6-phosphate dehydrogenase deficiency,0000413,GHR,https://ghr.nlm.nih.gov/condition/glucose-6-phosphate-dehydrogenase-deficiency,C2939465,T047,Disorders
What are the genetic changes related to glucose-6-phosphate dehydrogenase deficiency ?,0000413-3,genetic changes,"Mutations in the G6PD gene cause glucose-6-phosphate dehydrogenase deficiency.  The G6PD gene provides instructions for making an enzyme called glucose-6-phosphate dehydrogenase. This enzyme is involved in the normal processing of carbohydrates. It also protects red blood cells from the effects of potentially harmful molecules called reactive oxygen species. Reactive oxygen species are byproducts of normal cellular functions. Chemical reactions involving glucose-6-phosphate dehydrogenase produce compounds that prevent reactive oxygen species from building up to toxic levels within red blood cells.  If mutations in the G6PD gene reduce the amount of glucose-6-phosphate dehydrogenase or alter its structure, this enzyme can no longer play its protective role. As a result, reactive oxygen species can accumulate and damage red blood cells. Factors such as infections, certain drugs, or ingesting fava beans can increase the levels of reactive oxygen species, causing red blood cells to be destroyed faster than the body can replace them. A reduction in the amount of red blood cells causes the signs and symptoms of hemolytic anemia.  Researchers believe that carriers of a G6PD mutation may be partially protected against malaria, an infectious disease carried by a certain type of mosquito. A reduction in the amount of functional glucose-6-dehydrogenase appears to make it more difficult for this parasite to invade red blood cells. Glucose-6-phosphate dehydrogenase deficiency occurs most frequently in areas of the world where malaria is common.",glucose-6-phosphate dehydrogenase deficiency,0000413,GHR,https://ghr.nlm.nih.gov/condition/glucose-6-phosphate-dehydrogenase-deficiency,C2939465,T047,Disorders
Is glucose-6-phosphate dehydrogenase deficiency inherited ?,0000413-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",glucose-6-phosphate dehydrogenase deficiency,0000413,GHR,https://ghr.nlm.nih.gov/condition/glucose-6-phosphate-dehydrogenase-deficiency,C2939465,T047,Disorders
What are the treatments for glucose-6-phosphate dehydrogenase deficiency ?,0000413-5,treatment,These resources address the diagnosis or management of glucose-6-phosphate dehydrogenase deficiency:  - Baby's First Test  - Genetic Testing Registry: Glucose 6 phosphate dehydrogenase deficiency  - MedlinePlus Encyclopedia: Glucose-6-phosphate dehydrogenase deficiency  - MedlinePlus Encyclopedia: Glucose-6-phosphate dehydrogenase test  - MedlinePlus Encyclopedia: Hemolytic anemia  - MedlinePlus Encyclopedia: Newborn jaundice   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,glucose-6-phosphate dehydrogenase deficiency,0000413,GHR,https://ghr.nlm.nih.gov/condition/glucose-6-phosphate-dehydrogenase-deficiency,C2939465,T047,Disorders
What is (are) glucose-galactose malabsorption ?,0000414-1,information,"Glucose-galactose malabsorption is a condition in which the cells lining the intestine cannot take in the sugars glucose and galactose, which prevents proper digestion of these molecules and larger molecules made from them.  Glucose and galactose are called simple sugars, or monosaccharides. Sucrose (table sugar) and lactose (the sugar found in milk) are called disaccharides because they are made from two simple sugars, and are broken down into these simple sugars during digestion. Sucrose is broken down into glucose and another simple sugar called fructose, and lactose is broken down into glucose and galactose. As a result, lactose, sucrose and other compounds made from sugar molecules (carbohydrates) cannot be digested by individuals with glucose-galactose malabsorption.  Glucose-galactose malabsorption generally becomes apparent in the first few weeks of a baby's life. Affected infants experience severe diarrhea resulting in life-threatening dehydration, increased acidity of the blood and tissues (acidosis), and weight loss when fed breast milk or regular infant formulas. However, they are able to digest fructose-based formulas that do not contain glucose or galactose. Some affected children are better able to tolerate glucose and galactose as they get older.  Small amounts of glucose in the urine (mild glucosuria) may occur intermittently in this disorder. Affected individuals may also develop kidney stones or more widespread deposits of calcium within the kidneys.",glucose-galactose malabsorption,0000414,GHR,https://ghr.nlm.nih.gov/condition/glucose-galactose-malabsorption,C0268186,T019,Disorders
How many people are affected by glucose-galactose malabsorption ?,0000414-2,frequency,"Glucose-galactose malabsorption is a rare disorder; only a few hundred cases have been identified worldwide. However, as many as 10 percent of the population may have a somewhat reduced capacity for glucose absorption without associated health problems. This condition may be a milder variation of glucose-galactose malabsorption.",glucose-galactose malabsorption,0000414,GHR,https://ghr.nlm.nih.gov/condition/glucose-galactose-malabsorption,C0268186,T019,Disorders
What are the genetic changes related to glucose-galactose malabsorption ?,0000414-3,genetic changes,"Mutations in the SLC5A1 gene cause glucose-galactose malabsorption.  The SLC5A1 gene provides instructions for producing a sodium/glucose cotransporter protein called SGLT1. This protein is found mainly in the intestinal tract and, to a lesser extent, in the kidneys, where it is involved in transporting glucose and the structurally similar galactose across cell membranes.  The sodium/glucose cotransporter protein is important in the functioning of intestinal epithelial cells, which are cells that line the walls of the intestine. These cells have fingerlike projections called microvilli that absorb nutrients from food as it passes through the intestine. Based on their appearance, groups of these microvilli are known collectively as the brush border. The sodium/glucose cotransporter protein is involved in the process of using energy to move glucose and galactose across the brush border membrane for absorption, a mechanism called active transport. Sodium and water are transported across the brush border along with the sugars in this process.  Mutations that prevent the sodium/glucose cotransporter protein from performing this function result in a buildup of glucose and galactose in the intestinal tract. This failure of active transport prevents the glucose and galactose from being absorbed and providing nourishment to the body. In addition, the water that normally would have been transported across the brush border with the sugar instead remains in the intestinal tract to be expelled with the stool, resulting in dehydration of the body's tissues and severe diarrhea.",glucose-galactose malabsorption,0000414,GHR,https://ghr.nlm.nih.gov/condition/glucose-galactose-malabsorption,C0268186,T019,Disorders
Is glucose-galactose malabsorption inherited ?,0000414-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition. In some cases, individuals with one altered gene have reduced levels of glucose absorption capacity as measured in laboratory tests, but this has not generally been shown to have significant health effects.",glucose-galactose malabsorption,0000414,GHR,https://ghr.nlm.nih.gov/condition/glucose-galactose-malabsorption,C0268186,T019,Disorders
What are the treatments for glucose-galactose malabsorption ?,0000414-5,treatment,These resources address the diagnosis or management of glucose-galactose malabsorption:  - Genetic Testing Registry: Congenital glucose-galactose malabsorption   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,glucose-galactose malabsorption,0000414,GHR,https://ghr.nlm.nih.gov/condition/glucose-galactose-malabsorption,C0268186,T019,Disorders
What is (are) GLUT1 deficiency syndrome ?,0000415-1,information,"GLUT1 deficiency syndrome is a disorder affecting the nervous system that can have a variety of neurological signs and symptoms. Approximately 90 percent of affected individuals have a form of the disorder often referred to as common GLUT1 deficiency syndrome. These individuals generally have frequent seizures (epilepsy) beginning in the first months of life. In newborns, the first sign of the disorder may be involuntary eye movements that are rapid and irregular. Babies with common GLUT1 deficiency syndrome have a normal head size at birth, but growth of the brain and skull is often slow, which can result in an abnormally small head size (microcephaly). People with this form of GLUT1 deficiency syndrome may have developmental delay or intellectual disability. Most affected individuals also have other neurological problems, such as stiffness caused by abnormal tensing of the muscles (spasticity), difficulty in coordinating movements (ataxia), and speech difficulties (dysarthria). Some experience episodes of confusion, lack of energy (lethargy), headaches, or muscle twitches (myoclonus), particularly during periods without food (fasting).  About 10 percent of individuals with GLUT1 deficiency syndrome have a form of the disorder often known as non-epileptic GLUT1 deficiency syndrome, which is usually less severe than the common form. People with the non-epileptic form do not have seizures, but they may still have developmental delay and intellectual disability. Most have movement problems such as ataxia or involuntary tensing of various muscles (dystonia); the movement problems may be more pronounced than in the common form.  Several conditions that were originally given other names have since been recognized to be variants of GLUT1 deficiency syndrome. These include paroxysmal choreoathetosis with spasticity (dystonia 9); paroxysmal exercise-induced dyskinesia and epilepsy (dystonia 18); and certain types of epilepsy. In rare cases, people with variants of GLUT1 deficiency syndrome produce abnormal red blood cells and have uncommon forms of a blood condition known as anemia, which is characterized by a shortage of red blood cells.",GLUT1 deficiency syndrome,0000415,GHR,https://ghr.nlm.nih.gov/condition/glut1-deficiency-syndrome,C1847501,T047,Disorders
How many people are affected by GLUT1 deficiency syndrome ?,0000415-2,frequency,"GLUT1 deficiency syndrome is a rare disorder. Approximately 500 cases have been reported worldwide since the disorder was first identified in 1991. In Australia, the prevalence of the disorder has been estimated at 1 in 90,000 people. However, researchers suggest that the disorder may be underdiagnosed, because many neurological disorders can cause similar symptoms.",GLUT1 deficiency syndrome,0000415,GHR,https://ghr.nlm.nih.gov/condition/glut1-deficiency-syndrome,C1847501,T047,Disorders
What are the genetic changes related to GLUT1 deficiency syndrome ?,0000415-3,genetic changes,"GLUT1 deficiency syndrome is caused by mutations in the SLC2A1 gene. This gene provides instructions for producing a protein called the glucose transporter protein type 1 (GLUT1). The GLUT1 protein is embedded in the outer membrane surrounding cells, where it transports a simple sugar called glucose into cells from the blood or from other cells for use as fuel.  In the brain, the GLUT1 protein is involved in moving glucose, which is the brain's main energy source, across the blood-brain barrier. The blood-brain barrier acts as a boundary between tiny blood vessels (capillaries) and the surrounding brain tissue; it protects the brain's delicate nerve tissue by preventing many other types of molecules from entering the brain. The GLUT1 protein also moves glucose between cells in the brain called glia, which protect and maintain nerve cells (neurons).  SLC2A1 gene mutations reduce or eliminate the function of the GLUT1 protein. Having less functional GLUT1 protein reduces the amount of glucose available to brain cells, which affects brain development and function.",GLUT1 deficiency syndrome,0000415,GHR,https://ghr.nlm.nih.gov/condition/glut1-deficiency-syndrome,C1847501,T047,Disorders
Is GLUT1 deficiency syndrome inherited ?,0000415-4,inheritance,"This condition is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. About 90 percent of cases of GLUT1 deficiency syndrome result from new mutations in the gene. These cases occur in people with no history of the disorder in their family. In other cases, an affected person inherits the mutation from an affected parent.  In a small number of families, GLUT1 deficiency syndrome is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",GLUT1 deficiency syndrome,0000415,GHR,https://ghr.nlm.nih.gov/condition/glut1-deficiency-syndrome,C1847501,T047,Disorders
What are the treatments for GLUT1 deficiency syndrome ?,0000415-5,treatment,These resources address the diagnosis or management of GLUT1 deficiency syndrome:  - G1D Registry  - Gene Review: Gene Review: Glucose Transporter Type 1 Deficiency Syndrome  - Genetic Testing Registry: Glucose transporter type 1 deficiency syndrome  - The Glucose Transporter Type 1 Deficiency Syndrome Research Consortium (G1DRC)   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,GLUT1 deficiency syndrome,0000415,GHR,https://ghr.nlm.nih.gov/condition/glut1-deficiency-syndrome,C1847501,T047,Disorders
What is (are) glutamate formiminotransferase deficiency ?,0000416-1,information,"Glutamate formiminotransferase deficiency is an inherited disorder that affects physical and mental development. There are two forms of this condition, which are distinguished by the severity of symptoms.  People with the mild form of glutamate formiminotransferase deficiency have minor delays in physical and mental development and may have mild intellectual disability. They also have unusually high levels of a molecule called formiminoglutamate (FIGLU) in their urine.  Individuals affected by the severe form of this disorder have profound intellectual disability and delayed development of motor skills such as sitting, standing, and walking. In addition to FIGLU in their urine, they have elevated amounts of certain B vitamins (called folates) in their blood.  The severe form of glutamate formiminotransferase deficiency is also characterized by megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number of red blood cells (anemia), and the remaining red blood cells are larger than normal (megaloblastic). The symptoms of this blood disorder may include decreased appetite, lack of energy, headaches, pale skin, and tingling or numbness in the hands and feet.",glutamate formiminotransferase deficiency,0000416,GHR,https://ghr.nlm.nih.gov/condition/glutamate-formiminotransferase-deficiency,C0268609,T047,Disorders
How many people are affected by glutamate formiminotransferase deficiency ?,0000416-2,frequency,"Glutamate formiminotransferase deficiency is a rare disorder; approximately 20 affected individuals have been identified. Of these, about one-quarter have the severe form of the disorder. Everyone reported with the severe form has been of Japanese origin. The remaining individuals, who come from a variety of ethnic backgrounds, are affected by the mild form of the condition.",glutamate formiminotransferase deficiency,0000416,GHR,https://ghr.nlm.nih.gov/condition/glutamate-formiminotransferase-deficiency,C0268609,T047,Disorders
What are the genetic changes related to glutamate formiminotransferase deficiency ?,0000416-3,genetic changes,"Mutations in the FTCD gene cause glutamate formiminotransferase deficiency. The FTCD gene provides instructions for making the enzyme formiminotransferase cyclodeaminase. This enzyme is involved in the last two steps in the breakdown (metabolism) of the amino acid histidine, a building block of most proteins. It also plays a role in producing one of several forms of the vitamin folate, which has many important functions in the body.  FTCD gene mutations that cause glutamate formiminotransferase deficiency reduce or eliminate the function of the enzyme. It is unclear how these changes are related to the specific health problems associated with the mild and severe forms of glutamate formiminotransferase deficiency, or why individuals are affected by one form or the other.",glutamate formiminotransferase deficiency,0000416,GHR,https://ghr.nlm.nih.gov/condition/glutamate-formiminotransferase-deficiency,C0268609,T047,Disorders
Is glutamate formiminotransferase deficiency inherited ?,0000416-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",glutamate formiminotransferase deficiency,0000416,GHR,https://ghr.nlm.nih.gov/condition/glutamate-formiminotransferase-deficiency,C0268609,T047,Disorders
What are the treatments for glutamate formiminotransferase deficiency ?,0000416-5,treatment,These resources address the diagnosis or management of glutamate formiminotransferase deficiency:  - Baby's First Test  - Genetic Testing Registry: Glutamate formiminotransferase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,glutamate formiminotransferase deficiency,0000416,GHR,https://ghr.nlm.nih.gov/condition/glutamate-formiminotransferase-deficiency,C0268609,T047,Disorders
What is (are) glutaric acidemia type I ?,0000417-1,information,"Glutaric acidemia type I is an inherited disorder in which the body is unable to process certain proteins properly. People with this disorder have inadequate levels of an enzyme that helps break down the amino acids lysine, hydroxylysine, and tryptophan, which are building blocks of protein. Excessive levels of these amino acids and their intermediate breakdown products can accumulate and cause damage to the brain, particularly the basal ganglia, which are regions that help control movement. Intellectual disability may also occur.  The severity of glutaric acidemia type I varies widely; some individuals are only mildly affected, while others have severe problems. In most cases, signs and symptoms first occur in infancy or early childhood, but in a small number of affected individuals, the disorder first becomes apparent in adolescence or adulthood.  Some babies with glutaric acidemia type I are born with unusually large heads (macrocephaly). Affected individuals may have difficulty moving and may experience spasms, jerking, rigidity, or decreased muscle tone. Some individuals with glutaric acidemia have developed bleeding in the brain or eyes that could be mistaken for the effects of child abuse. Strict dietary control may help limit progression of the neurological damage. Stress caused by infection, fever or other demands on the body may lead to worsening of the signs and symptoms, with only partial recovery.",glutaric acidemia type I,0000417,GHR,https://ghr.nlm.nih.gov/condition/glutaric-acidemia-type-i,C0268595,T046,Disorders
How many people are affected by glutaric acidemia type I ?,0000417-2,frequency,"Glutaric acidemia type I occurs in approximately 1 of every 30,000 to 40,000 individuals. It is much more common in the Amish community and in the Ojibwa population of Canada, where up to 1 in 300 newborns may be affected.",glutaric acidemia type I,0000417,GHR,https://ghr.nlm.nih.gov/condition/glutaric-acidemia-type-i,C0268595,T046,Disorders
What are the genetic changes related to glutaric acidemia type I ?,0000417-3,genetic changes,"Mutations in the GCDH gene cause glutaric acidemia type I.  The GCDH gene provides instructions for making the enzyme glutaryl-CoA dehydrogenase. This enzyme is involved in processing the amino acids lysine, hydroxylysine, and tryptophan.  Mutations in the GCDH gene prevent production of the enzyme or result in the production of a defective enzyme that cannot function. This enzyme deficiency allows lysine, hydroxylysine and tryptophan and their intermediate breakdown products to build up to abnormal levels, especially at times when the body is under stress.  The intermediate breakdown products resulting from incomplete processing of lysine, hydroxylysine, and tryptophan can damage the brain, particularly the basal ganglia, causing the signs and symptoms of glutaric acidemia type I.",glutaric acidemia type I,0000417,GHR,https://ghr.nlm.nih.gov/condition/glutaric-acidemia-type-i,C0268595,T046,Disorders
Is glutaric acidemia type I inherited ?,0000417-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",glutaric acidemia type I,0000417,GHR,https://ghr.nlm.nih.gov/condition/glutaric-acidemia-type-i,C0268595,T046,Disorders
What are the treatments for glutaric acidemia type I ?,0000417-5,treatment,"These resources address the diagnosis or management of glutaric acidemia type I:  - Baby's First Test  - Genetic Testing Registry: Glutaric aciduria, type 1   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",glutaric acidemia type I,0000417,GHR,https://ghr.nlm.nih.gov/condition/glutaric-acidemia-type-i,C0268595,T046,Disorders
What is (are) glutaric acidemia type II ?,0000418-1,information,"Glutaric acidemia type II is an inherited disorder that interferes with the body's ability to break down proteins and fats to produce energy. Incompletely processed proteins and fats can build up in the body and cause the blood and tissues to become too acidic (metabolic acidosis).  Glutaric acidemia type II usually appears in infancy or early childhood as a sudden episode called a metabolic crisis, in which acidosis and low blood sugar (hypoglycemia) cause weakness, behavior changes such as poor feeding and decreased activity, and vomiting. These metabolic crises, which can be life-threatening, may be triggered by common childhood illnesses or other stresses.  In the most severe cases of glutaric acidemia type II, affected individuals may also be born with physical abnormalities. These may include brain malformations, an enlarged liver (hepatomegaly), a weakened and enlarged heart (dilated cardiomyopathy), fluid-filled cysts and other malformations of the kidneys, unusual facial features, and genital abnormalities. Glutaric acidemia type II may also cause a characteristic odor resembling that of sweaty feet.  Some affected individuals have less severe symptoms that begin later in childhood or in adulthood. In the mildest forms of glutaric acidemia type II, muscle weakness developing in adulthood may be the first sign of the disorder.",glutaric acidemia type II,0000418,GHR,https://ghr.nlm.nih.gov/condition/glutaric-acidemia-type-ii,C0268596,T046,Disorders
How many people are affected by glutaric acidemia type II ?,0000418-2,frequency,Glutaric acidemia type II is a very rare disorder; its precise incidence is unknown. It has been reported in several different ethnic groups.,glutaric acidemia type II,0000418,GHR,https://ghr.nlm.nih.gov/condition/glutaric-acidemia-type-ii,C0268596,T046,Disorders
What are the genetic changes related to glutaric acidemia type II ?,0000418-3,genetic changes,"Mutations in any of three genes, ETFA, ETFB, and ETFDH, can result in glutaric acidemia type II. The ETFA and ETFB genes provide instructions for producing two protein segments, or subunits, that come together to make an enzyme called electron transfer flavoprotein. The ETFDH gene provides instructions for making another enzyme called electron transfer flavoprotein dehydrogenase.  Glutaric acidemia type II is caused by a deficiency in either of these two enzymes. Electron transfer flavoprotein and electron transfer flavoprotein dehydrogenase are normally active in the mitochondria, which are the energy-producing centers of cells. These enzymes help break down proteins and fats to provide energy for the body. When one of the enzymes is defective or missing, partially broken down nutrients accumulate in the cells and damage them, causing the signs and symptoms of glutaric acidemia type II.  People with mutations that result in a complete loss of either enzyme produced from the ETFA, ETFB or ETFDH genes are likely to experience the most severe symptoms of glutaric acidemia type II. Mutations that allow the enzyme to retain some activity may result in milder forms of the disorder.",glutaric acidemia type II,0000418,GHR,https://ghr.nlm.nih.gov/condition/glutaric-acidemia-type-ii,C0268596,T046,Disorders
Is glutaric acidemia type II inherited ?,0000418-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",glutaric acidemia type II,0000418,GHR,https://ghr.nlm.nih.gov/condition/glutaric-acidemia-type-ii,C0268596,T046,Disorders
What are the treatments for glutaric acidemia type II ?,0000418-5,treatment,"These resources address the diagnosis or management of glutaric acidemia type II:  - Baby's First Test  - Genetic Testing Registry: Glutaric aciduria, type 2   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",glutaric acidemia type II,0000418,GHR,https://ghr.nlm.nih.gov/condition/glutaric-acidemia-type-ii,C0268596,T046,Disorders
What is (are) glutathione synthetase deficiency ?,0000419-1,information,"Glutathione synthetase deficiency is a disorder that prevents the production of an important molecule called glutathione. Glutathione helps prevent damage to cells by neutralizing harmful molecules generated during energy production. Glutathione also plays a role in processing medications and cancer-causing compounds (carcinogens), and building DNA, proteins, and other important cellular components.  Glutathione synthetase deficiency can be classified into three types: mild, moderate, and severe. Mild glutathione synthetase deficiency usually results in the destruction of red blood cells (hemolytic anemia). In addition, affected individuals may release large amounts of a compound called 5-oxoproline in their urine (5-oxoprolinuria). This compound builds up when glutathione is not processed correctly in cells.  Individuals with moderate glutathione synthetase deficiency may experience symptoms beginning shortly after birth including hemolytic anemia, 5-oxoprolinuria, and elevated acidity in the blood and tissues (metabolic acidosis).  In addition to the features present in moderate glutathione synthetase deficiency, individuals affected by the severe form of this disorder may experience neurological symptoms. These problems may include seizures; a generalized slowing down of physical reactions, movements, and speech (psychomotor retardation); intellectual disability; and a loss of coordination (ataxia). Some people with severe glutathione synthetase deficiency also develop recurrent bacterial infections.",glutathione synthetase deficiency,0000419,GHR,https://ghr.nlm.nih.gov/condition/glutathione-synthetase-deficiency,C0398746,T047,Disorders
How many people are affected by glutathione synthetase deficiency ?,0000419-2,frequency,Glutathione synthetase deficiency is very rare. This disorder has been described in more than 70 people worldwide.,glutathione synthetase deficiency,0000419,GHR,https://ghr.nlm.nih.gov/condition/glutathione-synthetase-deficiency,C0398746,T047,Disorders
What are the genetic changes related to glutathione synthetase deficiency ?,0000419-3,genetic changes,"Mutations in the GSS gene cause glutathione synthetase deficiency. The GSS gene provides instructions for making an enzyme called glutathione synthetase. This enzyme is involved in a process called the gamma-glutamyl cycle, which takes place in most of the body's cells. This cycle is necessary for producing a molecule called glutathione. Glutathione protects cells from damage caused by unstable oxygen-containing molecules, which are byproducts of energy production. Glutathione is called an antioxidant because of its role in protecting cells from the damaging effects of these unstable molecules. Mutations in the GSS gene prevent cells from making adequate levels of glutathione, leading to the signs and symptoms of glutathione synthetase deficiency.",glutathione synthetase deficiency,0000419,GHR,https://ghr.nlm.nih.gov/condition/glutathione-synthetase-deficiency,C0398746,T047,Disorders
Is glutathione synthetase deficiency inherited ?,0000419-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",glutathione synthetase deficiency,0000419,GHR,https://ghr.nlm.nih.gov/condition/glutathione-synthetase-deficiency,C0398746,T047,Disorders
What are the treatments for glutathione synthetase deficiency ?,0000419-5,treatment,"These resources address the diagnosis or management of glutathione synthetase deficiency:  - Baby's First Test  - Genetic Testing Registry: Glutathione synthetase deficiency of erythrocytes, hemolytic anemia due to  - Genetic Testing Registry: Gluthathione synthetase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",glutathione synthetase deficiency,0000419,GHR,https://ghr.nlm.nih.gov/condition/glutathione-synthetase-deficiency,C0398746,T047,Disorders
What is (are) glycine encephalopathy ?,0000420-1,information,"Glycine encephalopathy, which is also known as nonketotic hyperglycinemia or NKH, is a genetic disorder characterized by abnormally high levels of a molecule called glycine. This molecule is an amino acid, which is a building block of proteins. Glycine also acts as a neurotransmitter, which is a chemical messenger that transmits signals in the brain. Glycine encephalopathy is caused by the shortage of an enzyme that normally breaks down glycine in the body. A lack of this enzyme allows excess glycine to build up in tissues and organs, particularly the brain, leading to serious medical problems.  The most common form of glycine encephalopathy, called the classical type, appears shortly after birth. Affected infants experience a progressive lack of energy (lethargy), feeding difficulties, weak muscle tone (hypotonia), abnormal jerking movements, and life-threatening problems with breathing. Most children who survive these early signs and symptoms develop profound intellectual disability and seizures that are difficult to treat. For unknown reasons, affected males are more likely to survive and have less severe developmental problems than affected females.  Researchers have identified several other types of glycine encephalopathy with variable signs and symptoms. The most common of these atypical types is called the infantile form. Children with this condition develop normally until they are about 6 months old, when they experience delayed development and may begin having seizures. As they get older, many develop intellectual disability, abnormal movements, and behavioral problems. Other atypical types of glycine encephalopathy appear later in childhood or adulthood and cause a variety of medical problems that primarily affect the nervous system.  Rarely, the characteristic features of classical glycine encephalopathy improve with time. These cases are classified as transient glycine encephalopathy. In this form of the condition, glycine levels decrease to normal or near-normal after being very high at birth. Many children with temporarily high glycine levels go on to develop normally and experience few long-term medical problems. Intellectual disability and seizures occur in some affected individuals, however, even after glycine levels decrease.",glycine encephalopathy,0000420,GHR,https://ghr.nlm.nih.gov/condition/glycine-encephalopathy,C0751748,T047,Disorders
How many people are affected by glycine encephalopathy ?,0000420-2,frequency,"The worldwide incidence of glycine encephalopathy is unknown. Its frequency has been studied in only a few regions: this condition affects about 1 in 55,000 newborns in Finland and about 1 in 63,000 newborns in British Columbia, Canada.",glycine encephalopathy,0000420,GHR,https://ghr.nlm.nih.gov/condition/glycine-encephalopathy,C0751748,T047,Disorders
What are the genetic changes related to glycine encephalopathy ?,0000420-3,genetic changes,"Mutations in the AMT and GLDC genes cause glycine encephalopathy.  About 80 percent of cases of glycine encephalopathy result from mutations in the GLDC gene, while AMT mutations cause 10 percent to 15 percent of all cases. In a small percentage of affected individuals, the cause of this condition is unknown.  The AMT and GLDC genes provide instructions for making proteins that work together as part of a larger enzyme complex. This complex, known as glycine cleavage enzyme, is responsible for breaking down glycine into smaller pieces. Mutations in either the AMT or GLDC gene prevent the complex from breaking down glycine properly. When glycine cleavage enzyme is defective, excess glycine can build up to toxic levels in the body's organs and tissues. Damage caused by harmful amounts of this molecule in the brain and spinal cord is responsible for the intellectual disability, seizures, and breathing difficulties characteristic of glycine encephalopathy.",glycine encephalopathy,0000420,GHR,https://ghr.nlm.nih.gov/condition/glycine-encephalopathy,C0751748,T047,Disorders
Is glycine encephalopathy inherited ?,0000420-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",glycine encephalopathy,0000420,GHR,https://ghr.nlm.nih.gov/condition/glycine-encephalopathy,C0751748,T047,Disorders
What are the treatments for glycine encephalopathy ?,0000420-5,treatment,These resources address the diagnosis or management of glycine encephalopathy:  - Baby's First Test  - Gene Review: Gene Review: Glycine Encephalopathy  - Genetic Testing Registry: Non-ketotic hyperglycinemia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,glycine encephalopathy,0000420,GHR,https://ghr.nlm.nih.gov/condition/glycine-encephalopathy,C0751748,T047,Disorders
What is (are) glycogen storage disease type 0 ?,0000421-1,information,"Glycogen storage disease type 0 (also known as GSD 0) is a condition caused by the body's inability to form a complex sugar called glycogen, which is a major source of stored energy in the body. GSD 0 has two types: in muscle GSD 0, glycogen formation in the muscles is impaired, and in liver GSD 0, glycogen formation in the liver is impaired.  The signs and symptoms of muscle GSD 0 typically begin in early childhood. Affected individuals often experience muscle pain and weakness or episodes of fainting (syncope) following moderate physical activity, such as walking up stairs. The loss of consciousness that occurs with fainting typically lasts up to several hours. Some individuals with muscle GSD 0 have a disruption of the heart's normal rhythm (arrhythmia) known as long QT syndrome. In all affected individuals, muscle GSD 0 impairs the heart's ability to effectively pump blood and increases the risk of cardiac arrest and sudden death, particularly after physical activity. Sudden death from cardiac arrest can occur in childhood or adolescence in people with muscle GSD 0.  Individuals with liver GSD 0 usually show signs and symptoms of the disorder in infancy. People with this disorder develop low blood sugar (hypoglycemia) after going long periods of time without food (fasting). Signs of hypoglycemia become apparent when affected infants begin sleeping through the night and stop late-night feedings; these infants exhibit extreme tiredness (lethargy), pale skin (pallor), and nausea. During episodes of fasting, ketone levels in the blood may increase (ketosis). Ketones are molecules produced during the breakdown of fats, which occurs when stored sugars (such as glycogen) are unavailable. These short-term signs and symptoms of liver GSD 0 often improve when food is eaten and sugar levels in the body return to normal. The features of liver GSD 0 vary; they can be mild and go unnoticed for years, or they can include developmental delay and growth failure.",glycogen storage disease type 0,0000421,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-0,C0342748,T047,Disorders
How many people are affected by glycogen storage disease type 0 ?,0000421-2,frequency,"The prevalence of GSD 0 is unknown; fewer than 10 people with the muscle type and fewer than 30 people with the liver type have been described in the scientific literature. Because some people with muscle GSD 0 die from sudden cardiac arrest early in life before a diagnosis is made and many with liver GSD 0 have mild signs and symptoms, it is thought that GSD 0 may be underdiagnosed.",glycogen storage disease type 0,0000421,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-0,C0342748,T047,Disorders
What are the genetic changes related to glycogen storage disease type 0 ?,0000421-3,genetic changes,"Mutations in the GYS1 gene cause muscle GSD 0, and mutations in the GYS2 gene cause liver GSD 0. These genes provide instructions for making different versions of an enzyme called glycogen synthase. Both versions of glycogen synthase have the same function, to form glycogen molecules by linking together molecules of the simple sugar glucose, although they perform this function in different regions of the body.  The GYS1 gene provides instructions for making muscle glycogen synthase; this form of the enzyme is produced in most cells, but it is especially abundant in heart (cardiac) muscle and the muscles used for movement (skeletal muscles). During cardiac muscle contractions or rapid or sustained movement of skeletal muscle, glycogen stored in muscle cells is broken down to supply the cells with energy.  The GYS2 gene provides instructions for making liver glycogen synthase, which is produced solely in liver cells. Glycogen that is stored in the liver can be broken down rapidly when glucose is needed to maintain normal blood sugar levels between meals.  Mutations in the GYS1 or GYS2 gene lead to a lack of functional glycogen synthase, which prevents the production of glycogen from glucose. Mutations that cause GSD 0 result in a complete absence of glycogen in either liver or muscle cells. As a result, these cells do not have glycogen as a source of stored energy to draw upon following physical activity or fasting. This shortage of glycogen leads to the signs and symptoms of GSD 0.",glycogen storage disease type 0,0000421,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-0,C0342748,T047,Disorders
Is glycogen storage disease type 0 inherited ?,0000421-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",glycogen storage disease type 0,0000421,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-0,C0342748,T047,Disorders
What are the treatments for glycogen storage disease type 0 ?,0000421-5,treatment,"These resources address the diagnosis or management of glycogen storage disease type 0:  - Genetic Testing Registry: Glycogen storage disease 0, muscle  - Genetic Testing Registry: Hypoglycemia with deficiency of glycogen synthetase in the liver   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",glycogen storage disease type 0,0000421,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-0,C0342748,T047,Disorders
What is (are) glycogen storage disease type I ?,0000422-1,information,"Glycogen storage disease type I (also known as GSDI or von Gierke disease) is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. The accumulation of glycogen in certain organs and tissues, especially the liver, kidneys, and small intestines, impairs their ability to function normally.  Signs and symptoms of this condition typically appear around the age of 3 or 4 months, when babies start to sleep through the night and do not eat as frequently as newborns. Affected infants may have low blood sugar (hypoglycemia), which can lead to seizures. They can also have a buildup of lactic acid in the body (lactic acidosis), high blood levels of a waste product called uric acid (hyperuricemia), and excess amounts of fats in the blood (hyperlipidemia). As they get older, children with GSDI have thin arms and legs and short stature. An enlarged liver may give the appearance of a protruding abdomen. The kidneys may also be enlarged. Affected individuals may also have diarrhea and deposits of cholesterol in the skin (xanthomas).  People with GSDI may experience delayed puberty. Beginning in young to mid-adulthood, affected individuals may have thinning of the bones (osteoporosis), a form of arthritis resulting from uric acid crystals in the joints (gout), kidney disease, and high blood pressure in the blood vessels that supply the lungs (pulmonary hypertension). Females with this condition may also have abnormal development of the ovaries (polycystic ovaries). In affected teens and adults, tumors called adenomas may form in the liver. Adenomas are usually noncancerous (benign), but occasionally these tumors can become cancerous (malignant).  Researchers have described two types of GSDI, which differ in their signs and symptoms and genetic cause. These types are known as glycogen storage disease type Ia (GSDIa) and glycogen storage disease type Ib (GSDIb). Two other forms of GSDI have been described, and they were originally named types Ic and Id. However, these types are now known to be variations of GSDIb; for this reason, GSDIb is sometimes called GSD type I non-a.  Many people with GSDIb have a shortage of white blood cells (neutropenia), which can make them prone to recurrent bacterial infections. Neutropenia is usually apparent by age 1. Many affected individuals also have inflammation of the intestinal walls (inflammatory bowel disease). People with GSDIb may have oral problems including cavities, inflammation of the gums (gingivitis), chronic gum (periodontal) disease, abnormal tooth development, and open sores (ulcers) in the mouth. The neutropenia and oral problems are specific to people with GSDIb and are typically not seen in people with GSDIa.",glycogen storage disease type I,0000422,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-i,C0017920,T047,Disorders
How many people are affected by glycogen storage disease type I ?,0000422-2,frequency,"The overall incidence of GSDI is 1 in 100,000 individuals. GSDIa is more common than GSDIb, accounting for 80 percent of all GSDI cases.",glycogen storage disease type I,0000422,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-i,C0017920,T047,Disorders
What are the genetic changes related to glycogen storage disease type I ?,0000422-3,genetic changes,"Mutations in two genes, G6PC and SLC37A4, cause GSDI. G6PC gene mutations cause GSDIa, and SLC37A4 gene mutations cause GSDIb.  The proteins produced from the G6PC and SLC37A4 genes work together to break down a type of sugar molecule called glucose 6-phosphate. The breakdown of this molecule produces the simple sugar glucose, which is the primary energy source for most cells in the body.  Mutations in the G6PC and SLC37A4 genes prevent the effective breakdown of glucose 6-phosphate. Glucose 6-phosphate that is not broken down to glucose is converted to glycogen and fat so it can be stored within cells. Too much glycogen and fat stored within a cell can be toxic. This buildup damages organs and tissues throughout the body, particularly the liver and kidneys, leading to the signs and symptoms of GSDI.",glycogen storage disease type I,0000422,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-i,C0017920,T047,Disorders
Is glycogen storage disease type I inherited ?,0000422-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",glycogen storage disease type I,0000422,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-i,C0017920,T047,Disorders
What are the treatments for glycogen storage disease type I ?,0000422-5,treatment,"These resources address the diagnosis or management of glycogen storage disease type I:  - American Liver Foundation  - Canadian Liver Foundation  - Gene Review: Gene Review: Glycogen Storage Disease Type I  - Genetic Testing Registry: Glucose-6-phosphate transport defect  - Genetic Testing Registry: Glycogen storage disease type 1A  - Genetic Testing Registry: Glycogen storage disease, type I  - MedlinePlus Encyclopedia: Von Gierke Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",glycogen storage disease type I,0000422,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-i,C0017920,T047,Disorders
What is (are) glycogen storage disease type III ?,0000423-1,information,"Glycogen storage disease type III (also known as GSDIII or Cori disease) is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. The accumulated glycogen is structurally abnormal and impairs the function of certain organs and tissues, especially the liver and muscles.  GSDIII is divided into types IIIa, IIIb, IIIc, and IIId, which are distinguished by their pattern of signs and symptoms. GSD types IIIa and IIIc mainly affect the liver and muscles, and GSD types IIIb and IIId typically affect only the liver. It is very difficult to distinguish between the types of GSDIII that affect the same tissues. GSD types IIIa and IIIb are the most common forms of this condition.  Beginning in infancy, individuals with any type of GSDIII may have low blood sugar (hypoglycemia), excess amounts of fats in the blood (hyperlipidemia), and elevated blood levels of liver enzymes. As they get older, children with this condition typically develop an enlarged liver (hepatomegaly). Liver size usually returns to normal during adolescence, but some affected individuals develop chronic liver disease (cirrhosis) and liver failure later in life. People with GSDIII often have slow growth because of their liver problems, which can lead to short stature. In a small percentage of people with GSDIII, noncancerous (benign) tumors called adenomas may form in the liver.  Individuals with GSDIIIa may develop muscle weakness (myopathy) later in life. These muscle problems can affect both heart (cardiac) muscle and the muscles that are used for movement (skeletal muscles). Muscle involvement varies greatly among affected individuals. The first signs and symptoms are typically poor muscle tone (hypotonia) and mild myopathy in early childhood. The myopathy may become severe by early to mid-adulthood. Some people with GSDIIIa have a weakened heart muscle (cardiomyopathy), but affected individuals usually do not experience heart failure. Other people affected with GSDIIIa have no cardiac muscle problems.",glycogen storage disease type III,0000423,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-iii,C0267971,T047,Disorders
How many people are affected by glycogen storage disease type III ?,0000423-2,frequency,"The incidence of GSDIII in the United States is 1 in 100,000 individuals. This condition is seen more frequently in people of North African Jewish ancestry; in this population, 1 in 5,400 individuals are estimated to be affected.  GSDIIIa is the most common form of GSDIII, accounting for about 85 percent of all cases. GSDIIIb accounts for about 15 percent of cases. GSD types IIIc and IIId are very rare, and their signs and symptoms are poorly defined. Only a small number of affected individuals have been suspected to have GSD types IIIc and IIId.",glycogen storage disease type III,0000423,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-iii,C0267971,T047,Disorders
What are the genetic changes related to glycogen storage disease type III ?,0000423-3,genetic changes,"Mutations in the AGL gene cause GSDIII. The AGL gene provides instructions for making the glycogen debranching enzyme. This enzyme is involved in the breakdown of glycogen, which is a major source of stored energy in the body. Between meals the body breaks down stores of energy, such as glycogen, to use for fuel.  Most AGL gene mutations lead to the production of a nonfunctional glycogen debranching enzyme. These mutations typically cause GSD types IIIa and IIIb. The mutations that cause GSD types IIIc and IIId are thought to lead to the production of an enzyme with reduced function. All AGL gene mutations lead to storage of abnormal, partially broken down glycogen molecules within cells. A buildup of abnormal glycogen damages organs and tissues throughout the body, particularly the liver and muscles, leading to the signs and symptoms of GSDIII.",glycogen storage disease type III,0000423,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-iii,C0267971,T047,Disorders
Is glycogen storage disease type III inherited ?,0000423-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",glycogen storage disease type III,0000423,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-iii,C0267971,T047,Disorders
What are the treatments for glycogen storage disease type III ?,0000423-5,treatment,These resources address the diagnosis or management of glycogen storage disease type III:  - Gene Review: Gene Review: Glycogen Storage Disease Type III  - Genetic Testing Registry: Glycogen storage disease type III   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,glycogen storage disease type III,0000423,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-iii,C0267971,T047,Disorders
What is (are) glycogen storage disease type IV ?,0000424-1,information,"Glycogen storage disease type IV (GSD IV) is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. The accumulated glycogen is structurally abnormal and impairs the function of certain organs and tissues, especially the liver and muscles. There are five types of GSD IV, which are distinguished by their severity, signs, and symptoms.  The fatal perinatal neuromuscular type is the most severe form of GSD IV, with signs developing before birth. Excess fluid may build up around the fetus (polyhydramnios) and in the fetus' body. Affected fetuses have a condition called fetal akinesia deformation sequence, which causes a decrease in fetal movement and can lead to joint stiffness (arthrogryposis) after birth. Infants with the fatal perinatal neuromuscular type of GSD IV have very low muscle tone (severe hypotonia) and muscle wasting (atrophy). These infants usually do not survive past the newborn period due to weakened heart and breathing muscles.  The congenital muscular type of GSD IV is usually not evident before birth but develops in early infancy. Affected infants have severe hypotonia, which affects the muscles needed for breathing. These babies often have dilated cardiomyopathy, which enlarges and weakens the heart (cardiac) muscle, preventing the heart from pumping blood efficiently. Infants with the congenital muscular type of GSD IV typically survive only a few months.  The progressive hepatic type is the most common form of GSD IV. Within the first months of life, affected infants have difficulty gaining weight and growing at the expected rate (failure to thrive) and develop an enlarged liver (hepatomegaly). Children with this type develop a form of liver disease called cirrhosis that often is irreversible. High blood pressure in the vein that supplies blood to the liver (portal hypertension) and an abnormal buildup of fluid in the abdominal cavity (ascites) can also occur. By age 1 or 2, affected children develop hypotonia. Children with the progressive hepatic type of GSD IV often die of liver failure in early childhood.  The non-progressive hepatic type of GSD IV has many of the same features as the progressive hepatic type, but the liver disease is not as severe. In the non-progressive hepatic type, hepatomegaly and liver disease are usually evident in early childhood, but affected individuals typically do not develop cirrhosis. People with this type of the disorder can also have hypotonia and muscle weakness (myopathy). Most individuals with this type survive into adulthood, although life expectancy varies depending on the severity of the signs and symptoms.  The childhood neuromuscular type of GSD IV develops in late childhood and is characterized by myopathy and dilated cardiomyopathy. The severity of this type of GSD IV varies greatly; some people have only mild muscle weakness while others have severe cardiomyopathy and die in early adulthood.",glycogen storage disease type IV,0000424,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-iv,C0267971,T047,Disorders
How many people are affected by glycogen storage disease type IV ?,0000424-2,frequency,"GSD IV is estimated to occur in 1 in 600,000 to 800,000 individuals worldwide. Type IV accounts for roughly 3 percent of all cases of glycogen storage disease.",glycogen storage disease type IV,0000424,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-iv,C0267971,T047,Disorders
What are the genetic changes related to glycogen storage disease type IV ?,0000424-3,genetic changes,"Mutations in the GBE1 gene cause GSD IV. The GBE1 gene provides instructions for making the glycogen branching enzyme. This enzyme is involved in the production of glycogen, which is a major source of stored energy in the body. GBE1 gene mutations that cause GSD IV lead to a shortage (deficiency) of the glycogen branching enzyme. As a result, glycogen is not formed properly. Abnormal glycogen molecules called polyglucosan bodies accumulate in cells, leading to damage and cell death. Polyglucosan bodies accumulate in cells throughout the body, but liver cells and muscle cells are most severely affected in GSD IV. Glycogen accumulation in the liver leads to hepatomegaly and interferes with liver functioning. The inability of muscle cells to break down glycogen for energy leads to muscle weakness and wasting.  Generally, the severity of the disorder is linked to the amount of functional glycogen branching enzyme that is produced. Individuals with the fatal perinatal neuromuscular type tend to produce less than 5 percent of usable enzyme, while those with the childhood neuromuscular type may have around 20 percent of enzyme function. The other types of GSD IV are usually associated with between 5 and 20 percent of working enzyme. These estimates, however, vary among the different types.",glycogen storage disease type IV,0000424,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-iv,C0267971,T047,Disorders
Is glycogen storage disease type IV inherited ?,0000424-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",glycogen storage disease type IV,0000424,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-iv,C0267971,T047,Disorders
What are the treatments for glycogen storage disease type IV ?,0000424-5,treatment,"These resources address the diagnosis or management of glycogen storage disease type IV:  - Gene Review: Gene Review: Glycogen Storage Disease Type IV  - Genetic Testing Registry: Glycogen storage disease, type IV  - MedlinePlus Encyclopedia: Dilated Cardiomyopathy  - MedlinePlus Encyclopedia: Failure to Thrive   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",glycogen storage disease type IV,0000424,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-iv,C0267971,T047,Disorders
What is (are) glycogen storage disease type IX ?,0000425-1,information,"Glycogen storage disease type IX (also known as GSD IX) is a condition caused by the inability to break down a complex sugar called glycogen. The different forms of the condition can affect glycogen breakdown in liver cells or muscle cells or sometimes both. A lack of glycogen breakdown interferes with the normal function of the affected tissue.  When GSD IX affects the liver, the signs and symptoms typically begin in early childhood. The initial features are usually an enlarged liver (hepatomegaly) and slow growth. Affected children are often shorter than normal. During prolonged periods without food (fasting), affected individuals may have low blood sugar (hypoglycemia) or elevated levels of ketones in the blood (ketosis). Ketones are molecules produced during the breakdown of fats, which occurs when stored sugars are unavailable. Affected children may have delayed development of motor skills, such as sitting, standing, or walking, and some have mild muscle weakness. Puberty is delayed in some adolescents with GSD IX. In the form of the condition that affects the liver, the signs and symptoms usually improve with age. Typically, individuals catch up developmentally, and adults reach normal height. However, some affected individuals have a buildup of scar tissue (fibrosis) in the liver, which can rarely progress to irreversible liver disease (cirrhosis).  GSD IX can affect muscle tissue, although this form of the condition is very rare and not well understood. The features of this form of the condition can appear anytime from childhood to adulthood. Affected individuals may experience fatigue, muscle pain, and cramps, especially during exercise (exercise intolerance). Most affected individuals have muscle weakness that worsens over time. GSD IX can cause myoglobinuria, which occurs when muscle tissue breaks down abnormally and releases a protein called myoglobin that is excreted in the urine. Myoglobinuria can cause the urine to be red or brown.  In a small number of people with GSD IX, the liver and muscles are both affected. These individuals develop a combination of the features described above, although the muscle problems are usually mild.",glycogen storage disease type IX,0000425,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-ix,C0268147,T047,Disorders
How many people are affected by glycogen storage disease type IX ?,0000425-2,frequency,"GSD IX that affects the liver is estimated to occur in 1 in 100,000 people. The forms of the disease that affect muscles or both muscles and liver are much less common, although the prevalence is unknown.",glycogen storage disease type IX,0000425,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-ix,C0268147,T047,Disorders
What are the genetic changes related to glycogen storage disease type IX ?,0000425-3,genetic changes,"Mutations in the PHKA1, PHKA2, PHKB, or PHKG2 genes are known to cause GSD IX. These genes provide instructions for making pieces (subunits) of an enzyme called phosphorylase b kinase. The enzyme is made up of 16 subunits, four each of the alpha, beta, gamma, and delta subunits. At least two different versions of phosphorylase b kinase are formed from the subunits: one is most abundant in liver cells and the other in muscle cells.  The PHKA1 and PHKA2 genes provide instructions for making alpha subunits of phosphorylase b kinase. The protein produced from the PHKA1 gene is a subunit of the muscle enzyme, while the protein produced from the PHKA2 gene is part of the liver enzyme. The PHKB gene provides instructions for making the beta subunit, which is found in both the muscle and the liver. The PHKG2 gene provides instructions for making the gamma subunit of the liver enzyme.  Whether in the liver or the muscles, phosphorylase b kinase plays an important role in providing energy for cells. The main source of cellular energy is a simple sugar called glucose. Glucose is stored in muscle and liver cells in a form called glycogen. Glycogen can be broken down rapidly when glucose is needed, for instance to maintain normal levels of glucose in the blood between meals or for energy during exercise. Phosphorylase b kinase turns on (activates) the enzyme that breaks down glycogen.  Although the effects of gene mutations on the respective protein subunits are unknown, mutations in the PHKA1, PHKA2, PHKB, and PHKG2 genes reduce the activity of phosphorylase b kinase in liver or muscle cells and in blood cells. Reduction of this enzyme's function impairs glycogen breakdown. As a result, glycogen accumulates in and damages cells, and glucose is not available for energy. Glycogen accumulation in the liver leads to hepatomegaly, and the liver's inability to break down glycogen for glucose contributes to hypoglycemia and ketosis. Reduced energy production in muscle cells leads to muscle weakness, pain, and cramping.",glycogen storage disease type IX,0000425,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-ix,C0268147,T047,Disorders
Is glycogen storage disease type IX inherited ?,0000425-4,inheritance,"GSD IX can have different inheritance patterns depending on the genetic cause of the condition.  When caused by mutations in the PHKA1 or PHKA2 gene, GSD IX is inherited in an X-linked recessive pattern. These genes are located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. However, some women with one altered copy of the PHKA2 gene have signs and symptoms of GSD IX, such as mild hepatomegaly or short stature in childhood. These features are usually mild but can be more severe in rare cases. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  When the condition is caused by mutations in the PHKB or PHKG2 gene, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",glycogen storage disease type IX,0000425,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-ix,C0268147,T047,Disorders
What are the treatments for glycogen storage disease type IX ?,0000425-5,treatment,These resources address the diagnosis or management of glycogen storage disease type IX:  - Gene Review: Gene Review: Phosphorylase Kinase Deficiency  - Genetic Testing Registry: Glycogen storage disease IXb  - Genetic Testing Registry: Glycogen storage disease IXc  - Genetic Testing Registry: Glycogen storage disease IXd  - Genetic Testing Registry: Glycogen storage disease type IXa1   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,glycogen storage disease type IX,0000425,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-ix,C0268147,T047,Disorders
What is (are) glycogen storage disease type V ?,0000426-1,information,"Glycogen storage disease type V (also known as GSDV or McArdle disease) is an inherited disorder caused by an inability to break down a complex sugar called glycogen in muscle cells. A lack of glycogen breakdown interferes with the function of muscle cells.  People with GSDV typically experience fatigue, muscle pain, and cramps during the first few minutes of exercise (exercise intolerance). Exercise such as weight lifting or jogging usually triggers these symptoms in affected individuals. The discomfort is generally alleviated with rest. If individuals rest after brief exercise and wait for their pain to go away, they can usually resume exercising with little or no discomfort (a characteristic phenomenon known as ""second wind"").  Prolonged or intense exercise can cause muscle damage in people with GSDV. About half of people with GSDV experience breakdown of muscle tissue (rhabdomyolysis). In severe episodes, the destruction of muscle tissue releases a protein called myoglobin, which is filtered through the kidneys and released in the urine (myoglobinuria). Myoglobin causes the urine to be red or brown. This protein can also damage the kidneys, and it is estimated that half of those individuals with GSDV who have myoglobinuria will develop life-threatening kidney failure.  The signs and symptoms of GSDV can vary significantly in affected individuals. The features of this condition typically begin in a person's teens or twenties, but they can appear anytime from infancy to adulthood. In most people with GSDV, the muscle weakness worsens over time; however, in about one-third of affected individuals, the muscle weakness is stable. Some people with GSDV experience mild symptoms such as poor stamina; others do not experience any symptoms.",glycogen storage disease type V,0000426,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-v,C0267971,T047,Disorders
How many people are affected by glycogen storage disease type V ?,0000426-2,frequency,"GSDV is a rare disorder; however, its prevalence is unknown. In the Dallas-Fort Worth area of Texas, where the prevalence of GSDV has been studied, the condition is estimated to affect 1 in 100,000 individuals.",glycogen storage disease type V,0000426,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-v,C0267971,T047,Disorders
What are the genetic changes related to glycogen storage disease type V ?,0000426-3,genetic changes,"Mutations in the PYGM gene cause GSDV. The PYGM gene provides instructions for making an enzyme called myophosphorylase. This enzyme is found only in muscle cells, where it breaks down glycogen into a simpler sugar called glucose-1-phosphate. Additional steps convert glucose-1-phosphate into glucose, a simple sugar that is the main energy source for most cells.  PYGM gene mutations prevent myophosphorylase from breaking down glycogen effectively. As a result, muscle cells cannot produce enough energy, so muscles become easily fatigued. Reduced energy production in muscle cells leads to the major features of GSDV.",glycogen storage disease type V,0000426,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-v,C0267971,T047,Disorders
Is glycogen storage disease type V inherited ?,0000426-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",glycogen storage disease type V,0000426,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-v,C0267971,T047,Disorders
What are the treatments for glycogen storage disease type V ?,0000426-5,treatment,"These resources address the diagnosis or management of glycogen storage disease type V:  - Gene Review: Gene Review: Glycogen Storage Disease Type V  - Genetic Testing Registry: Glycogen storage disease, type V  - MedlinePlus Encyclopedia: McArdle syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",glycogen storage disease type V,0000426,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-v,C0267971,T047,Disorders
What is (are) glycogen storage disease type VI ?,0000427-1,information,Glycogen storage disease type VI (also known as GSDVI or Hers disease) is an inherited disorder caused by an inability to break down a complex sugar called glycogen in liver cells. A lack of glycogen breakdown interferes with the normal function of the liver.  The signs and symptoms of GSDVI typically begin in infancy to early childhood. The first sign is usually an enlarged liver (hepatomegaly). Affected individuals may also have low blood sugar (hypoglycemia) or a buildup of lactic acid in the body (lactic acidosis) during prolonged periods without food (fasting).  The signs and symptoms of GSDVI tend to improve with age; most adults with this condition do not have any related health problems.,glycogen storage disease type VI,0000427,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-vi,C0267971,T047,Disorders
How many people are affected by glycogen storage disease type VI ?,0000427-2,frequency,"The exact prevalence of GSDVI is unknown. At least 11 cases have been reported in the medical literature, although this condition is likely to be underdiagnosed because it can be difficult to detect in children with mild symptoms or adults with no symptoms. GSDVI is more common in the Old Older Mennonite population, with an estimated incidence of 1 in 1,000 individuals.",glycogen storage disease type VI,0000427,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-vi,C0267971,T047,Disorders
What are the genetic changes related to glycogen storage disease type VI ?,0000427-3,genetic changes,"Mutations in the PYGL gene cause GSDVI. The PYGL gene provides instructions for making an enzyme called liver glycogen phosphorylase. This enzyme is found only in liver cells, where it breaks down glycogen into a type of sugar called glucose-1-phosphate. Additional steps convert glucose-1-phosphate into glucose, a simple sugar that is the main energy source for most cells in the body.  PYGL gene mutations prevent liver glycogen phosphorylase from breaking down glycogen effectively. As a result, liver cells cannot use glycogen for energy. Since glycogen cannot be broken down, it accumulates within liver cells, causing these cells to become enlarged and dysfunctional.",glycogen storage disease type VI,0000427,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-vi,C0267971,T047,Disorders
Is glycogen storage disease type VI inherited ?,0000427-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",glycogen storage disease type VI,0000427,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-vi,C0267971,T047,Disorders
What are the treatments for glycogen storage disease type VI ?,0000427-5,treatment,"These resources address the diagnosis or management of glycogen storage disease type VI:  - Gene Review: Gene Review: Glycogen Storage Disease Type VI  - Genetic Testing Registry: Glycogen storage disease, type VI   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",glycogen storage disease type VI,0000427,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-vi,C0267971,T047,Disorders
What is (are) glycogen storage disease type VII ?,0000428-1,information,"Glycogen storage disease type VII (GSDVII) is an inherited disorder caused by an inability to break down a complex sugar called glycogen in muscle cells. A lack of glycogen breakdown interferes with the function of muscle cells.  There are four types of GSDVII. They are differentiated by their signs and symptoms and the age at which symptoms first appear.  The classical form of GSDVII is the most common form. Its features usually appear in childhood. This form is characterized by muscle pain and cramps, often following moderate exercise; strenuous exercise can lead to nausea and vomiting. During exercise, muscle tissue can be abnormally broken down, releasing a protein called myoglobin. This protein is processed by the kidneys and released in the urine (myoglobinuria). If untreated, myoglobinuria can damage the kidneys and lead to kidney failure. Some people with the classical form of GSDVII develop high levels of a waste product called uric acid in the blood (hyperuricemia) because the damaged kidneys are unable to remove uric acid effectively. Affected individuals may also have elevated levels of a molecule called bilirubin in the blood that can cause yellowing of the skin and whites of the eyes (jaundice). Individuals with classical GSDVII often have elevated levels of an enzyme called creatine kinase in their blood. This finding is a common indicator of muscle disease.  Infants with the severe infantile form of GSDVII have low muscle tone (hypotonia) at birth, which leads to muscle weakness (myopathy) that worsens over time. Affected infants have a weakened and enlarged heart (cardiomyopathy) and difficulty breathing normally. Individuals with this form of GSDVII usually do not survive past their first year of life.  In the late-onset form of GSDVII, myopathy is typically the only feature. The muscle weakness appears in adulthood, although some individuals have difficulty with sustained exercise starting in childhood. The weakness generally affects the muscles closest to the center of the body (proximal muscles).  The hemolytic form of GSDVII is characterized by hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely, causing a shortage of red blood cells (anemia). People with the hemolytic form of GSDVII do not experience any signs or symptoms of muscle pain or weakness related to the disorder.",glycogen storage disease type VII,0000428,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-vii,C0267971,T047,Disorders
How many people are affected by glycogen storage disease type VII ?,0000428-2,frequency,GSDVII is thought to be a rare condition; more than 100 cases have been described in the scientific literature.,glycogen storage disease type VII,0000428,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-vii,C0267971,T047,Disorders
What are the genetic changes related to glycogen storage disease type VII ?,0000428-3,genetic changes,"Mutations in the PFKM gene cause GSDVII. This gene provides instructions for making one piece (the PFKM subunit) of an enzyme called phosphofructokinase, which plays a role in the breakdown of glycogen. The phosphofructokinase enzyme is made up of four subunits and is found in a variety of tissues. Different combinations of subunits are found in different tissues. In muscles used for movement (skeletal muscles), the phosphofructokinase enzyme is composed solely of PFKM subunits.  In skeletal muscle, the cells' main source of energy is stored as glycogen. Glycogen can be broken down rapidly into the simple sugar glucose when energy is needed, for instance to maintain normal blood sugar levels between meals or for energy during exercise. Phosphofructokinase is involved in the sequence of events that breaks down glycogen to provide energy to muscle cells.  PFKM gene mutations result in the production of PFKM subunits that have little or no function. As a result, no functional phosphofructokinase is formed in skeletal muscles, and glycogen cannot be completely broken down. Partially broken down glycogen then builds up in muscle cells. Muscles that do not have access to glycogen as an energy source become weakened and cramped following moderate strain, such as exercise, and in some cases, begin to break down. In other tissues, other subunits that make up the phosphofructokinase enzyme likely compensate for the lack of PFKM subunits, and the enzyme is able to retain some function. This compensation may help explain why other tissues are not affected by PFKM gene mutations. It is unclear why some individuals with GSDVII are affected with more severe forms of the disorder than others.",glycogen storage disease type VII,0000428,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-vii,C0267971,T047,Disorders
Is glycogen storage disease type VII inherited ?,0000428-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",glycogen storage disease type VII,0000428,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-vii,C0267971,T047,Disorders
What are the treatments for glycogen storage disease type VII ?,0000428-5,treatment,"These resources address the diagnosis or management of glycogen storage disease type VII:  - Genetic Testing Registry: Glycogen storage disease, type VII  - The Swedish Information Centre for Rare Diseases   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",glycogen storage disease type VII,0000428,GHR,https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-vii,C0267971,T047,Disorders
What is (are) GM1 gangliosidosis ?,0000429-1,information,"GM1 gangliosidosis is an inherited disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord. Some researchers classify this condition into three major types based on the age at which signs and symptoms first appear. Although the three types differ in severity, their features can overlap significantly. Because of this overlap, other researchers believe that GM1 gangliosidosis represents a continuous disease spectrum instead of three distinct types.  The signs and symptoms of the most severe form of GM1 gangliosidosis, called type I or the infantile form, usually become apparent by the age of 6 months. Infants with this form of the disorder typically appear normal until their development slows and muscles used for movement weaken. Affected infants eventually lose the skills they had previously acquired (developmentally regress) and may develop an exaggerated startle reaction to loud noises. As the disease progresses, children with GM1 gangliosidosis type I develop an enlarged liver and spleen (hepatosplenomegaly), skeletal abnormalities, seizures, profound intellectual disability, and clouding of the clear outer covering of the eye (the cornea). Loss of vision occurs as the light-sensing tissue at the back of the eye (the retina) gradually deteriorates. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. In some cases, affected individuals have distinctive facial features that are described as ""coarse,"" enlarged gums (gingival hypertrophy), and an enlarged and weakened heart muscle (cardiomyopathy). Individuals with GM1 gangliosidosis type I usually do not survive past early childhood.  Type II GM1 gangliosidosis consists of intermediate forms of the condition, also known as the late infantile and juvenile forms. Children with GM1 gangliosidosis type II have normal early development, but they begin to develop signs and symptoms of the condition around the age of 18 months (late infantile form) or 5 years (juvenile form). Individuals with GM1 gangliosidosis type II experience developmental regression but usually do not have cherry-red spots, distinctive facial features, or enlarged organs. Type II usually progresses more slowly than type I, but still causes a shortened life expectancy. People with the late infantile form typically survive into mid-childhood, while those with the juvenile form may live into early adulthood.  The third type of GM1 gangliosidosis is known as the adult or chronic form, and it represents the mildest end of the disease spectrum. The age at which symptoms first appear varies in GM1 gangliosidosis type III, although most affected individuals develop signs and symptoms in their teens. The characteristic features of this type include involuntary tensing of various muscles (dystonia) and abnormalities of the spinal bones (vertebrae). Life expectancy varies among people with GM1 gangliosidosis type III.",GM1 gangliosidosis,0000429,GHR,https://ghr.nlm.nih.gov/condition/gm1-gangliosidosis,C0017083,T047,Disorders
How many people are affected by GM1 gangliosidosis ?,0000429-2,frequency,"GM1 gangliosidosis is estimated to occur in 1 in 100,000 to 200,000 newborns. Type I is reported more frequently than the other forms of this condition. Most individuals with type III are of Japanese descent.",GM1 gangliosidosis,0000429,GHR,https://ghr.nlm.nih.gov/condition/gm1-gangliosidosis,C0017083,T047,Disorders
What are the genetic changes related to GM1 gangliosidosis ?,0000429-3,genetic changes,"Mutations in the GLB1 gene cause GM1 gangliosidosis. The GLB1 gene provides instructions for making an enzyme called beta-galactosidase (-galactosidase), which plays a critical role in the brain. This enzyme is located in lysosomes, which are compartments within cells that break down and recycle different types of molecules. Within lysosomes, -galactosidase helps break down several molecules, including a substance called GM1 ganglioside. GM1 ganglioside is important for normal functioning of nerve cells in the brain.  Mutations in the GLB1 gene reduce or eliminate the activity of -galactosidase. Without enough functional -galactosidase, GM1 ganglioside cannot be broken down when it is no longer needed. As a result, this substance accumulates to toxic levels in many tissues and organs, particularly in the brain. Progressive damage caused by the buildup of GM1 ganglioside leads to the destruction of nerve cells in the brain, causing many of the signs and symptoms of GM1 gangliosidosis. In general, the severity of GM1 gangliosidosis is related to the level of -galactosidase activity. Individuals with higher enzyme activity levels usually have milder signs and symptoms than those with lower activity levels because they have less accumulation of GM1 ganglioside within the body.  Conditions such as GM1 gangliosidosis that cause molecules to build up inside the lysosomes are called lysosomal storage disorders.",GM1 gangliosidosis,0000429,GHR,https://ghr.nlm.nih.gov/condition/gm1-gangliosidosis,C0017083,T047,Disorders
Is GM1 gangliosidosis inherited ?,0000429-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",GM1 gangliosidosis,0000429,GHR,https://ghr.nlm.nih.gov/condition/gm1-gangliosidosis,C0017083,T047,Disorders
What are the treatments for GM1 gangliosidosis ?,0000429-5,treatment,These resources address the diagnosis or management of GM1 gangliosidosis:  - Genetic Testing Registry: Gangliosidosis GM1 type 3  - Genetic Testing Registry: Gangliosidosis generalized GM1 type 1  - Genetic Testing Registry: Infantile GM1 gangliosidosis  - Genetic Testing Registry: Juvenile GM>1< gangliosidosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,GM1 gangliosidosis,0000429,GHR,https://ghr.nlm.nih.gov/condition/gm1-gangliosidosis,C0017083,T047,Disorders
"What is (are) GM2-gangliosidosis, AB variant ?",0000430-1,information,"GM2-gangliosidosis, AB variant is a rare inherited disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord.  Signs and symptoms of the AB variant become apparent in infancy. Infants with this disorder typically appear normal until the age of 3 to 6 months, when their development slows and muscles used for movement weaken. Affected infants lose motor skills such as turning over, sitting, and crawling. They also develop an exaggerated startle reaction to loud noises. As the disease progresses, children with the AB variant experience seizures, vision and hearing loss, intellectual disability, and paralysis. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. Children with the AB variant usually live only into early childhood.","GM2-gangliosidosis, AB variant",0000430,GHR,https://ghr.nlm.nih.gov/condition/gm2-gangliosidosis-ab-variant,C0268275,T047,Disorders
"How many people are affected by GM2-gangliosidosis, AB variant ?",0000430-2,frequency,The AB variant is extremely rare; only a few cases have been reported worldwide.,"GM2-gangliosidosis, AB variant",0000430,GHR,https://ghr.nlm.nih.gov/condition/gm2-gangliosidosis-ab-variant,C0268275,T047,Disorders
"What are the genetic changes related to GM2-gangliosidosis, AB variant ?",0000430-3,genetic changes,"Mutations in the GM2A gene cause GM2-gangliosidosis, AB variant. The GM2A gene provides instructions for making a protein called the GM2 ganglioside activator. This protein is required for the normal function of an enzyme called beta-hexosaminidase A, which plays a critical role in the brain and spinal cord. Beta-hexosaminidase A and the GM2 ganglioside activator protein work together in lysosomes, which are structures in cells that break down toxic substances and act as recycling centers. Within lysosomes, the activator protein binds to a fatty substance called GM2 ganglioside and presents it to beta-hexosaminidase A to be broken down.  Mutations in the GM2A gene disrupt the activity of the GM2 ganglioside activator, which prevents beta-hexosaminidase A from breaking down GM2 ganglioside. As a result, this substance accumulates to toxic levels, particularly in neurons in the brain and spinal cord. Progressive damage caused by the buildup of GM2 ganglioside leads to the destruction of these neurons, which causes the signs and symptoms of the AB variant.  Because the AB variant impairs the function of a lysosomal enzyme and involves the buildup of GM2 ganglioside, this condition is sometimes referred to as a lysosomal storage disorder or a GM2-gangliosidosis.","GM2-gangliosidosis, AB variant",0000430,GHR,https://ghr.nlm.nih.gov/condition/gm2-gangliosidosis-ab-variant,C0268275,T047,Disorders
"Is GM2-gangliosidosis, AB variant inherited ?",0000430-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.","GM2-gangliosidosis, AB variant",0000430,GHR,https://ghr.nlm.nih.gov/condition/gm2-gangliosidosis-ab-variant,C0268275,T047,Disorders
"What are the treatments for GM2-gangliosidosis, AB variant ?",0000430-5,treatment,"These resources address the diagnosis or management of GM2-gangliosidosis, AB variant:  - Genetic Testing Registry: Tay-Sachs disease, variant AB   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","GM2-gangliosidosis, AB variant",0000430,GHR,https://ghr.nlm.nih.gov/condition/gm2-gangliosidosis-ab-variant,C0268275,T047,Disorders
What is (are) GM3 synthase deficiency ?,0000431-1,information,"GM3 synthase deficiency is characterized by recurrent seizures (epilepsy) and problems with brain development. Within the first few weeks after birth, affected infants become irritable and develop feeding difficulties and vomiting that prevent them from growing and gaining weight at the usual rate. Seizures begin within the first year of life and worsen over time. Multiple types of seizures are possible, including generalized tonic-clonic seizures (also known as grand mal seizures), which cause muscle rigidity, convulsions, and loss of consciousness. Some affected children also experience prolonged episodes of seizure activity called nonconvulsive status epilepticus. The seizures associated with GM3 synthase deficiency tend to be resistant (refractory) to treatment with antiseizure medications.  GM3 synthase deficiency profoundly disrupts brain development. Most affected children have severe intellectual disability and do not develop skills such as reaching for objects, speaking, sitting without support, or walking. Some have involuntary twisting or jerking movements of the arms that are described as choreoathetoid. Although affected infants can likely see and hear at birth, vision and hearing become impaired as the disease worsens. It is unknown how long people with GM3 synthase deficiency usually survive.  Some affected individuals have changes in skin coloring (pigmentation), including dark freckle-like spots on the arms and legs and light patches on the arms, legs, and face. These changes appear in childhood and may become more or less apparent over time. The skin changes do not cause any symptoms, but they can help doctors diagnose GM3 synthase deficiency in children who also have seizures and delayed development.",GM3 synthase deficiency,0000431,GHR,https://ghr.nlm.nih.gov/condition/gm3-synthase-deficiency,C1836824,T047,Disorders
How many people are affected by GM3 synthase deficiency ?,0000431-2,frequency,"GM3 synthase deficiency appears to be a rare condition. About 50 cases have been reported, mostly from Old Order Amish communities.",GM3 synthase deficiency,0000431,GHR,https://ghr.nlm.nih.gov/condition/gm3-synthase-deficiency,C1836824,T047,Disorders
What are the genetic changes related to GM3 synthase deficiency ?,0000431-3,genetic changes,"Mutations in the ST3GAL5 gene have been found to cause GM3 synthase deficiency. This gene provides instructions for making an enzyme called GM3 synthase, which carries out a chemical reaction that is the first step in the production of molecules called gangliosides. These molecules are present in cells and tissues throughout the body, and they are particularly abundant in the nervous system. Although their exact functions are unclear, gangliosides appear to be important for normal brain development and function.  ST3GAL5 gene mutations prevent the production of any functional GM3 synthase. Without this enzyme, cells cannot produce gangliosides normally. It is unclear how a loss of this enzyme leads to the signs and symptoms of GM3 synthase deficiency. Researchers are working to determine whether it is the lack of gangliosides or a buildup of compounds used to make gangliosides, or both, that underlies the seizures and other problems with brain development that occur in this condition. The connection between a shortage of GM3 synthase and changes in skin pigmentation is also unknown.",GM3 synthase deficiency,0000431,GHR,https://ghr.nlm.nih.gov/condition/gm3-synthase-deficiency,C1836824,T047,Disorders
Is GM3 synthase deficiency inherited ?,0000431-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",GM3 synthase deficiency,0000431,GHR,https://ghr.nlm.nih.gov/condition/gm3-synthase-deficiency,C1836824,T047,Disorders
What are the treatments for GM3 synthase deficiency ?,0000431-5,treatment,"These resources address the diagnosis or management of GM3 synthase deficiency:  - American Epilepsy Society: Find a Doctor  - Clinic for Special Children (Strasburg, Pennsylvania)  - Genetic Testing Registry: Amish infantile epilepsy syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",GM3 synthase deficiency,0000431,GHR,https://ghr.nlm.nih.gov/condition/gm3-synthase-deficiency,C1836824,T047,Disorders
What is (are) gnathodiaphyseal dysplasia ?,0000432-1,information,"Gnathodiaphyseal dysplasia is a disorder that affects the bones. People with this condition have reduced bone mineral density (osteopenia), which causes the bones to be unusually fragile. As a result, affected individuals typically experience multiple bone fractures in childhood, often from mild trauma or with no apparent cause.  While most bone tissue is less dense than normal in gnathodiaphyseal dysplasia, the outer layer (cortex) of the shafts of the long bones in the arms and legs is abnormally hard and thick (diaphyseal sclerosis). Bowing of the long bones also occurs in this disorder.  Jaw problems are common in gnathodiaphyseal dysplasia; the prefix ""gnatho-"" in the condition name refers to the jaw. Affected individuals may develop bone infections (osteomyelitis) in the jaw, which can lead to pain, swelling, discharge of pus from the gums, loose teeth, and slow healing after teeth are lost or extracted. Areas of the jawbone may lose the protective coverage of the gums, which can result in deterioration of the exposed bone (osteonecrosis of the jaw). Also, normal bone in areas of the jaw may be replaced by fibrous tissue and a hard material called cementum, which normally surrounds the roots of teeth and anchors them in the jaw. These areas of abnormal bone, called cementoosseous lesions, may be present at birth or develop later in life.  When gnathodiaphyseal dysplasia was first described, it was thought to be a variation of another bone disorder called osteogenesis imperfecta, which is also characterized by frequent bone fractures. However, gnathodiaphyseal dysplasia is now generally considered to be a separate condition. Unlike in osteogenesis imperfecta, the fractures in gnathodiaphyseal dysplasia heal normally without causing deformity or loss of height.",gnathodiaphyseal dysplasia,0000432,GHR,https://ghr.nlm.nih.gov/condition/gnathodiaphyseal-dysplasia,C1833736,T047,Disorders
How many people are affected by gnathodiaphyseal dysplasia ?,0000432-2,frequency,"The prevalence of gnathodiaphyseal dysplasia is unknown, but it is thought to be a rare disorder. A few affected individuals and families have been described in the medical literature.",gnathodiaphyseal dysplasia,0000432,GHR,https://ghr.nlm.nih.gov/condition/gnathodiaphyseal-dysplasia,C1833736,T047,Disorders
What are the genetic changes related to gnathodiaphyseal dysplasia ?,0000432-3,genetic changes,"Gnathodiaphyseal dysplasia is caused by mutations in the ANO5 gene, which provides instructions for making a protein called anoctamin-5. While the specific function of this protein is not well understood, it belongs to a family of proteins, called anoctamins, that act as chloride channels. Studies suggest that most anoctamin channels are turned on (activated) in the presence of positively charged calcium atoms (calcium ions); these channels are known as calcium-activated chloride channels. The mechanism for this calcium activation is unclear.  The ANO5 gene mutations that have been identified in people with gnathodiaphyseal dysplasia change single protein building blocks (amino acids) in the anoctamin-5 protein. It is unclear how these protein changes lead to the fragile bones, jaw problems, and other skeletal abnormalities that occur in gnathodiaphyseal dysplasia. Researchers suggest that the mutations may affect the way cells process calcium, an important mineral in bone development and growth.",gnathodiaphyseal dysplasia,0000432,GHR,https://ghr.nlm.nih.gov/condition/gnathodiaphyseal-dysplasia,C1833736,T047,Disorders
Is gnathodiaphyseal dysplasia inherited ?,0000432-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",gnathodiaphyseal dysplasia,0000432,GHR,https://ghr.nlm.nih.gov/condition/gnathodiaphyseal-dysplasia,C1833736,T047,Disorders
What are the treatments for gnathodiaphyseal dysplasia ?,0000432-5,treatment,These resources address the diagnosis or management of gnathodiaphyseal dysplasia:  - Cleveland Clinic: Osteomyelitis  - MedlinePlus Encyclopedia: Bone Mineral Density Testing   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,gnathodiaphyseal dysplasia,0000432,GHR,https://ghr.nlm.nih.gov/condition/gnathodiaphyseal-dysplasia,C1833736,T047,Disorders
What is (are) Gorlin syndrome ?,0000433-1,information,"Gorlin syndrome, also known as nevoid basal cell carcinoma syndrome, is a condition that affects many areas of the body and increases the risk of developing various cancerous and noncancerous tumors.  In people with Gorlin syndrome, the type of cancer diagnosed most often is basal cell carcinoma, which is the most common form of skin cancer. Individuals with Gorlin syndrome typically begin to develop basal cell carcinomas during adolescence or early adulthood. These cancers occur most often on the face, chest, and back. The number of basal cell carcinomas that develop during a person's lifetime varies among affected individuals. Some people with Gorlin syndrome never develop any basal cell carcinomas, while others may develop thousands of these cancers. Individuals with lighter skin are more likely to develop basal cell carcinomas than are people with darker skin.  Most people with Gorlin syndrome also develop noncancerous (benign) tumors of the jaw, called keratocystic odontogenic tumors. These tumors usually first appear during adolescence, and new tumors form until about age 30. Keratocystic odontogenic tumors rarely develop later in adulthood. If untreated, these tumors may cause painful facial swelling and tooth displacement.  Individuals with Gorlin syndrome have a higher risk than the general population of developing other tumors. A small proportion of affected individuals develop a brain tumor called medulloblastoma during childhood. A type of benign tumor called a fibroma can occur in the heart or in a woman's ovaries. Heart (cardiac) fibromas often do not cause any symptoms, but they may obstruct blood flow or cause irregular heartbeats (arrhythmia). Ovarian fibromas are not thought to affect a woman's ability to have children (fertility).  Other features of Gorlin syndrome include small depressions (pits) in the skin of the palms of the hands and soles of the feet; an unusually large head size (macrocephaly) with a prominent forehead; and skeletal abnormalities involving the spine, ribs, or skull. These signs and symptoms are typically apparent from birth or become evident in early childhood.",Gorlin syndrome,0000433,GHR,https://ghr.nlm.nih.gov/condition/gorlin-syndrome,C0004779,T019,Disorders
How many people are affected by Gorlin syndrome ?,0000433-2,frequency,"Gorlin syndrome affects an estimated 1 in 31,000 people. While more than 1 million new cases of basal cell carcinoma are diagnosed each year in the United States, fewer than 1 percent of these skin cancers are related to Gorlin syndrome.",Gorlin syndrome,0000433,GHR,https://ghr.nlm.nih.gov/condition/gorlin-syndrome,C0004779,T019,Disorders
What are the genetic changes related to Gorlin syndrome ?,0000433-3,genetic changes,"Mutations in the PTCH1 gene cause Gorlin syndrome. This gene provides instructions for making a protein called patched-1, which functions as a receptor. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. Together, ligands and their receptors trigger signals that affect cell development and function. A protein called Sonic Hedgehog is the ligand for the patched-1 receptor. Patched-1 blocks cell growth and division (proliferation) until Sonic Hedgehog is attached.  The PTCH1 gene is a tumor suppressor gene, which means it stops cells from proliferating too rapidly or in an uncontrolled way. Mutations in this gene prevent the production of patched-1 or lead to the production of an abnormal version of the receptor. An altered or missing patched-1 receptor cannot effectively suppress cell growth and division. As a result, cells proliferate uncontrollably to form the tumors that are characteristic of Gorlin syndrome. It is less clear how PTCH1 gene mutations cause the other signs and symptoms related to this condition.  The characteristic features of Gorlin syndrome can also be associated with a chromosomal change called a 9q22.3 microdeletion, in which a small piece of chromosome 9 is deleted in each cell. This deletion includes the segment of chromosome 9 that contains the PTCH1 gene, and as a result, people with a 9q22.3 microdeletion are missing one copy of this gene. Loss of this gene underlies the signs and symptoms of Gorlin syndrome in people with 9q22.3 microdeletions. Affected individuals also have features that are not typically associated with Gorlin syndrome, including delayed development, intellectual disability, overgrowth of the body (macrosomia), and other physical abnormalities. Researchers believe that these other signs and symptoms may result from the loss of additional genes in the deleted region of chromosome 9.",Gorlin syndrome,0000433,GHR,https://ghr.nlm.nih.gov/condition/gorlin-syndrome,C0004779,T019,Disorders
Is Gorlin syndrome inherited ?,0000433-4,inheritance,"Gorlin syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the condition. In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the PTCH1 gene and occur in people with no history of the disorder in their family.  Having one mutated copy of the PTCH1 gene in each cell is enough to cause the features of Gorlin syndrome that are present early in life, including macrocephaly and skeletal abnormalities. For basal cell carcinomas and other tumors to develop, a mutation in the second copy of the PTCH1 gene must also occur in certain cells during the person's lifetime. Most people who are born with one PTCH1 gene mutation eventually acquire a second mutation in some cells and consequently develop various types of tumors.",Gorlin syndrome,0000433,GHR,https://ghr.nlm.nih.gov/condition/gorlin-syndrome,C0004779,T019,Disorders
What are the treatments for Gorlin syndrome ?,0000433-5,treatment,These resources address the diagnosis or management of Gorlin syndrome:  - Gene Review: Gene Review: Nevoid Basal Cell Carcinoma Syndrome  - Genetic Testing Registry: Gorlin syndrome  - MedlinePlus Encyclopedia: Basal Cell Nevus Syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Gorlin syndrome,0000433,GHR,https://ghr.nlm.nih.gov/condition/gorlin-syndrome,C0004779,T019,Disorders
What is (are) GRACILE syndrome ?,0000434-1,information,"GRACILE syndrome is a severe disorder that begins before birth. GRACILE stands for the condition's characteristic features: growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis, and early death.  In GRACILE syndrome, growth before birth is slow (intrauterine growth retardation). Affected newborns are smaller than average and have an inability to grow and gain weight at the expected rate (failure to thrive). A characteristic of GRACILE syndrome is excess iron in the liver, which likely begins before birth. Iron levels may begin to improve after birth, although they typically remain elevated. Within the first day of life, infants with GRACILE syndrome have a buildup of a chemical called lactic acid in the body (lactic acidosis). They also have kidney problems that lead to an excess of molecules called amino acids in the urine (aminoaciduria). Babies with GRACILE syndrome have cholestasis, which is a reduced ability to produce and release a digestive fluid called bile. Cholestasis leads to irreversible liver disease (cirrhosis) in the first few months of life.  Because of the severe health problems caused by GRACILE syndrome, infants with this condition do not survive for more than a few months, and about half die within a few days of birth.",GRACILE syndrome,0000434,GHR,https://ghr.nlm.nih.gov/condition/gracile-syndrome,C1864002,T047,Disorders
How many people are affected by GRACILE syndrome ?,0000434-2,frequency,"GRACILE syndrome is found almost exclusively in Finland, where it is estimated to affect 1 in 47,000 infants. At least 32 affected infants have been described in the medical literature.",GRACILE syndrome,0000434,GHR,https://ghr.nlm.nih.gov/condition/gracile-syndrome,C1864002,T047,Disorders
What are the genetic changes related to GRACILE syndrome ?,0000434-3,genetic changes,"GRACILE syndrome is caused by a mutation in the BCS1L gene. The protein produced from this gene is found in cell structures called mitochondria, which convert the energy from food into a form that cells can use. In mitochondria, the BCS1L protein plays a role in oxidative phosphorylation, which is a multistep process through which cells derive much of their energy. The BCS1L protein is critical for the formation of a group of proteins known as complex III, which is one of several protein complexes involved in oxidative phosphorylation.  The genetic change involved in GRACILE syndrome alters the BCS1L protein, and the abnormal protein is broken down more quickly than the normal protein. What little protein remains is able to help form some complete complex III, although the amount is severely reduced, particularly in the liver and kidneys. As a result, complex III activity and oxidative phosphorylation are decreased in these organs in people with GRACILE syndrome. Without energy, these organs become damaged, leading to many of the features of GRACILE syndrome. It is not clear why a change in the BCS1L gene leads to iron accumulation in people with this condition.",GRACILE syndrome,0000434,GHR,https://ghr.nlm.nih.gov/condition/gracile-syndrome,C1864002,T047,Disorders
Is GRACILE syndrome inherited ?,0000434-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",GRACILE syndrome,0000434,GHR,https://ghr.nlm.nih.gov/condition/gracile-syndrome,C1864002,T047,Disorders
What are the treatments for GRACILE syndrome ?,0000434-5,treatment,These resources address the diagnosis or management of GRACILE syndrome:  - Genetic Testing Registry: GRACILE syndrome  - MedlinePlus Encyclopedia: Aminoaciduria  - MedlinePlus Encyclopedia: Cholestasis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,GRACILE syndrome,0000434,GHR,https://ghr.nlm.nih.gov/condition/gracile-syndrome,C1864002,T047,Disorders
What is (are) granulomatosis with polyangiitis ?,0000435-1,information,"Granulomatosis with polyangiitis (GPA) is a condition that causes inflammation that primarily affects the respiratory tract (including the lungs and airways) and the kidneys. This disorder is also commonly known as Wegener granulomatosis. A characteristic feature of GPA is inflammation of blood vessels (vasculitis), particularly the small- and medium-sized blood vessels in the lungs, nose, sinuses, windpipe, and kidneys, although vessels in any organ can be involved. Polyangiitis refers to the inflammation of multiple types of vessels, such as small arteries and veins. Vasculitis causes scarring and tissue death in the vessels and impedes blood flow to tissues and organs.  Another characteristic feature of GPA is the formation of granulomas, which are small areas of inflammation composed of immune cells that aid in the inflammatory reaction. The granulomas usually occur in the lungs or airways of people with this condition, although they can occur in the eyes or other organs. As granulomas grow, they can invade surrounding areas, causing tissue damage.  The signs and symptoms of GPA vary based on the tissues and organs affected by vasculitis. Many people with this condition experience a vague feeling of discomfort (malaise), fever, weight loss, or other general symptoms of the body's immune reaction. In most people with GPA, inflammation begins in the vessels of the respiratory tract, leading to nasal congestion, frequent nosebleeds, shortness of breath, or coughing. Severe inflammation in the nose can lead to a hole in the tissue that separates the two nostrils (nasal septum perforation) or a collapse of the septum, causing a sunken bridge of the nose (saddle nose).  The kidneys are commonly affected in people with GPA. Tissue damage caused by vasculitis in the kidneys can lead to decreased kidney function, which may cause increased blood pressure or blood in the urine, and life-threatening kidney failure. Inflammation can also occur in other regions of the body, including the eyes, middle and inner ear structures, skin, joints, nerves, heart, and brain. Depending on which systems are involved, additional symptoms can include skin rashes, inner ear pain, swollen and painful joints, and numbness or tingling in the limbs.  GPA is most common in middle-aged adults, although it can occur at any age. If untreated, the condition is usually fatal within 2 years of diagnosis. Even after treatment, vasculitis can return.",granulomatosis with polyangiitis,0000435,GHR,https://ghr.nlm.nih.gov/condition/granulomatosis-with-polyangiitis,C0043092,T047,Disorders
How many people are affected by granulomatosis with polyangiitis ?,0000435-2,frequency,"GPA is a rare disorder that affects an estimated 3 in 100,000 people in the United States.",granulomatosis with polyangiitis,0000435,GHR,https://ghr.nlm.nih.gov/condition/granulomatosis-with-polyangiitis,C0043092,T047,Disorders
What are the genetic changes related to granulomatosis with polyangiitis ?,0000435-3,genetic changes,"The genetic basis of GPA is not well understood. Having a particular version of the HLA-DPB1 gene is the strongest genetic risk factor for developing this condition, although several other genes, some of which have not been identified, may be involved. It is likely that a combination of genetic and environmental factors lead to GPA.  GPA is an autoimmune disorder. Such disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. Approximately 90 percent of people with GPA have an abnormal immune protein called an anti-neutrophil cytoplasmic antibody (ANCA) in their blood. Antibodies normally bind to specific foreign particles and germs, marking them for destruction, but ANCAs attack normal human proteins. Most people with GPA have an ANCA that attacks the human protein proteinase 3 (PR3). A few affected individuals have an ANCA that attacks a protein called myeloperoxidase (MPO). When these antibodies attach to the protein they recognize, they trigger inflammation, which contributes to the signs and symptoms of GPA.  The HLA-DPB1 gene belongs to a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Each HLA gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. A particular variant of the HLA-DPB1 gene called HLA-DPB1*0401 has been found more frequently in people with GPA, especially those with ANCAs, than in people without the condition.  Because the HLA-DPB1 gene is involved in the immune system, changes in it might be related to the autoimmune response and inflammation in the respiratory tract and kidneys characteristic of GPA. However, it is unclear what specific role the HLA-DPB1*0401 gene variant plays in development of this condition.",granulomatosis with polyangiitis,0000435,GHR,https://ghr.nlm.nih.gov/condition/granulomatosis-with-polyangiitis,C0043092,T047,Disorders
Is granulomatosis with polyangiitis inherited ?,0000435-4,inheritance,The inheritance pattern of GPA is unknown. Most instances are sporadic and occur in individuals with no history of the disorder in their family. Only rarely is more than one member of the same family affected by the disorder.,granulomatosis with polyangiitis,0000435,GHR,https://ghr.nlm.nih.gov/condition/granulomatosis-with-polyangiitis,C0043092,T047,Disorders
What are the treatments for granulomatosis with polyangiitis ?,0000435-5,treatment,These resources address the diagnosis or management of granulomatosis with polyangiitis:  - Genetic Testing Registry: Wegener's granulomatosis  - Johns Hopkins Vasculitis Center: How is Wegener's Granulomatosis Diagnosed?  - MedlinePlus Encyclopedia: Wegener's Granulomatosis  - Merck Manual Home Health Edition   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,granulomatosis with polyangiitis,0000435,GHR,https://ghr.nlm.nih.gov/condition/granulomatosis-with-polyangiitis,C0043092,T047,Disorders
What is (are) Graves disease ?,0000436-1,information,"Graves disease is a condition that affects the function of the thyroid, which is a butterfly-shaped gland in the lower neck. The thyroid makes hormones that help regulate a wide variety of critical body functions. For example, thyroid hormones influence growth and development, body temperature, heart rate, menstrual cycles, and weight. In people with Graves disease, the thyroid is overactive and makes more hormones than the body needs. The condition usually appears in mid-adulthood, although it may occur at any age.  Excess thyroid hormones can cause a variety of signs and symptoms. These include nervousness or anxiety, extreme tiredness (fatigue), a rapid and irregular heartbeat, hand tremors, frequent bowel movements or diarrhea, increased sweating and difficulty tolerating hot conditions, trouble sleeping, and weight loss in spite of an increased appetite. Affected women may have menstrual irregularities, such as an unusually light menstrual flow and infrequent periods. Some people with Graves disease develop an enlargement of the thyroid called a goiter. Depending on its size, the enlarged thyroid can cause the neck to look swollen and may interfere with breathing and swallowing.  Between 25 and 50 percent of people with Graves disease have eye abnormalities, which are known as Graves ophthalmopathy. These eye problems can include swelling and inflammation, redness, dryness, puffy eyelids, and a gritty sensation like having sand or dirt in the eyes. Some people develop bulging of the eyes caused by inflammation of tissues behind the eyeball and ""pulling back"" (retraction) of the eyelids. Rarely, affected individuals have more serious eye problems, such as pain, double vision, and pinching (compression) of the optic nerve connecting the eye and the brain, which can cause vision loss.  A small percentage of people with Graves disease develop a skin abnormality called pretibial myxedema or Graves dermopathy. This abnormality causes the skin on the front of the lower legs and the tops of the feet to become thick, lumpy, and red. It is not usually painful.",Graves disease,0000436,GHR,https://ghr.nlm.nih.gov/condition/graves-disease,C0018213,T047,Disorders
How many people are affected by Graves disease ?,0000436-2,frequency,"Graves disease affects about 1 in 200 people. The disease occurs more often in women than in men, which may be related to hormonal factors. Graves disease is the most common cause of thyroid overactivity (hyperthyroidism) in the United States.",Graves disease,0000436,GHR,https://ghr.nlm.nih.gov/condition/graves-disease,C0018213,T047,Disorders
What are the genetic changes related to Graves disease ?,0000436-3,genetic changes,"Graves disease is thought to result from a combination of genetic and environmental factors. Some of these factors have been identified, but many remain unknown.  Graves disease is classified as an autoimmune disorder, one of a large group of conditions that occur when the immune system attacks the body's own tissues and organs. In people with Graves disease, the immune system creates a protein (antibody) called thyroid-stimulating immunoglobulin (TSI). TSI signals the thyroid to increase its production of hormones abnormally. The resulting overactivity of the thyroid causes many of the signs and symptoms of Graves disease. Studies suggest that immune system abnormalities also underlie Graves ophthalmopathy and pretibial myxedema.  People with Graves disease have an increased risk of developing other autoimmune disorders, including rheumatoid arthritis, pernicious anemia, systemic lupus erythematosus, Addison disease, celiac disease, type 1 diabetes, and vitiligo.  Variations in many genes have been studied as possible risk factors for Graves disease. Some of these genes are part of a family called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Other genes that have been associated with Graves disease help regulate the immune system or are involved in normal thyroid function. Most of the genetic variations that have been discovered are thought to have a small impact on a person's overall risk of developing this condition.  Other, nongenetic factors are also believed to play a role in Graves disease. These factors may trigger the condition in people who are at risk, although the mechanism is unclear. Potential triggers include changes in sex hormones (particularly in women), viral or bacterial infections, certain medications, and having too much or too little iodine (a substance critical for thyroid hormone production). Smoking increases the risk of eye problems and is associated with more severe eye abnormalities in people with Graves disease.",Graves disease,0000436,GHR,https://ghr.nlm.nih.gov/condition/graves-disease,C0018213,T047,Disorders
Is Graves disease inherited ?,0000436-4,inheritance,"The inheritance pattern of Graves disease is unclear because many genetic and environmental factors appear to be involved. However, the condition can cluster in families, and having a close relative with Graves disease or another autoimmune disorder likely increases a person's risk of developing the condition.",Graves disease,0000436,GHR,https://ghr.nlm.nih.gov/condition/graves-disease,C0018213,T047,Disorders
What are the treatments for Graves disease ?,0000436-5,treatment,"These resources address the diagnosis or management of Graves disease:  - American Thyroid Association: Thyroid Function Tests  - Genetic Testing Registry: Graves disease 2  - Genetic Testing Registry: Graves disease 3  - Genetic Testing Registry: Graves disease, susceptibility to, X-linked 1  - Genetic Testing Registry: Graves' disease  - Graves' Disease & Thyroid Foundation: Treatment Options  - MedlinePlus Encyclopedia: TSI  - National Institute of Diabetes and Digestive and Kidney Diseases: Thyroid Function Tests  - Thyroid Disease Manager: Diagnosis and Treatment of Graves Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Graves disease,0000436,GHR,https://ghr.nlm.nih.gov/condition/graves-disease,C0018213,T047,Disorders
What is (are) gray platelet syndrome ?,0000437-1,information,"Gray platelet syndrome is a bleeding disorder associated with abnormal platelets, which are blood cell fragments involved in blood clotting. People with this condition tend to bruise easily and have an increased risk of nosebleeds (epistaxis). They may also experience abnormally heavy or extended bleeding following surgery, dental work, or minor trauma. Women with gray platelet syndrome often have irregular, heavy periods (menometrorrhagia). These bleeding problems are usually mild to moderate, but they have been life-threatening in a few affected individuals.  A condition called myelofibrosis, which is a buildup of scar tissue (fibrosis) in the bone marrow, is another common feature of gray platelet syndrome. Bone marrow is the spongy tissue in the center of long bones that produces most of the blood cells the body needs, including platelets. The scarring associated with myelofibrosis damages bone marrow, preventing it from making enough blood cells. Other organs, particularly the spleen, start producing more blood cells to compensate; this process often leads to an enlarged spleen (splenomegaly).",gray platelet syndrome,0000437,GHR,https://ghr.nlm.nih.gov/condition/gray-platelet-syndrome,C0272302,T047,Disorders
How many people are affected by gray platelet syndrome ?,0000437-2,frequency,Gray platelet syndrome appears to be a rare disorder. About 60 cases have been reported worldwide.,gray platelet syndrome,0000437,GHR,https://ghr.nlm.nih.gov/condition/gray-platelet-syndrome,C0272302,T047,Disorders
What are the genetic changes related to gray platelet syndrome ?,0000437-3,genetic changes,"Gray platelet syndrome can be caused by mutations in the NBEAL2 gene. Little is known about the protein produced from this gene. It appears to play a role in the formation of alpha-granules, which are sacs inside platelets that contain growth factors and other proteins that are important for blood clotting and wound healing. In response to an injury that causes bleeding, the proteins stored in alpha-granules help platelets stick to one another to form a plug that seals off damaged blood vessels and prevents further blood loss.  Mutations in the NBEAL2 gene disrupt the normal production of alpha-granules. Without alpha-granules, platelets are unusually large and fewer in number than usual (macrothrombocytopenia). The abnormal platelets also appear gray when viewed under a microscope, which gives this condition its name. A lack of alpha-granules impairs the normal activity of platelets during blood clotting, increasing the risk of abnormal bleeding. Myelofibrosis is thought to occur because the growth factors and other proteins that are normally packaged into alpha-granules leak out into the bone marrow. The proteins lead to fibrosis that affects the bone marrow's ability to make new blood cells.  Some people with gray platelet syndrome do not have an identified mutation in the NBEAL2 gene. In these individuals, the cause of the condition is unknown.",gray platelet syndrome,0000437,GHR,https://ghr.nlm.nih.gov/condition/gray-platelet-syndrome,C0272302,T047,Disorders
Is gray platelet syndrome inherited ?,0000437-4,inheritance,"When gray platelet syndrome is caused by NBEAL2 gene mutations, it has an autosomal recessive pattern of inheritance, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene in each cell.  Gray platelet syndrome can also be inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. An affected person often inherits the condition from one affected parent. Researchers are working to determine which gene or genes are associated with the autosomal dominant form of gray platelet syndrome.",gray platelet syndrome,0000437,GHR,https://ghr.nlm.nih.gov/condition/gray-platelet-syndrome,C0272302,T047,Disorders
What are the treatments for gray platelet syndrome ?,0000437-5,treatment,These resources address the diagnosis or management of gray platelet syndrome:  - Genetic Testing Registry: Gray platelet syndrome  - National Heart Lung and Blood Institute: How is Thrombocytopenia Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,gray platelet syndrome,0000437,GHR,https://ghr.nlm.nih.gov/condition/gray-platelet-syndrome,C0272302,T047,Disorders
What is (are) Greenberg dysplasia ?,0000438-1,information,"Greenberg dysplasia is a severe condition characterized by specific bone abnormalities in the developing fetus. This condition is fatal before birth.  The bones of affected individuals do not develop properly, causing a distinctive spotted appearance called moth-eaten bone, which is visible on x-ray images. In addition, the bones have abnormal calcium deposits (ectopic calcification). Affected individuals have extremely short bones in the arms and legs and abnormally flat vertebrae (platyspondyly). Other skeletal abnormalities may include short ribs and extra fingers (polydactyly). In addition, affected fetuses have extensive swelling of the body caused by fluid accumulation (hydrops fetalis). Greenberg dysplasia is also called hydrops-ectopic calcification-moth-eaten skeletal dysplasia (HEM), which reflects the condition's most common features.",Greenberg dysplasia,0000438,GHR,https://ghr.nlm.nih.gov/condition/greenberg-dysplasia,C2931048,T047,Disorders
How many people are affected by Greenberg dysplasia ?,0000438-2,frequency,Greenberg dysplasia is a very rare condition. Approximately ten cases have been reported in the scientific literature.,Greenberg dysplasia,0000438,GHR,https://ghr.nlm.nih.gov/condition/greenberg-dysplasia,C2931048,T047,Disorders
What are the genetic changes related to Greenberg dysplasia ?,0000438-3,genetic changes,"Mutations in the LBR gene cause Greenberg dysplasia. This gene provides instructions for making a protein called the lamin B receptor. One region of this protein, called the sterol reductase domain, plays an important role in the production (synthesis) of cholesterol. Cholesterol is a type of fat that is produced in the body and obtained from foods that come from animals: eggs, meat, fish, and dairy products. Cholesterol is necessary for normal embryonic development and has important functions both before and after birth. Cholesterol is an important component of cell membranes and the protective substance covering nerve cells (myelin). Additionally, cholesterol plays a role in the production of certain hormones and digestive acids. During cholesterol synthesis, the sterol reductase function of the lamin B receptor allows the protein to perform one of several steps that convert a molecule called lanosterol to cholesterol.  LBR gene mutations involved in Greenberg dysplasia lead to loss of the sterol reductase function of the lamin B receptor, and research suggests that this loss causes the condition. Absence of the sterol reductase function disrupts the normal synthesis of cholesterol within cells. This absence may also allow potentially toxic byproducts of cholesterol synthesis to build up in the body's tissues. Researchers suspect that low cholesterol levels or an accumulation of other substances disrupts the growth and development of many parts of the body. It is not known, however, how a disturbance of cholesterol synthesis leads to the specific features of Greenberg dysplasia.",Greenberg dysplasia,0000438,GHR,https://ghr.nlm.nih.gov/condition/greenberg-dysplasia,C2931048,T047,Disorders
Is Greenberg dysplasia inherited ?,0000438-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Greenberg dysplasia,0000438,GHR,https://ghr.nlm.nih.gov/condition/greenberg-dysplasia,C2931048,T047,Disorders
What are the treatments for Greenberg dysplasia ?,0000438-5,treatment,These resources address the diagnosis or management of Greenberg dysplasia:  - Genetic Testing Registry: Greenberg dysplasia  - Lurie Children's Hospital of Chicago: Fetal Skeletal Dysplasia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Greenberg dysplasia,0000438,GHR,https://ghr.nlm.nih.gov/condition/greenberg-dysplasia,C2931048,T047,Disorders
What is (are) Greig cephalopolysyndactyly syndrome ?,0000439-1,information,"Greig cephalopolysyndactyly syndrome is a disorder that affects development of the limbs, head, and face. The features of this syndrome are highly variable, ranging from very mild to severe. People with this condition typically have one or more extra fingers or toes (polydactyly) or an abnormally wide thumb or big toe (hallux). The skin between the fingers and toes may be fused (cutaneous syndactyly). This disorder is also characterized by widely spaced eyes (ocular hypertelorism), an abnormally large head size (macrocephaly), and a high, prominent forehead. Rarely, affected individuals may have more serious medical problems including seizures, developmental delay, and intellectual disability.",Greig cephalopolysyndactyly syndrome,0000439,GHR,https://ghr.nlm.nih.gov/condition/greig-cephalopolysyndactyly-syndrome,C0265306,T019,Disorders
How many people are affected by Greig cephalopolysyndactyly syndrome ?,0000439-2,frequency,This condition is very rare; its prevalence is unknown.,Greig cephalopolysyndactyly syndrome,0000439,GHR,https://ghr.nlm.nih.gov/condition/greig-cephalopolysyndactyly-syndrome,C0265306,T019,Disorders
What are the genetic changes related to Greig cephalopolysyndactyly syndrome ?,0000439-3,genetic changes,"Mutations in the GLI3 gene cause Greig cephalopolysyndactyly syndrome. The GLI3 gene provides instructions for making a protein that controls gene expression, which is a process that regulates whether genes are turned on or off in particular cells. By interacting with certain genes at specific times during development, the GLI3 protein plays a role in the normal shaping (patterning) of many organs and tissues before birth.  Different genetic changes involving the GLI3 gene can cause Greig cephalopolysyndactyly syndrome. In some cases, the condition results from a chromosomal abnormalitysuch as a large deletion or rearrangement of genetic materialin the region of chromosome 7 that contains the GLI3 gene. In other cases, a mutation in the GLI3 gene itself is responsible for the disorder. Each of these genetic changes prevents one copy of the gene in each cell from producing any functional protein. It remains unclear how a reduced amount of this protein disrupts early development and causes the characteristic features of Greig cephalopolysyndactyly syndrome.",Greig cephalopolysyndactyly syndrome,0000439,GHR,https://ghr.nlm.nih.gov/condition/greig-cephalopolysyndactyly-syndrome,C0265306,T019,Disorders
Is Greig cephalopolysyndactyly syndrome inherited ?,0000439-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one altered or missing copy of the GLI3 gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits a gene mutation or chromosomal abnormality from one affected parent. Other cases occur in people with no history of the condition in their family.",Greig cephalopolysyndactyly syndrome,0000439,GHR,https://ghr.nlm.nih.gov/condition/greig-cephalopolysyndactyly-syndrome,C0265306,T019,Disorders
What are the treatments for Greig cephalopolysyndactyly syndrome ?,0000439-5,treatment,These resources address the diagnosis or management of Greig cephalopolysyndactyly syndrome:  - Gene Review: Gene Review: Greig Cephalopolysyndactyly Syndrome  - Genetic Testing Registry: Greig cephalopolysyndactyly syndrome  - MedlinePlus Encyclopedia: Polydactyly  - MedlinePlus Encyclopedia: Syndactyly (image)   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Greig cephalopolysyndactyly syndrome,0000439,GHR,https://ghr.nlm.nih.gov/condition/greig-cephalopolysyndactyly-syndrome,C0265306,T019,Disorders
What is (are) Griscelli syndrome ?,0000440-1,information,"Griscelli syndrome is an inherited condition characterized by unusually light (hypopigmented) skin and light silvery-gray hair starting in infancy. Researchers have identified three types of this disorder, which are distinguished by their genetic cause and pattern of signs and symptoms.  Griscelli syndrome type 1 involves severe problems with brain function in addition to the distinctive skin and hair coloring. Affected individuals typically have delayed development, intellectual disability, seizures, weak muscle tone (hypotonia), and eye and vision abnormalities. Another condition called Elejalde disease has many of the same signs and symptoms, and some researchers have proposed that Griscelli syndrome type 1 and Elejalde disease are actually the same disorder.  People with Griscelli syndrome type 2 have immune system abnormalities in addition to having hypopigmented skin and hair. Affected individuals are prone to recurrent infections. They also develop an immune condition called hemophagocytic lymphohistiocytosis (HLH), in which the immune system produces too many activated immune cells called T-lymphocytes and macrophages (histiocytes). Overactivity of these cells can damage organs and tissues throughout the body, causing life-threatening complications if the condition is untreated. People with Griscelli syndrome type 2 do not have the neurological abnormalities of type 1.  Unusually light skin and hair coloring are the only features of Griscelli syndrome type 3. People with this form of the disorder do not have neurological abnormalities or immune system problems.",Griscelli syndrome,0000440,GHR,https://ghr.nlm.nih.gov/condition/griscelli-syndrome,C0039082,T047,Disorders
How many people are affected by Griscelli syndrome ?,0000440-2,frequency,Griscelli syndrome is a rare condition; its prevalence is unknown. Type 2 appears to be the most common of the three known types.,Griscelli syndrome,0000440,GHR,https://ghr.nlm.nih.gov/condition/griscelli-syndrome,C0039082,T047,Disorders
What are the genetic changes related to Griscelli syndrome ?,0000440-3,genetic changes,"The three types of Griscelli syndrome are caused by mutations in different genes: Type 1 results from mutations in the MYO5A gene, type 2 is caused by mutations in the RAB27A gene, and type 3 results from mutations in the MLPH gene.  The proteins produced from these genes are found in pigment-producing cells called melanocytes. Within these cells, the proteins work together to transport structures called melanosomes. These structures produce a pigment called melanin, which is the substance that gives skin, hair, and eyes their color (pigmentation). Melanosomes are formed near the center of melanocytes, but they must be transported to the outer edge of these cells and then transferred into other types of cells to provide normal pigmentation.  Mutations in any of the three genes, MYO5A, RAB27A, or MLPH, impair the normal transport of melanosomes within melanocytes. As a result, these structures clump near the center of melanocytes, trapping melanin within these cells and preventing normal pigmentation of skin and hair. The clumps of pigment, which can be seen in hair shafts when viewed under a microscope, are a hallmark feature of the condition.  In addition to their roles in melanosome transport, the MYO5A and RAB27A genes have functions elsewhere in the body. Specifically, the protein produced from the MYO5A gene transports materials within nerve cells (neurons) that appear to be critical for cell function. The protein produced from the RAB27A gene is found in immune system cells, where it is involved in the release of certain compounds that kill foreign invaders (such as viruses and bacteria). Mutations in these genes impair these critical cell activities, leading to the neurological problems and immune system abnormalities found in Griscelli syndrome types 1 and 2, respectively.",Griscelli syndrome,0000440,GHR,https://ghr.nlm.nih.gov/condition/griscelli-syndrome,C0039082,T047,Disorders
Is Griscelli syndrome inherited ?,0000440-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Griscelli syndrome,0000440,GHR,https://ghr.nlm.nih.gov/condition/griscelli-syndrome,C0039082,T047,Disorders
What are the treatments for Griscelli syndrome ?,0000440-5,treatment,These resources address the diagnosis or management of Griscelli syndrome:  - Genetic Testing Registry: Griscelli syndrome type 1  - Genetic Testing Registry: Griscelli syndrome type 2  - Genetic Testing Registry: Griscelli syndrome type 3   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Griscelli syndrome,0000440,GHR,https://ghr.nlm.nih.gov/condition/griscelli-syndrome,C0039082,T047,Disorders
What is (are) GRN-related frontotemporal dementia ?,0000441-1,information,"GRN-related frontotemporal dementia is a progressive brain disorder that can affect behavior, language, and movement. The symptoms of this disorder usually become noticeable in a person's fifties or sixties, and affected people typically survive 6 to 7 years after the appearance of symptoms. However, the features of this condition vary significantly, even among affected members of the same family.  Behavioral changes are the most common early signs of GRN-related frontotemporal dementia. These include marked changes in personality, judgment, and insight. It may become difficult for affected individuals to interact with others in a socially appropriate manner. Affected people may also become easily distracted and unable to complete tasks. They increasingly require help with personal care and other activities of daily living.  Many people with GRN-related frontotemporal dementia develop progressive problems with speech and language (aphasia). Affected individuals may have trouble speaking, remembering words and names (dysnomia), and understanding speech. Over time, they may completely lose the ability to communicate.  Some people with GRN-related frontotemporal dementia also develop movement disorders, such as parkinsonism and corticobasal syndrome. The signs and symptoms of these disorders include tremors, rigidity, unusually slow movement (bradykinesia), involuntary muscle spasms (myoclonus), uncontrolled muscle tensing (dystonia), and an inability to carry out purposeful movements (apraxia).",GRN-related frontotemporal dementia,0000441,GHR,https://ghr.nlm.nih.gov/condition/grn-related-frontotemporal-dementia,C3811918,T047,Disorders
How many people are affected by GRN-related frontotemporal dementia ?,0000441-2,frequency,"GRN-related frontotemporal dementia affects an estimated 3 to 15 per 100,000 people aged 45 to 64. This condition accounts for 5 to 10 percent of all cases of frontotemporal dementia.",GRN-related frontotemporal dementia,0000441,GHR,https://ghr.nlm.nih.gov/condition/grn-related-frontotemporal-dementia,C3811918,T047,Disorders
What are the genetic changes related to GRN-related frontotemporal dementia ?,0000441-3,genetic changes,"GRN-related frontotemporal dementia results from mutations in the GRN gene. This gene provides instructions for making a protein called granulin (also known as progranulin). Granulin is active in many different tissues in the body, where it helps control the growth, division, and survival of cells. Granulin's function in the brain is not well understood, although it appears to play an important role in the survival of nerve cells (neurons).  Most mutations in the GRN gene prevent any granulin from being produced from one copy of the gene in each cell. As a result, cells make only half the usual amount of granulin. It is unclear how a shortage of this protein leads to the features of GRN-related frontotemporal dementia. However, studies have shown that the disorder is characterized by the buildup of a protein called TAR DNA-binding protein (TDP-43) in certain brain cells. The TDP-43 protein forms clumps (aggregates) that may interfere with cell functions and ultimately lead to cell death. Researchers are working to determine how mutations in the GRN gene, and the resulting loss of granulin, are related to a buildup of TDP-43 in the brain.  The features of GRN-related frontotemporal dementia result from the gradual loss of neurons in regions near the front of the brain called the frontal and temporal lobes. The frontal lobes are involved in reasoning, planning, judgment, and problem-solving, while the temporal lobes help process hearing, speech, memory, and emotion. The death of neurons in these areas causes problems with many critical brain functions. However, it is unclear why the loss of neurons occurs in the frontal and temporal lobes more often than other brain regions in people with GRN-related frontotemporal dementia.",GRN-related frontotemporal dementia,0000441,GHR,https://ghr.nlm.nih.gov/condition/grn-related-frontotemporal-dementia,C3811918,T047,Disorders
Is GRN-related frontotemporal dementia inherited ?,0000441-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has a parent and other family members with the condition.",GRN-related frontotemporal dementia,0000441,GHR,https://ghr.nlm.nih.gov/condition/grn-related-frontotemporal-dementia,C3811918,T047,Disorders
What are the treatments for GRN-related frontotemporal dementia ?,0000441-5,treatment,"These resources address the diagnosis or management of GRN-related frontotemporal dementia:  - Family Caregiver Alliance  - Gene Review: Gene Review: GRN-Related Frontotemporal Dementia  - Genetic Testing Registry: Frontotemporal dementia, ubiquitin-positive   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",GRN-related frontotemporal dementia,0000441,GHR,https://ghr.nlm.nih.gov/condition/grn-related-frontotemporal-dementia,C3811918,T047,Disorders
What is (are) guanidinoacetate methyltransferase deficiency ?,0000442-1,information,"Guanidinoacetate methyltransferase deficiency is an inherited disorder that primarily affects the brain and muscles. Without early treatment, people with this disorder have neurological problems that are usually severe. These problems include intellectual disability, speech development limited to a few words, and recurrent seizures (epilepsy). Affected individuals may also exhibit autistic behaviors that affect communication and social interaction or self-injurious behaviors such as head-banging. Other features of this disorder can include involuntary movements (extrapyramidal dysfunction) such as tremors or facial tics.  People with guanidinoacetate methyltransferase deficiency may have weak muscle tone and delayed development of motor skills such as sitting or walking. In severe cases they may lose previously acquired skills such as the ability to support their head or to sit unsupported.",guanidinoacetate methyltransferase deficiency,0000442,GHR,https://ghr.nlm.nih.gov/condition/guanidinoacetate-methyltransferase-deficiency,C0574080,T047,Disorders
How many people are affected by guanidinoacetate methyltransferase deficiency ?,0000442-2,frequency,"Guanidinoacetate methyltransferase deficiency is a very rare disorder. About 80 affected individuals have been described in the medical literature. Of these, approximately one-third are of Portuguese origin.",guanidinoacetate methyltransferase deficiency,0000442,GHR,https://ghr.nlm.nih.gov/condition/guanidinoacetate-methyltransferase-deficiency,C0574080,T047,Disorders
What are the genetic changes related to guanidinoacetate methyltransferase deficiency ?,0000442-3,genetic changes,"Mutations in the GAMT gene cause guanidinoacetate methyltransferase deficiency. The GAMT gene provides instructions for making the enzyme guanidinoacetate methyltransferase. This enzyme participates in the two-step production (synthesis) of the compound creatine from the protein building blocks (amino acids) glycine, arginine, and methionine. Specifically, guanidinoacetate methyltransferase controls the second step of this process. In this step, creatine is produced from another compound called guanidinoacetate. Creatine is needed for the body to store and use energy properly.  GAMT gene mutations impair the ability of the guanidinoacetate methyltransferase enzyme to participate in creatine synthesis, resulting in a shortage of creatine. The effects of guanidinoacetate methyltransferase deficiency are most severe in organs and tissues that require large amounts of energy, especially the brain.",guanidinoacetate methyltransferase deficiency,0000442,GHR,https://ghr.nlm.nih.gov/condition/guanidinoacetate-methyltransferase-deficiency,C0574080,T047,Disorders
Is guanidinoacetate methyltransferase deficiency inherited ?,0000442-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",guanidinoacetate methyltransferase deficiency,0000442,GHR,https://ghr.nlm.nih.gov/condition/guanidinoacetate-methyltransferase-deficiency,C0574080,T047,Disorders
What are the treatments for guanidinoacetate methyltransferase deficiency ?,0000442-5,treatment,These resources address the diagnosis or management of guanidinoacetate methyltransferase deficiency:  - Gene Review: Gene Review: Creatine Deficiency Syndromes  - Genetic Testing Registry: Deficiency of guanidinoacetate methyltransferase   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,guanidinoacetate methyltransferase deficiency,0000442,GHR,https://ghr.nlm.nih.gov/condition/guanidinoacetate-methyltransferase-deficiency,C0574080,T047,Disorders
What is (are) Guillain-Barr syndrome ?,0000443-1,information,"Guillain-Barr syndrome is an autoimmune disorder that affects the nerves. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. In Guillain-Barr syndrome, the immune response damages peripheral nerves, which are the nerves that connect the central nervous system (the brain and spinal cord) to the limbs and organs. Specifically, the immune response affects a particular part of peripheral nerves called axons, which are the extensions of nerve cells (neurons) that transmit nerve impulses. Guillain-Barr syndrome can affect the neurons that control muscle movement (motor neurons); the neurons that transmit sensory signals such as pain, temperature, and touch (sensory neurons); or both. As a result, affected individuals can experience muscle weakness or lose the ability to feel certain sensations.  Muscle weakness or paralysis are the characteristic features of Guillain-Barr syndrome. The weakness often begins in the legs and spreads to the arms, torso, and face and is commonly accompanied by numbness, tingling, or pain. Additional signs and symptoms of the condition include difficulty swallowing and difficulty breathing. Occasionally, the nerves that control involuntary functions of the body such as blood pressure and heart rate are affected, which can lead to fluctuating blood pressure or an abnormal heartbeat (cardiac arrhythmia).  There are several types of Guillain-Barr syndrome, classified by the part of the peripheral nerve involved in the condition. The most common type of Guillain-Barr syndrome is acute inflammatory demyelinating polyradiculoneuropathy (AIDP). In AIDP, the immune response damages myelin, which is the covering that protects axons and promotes the efficient transmission of nerve impulses. In two other types of Guillain-Barr syndrome, acute motor axonal neuropathy (AMAN) and acute motor-sensory axonal neuropathy (AMSAN), the axons themselves are damaged by the immune response. In AMAN, only the axons of motor neurons are damaged. In AMSAN, the axons of sensory neurons are also damaged. Because of sensory nerve damage, affected individuals can lose the ability to sense the position of their limbs and can have abnormal or absent reflexes (areflexia).  Miller Fisher syndrome, another type of Guillain-Barr syndrome, involves cranial nerves, which extend from the brain to various areas of the head and neck. Miller Fisher syndrome is characterized by three features: weakness or paralysis of the muscles that move the eyes (ophthalmoplegia), problems with balance and coordination (ataxia), and areflexia. People with this condition can have other signs and symptoms common in Guillain-Barr syndrome, such as muscle weakness.  Guillain-Barr syndrome occurs in people of all ages. The development of the condition usually follows a pattern. Prior to developing the condition, most people with Guillain-Barr syndrome have a bacterial or viral infection. The first phase of Guillain-Barr syndrome, during which signs and symptoms of the condition worsen, can last up to four weeks, although the peak of the illness is usually reached in one to two weeks. During the second phase, called the plateau, signs and symptoms of Guillain-Barr syndrome stabilize. This phase can last weeks or months. During the recovery phase, symptoms improve. However, some people with Guillain-Barr syndrome never fully recover and can still experience excessive tiredness (fatigue), muscle weakness, or muscle pain.",Guillain-Barr syndrome,0000443,GHR,https://ghr.nlm.nih.gov/condition/guillain-barre-syndrome,C0039082,T047,Disorders
How many people are affected by Guillain-Barr syndrome ?,0000443-2,frequency,"The prevalence of Guillain-Barr syndrome is estimated to be 6 to 40 cases per 1 million people. The occurrence of the different types of Guillain-Barr syndrome varies across regions. AIDP is the most common type in North America and Europe, accounting for approximately 90 percent of cases of Guillain-Barr syndrome in those regions. AMAN and AMSAN together account for 30 to 50 percent of cases in Asian countries and Latin America but only 3 to 5 percent of cases in North America and Europe. Miller Fisher syndrome is also more common in Asian countries, accounting for approximately 20 percent of cases in these countries but less than 5 percent in North America and Europe.",Guillain-Barr syndrome,0000443,GHR,https://ghr.nlm.nih.gov/condition/guillain-barre-syndrome,C0039082,T047,Disorders
What are the genetic changes related to Guillain-Barr syndrome ?,0000443-3,genetic changes,"Some studies show that normal variations in certain genes may be associated with an increased risk of developing Guillain-Barr syndrome; however, more research is necessary to identify and confirm associated genes. Many of the genes that may increase the risk of Guillain-Barr syndrome are involved in the immune system, and their roles in fighting infection may contribute to the development of the condition.  Most people who develop Guillain-Barr syndrome have a bacterial or viral infection prior to developing the signs and symptoms of the condition. However, only a very small percentage of people who have an infection develop Guillain-Barr syndrome. In order to fight the infection, specialized immune cells produce proteins called antibodies that recognize specific proteins or molecules on the bacteria or virus (pathogen). Some research shows that antibodies that recognize molecules on some pathogens may also recognize proteins on the body's own nerves. As a result, the immune system attacks the nerves, causing inflammation and damaging the axons and myelin, which can lead to the signs and symptoms of Guillain-Barr syndrome.",Guillain-Barr syndrome,0000443,GHR,https://ghr.nlm.nih.gov/condition/guillain-barre-syndrome,C0039082,T047,Disorders
Is Guillain-Barr syndrome inherited ?,0000443-4,inheritance,"Almost all cases of Guillain-Barr syndrome are sporadic, which means they occur in people with no history of the condition in their family. A few families with more than one affected family member have been described; however, the condition does not have a clear pattern of inheritance. Multiple genetic and environmental factors likely play a part in determining the risk of developing this condition. As a result, inheriting a genetic variation linked with Guillain-Barr syndrome does not mean that a person will develop the condition.",Guillain-Barr syndrome,0000443,GHR,https://ghr.nlm.nih.gov/condition/guillain-barre-syndrome,C0039082,T047,Disorders
What are the treatments for Guillain-Barr syndrome ?,0000443-5,treatment,"These resources address the diagnosis or management of Guillain-Barr syndrome:  - Genetic Testing Registry: Guillain-Barre syndrome, familial  - National Institute of Neurological Disorders and Stroke: Guillain-Barr Syndrome Fact Sheet   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Guillain-Barr syndrome,0000443,GHR,https://ghr.nlm.nih.gov/condition/guillain-barre-syndrome,C0039082,T047,Disorders
What is (are) gyrate atrophy of the choroid and retina ?,0000444-1,information,"Gyrate atrophy of the choroid and retina, which is often shortened to gyrate atrophy, is an inherited disorder characterized by progressive vision loss. People with this disorder have an ongoing loss of cells (atrophy) in the retina, which is the specialized light-sensitive tissue that lines the back of the eye, and in a nearby tissue layer called the choroid. During childhood, they begin experiencing nearsightedness (myopia), difficulty seeing in low light (night blindness), and loss of side (peripheral) vision. Over time, their field of vision continues to narrow, resulting in tunnel vision. Many people with gyrate atrophy also develop clouding of the lens of the eyes (cataracts). These progressive vision changes lead to blindness by about the age of 50.  Most people with gyrate atrophy have no symptoms other than vision loss, but some have additional features of the disorder. Occasionally, newborns with gyrate atrophy develop excess ammonia in the blood (hyperammonemia), which may lead to poor feeding, vomiting, seizures, or coma. Neonatal hyperammonemia associated with gyrate atrophy generally responds quickly to treatment and does not recur after the newborn period.  Gyrate atrophy usually does not affect intelligence; however, abnormalities may be observed in brain imaging or other neurological testing. In some cases, mild to moderate intellectual disability is associated with gyrate atrophy.  Gyrate atrophy may also cause disturbances in the nerves connecting the brain and spinal cord to muscles and sensory cells (peripheral nervous system). In some people with the disorder these abnormalities lead to numbness, tingling, or pain in the hands or feet, while in others they are detectable only by electrical testing of the nerve impulses.  In some people with gyrate atrophy, a particular type of muscle fibers (type II fibers) break down over time. While this muscle abnormality usually causes no symptoms, it may result in mild weakness.",gyrate atrophy of the choroid and retina,0000444,GHR,https://ghr.nlm.nih.gov/condition/gyrate-atrophy-of-the-choroid-and-retina,C0018425,T047,Disorders
How many people are affected by gyrate atrophy of the choroid and retina ?,0000444-2,frequency,More than 150 individuals with gyrate atrophy have been identified; approximately one third are from Finland.,gyrate atrophy of the choroid and retina,0000444,GHR,https://ghr.nlm.nih.gov/condition/gyrate-atrophy-of-the-choroid-and-retina,C0018425,T047,Disorders
What are the genetic changes related to gyrate atrophy of the choroid and retina ?,0000444-3,genetic changes,"Mutations in the OAT gene cause gyrate atrophy. The OAT gene provides instructions for making the enzyme ornithine aminotransferase. This enzyme is active in the energy-producing centers of cells (mitochondria), where it helps break down a molecule called ornithine. Ornithine is involved in the urea cycle, which processes excess nitrogen (in the form of ammonia) that is generated when protein is broken down by the body. In addition to its role in the urea cycle, ornithine participates in several reactions that help ensure the proper balance of protein building blocks (amino acids) in the body. This balance is important because a specific sequence of amino acids is required to build each of the many different proteins needed for the body's functions. The ornithine aminotransferase enzyme helps convert ornithine into another molecule called pyrroline-5-carboxylate (P5C). P5C can be converted into the amino acids glutamate and proline.  OAT gene mutations that cause gyrate atrophy result in a reduced amount of functional ornithine aminotransferase enzyme. A shortage of this enzyme impedes the conversion of ornithine into P5C. As a result, excess ornithine accumulates in the blood (hyperornithinemia), and less P5C than normal is produced. It is not clear how these changes result in the specific signs and symptoms of gyrate atrophy. Researchers have suggested that a deficiency of P5C may interfere with the function of the retina. It has also been proposed that excess ornithine may suppress the production of a molecule called creatine. Creatine is needed for many tissues in the body to store and use energy properly. It is involved in providing energy for muscle contraction, and it is also important in nervous system functioning.",gyrate atrophy of the choroid and retina,0000444,GHR,https://ghr.nlm.nih.gov/condition/gyrate-atrophy-of-the-choroid-and-retina,C0018425,T047,Disorders
Is gyrate atrophy of the choroid and retina inherited ?,0000444-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",gyrate atrophy of the choroid and retina,0000444,GHR,https://ghr.nlm.nih.gov/condition/gyrate-atrophy-of-the-choroid-and-retina,C0018425,T047,Disorders
What are the treatments for gyrate atrophy of the choroid and retina ?,0000444-5,treatment,These resources address the diagnosis or management of gyrate atrophy:  - Baby's First Test  - Genetic Testing Registry: Ornithine aminotransferase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,gyrate atrophy of the choroid and retina,0000444,GHR,https://ghr.nlm.nih.gov/condition/gyrate-atrophy-of-the-choroid-and-retina,C0018425,T047,Disorders
What is (are) Hajdu-Cheney syndrome ?,0000445-1,information,"Hajdu-Cheney syndrome is a rare disorder that can affect many parts of the body, particularly the bones. Loss of bone tissue from the hands and feet (acro-osteolysis) is a characteristic feature of the condition. The fingers and toes are short and broad, and they may become shorter over time as bone at the tips continues to break down. Bone loss in the fingers can interfere with fine motor skills, such as picking up small objects.  Bone abnormalities throughout the body are common in Hajdu-Cheney syndrome. Affected individuals develop osteoporosis, which causes the bones to be brittle and prone to fracture. Many affected individuals experience breakage (compression fractures) of the spinal bones (vertebrae). Some also develop abnormal curvature of the spine (scoliosis or kyphosis). Hajdu-Cheney syndrome also affects the shape and strength of the long bones in the arms and legs. The abnormalities associated with this condition lead to short stature.  Hajdu-Cheney syndrome also causes abnormalities of the skull bones, including the bones of the face. The shape of the skull is often described as dolichocephalic, which means it is elongated from back to front. In many affected individuals, the bone at the back of the skull bulges outward, causing a bump called a prominent occiput. Distinctive facial features associated with this condition include widely spaced and downward-slanting eyes, eyebrows that grow together in the middle (synophrys), low-set ears, a sunken appearance of the middle of the face (midface hypoplasia), and a large space between the nose and upper lip (a long philtrum). Some affected children are born with an opening in the roof of the mouth called a cleft palate or with a high arched palate. In affected adults, the facial features are often described as ""coarse.""  Other features of Hajdu-Cheney syndrome found in some affected individuals include joint abnormalities, particularly an unusually large range of joint movement (hypermobility); dental problems; hearing loss; a deep, gravelly voice; excess body hair; recurrent infections in childhood; heart defects; and kidney abnormalities such as the growth of multiple fluid-filled cysts (polycystic kidneys). Some people with this condition have delayed development in childhood, but the delays are usually mild.  The most serious complications of Hajdu-Cheney syndrome, which occur in about half of all affected individuals, are abnormalities known as platybasia and basilar invagination. Platybasia is a flattening of the base of the skull caused by thinning and softening of the skull bones. Basilar invagination occurs when the softened bones allow part of the spine to protrude abnormally through the opening at the bottom of the skull, pushing into the lower parts of the brain. These abnormalities can lead to severe neurological problems, including headaches, abnormal vision and balance, a buildup of fluid in the brain (hydrocephalus), abnormal breathing, and sudden death.  The signs and symptoms of Hajdu-Cheney syndrome vary greatly among affected individuals, even among members of the same family. Many of the disorder's features, such as acro-osteolysis and some of the characteristic facial features, are not present at birth but become apparent in childhood or later. The risk of developing platybasia and basilar invagination also increases over time.  The features of Hajdu-Cheney syndrome overlap significantly with those of a condition called serpentine fibula-polycystic kidney syndrome (SFPKS). Although they used to be considered separate disorders, researchers discovered that the two conditions are associated with mutations in the same gene. Based on these similarities, many researchers now consider Hajdu-Cheney syndrome and SFPKS to be variants of the same condition.",Hajdu-Cheney syndrome,0000445,GHR,https://ghr.nlm.nih.gov/condition/hajdu-cheney-syndrome,C0917715,T019,Disorders
How many people are affected by Hajdu-Cheney syndrome ?,0000445-2,frequency,Hajdu-Cheney syndrome is a rare disease; its prevalence is unknown. Fewer than 100 affected individuals have been described in the medical literature.,Hajdu-Cheney syndrome,0000445,GHR,https://ghr.nlm.nih.gov/condition/hajdu-cheney-syndrome,C0917715,T019,Disorders
What are the genetic changes related to Hajdu-Cheney syndrome ?,0000445-3,genetic changes,"Hajdu-Cheney syndrome is associated with mutations in the NOTCH2 gene. This gene provides instructions for making a receptor called Notch2. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. When a ligand binds to the Notch2 receptor, it triggers signals that are important for the normal development and function of many different types of cells. Studies suggest that signaling through the Notch2 receptor is important for the early development of bones and later for bone remodeling, a normal process in which old bone is removed and new bone is created to replace it. Notch2 signaling also appears to be involved in the development of the heart, kidneys, teeth, and other parts of the body.  Mutations in a specific area near the end of the NOTCH2 gene are associated with Hajdu-Cheney syndrome. These mutations lead to a version of the Notch2 receptor that cannot be broken down normally. As a result, the receptor continues to be active even after signaling should stop. Researchers are unsure how excessive Notch2 signaling is related to the varied features of Hajdu-Cheney syndrome. They suspect that the skeletal features of the disorder, including acro-osteolysis, osteoporosis, and distinctive facial features, likely result from abnormal bone development and remodeling. Excess signaling through the overactive Notch2 receptor may increase the removal of old bone, reduce the formation of new bone, or both. It is less clear how the overactive receptor contributes to the other signs and symptoms of this condition.",Hajdu-Cheney syndrome,0000445,GHR,https://ghr.nlm.nih.gov/condition/hajdu-cheney-syndrome,C0917715,T019,Disorders
Is Hajdu-Cheney syndrome inherited ?,0000445-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered NOTCH2 gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family. Less commonly, an affected person inherits the mutation from one affected parent.",Hajdu-Cheney syndrome,0000445,GHR,https://ghr.nlm.nih.gov/condition/hajdu-cheney-syndrome,C0917715,T019,Disorders
What are the treatments for Hajdu-Cheney syndrome ?,0000445-5,treatment,These resources address the diagnosis or management of Hajdu-Cheney syndrome:  - Genetic Testing Registry: Hajdu-Cheney syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Hajdu-Cheney syndrome,0000445,GHR,https://ghr.nlm.nih.gov/condition/hajdu-cheney-syndrome,C0917715,T019,Disorders
What is (are) hand-foot-genital syndrome ?,0000446-1,information,"Hand-foot-genital syndrome is a rare condition that affects the development of the hands and feet, the urinary tract, and the reproductive system. People with this condition have abnormally short thumbs and first (big) toes, small fifth fingers that curve inward (clinodactyly), short feet, and fusion or delayed hardening of bones in the wrists and ankles. The other bones in the arms and legs are normal.  Abnormalities of the genitals and urinary tract can vary among affected individuals. Many people with hand-foot-genital syndrome have defects in the ureters, which are tubes that carry urine from each kidney to the bladder, or in the urethra, which carries urine from the bladder to the outside of the body. Recurrent urinary tract infections and an inability to control the flow of urine (urinary incontinence) have been reported. About half of males with this disorder have the urethra opening on the underside of the penis (hypospadias).  People with hand-foot-genital syndrome are usually able to have children (fertile). In some affected females, problems in the early development of the uterus can later increase the risk of pregnancy loss, premature labor, and stillbirth.",hand-foot-genital syndrome,0000446,GHR,https://ghr.nlm.nih.gov/condition/hand-foot-genital-syndrome,C1841679,T047,Disorders
How many people are affected by hand-foot-genital syndrome ?,0000446-2,frequency,Hand-foot-genital syndrome is very rare; only a few families with the condition have been reported worldwide.,hand-foot-genital syndrome,0000446,GHR,https://ghr.nlm.nih.gov/condition/hand-foot-genital-syndrome,C1841679,T047,Disorders
What are the genetic changes related to hand-foot-genital syndrome ?,0000446-3,genetic changes,"Mutations in the HOXA13 gene cause hand-foot-genital syndrome. The HOXA13 gene provides instructions for producing a protein that plays an important role in development before birth. Specifically, this protein appears to be critical for the formation and development of the limbs (particularly the hands and feet), urinary tract, and reproductive system. Mutations in the HOXA13 gene cause the characteristic features of hand-foot-genital syndrome by disrupting the early development of these structures. Some mutations in the HOXA13 gene result in the production of a nonfunctional version of the HOXA13 protein. Other mutations alter the protein's structure and interfere with its normal function within cells. Mutations that result in an altered but functional HOXA13 protein may cause more severe signs and symptoms than mutations that lead to a nonfunctional HOXA13 protein.",hand-foot-genital syndrome,0000446,GHR,https://ghr.nlm.nih.gov/condition/hand-foot-genital-syndrome,C1841679,T047,Disorders
Is hand-foot-genital syndrome inherited ?,0000446-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",hand-foot-genital syndrome,0000446,GHR,https://ghr.nlm.nih.gov/condition/hand-foot-genital-syndrome,C1841679,T047,Disorders
What are the treatments for hand-foot-genital syndrome ?,0000446-5,treatment,These resources address the diagnosis or management of hand-foot-genital syndrome:  - Gene Review: Gene Review: Hand-Foot-Genital Syndrome  - Genetic Testing Registry: Hand foot uterus syndrome  - MedlinePlus Encyclopedia: Hypospadias  - MedlinePlus Encyclopedia: Urinary Tract Infection   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hand-foot-genital syndrome,0000446,GHR,https://ghr.nlm.nih.gov/condition/hand-foot-genital-syndrome,C1841679,T047,Disorders
What is (are) harlequin ichthyosis ?,0000447-1,information,"Harlequin ichthyosis is a severe genetic disorder that mainly affects the skin. Infants with this condition are born with very hard, thick skin covering most of their bodies. The skin forms large, diamond-shaped plates that are separated by deep cracks (fissures). These skin abnormalities affect the shape of the eyelids, nose, mouth, and ears, and limit movement of the arms and legs. Restricted movement of the chest can lead to breathing difficulties and respiratory failure.  The skin normally forms a protective barrier between the body and its surrounding environment. The skin abnormalities associated with harlequin ichthyosis disrupt this barrier, making it more difficult for affected infants to control water loss, regulate their body temperature, and fight infections. Infants with harlequin ichthyosis often experience an excessive loss of fluids (dehydration) and develop life-threatening infections in the first few weeks of life. It used to be very rare for affected infants to survive the newborn period. However, with intensive medical support and improved treatment, people with this disorder now have a better chance of living into childhood and adolescence.",harlequin ichthyosis,0000447,GHR,https://ghr.nlm.nih.gov/condition/harlequin-ichthyosis,C0239849,T019,Disorders
How many people are affected by harlequin ichthyosis ?,0000447-2,frequency,Harlequin ichthyosis is very rare; its exact incidence is unknown.,harlequin ichthyosis,0000447,GHR,https://ghr.nlm.nih.gov/condition/harlequin-ichthyosis,C0239849,T019,Disorders
What are the genetic changes related to harlequin ichthyosis ?,0000447-3,genetic changes,"Mutations in the ABCA12 gene cause harlequin ichthyosis. The ABCA12 gene provides instructions for making a protein that is essential for the normal development of skin cells. This protein plays a major role in the transport of fats (lipids) in the outermost layer of skin (the epidermis). Some mutations in the ABCA12 gene prevent the cell from making any ABCA12 protein. Other mutations lead to the production of an abnormally small version of the protein that cannot transport lipids properly. A loss of functional ABCA12 protein disrupts the normal development of the epidermis, resulting in the hard, thick scales characteristic of harlequin ichthyosis.",harlequin ichthyosis,0000447,GHR,https://ghr.nlm.nih.gov/condition/harlequin-ichthyosis,C0239849,T019,Disorders
Is harlequin ichthyosis inherited ?,0000447-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",harlequin ichthyosis,0000447,GHR,https://ghr.nlm.nih.gov/condition/harlequin-ichthyosis,C0239849,T019,Disorders
What are the treatments for harlequin ichthyosis ?,0000447-5,treatment,These resources address the diagnosis or management of harlequin ichthyosis:  - Gene Review: Gene Review: Autosomal Recessive Congenital Ichthyosis  - Genetic Testing Registry: Autosomal recessive congenital ichthyosis 4B   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,harlequin ichthyosis,0000447,GHR,https://ghr.nlm.nih.gov/condition/harlequin-ichthyosis,C0239849,T019,Disorders
What is (are) Hashimoto thyroiditis ?,0000448-1,information,"Hashimoto thyroiditis is a condition that affects the function of the thyroid, which is a butterfly-shaped gland in the lower neck. The thyroid makes hormones that help regulate a wide variety of critical body functions. For example, thyroid hormones influence growth and development, body temperature, heart rate, menstrual cycles, and weight. Hashimoto thyroiditis is a form of chronic inflammation that can damage the thyroid, reducing its ability to produce hormones.  One of the first signs of Hashimoto thyroiditis is an enlargement of the thyroid called a goiter. Depending on its size, the enlarged thyroid can cause the neck to look swollen and may interfere with breathing and swallowing. As damage to the thyroid continues, the gland can shrink over a period of years and the goiter may eventually disappear.  Other signs and symptoms resulting from an underactive thyroid can include excessive tiredness (fatigue), weight gain or difficulty losing weight, hair that is thin and dry, a slow heart rate, joint or muscle pain, and constipation. People with this condition may also have a pale, puffy face and feel cold even when others around them are warm. Affected women can have heavy or irregular menstrual periods and difficulty conceiving a child (impaired fertility). Difficulty concentrating and depression can also be signs of a shortage of thyroid hormones.  Hashimoto thyroiditis usually appears in mid-adulthood, although it can occur earlier or later in life. Its signs and symptoms tend to develop gradually over months or years.",Hashimoto thyroiditis,0000448,GHR,https://ghr.nlm.nih.gov/condition/hashimoto-thyroiditis,C0040147,T047,Disorders
How many people are affected by Hashimoto thyroiditis ?,0000448-2,frequency,"Hashimoto thyroiditis affects 1 to 2 percent of people in the United States. It occurs more often in women than in men, which may be related to hormonal factors. The condition is the most common cause of thyroid underactivity (hypothyroidism) in the United States.",Hashimoto thyroiditis,0000448,GHR,https://ghr.nlm.nih.gov/condition/hashimoto-thyroiditis,C0040147,T047,Disorders
What are the genetic changes related to Hashimoto thyroiditis ?,0000448-3,genetic changes,"Hashimoto thyroiditis is thought to result from a combination of genetic and environmental factors. Some of these factors have been identified, but many remain unknown.  Hashimoto thyroiditis is classified as an autoimmune disorder, one of a large group of conditions that occur when the immune system attacks the body's own tissues and organs. In people with Hashimoto thyroiditis, white blood cells called lymphocytes accumulate abnormally in the thyroid, which can damage it. The lymphocytes make immune system proteins called antibodies that attack and destroy thyroid cells. When too many thyroid cells become damaged or die, the thyroid can no longer make enough hormones to regulate body functions. This shortage of thyroid hormones underlies the signs and symptoms of Hashimoto thyroiditis. However, some people with thyroid antibodies never develop hypothyroidism or experience any related signs or symptoms.  People with Hashimoto thyroiditis have an increased risk of developing other autoimmune disorders, including vitiligo, rheumatoid arthritis, Addison disease, type 1 diabetes, multiple sclerosis, and pernicious anemia.  Variations in several genes have been studied as possible risk factors for Hashimoto thyroiditis. Some of these genes are part of a family called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Other genes that have been associated with Hashimoto thyroiditis help regulate the immune system or are involved in normal thyroid function. Most of the genetic variations that have been discovered are thought to have a small impact on a person's overall risk of developing this condition.  Other, nongenetic factors also play a role in Hashimoto thyroiditis. These factors may trigger the condition in people who are at risk, although the mechanism is unclear. Potential triggers include changes in sex hormones (particularly in women), viral infections, certain medications, exposure to ionizing radiation, and excess consumption of iodine (a substance involved in thyroid hormone production).",Hashimoto thyroiditis,0000448,GHR,https://ghr.nlm.nih.gov/condition/hashimoto-thyroiditis,C0040147,T047,Disorders
Is Hashimoto thyroiditis inherited ?,0000448-4,inheritance,"The inheritance pattern of Hashimoto thyroiditis is unclear because many genetic and environmental factors appear to be involved. However, the condition can cluster in families, and having a close relative with Hashimoto thyroiditis or another autoimmune disorder likely increases a person's risk of developing the condition.",Hashimoto thyroiditis,0000448,GHR,https://ghr.nlm.nih.gov/condition/hashimoto-thyroiditis,C0040147,T047,Disorders
What are the treatments for Hashimoto thyroiditis ?,0000448-5,treatment,These resources address the diagnosis or management of Hashimoto thyroiditis:  - American Thyroid Association: Thyroid Function Tests  - Genetic Testing Registry: Hashimoto thyroiditis  - National Institute of Diabetes and Digestive and Kidney Diseases: Thyroid Function Tests   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Hashimoto thyroiditis,0000448,GHR,https://ghr.nlm.nih.gov/condition/hashimoto-thyroiditis,C0040147,T047,Disorders
What is (are) head and neck squamous cell carcinoma ?,0000449-1,information,"Squamous cell carcinoma is a cancer that arises from particular cells called squamous cells. Squamous cells are found in the outer layer of skin and in the mucous membranes, which are the moist tissues that line body cavities such as the airways and intestines. Head and neck squamous cell carcinoma (HNSCC) develops in the mucous membranes of the mouth, nose, and throat.  HNSCC is classified by its location: it can occur in the mouth (oral cavity), the middle part of the throat near the mouth (oropharynx), the space behind the nose (nasal cavity and paranasal sinuses), the upper part of the throat near the nasal cavity (nasopharynx), the voicebox (larynx), or the lower part of the throat near the larynx (hypopharynx). Depending on the location, the cancer can cause abnormal patches or open sores (ulcers) in the mouth and throat, unusual bleeding or pain in the mouth, sinus congestion that does not clear, sore throat, earache, pain when swallowing or difficulty swallowing, a hoarse voice, difficulty breathing, or enlarged lymph nodes.  HNSCC can spread (metastasize) to other parts of the body, such as the lymph nodes or lungs. If it spreads, the cancer has a worse prognosis and can be fatal. About half of affected individuals survive more than five years after diagnosis.",head and neck squamous cell carcinoma,0000449,GHR,https://ghr.nlm.nih.gov/condition/head-and-neck-squamous-cell-carcinoma,C0007137,T191,Disorders
How many people are affected by head and neck squamous cell carcinoma ?,0000449-2,frequency,"HNSCC is the seventh most common cancer worldwide. Approximately 600,000 new cases are diagnosed each year, including about 50,000 in the United States. HNSCC occurs most often in men in their 50s or 60s, although the incidence among younger individuals is increasing.",head and neck squamous cell carcinoma,0000449,GHR,https://ghr.nlm.nih.gov/condition/head-and-neck-squamous-cell-carcinoma,C0007137,T191,Disorders
What are the genetic changes related to head and neck squamous cell carcinoma ?,0000449-3,genetic changes,"HNSCC is caused by a variety of factors that can alter the DNA in cells. The strongest risk factors for developing this form of cancer are tobacco use (including smoking or using chewing tobacco) and heavy alcohol consumption. In addition, studies have shown that infection with certain strains of human papillomavirus (HPV) is linked to the development of HNSCC. HPV infection accounts for the increasing incidence of HNSCC in younger people.  Researchers have identified mutations in many genes in people with HNSCC; however, it is not yet clear what role most of these mutations play in the development or progression of cancer. The proteins produced from several of the genes associated with HNSCC, including TP53, NOTCH1, and CDKN2A, function as tumor suppressors, which means they normally keep cells from growing and dividing too rapidly or in an uncontrolled way. When tumor suppressors are impaired, cells can grow and divide without control, leading to tumor formation. It is likely that a series of changes in multiple genes is involved in the development and progression of HNSCC.",head and neck squamous cell carcinoma,0000449,GHR,https://ghr.nlm.nih.gov/condition/head-and-neck-squamous-cell-carcinoma,C0007137,T191,Disorders
Is head and neck squamous cell carcinoma inherited ?,0000449-4,inheritance,"HNSCC is generally not inherited; it typically arises from mutations in the body's cells that occur during an individual's lifetime. This type of alteration is called a somatic mutation.  Rarely, HNSCC is found in several members of a family. These families have inherited disorders that increase the risk of multiple types of cancer.",head and neck squamous cell carcinoma,0000449,GHR,https://ghr.nlm.nih.gov/condition/head-and-neck-squamous-cell-carcinoma,C0007137,T191,Disorders
What are the treatments for head and neck squamous cell carcinoma ?,0000449-5,treatment,These resources address the diagnosis or management of head and neck squamous cell carcinoma:  - Cancer.Net: Head and Neck Cancer: Treatment Options  - National Cancer Institute: Head and Neck Cancers   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,head and neck squamous cell carcinoma,0000449,GHR,https://ghr.nlm.nih.gov/condition/head-and-neck-squamous-cell-carcinoma,C0007137,T191,Disorders
What is (are) hemophilia ?,0000450-1,information,"Hemophilia is a bleeding disorder that slows the blood clotting process. People with this condition experience prolonged bleeding or oozing following an injury, surgery, or having a tooth pulled. In severe cases of hemophilia, continuous bleeding occurs after minor trauma or even in the absence of injury (spontaneous bleeding). Serious complications can result from bleeding into the joints, muscles, brain, or other internal organs. Milder forms of hemophilia do not necessarily involve spontaneous bleeding, and the condition may not become apparent until abnormal bleeding occurs following surgery or a serious injury.  The major types of this condition are hemophilia A (also known as classic hemophilia or factor VIII deficiency) and hemophilia B (also known as Christmas disease or factor IX deficiency). Although the two types have very similar signs and symptoms, they are caused by mutations in different genes. People with an unusual form of hemophilia B, known as hemophilia B Leyden, experience episodes of excessive bleeding in childhood but have few bleeding problems after puberty.",hemophilia,0000450,GHR,https://ghr.nlm.nih.gov/condition/hemophilia,C0684275,T047,Disorders
How many people are affected by hemophilia ?,0000450-2,frequency,"The two major forms of hemophilia occur much more commonly in males than in females. Hemophilia A is the most common type of the condition; 1 in 4,000 to 1 in 5,000 males worldwide are born with this disorder. Hemophilia B occurs in approximately 1 in 20,000 newborn males worldwide.",hemophilia,0000450,GHR,https://ghr.nlm.nih.gov/condition/hemophilia,C0684275,T047,Disorders
What are the genetic changes related to hemophilia ?,0000450-3,genetic changes,"Changes in the F8 gene are responsible for hemophilia A, while mutations in the F9 gene cause hemophilia B. The F8 gene provides instructions for making a protein called coagulation factor VIII. A related protein, coagulation factor IX, is produced from the F9 gene. Coagulation factors are proteins that work together in the blood clotting process. After an injury, blood clots protect the body by sealing off damaged blood vessels and preventing excessive blood loss.  Mutations in the F8 or F9 gene lead to the production of an abnormal version of coagulation factor VIII or coagulation factor IX, or reduce the amount of one of these proteins. The altered or missing protein cannot participate effectively in the blood clotting process. As a result, blood clots cannot form properly in response to injury. These problems with blood clotting lead to continuous bleeding that can be difficult to control. The mutations that cause severe hemophilia almost completely eliminate the activity of coagulation factor VIII or coagulation factor IX. The mutations responsible for mild and moderate hemophilia reduce but do not eliminate the activity of one of these proteins.  Another form of the disorder, known as acquired hemophilia, is not caused by inherited gene mutations. This rare condition is characterized by abnormal bleeding into the skin, muscles, or other soft tissues, usually beginning in adulthood. Acquired hemophilia results when the body makes specialized proteins called autoantibodies that attack and disable coagulation factor VIII. The production of autoantibodies is sometimes associated with pregnancy, immune system disorders, cancer, or allergic reactions to certain drugs. In about half of cases, the cause of acquired hemophilia is unknown.",hemophilia,0000450,GHR,https://ghr.nlm.nih.gov/condition/hemophilia,C0684275,T047,Disorders
Is hemophilia inherited ?,0000450-4,inheritance,"Hemophilia A and hemophilia B are inherited in an X-linked recessive pattern. The genes associated with these conditions are located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, it is very rare for females to have hemophilia. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In X-linked recessive inheritance, a female with one altered copy of the gene in each cell is called a carrier. Carrier females have about half the usual amount of coagulation factor VIII or coagulation factor IX, which is generally enough for normal blood clotting. However, about 10 percent of carrier females have less than half the normal amount of one of these coagulation factors; these individuals are at risk for abnormal bleeding, particularly after an injury, surgery, or tooth extraction.",hemophilia,0000450,GHR,https://ghr.nlm.nih.gov/condition/hemophilia,C0684275,T047,Disorders
What are the treatments for hemophilia ?,0000450-5,treatment,"These resources address the diagnosis or management of hemophilia:  - Gene Review: Gene Review: Hemophilia A  - Gene Review: Gene Review: Hemophilia B  - Genetic Testing Registry: HEMOPHILIA B(M)  - Genetic Testing Registry: Hemophilia  - Genetic Testing Registry: Hereditary factor IX deficiency disease  - Genetic Testing Registry: Hereditary factor VIII deficiency disease  - Genomics Education Programme (UK): Haemophilia A  - MedlinePlus Encyclopedia: Factor IX Assay  - MedlinePlus Encyclopedia: Factor VIII Assay  - MedlinePlus Encyclopedia: Hemophilia A  - MedlinePlus Encyclopedia: Hemophilia B  - National Heart, Lung, and Blood Institute: How is Hemophilia Diagnosed?  - National Heart, Lung, and Blood Institute: How is Hemophilia Treated?  - National Hemophilia Foundation: Hemophilia Treatment Centers   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",hemophilia,0000450,GHR,https://ghr.nlm.nih.gov/condition/hemophilia,C0684275,T047,Disorders
What is (are) Hennekam syndrome ?,0000451-1,information,"Hennekam syndrome is an inherited disorder resulting from malformation of the lymphatic system, which is part of both the circulatory system and immune system. The lymphatic system consists of a network of vessels that transport lymph fluid and immune cells throughout the body.  The characteristic signs and symptoms of Hennekam syndrome are lymphatic vessels that are abnormally expanded (lymphangiectasia), particularly the vessels that transport lymph fluid to and from the intestines; puffiness or swelling caused by a buildup of fluid (lymphedema); and unusual facial features.  Lymphangiectasia often impedes the flow of lymph fluid and can cause the affected vessels to break open (rupture). In the intestines, ruptured vessels can lead to accumulation of lymph fluid, which interferes with the absorption of nutrients, fats, and proteins. Accumulation of lymph fluid in the abdomen can cause swelling (chylous ascites). Lymphangiectasia can also affect the kidneys, thyroid gland, the outer covering of the lungs (the pleura), the membrane covering the heart (pericardium), or the skin.  The lymphedema in Hennekam syndrome is often noticeable at birth and usually affects the face and limbs. Severely affected infants may have extensive swelling caused by fluid accumulation before birth (hydrops fetalis). The lymphedema usually affects one side of the body more severely than the other (asymmetric) and slowly worsens over time.  Facial features of people with Hennekam syndrome may include a flattened appearance to the middle of the face and the bridge of the nose, puffy eyelids, widely spaced eyes (hypertelorism), small ears, and a small mouth with overgrowth of the gums (gingival hypertrophy). Affected individuals may also have an unusually small head (microcephaly) and premature fusion of the skull bones (craniosynostosis).  Individuals with Hennekam syndrome often have intellectual disability that ranges from mild to severe, although most are on the mild end of the range and some have normal intellect. Many individuals with Hennekam syndrome have growth delay, respiratory problems, permanently bent fingers and toes (camptodactyly), or fusion of the skin between the fingers and toes (cutaneous syndactyly).  Abnormalities found in a few individuals with Hennekam syndrome include a moderate to severe shortage of red blood cells (anemia) resulting from an inadequate amount (deficiency) of iron in the bloodstream, multiple spleens (polysplenia), misplaced kidneys, genital anomalies, a soft out-pouching around the belly-button (umbilical hernia), heart abnormalities, hearing loss, excessive body hair growth (hirsutism), a narrow upper chest that may have a sunken appearance (pectus excavatum), an abnormal side-to-side curvature of the spine (scoliosis), and inward- and upward-turning feet (clubfeet).  The signs and symptoms of Hennekam syndrome vary widely among affected individuals, even those within the same family. Life expectancy depends on the severity of the condition and can vary from death in childhood to survival into adulthood.",Hennekam syndrome,0000451,GHR,https://ghr.nlm.nih.gov/condition/hennekam-syndrome,C0795972,T047,Disorders
How many people are affected by Hennekam syndrome ?,0000451-2,frequency,At least 50 cases of Hennekam syndrome have been reported worldwide.,Hennekam syndrome,0000451,GHR,https://ghr.nlm.nih.gov/condition/hennekam-syndrome,C0795972,T047,Disorders
What are the genetic changes related to Hennekam syndrome ?,0000451-3,genetic changes,"Mutations in the CCBE1 or FAT4 gene can cause Hennekam syndrome.  The CCBE1 gene provides instructions for making a protein that is found in the lattice of proteins and other molecules outside the cell (extracellular matrix). The CCBE1 protein is involved in the maturation (differentiation) and movement (migration) of immature cells called lymphangioblasts that will eventually form the lining (epithelium) of lymphatic vessels.  The function of the protein produced from the FAT4 gene is largely unknown. Research shows that the FAT4 protein may be involved in determining the position of various components within cells (cell polarity).  CCBE1 gene mutations that cause Hennekam syndrome change the three-dimensional shape of the protein and severely decrease its function. The abnormal protein cannot play its role in the formation of the lymphatic vessel epithelium. The resulting malformation of lymphatic vessels leads to lymphangiectasia, lymphedema, and other features of Hennekam syndrome. Since the lymphatic system extends throughout the body, a disruption to the vessels can affect almost any organ. Altered lymphatic development before birth may change the balance of fluids and impair normal development, contributing to many of the other signs of Hennekam syndrome such as unusual facial features.  FAT4 gene mutations that cause Hennekam syndrome result in a FAT4 protein with decreased function. Reduced FAT4 protein activity seems to impair normal development of the lymphatic system, but the mechanism is unknown.  Together, mutations in the CCBE1 and FAT4 genes are responsible for approximately half of all Hennekam syndrome cases. The cause of the remaining cases is unknown.",Hennekam syndrome,0000451,GHR,https://ghr.nlm.nih.gov/condition/hennekam-syndrome,C0795972,T047,Disorders
Is Hennekam syndrome inherited ?,0000451-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Hennekam syndrome,0000451,GHR,https://ghr.nlm.nih.gov/condition/hennekam-syndrome,C0795972,T047,Disorders
What are the treatments for Hennekam syndrome ?,0000451-5,treatment,These resources address the diagnosis or management of Hennekam syndrome:  - Great Ormond Street Hospital for Children (UK): Primary Intestinal Lymphangiectasia Information  - Johns Hopkins Medicine: Lymphedema Management  - VascularWeb: Lymphedema   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Hennekam syndrome,0000451,GHR,https://ghr.nlm.nih.gov/condition/hennekam-syndrome,C0795972,T047,Disorders
What is (are) hepatic lipase deficiency ?,0000452-1,information,"Hepatic lipase deficiency is a disorder that affects the body's ability to break down fats (lipids). People with this disorder have increased amounts of certain fats, known as triglycerides and cholesterol, in the blood. These individuals also have increased amounts of molecules known as high-density lipoproteins (HDLs) and decreased amounts of molecules called low-density lipoproteins (LDL). These molecules transport triglycerides and cholesterol throughout the body. In people with hepatic lipase deficiency, the LDL molecules are often abnormally large.  Normally, high levels of HDL (known as ""good cholesterol"") and low levels of LDL (known as ""bad cholesterol"") are protective against an accumulation of fatty deposits on the artery walls (atherosclerosis) and heart disease. However, some individuals with hepatic lipase deficiency, who have this imbalance of HDL and LDL, develop atherosclerosis and heart disease in mid-adulthood, while others do not. It is unknown whether people with hepatic lipase deficiency have a greater risk of developing atherosclerosis or heart disease than individuals in the general population. Similarly, it is unclear how increased blood triglycerides and cholesterol levels affect the risk of atherosclerosis and heart disease in people with hepatic lipase deficiency.",hepatic lipase deficiency,0000452,GHR,https://ghr.nlm.nih.gov/condition/hepatic-lipase-deficiency,C3151466,T047,Disorders
How many people are affected by hepatic lipase deficiency ?,0000452-2,frequency,Hepatic lipase deficiency is likely a rare disorder; only a few affected families have been reported in the scientific literature.,hepatic lipase deficiency,0000452,GHR,https://ghr.nlm.nih.gov/condition/hepatic-lipase-deficiency,C3151466,T047,Disorders
What are the genetic changes related to hepatic lipase deficiency ?,0000452-3,genetic changes,"Hepatic lipase deficiency is caused by mutations in the LIPC gene. This gene provides instructions for making an enzyme called hepatic lipase. This enzyme is produced by liver cells and released into the bloodstream where it helps convert very low-density lipoproteins (VLDLs) and intermediate-density lipoproteins (IDLs) to LDLs. The enzyme also assists in transporting HDLs that carry cholesterol and triglycerides from the blood to the liver, where the HDLs deposit these fats so they can be redistributed to other tissues or removed from the body.  LIPC gene mutations prevent the release of hepatic lipase from the liver or decrease the enzyme's activity in the bloodstream. As a result, VLDLs and IDLs are not efficiently converted into LDLs, and HDLs carrying cholesterol and triglycerides remain in the bloodstream. It is unclear what effect this change in lipid levels has on people with hepatic lipase deficiency.",hepatic lipase deficiency,0000452,GHR,https://ghr.nlm.nih.gov/condition/hepatic-lipase-deficiency,C3151466,T047,Disorders
Is hepatic lipase deficiency inherited ?,0000452-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",hepatic lipase deficiency,0000452,GHR,https://ghr.nlm.nih.gov/condition/hepatic-lipase-deficiency,C3151466,T047,Disorders
What are the treatments for hepatic lipase deficiency ?,0000452-5,treatment,These resources address the diagnosis or management of hepatic lipase deficiency:  - Genetic Testing Registry: Hepatic lipase deficiency  - MedlinePlus Encyclopedia: Cholesterol Testing and Results  - MedlinePlus Encyclopedia: Triglyceride Level   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hepatic lipase deficiency,0000452,GHR,https://ghr.nlm.nih.gov/condition/hepatic-lipase-deficiency,C3151466,T047,Disorders
What is (are) hepatic veno-occlusive disease with immunodeficiency ?,0000453-1,information,"Hepatic veno-occlusive disease with immunodeficiency (also called VODI) is a hereditary disorder of the liver and immune system. Its signs and symptoms appear after the first few months of life.  Hepatic veno-occlusive disease is a condition that blocks (occludes) small veins in the liver, disrupting blood flow in this organ. This condition can lead to enlargement of the liver (hepatomegaly), a buildup of scar tissue (hepatic fibrosis), and liver failure.  Children with VODI are prone to recurrent infections caused by certain bacteria, viruses, and fungi. The organisms that cause infection in people with this disorder are described as opportunistic because they ordinarily do not cause illness in healthy people. These infections are usually serious and may be life-threatening. In most people with VODI, infections occur before hepatic veno-occlusive disease becomes evident.  Many people with VODI live only into childhood, although some affected individuals have lived to early adulthood.",hepatic veno-occlusive disease with immunodeficiency,0000453,GHR,https://ghr.nlm.nih.gov/condition/hepatic-veno-occlusive-disease-with-immunodeficiency,C1856128,T047,Disorders
How many people are affected by hepatic veno-occlusive disease with immunodeficiency ?,0000453-2,frequency,"VODI appears to be a rare disorder; approximately 20 affected families have been reported worldwide. Most people diagnosed with the condition have been of Lebanese ancestry. However, the disorder has also been identified in several individuals with other backgrounds in the United States and Italy.",hepatic veno-occlusive disease with immunodeficiency,0000453,GHR,https://ghr.nlm.nih.gov/condition/hepatic-veno-occlusive-disease-with-immunodeficiency,C1856128,T047,Disorders
What are the genetic changes related to hepatic veno-occlusive disease with immunodeficiency ?,0000453-3,genetic changes,"VODI results from mutations in the SP110 gene. This gene provides instructions for making a protein called SP110 nuclear body protein, which is involved in the normal function of the immune system. This protein likely helps regulate the activity of genes needed for the body's immune response to foreign invaders (such as viruses and bacteria).  Mutations in the SP110 gene prevent cells from making functional SP110 nuclear body protein, which impairs the immune system's ability to fight off infections. It is unclear how a lack of this protein affects blood flow in the liver.",hepatic veno-occlusive disease with immunodeficiency,0000453,GHR,https://ghr.nlm.nih.gov/condition/hepatic-veno-occlusive-disease-with-immunodeficiency,C1856128,T047,Disorders
Is hepatic veno-occlusive disease with immunodeficiency inherited ?,0000453-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",hepatic veno-occlusive disease with immunodeficiency,0000453,GHR,https://ghr.nlm.nih.gov/condition/hepatic-veno-occlusive-disease-with-immunodeficiency,C1856128,T047,Disorders
What are the treatments for hepatic veno-occlusive disease with immunodeficiency ?,0000453-5,treatment,These resources address the diagnosis or management of VODI:  - Gene Review: Gene Review: Hepatic Veno-Occlusive Disease with Immunodeficiency  - Genetic Testing Registry: Hepatic venoocclusive disease with immunodeficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hepatic veno-occlusive disease with immunodeficiency,0000453,GHR,https://ghr.nlm.nih.gov/condition/hepatic-veno-occlusive-disease-with-immunodeficiency,C1856128,T047,Disorders
What is (are) hereditary angioedema ?,0000454-1,information,"Hereditary angioedema is a disorder characterized by recurrent episodes of severe swelling (angioedema). The most common areas of the body to develop swelling are the limbs, face, intestinal tract, and airway. Minor trauma or stress may trigger an attack, but swelling often occurs without a known trigger. Episodes involving the intestinal tract cause severe abdominal pain, nausea, and vomiting. Swelling in the airway can restrict breathing and lead to life-threatening obstruction of the airway. About one-third of people with this condition develop a non-itchy rash called erythema marginatum during an attack.  Symptoms of hereditary angioedema typically begin in childhood and worsen during puberty. On average, untreated individuals have an attack every 1 to 2 weeks, and most episodes last for about 3 to 4 days. The frequency and duration of attacks vary greatly among people with hereditary angioedema, even among people in the same family.  There are three types of hereditary angioedema, called types I, II, and III, which can be distinguished by their underlying causes and levels of a protein called C1 inhibitor in the blood. The different types have similar signs and symptoms. Type III was originally thought to occur only in women, but families with affected males have been identified.",hereditary angioedema,0000454,GHR,https://ghr.nlm.nih.gov/condition/hereditary-angioedema,C0002994,T046,Disorders
How many people are affected by hereditary angioedema ?,0000454-2,frequency,"Hereditary angioedema is estimated to affect 1 in 50,000 people. Type I is the most common, accounting for 85 percent of cases. Type II occurs in 15 percent of cases, and type III is very rare.",hereditary angioedema,0000454,GHR,https://ghr.nlm.nih.gov/condition/hereditary-angioedema,C0002994,T046,Disorders
What are the genetic changes related to hereditary angioedema ?,0000454-3,genetic changes,"Mutations in the SERPING1 gene cause hereditary angioedema type I and type II. The SERPING1 gene provides instructions for making the C1 inhibitor protein, which is important for controlling inflammation. C1 inhibitor blocks the activity of certain proteins that promote inflammation. Mutations that cause hereditary angioedema type I lead to reduced levels of C1 inhibitor in the blood, while mutations that cause type II result in the production of a C1 inhibitor that functions abnormally. Without the proper levels of functional C1 inhibitor, excessive amounts of a protein fragment (peptide) called bradykinin are generated. Bradykinin promotes inflammation by increasing the leakage of fluid through the walls of blood vessels into body tissues. Excessive accumulation of fluids in body tissues causes the episodes of swelling seen in individuals with hereditary angioedema type I and type II.  Mutations in the F12 gene are associated with some cases of hereditary angioedema type III. This gene provides instructions for making a protein called coagulation factor XII. In addition to playing a critical role in blood clotting (coagulation), factor XII is also an important stimulator of inflammation and is involved in the production of bradykinin. Certain mutations in the F12 gene result in the production of factor XII with increased activity. As a result, more bradykinin is generated and blood vessel walls become more leaky, which leads to episodes of swelling in people with hereditary angioedema type III.  The cause of other cases of hereditary angioedema type III remains unknown. Mutations in one or more as-yet unidentified genes may be responsible for the disorder in these cases.",hereditary angioedema,0000454,GHR,https://ghr.nlm.nih.gov/condition/hereditary-angioedema,C0002994,T046,Disorders
Is hereditary angioedema inherited ?,0000454-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",hereditary angioedema,0000454,GHR,https://ghr.nlm.nih.gov/condition/hereditary-angioedema,C0002994,T046,Disorders
What are the treatments for hereditary angioedema ?,0000454-5,treatment,These resources address the diagnosis or management of hereditary angioedema:  - Genetic Testing Registry: Hereditary C1 esterase inhibitor deficiency - dysfunctional factor  - Genetic Testing Registry: Hereditary angioneurotic edema  - Genetic Testing Registry: Hereditary angioneurotic edema with normal C1 esterase inhibitor activity  - MedlinePlus Encyclopedia: Hereditary angioedema   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hereditary angioedema,0000454,GHR,https://ghr.nlm.nih.gov/condition/hereditary-angioedema,C0002994,T046,Disorders
"What is (are) hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome ?",0000455-1,information,"Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is part of a group of conditions called the COL4A1-related disorders. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. HANAC syndrome is characterized by angiopathy, which is a disorder of the blood vessels. In people with HANAC syndrome, angiopathy affects several parts of the body. The blood vessels as well as thin sheet-like structures called basement membranes that separate and support cells are weakened and more susceptible to breakage.  People with HANAC syndrome develop kidney disease (nephropathy). Fragile or damaged blood vessels or basement membranes in the kidneys can lead to blood in the urine (hematuria). Cysts can also form in one or both kidneys, and the cysts may grow larger over time.  Compared to other COL4A1-related disorders, the brain is only mildly affected in HANAC syndrome. People with this condition may have a bulge in one or multiple blood vessels in the brain (intracranial aneurysms). These aneurysms have the potential to burst, causing bleeding within the brain (hemorrhagic stroke). However, in people with HANAC syndrome, these aneurysms typically do not burst. About half of people with this condition also have leukoencephalopathy, which is a change in a type of brain tissue called white matter that can be seen with magnetic resonance imaging (MRI).  Muscle cramps experienced by most people with HANAC syndrome typically begin in early childhood. Any muscle may be affected, and cramps usually last from a few seconds to a few minutes, although in some cases they can last for several hours. Muscle cramps can be spontaneous or triggered by exercise.  Individuals with HANAC syndrome also experience a variety of eye problems. All individuals with this condition have arteries that twist and turn abnormally within the light-sensitive tissue at the back of the eyes (arterial retinal tortuosity). This blood vessel abnormality can cause episodes of bleeding within the eyes following any minor trauma to the eyes, leading to temporary vision loss. Other eye problems associated with HANAC syndrome include a clouding of the lens of the eye (cataract) and an abnormality called Axenfeld-Rieger anomaly. Axenfeld-Rieger anomaly is associated with various other eye abnormalities, including underdevelopment and eventual tearing of the colored part of the eye (iris), and a pupil that is not in the center of the eye.  Rarely, affected individuals will have a condition called Raynaud phenomenon in which the blood vessels in the fingers and toes temporarily narrow, restricting blood flow to the fingertips and the ends of the toes. As a result, the skin around the affected area may turn white or blue for a brief period of time and the area may tingle or throb. Raynaud phenomenon is typically triggered by changes in temperature and usually causes no long term damage.","hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome",0000455,GHR,https://ghr.nlm.nih.gov/condition/hereditary-angiopathy-with-nephropathy-aneurysms-and-muscle-cramps-syndrome,C0042373,T047,Disorders
"How many people are affected by hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome ?",0000455-2,frequency,"HANAC syndrome is a rare condition, although the exact prevalence is unknown. At least six affected families have been described in the scientific literature.","hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome",0000455,GHR,https://ghr.nlm.nih.gov/condition/hereditary-angiopathy-with-nephropathy-aneurysms-and-muscle-cramps-syndrome,C0042373,T047,Disorders
"What are the genetic changes related to hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome ?",0000455-3,genetic changes,"Mutations in the COL4A1 gene cause HANAC syndrome. The COL4A1 gene provides instructions for making one component of a protein called type IV collagen. Type IV collagen molecules attach to each other to form complex protein networks. These protein networks are the main component of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. Type IV collagen networks play an important role in the basement membranes in virtually all tissues throughout the body, particularly the basement membranes surrounding the body's blood vessels (vasculature).  The COL4A1 gene mutations that cause HANAC syndrome result in the production of a protein that disrupts the structure of type IV collagen. As a result, type IV collagen molecules cannot attach to each other to form the protein networks in basement membranes. Basement membranes without these networks are unstable, leading to weakening of the tissues that they surround. In people with HANAC syndrome, the vasculature and other tissues within the kidneys, brain, muscles, eyes, and throughout the body weaken.","hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome",0000455,GHR,https://ghr.nlm.nih.gov/condition/hereditary-angiopathy-with-nephropathy-aneurysms-and-muscle-cramps-syndrome,C0042373,T047,Disorders
"Is hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome inherited ?",0000455-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.","hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome",0000455,GHR,https://ghr.nlm.nih.gov/condition/hereditary-angiopathy-with-nephropathy-aneurysms-and-muscle-cramps-syndrome,C0042373,T047,Disorders
"What are the treatments for hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome ?",0000455-5,treatment,"These resources address the diagnosis or management of HANAC syndrome:  - Gene Review: Gene Review: COL4A1-Related Disorders  - Genetic Testing Registry: Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome",0000455,GHR,https://ghr.nlm.nih.gov/condition/hereditary-angiopathy-with-nephropathy-aneurysms-and-muscle-cramps-syndrome,C0042373,T047,Disorders
What is (are) hereditary antithrombin deficiency ?,0000456-1,information,"Hereditary antithrombin deficiency is a disorder of blood clotting. People with this condition are at higher than average risk for developing abnormal blood clots, particularly a type of clot that occurs in the deep veins of the legs. This type of clot is called a deep vein thrombosis (DVT). Affected individuals also have an increased risk of developing a pulmonary embolism (PE), which is a clot that travels through the bloodstream and lodges in the lungs. In hereditary antithrombin deficiency, abnormal blood clots usually form only in veins, although they may rarely occur in arteries.  About half of people with hereditary antithrombin deficiency will develop at least one abnormal blood clot during their lifetime. These clots usually develop after adolescence.  Other factors can increase the risk of abnormal blood clots in people with hereditary antithrombin deficiency. These factors include increasing age, surgery, or immobility. The combination of hereditary antithrombin deficiency and other inherited disorders of blood clotting can also influence risk. Women with hereditary antithrombin deficiency are at increased risk of developing an abnormal blood clot during pregnancy or soon after delivery. They also may have an increased risk for pregnancy loss (miscarriage) or stillbirth.",hereditary antithrombin deficiency,0000456,GHR,https://ghr.nlm.nih.gov/condition/hereditary-antithrombin-deficiency,C3658294,T047,Disorders
How many people are affected by hereditary antithrombin deficiency ?,0000456-2,frequency,"Hereditary antithrombin deficiency is estimated to occur in about 1 in 2,000 to 3,000 individuals. Of people who have experienced an abnormal blood clot, about 1 in 20 to 200 have hereditary antithrombin deficiency.",hereditary antithrombin deficiency,0000456,GHR,https://ghr.nlm.nih.gov/condition/hereditary-antithrombin-deficiency,C3658294,T047,Disorders
What are the genetic changes related to hereditary antithrombin deficiency ?,0000456-3,genetic changes,"Hereditary antithrombin deficiency is caused by mutations in the SERPINC1 gene. This gene provides instructions for producing a protein called antithrombin (previously known as antithrombin III). This protein is found in the bloodstream and is important for controlling blood clotting. Antithrombin blocks the activity of proteins that promote blood clotting, especially a protein called thrombin.  Most of the mutations that cause hereditary antithrombin deficiency change single protein building blocks (amino acids) in antithrombin, which disrupts its ability to control blood clotting. Individuals with this condition do not have enough functional antithrombin to inactivate clotting proteins, which results in the increased risk of developing abnormal blood clots.",hereditary antithrombin deficiency,0000456,GHR,https://ghr.nlm.nih.gov/condition/hereditary-antithrombin-deficiency,C3658294,T047,Disorders
Is hereditary antithrombin deficiency inherited ?,0000456-4,inheritance,"Hereditary antithrombin deficiency is typically inherited in an autosomal dominant pattern, which means one altered copy of the SERPINC1 gene in each cell is sufficient to cause the disorder. Inheriting two altered copies of this gene in each cell is usually incompatible with life; however, a few severely affected individuals have been reported with mutations in both copies of the SERPINC1 gene in each cell.",hereditary antithrombin deficiency,0000456,GHR,https://ghr.nlm.nih.gov/condition/hereditary-antithrombin-deficiency,C3658294,T047,Disorders
What are the treatments for hereditary antithrombin deficiency ?,0000456-5,treatment,These resources address the diagnosis or management of hereditary antithrombin deficiency:  - Genetic Testing Registry: Antithrombin III deficiency  - MedlinePlus Encyclopedia: Blood Clots  - MedlinePlus Encyclopedia: Congenital Antithrombin III Deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hereditary antithrombin deficiency,0000456,GHR,https://ghr.nlm.nih.gov/condition/hereditary-antithrombin-deficiency,C3658294,T047,Disorders
What is (are) hereditary cerebral amyloid angiopathy ?,0000457-1,information,"Hereditary cerebral amyloid angiopathy is a condition that can cause a progressive loss of intellectual function (dementia), stroke, and other neurological problems starting in mid-adulthood. Due to neurological decline, this condition is typically fatal in one's sixties, although there is variation depending on the severity of the signs and symptoms. Most affected individuals die within a decade after signs and symptoms first appear, although some people with the disease have survived longer.  There are many different types of hereditary cerebral amyloid angiopathy. The different types are distinguished by their genetic cause and the signs and symptoms that occur. The various types of hereditary cerebral amyloid angiopathy are named after the regions where they were first diagnosed.  The Dutch type of hereditary cerebral amyloid angiopathy is the most common form. Stroke is frequently the first sign of the Dutch type and is fatal in about one third of people who have this condition. Survivors often develop dementia and have recurrent strokes. About half of individuals with the Dutch type who have one or more strokes will have recurrent seizures (epilepsy).  People with the Flemish and Italian types of hereditary cerebral amyloid angiopathy are prone to recurrent strokes and dementia. Individuals with the Piedmont type may have one or more strokes and typically experience impaired movements, numbness or tingling (paresthesias), confusion, or dementia.  The first sign of the Icelandic type of hereditary cerebral amyloid angiopathy is typically a stroke followed by dementia. Strokes associated with the Icelandic type usually occur earlier than the other types, with individuals typically experiencing their first stroke in their twenties or thirties.  Strokes are rare in people with the Arctic type of hereditary cerebral amyloid angiopathy, in which the first sign is usually memory loss that then progresses to severe dementia. Strokes are also uncommon in individuals with the Iowa type. This type is characterized by memory loss, problems with vocabulary and the production of speech, personality changes, and involuntary muscle twitches (myoclonus).  Two types of hereditary cerebral amyloid angiopathy, known as familial British dementia and familial Danish dementia, are characterized by dementia and movement problems. Strokes are uncommon in these types. People with the Danish type may also have clouding of the lens of the eyes (cataracts) or deafness.",hereditary cerebral amyloid angiopathy,0000457,GHR,https://ghr.nlm.nih.gov/condition/hereditary-cerebral-amyloid-angiopathy,C0085220,T047,Disorders
How many people are affected by hereditary cerebral amyloid angiopathy ?,0000457-2,frequency,"The prevalence of hereditary cerebral amyloid angiopathy is unknown. The Dutch type is the most common, with over 200 affected individuals reported in the scientific literature.",hereditary cerebral amyloid angiopathy,0000457,GHR,https://ghr.nlm.nih.gov/condition/hereditary-cerebral-amyloid-angiopathy,C0085220,T047,Disorders
What are the genetic changes related to hereditary cerebral amyloid angiopathy ?,0000457-3,genetic changes,"Mutations in the APP gene are the most common cause of hereditary cerebral amyloid angiopathy. APP gene mutations cause the Dutch, Italian, Arctic, Iowa, Flemish, and Piedmont types of this condition. Mutations in the CST3 gene cause the Icelandic type. Familial British and Danish dementia are caused by mutations in the ITM2B gene.  The APP gene provides instructions for making a protein called amyloid precursor protein. This protein is found in many tissues and organs, including the brain and spinal cord (central nervous system). The precise function of this protein is unknown, but researchers speculate that it may attach (bind) to other proteins on the surface of cells or help cells attach to one another. In the brain, the amyloid precursor protein plays a role in the development and maintenance of nerve cells (neurons).  The CST3 gene provides instructions for making a protein called cystatin C. This protein inhibits the activity of enzymes called cathepsins that cut apart other proteins in order to break them down. Cystatin C is found in biological fluids, such as blood. Its levels are especially high in the fluid that surrounds and protects the brain and spinal cord (the cerebrospinal fluid or CSF).  The ITM2B gene provides instructions for producing a protein that is found in all tissues. The function of the ITM2B protein is unclear. It is thought to play a role in triggering the self-destruction of cells (apoptosis) and keeping cells from growing and dividing too fast or in an uncontrolled way. Additionally, the ITM2B protein may be involved in processing the amyloid precursor protein.  Mutations in the APP, CST3, or ITM2B gene lead to the production of proteins that are less stable than normal and that tend to cluster together (aggregate). These aggregated proteins form protein clumps called amyloid deposits that accumulate in certain areas of the brain and in its blood vessels. The amyloid deposits, known as plaques, damage brain cells, eventually causing cell death and impairing various parts of the brain. Brain cell loss in people with hereditary cerebral amyloid angiopathy can lead to seizures, movement abnormalities, and other neurological problems. In blood vessels, amyloid plaques replace the muscle fibers and elastic fibers that give the blood vessels flexibility, causing them to become weak and prone to breakage. A break in a blood vessel in the brain causes bleeding in the brain (hemorrhagic stroke), which can lead to brain damage and dementia.",hereditary cerebral amyloid angiopathy,0000457,GHR,https://ghr.nlm.nih.gov/condition/hereditary-cerebral-amyloid-angiopathy,C0085220,T047,Disorders
Is hereditary cerebral amyloid angiopathy inherited ?,0000457-4,inheritance,"Hereditary cerebral amyloid angiopathy caused by mutations in the APP, CST3, or ITM2B gene is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  There is also a non-hereditary form of cerebral amyloid angiopathy that occurs in people with no history of the disorder in their family. The cause of this form of the condition is unknown. These cases are described as sporadic and are not inherited.",hereditary cerebral amyloid angiopathy,0000457,GHR,https://ghr.nlm.nih.gov/condition/hereditary-cerebral-amyloid-angiopathy,C0085220,T047,Disorders
What are the treatments for hereditary cerebral amyloid angiopathy ?,0000457-5,treatment,"These resources address the diagnosis or management of hereditary cerebral amyloid angiopathy:  - Genetic Testing Registry: Cerebral amyloid angiopathy, APP-related  - Genetic Testing Registry: Dementia familial British  - Genetic Testing Registry: Dementia, familial Danish  - Genetic Testing Registry: Hereditary cerebral amyloid angiopathy, Icelandic type  - Johns Hopkins Medicine: Intracerebral Hemorrhage  - MedlinePlus Encyclopedia: Cerebral Amyloid Angiopathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",hereditary cerebral amyloid angiopathy,0000457,GHR,https://ghr.nlm.nih.gov/condition/hereditary-cerebral-amyloid-angiopathy,C0085220,T047,Disorders
What is (are) hereditary diffuse gastric cancer ?,0000458-1,information,"Hereditary diffuse gastric cancer (HDGC) is an inherited disorder that greatly increases the chance of developing a form of stomach (gastric) cancer. In this form, known as diffuse gastric cancer, there is no solid tumor. Instead cancerous (malignant) cells multiply underneath the stomach lining, making the lining thick and rigid. The invasive nature of this type of cancer makes it highly likely that these cancer cells will spread (metastasize) to other tissues, such as the liver or nearby bones.  Symptoms of diffuse gastric cancer occur late in the disease and can include stomach pain, nausea, vomiting, difficulty swallowing (dysphagia), decreased appetite, and weight loss. If the cancer metastasizes to other tissues, it may lead to an enlarged liver, yellowing of the eyes and skin (jaundice), an abnormal buildup of fluid in the abdominal cavity (ascites), firm lumps under the skin, or broken bones.  In HDGC, gastric cancer usually occurs in a person's late thirties or early forties, although it can develop anytime during adulthood. If diffuse gastric cancer is detected early, the survival rate is high; however, because this type of cancer is hidden underneath the stomach lining, it is usually not diagnosed until the cancer has become widely invasive. At that stage of the disease, the survival rate is approximately 20 percent.  Some people with HDGC have an increased risk of developing other types of cancer, such as a form of breast cancer in women that begins in the milk-producing glands (lobular breast cancer); prostate cancer; and cancers of the colon (large intestine) and rectum, which are collectively referred to as colorectal cancer. Most people with HDGC have family members who have had one of the types of cancer associated with HDGC. In some families, all the affected members have diffuse gastric cancer. In other families, some affected members have diffuse gastric cancer and others have another associated form of cancer, such as lobular breast cancer. Frequently, HDGC-related cancers develop in individuals before the age of 50.",hereditary diffuse gastric cancer,0000458,GHR,https://ghr.nlm.nih.gov/condition/hereditary-diffuse-gastric-cancer,C0024623,T191,Disorders
How many people are affected by hereditary diffuse gastric cancer ?,0000458-2,frequency,"Gastric cancer is the fourth most common form of cancer worldwide, affecting 900,000 people per year. HDGC probably accounts for less than 1 percent of these cases.",hereditary diffuse gastric cancer,0000458,GHR,https://ghr.nlm.nih.gov/condition/hereditary-diffuse-gastric-cancer,C0024623,T191,Disorders
What are the genetic changes related to hereditary diffuse gastric cancer ?,0000458-3,genetic changes,"It is likely that 30 to 40 percent of individuals with HDGC have a mutation in the CDH1 gene. The CDH1 gene provides instructions for making a protein called epithelial cadherin or E-cadherin. This protein is found within the membrane that surrounds epithelial cells, which are the cells that line the surfaces and cavities of the body. E-cadherin helps neighboring cells stick to one another (cell adhesion) to form organized tissues. E-cadherin has many other functions including acting as a tumor suppressor protein, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way.  People with HDGC caused by CDH1 gene mutations are born with one mutated copy of the gene in each cell. These mutations cause the production of an abnormally short, nonfunctional version of E-cadherin or alter the protein's structure. For diffuse gastric cancer to develop, a second mutation involving the other copy of the CDH1 gene must occur in the cells of the stomach lining during a person's lifetime. People who are born with one mutated copy of the CDH1 gene have a 80 percent chance of acquiring a second mutation in the other copy of the gene and developing gastric cancer in their lifetimes.  When both copies of the CDH1 gene are mutated in a particular cell, that cell cannot produce any functional E-cadherin. The loss of this protein prevents it from acting as a tumor suppressor, contributing to the uncontrollable growth and division of cells. A lack of E-cadherin also impairs cell adhesion, increasing the likelihood that cancer cells will not come together to form a tumor but will invade the stomach wall and metastasize as small clusters of cancer cells into nearby tissues.  These CDH1 gene mutations also lead to a 40 to 50 percent chance of lobular breast cancer in women, a slightly increased risk of prostate cancer in men, and a slightly increased risk of colorectal cancer. It is unclear why CDH1 gene mutations primarily occur in the stomach lining and these other tissues.  About 60 to 70 percent of individuals with HDGC do not have an identified mutation in the CDH1 gene. The cancer-causing mechanism in these individuals is unknown.",hereditary diffuse gastric cancer,0000458,GHR,https://ghr.nlm.nih.gov/condition/hereditary-diffuse-gastric-cancer,C0024623,T191,Disorders
Is hereditary diffuse gastric cancer inherited ?,0000458-4,inheritance,"HDGC is inherited in an autosomal dominant pattern, which means one copy of the altered CDH1 gene in each cell is sufficient to increase the risk of developing cancer.  In most cases, an affected person has one parent with the condition.",hereditary diffuse gastric cancer,0000458,GHR,https://ghr.nlm.nih.gov/condition/hereditary-diffuse-gastric-cancer,C0024623,T191,Disorders
What are the treatments for hereditary diffuse gastric cancer ?,0000458-5,treatment,These resources address the diagnosis or management of hereditary diffuse gastric cancer:  - American Cancer Society: How is Stomach Cancer Diagnosed?  - Gene Review: Gene Review: Hereditary Diffuse Gastric Cancer  - Genetic Testing Registry: Hereditary diffuse gastric cancer  - MedlinePlus Encyclopedia: Gastric Cancer  - Memorial Sloan-Kettering Cancer Center: Early Onset and Familial Gastric Cancer Registry  - National Cancer Institute: Gastric Cancer Treatment Option Overview   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hereditary diffuse gastric cancer,0000458,GHR,https://ghr.nlm.nih.gov/condition/hereditary-diffuse-gastric-cancer,C0024623,T191,Disorders
What is (are) hereditary folate malabsorption ?,0000459-1,information,"Hereditary folate malabsorption is a disorder that interferes with the body's ability to absorb certain B vitamins (called folates) from food. Folates are important for many cell functions, including the production of DNA and its chemical cousin, RNA.  Infants with hereditary folate malabsorption are born with normal amounts of folates in their body because they obtain these vitamins from their mother's blood before birth. They generally begin to show signs and symptoms of the disorder within the first few months of life because their ability to absorb folates from food is impaired.  Infants with hereditary folate malabsorption experience feeding difficulties, diarrhea, and failure to gain weight and grow at the expected rate (failure to thrive). Affected individuals usually develop a blood disorder called megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number of red blood cells (anemia), and the remaining red blood cells are larger than normal (megaloblastic). The symptoms of this blood disorder may include decreased appetite, lack of energy, headaches, pale skin, and tingling or numbness in the hands and feet. People with hereditary folate malabsorption may also have a deficiency of white blood cells (leukopenia), leading to increased susceptibility to infections. In addition, they may have a reduction in the amount of platelets (thrombocytopenia), which can result in easy bruising and abnormal bleeding.  Some infants with hereditary folate malabsorption exhibit neurological problems such as developmental delay and seizures. Over time, untreated individuals may develop intellectual disability and difficulty coordinating movements (ataxia).",hereditary folate malabsorption,0000459,GHR,https://ghr.nlm.nih.gov/condition/hereditary-folate-malabsorption,C2749650,T047,Disorders
How many people are affected by hereditary folate malabsorption ?,0000459-2,frequency,"The prevalence of hereditary folate malabsorption is unknown. Approximately 15 affected families have been reported worldwide. Researchers believe that some infants with this disorder may not get diagnosed or treated, particularly in areas where advanced medical care is not available.",hereditary folate malabsorption,0000459,GHR,https://ghr.nlm.nih.gov/condition/hereditary-folate-malabsorption,C2749650,T047,Disorders
What are the genetic changes related to hereditary folate malabsorption ?,0000459-3,genetic changes,"The SLC46A1 gene provides instructions for making a protein called the proton-coupled folate transporter (PCFT). PCFT is important for normal functioning of intestinal epithelial cells, which are cells that line the walls of the intestine. These cells have fingerlike projections called microvilli that absorb nutrients from food as it passes through the intestine. Based on their appearance, groups of these microvilli are known collectively as the brush border. PCFT is involved in the process of using energy to move folates across the brush border membrane, a mechanism called active transport. It is also involved in the transport of folates between the brain and the fluid that surrounds it (cerebrospinal fluid).  Mutations in the SLC46A1 gene result in a PCFT protein that has little or no activity. In some cases the mutated protein is not transported to the cell membrane, and so it is unable to perform its function. A lack of functional PCFT impairs the body's ability to absorb folates from food, resulting in the signs and symptoms of hereditary folate malabsorption.",hereditary folate malabsorption,0000459,GHR,https://ghr.nlm.nih.gov/condition/hereditary-folate-malabsorption,C2749650,T047,Disorders
Is hereditary folate malabsorption inherited ?,0000459-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",hereditary folate malabsorption,0000459,GHR,https://ghr.nlm.nih.gov/condition/hereditary-folate-malabsorption,C2749650,T047,Disorders
What are the treatments for hereditary folate malabsorption ?,0000459-5,treatment,These resources address the diagnosis or management of hereditary folate malabsorption:  - Gene Review: Gene Review: Hereditary Folate Malabsorption  - Genetic Testing Registry: Congenital defect of folate absorption  - MedlinePlus Encyclopedia: Folate  - MedlinePlus Encyclopedia: Folate Deficiency  - MedlinePlus Encyclopedia: Folate-Deficiency Anemia  - MedlinePlus Encyclopedia: Malabsorption   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hereditary folate malabsorption,0000459,GHR,https://ghr.nlm.nih.gov/condition/hereditary-folate-malabsorption,C2749650,T047,Disorders
What is (are) hereditary fructose intolerance ?,0000460-1,information,"Hereditary fructose intolerance is a condition that affects a person's ability to digest the sugar fructose. Fructose is a simple sugar found primarily in fruits. Affected individuals develop signs and symptoms of the disorder in infancy when fruits, juices, or other foods containing fructose are introduced into the diet. After ingesting fructose, individuals with hereditary fructose intolerance may experience nausea, bloating, abdominal pain, diarrhea, vomiting, and low blood sugar (hypoglycemia). Affected infants may fail to grow and gain weight at the expected rate (failure to thrive).  Repeated ingestion of fructose-containing foods can lead to liver and kidney damage. The liver damage can result in a yellowing of the skin and whites of the eyes (jaundice), an enlarged liver (hepatomegaly), and chronic liver disease (cirrhosis). Continued exposure to fructose may result in seizures, coma, and ultimately death from liver and kidney failure. Due to the severity of symptoms experienced when fructose is ingested, most people with hereditary fructose intolerance develop a dislike for fruits, juices, and other foods containing fructose.  Hereditary fructose intolerance should not be confused with a condition called fructose malabsorption. In people with fructose malabsorption, the cells of the intestine cannot absorb fructose normally, leading to bloating, diarrhea or constipation, flatulence, and stomach pain. Fructose malabsorption is thought to affect approximately 40 percent of individuals in the Western hemisphere; its cause is unknown.",hereditary fructose intolerance,0000460,GHR,https://ghr.nlm.nih.gov/condition/hereditary-fructose-intolerance,C0016751,T047,Disorders
How many people are affected by hereditary fructose intolerance ?,0000460-2,frequency,"The incidence of hereditary fructose intolerance is estimated to be 1 in 20,000 to 30,000 individuals each year worldwide.",hereditary fructose intolerance,0000460,GHR,https://ghr.nlm.nih.gov/condition/hereditary-fructose-intolerance,C0016751,T047,Disorders
What are the genetic changes related to hereditary fructose intolerance ?,0000460-3,genetic changes,"Mutations in the ALDOB gene cause hereditary fructose intolerance. The ALDOB gene provides instructions for making the aldolase B enzyme. This enzyme is found primarily in the liver and is involved in the breakdown (metabolism) of fructose so this sugar can be used as energy. Aldolase B is responsible for the second step in the metabolism of fructose, which breaks down the molecule fructose-1-phosphate into other molecules called glyceraldehyde and dihydroxyacetone phosphate.  ALDOB gene mutations reduce the function of the enzyme, impairing its ability to metabolize fructose. A lack of functional aldolase B results in an accumulation of fructose-1-phosphate in liver cells. This buildup is toxic, resulting in the death of liver cells over time. Additionally, the breakdown products of fructose-1-phosphase are needed in the body to produce energy and to maintain blood sugar levels. The combination of decreased cellular energy, low blood sugar, and liver cell death leads to the features of hereditary fructose intolerance.",hereditary fructose intolerance,0000460,GHR,https://ghr.nlm.nih.gov/condition/hereditary-fructose-intolerance,C0016751,T047,Disorders
Is hereditary fructose intolerance inherited ?,0000460-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",hereditary fructose intolerance,0000460,GHR,https://ghr.nlm.nih.gov/condition/hereditary-fructose-intolerance,C0016751,T047,Disorders
What are the treatments for hereditary fructose intolerance ?,0000460-5,treatment,These resources address the diagnosis or management of hereditary fructose intolerance:  - Boston University: Specifics of Hereditary Fructose Intolerance and Its Diagnosis  - Gene Review: Gene Review: Hereditary Fructose Intolerance  - Genetic Testing Registry: Hereditary fructosuria  - MedlinePlus Encyclopedia: Hereditary Fructose Intolerance   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hereditary fructose intolerance,0000460,GHR,https://ghr.nlm.nih.gov/condition/hereditary-fructose-intolerance,C0016751,T047,Disorders
What is (are) hereditary hemochromatosis ?,0000461-1,information,"Hereditary hemochromatosis is a disorder that causes the body to absorb too much iron from the diet. The excess iron is stored in the body's tissues and organs, particularly the skin, heart, liver, pancreas, and joints. Because humans cannot increase the excretion of iron, excess iron can overload and eventually damage tissues and organs. For this reason, hereditary hemochromatosis is also called an iron overload disorder.  Early symptoms of hereditary hemochromatosis are nonspecific and may include fatigue, joint pain, abdominal pain, and loss of sex drive. Later signs and symptoms can include arthritis, liver disease, diabetes, heart abnormalities, and skin discoloration. The appearance and progression of symptoms can be affected by environmental and lifestyle factors such as the amount of iron in the diet, alcohol use, and infections.  Hereditary hemochromatosis is classified by type depending on the age of onset and other factors such as genetic cause and mode of inheritance. Type 1, the most common form of the disorder, and type 4 (also called ferroportin disease) begin in adulthood. Men with type 1 or type 4 hemochromatosis typically develop symptoms between the ages of 40 and 60, and women usually develop symptoms after menopause.  Type 2 hemochromatosis is a juvenile-onset disorder. Iron accumulation begins early in life, and symptoms may appear in childhood. By age 20, decreased or absent secretion of sex hormones is evident. Females usually begin menstruation in a normal manner, but menses stop after a few years. Males may experience delayed puberty or symptoms related to a shortage of sex hormones. If the disorder is untreated, heart disease becomes evident by age 30.  The onset of type 3 hemochromatosis is usually intermediate between types 1 and 2. Symptoms of type 3 hemochromatosis generally begin before age 30.",hereditary hemochromatosis,0000461,GHR,https://ghr.nlm.nih.gov/condition/hereditary-hemochromatosis,C0392514,T047,Disorders
How many people are affected by hereditary hemochromatosis ?,0000461-2,frequency,"Type 1 hemochromatosis is one of the most common genetic disorders in the United States, affecting about 1 million people. It most often affects people of Northern European descent. The other types of hemochromatosis are considered rare and have been studied in only a small number of families worldwide.",hereditary hemochromatosis,0000461,GHR,https://ghr.nlm.nih.gov/condition/hereditary-hemochromatosis,C0392514,T047,Disorders
What are the genetic changes related to hereditary hemochromatosis ?,0000461-3,genetic changes,"Mutations in the HAMP, HFE, HFE2, SLC40A1, and TFR2 genes cause hereditary hemochromatosis. Type 1 hemochromatosis results from mutations in the HFE gene, and type 2 hemochromatosis results from mutations in either the HFE2 or HAMP gene. Mutations in the TFR2 gene cause type 3 hemochromatosis, and mutations in the SLC40A1 gene cause type 4 hemochromatosis.  The proteins produced from these genes play important roles in regulating the absorption, transport, and storage of iron. Mutations in any of these genes impair the control of iron absorption during digestion and alter the distribution of iron to other parts of the body. As a result, iron accumulates in tissues and organs, which can disrupt their normal functions.",hereditary hemochromatosis,0000461,GHR,https://ghr.nlm.nih.gov/condition/hereditary-hemochromatosis,C0392514,T047,Disorders
Is hereditary hemochromatosis inherited ?,0000461-4,inheritance,"Types 1, 2, and 3 hemochromatosis are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene but do not show signs and symptoms of the condition.  Type 4 hemochromatosis is distinguished by its autosomal dominant inheritance pattern. With this type of inheritance, one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.",hereditary hemochromatosis,0000461,GHR,https://ghr.nlm.nih.gov/condition/hereditary-hemochromatosis,C0392514,T047,Disorders
What are the treatments for hereditary hemochromatosis ?,0000461-5,treatment,These resources address the diagnosis or management of hereditary hemochromatosis:  - Gene Review: Gene Review: HFE-Associated Hereditary Hemochromatosis  - Gene Review: Gene Review: Juvenile Hereditary Hemochromatosis  - Gene Review: Gene Review: TFR2-Related Hereditary Hemochromatosis  - GeneFacts: Hereditary Hemochromatosis: Diagnosis  - GeneFacts: Hereditary Hemochromatosis: Management  - Genetic Testing Registry: Hemochromatosis type 1  - Genetic Testing Registry: Hemochromatosis type 2A  - Genetic Testing Registry: Hemochromatosis type 3  - Genetic Testing Registry: Hemochromatosis type 4  - MedlinePlus Encyclopedia: Hemochromatosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hereditary hemochromatosis,0000461,GHR,https://ghr.nlm.nih.gov/condition/hereditary-hemochromatosis,C0392514,T047,Disorders
What is (are) hereditary hemorrhagic telangiectasia ?,0000462-1,information,"Hereditary hemorrhagic telangiectasia is a disorder that results in the development of multiple abnormalities in the blood vessels.  In the circulatory system, blood carrying oxygen from the lungs is normally pumped by the heart into the arteries at high pressure. The pressure allows the blood to make its way through the arteries to the smaller vessels (arterioles and capillaries) that supply oxygen to the body's tissues. By the time blood reaches the capillaries, the pressure is much lower. The blood then proceeds from the capillaries into veins, through which it eventually returns to the heart.  In hereditary hemorrhagic telangiectasia, some arterial vessels flow directly into veins rather than into the capillaries. These abnormalities are called arteriovenous malformations. When they occur in vessels near the surface of the skin, where they are visible as red markings, they are known as telangiectases (the singular is telangiectasia).  Without the normal buffer of the capillaries, the blood moves from the arteries at high pressure into the thinner walled, less elastic veins. The extra pressure tends to strain and enlarge these blood vessels, and may result in compression or irritation of adjacent tissues and frequent episodes of severe bleeding (hemorrhage). Nosebleeds are very common in people with hereditary hemorrhagic telangiectasia, and more serious problems may arise from hemorrhages in the brain, liver, lungs, or other organs.  Forms of hereditary hemorrhagic telangiectasia include type 1, type 2, type 3, and juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome. People with type 1 tend to develop symptoms earlier than those with type 2, and are more likely to have blood vessel malformations in the lungs and brain. Type 2 and type 3 may be associated with a higher risk of liver involvement. Women are more likely than men to develop blood vessel malformations in the lungs with type 1, and are also at higher risk of liver involvement with both type 1 and type 2. Individuals with any form of hereditary hemorrhagic telangiectasia, however, can have any of these problems.  Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome is a condition that involves both arteriovenous malformations and a tendency to develop growths (polyps) in the gastrointestinal tract. Types 1, 2 and 3 do not appear to increase the likelihood of such polyps.",hereditary hemorrhagic telangiectasia,0000462,GHR,https://ghr.nlm.nih.gov/condition/hereditary-hemorrhagic-telangiectasia,C0039446,T047,Disorders
How many people are affected by hereditary hemorrhagic telangiectasia ?,0000462-2,frequency,"The incidence of hereditary hemorrhagic telangiectasia is difficult to determine because the severity of symptoms can vary widely and some symptoms, such as frequent nosebleeds, are common in the general population. In addition, arteriovenous malformations may be associated with other medical conditions. Hereditary hemorrhagic telangiectasia is widely distributed, occurring in many ethnic groups around the world. It is believed to affect between 1 in 5,000 and 1 in 10,000 people.",hereditary hemorrhagic telangiectasia,0000462,GHR,https://ghr.nlm.nih.gov/condition/hereditary-hemorrhagic-telangiectasia,C0039446,T047,Disorders
What are the genetic changes related to hereditary hemorrhagic telangiectasia ?,0000462-3,genetic changes,"Mutations in the ACVRL1, ENG, and SMAD4 genes cause hereditary hemorrhagic telangiectasia.  Hereditary hemorrhagic telangiectasia type 1 is caused by mutations in the gene ENG. Type 2 is caused by mutations in the gene ACVRL1. Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome is caused by mutations in the gene SMAD4. All these genes provide instructions for making proteins that are found in the lining of the blood vessels. These proteins interact with growth factors that control blood vessel development. The gene involved in hereditary hemorrhagic telangiectasia type 3 is not known, but is believed to be located on chromosome 5.  Mutations in these genes generally prevent the production of the associated protein, or result in the production of a defective protein that cannot fulfill its function. An individual with a mutated gene will therefore have a reduced amount of the functional protein available in the tissue lining the blood vessels. This deficiency is believed to result in the signs and symptoms of hereditary hemorrhagic telangiectasia.",hereditary hemorrhagic telangiectasia,0000462,GHR,https://ghr.nlm.nih.gov/condition/hereditary-hemorrhagic-telangiectasia,C0039446,T047,Disorders
Is hereditary hemorrhagic telangiectasia inherited ?,0000462-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",hereditary hemorrhagic telangiectasia,0000462,GHR,https://ghr.nlm.nih.gov/condition/hereditary-hemorrhagic-telangiectasia,C0039446,T047,Disorders
What are the treatments for hereditary hemorrhagic telangiectasia ?,0000462-5,treatment,These resources address the diagnosis or management of hereditary hemorrhagic telangiectasia:  - Gene Review: Gene Review: Hereditary Hemorrhagic Telangiectasia  - Genetic Testing Registry: Hereditary hemorrhagic telangiectasia type 2  - Genetic Testing Registry: Hereditary hemorrhagic telangiectasia type 3  - Genetic Testing Registry: Hereditary hemorrhagic telangiectasia type 4  - Genetic Testing Registry: Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome  - Genetic Testing Registry: Osler hemorrhagic telangiectasia syndrome  - MedlinePlus Encyclopedia: Osler-Weber-Rendu syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hereditary hemorrhagic telangiectasia,0000462,GHR,https://ghr.nlm.nih.gov/condition/hereditary-hemorrhagic-telangiectasia,C0039446,T047,Disorders
What is (are) hereditary hyperekplexia ?,0000463-1,information,"Hereditary hyperekplexia is a condition in which affected infants have increased muscle tone (hypertonia) and an exaggerated startle reaction to unexpected stimuli, especially loud noises. Following the startle reaction, infants experience a brief period in which they are very rigid and unable to move. During these rigid periods, some infants stop breathing, which, if prolonged, can be fatal. This condition may explain some cases of sudden infant death syndrome (SIDS), which is a major cause of unexplained death in babies younger than 1 year. Infants with hereditary hyperekplexia have hypertonia at all times, except when they are sleeping.  Other signs and symptoms of hereditary hyperekplexia can include muscle twitches when falling asleep (hypnagogic myoclonus) and movements of the arms or legs while asleep. Some infants, when tapped on the nose, extend their head forward and have spasms of the limb and neck muscles. Rarely, infants with hereditary hyperekplexia experience recurrent seizures (epilepsy).  The signs and symptoms of hereditary hyperekplexia typically fade by age 1. However, older individuals with hereditary hyperekplexia may still startle easily and have periods of rigidity, which can cause them to fall down. Some individuals with this condition have a low tolerance for crowded places and loud noises. Some affected people have persistent limb movements during sleep. Affected individuals who have epilepsy have the disorder throughout their lives.",hereditary hyperekplexia,0000463,GHR,https://ghr.nlm.nih.gov/condition/hereditary-hyperekplexia,C0234166,T047,Disorders
How many people are affected by hereditary hyperekplexia ?,0000463-2,frequency,The exact prevalence of hereditary hyperekplexia is unknown. This condition has been identified in more than 70 families worldwide.,hereditary hyperekplexia,0000463,GHR,https://ghr.nlm.nih.gov/condition/hereditary-hyperekplexia,C0234166,T047,Disorders
What are the genetic changes related to hereditary hyperekplexia ?,0000463-3,genetic changes,"At least five genes are associated with hereditary hyperekplexia. Most of these genes provide instructions for producing proteins that are found in nerve cells (neurons). They play a role in how neurons respond to a molecule called glycine. This molecule acts as a neurotransmitter, which is a chemical messenger that transmits signals in the nervous system. Gene mutations that cause hereditary hyperekplexia disrupt normal cell signaling in the spinal cord and the part of the brain that is connected to the spinal cord (the brainstem).  Approximately 80 percent of cases of hereditary hyperekplexia are caused by mutations in the GLRA1 gene. The GLRA1 gene provides instructions for making one part, the alpha ()1 subunit, of the glycine receptor protein. GLRA1 gene mutations lead to the production of a receptor that cannot properly respond to glycine. As a result, glycine is less able to transmit signals in the spinal cord and brainstem. Mutations in the other four genes account for a small percentage of all cases of hereditary hyperekplexia.  A disruption in cell signaling caused by mutations in the five genes associated with hereditary hyperekplexia is thought to cause the abnormal muscle movements, exaggerated startle reaction, and other symptoms characteristic of this disorder.",hereditary hyperekplexia,0000463,GHR,https://ghr.nlm.nih.gov/condition/hereditary-hyperekplexia,C0234166,T047,Disorders
Is hereditary hyperekplexia inherited ?,0000463-4,inheritance,"Hereditary hyperekplexia has different inheritance patterns.  This condition can be inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.  Hereditary hyperekplexia can also be inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive disorder typically each carry one copy of the altered gene, but do not show signs and symptoms of the disorder.  Rarely, hereditary hyperekplexia is inherited in an X-linked pattern. In these cases, the gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",hereditary hyperekplexia,0000463,GHR,https://ghr.nlm.nih.gov/condition/hereditary-hyperekplexia,C0234166,T047,Disorders
What are the treatments for hereditary hyperekplexia ?,0000463-5,treatment,These resources address the diagnosis or management of hereditary hyperekplexia:  - Gene Review: Gene Review: Hyperekplexia  - Genetic Testing Registry: Early infantile epileptic encephalopathy 8  - Genetic Testing Registry: Hyperekplexia hereditary   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hereditary hyperekplexia,0000463,GHR,https://ghr.nlm.nih.gov/condition/hereditary-hyperekplexia,C0234166,T047,Disorders
What is (are) hereditary hypophosphatemic rickets ?,0000464-1,information,"Hereditary hypophosphatemic rickets is a disorder related to low levels of phosphate in the blood (hypophosphatemia). Phosphate is a mineral that is essential for the normal formation of bones and teeth.  In most cases, the signs and symptoms of hereditary hypophosphatemic rickets begin in early childhood. The features of the disorder vary widely, even among affected members of the same family. Mildly affected individuals may have hypophosphatemia without other signs and symptoms. More severely affected children experience slow growth and are shorter than their peers. They develop bone abnormalities that can interfere with movement and cause bone pain. The most noticeable of these abnormalities are bowed legs or knock knees (a condition in which the lower legs are positioned at an outward angle). These abnormalities become apparent with weight-bearing activities such as walking. If untreated, they tend to worsen with time.  Other signs and symptoms of hereditary hypophosphatemic rickets can include premature fusion of the skull bones (craniosynostosis) and dental abnormalities. The disorder may also cause abnormal bone growth where ligaments and tendons attach to joints (enthesopathy). In adults, hypophosphatemia is characterized by a softening of the bones known as osteomalacia.  Researchers have described several forms of hereditary hypophosphatemic rickets, which are distinguished by their pattern of inheritance and genetic cause. The most common form of the disorder is known as X-linked hypophosphatemic rickets (XLH). It has an X-linked dominant pattern of inheritance. X-linked recessive, autosomal dominant, and autosomal recessive forms of the disorder are much rarer. The different inheritance patterns are described below.  Another rare type of the disorder is known as hereditary hypophosphatemic rickets with hypercalciuria (HHRH). In addition to hypophosphatemia, this condition is characterized by the excretion of high levels of calcium in the urine (hypercalciuria).",hereditary hypophosphatemic rickets,0000464,GHR,https://ghr.nlm.nih.gov/condition/hereditary-hypophosphatemic-rickets,C1704375,T047,Disorders
How many people are affected by hereditary hypophosphatemic rickets ?,0000464-2,frequency,"X-linked hypophosphatemic rickets is the most common form of rickets that runs in families. It affects about 1 in 20,000 newborns. Each of the other forms of hereditary hypophosphatemic rickets has been identified in only a few families.",hereditary hypophosphatemic rickets,0000464,GHR,https://ghr.nlm.nih.gov/condition/hereditary-hypophosphatemic-rickets,C1704375,T047,Disorders
What are the genetic changes related to hereditary hypophosphatemic rickets ?,0000464-3,genetic changes,"Hereditary hypophosphatemic rickets can result from mutations in several genes. Mutations in the PHEX gene, which are responsible for X-linked hypophosphatemic rickets, occur most frequently. Mutations in other genes cause the less common forms of the condition.  Hereditary hypophosphatemic rickets is characterized by a phosphate imbalance in the body. Among its many functions, phosphate plays a critical role in the formation and growth of bones in childhood and helps maintain bone strength in adults. Phosphate levels are controlled in large part by the kidneys. The kidneys normally excrete excess phosphate in urine, and they reabsorb this mineral into the bloodstream when more is needed. However, in people with hereditary hypophosphatemic rickets, the kidneys cannot reabsorb phosphate effectively and too much of this mineral is excreted from the body in urine. As a result, not enough phosphate is available in the bloodstream to participate in normal bone development and maintenance.  The genes associated with hereditary hypophosphatemic rickets are involved in maintaining the proper balance of phosphate. Many of these genes, including the PHEX gene, directly or indirectly regulate a protein called fibroblast growth factor 23 (produced from the FGF23 gene). This protein normally inhibits the kidneys' ability to reabsorb phosphate into the bloodstream. Gene mutations increase the production or reduce the breakdown of fibroblast growth factor 23. The resulting overactivity of this protein reduces phosphate reabsorption by the kidneys, leading to hypophosphatemia and the related features of hereditary hypophosphatemic rickets.",hereditary hypophosphatemic rickets,0000464,GHR,https://ghr.nlm.nih.gov/condition/hereditary-hypophosphatemic-rickets,C1704375,T047,Disorders
Is hereditary hypophosphatemic rickets inherited ?,0000464-4,inheritance,"Hereditary hypophosphatemic rickets can have several patterns of inheritance. When the condition results from mutations in the PHEX gene, it is inherited in an X-linked dominant pattern. The PHEX gene is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  Less commonly, hereditary hypophosphatemic rickets can have an X-linked recessive pattern of inheritance. This form of the condition is often called Dent disease. Like the PHEX gene, the gene associated with Dent disease is located on the X chromosome. In males, one altered copy of the gene in each cell is sufficient to cause the condition. In females, a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females.  In a few families, hereditary hypophosphatemic rickets has had an autosomal dominant inheritance pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. The rare condition HHRH has an autosomal recessive pattern of inheritance, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. However, some parents of children with HHRH have experienced hypercalcuria and kidney stones.",hereditary hypophosphatemic rickets,0000464,GHR,https://ghr.nlm.nih.gov/condition/hereditary-hypophosphatemic-rickets,C1704375,T047,Disorders
What are the treatments for hereditary hypophosphatemic rickets ?,0000464-5,treatment,"These resources address the diagnosis or management of hereditary hypophosphatemic rickets:  - Gene Review: Gene Review: X-Linked Hypophosphatemia  - Genetic Testing Registry: Autosomal dominant hypophosphatemic rickets  - Genetic Testing Registry: Autosomal recessive hypophosphatemic bone disease  - Genetic Testing Registry: Autosomal recessive hypophosphatemic vitamin D refractory rickets  - Genetic Testing Registry: Familial X-linked hypophosphatemic vitamin D refractory rickets  - Genetic Testing Registry: Hypophosphatemic rickets, autosomal recessive, 2   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",hereditary hypophosphatemic rickets,0000464,GHR,https://ghr.nlm.nih.gov/condition/hereditary-hypophosphatemic-rickets,C1704375,T047,Disorders
What is (are) hereditary leiomyomatosis and renal cell cancer ?,0000465-1,information,"Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a disorder in which affected individuals tend to develop benign tumors containing smooth muscle tissue (leiomyomas) in the skin and, in females, the uterus. This condition also increases the risk of kidney cancer.  In this disorder, growths on the skin (cutaneous leiomyomas) typically develop in the third decade of life. Most of these growths arise from the tiny muscles around the hair follicles that cause ""goosebumps"". They appear as bumps or nodules on the trunk, arms, legs, and occasionally on the face. Cutaneous leiomyomas may be the same color as the surrounding skin, or they may be darker. Some affected individuals have no cutaneous leiomyomas or only a few, but the growths tend to increase in size and number over time. Cutaneous leiomyomas are often more sensitive than the surrounding skin to cold or light touch, and may be painful.  Most women with HLRCC also develop uterine leiomyomas (fibroids). While uterine fibroids are very common in the general population, women with HLRCC tend to have numerous large fibroids that appear earlier than in the general population.  Approximately 10 percent to 16 percent of people with HLRCC develop a type of kidney cancer called renal cell cancer. The signs and symptoms of renal cell cancer may include lower back pain, blood in the urine, or a mass in the kidney that can be felt upon physical examination. Some people with renal cell cancer have no symptoms until the disease is advanced. The average age at which people with HLRCC are diagnosed with kidney cancer is in their forties.  This disorder, especially if it appears in individuals or families without renal cell cancer, is also sometimes called multiple cutaneous leiomyomatosis (MCL) or multiple cutaneous and uterine leiomyomatosis (MCUL).",hereditary leiomyomatosis and renal cell cancer,0000465,GHR,https://ghr.nlm.nih.gov/condition/hereditary-leiomyomatosis-and-renal-cell-cancer,C0206654,T191,Disorders
How many people are affected by hereditary leiomyomatosis and renal cell cancer ?,0000465-2,frequency,HLRCC has been reported in approximately 100 families worldwide. Its prevalence is unknown.,hereditary leiomyomatosis and renal cell cancer,0000465,GHR,https://ghr.nlm.nih.gov/condition/hereditary-leiomyomatosis-and-renal-cell-cancer,C0206654,T191,Disorders
What are the genetic changes related to hereditary leiomyomatosis and renal cell cancer ?,0000465-3,genetic changes,"Mutations in the FH gene cause hereditary leiomyomatosis and renal cell cancer. The FH gene provides instructions for making an enzyme called fumarase (also known as fumarate hydratase). This enzyme participates in an important series of reactions known as the citric acid cycle or Krebs cycle, which allows cells to use oxygen and generate energy. Specifically, fumarase helps convert a molecule called fumarate to a molecule called malate.  People with HLRCC are born with one mutated copy of the FH gene in each cell. The second copy of the FH gene in certain cells may also acquire mutations as a result of environmental factors such as ultraviolet radiation from the sun or a mistake that occurs as DNA copies itself during cell division.  FH gene mutations may interfere with the enzyme's role in the citric acid cycle, resulting in a buildup of fumarate. Researchers believe that the excess fumarate may interfere with the regulation of oxygen levels in the cell. Chronic oxygen deficiency (hypoxia) in cells with two mutated copies of the FH gene may encourage tumor formation and result in the tendency to develop leiomyomas and renal cell cancer.",hereditary leiomyomatosis and renal cell cancer,0000465,GHR,https://ghr.nlm.nih.gov/condition/hereditary-leiomyomatosis-and-renal-cell-cancer,C0206654,T191,Disorders
Is hereditary leiomyomatosis and renal cell cancer inherited ?,0000465-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",hereditary leiomyomatosis and renal cell cancer,0000465,GHR,https://ghr.nlm.nih.gov/condition/hereditary-leiomyomatosis-and-renal-cell-cancer,C0206654,T191,Disorders
What are the treatments for hereditary leiomyomatosis and renal cell cancer ?,0000465-5,treatment,These resources address the diagnosis or management of HLRCC:  - Gene Review: Gene Review: Hereditary Leiomyomatosis and Renal Cell Cancer  - Genetic Testing Registry: Hereditary leiomyomatosis and renal cell cancer  - MedlinePlus Encyclopedia: Renal Cell Carcinoma   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hereditary leiomyomatosis and renal cell cancer,0000465,GHR,https://ghr.nlm.nih.gov/condition/hereditary-leiomyomatosis-and-renal-cell-cancer,C0206654,T191,Disorders
What is (are) hereditary multiple osteochondromas ?,0000466-1,information,"Hereditary multiple osteochondromas is a condition in which people develop multiple benign (noncancerous) bone tumors called osteochondromas. The number of osteochondromas and the bones on which they are located vary greatly among affected individuals. The osteochondromas are not present at birth, but approximately 96 percent of affected people develop multiple osteochondromas by the time they are 12 years old. Osteochondromas typically form at the end of long bones and on flat bones such as the hip and shoulder blade. Once people with hereditary multiple osteochondromas reach adult height and their bones stop growing, the development of new osteochondromas also usually stops.  Multiple osteochondromas can disrupt bone growth and can cause growth disturbances of the arms, hands, and legs, leading to short stature. Often these problems with bone growth do not affect the right and left limb equally, resulting in uneven limb lengths (limb length discrepancy). Bowing of the forearm or ankle and abnormal development of the hip joints (hip dysplasia) caused by osteochondromas can lead to difficulty walking and general discomfort. Multiple osteochondromas may also result in pain, limited range of joint movement, and pressure on nerves, blood vessels, the spinal cord, and tissues surrounding the osteochondromas.  Osteochondromas are typically benign; however, in some instances these tumors become malignant (cancerous). Researchers estimate that people with hereditary multiple osteochondromas have a 1 in 20 to 1 in 200 lifetime risk of developing cancerous osteochondromas (called sarcomas).",hereditary multiple osteochondromas,0000466,GHR,https://ghr.nlm.nih.gov/condition/hereditary-multiple-osteochondromas,C0015306,T019,Disorders
How many people are affected by hereditary multiple osteochondromas ?,0000466-2,frequency,"The incidence of hereditary multiple osteochondromas is estimated to be 1 in 50,000 individuals. This condition occurs more frequently in some isolated populations: the incidence is approximately 1 in 1,000 in the Chamorro population of Guam and 1 in 77 in the Ojibway Indian population of Manitoba, Canada.",hereditary multiple osteochondromas,0000466,GHR,https://ghr.nlm.nih.gov/condition/hereditary-multiple-osteochondromas,C0015306,T019,Disorders
What are the genetic changes related to hereditary multiple osteochondromas ?,0000466-3,genetic changes,"Mutations in the EXT1 and EXT2 genes cause hereditary multiple osteochondromas. The EXT1 gene and the EXT2 gene provide instructions for producing the proteins exostosin-1 and exostosin-2, respectively. The two exostosin proteins bind together and form a complex found in a cell structure called the Golgi apparatus, which modifies newly produced enzymes and other proteins. In the Golgi apparatus, the exostosin-1 and exostosin-2 complex modifies a protein called heparan sulfate so it can be used by the cell.  When there is a mutation in exostosin-1 or exostosin-2, heparan sulfate cannot be processed correctly and is nonfunctional. Although heparan sulfate is involved in many bodily processes, it is unclear how the lack of this protein contributes to the development of osteochondromas.  If the condition is caused by a mutation in the EXT1 gene it is called hereditary multiple osteochondromas type 1. A mutation in the EXT2 gene causes hereditary multiple osteochondromas type 2. While both type 1 and type 2 involve multiple osteochondromas, mutations in the EXT1 gene likely account for 55 to 75 percent of all cases of hereditary multiple osteochondromas, and the severity of symptoms associated with osteochondromas seems to be greater in type 1.  Researchers estimate that about 15 percent of people with hereditary multiple osteochondromas have no mutation in either the EXT1 or the EXT2 gene. It is not known why multiple osteochondromas form in these individuals.",hereditary multiple osteochondromas,0000466,GHR,https://ghr.nlm.nih.gov/condition/hereditary-multiple-osteochondromas,C0015306,T019,Disorders
Is hereditary multiple osteochondromas inherited ?,0000466-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",hereditary multiple osteochondromas,0000466,GHR,https://ghr.nlm.nih.gov/condition/hereditary-multiple-osteochondromas,C0015306,T019,Disorders
What are the treatments for hereditary multiple osteochondromas ?,0000466-5,treatment,These resources address the diagnosis or management of hereditary multiple osteochondromas:  - Gene Review: Gene Review: Hereditary Multiple Osteochondromas  - Genetic Testing Registry: Multiple congenital exostosis  - Genetic Testing Registry: Multiple exostoses type 2   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hereditary multiple osteochondromas,0000466,GHR,https://ghr.nlm.nih.gov/condition/hereditary-multiple-osteochondromas,C0015306,T019,Disorders
What is (are) hereditary myopathy with early respiratory failure ?,0000467-1,information,"Hereditary myopathy with early respiratory failure (HMERF) is an inherited muscle disease that predominantly affects muscles close to the center of the body (proximal muscles) and muscles that are needed for breathing.  The major signs and symptoms of HMERF usually appear in adulthood, on average around age 35. Among the earliest muscles affected in HMERF are the neck flexors, which are muscles at the front of the neck that help hold the head up. Other proximal muscles that become weak in people with HMERF include those of the hips, thighs, and upper arms. Some affected individuals have also reported weakness in muscles of the lower leg and foot called the dorsal foot extensors.  HMERF also causes severe weakness in muscles of the chest that are involved in breathing, particularly the diaphragm. This weakness leads to breathing problems and life-threatening respiratory failure.",hereditary myopathy with early respiratory failure,0000467,GHR,https://ghr.nlm.nih.gov/condition/hereditary-myopathy-with-early-respiratory-failure,C3807376,T047,Disorders
How many people are affected by hereditary myopathy with early respiratory failure ?,0000467-2,frequency,"HMERF is a rare condition. It has been reported in several families of Swedish and French descent, and in at least one individual from Italy.",hereditary myopathy with early respiratory failure,0000467,GHR,https://ghr.nlm.nih.gov/condition/hereditary-myopathy-with-early-respiratory-failure,C3807376,T047,Disorders
What are the genetic changes related to hereditary myopathy with early respiratory failure ?,0000467-3,genetic changes,"HMERF can be caused by a mutation in the TTN gene. This gene provides instructions for making a protein called titin. Titin plays an important role in muscles the body uses for movement (skeletal muscles) and in heart (cardiac) muscle.  Within muscle cells, titin is an essential component of structures called sarcomeres. Sarcomeres are the basic units of muscle contraction; they are made of proteins that generate the mechanical force needed for muscles to contract. Titin has several functions within sarcomeres. One of its most important jobs is to provide structure, flexibility, and stability to these cell structures. Titin also plays a role in chemical signaling and in assembling new sarcomeres.  The TTN gene mutation responsible for HMERF leads to the production of an altered version of the titin protein. Studies suggest that this change may disrupt titin's interactions with other proteins within sarcomeres and interfere with the protein's role in chemical signaling. Consequently, muscle fibers become damaged and weaken over time. It is unclear why these effects are usually limited to proximal muscles and muscles involved in breathing.  Some people with the characteristic features of HMERF do not have identified mutations in the TTN gene. In these cases, the genetic cause of the condition is unknown.",hereditary myopathy with early respiratory failure,0000467,GHR,https://ghr.nlm.nih.gov/condition/hereditary-myopathy-with-early-respiratory-failure,C3807376,T047,Disorders
Is hereditary myopathy with early respiratory failure inherited ?,0000467-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",hereditary myopathy with early respiratory failure,0000467,GHR,https://ghr.nlm.nih.gov/condition/hereditary-myopathy-with-early-respiratory-failure,C3807376,T047,Disorders
What are the treatments for hereditary myopathy with early respiratory failure ?,0000467-5,treatment,"These resources address the diagnosis or management of HMERF:  - Gene Review: Gene Review: Hereditary Myopathy with Early Respiratory Failure (HMERF)  - Genetic Testing Registry: Hereditary myopathy with early respiratory failure  - National Heart, Lung, and Blood Institute: How Is Respiratory Failure Diagnosed?  - National Heart, Lung, and Blood Institute: How Is Respiratory Failure Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",hereditary myopathy with early respiratory failure,0000467,GHR,https://ghr.nlm.nih.gov/condition/hereditary-myopathy-with-early-respiratory-failure,C3807376,T047,Disorders
What is (are) hereditary neuralgic amyotrophy ?,0000468-1,information,"Hereditary neuralgic amyotrophy is a disorder characterized by episodes of severe pain and muscle wasting (amyotrophy) in one or both shoulders and arms. Neuralgic pain is felt along the path of one or more nerves and often has no obvious physical cause. The network of nerves involved in hereditary neuralgic amyotrophy, called the brachial plexus, controls movement and sensation in the shoulders and arms.  People with hereditary neuralgic amyotrophy usually begin experiencing attacks in their twenties, but episodes have occurred as early as the age of 1 year in some individuals. The attacks may be spontaneous or triggered by stress such as strenuous exercise, childbirth, surgery, exposure to cold, infections, immunizations, or emotional disturbance. While the frequency of the episodes tends to decrease with age, affected individuals are often left with residual problems, such as chronic pain and impaired movement, that accumulate over time.  Typically an attack begins with severe pain on one or both sides of the body; right-sided involvement is most common. The pain may be difficult to control with medication and usually lasts about a month. Within a period of time ranging from a few hours to a couple of weeks, the muscles in the affected area begin to weaken and waste away (atrophy), and movement becomes difficult. Muscle wasting may cause changes in posture or in the appearance of the shoulder, back, and arm. In particular, weak shoulder muscles tend to make the shoulder blades (scapulae) ""stick out"" from the back, a common sign known as scapular winging. Additional features of hereditary neuralgic amyotrophy may include decreased sensation (hypoesthesia) and abnormal sensations in the skin such as numbness or tingling (paresthesias). Areas other than the shoulder and arm may also be involved.  In a few affected families, individuals with hereditary neuralgic amyotrophy also have unusual physical characteristics including short stature, excess skin folds on the neck and arms, an opening in the roof of the mouth (cleft palate), a split in the soft flap of tissue that hangs from the back of the mouth (bifid uvula), and partially webbed or fused fingers or toes (partial syndactyly). They may also have distinctive facial features including eyes set close together (ocular hypotelorism), a narrow opening of the eyelids (short palpebral fissures) with a skin fold covering the inner corner of the eye (epicanthal fold), a long nasal bridge, a narrow mouth, and differences between one side of the face and the other (facial asymmetry).",hereditary neuralgic amyotrophy,0000468,GHR,https://ghr.nlm.nih.gov/condition/hereditary-neuralgic-amyotrophy,C0221759,T047,Disorders
How many people are affected by hereditary neuralgic amyotrophy ?,0000468-2,frequency,"Hereditary neuralgic amyotrophy is a rare disorder, but its specific prevalence is unknown. Approximately 200 families affected by the disorder have been identified worldwide.",hereditary neuralgic amyotrophy,0000468,GHR,https://ghr.nlm.nih.gov/condition/hereditary-neuralgic-amyotrophy,C0221759,T047,Disorders
What are the genetic changes related to hereditary neuralgic amyotrophy ?,0000468-3,genetic changes,"Mutations in the SEPT9 gene cause hereditary neuralgic amyotrophy. The SEPT9 gene provides instructions for making a protein called septin-9, which is part of a group of proteins called septins. Septins are involved in a process called cytokinesis, which is the step in cell division when the fluid inside the cell (cytoplasm) divides to form two separate cells.  The SEPT9 gene seems to be turned on (active) in cells throughout the body. Approximately 15 slightly different versions (isoforms) of the septin-9 protein may be produced from this gene. Some types of cells make certain isoforms, while other cell types produce other isoforms. However, the specific distribution of these isoforms in the body's tissues is not well understood. Septin-9 isoforms interact with other septin proteins to perform some of their functions.  Mutations in the SEPT9 gene may change the sequence of protein building blocks (amino acids) in certain septin-9 isoforms in ways that interfere with their function. These mutations may also change the distribution of septin-9 isoforms and their interactions with other septin proteins in some of the body's tissues. This change in the functioning of septin proteins seems to particularly affect the brachial plexus, but the reason for this is unknown.  Because many of the triggers for hereditary neuralgic amyotrophy also affect the immune system, researchers believe that an autoimmune reaction may be involved in this disorder. However, the relation between SEPT9 mutations and immune function is unclear. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. An autoimmune attack on the nerves in the brachial plexus likely results in the signs and symptoms of hereditary neuralgic amyotrophy.  At least 15 percent of families affected by hereditary neuralgic amyotrophy do not have SEPT9 gene mutations. In these cases, the disorder is believed to be caused by mutations in a gene that has not been identified.",hereditary neuralgic amyotrophy,0000468,GHR,https://ghr.nlm.nih.gov/condition/hereditary-neuralgic-amyotrophy,C0221759,T047,Disorders
Is hereditary neuralgic amyotrophy inherited ?,0000468-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",hereditary neuralgic amyotrophy,0000468,GHR,https://ghr.nlm.nih.gov/condition/hereditary-neuralgic-amyotrophy,C0221759,T047,Disorders
What are the treatments for hereditary neuralgic amyotrophy ?,0000468-5,treatment,These resources address the diagnosis or management of hereditary neuralgic amyotrophy:  - Gene Review: Gene Review: Hereditary Neuralgic Amyotrophy  - Genetic Testing Registry: Hereditary neuralgic amyotrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hereditary neuralgic amyotrophy,0000468,GHR,https://ghr.nlm.nih.gov/condition/hereditary-neuralgic-amyotrophy,C0221759,T047,Disorders
What is (are) hereditary neuropathy with liability to pressure palsies ?,0000469-1,information,"Hereditary neuropathy with liability to pressure palsies is a disorder that affects peripheral nerves. These nerves connect the brain and spinal cord to muscles as well as sensory cells that detect touch, pain, and temperature. In people with this disorder, the peripheral nerves are unusually sensitive to pressure.  Hereditary neuropathy with liability to pressure palsies causes recurrent episodes of numbness, tingling, and/or loss of muscle function (palsy). An episode can last from several minutes to several months, but recovery is usually complete. Repeated incidents, however, can cause permanent muscle weakness or loss of sensation. This disorder is also associated with pain in the limbs, especially the hands.  A pressure palsy episode results from problems in a single nerve, but any peripheral nerve can be affected. Episodes often recur, but not always at the same site. The most common problem sites involve nerves in wrists, elbows, and knees. Fingers, shoulders, hands, feet, and the scalp can also be affected. Many people with this disorder experience carpal tunnel syndrome when a nerve in the wrist (the median nerve) is involved. Carpal tunnel syndrome is characterized by numbness, tingling, and weakness in the hand and fingers. An episode in the hand may affect fine motor activities such as writing, opening jars, and fastening buttons. An episode in the leg can make walking, climbing stairs, or driving difficult or impossible.  Symptoms usually begin during adolescence or early adulthood but may develop anytime from childhood to late adulthood. Symptoms vary in severity; many people never realize they have the disorder, while some people experience prolonged disability. Hereditary neuropathy with liability to pressure palsies does not affect life expectancy.",hereditary neuropathy with liability to pressure palsies,0000469,GHR,https://ghr.nlm.nih.gov/condition/hereditary-neuropathy-with-liability-to-pressure-palsies,C0460139,T047,Disorders
How many people are affected by hereditary neuropathy with liability to pressure palsies ?,0000469-2,frequency,"Hereditary neuropathy with liability to pressure palsies is estimated to occur in 2 to 5 per 100,000 individuals.",hereditary neuropathy with liability to pressure palsies,0000469,GHR,https://ghr.nlm.nih.gov/condition/hereditary-neuropathy-with-liability-to-pressure-palsies,C0460139,T047,Disorders
What are the genetic changes related to hereditary neuropathy with liability to pressure palsies ?,0000469-3,genetic changes,"Mutations in the PMP22 gene cause hereditary neuropathy with liability to pressure palsies.  Hereditary neuropathy with liability to pressure palsies is caused by the loss of one copy of the PMP22 gene or alterations within the gene. The consequences of PMP22 gene mutations are not clearly understood. Most likely, PMP22 gene mutations affect myelin, the protective substance that covers nerve cells. As a result of these mutations, some of the protective myelin covering may become unstable, which leads to increased sensitivity to pressure on the nerves.",hereditary neuropathy with liability to pressure palsies,0000469,GHR,https://ghr.nlm.nih.gov/condition/hereditary-neuropathy-with-liability-to-pressure-palsies,C0460139,T047,Disorders
Is hereditary neuropathy with liability to pressure palsies inherited ?,0000469-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",hereditary neuropathy with liability to pressure palsies,0000469,GHR,https://ghr.nlm.nih.gov/condition/hereditary-neuropathy-with-liability-to-pressure-palsies,C0460139,T047,Disorders
What are the treatments for hereditary neuropathy with liability to pressure palsies ?,0000469-5,treatment,These resources address the diagnosis or management of hereditary neuropathy with liability to pressure palsies:  - Gene Review: Gene Review: Hereditary Neuropathy with Liability to Pressure Palsies  - Genetic Testing Registry: Hereditary liability to pressure palsies  - MedlinePlus Encyclopedia: carpal tunnel syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hereditary neuropathy with liability to pressure palsies,0000469,GHR,https://ghr.nlm.nih.gov/condition/hereditary-neuropathy-with-liability-to-pressure-palsies,C0460139,T047,Disorders
What is (are) hereditary pancreatitis ?,0000470-1,information,"Hereditary pancreatitis is a genetic condition characterized by recurrent episodes of inflammation of the pancreas (pancreatitis). The pancreas produces enzymes that help digest food, and it also produces insulin, a hormone that controls blood sugar levels in the body. Episodes of pancreatitis can lead to permanent tissue damage and loss of pancreatic function.  Signs and symptoms of this condition usually begin in late childhood with an episode of acute pancreatitis. A sudden (acute) attack can cause abdominal pain, fever, nausea, or vomiting. An episode typically lasts from one to three days, although some people may experience severe episodes that last longer. Hereditary pancreatitis progresses to recurrent acute pancreatitis with multiple episodes of acute pancreatitis that recur over a period of at least a year; the number of episodes a person experiences varies. Recurrent acute pancreatitis leads to chronic pancreatitis, which occurs when the pancreas is persistently inflamed. Chronic pancreatitis usually develops by early adulthood in affected individuals. Signs and symptoms of chronic pancreatitis include occasional or frequent abdominal pain of varying severity, flatulence, and bloating. Many individuals with hereditary pancreatitis also develop abnormal calcium deposits in the pancreas (pancreatic calcifications) by early adulthood.  Years of inflammation damage the pancreas, causing the formation of scar tissue (fibrosis) in place of functioning pancreatic tissue. Pancreatic fibrosis leads to the loss of pancreatic function in many affected individuals. This loss of function can impair the production of digestive enzymes and disrupt normal digestion, leading to fatty stool (steatorrhea), weight loss, and protein and vitamin deficiencies. Because of a decrease in insulin production due to a loss of pancreatic function, about a quarter of individuals with hereditary pancreatitis will develop type 1 diabetes mellitus by mid-adulthood; the risk of developing diabetes increases with age.  Chronic pancreatic inflammation and damage to the pancreas increase the risk of developing pancreatic cancer. The risk is particularly high in people with hereditary pancreatitis who also smoke, use alcohol, have type 1 diabetes mellitus, or have a family history of cancer. In affected individuals who develop pancreatic cancer, it is typically diagnosed in mid-adulthood.  Complications from pancreatic cancer and type 1 diabetes mellitus are the most common causes of death in individuals with hereditary pancreatitis, although individuals with this condition are thought to have a normal life expectancy.",hereditary pancreatitis,0000470,GHR,https://ghr.nlm.nih.gov/condition/hereditary-pancreatitis,C0238339,T047,Disorders
How many people are affected by hereditary pancreatitis ?,0000470-2,frequency,"Hereditary pancreatitis is thought to be a rare condition. In Europe, its prevalence is estimated to be 3 to 6 per million individuals.",hereditary pancreatitis,0000470,GHR,https://ghr.nlm.nih.gov/condition/hereditary-pancreatitis,C0238339,T047,Disorders
What are the genetic changes related to hereditary pancreatitis ?,0000470-3,genetic changes,"Mutations in the PRSS1 gene cause most cases of hereditary pancreatitis. The PRSS1 gene provides instructions for making an enzyme called cationic trypsinogen. This enzyme is produced in the pancreas and helps with the digestion of food. When cationic trypsinogen is needed, it is released (secreted) from the pancreas and transported to the small intestine, where it is cut (cleaved) into its working or active form called trypsin. When digestion is complete and trypsin is no longer needed, the enzyme is broken down.  Some PRSS1 gene mutations that cause hereditary pancreatitis result in the production of a cationic trypsinogen enzyme that is prematurely converted to trypsin while it is still in the pancreas. Other mutations prevent trypsin from being broken down. These changes result in elevated levels of trypsin in the pancreas. Trypsin activity in the pancreas can damage pancreatic tissue and can also trigger an immune response, causing inflammation in the pancreas.  It is estimated that 65 to 80 percent of people with hereditary pancreatitis have mutations in the PRSS1 gene. The remaining cases are caused by mutations in other genes, some of which have not been identified.",hereditary pancreatitis,0000470,GHR,https://ghr.nlm.nih.gov/condition/hereditary-pancreatitis,C0238339,T047,Disorders
Is hereditary pancreatitis inherited ?,0000470-4,inheritance,"When hereditary pancreatitis is caused by mutations in the PRSS1 gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the PRSS1 gene mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  It is estimated that 20 percent of people who have the altered PRSS1 gene never have an episode of pancreatitis. (This situation is known as reduced penetrance.) It is unclear why some people with a mutated gene never develop signs and symptoms of the disease.",hereditary pancreatitis,0000470,GHR,https://ghr.nlm.nih.gov/condition/hereditary-pancreatitis,C0238339,T047,Disorders
What are the treatments for hereditary pancreatitis ?,0000470-5,treatment,These resources address the diagnosis or management of hereditary pancreatitis:  - Encyclopedia: Chronic Pancreatitis  - Gene Review: Gene Review: PRSS1-Related Hereditary Pancreatitis  - Gene Review: Gene Review: Pancreatitis Overview  - Genetic Testing Registry: Hereditary pancreatitis  - Johns Hopkins Medicine: Treatment Options for Pancreatitis  - MD Anderson Cancer Center: Pancreatic Cancer Diagnosis  - MedlinePlus Encyclopedia: Acute Pancreatitis  - MedlinePlus Encyclopedia: Chronic Pancreatitis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hereditary pancreatitis,0000470,GHR,https://ghr.nlm.nih.gov/condition/hereditary-pancreatitis,C0238339,T047,Disorders
What is (are) hereditary paraganglioma-pheochromocytoma ?,0000471-1,information,"Hereditary paraganglioma-pheochromocytoma is a condition characterized by the growth of noncancerous (benign) tumors in structures called paraganglia. Paraganglia are groups of cells that are found near nerve cell bunches called ganglia. A tumor involving the paraganglia is known as a paraganglioma. A type of paraganglioma known as a pheochromocytoma develops in the adrenal glands, which are located on top of each kidney and produce hormones in response to stress. Other types of paraganglioma are usually found in the head, neck, or trunk. People with hereditary paraganglioma-pheochromocytoma develop one or more paragangliomas, which may include pheochromocytomas.  Pheochromocytomas and some other paragangliomas are associated with ganglia of the sympathetic nervous system. The sympathetic nervous system controls the ""fight-or-flight"" response, a series of changes in the body due to hormones released in response to stress. Sympathetic paragangliomas found outside the adrenal glands, usually in the abdomen, are called extra-adrenal paragangliomas. Most sympathetic paragangliomas, including pheochromocytomas, produce hormones called catecholamines, such as epinephrine (adrenaline) or norepinephrine. These excess catecholamines can cause signs and symptoms such as high blood pressure (hypertension), episodes of rapid heartbeat (palpitations), headaches, or sweating.  Most paragangliomas are associated with ganglia of the parasympathetic nervous system, which controls involuntary body functions such as digestion and saliva formation. Parasympathetic paragangliomas, typically found in the head and neck, usually do not produce hormones. However, large tumors may cause signs and symptoms such as coughing, hearing loss in one ear, or difficulty swallowing.  Although most paragangliomas and pheochromocytomas are noncancerous, some can become cancerous (malignant) and spread to other parts of the body (metastasize). Extra-adrenal paragangliomas become malignant more often than other types of paraganglioma or pheochromocytoma.  Researchers have identified four types of hereditary paraganglioma-pheochromocytoma, named types 1 through 4. Each type is distinguished by its genetic cause. People with types 1, 2, and 3 typically develop paragangliomas in the head or neck region. People with type 4 usually develop extra-adrenal paragangliomas in the abdomen and are at higher risk for malignant tumors that metastasize. Hereditary paraganglioma-pheochromocytoma is typically diagnosed in a person's 30s.",hereditary paraganglioma-pheochromocytoma,0000471,GHR,https://ghr.nlm.nih.gov/condition/hereditary-paraganglioma-pheochromocytoma,C0030421,T191,Disorders
How many people are affected by hereditary paraganglioma-pheochromocytoma ?,0000471-2,frequency,Hereditary paraganglioma-pheochromocytoma occurs in approximately 1 in 1 million people.,hereditary paraganglioma-pheochromocytoma,0000471,GHR,https://ghr.nlm.nih.gov/condition/hereditary-paraganglioma-pheochromocytoma,C0030421,T191,Disorders
What are the genetic changes related to hereditary paraganglioma-pheochromocytoma ?,0000471-3,genetic changes,"Mutations in at least four genes increase the risk of developing the different types of hereditary paraganglioma-pheochromocytoma. Mutations in the SDHD gene predispose an individual to hereditary paraganglioma-pheochromocytoma type 1; mutations in the SDHAF2 gene predispose to type 2; mutations in the SDHC gene predispose to type 3; and mutations in the SDHB gene predispose to type 4.  The SDHB, SDHC, and SDHD genes provide instructions for making three of the four subunits of an enzyme called succinate dehydrogenase (SDH). In addition, the protein made by the SDHAF2 gene is required for the SDH enzyme to function. The SDH enzyme links two important cellular pathways called the citric acid cycle (or Krebs cycle) and oxidative phosphorylation. These pathways are critical in converting the energy from food into a form that cells can use.  As part of the citric acid cycle, the SDH enzyme converts a compound called succinate to another compound called fumarate. Succinate acts as an oxygen sensor in the cell and can help turn on specific pathways that stimulate cells to grow in a low-oxygen environment (hypoxia).  Mutations in the SDHB, SDHC, SDHD, and SDHAF2 genes lead to the loss or reduction of SDH enzyme activity. Because the mutated SDH enzyme cannot convert succinate to fumarate, succinate accumulates in the cell. As a result, the hypoxia pathways are triggered in normal oxygen conditions, which lead to abnormal cell growth and tumor formation.",hereditary paraganglioma-pheochromocytoma,0000471,GHR,https://ghr.nlm.nih.gov/condition/hereditary-paraganglioma-pheochromocytoma,C0030421,T191,Disorders
Is hereditary paraganglioma-pheochromocytoma inherited ?,0000471-4,inheritance,"Hereditary paraganglioma-pheochromocytoma is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing tumors. An additional mutation that deletes the normal copy of the gene is needed to cause the condition. This second mutation, called a somatic mutation, is acquired during a person's lifetime and is present only in tumor cells.  The risk of developing hereditary paraganglioma-pheochromocytoma types 1 and 2 is passed on only if the mutated copy of the gene is inherited from the father. The mechanism of this pattern of inheritance is unknown. The risk of developing types 3 and 4 can be inherited from the mother or the father.",hereditary paraganglioma-pheochromocytoma,0000471,GHR,https://ghr.nlm.nih.gov/condition/hereditary-paraganglioma-pheochromocytoma,C0030421,T191,Disorders
What are the treatments for hereditary paraganglioma-pheochromocytoma ?,0000471-5,treatment,These resources address the diagnosis or management of hereditary paraganglioma-pheochromocytoma:  - Gene Review: Gene Review: Hereditary Paraganglioma-Pheochromocytoma Syndromes  - Genetic Testing Registry: Paragangliomas 1  - Genetic Testing Registry: Paragangliomas 2  - Genetic Testing Registry: Paragangliomas 3  - Genetic Testing Registry: Paragangliomas 4  - MedlinePlus Encyclopedia: Pheochromocytoma  - National Cancer Institute: Pheochromocytoma and Paraganglioma   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hereditary paraganglioma-pheochromocytoma,0000471,GHR,https://ghr.nlm.nih.gov/condition/hereditary-paraganglioma-pheochromocytoma,C0030421,T191,Disorders
What is (are) hereditary sensory and autonomic neuropathy type IE ?,0000472-1,information,"Hereditary sensory and autonomic neuropathy type IE (HSAN IE) is a disorder that affects the nervous system. Affected individuals have a gradual loss of intellectual function (dementia), typically beginning in their thirties. In some people with this disorder, changes in personality become apparent before problems with thinking skills.  People with HSAN IE also develop hearing loss that is caused by abnormalities in the inner ear (sensorineural hearing loss). The hearing loss gets worse over time and usually progresses to moderate or severe deafness between the ages of 20 and 35.  HSAN IE is characterized by impaired function of nerve cells called sensory neurons, which transmit information about sensations such as pain, temperature, and touch. Sensations in the feet and legs are particularly affected in people with HSAN IE. Gradual loss of sensation in the feet (peripheral neuropathy), which usually begins in adolescence or early adulthood, can lead to difficulty walking. Affected individuals may not be aware of injuries to their feet, which can lead to open sores and infections. If these complications are severe, amputation of the affected areas may be required.  HSAN IE is also characterized by a loss of the ability to sweat (sudomotor function), especially on the hands and feet. Sweating is a function of the autonomic nervous system, which also controls involuntary body functions such as heart rate, digestion, and breathing. These other autonomic functions are unaffected in people with HSAN IE.  The severity of the signs and symptoms of HSAN IE and their age of onset are variable, even within the same family.",hereditary sensory and autonomic neuropathy type IE,0000472,GHR,https://ghr.nlm.nih.gov/condition/hereditary-sensory-and-autonomic-neuropathy-type-ie,C3279885,T047,Disorders
How many people are affected by hereditary sensory and autonomic neuropathy type IE ?,0000472-2,frequency,HSAN IE is a rare disorder; its prevalence is unknown. Small numbers of affected families have been identified in populations around the world.,hereditary sensory and autonomic neuropathy type IE,0000472,GHR,https://ghr.nlm.nih.gov/condition/hereditary-sensory-and-autonomic-neuropathy-type-ie,C3279885,T047,Disorders
What are the genetic changes related to hereditary sensory and autonomic neuropathy type IE ?,0000472-3,genetic changes,"HSAN IE is caused by mutations in the DNMT1 gene. This gene provides instructions for making an enzyme called DNA (cytosine-5)-methyltransferase 1. This enzyme is involved in DNA methylation, which is the addition of methyl groups, consisting of one carbon atom and three hydrogen atoms, to DNA molecules. In particular, the enzyme helps add methyl groups to DNA building blocks (nucleotides) called cytosines.  DNA methylation is important in many cellular functions. These include determining whether the instructions in a particular segment of DNA are carried out or suppressed (gene silencing), regulating reactions involving proteins and fats (lipids), and controlling the processing of chemicals that relay signals in the nervous system (neurotransmitters). DNA (cytosine-5)-methyltransferase 1 is active in the adult nervous system. Although its specific function is not well understood, the enzyme may help regulate nerve cell (neuron) maturation and specialization (differentiation), the ability of neurons to migrate where needed and connect with each other, and neuron survival.  DNMT1 gene mutations that cause HSAN IE reduce or eliminate the enzyme's methylation function, resulting in abnormalities in the maintenance of the neurons that make up the nervous system. However, it is not known how the mutations cause the specific signs and symptoms of HSAN IE.",hereditary sensory and autonomic neuropathy type IE,0000472,GHR,https://ghr.nlm.nih.gov/condition/hereditary-sensory-and-autonomic-neuropathy-type-ie,C3279885,T047,Disorders
Is hereditary sensory and autonomic neuropathy type IE inherited ?,0000472-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.",hereditary sensory and autonomic neuropathy type IE,0000472,GHR,https://ghr.nlm.nih.gov/condition/hereditary-sensory-and-autonomic-neuropathy-type-ie,C3279885,T047,Disorders
What are the treatments for hereditary sensory and autonomic neuropathy type IE ?,0000472-5,treatment,"These resources address the diagnosis or management of hereditary sensory and autonomic neuropathy type IE:  - Gene Review: Gene Review: DNMT1-Related Dementia, Deafness, and Sensory Neuropathy  - University of Chicago: Center for Peripheral Neuropathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",hereditary sensory and autonomic neuropathy type IE,0000472,GHR,https://ghr.nlm.nih.gov/condition/hereditary-sensory-and-autonomic-neuropathy-type-ie,C3279885,T047,Disorders
What is (are) hereditary sensory and autonomic neuropathy type II ?,0000473-1,information,"Hereditary sensory and autonomic neuropathy type II (HSAN2) is a condition that primarily affects the sensory nerve cells (sensory neurons), which transmit information about sensations such as pain, temperature, and touch. These sensations are impaired in people with HSAN2. In some affected people, the condition may also cause mild abnormalities of the autonomic nervous system, which controls involuntary body functions such as heart rate, digestion, and breathing. The signs and symptoms of HSAN2 typically begin in infancy or early childhood.  The first sign of HSAN2 is usually numbness in the hands and feet. Soon after, affected individuals lose the ability to feel pain or sense hot and cold. People with HSAN2 often develop open sores (ulcers) on their hands and feet. Because affected individuals cannot feel the pain of these sores, they may not seek treatment right away. Without treatment, the ulcers can become infected and may lead to amputation of the affected area. Unintentional self-injury is common in people with HSAN2, typically by biting the tongue, lips, or fingers. These injuries may lead to spontaneous amputation of the affected areas. Affected individuals often have injuries and fractures in their hands, feet, limbs, and joints that go untreated because of the inability to feel pain. Repeated injury can lead to a condition called Charcot joints, in which the bones and tissue surrounding joints are destroyed.  The effects of HSAN2 on the autonomic nervous system are more variable. Some infants with HSAN2 have trouble sucking, which makes it difficult for them to eat. People with HSAN2 may experience episodes in which breathing slows or stops for short periods (apnea); digestive problems such as the backflow of stomach acids into the esophagus (gastroesophageal reflux); or slow eye blink or gag reflexes. Affected individuals may also have weak deep tendon reflexes, such as the reflex being tested when a doctor taps the knee with a hammer.  Some people with HSAN2 lose a type of taste bud on the tip of the tongue called lingual fungiform papillae and have a diminished sense of taste.",hereditary sensory and autonomic neuropathy type II,0000473,GHR,https://ghr.nlm.nih.gov/condition/hereditary-sensory-and-autonomic-neuropathy-type-ii,C0259749,T047,Disorders
How many people are affected by hereditary sensory and autonomic neuropathy type II ?,0000473-2,frequency,"HSAN2 is a rare disease; however, the prevalence is unknown.",hereditary sensory and autonomic neuropathy type II,0000473,GHR,https://ghr.nlm.nih.gov/condition/hereditary-sensory-and-autonomic-neuropathy-type-ii,C0259749,T047,Disorders
What are the genetic changes related to hereditary sensory and autonomic neuropathy type II ?,0000473-3,genetic changes,"There are two types of HSAN2, called HSAN2A and HSAN2B, each caused by mutations in a different gene. HSAN2A is caused by mutations in the WNK1 gene, and HSAN2B is caused by mutations in the FAM134B gene. Although two different genes are involved, the signs and symptoms of HSAN2A and HSAN2B are the same.  The WNK1 gene provides instructions for making multiple versions (isoforms) of the WNK1 protein. HSAN2A is caused by mutations that affect a particular isoform called the WNK1/HSN2 protein. This protein is found in the cells of the nervous system, including nerve cells that transmit the sensations of pain, temperature, and touch (sensory neurons). The mutations involved in HSAN2A result in an abnormally short WNK1/HSN2 protein. Although the function of this protein is unknown, it is likely that the abnormally short version cannot function properly. People with HSAN2A have a reduction in the number of sensory neurons; however, the role that WNK1/HSN2 mutations play in that loss is unclear.  HSAN2B is caused by mutations in the FAM134B gene. These mutations may lead to an abnormally short and nonfunctional protein. The FAM134B protein is found in sensory and autonomic neurons. It is involved in the survival of neurons, particularly those that transmit pain signals, which are called nociceptive neurons. When the FAM134B protein is nonfunctional, neurons die by a process of self-destruction called apoptosis.  The loss of neurons leads to the inability to feel pain, temperature, and touch sensations and to the impairment of the autonomic nervous system seen in people with HSAN2.",hereditary sensory and autonomic neuropathy type II,0000473,GHR,https://ghr.nlm.nih.gov/condition/hereditary-sensory-and-autonomic-neuropathy-type-ii,C0259749,T047,Disorders
Is hereditary sensory and autonomic neuropathy type II inherited ?,0000473-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",hereditary sensory and autonomic neuropathy type II,0000473,GHR,https://ghr.nlm.nih.gov/condition/hereditary-sensory-and-autonomic-neuropathy-type-ii,C0259749,T047,Disorders
What are the treatments for hereditary sensory and autonomic neuropathy type II ?,0000473-5,treatment,These resources address the diagnosis or management of HSAN2:  - Gene Review: Gene Review: Hereditary Sensory and Autonomic Neuropathy Type II  - Genetic Testing Registry: Hereditary sensory and autonomic neuropathy type IIA  - Genetic Testing Registry: Hereditary sensory and autonomic neuropathy type IIB   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hereditary sensory and autonomic neuropathy type II,0000473,GHR,https://ghr.nlm.nih.gov/condition/hereditary-sensory-and-autonomic-neuropathy-type-ii,C0259749,T047,Disorders
What is (are) hereditary sensory and autonomic neuropathy type V ?,0000474-1,information,"Hereditary sensory and autonomic neuropathy type V (HSAN5) is a condition that primarily affects the sensory nerve cells (sensory neurons), which transmit information about sensations such as pain, temperature, and touch. These sensations are impaired in people with HSAN5.  The signs and symptoms of HSAN5 appear early, usually at birth or during infancy. People with HSAN5 lose the ability to feel pain, heat, and cold. Deep pain perception, the feeling of pain from injuries to bones, ligaments, or muscles, is especially affected in people with HSAN5. Because of the inability to feel deep pain, affected individuals suffer repeated severe injuries such as bone fractures and joint injuries that go unnoticed. Repeated trauma can lead to a condition called Charcot joints, in which the bones and tissue surrounding joints are destroyed.",hereditary sensory and autonomic neuropathy type V,0000474,GHR,https://ghr.nlm.nih.gov/condition/hereditary-sensory-and-autonomic-neuropathy-type-v,C0259749,T047,Disorders
How many people are affected by hereditary sensory and autonomic neuropathy type V ?,0000474-2,frequency,HSAN5 is very rare. Only a few people with the condition have been identified.,hereditary sensory and autonomic neuropathy type V,0000474,GHR,https://ghr.nlm.nih.gov/condition/hereditary-sensory-and-autonomic-neuropathy-type-v,C0259749,T047,Disorders
What are the genetic changes related to hereditary sensory and autonomic neuropathy type V ?,0000474-3,genetic changes,"Mutations in the NGF gene cause HSAN5. The NGF gene provides instructions for making a protein called nerve growth factor beta (NGF) that is important in the development and survival of nerve cells (neurons), including sensory neurons. The NGF protein functions by attaching (binding) to its receptors, which are found on the surface of neurons. Binding of the NGF protein to its receptor transmits signals to the cell to grow and to mature and take on specialized functions (differentiate). This binding also blocks signals in the cell that initiate the process of self-destruction (apoptosis). Additionally, NGF signaling plays a role in pain sensation. Mutation of the NGF gene leads to the production of a protein that cannot bind to the receptor and does not transmit signals properly. Without the proper signaling, sensory neurons die and pain sensation is altered, resulting in the inability of people with HSAN5 to feel pain.",hereditary sensory and autonomic neuropathy type V,0000474,GHR,https://ghr.nlm.nih.gov/condition/hereditary-sensory-and-autonomic-neuropathy-type-v,C0259749,T047,Disorders
Is hereditary sensory and autonomic neuropathy type V inherited ?,0000474-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",hereditary sensory and autonomic neuropathy type V,0000474,GHR,https://ghr.nlm.nih.gov/condition/hereditary-sensory-and-autonomic-neuropathy-type-v,C0259749,T047,Disorders
What are the treatments for hereditary sensory and autonomic neuropathy type V ?,0000474-5,treatment,These resources address the diagnosis or management of HSAN5:  - Genetic Testing Registry: Congenital sensory neuropathy with selective loss of small myelinated fibers   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hereditary sensory and autonomic neuropathy type V,0000474,GHR,https://ghr.nlm.nih.gov/condition/hereditary-sensory-and-autonomic-neuropathy-type-v,C0259749,T047,Disorders
What is (are) hereditary sensory neuropathy type IA ?,0000475-1,information,"Hereditary sensory neuropathy type IA is a condition characterized by nerve abnormalities in the legs and feet (peripheral neuropathy). Many people with this condition experience prickling or tingling sensations (paresthesias), numbness, and a reduced ability to feel pain and sense hot and cold. Some affected individuals do not lose sensation, but instead feel shooting pains in their legs and feet. As the disorder progresses, the sensory abnormalities can affect the hands, arms, shoulders, joints, and abdomen. Affected individuals may also experience muscle wasting and weakness as they get older. Weakness in the ankle muscles can make walking difficult. As the condition progresses, some people with hereditary sensory neuropathy type IA require wheelchair assistance.  Individuals with hereditary sensory neuropathy type IA typically get open sores (ulcers) on their feet or hands or infections of the soft tissue of the fingertips (whitlows) that are slow to heal. Because affected individuals cannot feel the pain of these sores, they may not seek immediate treatment. Without treatment, the ulcers can become infected and may require amputation of the surrounding area or limb.  Some people with hereditary sensory neuropathy type IA develop hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss). Hearing loss typically develops in middle to late adulthood.  The signs and symptoms of hereditary sensory neuropathy type IA can begin anytime between adolescence and late adulthood. While the features of this condition tend to worsen over time, affected individuals have a normal life expectancy if signs and symptoms are properly treated.",hereditary sensory neuropathy type IA,0000475,GHR,https://ghr.nlm.nih.gov/condition/hereditary-sensory-neuropathy-type-ia,C0020071,T047,Disorders
How many people are affected by hereditary sensory neuropathy type IA ?,0000475-2,frequency,"Hereditary sensory neuropathy type IA is a rare condition; its prevalence is estimated to be 1 to 2 per 100,000 individuals.",hereditary sensory neuropathy type IA,0000475,GHR,https://ghr.nlm.nih.gov/condition/hereditary-sensory-neuropathy-type-ia,C0020071,T047,Disorders
What are the genetic changes related to hereditary sensory neuropathy type IA ?,0000475-3,genetic changes,"Mutations in the SPTLC1 gene cause hereditary sensory neuropathy type IA. The SPTLC1 gene provides instructions for making one part (subunit) of an enzyme called serine palmitoyltransferase (SPT). The SPT enzyme is involved in making certain fats called sphingolipids. Sphingolipids are important components of cell membranes and play a role in many cell functions.  SPTLC1 gene mutations reduce the amount of functional SPTLC1 subunit that is produced, which results in an SPT enzyme with altered activity. This altered enzyme makes molecules called deoxysphingoid bases, which it does not normally produce. Because of this new function, the SPT enzyme's production of sphingolipid is reduced. Overall, there does not seem to be a decrease in sphingolipid production because the body is able to compensate for the SPT enzyme's reduced production. When accumulated, deoxysphingoid bases are toxic to neurons. The gradual destruction of nerve cells caused by the buildup of these toxic molecules results in loss of sensation and muscle weakness in people with hereditary sensory neuropathy type IA. Although the SPT enzyme does not produce a normal amount of sphingolipids, the body is able to compensate, and there does not seem to be an overall reduction of these fats in the body.",hereditary sensory neuropathy type IA,0000475,GHR,https://ghr.nlm.nih.gov/condition/hereditary-sensory-neuropathy-type-ia,C0020071,T047,Disorders
Is hereditary sensory neuropathy type IA inherited ?,0000475-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",hereditary sensory neuropathy type IA,0000475,GHR,https://ghr.nlm.nih.gov/condition/hereditary-sensory-neuropathy-type-ia,C0020071,T047,Disorders
What are the treatments for hereditary sensory neuropathy type IA ?,0000475-5,treatment,These resources address the diagnosis or management of hereditary sensory neuropathy type IA:  - Gene Review: Gene Review: Hereditary Sensory Neuropathy Type IA  - Genetic Testing Registry: Neuropathy hereditary sensory and autonomic type 1  - Rare Diseases Clinical Research Network: Inherited Neuropathies Consortium  - The Foundation for Peripheral Neuropathy: Symptoms   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hereditary sensory neuropathy type IA,0000475,GHR,https://ghr.nlm.nih.gov/condition/hereditary-sensory-neuropathy-type-ia,C0020071,T047,Disorders
What is (are) hereditary spherocytosis ?,0000476-1,information,"Hereditary spherocytosis is a condition that affects red blood cells. People with this condition typically experience a shortage of red blood cells (anemia), yellowing of the eyes and skin (jaundice), and an enlarged spleen (splenomegaly). Most newborns with hereditary spherocytosis have severe anemia, although it improves after the first year of life. Splenomegaly can occur anytime from early childhood to adulthood. About half of affected individuals develop hard deposits in the gallbladder called gallstones, which typically occur from late childhood to mid-adulthood.  There are four forms of hereditary spherocytosis, which are distinguished by the severity of signs and symptoms. They are known as the mild form, the moderate form, the moderate/severe form, and the severe form. It is estimated that 20 to 30 percent of people with hereditary spherocytosis have the mild form, 60 to 70 percent have the moderate form, 10 percent have the moderate/severe form, and 3 to 5 percent have the severe form.  People with the mild form may have very mild anemia or sometimes have no symptoms. People with the moderate form typically have anemia, jaundice, and splenomegaly. Many also develop gallstones. The signs and symptoms of moderate hereditary spherocytosis usually appear in childhood. Individuals with the moderate/severe form have all the features of the moderate form but also have severe anemia. Those with the severe form have life-threatening anemia that requires frequent blood transfusions to replenish their red blood cell supply. They also have severe splenomegaly, jaundice, and a high risk for developing gallstones. Some individuals with the severe form have short stature, delayed sexual development, and skeletal abnormalities.",hereditary spherocytosis,0000476,GHR,https://ghr.nlm.nih.gov/condition/hereditary-spherocytosis,C0553720,T047,Disorders
How many people are affected by hereditary spherocytosis ?,0000476-2,frequency,"Hereditary spherocytosis occurs in 1 in 2,000 individuals of Northern European ancestry. This condition is the most common cause of inherited anemia in that population. The prevalence of hereditary spherocytosis in people of other ethnic backgrounds is unknown, but it is much less common.",hereditary spherocytosis,0000476,GHR,https://ghr.nlm.nih.gov/condition/hereditary-spherocytosis,C0553720,T047,Disorders
What are the genetic changes related to hereditary spherocytosis ?,0000476-3,genetic changes,"Mutations in at least five genes cause hereditary spherocytosis. These genes provide instructions for producing proteins that are found on the membranes of red blood cells. These proteins transport molecules into and out of cells, attach to other proteins, and maintain cell structure. Some of these proteins allow for cell flexibility; red blood cells have to be flexible to travel from the large blood vessels (arteries) to the smaller blood vessels (capillaries). The proteins allow the cell to change shape without breaking when passing through narrow capillaries.  Mutations in red blood cell membrane proteins result in an overly rigid, misshapen cell. Instead of a flattened disc shape, these cells are spherical. Dysfunctional membrane proteins interfere with the cell's ability to change shape when traveling through the blood vessels. The misshapen red blood cells, called spherocytes, are removed from circulation and taken to the spleen for destruction. Within the spleen, the red blood cells break down (undergo hemolysis). The shortage of red blood cells in circulation and the abundance of cells in the spleen are responsible for the signs and symptoms of hereditary spherocytosis.  Mutations in the ANK1 gene are responsible for approximately half of all cases of hereditary spherocytosis. The other genes associated with hereditary spherocytosis each account for a smaller percentage of cases of this condition.",hereditary spherocytosis,0000476,GHR,https://ghr.nlm.nih.gov/condition/hereditary-spherocytosis,C0553720,T047,Disorders
Is hereditary spherocytosis inherited ?,0000476-4,inheritance,"In about 75 percent of cases, hereditary spherocytosis is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  This condition can also be inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",hereditary spherocytosis,0000476,GHR,https://ghr.nlm.nih.gov/condition/hereditary-spherocytosis,C0553720,T047,Disorders
What are the treatments for hereditary spherocytosis ?,0000476-5,treatment,"These resources address the diagnosis or management of hereditary spherocytosis:  - Genetic Testing Registry: Hereditary spherocytosis  - Genetic Testing Registry: Spherocytosis type 2  - Genetic Testing Registry: Spherocytosis type 3  - Genetic Testing Registry: Spherocytosis type 4  - Genetic Testing Registry: Spherocytosis type 5  - Genetic Testing Registry: Spherocytosis, type 1, autosomal recessive  - Seattle Children's Hospital: Hereditary Spherocytosis Treatment Options   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",hereditary spherocytosis,0000476,GHR,https://ghr.nlm.nih.gov/condition/hereditary-spherocytosis,C0553720,T047,Disorders
What is (are) hereditary xanthinuria ?,0000477-1,information,"Hereditary xanthinuria is a condition that most often affects the kidneys. It is characterized by high levels of a compound called xanthine and very low levels of another compound called uric acid in the blood and urine. The excess xanthine can accumulate in the kidneys and other tissues. In the kidneys, xanthine forms tiny crystals that occasionally build up to create kidney stones. These stones can impair kidney function and ultimately cause kidney failure. Related signs and symptoms can include abdominal pain, recurrent urinary tract infections, and blood in the urine (hematuria). Less commonly, xanthine crystals build up in the muscles, causing pain and cramping. In some people with hereditary xanthinuria, the condition does not cause any health problems.  Researchers have described two major forms of hereditary xanthinuria, types I and II. The types are distinguished by the enzymes involved; they have the same signs and symptoms.",hereditary xanthinuria,0000477,GHR,https://ghr.nlm.nih.gov/condition/hereditary-xanthinuria,C0220988,T047,Disorders
How many people are affected by hereditary xanthinuria ?,0000477-2,frequency,"The combined incidence of hereditary xanthinuria types I and II is estimated to be about 1 in 69,000 people worldwide. However, researchers suspect that the true incidence may be higher because some affected individuals have no symptoms and are never diagnosed with the condition. Hereditary xanthinuria appears to be more common in people of Mediterranean or Middle Eastern ancestry. About 150 cases of this condition have been reported in the medical literature.",hereditary xanthinuria,0000477,GHR,https://ghr.nlm.nih.gov/condition/hereditary-xanthinuria,C0220988,T047,Disorders
What are the genetic changes related to hereditary xanthinuria ?,0000477-3,genetic changes,"Hereditary xanthinuria type I is caused by mutations in the XDH gene. This gene provides instructions for making an enzyme called xanthine dehydrogenase. This enzyme is involved in the normal breakdown of purines, which are building blocks of DNA and its chemical cousin, RNA. Specifically, xanthine dehydrogenase carries out the final two steps in the process, including the conversion of xanthine to uric acid (which is excreted in urine and feces). Mutations in the XDH gene reduce or eliminate the activity of xanthine dehydrogenase. As a result, the enzyme is not available to help carry out the last two steps of purine breakdown. Because xanthine is not converted to uric acid, affected individuals have high levels of xanthine and very low levels of uric acid in their blood and urine. The excess xanthine can cause damage to the kidneys and other tissues.  Hereditary xanthinuria type II results from mutations in the MOCOS gene. This gene provides instructions for making an enzyme called molybdenum cofactor sulfurase. This enzyme is necessary for the normal function of xanthine dehydrogenase, described above, and another enzyme called aldehyde oxidase. Mutations in the MOCOS gene prevent xanthine dehydrogenase and aldehyde oxidase from being turned on (activated). The loss of xanthine dehydrogenase activity prevents the conversion of xanthine to uric acid, leading to an accumulation of xanthine in the kidneys and other tissues. The loss of aldehyde oxidase activity does not appear to cause any health problems.",hereditary xanthinuria,0000477,GHR,https://ghr.nlm.nih.gov/condition/hereditary-xanthinuria,C0220988,T047,Disorders
Is hereditary xanthinuria inherited ?,0000477-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",hereditary xanthinuria,0000477,GHR,https://ghr.nlm.nih.gov/condition/hereditary-xanthinuria,C0220988,T047,Disorders
What are the treatments for hereditary xanthinuria ?,0000477-5,treatment,These resources address the diagnosis or management of hereditary xanthinuria:  - Genetic Testing Registry: Deficiency of xanthine oxidase  - Genetic Testing Registry: Xanthinuria type 2  - MedlinePlus Encyclopedia: Uric Acid - Blood   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hereditary xanthinuria,0000477,GHR,https://ghr.nlm.nih.gov/condition/hereditary-xanthinuria,C0220988,T047,Disorders
What is (are) Hermansky-Pudlak syndrome ?,0000478-1,information,"Hermansky-Pudlak syndrome is a disorder characterized by a condition called oculocutaneous albinism, which causes abnormally light coloring (pigmentation) of the skin, hair, and eyes. Affected individuals typically have fair skin and white or light-colored hair. People with this disorder have a higher than average risk of skin damage and skin cancers caused by long-term sun exposure. Oculocutaneous albinism reduces pigmentation of the colored part of the eye (iris) and the light-sensitive tissue at the back of the eye (retina). Reduced vision, rapid and involuntary eye movements (nystagmus), and increased sensitivity to light (photophobia) are also common in oculocutaneous albinism. In Hermansky-Pudlak syndrome, these vision problems usually remain stable after early childhood.  People with Hermansky-Pudlak syndrome also have problems with blood clotting (coagulation) that lead to easy bruising and prolonged bleeding.  Some individuals with Hermansky-Pudlak syndrome develop breathing problems due to a lung disease called pulmonary fibrosis, which causes scar tissue to form in the lungs. The symptoms of pulmonary fibrosis usually appear during an individual's early thirties and rapidly worsen. Individuals with Hermansky-Pudlak syndrome who develop pulmonary fibrosis often do not live for more than a decade after they begin to experience breathing problems.  Other, less common features of Hermansky-Pudlak syndrome include inflammation of the large intestine (granulomatous colitis) and kidney failure.  There are nine different types of Hermansky-Pudlak syndrome, which can be distinguished by their signs and symptoms and underlying genetic cause. Types 1 and 4 are the most severe forms of the disorder. Types 1, 2, and 4 are the only types associated with pulmonary fibrosis. Individuals with type 3, 5, or 6 have the mildest symptoms. Little is known about the signs, symptoms, and severity of types 7, 8, and 9.",Hermansky-Pudlak syndrome,0000478,GHR,https://ghr.nlm.nih.gov/condition/hermansky-pudlak-syndrome,C0079504,T019,Disorders
How many people are affected by Hermansky-Pudlak syndrome ?,0000478-2,frequency,"Hermansky-Pudlak syndrome is a rare disorder in most populations and is estimated to affect 1 in 500,000 to 1,000,000 individuals worldwide. Type 1 is more common in Puerto Rico, particularly in the northwestern part of the island where about 1 in 1,800 people are affected. Type 3 is common in people from central Puerto Rico. Groups of affected individuals have been identified in many other regions, including India, Japan, the United Kingdom, and Western Europe.",Hermansky-Pudlak syndrome,0000478,GHR,https://ghr.nlm.nih.gov/condition/hermansky-pudlak-syndrome,C0079504,T019,Disorders
What are the genetic changes related to Hermansky-Pudlak syndrome ?,0000478-3,genetic changes,"At least nine genes are associated with Hermansky-Pudlak syndrome. These genes provide instructions for making proteins that are used to make four distinct protein complexes. These protein complexes play a role in the formation and movement (trafficking) of a group of cell structures called lysosome-related organelles (LROs). LROs are very similar to compartments within the cell called lysosomes, which digest and recycle materials. However, LROs perform specialized functions and are found only in certain cell types. LROs have been identified in pigment-producing cells (melanocytes), blood-clotting cells (platelets), and lung cells.  Mutations in the genes associated with Hermansky-Pudlak syndrome prevent the formation of LROs or impair the functioning of these cell structures. In general, mutations in genes that involve the same protein complex cause similar signs and symptoms. People with this syndrome have oculocutaneous albinism because the LROs within melanocytes cannot produce and distribute the substance that gives skin, hair, and eyes their color (melanin). Bleeding problems are caused by the absence of LROs within platelets, which affects the ability of platelets to stick together and form a blood clot. Mutations in some of the genes that cause Hermansky-Pudlak syndrome affect the normal functioning of LROs in lung cells, leading to pulmonary fibrosis.  Mutations in the HPS1 gene cause approximately 75 percent of the Hermansky-Pudlak syndrome cases from Puerto Rico. About 45 percent of affected individuals from other populations have mutations in the HPS1 gene. Mutations in the HPS3 gene are found in about 25 percent of affected people from Puerto Rico and in approximately 20 percent of affected individuals from other areas. The other genes associated with Hermansky-Pudlak syndrome each account for a small percentage of cases of this condition.  In some people with Hermansky-Pudlak syndrome, the genetic cause of the disorder is unknown.",Hermansky-Pudlak syndrome,0000478,GHR,https://ghr.nlm.nih.gov/condition/hermansky-pudlak-syndrome,C0079504,T019,Disorders
Is Hermansky-Pudlak syndrome inherited ?,0000478-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Hermansky-Pudlak syndrome,0000478,GHR,https://ghr.nlm.nih.gov/condition/hermansky-pudlak-syndrome,C0079504,T019,Disorders
What are the treatments for Hermansky-Pudlak syndrome ?,0000478-5,treatment,These resources address the diagnosis or management of Hermansky-Pudlak syndrome:  - Gene Review: Gene Review: Hermansky-Pudlak Syndrome  - Genetic Testing Registry: Hermansky-Pudlak syndrome  - Genetic Testing Registry: Hermansky-Pudlak syndrome 1  - MedlinePlus Encyclopedia: Albinism  - MedlinePlus Encyclopedia: Colitis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Hermansky-Pudlak syndrome,0000478,GHR,https://ghr.nlm.nih.gov/condition/hermansky-pudlak-syndrome,C0079504,T019,Disorders
What is (are) heterotaxy syndrome ?,0000479-1,information,"Heterotaxy syndrome is a condition in which the internal organs are abnormally arranged in the chest and abdomen. The term ""heterotaxy"" is from the Greek words ""heteros,"" meaning ""other than,"" and ""taxis,"" meaning ""arrangement."" Individuals with this condition have complex birth defects affecting the heart, lungs, liver, spleen, intestines, and other organs.  In the normal body, most of the organs in the chest and abdomen have a particular location on the right or left side. For example, the heart, spleen, and pancreas are on the left side of the body, and most of the liver is on the right. This normal arrangement of the organs is known as ""situs solitus."" Rarely, the orientation of the internal organs is completely flipped from right to left, a situation known as ""situs inversus."" This mirror-image orientation usually does not cause any health problems, unless it occurs as part of a syndrome affecting other parts of the body. Heterotaxy syndrome is an arrangement of internal organs somewhere between situs solitus and situs inversus; this condition is also known as ""situs ambiguus."" Unlike situs inversus, the abnormal arrangement of organs in heterotaxy syndrome often causes serious health problems.  Heterotaxy syndrome alters the structure of the heart, including the attachment of the large blood vessels that carry blood to and from the rest of the body. It can also affect the structure of the lungs, such as the number of lobes in each lung and the length of the tubes (called bronchi) that lead from the windpipe to the lungs. In the abdomen, the condition can cause a person to have no spleen (asplenia) or multiple small, poorly functioning spleens (polysplenia). The liver may lie across the middle of the body instead of being in its normal position to the right of the stomach. Some affected individuals also have intestinal malrotation, which is an abnormal twisting of the intestines that occurs in the early stages of development before birth.  Depending on the organs involved, signs and symptoms of heterotaxy syndrome can include a bluish appearance of the skin or lips (cyanosis, which is due to a shortage of oxygen), breathing difficulties, an increased risk of infections, and problems with digesting food. The most serious complications are generally caused by critical congenital heart disease, a group of complex heart defects that are present from birth. Biliary atresia, a problem with the bile ducts in the liver, can also cause severe health problems in infancy. Heterotaxy syndrome is often life-threatening in infancy or childhood, even with treatment, although its severity depends on the specific abnormalities involved.",heterotaxy syndrome,0000479,GHR,https://ghr.nlm.nih.gov/condition/heterotaxy-syndrome,C3178805,T019,Disorders
How many people are affected by heterotaxy syndrome ?,0000479-2,frequency,"The prevalence of heterotaxy syndrome is estimated to be 1 in 10,000 people worldwide. However, researchers suspect that the condition is underdiagnosed, and so it may actually be more common than this. Heterotaxy syndrome accounts for approximately 3 percent of all congenital heart defects. For reasons that are unknown, the condition appears to be more common in Asian populations than in North America and Europe. Recent studies report that in the United States, the condition occurs more frequently in children born to black or Hispanic mothers than in children born to white mothers.",heterotaxy syndrome,0000479,GHR,https://ghr.nlm.nih.gov/condition/heterotaxy-syndrome,C3178805,T019,Disorders
What are the genetic changes related to heterotaxy syndrome ?,0000479-3,genetic changes,"Heterotaxy syndrome can be caused by mutations in many different genes. The proteins produced from most of these genes play roles in determining which structures should be on the right side of the body and which should be on the left, a process known as establishing left-right asymmetry. This process occurs during the earliest stages of embryonic development. Dozens of genes are probably involved in establishing left-right asymmetry; mutations in at least 20 of these genes have been identified in people with heterotaxy syndrome.  In some cases, heterotaxy syndrome is caused by mutations in genes whose involvement in determining left-right asymmetry is unknown. Rarely, chromosomal changes such as insertions, deletions, duplications, and other rearrangements of genetic material have been associated with this condition.  Heterotaxy syndrome can occur by itself, or it can be a feature of other genetic syndromes that have additional signs and symptoms. For example, at least 12 percent of people with a condition called primary ciliary dyskinesia have heterotaxy syndrome. In addition to abnormally positioned internal organs, primary ciliary dyskinesia is characterized by chronic respiratory tract infections and an inability to have children (infertility). The signs and symptoms of this condition are caused by abnormal cilia, which are microscopic, finger-like projections that stick out from the surface of cells. It appears that cilia play a critical role in establishing left-right asymmetry before birth.  Studies suggest that certain factors affecting a woman during pregnancy may also contribute to the risk of heterotaxy syndrome in her child. These include diabetes mellitus; smoking; and exposure to hair dyes, cocaine, and certain laboratory chemicals.  Some people with heterotaxy syndrome have no identified gene mutations or other risk factors. In these cases, the cause of the condition is unknown.",heterotaxy syndrome,0000479,GHR,https://ghr.nlm.nih.gov/condition/heterotaxy-syndrome,C3178805,T019,Disorders
Is heterotaxy syndrome inherited ?,0000479-4,inheritance,"Most often, heterotaxy syndrome is sporadic, meaning that only one person in a family is affected. However, about 10 percent of people with heterotaxy syndrome have a close relative (such as a parent or sibling) who has a congenital heart defect without other apparent features of heterotaxy syndrome. Isolated congenital heart defects and heterotaxy syndrome may represent a range of signs and symptoms that can result from a particular genetic mutation; this situation is known as variable expressivity. It is also possible that different genetic and environmental factors combine to produce isolated congenital heart defects in some family members and heterotaxy syndrome in others.  When heterotaxy syndrome runs in families, it can have an autosomal dominant, autosomal recessive, or X-linked pattern of inheritance, depending on which gene is involved. Autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder. Autosomal recessive inheritance means that both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. In X-linked inheritance, the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell.  When heterotaxy syndrome occurs as a feature of primary ciliary dyskinesia, it has an autosomal recessive pattern of inheritance.",heterotaxy syndrome,0000479,GHR,https://ghr.nlm.nih.gov/condition/heterotaxy-syndrome,C3178805,T019,Disorders
What are the treatments for heterotaxy syndrome ?,0000479-5,treatment,"These resources address the diagnosis or management of heterotaxy syndrome:  - Boston Children's Hospital: Tests for Heterotaxy Syndrome  - Gene Review: Gene Review: Primary Ciliary Dyskinesia  - Genetic Testing Registry: Atrioventricular septal defect, partial, with heterotaxy syndrome  - Genetic Testing Registry: Heterotaxy syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",heterotaxy syndrome,0000479,GHR,https://ghr.nlm.nih.gov/condition/heterotaxy-syndrome,C3178805,T019,Disorders
What is (are) hidradenitis suppurativa ?,0000480-1,information,"Hidradenitis suppurativa, also known as acne inversa, is a chronic skin disease characterized by recurrent boil-like lumps (nodules) under the skin. The nodules become inflamed and painful. They tend to break open (rupture), causing abscesses that drain fluid and pus. As the abscesses heal, they produce significant scarring of the skin.  The signs and symptoms of hidradenitis suppurativa appear after puberty, usually in a person's teens or twenties. Nodules are most likely to form in the armpits and groin. They may also develop around the anus, on the buttocks, or under the breasts. In some cases, nodules appear in other areas, such as the nape of the neck, waist, and inner thighs.  The recurrent nodules and abscesses cause chronic pain and can lead to self-consciousness, social isolation, and depression. Rarely, nodules on the buttocks can develop into a type of skin cancer called squamous cell carcinoma.",hidradenitis suppurativa,0000480,GHR,https://ghr.nlm.nih.gov/condition/hidradenitis-suppurativa,C0162836,T047,Disorders
How many people are affected by hidradenitis suppurativa ?,0000480-2,frequency,"Hidradenitis suppurativa was once thought to be a rare condition because only the most severe cases were reported. However, recent studies have shown that the condition affects at least 1 in 100 people when milder cases are also considered. For reasons that are unclear, women are about twice as likely as men to develop the condition.",hidradenitis suppurativa,0000480,GHR,https://ghr.nlm.nih.gov/condition/hidradenitis-suppurativa,C0162836,T047,Disorders
What are the genetic changes related to hidradenitis suppurativa ?,0000480-3,genetic changes,"In most cases, the cause of hidradenitis suppurativa is unknown. The condition probably results from a combination of genetic and environmental factors. Originally, researchers believed that the disorder was caused by the blockage of specialized sweat glands called apocrine glands. However, recent studies have shown that the condition actually begins with a blockage of hair follicles in areas of the body that also contain a high concentration of apocrine glands (such as the armpits and groin). The blocked hair follicles trap bacteria, leading to inflammation and rupture. It remains unclear what initially causes the follicles to become blocked and why the nodules tend to recur.  Genetic factors clearly play a role in causing hidradenitis suppurativa. Some cases have been found to result from mutations in the NCSTN, PSEN1, or PSENEN gene. The proteins produced from these genes are all components of a complex called gamma- (-) secretase. This complex cuts apart (cleaves) many different proteins, which is an important step in several chemical signaling pathways. One of these pathways, known as Notch signaling, is essential for the normal maturation and division of hair follicle cells and other types of skin cells. Notch signaling is also involved in normal immune system function. Studies suggest that mutations in the NCSTN, PSEN1, or PSENEN gene impair Notch signaling in hair follicles. Although little is known about the mechanism, abnormal Notch signaling appears to promote the development of nodules and lead to inflammation in the skin. Researchers are working to determine whether additional genes, particularly those that provide instructions for making other -secretase components, are also associated with hidradenitis suppurativa.  Researchers have studied many other possible risk factors for hidradenitis suppurativa. Obesity and smoking both appear to increase the risk of the disorder, and obesity is also associated with increased severity of signs and symptoms in affected individuals. Studies suggest that neither abnormal immune system function nor hormonal factors play a significant role in causing the disease. Other factors that were mistakenly thought to be associated with this condition include poor hygiene, the use of underarm deodorants and antiperspirants, and shaving or the use of depilatory products to remove hair.",hidradenitis suppurativa,0000480,GHR,https://ghr.nlm.nih.gov/condition/hidradenitis-suppurativa,C0162836,T047,Disorders
Is hidradenitis suppurativa inherited ?,0000480-4,inheritance,"Hidradenitis suppurativa has been reported to run in families. Studies have found that 30 to 40 percent of affected individuals have at least one family member with the disorder. However, this finding may be an underestimate because affected individuals do not always tell their family members that they have the condition, and hidradenitis suppurativa is sometimes misdiagnosed as other skin disorders.  In some families, including those with an NCSTN, PSEN1, or PSENEN gene mutation, hidradenitis suppurativa appears to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of an altered gene in each cell is sufficient to cause the disorder. In many cases, an affected person inherits the altered gene from a parent who has the condition.",hidradenitis suppurativa,0000480,GHR,https://ghr.nlm.nih.gov/condition/hidradenitis-suppurativa,C0162836,T047,Disorders
What are the treatments for hidradenitis suppurativa ?,0000480-5,treatment,"These resources address the diagnosis or management of hidradenitis suppurativa:  - American Academy of Dermatology: Hidradenitis Suppurativa: Diagnosis, Treatment, and Outcome  - Genetic Testing Registry: Hidradenitis suppurativa, familial   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",hidradenitis suppurativa,0000480,GHR,https://ghr.nlm.nih.gov/condition/hidradenitis-suppurativa,C0162836,T047,Disorders
What is (are) Hirschsprung disease ?,0000481-1,information,"Hirschsprung disease is an intestinal disorder characterized by the absence of nerves in parts of the intestine. This condition occurs when the nerves in the intestine (enteric nerves) do not form properly during development before birth (embryonic development). This condition is usually identified in the first two months of life, although less severe cases may be diagnosed later in childhood.  Enteric nerves trigger the muscle contractions that move stool through the intestine. Without these nerves in parts of the intestine, the material cannot be pushed through, causing severe constipation or complete blockage of the intestine in people with Hirschsprung disease. Other signs and symptoms of this condition include vomiting, abdominal pain or swelling, diarrhea, poor feeding, malnutrition, and slow growth. People with this disorder are at risk of developing more serious conditions such as inflammation of the intestine (enterocolitis) or a hole in the wall of the intestine (intestinal perforation), which can cause serious infection and may be fatal.  There are two main types of Hirschsprung disease, known as short-segment disease and long-segment disease, which are defined by the region of the intestine lacking nerve cells. In short-segment disease, nerve cells are missing from only the last segment of the large intestine. This type is most common, occurring in approximately 80 percent of people with Hirschsprung disease. For unknown reasons, short-segment disease is four times more common in men than in women. Long-segment disease occurs when nerve cells are missing from most of the large intestine and is the more severe type. Long-segment disease is found in approximately 20 percent of people with Hirschsprung disease and affects men and women equally. Very rarely, nerve cells are missing from the entire large intestine and sometimes part of the small intestine (total colonic aganglionosis) or from all of the large and small intestine (total intestinal aganglionosis).  Hirschsprung disease can occur in combination with other conditions, such as Waardenburg syndrome, type IV; Mowat-Wilson syndrome; or congenital central hypoventilation syndrome. These cases are described as syndromic. Hirschsprung disease can also occur without other conditions, and these cases are referred to as isolated or nonsyndromic.",Hirschsprung disease,0000481,GHR,https://ghr.nlm.nih.gov/condition/hirschsprung-disease,C0019569,T019,Disorders
How many people are affected by Hirschsprung disease ?,0000481-2,frequency,"Hirschsprung disease occurs in approximately 1 in 5,000 newborns.",Hirschsprung disease,0000481,GHR,https://ghr.nlm.nih.gov/condition/hirschsprung-disease,C0019569,T019,Disorders
What are the genetic changes related to Hirschsprung disease ?,0000481-3,genetic changes,"Isolated Hirschsprung disease can result from mutations in one of several genes, including the RET, EDNRB, and EDN3 genes. However, the genetics of this condition appear complex and are not completely understood. While a mutation in a single gene sometimes causes the condition, mutations in multiple genes may be required in some cases. The genetic cause of the condition is unknown in approximately half of affected individuals.  Mutations in the RET gene are the most common known genetic cause of Hirschsprung disease. The RET gene provides instructions for producing a protein that is involved in signaling within cells. This protein appears to be essential for the normal development of several kinds of nerve cells, including nerves in the intestine. Mutations in the RET gene that cause Hirschsprung disease result in a nonfunctional version of the RET protein that cannot transmit signals within cells. Without RET protein signaling, enteric nerves do not develop properly. Absence of these nerves leads to the intestinal problems characteristic of Hirschsprung disease.  The EDNRB gene provides instructions for making a protein called endothelin receptor type B. When this protein interacts with other proteins called endothelins, it transmits information from outside the cell to inside the cell, signaling for many important cellular processes. The EDN3 gene provides instructions for a protein called endothelin 3, one of the endothelins that interacts with endothelin receptor type B. Together, endothelin 3 and endothelin receptor type B play an important role in the normal formation of enteric nerves. Changes in either the EDNRB gene or the EDN3 gene disrupt the normal functioning of the endothelin receptor type B or the endothelin 3 protein, preventing them from transmitting signals important for the development of enteric nerves. As a result, these nerves do not form normally during embryonic development. A lack of enteric nerves prevents stool from being moved through the intestine, leading to severe constipation and intestinal blockage.",Hirschsprung disease,0000481,GHR,https://ghr.nlm.nih.gov/condition/hirschsprung-disease,C0019569,T019,Disorders
Is Hirschsprung disease inherited ?,0000481-4,inheritance,"Approximately 20 percent of cases of Hirschsprung disease occur in multiple members of the same family. The remainder of cases occur in people with no history of the disorder in their families.  Hirschsprung disease appears to have a dominant pattern of inheritance, which means one copy of the altered gene in each cell may be sufficient to cause the disorder. The inheritance is considered to have incomplete penetrance because not everyone who inherits the altered gene from a parent develops Hirschsprung disease.",Hirschsprung disease,0000481,GHR,https://ghr.nlm.nih.gov/condition/hirschsprung-disease,C0019569,T019,Disorders
What are the treatments for Hirschsprung disease ?,0000481-5,treatment,"These resources address the diagnosis or management of Hirschsprung disease:  - Cedars-Sinai: Treating Hirschsprung's Disease (Colonic Aganglionosis)  - Gene Review: Gene Review: Hirschsprung Disease Overview  - Genetic Testing Registry: Hirschsprung disease 1  - Genetic Testing Registry: Hirschsprung disease 2  - Genetic Testing Registry: Hirschsprung disease 3  - Genetic Testing Registry: Hirschsprung disease 4  - North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition: Hirschsprung's Disease  - Seattle Children's: Hirschsprung's Disease: Symptoms and Diagnosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Hirschsprung disease,0000481,GHR,https://ghr.nlm.nih.gov/condition/hirschsprung-disease,C0019569,T019,Disorders
What is (are) histidinemia ?,0000482-1,information,"Histidinemia is an inherited condition characterized by elevated blood levels of the amino acid histidine, a building block of most proteins. Histidinemia is caused by the shortage (deficiency) of the enzyme that breaks down histidine. Histidinemia typically causes no health problems, and most people with elevated histidine levels are unaware that they have this condition.  The combination of histidinemia and a medical complication during or soon after birth (such as a temporary lack of oxygen) might increase a person's chances of developing intellectual disability, behavioral problems, or learning disorders.",histidinemia,0000482,GHR,https://ghr.nlm.nih.gov/condition/histidinemia,C0220992,T047,Disorders
How many people are affected by histidinemia ?,0000482-2,frequency,"Estimates of the incidence of histidinemia vary widely, ranging between 1 in 8,600 to 1 in 90,000 people.",histidinemia,0000482,GHR,https://ghr.nlm.nih.gov/condition/histidinemia,C0220992,T047,Disorders
What are the genetic changes related to histidinemia ?,0000482-3,genetic changes,"Histidinemia is caused by mutations in the HAL gene, which provides instructions for making an enzyme called histidase. Histidase breaks down histidine to a molecule called urocanic acid. Histidase is active (expressed) primarily in the liver and the skin.  HAL gene mutations lead to the production of a histidase enzyme that cannot break down histidine, which results in elevated levels of histidine in the blood and urine. These increased levels of histidine do not appear to have any negative effects on the body.",histidinemia,0000482,GHR,https://ghr.nlm.nih.gov/condition/histidinemia,C0220992,T047,Disorders
Is histidinemia inherited ?,0000482-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",histidinemia,0000482,GHR,https://ghr.nlm.nih.gov/condition/histidinemia,C0220992,T047,Disorders
What are the treatments for histidinemia ?,0000482-5,treatment,These resources address the diagnosis or management of histidinemia:  - Genetic Testing Registry: Histidinemia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,histidinemia,0000482,GHR,https://ghr.nlm.nih.gov/condition/histidinemia,C0220992,T047,Disorders
What is (are) histiocytosis-lymphadenopathy plus syndrome ?,0000483-1,information,"Histiocytosis-lymphadenopathy plus syndrome (also known as SLC29A3 spectrum disorder) is a group of conditions with overlapping signs and symptoms that affect many parts of the body. This group of disorders includes H syndrome, pigmented hypertrichosis with insulin-dependent diabetes mellitus (PHID), Faisalabad histiocytosis, and familial Rosai-Dorfman disease (also known as sinus histiocytosis with massive lymphadenopathy or SHML). These conditions were once thought to be distinct disorders; however, because of the overlapping features and shared genetic cause, they are now considered to be part of the same disease spectrum. While some affected individuals have signs and symptoms characteristic of one of the conditions, others have a range of features from two or more of the conditions. The pattern of signs and symptoms can vary even within the same family.  A feature common to the disorders in this spectrum is histiocytosis, which is the overgrowth of immune system cells called histiocytes. The cells abnormally accumulate in one or more tissues in the body, which can lead to organ or tissue damage. The buildup often occurs in the lymph nodes, leading to swelling of the lymph nodes (lymphadenopathy). Other areas of cell accumulation can include the skin, kidneys, brain and spinal cord (central nervous system), or digestive tract.  This spectrum is known as histiocytosis-lymphadenopathy plus syndrome because the disorders that make up the spectrum can have additional signs and symptoms. A characteristic feature of H syndrome is abnormal patches of skin (lesions), typically on the lower body. These lesions are unusually dark (hyperpigmented) and have excessive hair growth (hypertrichosis). In addition, histiocytes accumulate at the site of the skin lesions. Other features of H syndrome include enlargement of the liver (hepatomegaly), heart abnormalities, hearing loss, reduced amounts of hormones that direct sexual development (hypogonadism), and short stature.  Like H syndrome, PHID causes patches of hyperpigmented skin with hypertrichosis. PHID is also characterized by the development of type 1 diabetes (also known as insulin-dependent diabetes mellitus), which usually begins in childhood. Type 1 diabetes occurs when the body does not produce enough of the hormone insulin, leading to dysregulation of blood sugar levels.  Faisalabad histiocytosis typically causes lymphadenopathy and swelling of the eyelids due to accumulation of histiocytes. Affected individuals can also have joint deformities called contractures in their fingers or toes and hearing loss.  The most common feature of familial Rosai-Dorfman disease is lymphadenopathy, usually affecting lymph nodes in the neck. Histiocytes can also accumulate in other parts of the body.",histiocytosis-lymphadenopathy plus syndrome,0000483,GHR,https://ghr.nlm.nih.gov/condition/histiocytosis-lymphadenopathy-plus-syndrome,C1864445,T047,Disorders
How many people are affected by histiocytosis-lymphadenopathy plus syndrome ?,0000483-2,frequency,"Histiocytosis-lymphadenopathy plus syndrome is a rare disorder, affecting approximately 100 individuals worldwide.",histiocytosis-lymphadenopathy plus syndrome,0000483,GHR,https://ghr.nlm.nih.gov/condition/histiocytosis-lymphadenopathy-plus-syndrome,C1864445,T047,Disorders
What are the genetic changes related to histiocytosis-lymphadenopathy plus syndrome ?,0000483-3,genetic changes,"Histiocytosis-lymphadenopathy plus syndrome is caused by mutations in the SLC29A3 gene, which provides instructions for making a protein called equilibrative nucleoside transporter 3 (ENT3). ENT3 belongs to a family of proteins that transport molecules called nucleosides in cells. With chemical modification, nucleosides become the building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP, which serve as energy sources in the cell. Molecules derived from nucleosides play an important role in many functions throughout the body.  ENT3 is found in cellular structures called lysosomes, which break down large molecules into smaller ones that can be reused by cells. Researchers believe that this protein transports nucleosides generated by the breakdown of DNA and RNA out of lysosomes into the cell so they can be reused. The protein is also thought to transport nucleosides into structures called mitochondria, which are the energy-producing centers of cells. In mitochondria, nucleosides are likely used in the formation or repair of DNA found in these structures, known as mitochondrial DNA.  The SLC29A3 gene mutations involved in histiocytosis-lymphadenopathy plus syndrome reduce or eliminate the activity of the ENT3 protein. Researchers speculate that the resulting impairment of nucleoside transport leads to a buildup of nucleosides in lysosomes, which may be damaging to cell function. A lack of ENT3 activity may also lead to a reduction in the amount of nucleosides in mitochondria. This nucleoside shortage could impair cellular energy production, which would impact many body systems. It is unclear how the mutations lead to histiocytosis and other features of the condition or why affected individuals can have different patterns of signs and symptoms.",histiocytosis-lymphadenopathy plus syndrome,0000483,GHR,https://ghr.nlm.nih.gov/condition/histiocytosis-lymphadenopathy-plus-syndrome,C1864445,T047,Disorders
Is histiocytosis-lymphadenopathy plus syndrome inherited ?,0000483-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",histiocytosis-lymphadenopathy plus syndrome,0000483,GHR,https://ghr.nlm.nih.gov/condition/histiocytosis-lymphadenopathy-plus-syndrome,C1864445,T047,Disorders
What are the treatments for histiocytosis-lymphadenopathy plus syndrome ?,0000483-5,treatment,These resources address the diagnosis or management of histiocytosis-lymphadenopathy plus syndrome:  - Genetic Testing Registry: Histiocytosis-lymphadenopathy plus syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,histiocytosis-lymphadenopathy plus syndrome,0000483,GHR,https://ghr.nlm.nih.gov/condition/histiocytosis-lymphadenopathy-plus-syndrome,C1864445,T047,Disorders
What is (are) holocarboxylase synthetase deficiency ?,0000484-1,information,"Holocarboxylase synthetase deficiency is an inherited disorder in which the body is unable to use the vitamin biotin effectively. This disorder is classified as a multiple carboxylase deficiency, a group of disorders characterized by impaired activity of certain enzymes that depend on biotin.  The signs and symptoms of holocarboxylase synthetase deficiency typically appear within the first few months of life, but the age of onset varies. Affected infants often have difficulty feeding, breathing problems, a skin rash, hair loss (alopecia), and a lack of energy (lethargy). Immediate treatment and lifelong management with biotin supplements may prevent many of these complications. If left untreated, the disorder can lead to delayed development, seizures, and coma. These medical problems may be life-threatening in some cases.",holocarboxylase synthetase deficiency,0000484,GHR,https://ghr.nlm.nih.gov/condition/holocarboxylase-synthetase-deficiency,C0268581,T047,Disorders
How many people are affected by holocarboxylase synthetase deficiency ?,0000484-2,frequency,"The exact incidence of this condition is unknown, but it is estimated to affect 1 in 87,000 people.",holocarboxylase synthetase deficiency,0000484,GHR,https://ghr.nlm.nih.gov/condition/holocarboxylase-synthetase-deficiency,C0268581,T047,Disorders
What are the genetic changes related to holocarboxylase synthetase deficiency ?,0000484-3,genetic changes,"Mutations in the HLCS gene cause holocarboxylase synthetase deficiency.  The HLCS gene provides instructions for making an enzyme called holocarboxylase synthetase. This enzyme is important for the effective use of biotin, a B vitamin found in foods such as liver, egg yolks, and milk. Holocarboxylase synthetase attaches biotin to certain enzymes that are essential for the normal production and breakdown of proteins, fats, and carbohydrates in the body. Mutations in the HLCS gene reduce the enzyme's ability to attach biotin to these enzymes, preventing them from processing nutrients properly and disrupting many cellular functions. These defects lead to the serious medical problems associated with holocarboxylase synthetase deficiency.",holocarboxylase synthetase deficiency,0000484,GHR,https://ghr.nlm.nih.gov/condition/holocarboxylase-synthetase-deficiency,C0268581,T047,Disorders
Is holocarboxylase synthetase deficiency inherited ?,0000484-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",holocarboxylase synthetase deficiency,0000484,GHR,https://ghr.nlm.nih.gov/condition/holocarboxylase-synthetase-deficiency,C0268581,T047,Disorders
What are the treatments for holocarboxylase synthetase deficiency ?,0000484-5,treatment,These resources address the diagnosis or management of holocarboxylase synthetase deficiency:  - Baby's First Test  - Genetic Testing Registry: Holocarboxylase synthetase deficiency  - MedlinePlus Encyclopedia: Pantothenic Acid and Biotin   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,holocarboxylase synthetase deficiency,0000484,GHR,https://ghr.nlm.nih.gov/condition/holocarboxylase-synthetase-deficiency,C0268581,T047,Disorders
What is (are) Holt-Oram syndrome ?,0000485-1,information,"Holt-Oram syndrome is characterized by skeletal abnormalities of the hands and arms (upper limbs) and heart problems.  People with Holt-Oram syndrome have abnormally developed bones in their upper limbs. At least one abnormality in the bones of the wrist (carpal bones) is present in affected individuals. Often, these wrist bone abnormalities can be detected only by x-ray. Individuals with Holt-Oram syndrome may have additional bone abnormalities including a missing thumb, a long thumb that looks like a finger, partial or complete absence of bones in the forearm, an underdeveloped bone of the upper arm, and abnormalities of the collar bone or shoulder blades. These skeletal abnormalities may affect one or both of the upper limbs. If both upper limbs are affected, the bone abnormalities can be the same or different on each side. In cases where the skeletal abnormalities are not the same on both sides of the body, the left side is usually more severely affected than the right side.  About 75 percent of individuals with Holt-Oram syndrome have heart (cardiac) problems, which can be life-threatening. The most common problem is a defect in the muscular wall (septum) that separates the right and left sides of the heart. A hole in the septum between the upper chambers of the heart (atria) is called an atrial septal defect (ASD), and a hole in the septum between the lower chambers of the heart (ventricles) is called a ventricular septal defect (VSD). Some people with Holt-Oram syndrome have cardiac conduction disease, which is caused by abnormalities in the electrical system that coordinates contractions of the heart chambers. Cardiac conduction disease can lead to problems such as a slower-than-normal heart rate (bradycardia) or a rapid and uncoordinated contraction of the heart muscle (fibrillation). Cardiac conduction disease can occur along with other heart defects (such as ASD or VSD) or as the only heart problem in people with Holt-Oram syndrome.  The features of Holt-Oram syndrome are similar to those of a condition called Duane-radial ray syndrome; however, these two disorders are caused by mutations in different genes.",Holt-Oram syndrome,0000485,GHR,https://ghr.nlm.nih.gov/condition/holt-oram-syndrome,C0265264,T019,Disorders
How many people are affected by Holt-Oram syndrome ?,0000485-2,frequency,"Holt-Oram syndrome is estimated to affect 1 in 100,000 individuals.",Holt-Oram syndrome,0000485,GHR,https://ghr.nlm.nih.gov/condition/holt-oram-syndrome,C0265264,T019,Disorders
What are the genetic changes related to Holt-Oram syndrome ?,0000485-3,genetic changes,"Mutations in the TBX5 gene cause Holt-Oram syndrome. This gene provides instructions for making a protein that plays a role in the development of the heart and upper limbs before birth. In particular, this gene appears to be important for the process that divides the developing heart into four chambers (cardiac septation). The TBX5 gene also appears to play a critical role in regulating the development of bones in the arm and hand. Mutations in this gene probably disrupt the development of the heart and upper limbs, leading to the characteristic features of Holt-Oram syndrome.",Holt-Oram syndrome,0000485,GHR,https://ghr.nlm.nih.gov/condition/holt-oram-syndrome,C0265264,T019,Disorders
Is Holt-Oram syndrome inherited ?,0000485-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Holt-Oram syndrome,0000485,GHR,https://ghr.nlm.nih.gov/condition/holt-oram-syndrome,C0265264,T019,Disorders
What are the treatments for Holt-Oram syndrome ?,0000485-5,treatment,These resources address the diagnosis or management of Holt-Oram syndrome:  - Gene Review: Gene Review: Holt-Oram Syndrome  - Genetic Testing Registry: Holt-Oram syndrome  - MedlinePlus Encyclopedia: Atrial Septal Defect  - MedlinePlus Encyclopedia: Skeletal Limb Abnormalities  - MedlinePlus Encyclopedia: Ventricular Septal Defect   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Holt-Oram syndrome,0000485,GHR,https://ghr.nlm.nih.gov/condition/holt-oram-syndrome,C0265264,T019,Disorders
What is (are) homocystinuria ?,0000486-1,information,"Homocystinuria is an inherited disorder in which the body is unable to process certain building blocks of proteins (amino acids) properly. There are multiple forms of homocystinuria, which are distinguished by their signs and symptoms and genetic cause. The most common form of homocystinuria is characterized by nearsightedness (myopia), dislocation of the lens at the front of the eye, an increased risk of abnormal blood clotting, and brittle bones that are prone to fracture (osteoporosis) or other skeletal abnormalities. Some affected individuals also have developmental delay and learning problems.  Less common forms of homocystinuria can cause intellectual disability, failure to grow and gain weight at the expected rate (failure to thrive), seizures, problems with movement, and a blood disorder called megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number of red blood cells (anemia), and the remaining red blood cells are larger than normal (megaloblastic).  The signs and symptoms of homocystinuria typically develop within the first year of life, although some mildly affected people may not develop features until later in childhood or adulthood.",homocystinuria,0000486,GHR,https://ghr.nlm.nih.gov/condition/homocystinuria,C0019880,T047,Disorders
How many people are affected by homocystinuria ?,0000486-2,frequency,"The most common form of homocystinuria affects at least 1 in 200,000 to 335,000 people worldwide. The disorder appears to be more common in some countries, such as Ireland (1 in 65,000), Germany (1 in 17,800), Norway (1 in 6,400), and Qatar (1 in 1,800). The rarer forms of homocystinuria each have a small number of cases reported in the scientific literature.",homocystinuria,0000486,GHR,https://ghr.nlm.nih.gov/condition/homocystinuria,C0019880,T047,Disorders
What are the genetic changes related to homocystinuria ?,0000486-3,genetic changes,"Mutations in the CBS, MTHFR, MTR, MTRR, and MMADHC genes cause homocystinuria.  Mutations in the CBS gene cause the most common form of homocystinuria. The CBS gene provides instructions for producing an enzyme called cystathionine beta-synthase. This enzyme acts in a chemical pathway and is responsible for converting the amino acid homocysteine to a molecule called cystathionine. As a result of this pathway, other amino acids, including methionine, are produced. Mutations in the CBS gene disrupt the function of cystathionine beta-synthase, preventing homocysteine from being used properly. As a result, this amino acid and toxic byproducts substances build up in the blood. Some of the excess homocysteine is excreted in urine.  Rarely, homocystinuria can be caused by mutations in several other genes. The enzymes made by the MTHFR, MTR, MTRR, and MMADHC genes play roles in converting homocysteine to methionine. Mutations in any of these genes prevent the enzymes from functioning properly, which leads to a buildup of homocysteine in the body. Researchers have not determined how excess homocysteine and related compounds lead to the signs and symptoms of homocystinuria.",homocystinuria,0000486,GHR,https://ghr.nlm.nih.gov/condition/homocystinuria,C0019880,T047,Disorders
Is homocystinuria inherited ?,0000486-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.  Although people who carry one mutated copy and one normal copy of the CBS gene do not have homocystinuria, they are more likely than people without a CBS mutation to have shortages (deficiencies) of vitamin B12 and folic acid.",homocystinuria,0000486,GHR,https://ghr.nlm.nih.gov/condition/homocystinuria,C0019880,T047,Disorders
What are the treatments for homocystinuria ?,0000486-5,treatment,"These resources address the diagnosis or management of homocystinuria:  - Baby's First Test  - Gene Review: Gene Review: Disorders of Intracellular Cobalamin Metabolism  - Gene Review: Gene Review: Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency  - Genetic Testing Registry: Homocysteinemia due to MTHFR deficiency  - Genetic Testing Registry: Homocystinuria due to CBS deficiency  - Genetic Testing Registry: Homocystinuria, cblD type, variant 1  - Genetic Testing Registry: Homocystinuria-Megaloblastic anemia due to defect in cobalamin metabolism, cblE complementation type  - Genetic Testing Registry: METHYLCOBALAMIN DEFICIENCY, cblG TYPE  - Genetic Testing Registry: Methylmalonic acidemia with homocystinuria cblD  - Genetic Testing Registry: Methylmalonic aciduria, cblD type, variant 2  - MedlinePlus Encyclopedia: Homocystinuria  - New England Consortium of Metabolic Programs   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",homocystinuria,0000486,GHR,https://ghr.nlm.nih.gov/condition/homocystinuria,C0019880,T047,Disorders
What is (are) horizontal gaze palsy with progressive scoliosis ?,0000487-1,information,"Horizontal gaze palsy with progressive scoliosis (HGPPS) is a disorder that affects vision and also causes an abnormal curvature of the spine (scoliosis). People with this condition are unable to move their eyes side-to-side (horizontally). As a result, affected individuals must turn their head instead of moving their eyes to track moving objects. Up-and-down (vertical) eye movements are typically normal.  In people with HGPPS, an abnormal side-to-side curvature of the spine develops in infancy or childhood. It tends to be moderate to severe and worsens over time. Because the abnormal spine position can be painful and interfere with movement, it is often treated with surgery early in life.",horizontal gaze palsy with progressive scoliosis,0000487,GHR,https://ghr.nlm.nih.gov/condition/horizontal-gaze-palsy-with-progressive-scoliosis,C1846496,T047,Disorders
How many people are affected by horizontal gaze palsy with progressive scoliosis ?,0000487-2,frequency,HGPPS has been reported in several dozen families worldwide.,horizontal gaze palsy with progressive scoliosis,0000487,GHR,https://ghr.nlm.nih.gov/condition/horizontal-gaze-palsy-with-progressive-scoliosis,C1846496,T047,Disorders
What are the genetic changes related to horizontal gaze palsy with progressive scoliosis ?,0000487-3,genetic changes,"HGPPS is caused by mutations in the ROBO3 gene. This gene provides instructions for making a protein that is important for the normal development of certain nerve pathways in the brain. These include motor nerve pathways, which transmit information about voluntary muscle movement, and sensory nerve pathways, which transmit information about sensory input (such as touch, pain, and temperature). For the brain and the body to communicate effectively, these nerve pathways must cross from one side of the body to the other in the brainstem, a region that connects the upper parts of the brain with the spinal cord.  The ROBO3 protein plays a critical role in ensuring that motor and sensory nerve pathways cross over in the brainstem. In people with HGPPS, these pathways do not cross over, but stay on the same side of the body. Researchers believe that this miswiring in the brainstem is the underlying cause of the eye movement abnormalities associated with the disorder. The cause of progressive scoliosis in HGPPS is unclear. Researchers are working to determine why the effects of ROBO3 mutations appear to be limited to horizontal eye movement and scoliosis.",horizontal gaze palsy with progressive scoliosis,0000487,GHR,https://ghr.nlm.nih.gov/condition/horizontal-gaze-palsy-with-progressive-scoliosis,C1846496,T047,Disorders
Is horizontal gaze palsy with progressive scoliosis inherited ?,0000487-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",horizontal gaze palsy with progressive scoliosis,0000487,GHR,https://ghr.nlm.nih.gov/condition/horizontal-gaze-palsy-with-progressive-scoliosis,C1846496,T047,Disorders
What are the treatments for horizontal gaze palsy with progressive scoliosis ?,0000487-5,treatment,"These resources address the diagnosis or management of HGPPS:  - Genetic Testing Registry: Gaze palsy, familial horizontal, with progressive scoliosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",horizontal gaze palsy with progressive scoliosis,0000487,GHR,https://ghr.nlm.nih.gov/condition/horizontal-gaze-palsy-with-progressive-scoliosis,C1846496,T047,Disorders
What is (are) Horner syndrome ?,0000488-1,information,"Horner syndrome is a disorder that affects the eye and surrounding tissues on one side of the face and results from paralysis of certain nerves. Horner syndrome can appear at any time of life; in about 5 percent of affected individuals, the disorder is present from birth (congenital).  Horner syndrome is characterized by drooping of the upper eyelid (ptosis) on the affected side, a constricted pupil in the affected eye (miosis) resulting in unequal pupil size (anisocoria), and absent sweating (anhidrosis) on the affected side of the face. Sinking of the eye into its cavity (enophthalmos) and a bloodshot eye often occur in this disorder. In people with Horner syndrome that occurs before the age of 2, the colored part (iris) of the eyes may differ in color (iris heterochromia), with the iris of the affected eye being lighter in color than that of the unaffected eye. Individuals who develop Horner syndrome after age 2 do not generally have iris heterochromia.  The abnormalities in the eye area related to Horner syndrome do not generally affect vision or health. However, the nerve damage that causes Horner syndrome may result from other health problems, some of which can be life-threatening.",Horner syndrome,0000488,GHR,https://ghr.nlm.nih.gov/condition/horner-syndrome,C0338567,T047,Disorders
How many people are affected by Horner syndrome ?,0000488-2,frequency,"About 1 in 6,250 babies are born with Horner syndrome. The incidence of Horner syndrome that appears later is unknown, but it is considered an uncommon disorder.",Horner syndrome,0000488,GHR,https://ghr.nlm.nih.gov/condition/horner-syndrome,C0338567,T047,Disorders
What are the genetic changes related to Horner syndrome ?,0000488-3,genetic changes,"Although congenital Horner syndrome can be passed down in families, no associated genes have been identified. Horner syndrome that appears after the newborn period (acquired Horner syndrome) and most cases of congenital Horner syndrome result from damage to nerves called the cervical sympathetics. These nerves belong to the part of the nervous system that controls involuntary functions (the autonomic nervous system). Within the autonomic nervous system, the nerves are part of a subdivision called the sympathetic nervous system. The cervical sympathetic nerves control several functions in the eye and face such as dilation of the pupil and sweating. Problems with the function of these nerves cause the signs and symptoms of Horner syndrome. Horner syndrome that occurs very early in life can lead to iris heterochromia because the development of the pigmentation (coloring) of the iris is under the control of the cervical sympathetic nerves.  Damage to the cervical sympathetic nerves can be caused by a direct injury to the nerves themselves, which can result from trauma that might occur during a difficult birth, surgery, or accidental injury. The nerves related to Horner syndrome can also be damaged by a benign or cancerous tumor, for example a childhood cancer of the nerve tissues called a neuroblastoma.  Horner syndrome can also be caused by problems with the artery that supplies blood to the head and neck (the carotid artery) on the affected side, resulting in loss of blood flow to the nerves. Some individuals with congenital Horner syndrome have a lack of development (agenesis) of the carotid artery. Tearing of the layers of the carotid artery wall (carotid artery dissection) can also lead to Horner syndrome.  The signs and symptoms of Horner syndrome can also occur during a migraine headache. When the headache is gone, the signs and symptoms of Horner syndrome usually also go away.  Some people with Horner syndrome have neither a known problem that would lead to nerve damage nor any history of the disorder in their family. These cases are referred to as idiopathic Horner syndrome.",Horner syndrome,0000488,GHR,https://ghr.nlm.nih.gov/condition/horner-syndrome,C0338567,T047,Disorders
Is Horner syndrome inherited ?,0000488-4,inheritance,"Horner syndrome is usually not inherited and occurs in individuals with no history of the disorder in their family. Acquired Horner syndrome and most cases of congenital Horner syndrome have nongenetic causes. Rarely, congenital Horner syndrome is passed down within a family in a pattern that appears to be autosomal dominant, which means one copy of an altered gene in each cell is sufficient to cause the disorder. However, no genes associated with Horner syndrome have been identified.",Horner syndrome,0000488,GHR,https://ghr.nlm.nih.gov/condition/horner-syndrome,C0338567,T047,Disorders
What are the treatments for Horner syndrome ?,0000488-5,treatment,"These resources address the diagnosis or management of Horner syndrome:  - Genetic Testing Registry: Horner syndrome, congenital   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Horner syndrome,0000488,GHR,https://ghr.nlm.nih.gov/condition/horner-syndrome,C0338567,T047,Disorders
What is (are) Huntington disease ?,0000489-1,information,"Huntington disease is a progressive brain disorder that causes uncontrolled movements, emotional problems, and loss of thinking ability (cognition).  Adult-onset Huntington disease, the most common form of this disorder, usually appears in a person's thirties or forties. Early signs and symptoms can include irritability, depression, small involuntary movements, poor coordination, and trouble learning new information or making decisions. Many people with Huntington disease develop involuntary jerking or twitching movements known as chorea. As the disease progresses, these movements become more pronounced. Affected individuals may have trouble walking, speaking, and swallowing. People with this disorder also experience changes in personality and a decline in thinking and reasoning abilities. Individuals with the adult-onset form of Huntington disease usually live about 15 to 20 years after signs and symptoms begin.  A less common form of Huntington disease known as the juvenile form begins in childhood or adolescence. It also involves movement problems and mental and emotional changes. Additional signs of the juvenile form include slow movements, clumsiness, frequent falling, rigidity, slurred speech, and drooling. School performance declines as thinking and reasoning abilities become impaired. Seizures occur in 30 percent to 50 percent of children with this condition. Juvenile Huntington disease tends to progress more quickly than the adult-onset form; affected individuals usually live 10 to 15 years after signs and symptoms appear.",Huntington disease,0000489,GHR,https://ghr.nlm.nih.gov/condition/huntington-disease,C0020179,T047,Disorders
How many people are affected by Huntington disease ?,0000489-2,frequency,"Huntington disease affects an estimated 3 to 7 per 100,000 people of European ancestry. The disorder appears to be less common in some other populations, including people of Japanese, Chinese, and African descent.",Huntington disease,0000489,GHR,https://ghr.nlm.nih.gov/condition/huntington-disease,C0020179,T047,Disorders
What are the genetic changes related to Huntington disease ?,0000489-3,genetic changes,"Mutations in the HTT gene cause Huntington disease. The HTT gene provides instructions for making a protein called huntingtin. Although the function of this protein is unknown, it appears to play an important role in nerve cells (neurons) in the brain.  The HTT mutation that causes Huntington disease involves a DNA segment known as a CAG trinucleotide repeat. This segment is made up of a series of three DNA building blocks (cytosine, adenine, and guanine) that appear multiple times in a row. Normally, the CAG segment is repeated 10 to 35 times within the gene. In people with Huntington disease, the CAG segment is repeated 36 to more than 120 times. People with 36 to 39 CAG repeats may or may not develop the signs and symptoms of Huntington disease, while people with 40 or more repeats almost always develop the disorder.  An increase in the size of the CAG segment leads to the production of an abnormally long version of the huntingtin protein. The elongated protein is cut into smaller, toxic fragments that bind together and accumulate in neurons, disrupting the normal functions of these cells. The dysfunction and eventual death of neurons in certain areas of the brain underlie the signs and symptoms of Huntington disease.",Huntington disease,0000489,GHR,https://ghr.nlm.nih.gov/condition/huntington-disease,C0020179,T047,Disorders
Is Huntington disease inherited ?,0000489-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. An affected person usually inherits the altered gene from one affected parent. In rare cases, an individual with Huntington disease does not have a parent with the disorder.  As the altered HTT gene is passed from one generation to the next, the size of the CAG trinucleotide repeat often increases in size. A larger number of repeats is usually associated with an earlier onset of signs and symptoms. This phenomenon is called anticipation. People with the adult-onset form of Huntington disease typically have 40 to 50 CAG repeats in the HTT gene, while people with the juvenile form of the disorder tend to have more than 60 CAG repeats.  Individuals who have 27 to 35 CAG repeats in the HTT gene do not develop Huntington disease, but they are at risk of having children who will develop the disorder. As the gene is passed from parent to child, the size of the CAG trinucleotide repeat may lengthen into the range associated with Huntington disease (36 repeats or more).",Huntington disease,0000489,GHR,https://ghr.nlm.nih.gov/condition/huntington-disease,C0020179,T047,Disorders
What are the treatments for Huntington disease ?,0000489-5,treatment,These resources address the diagnosis or management of Huntington disease:  - Gene Review: Gene Review: Huntington Disease  - Genetic Testing Registry: Huntington's chorea  - Huntington's Disease Society of America: HD Care  - MedlinePlus Encyclopedia: Huntington Disease  - University of Washington Medical Center: Testing for Huntington Disease: Making an Informed Choice   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Huntington disease,0000489,GHR,https://ghr.nlm.nih.gov/condition/huntington-disease,C0020179,T047,Disorders
What is (are) Huntington disease-like syndrome ?,0000490-1,information,"As its name suggests, a Huntington disease-like (HDL) syndrome is a condition that resembles Huntington disease. Researchers have described four HDL syndromes, designated Huntington disease-like 1 (HDL1) through Huntington disease-like 4 (HDL4). These progressive brain disorders are characterized by uncontrolled movements, emotional problems, and loss of thinking ability. HDL syndromes occur in people with the characteristic features of Huntington disease who do not have a mutation in HD, the gene typically associated with that disorder.  HDL1, HDL2, and HDL4 usually appear in early to mid-adulthood, although they can begin earlier in life. The first signs and symptoms of these conditions often include irritability, emotional problems, small involuntary movements, poor coordination, and trouble learning new information or making decisions. Many affected people develop involuntary jerking or twitching movements known as chorea. As the disease progresses, these abnormal movements become more pronounced. Affected individuals may develop problems with walking, speaking, and swallowing. People with these disorders also experience changes in personality and a decline in thinking and reasoning abilities. Individuals with an HDL syndrome can live for a few years to more than a decade after signs and symptoms begin.  HDL3 begins much earlier in life than most of the other HDL syndromes (usually around age 3 or 4). Affected children experience a decline in thinking ability, difficulties with movement and speech, and seizures. Because HDL3 has a somewhat different pattern of signs and symptoms and a different pattern of inheritance, researchers are unsure whether it belongs in the same category as the other HDL syndromes.",Huntington disease-like syndrome,0000490,GHR,https://ghr.nlm.nih.gov/condition/huntington-disease-like-syndrome,C3711380,T047,Disorders
How many people are affected by Huntington disease-like syndrome ?,0000490-2,frequency,"Overall, HDL syndromes are rare. They are much less common than Huntington disease, which affects an estimated 3 to 7 per 100,000 people of European ancestry.  Of the four described HDL syndromes, HDL4 appears to be the most common. HDL2 is the second most common and occurs almost exclusively in people of African heritage (especially black South Africans). HDL1 has been reported in only one family. HDL3 has been found in two families, both of which were from Saudi Arabia.",Huntington disease-like syndrome,0000490,GHR,https://ghr.nlm.nih.gov/condition/huntington-disease-like-syndrome,C3711380,T047,Disorders
What are the genetic changes related to Huntington disease-like syndrome ?,0000490-3,genetic changes,"In about one percent of people with the characteristic features of Huntington disease, no mutation in the HD gene has been identified. Mutations in the PRNP, JPH3, and TBP genes have been found to cause the signs and symptoms in some of these individuals. HDL1 is caused by mutations in the PRNP gene, while HDL2 results from mutations in JPH3. Mutations in the TBP gene are responsible for HDL4 (also known as spinocerebellar ataxia type 17). The genetic cause of HDL3 is unknown.  The PRNP, JPH3, and TBP genes provide instructions for making proteins that are important for normal brain function. The features of HDL syndromes result from a particular type of mutation in any one of these genes. This mutation increases the length of a repeated segment of DNA within the gene, which leads to the production of an abnormal PRNP, JPH3, or TBP protein. The abnormal protein can build up in nerve cells (neurons) and disrupt the normal functions of these cells. The dysfunction and eventual death of neurons in certain areas of the brain underlie the signs and symptoms of HDL syndromes.  Other medical conditions and gene mutations may also cause signs and symptoms resembling Huntington disease. In some affected people, the cause of the disorder is never identified.",Huntington disease-like syndrome,0000490,GHR,https://ghr.nlm.nih.gov/condition/huntington-disease-like-syndrome,C3711380,T047,Disorders
Is Huntington disease-like syndrome inherited ?,0000490-4,inheritance,"HDL1, HDL2, and HDL4 are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent.  As the mutation responsible for HDL2 or HDL4 is passed down from one generation to the next, the length of the repeated DNA segment may increase. A longer repeat segment is often associated with more severe signs and symptoms that appear earlier in life. This phenomenon is known as anticipation.  HDL3 is probably inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they do not show signs and symptoms of the condition.",Huntington disease-like syndrome,0000490,GHR,https://ghr.nlm.nih.gov/condition/huntington-disease-like-syndrome,C3711380,T047,Disorders
What are the treatments for Huntington disease-like syndrome ?,0000490-5,treatment,These resources address the diagnosis or management of Huntington disease-like syndrome:  - Gene Review: Gene Review: Huntington Disease-Like 2  - Gene Review: Gene Review: Spinocerebellar Ataxia Type 17  - Genetic Testing Registry: Huntington disease-like 1  - Genetic Testing Registry: Huntington disease-like 2  - Genetic Testing Registry: Huntington disease-like 3  - Genetic Testing Registry: Spinocerebellar ataxia 17   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Huntington disease-like syndrome,0000490,GHR,https://ghr.nlm.nih.gov/condition/huntington-disease-like-syndrome,C3711380,T047,Disorders
What is (are) Hutchinson-Gilford progeria syndrome ?,0000491-1,information,"Hutchinson-Gilford progeria syndrome is a genetic condition characterized by the dramatic, rapid appearance of aging beginning in childhood. Affected children typically look normal at birth and in early infancy, but then grow more slowly than other children and do not gain weight at the expected rate (failure to thrive). They develop a characteristic facial appearance including prominent eyes, a thin nose with a beaked tip, thin lips, a small chin, and protruding ears. Hutchinson-Gilford progeria syndrome also causes hair loss (alopecia), aged-looking skin, joint abnormalities, and a loss of fat under the skin (subcutaneous fat). This condition does not disrupt intellectual development or the development of motor skills such as sitting, standing, and walking.  People with Hutchinson-Gilford progeria syndrome experience severe hardening of the arteries (arteriosclerosis) beginning in childhood. This condition greatly increases the chances of having a heart attack or stroke at a young age. These serious complications can worsen over time and are life-threatening for affected individuals.",Hutchinson-Gilford progeria syndrome,0000491,GHR,https://ghr.nlm.nih.gov/condition/hutchinson-gilford-progeria-syndrome,C0033300,T047,Disorders
How many people are affected by Hutchinson-Gilford progeria syndrome ?,0000491-2,frequency,This condition is very rare; it is reported to occur in 1 in 4 million newborns worldwide. More than 130 cases have been reported in the scientific literature since the condition was first described in 1886.,Hutchinson-Gilford progeria syndrome,0000491,GHR,https://ghr.nlm.nih.gov/condition/hutchinson-gilford-progeria-syndrome,C0033300,T047,Disorders
What are the genetic changes related to Hutchinson-Gilford progeria syndrome ?,0000491-3,genetic changes,"Mutations in the LMNA gene cause Hutchinson-Gilford progeria syndrome.  The LMNA gene provides instructions for making a protein called lamin A. This protein plays an important role in determining the shape of the nucleus within cells. It is an essential scaffolding (supporting) component of the nuclear envelope, which is the membrane that surrounds the nucleus. Mutations that cause Hutchinson-Gilford progeria syndrome result in the production of an abnormal version of the lamin A protein. The altered protein makes the nuclear envelope unstable and progressively damages the nucleus, making cells more likely to die prematurely. Researchers are working to determine how these changes lead to the characteristic features of Hutchinson-Gilford progeria syndrome.",Hutchinson-Gilford progeria syndrome,0000491,GHR,https://ghr.nlm.nih.gov/condition/hutchinson-gilford-progeria-syndrome,C0033300,T047,Disorders
Is Hutchinson-Gilford progeria syndrome inherited ?,0000491-4,inheritance,"Hutchinson-Gilford progeria syndrome is considered an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. The condition results from new mutations in the LMNA gene, and almost always occurs in people with no history of the disorder in their family.",Hutchinson-Gilford progeria syndrome,0000491,GHR,https://ghr.nlm.nih.gov/condition/hutchinson-gilford-progeria-syndrome,C0033300,T047,Disorders
What are the treatments for Hutchinson-Gilford progeria syndrome ?,0000491-5,treatment,These resources address the diagnosis or management of Hutchinson-Gilford progeria syndrome:  - Gene Review: Gene Review: Hutchinson-Gilford Progeria Syndrome  - Genetic Testing Registry: Hutchinson-Gilford syndrome  - MedlinePlus Encyclopedia: Progeria   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Hutchinson-Gilford progeria syndrome,0000491,GHR,https://ghr.nlm.nih.gov/condition/hutchinson-gilford-progeria-syndrome,C0033300,T047,Disorders
What is (are) hypercholesterolemia ?,0000492-1,information,"Hypercholesterolemia is a condition characterized by very high levels of cholesterol in the blood. Cholesterol is a waxy, fat-like substance that is produced in the body and obtained from foods that come from animals (particularly egg yolks, meat, poultry, fish, and dairy products). The body needs this substance to build cell membranes, make certain hormones, and produce compounds that aid in fat digestion. Too much cholesterol, however, increases a person's risk of developing heart disease.  People with hypercholesterolemia have a high risk of developing a form of heart disease called coronary artery disease. This condition occurs when excess cholesterol in the bloodstream is deposited in the walls of blood vessels, particularly in the arteries that supply blood to the heart (coronary arteries). The abnormal buildup of cholesterol forms clumps (plaque) that narrow and harden artery walls. As the clumps get bigger, they can clog the arteries and restrict the flow of blood to the heart. The buildup of plaque in coronary arteries causes a form of chest pain called angina and greatly increases a person's risk of having a heart attack.  Inherited forms of hypercholesterolemia can also cause health problems related to the buildup of excess cholesterol in other tissues. If cholesterol accumulates in tendons, it causes characteristic growths called tendon xanthomas. These growths most often affect the Achilles tendons and tendons in the hands and fingers. Yellowish cholesterol deposits under the skin of the eyelids are known as xanthelasmata. Cholesterol can also accumulate at the edges of the clear, front surface of the eye (the cornea), leading to a gray-colored ring called an arcus cornealis.",hypercholesterolemia,0000492,GHR,https://ghr.nlm.nih.gov/condition/hypercholesterolemia,C1522133,T047,Disorders
How many people are affected by hypercholesterolemia ?,0000492-2,frequency,"More than 34 million American adults have elevated blood cholesterol levels (higher than 240 mg/dL). Inherited forms of hypercholesterolemia, which cause even higher levels of cholesterol, occur less frequently. The most common inherited form of high cholesterol is called familial hypercholesterolemia. This condition affects about 1 in 500 people in most countries. Familial hypercholesterolemia occurs more frequently in certain populations, including Afrikaners in South Africa, French Canadians, Lebanese, and Finns.",hypercholesterolemia,0000492,GHR,https://ghr.nlm.nih.gov/condition/hypercholesterolemia,C1522133,T047,Disorders
What are the genetic changes related to hypercholesterolemia ?,0000492-3,genetic changes,"Mutations in the APOB, LDLR, LDLRAP1, and PCSK9 genes cause hypercholesterolemia.  High blood cholesterol levels typically result from a combination of genetic and environmental risk factors. Lifestyle choices including diet, exercise, and tobacco smoking strongly influence the amount of cholesterol in the blood. Additional factors that impact cholesterol levels include a person's gender, age, and health problems such as diabetes and obesity. A small percentage of all people with high cholesterol have an inherited form of hypercholesterolemia. The most common cause of inherited high cholesterol is a condition known as familial hypercholesterolemia, which results from mutations in the LDLR gene.  The LDLR gene provides instructions for making a protein called a low-density lipoprotein receptor. This type of receptor binds to particles called low-density lipoproteins (LDLs), which are the primary carriers of cholesterol in the blood. By removing low-density lipoproteins from the bloodstream, these receptors play a critical role in regulating cholesterol levels. Some LDLR mutations reduce the number of low-density lipoprotein receptors produced within cells. Other mutations disrupt the receptors' ability to remove low-density lipoproteins from the bloodstream. As a result, people with mutations in the LDLR gene have very high levels of blood cholesterol. As the excess cholesterol circulates through the bloodstream, it is deposited abnormally in tissues such as the skin, tendons, and arteries that supply blood to the heart.  Less commonly, hypercholesterolemia can be caused by mutations in the APOB, LDLRAP1, or PCSK9 gene. Changes in the APOB gene result in a form of inherited hypercholesterolemia known as familial defective apolipoprotein B-100 (FDB). LDLRAP1 mutations are responsible for another type of inherited high cholesterol, autosomal recessive hypercholesterolemia (ARH). Proteins produced from the APOB, LDLRAP1, and PCSK9 genes are essential for the normal function of low-density lipoprotein receptors. Mutations in any of these genes prevent the cell from making functional receptors or alter the receptors' function. Hypercholesterolemia results when low-density lipoprotein receptors are unable to remove cholesterol from the blood effectively.  Researchers are working to identify and characterize additional genes that may influence cholesterol levels and the risk of heart disease in people with hypercholesterolemia.",hypercholesterolemia,0000492,GHR,https://ghr.nlm.nih.gov/condition/hypercholesterolemia,C1522133,T047,Disorders
Is hypercholesterolemia inherited ?,0000492-4,inheritance,"Most cases of high cholesterol are not caused by a single inherited condition, but result from a combination of lifestyle choices and the effects of variations in many genes.  Inherited forms of hypercholesterolemia resulting from mutations in the LDLR, APOB, or PCSK9 gene have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of an altered gene in each cell is sufficient to cause the disorder. An affected person typically inherits one altered copy of the gene from an affected parent and one normal copy of the gene from the other parent.  Rarely, a person with familial hypercholesterolemia is born with two mutated copies of the LDLR gene. This situation occurs when the person has two affected parents, each of whom passes on one altered copy of the gene. The presence of two LDLR mutations results in a more severe form of hypercholesterolemia that usually appears in childhood.  When hypercholesterolemia is caused by mutations in the LDLRAP1 gene, the condition is inherited in an autosomal recessive pattern. Autosomal recessive inheritance means the condition results from two altered copies of the gene in each cell. The parents of an individual with autosomal recessive hypercholesterolemia each carry one copy of the altered gene, but their blood cholesterol levels are usually in the normal range.",hypercholesterolemia,0000492,GHR,https://ghr.nlm.nih.gov/condition/hypercholesterolemia,C1522133,T047,Disorders
What are the treatments for hypercholesterolemia ?,0000492-5,treatment,"These resources address the diagnosis or management of hypercholesterolemia:  - Gene Review: Gene Review: Familial Hypercholesterolemia  - GeneFacts: Familial Hypercholesterolemia: Diagnosis  - GeneFacts: Familial Hypercholesterolemia: Management  - Genetic Testing Registry: Familial hypercholesterolemia  - Genetic Testing Registry: Hypercholesterolemia, autosomal dominant, 3  - Genetic Testing Registry: Hypercholesterolemia, autosomal dominant, type B  - Genetic Testing Registry: Hypercholesterolemia, autosomal recessive  - Genomics Education Programme (UK)  - MedlinePlus Encyclopedia: Familial hypercholesterolemia  - MedlinePlus Encyclopedia: High blood cholesterol and triglycerides  - MedlinePlus Encyclopedia: Xanthoma   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",hypercholesterolemia,0000492,GHR,https://ghr.nlm.nih.gov/condition/hypercholesterolemia,C1522133,T047,Disorders
What is (are) hyperferritinemia-cataract syndrome ?,0000493-1,information,"Hyperferritinemia-cataract syndrome is a disorder characterized by an excess of an iron storage protein called ferritin in the blood (hyperferritinemia) and tissues of the body. A buildup of this protein begins early in life, leading to clouding of the lenses of the eyes (cataracts). In affected individuals, cataracts usually develop in infancy, rather than after age 60 as typically occurs in the general population. Cataracts that are not removed surgically cause progressive dimming and blurriness of vision because the clouded lenses reduce and distort incoming light.  Although the hyperferritinemia in this disorder does not usually cause any health problems other than cataracts, the elevated ferritin levels in the blood can be mistaken for a sign of certain liver disorders. These conditions result in excess iron in the body and may be treated by blood-drawing. However, individuals with hyperferritinemia-cataract syndrome do not have an excess of iron, and with repeated blood draws will develop reduced iron levels leading to a low number of red blood cells (anemia). Therefore, correct diagnosis of hyperferritinemia-cataract syndrome is important to avoid unnecessary treatments or invasive test procedures such as liver biopsies.",hyperferritinemia-cataract syndrome,0000493,GHR,https://ghr.nlm.nih.gov/condition/hyperferritinemia-cataract-syndrome,C0086543,T190,Disorders
How many people are affected by hyperferritinemia-cataract syndrome ?,0000493-2,frequency,"Hyperferritinemia-cataract syndrome has been estimated to occur in 1 in 200,000 individuals.",hyperferritinemia-cataract syndrome,0000493,GHR,https://ghr.nlm.nih.gov/condition/hyperferritinemia-cataract-syndrome,C0086543,T190,Disorders
What are the genetic changes related to hyperferritinemia-cataract syndrome ?,0000493-3,genetic changes,"Hyperferritinemia-cataract syndrome is caused by mutations in the FTL gene. This gene provides instructions for making the ferritin light chain, which is one part (subunit) of the protein ferritin. Ferritin is made up of 24 subunits formed into a hollow spherical molecule. The 24 subunits consist of varying numbers of the ferritin light chain and another subunit called the ferritin heavy chain, which is produced from another gene. The proportion of the two subunits varies in different tissues.  Ferritin stores and releases iron in cells. Each ferritin molecule can hold as many as 4,500 iron atoms inside its spherical structure. This storage capacity allows ferritin to regulate the amount of iron in cells and tissues.  The mutations that cause hyperferritinemia-cataract syndrome are found in a segment of the gene called the iron responsive element (IRE). The IRE normally can attach (bind) to a protein called the iron regulatory protein (IRP). When this binding occurs, the activity (expression) of the FTL gene is stopped to prevent too much ferritin light chain from being produced. This normally occurs when iron levels are low, because under those circumstances less ferritin is needed to store the iron. Mutations in the IRE segment of the FTL gene prevent it from binding with IRP, interfering with the mechanism by which ferritin production is matched to iron levels and resulting in excess ferritin being formed.",hyperferritinemia-cataract syndrome,0000493,GHR,https://ghr.nlm.nih.gov/condition/hyperferritinemia-cataract-syndrome,C0086543,T190,Disorders
Is hyperferritinemia-cataract syndrome inherited ?,0000493-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",hyperferritinemia-cataract syndrome,0000493,GHR,https://ghr.nlm.nih.gov/condition/hyperferritinemia-cataract-syndrome,C0086543,T190,Disorders
What are the treatments for hyperferritinemia-cataract syndrome ?,0000493-5,treatment,These resources address the diagnosis or management of hyperferritinemia-cataract syndrome:  - Boston Children's Hospital: Cataracts in Children  - Genetic Testing Registry: Hyperferritinemia cataract syndrome  - MedlinePlus Encyclopedia: Cataract Removal   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hyperferritinemia-cataract syndrome,0000493,GHR,https://ghr.nlm.nih.gov/condition/hyperferritinemia-cataract-syndrome,C0086543,T190,Disorders
What is (are) hyperkalemic periodic paralysis ?,0000494-1,information,"Hyperkalemic periodic paralysis is a condition that causes episodes of extreme muscle weakness or paralysis, usually beginning in infancy or early childhood. Most often, these episodes involve a temporary inability to move muscles in the arms and legs. Episodes tend to increase in frequency until mid-adulthood, after which they occur less frequently. Factors that can trigger attacks include rest after exercise, potassium-rich foods such as bananas and potatoes, stress, fatigue, alcohol, pregnancy, exposure to cold temperatures, certain medications, and periods without food (fasting). Muscle strength usually returns to normal between attacks, although many affected people continue to experience mild stiffness (myotonia), particularly in muscles of the face and hands.  Most people with hyperkalemic periodic paralysis have increased levels of potassium in their blood (hyperkalemia) during attacks. Hyperkalemia results when the weak or paralyzed muscles release potassium ions into the bloodstream. In other cases, attacks are associated with normal blood potassium levels (normokalemia). Ingesting potassium can trigger attacks in affected individuals, even if blood potassium levels do not go up.",hyperkalemic periodic paralysis,0000494,GHR,https://ghr.nlm.nih.gov/condition/hyperkalemic-periodic-paralysis,C0238357,T047,Disorders
How many people are affected by hyperkalemic periodic paralysis ?,0000494-2,frequency,"Hyperkalemic periodic paralysis affects an estimated 1 in 200,000 people.",hyperkalemic periodic paralysis,0000494,GHR,https://ghr.nlm.nih.gov/condition/hyperkalemic-periodic-paralysis,C0238357,T047,Disorders
What are the genetic changes related to hyperkalemic periodic paralysis ?,0000494-3,genetic changes,"Mutations in the SCN4A gene can cause hyperkalemic periodic paralysis. The SCN4A gene provides instructions for making a protein that plays an essential role in muscles used for movement (skeletal muscles). For the body to move normally, these muscles must tense (contract) and relax in a coordinated way. One of the changes that helps trigger muscle contractions is the flow of positively charged atoms (ions), including sodium, into muscle cells. The SCN4A protein forms channels that control the flow of sodium ions into these cells.  Mutations in the SCN4A gene alter the usual structure and function of sodium channels. The altered channels stay open too long or do not stay closed long enough, allowing more sodium ions to flow into muscle cells. This increase in sodium ions triggers the release of potassium from muscle cells, which causes more sodium channels to open and stimulates the flow of even more sodium ions into these cells. These changes in ion transport reduce the ability of skeletal muscles to contract, leading to episodes of muscle weakness or paralysis.  In 30 to 40 percent of cases, the cause of hyperkalemic periodic paralysis is unknown. Changes in other genes, which have not been identified, likely cause the disorder in these cases.",hyperkalemic periodic paralysis,0000494,GHR,https://ghr.nlm.nih.gov/condition/hyperkalemic-periodic-paralysis,C0238357,T047,Disorders
Is hyperkalemic periodic paralysis inherited ?,0000494-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",hyperkalemic periodic paralysis,0000494,GHR,https://ghr.nlm.nih.gov/condition/hyperkalemic-periodic-paralysis,C0238357,T047,Disorders
What are the treatments for hyperkalemic periodic paralysis ?,0000494-5,treatment,These resources address the diagnosis or management of hyperkalemic periodic paralysis:  - Gene Review: Gene Review: Hyperkalemic Periodic Paralysis  - Genetic Testing Registry: Familial hyperkalemic periodic paralysis  - Genetic Testing Registry: Hyperkalemic Periodic Paralysis Type 1  - MedlinePlus Encyclopedia: Hyperkalemic Periodic Paralysis  - Periodic Paralysis International: How is Periodic Paralysis Diagnosed?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hyperkalemic periodic paralysis,0000494,GHR,https://ghr.nlm.nih.gov/condition/hyperkalemic-periodic-paralysis,C0238357,T047,Disorders
What is (are) hyperlysinemia ?,0000495-1,information,"Hyperlysinemia is an inherited condition characterized by elevated blood levels of the amino acid lysine, a building block of most proteins. Hyperlysinemia is caused by the shortage (deficiency) of the enzyme that breaks down lysine. Hyperlysinemia typically causes no health problems, and most people with elevated lysine levels are unaware that they have this condition. Rarely, people with hyperlysinemia have intellectual disability or behavioral problems. It is not clear whether these problems are due to hyperlysinemia or another cause.",hyperlysinemia,0000495,GHR,https://ghr.nlm.nih.gov/condition/hyperlysinemia,C0268553,T047,Disorders
How many people are affected by hyperlysinemia ?,0000495-2,frequency,The incidence of hyperlysinemia is unknown.,hyperlysinemia,0000495,GHR,https://ghr.nlm.nih.gov/condition/hyperlysinemia,C0268553,T047,Disorders
What are the genetic changes related to hyperlysinemia ?,0000495-3,genetic changes,"Mutations in the AASS gene cause hyperlysinemia. The AASS gene provides instructions for making an enzyme called aminoadipic semialdehyde synthase. This enzyme performs two functions in the breakdown of lysine. First, the enzyme breaks down lysine to a molecule called saccharopine. It then breaks down saccharopine to a molecule called alpha-aminoadipate semialdehyde.  Mutations in the AASS gene that impair the breakdown of lysine result in elevated levels of lysine in the blood and urine. These increased levels of lysine do not appear to have any negative effects on the body.  When mutations in the AASS gene impair the breakdown of saccharopine, this molecule builds up in blood and urine. This buildup is sometimes referred to as saccharopinuria, which is considered to be a variant of hyperlysinemia. It is unclear if saccharopinuria causes any symptoms.",hyperlysinemia,0000495,GHR,https://ghr.nlm.nih.gov/condition/hyperlysinemia,C0268553,T047,Disorders
Is hyperlysinemia inherited ?,0000495-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",hyperlysinemia,0000495,GHR,https://ghr.nlm.nih.gov/condition/hyperlysinemia,C0268553,T047,Disorders
What are the treatments for hyperlysinemia ?,0000495-5,treatment,These resources address the diagnosis or management of hyperlysinemia:  - Genetic Testing Registry: Hyperlysinemia  - Genetic Testing Registry: Saccharopinuria   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hyperlysinemia,0000495,GHR,https://ghr.nlm.nih.gov/condition/hyperlysinemia,C0268553,T047,Disorders
"What is (are) hypermanganesemia with dystonia, polycythemia, and cirrhosis ?",0000496-1,information,"Hypermanganesemia with dystonia, polycythemia, and cirrhosis (HMDPC) is an inherited disorder in which excessive amounts of the element manganese accumulate in the body, particularly in the brain, liver, and blood (hypermanganesemia). Signs and symptoms of this condition can appear in childhood (early-onset), typically between ages 2 and 15, or in adulthood (adult-onset).  Manganese accumulates in a region of the brain responsible for the coordination of movement, causing neurological problems that make controlling movement difficult. Most children with the early-onset form of HMDPC experience involuntary tensing of the muscles in the arms and legs (four-limb dystonia), which often leads to a characteristic high-stepping walk described as a ""cock-walk gait."" Other neurological symptoms in affected children include involuntary trembling (tremor), unusually slow movement (bradykinesia), and slurred speech (dysarthria). The adult-onset form of HMDPC is characterized by a pattern of movement abnormalities known as parkinsonism, which includes bradykinesia, tremor, muscle rigidity, and an inability to hold the body upright and balanced (postural instability).  Affected individuals have an increased number of red blood cells (polycythemia) and low levels of iron stored in the body. Additional features of HMDPC can include an enlarged liver (hepatomegaly), scarring (fibrosis) in the liver, and irreversible liver disease (cirrhosis).","hypermanganesemia with dystonia, polycythemia, and cirrhosis",0000496,GHR,https://ghr.nlm.nih.gov/condition/hypermanganesemia-with-dystonia-polycythemia-and-cirrhosis,C0023890,T047,Disorders
"How many people are affected by hypermanganesemia with dystonia, polycythemia, and cirrhosis ?",0000496-2,frequency,The prevalence of HMDPC is unknown. A small number of cases have been described in the scientific literature.,"hypermanganesemia with dystonia, polycythemia, and cirrhosis",0000496,GHR,https://ghr.nlm.nih.gov/condition/hypermanganesemia-with-dystonia-polycythemia-and-cirrhosis,C0023890,T047,Disorders
"What are the genetic changes related to hypermanganesemia with dystonia, polycythemia, and cirrhosis ?",0000496-3,genetic changes,"Mutations in the SLC30A10 gene cause HMDPC. This gene provides instructions for making a protein that transports manganese across cell membranes. Manganese is important for many cellular functions, but large amounts are toxic, particularly to brain and liver cells. The SLC30A10 protein is found in the membranes surrounding liver cells and nerve cells in the brain, as well as in the membranes of structures within these cells. The protein protects these cells from high concentrations of manganese by removing manganese when levels become elevated.  Mutations in the SLC30A10 gene impair the transport of manganese out of cells, allowing the element to build up in the brain and liver. Manganese accumulation in the brain leads to the movement problems characteristic of HMDPC. Damage from manganese buildup in the liver leads to liver abnormalities in people with this condition. High levels of manganese help increase the production of red blood cells, so excess amounts of this element also result in polycythemia.","hypermanganesemia with dystonia, polycythemia, and cirrhosis",0000496,GHR,https://ghr.nlm.nih.gov/condition/hypermanganesemia-with-dystonia-polycythemia-and-cirrhosis,C0023890,T047,Disorders
"Is hypermanganesemia with dystonia, polycythemia, and cirrhosis inherited ?",0000496-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.","hypermanganesemia with dystonia, polycythemia, and cirrhosis",0000496,GHR,https://ghr.nlm.nih.gov/condition/hypermanganesemia-with-dystonia-polycythemia-and-cirrhosis,C0023890,T047,Disorders
"What are the treatments for hypermanganesemia with dystonia, polycythemia, and cirrhosis ?",0000496-5,treatment,"These resources address the diagnosis or management of HMDPC:  - Gene Review: Gene Review: Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, and Chronic Liver Disease  - Genetic Testing Registry: Hypermanganesemia with dystonia, polycythemia and cirrhosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","hypermanganesemia with dystonia, polycythemia, and cirrhosis",0000496,GHR,https://ghr.nlm.nih.gov/condition/hypermanganesemia-with-dystonia-polycythemia-and-cirrhosis,C0023890,T047,Disorders
What is (are) hypermethioninemia ?,0000497-1,information,"Hypermethioninemia is an excess of a particular protein building block (amino acid), called methionine, in the blood. This condition can occur when methionine is not broken down (metabolized) properly in the body.  People with hypermethioninemia often do not show any symptoms. Some individuals with hypermethioninemia exhibit intellectual disability and other neurological problems; delays in motor skills such as standing or walking; sluggishness; muscle weakness; liver problems; unusual facial features; and their breath, sweat, or urine may have a smell resembling boiled cabbage.  Hypermethioninemia can occur with other metabolic disorders, such as homocystinuria, tyrosinemia and galactosemia, which also involve the faulty breakdown of particular molecules. It can also result from liver disease or excessive dietary intake of methionine from consuming large amounts of protein or a methionine-enriched infant formula.",hypermethioninemia,0000497,GHR,https://ghr.nlm.nih.gov/condition/hypermethioninemia,C0268621,T047,Disorders
How many people are affected by hypermethioninemia ?,0000497-2,frequency,"Primary hypermethioninemia that is not caused by other disorders or excess methionine intake appears to be rare; only a small number of cases have been reported. The actual incidence is difficult to determine, however, since many individuals with hypermethioninemia have no symptoms.",hypermethioninemia,0000497,GHR,https://ghr.nlm.nih.gov/condition/hypermethioninemia,C0268621,T047,Disorders
What are the genetic changes related to hypermethioninemia ?,0000497-3,genetic changes,"Mutations in the AHCY, GNMT, and MAT1A genes cause hypermethioninemia.  Inherited hypermethioninemia that is not associated with other metabolic disorders can be caused by shortages (deficiencies) in the enzymes that break down methionine. These enzymes are produced from the MAT1A, GNMT and AHCY genes. The reactions involved in metabolizing methionine help supply some of the amino acids needed for protein production. These reactions are also involved in transferring methyl groups, consisting of a carbon atom and three hydrogen atoms, from one molecule to another (transmethylation), which is important in many cellular processes.  The MAT1A gene provides instructions for producing the enzyme methionine adenosyltransferase. This enzyme converts methionine into a compound called S-adenosylmethionine, also known as AdoMet or SAMe. The GNMT gene provides instructions for making the enzyme glycine N-methyltransferase. This enzyme starts the next step in the process, converting AdoMet to a compound called S-adenosyl homocysteine, or AdoHcy. The AHCY gene provides instructions for producing the enzyme S-adenosylhomocysteine hydrolase. This enzyme converts the AdoHcy into the compound homocysteine. Homocysteine may be converted back to methionine or into another amino acid, cysteine.  A deficiency of any of these enzymes results in a buildup of methionine in the body, and may cause signs and symptoms related to hypermethioninemia.",hypermethioninemia,0000497,GHR,https://ghr.nlm.nih.gov/condition/hypermethioninemia,C0268621,T047,Disorders
Is hypermethioninemia inherited ?,0000497-4,inheritance,"Hypermethioninemia can have different inheritance patterns. This condition is usually inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.  Hypermethioninemia is occasionally inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In these cases, an affected person usually has one parent with the condition.",hypermethioninemia,0000497,GHR,https://ghr.nlm.nih.gov/condition/hypermethioninemia,C0268621,T047,Disorders
What are the treatments for hypermethioninemia ?,0000497-5,treatment,These resources address the diagnosis or management of hypermethioninemia:  - Baby's First Test  - Genetic Testing Registry: Glycine N-methyltransferase deficiency  - Genetic Testing Registry: Hepatic methionine adenosyltransferase deficiency  - Genetic Testing Registry: Hypermethioninemia with s-adenosylhomocysteine hydrolase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hypermethioninemia,0000497,GHR,https://ghr.nlm.nih.gov/condition/hypermethioninemia,C0268621,T047,Disorders
What is (are) hyperparathyroidism-jaw tumor syndrome ?,0000498-1,information,"Hyperparathyroidism-jaw tumor syndrome is a condition characterized by overactivity of the parathyroid glands (hyperparathyroidism). The four parathyroid glands are located in the neck and secrete a hormone that regulates the body's use of calcium. Hyperparathyroidism disrupts the normal balance of calcium in the blood, which can lead to kidney stones, thinning of the bones (osteoporosis), nausea, vomiting, high blood pressure (hypertension), weakness, and fatigue.  In people with hyperthyroidism-jaw tumor syndrome, hyperparathyroidism is caused by tumors that form in the parathyroid glands. Typically only one of the four parathyroid glands is affected, but in some people, tumors are found in more than one gland. The tumors are usually noncancerous (benign), in which case they are called adenomas. Approximately 15 percent of people with hyperparathyroidism-jaw tumor syndrome develop a cancerous tumor called parathyroid carcinoma. People with hyperparathyroidism-jaw tumor syndrome may also have a type of benign tumor called a fibroma in the jaw. Even though jaw tumors are specified in the name of this condition, it is estimated that only 25 to 50 percent of affected individuals have this symptom.  Other tumors, both benign and cancerous, are often seen in hyperparathyroidism-jaw tumor syndrome. For example, tumors of the uterus occur in about 75 percent of women with this condition. The kidneys are affected in about 20 percent of people with hyperparathyroidism-jaw tumor syndrome. Benign kidney cysts are the most common kidney feature, but a rare tumor called Wilms tumor and other types of kidney tumor have also been found.",hyperparathyroidism-jaw tumor syndrome,0000498,GHR,https://ghr.nlm.nih.gov/condition/hyperparathyroidism-jaw-tumor-syndrome,C1704981,T191,Disorders
How many people are affected by hyperparathyroidism-jaw tumor syndrome ?,0000498-2,frequency,The exact prevalence of hyperparathyroidism-jaw tumor syndrome is unknown. Approximately 200 cases have been reported in the medical literature.,hyperparathyroidism-jaw tumor syndrome,0000498,GHR,https://ghr.nlm.nih.gov/condition/hyperparathyroidism-jaw-tumor-syndrome,C1704981,T191,Disorders
What are the genetic changes related to hyperparathyroidism-jaw tumor syndrome ?,0000498-3,genetic changes,"Mutations in the CDC73 gene (also known as the HRPT2 gene) cause hyperparathyroidism-jaw tumor syndrome. The CDC73 gene provides instructions for making a protein called parafibromin. This protein is found throughout the body and is likely involved in gene transcription, which is the first step in protein production. Parafibromin is also thought to play a role in cell growth and division (proliferation), either promoting or inhibiting cell proliferation depending on signals within the cell.  CDC73 gene mutations cause hyperparathyroidism-jaw tumor syndrome by reducing the amount of functional parafibromin that is produced. Most of these mutations result in a parafibromin protein that is abnormally short and nonfunctional. Without functional parafibromin, cell proliferation is not properly regulated. Uncontrolled cell division can lead to the formation of tumors. It is unknown why only certain tissues seem to be affected by changes in parafibromin.  Some people with hyperparathyroidism-jaw tumor syndrome do not have identified mutations in the CDC73 gene. The cause of the condition in these individuals is unknown.",hyperparathyroidism-jaw tumor syndrome,0000498,GHR,https://ghr.nlm.nih.gov/condition/hyperparathyroidism-jaw-tumor-syndrome,C1704981,T191,Disorders
Is hyperparathyroidism-jaw tumor syndrome inherited ?,0000498-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",hyperparathyroidism-jaw tumor syndrome,0000498,GHR,https://ghr.nlm.nih.gov/condition/hyperparathyroidism-jaw-tumor-syndrome,C1704981,T191,Disorders
What are the treatments for hyperparathyroidism-jaw tumor syndrome ?,0000498-5,treatment,These resources address the diagnosis or management of hyperparathyroidism-jaw tumor syndrome:  - Gene Review: Gene Review: CDC73-Related Disorders  - Genetic Testing Registry: Hyperparathyroidism 2  - MedlinePlus Encyclopedia: Hyperparathyroidism   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hyperparathyroidism-jaw tumor syndrome,0000498,GHR,https://ghr.nlm.nih.gov/condition/hyperparathyroidism-jaw-tumor-syndrome,C1704981,T191,Disorders
What is (are) hyperphosphatemic familial tumoral calcinosis ?,0000499-1,information,"Hyperphosphatemic familial tumoral calcinosis (HFTC) is a condition characterized by an increase in the levels of phosphate in the blood (hyperphosphatemia) and abnormal deposits of phosphate and calcium (calcinosis) in the body's tissues. Calcinosis typically develops in early childhood to early adulthood, although in some people the deposits first appear in infancy or in late adulthood. Calcinosis usually occurs in and just under skin tissue around the joints, most often the hips, shoulders, and elbows. Calcinosis may also develop in the soft tissue of the feet, legs, and hands. Rarely, calcinosis occurs in blood vessels or in the brain and can cause serious health problems. The deposits develop over time and vary in size. Larger deposits form masses that are noticeable under the skin and can interfere with the function of joints and impair movement. These large deposits may appear tumor-like (tumoral), but they are not tumors or cancerous. The number and frequency of deposits varies among affected individuals; some develop few deposits during their lifetime, while others may develop many in a short period of time.  Other features of HFTC include eye abnormalities such as calcium buildup in the clear front covering of the eye (corneal calcification) or angioid streaks that occur when tiny breaks form in the layer of tissue at the back of the eye called Bruch's membrane. Inflammation of the long bones (diaphysis) or excessive bone growth (hyperostosis) may occur. Some affected individuals have dental abnormalities. In males, small crystals of cholesterol can accumulate (microlithiasis) in the testicles, which usually causes no health problems.  A similar condition called hyperphosphatemia-hyperostosis syndrome (HHS) results in increased levels of phosphate in the blood, excessive bone growth, and bone lesions. This condition used to be considered a separate disorder, but it is now thought to be a mild variant of HFTC.",hyperphosphatemic familial tumoral calcinosis,0000499,GHR,https://ghr.nlm.nih.gov/condition/hyperphosphatemic-familial-tumoral-calcinosis,C1876187,T047,Disorders
How many people are affected by hyperphosphatemic familial tumoral calcinosis ?,0000499-2,frequency,"The prevalence of HFTC is unknown, but it is thought to be a rare condition. It occurs most often in Middle Eastern and African populations.",hyperphosphatemic familial tumoral calcinosis,0000499,GHR,https://ghr.nlm.nih.gov/condition/hyperphosphatemic-familial-tumoral-calcinosis,C1876187,T047,Disorders
What are the genetic changes related to hyperphosphatemic familial tumoral calcinosis ?,0000499-3,genetic changes,"Mutations in the FGF23, GALNT3, or KL gene cause HFTC. The proteins produced from these genes are all involved in the regulation of phosphate levels within the body (phosphate homeostasis). Among its many functions, phosphate plays a critical role in the formation and growth of bones in childhood and helps maintain bone strength in adults. Phosphate levels are controlled in large part by the kidneys. The kidneys normally rid the body of excess phosphate by excreting it in urine, and they reabsorb this mineral into the bloodstream when more is needed.  The FGF23 gene provides instructions for making a protein called fibroblast growth factor 23, which is produced in bone cells and signals the kidneys to stop reabsorbing phosphate. The proteins produced from the GALNT3 and KL genes help to regulate fibroblast growth factor 23. The protein produced from the GALNT3 gene, called ppGalNacT3, attaches sugar molecules to fibroblast growth factor 23 in a process called glycosylation. Glycosylation allows fibroblast growth factor 23 to move out of the cell and protects the protein from being broken down. Once outside the bone cell, fibroblast growth factor 23 must attach (bind) to a receptor protein that spans the membrane of kidney cells. The protein produced from the KL gene, called alpha-klotho, turns on (activates) the receptor protein so that fibroblast growth factor 23 can bind to it. Binding of fibroblast growth factor 23 to its receptor stimulates signaling that stops phosphate reabsorption into the bloodstream.  Mutations in the FGF23, GALNT3, or KL gene lead to a disruption in fibroblast growth factor 23 signaling. FGF23 gene mutations result in the production of a protein with decreased function that quickly gets broken down. Mutations in the GALNT3 gene result in the production of ppGalNacT3 protein with little or no function. As a result, the protein cannot glycosylate fibroblast growth factor 23, which is consequently trapped inside the cell and broken down rather than being released from the cell (secreted). KL gene mutations lead to a shortage of functional alpha-klotho. As a result, the receptor protein is not activated, causing it to be unavailable to be bound to fibroblast growth factor 23. All of these impairments to fibroblast growth factor 23 function and signaling lead to increased phosphate absorption by the kidneys. Calcinosis results when the excess phosphate combines with calcium to form deposits that build up in soft tissues. Although phosphate levels are increased, calcium is typically within the normal range.",hyperphosphatemic familial tumoral calcinosis,0000499,GHR,https://ghr.nlm.nih.gov/condition/hyperphosphatemic-familial-tumoral-calcinosis,C1876187,T047,Disorders
Is hyperphosphatemic familial tumoral calcinosis inherited ?,0000499-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",hyperphosphatemic familial tumoral calcinosis,0000499,GHR,https://ghr.nlm.nih.gov/condition/hyperphosphatemic-familial-tumoral-calcinosis,C1876187,T047,Disorders
What are the treatments for hyperphosphatemic familial tumoral calcinosis ?,0000499-5,treatment,"These resources address the diagnosis or management of hyperphosphatemic familial tumoral calcinosis:  - Genetic Testing Registry: Tumoral calcinosis, familial, hyperphosphatemic   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",hyperphosphatemic familial tumoral calcinosis,0000499,GHR,https://ghr.nlm.nih.gov/condition/hyperphosphatemic-familial-tumoral-calcinosis,C1876187,T047,Disorders
What is (are) hyperprolinemia ?,0000500-1,information,"Hyperprolinemia is an excess of a particular protein building block (amino acid), called proline, in the blood. This condition generally occurs when proline is not broken down properly by the body. There are two inherited forms of hyperprolinemia, called type I and type II.  People with hyperprolinemia type I often do not show any symptoms, although they have proline levels in their blood between 3 and 10 times the normal level. Some individuals with hyperprolinemia type I exhibit seizures, intellectual disability, or other neurological or psychiatric problems.  Hyperprolinemia type II results in proline levels in the blood between 10 and 15 times higher than normal, and high levels of a related compound called pyrroline-5-carboxylate. This form of the disorder has signs and symptoms that vary in severity, and is more likely than type I to involve seizures or intellectual disability.  Hyperprolinemia can also occur with other conditions, such as malnutrition or liver disease. In particular, individuals with conditions that cause elevated levels of lactic acid in the blood (lactic acidemia) may have hyperprolinemia as well, because lactic acid inhibits the breakdown of proline.",hyperprolinemia,0000500,GHR,https://ghr.nlm.nih.gov/condition/hyperprolinemia,C0268529,T047,Disorders
How many people are affected by hyperprolinemia ?,0000500-2,frequency,It is difficult to determine the prevalence of hyperprolinemia type I because most people with the condition do not have any symptoms. Hyperprolinemia type II is a rare condition; its prevalence is also unknown.,hyperprolinemia,0000500,GHR,https://ghr.nlm.nih.gov/condition/hyperprolinemia,C0268529,T047,Disorders
What are the genetic changes related to hyperprolinemia ?,0000500-3,genetic changes,"Mutations in the ALDH4A1 and PRODH genes cause hyperprolinemia.  Inherited hyperprolinemia is caused by deficiencies in the enzymes that break down (degrade) proline. Hyperprolinemia type I is caused by a mutation in the PRODH gene, which provides instructions for producing the enzyme proline oxidase. This enzyme begins the process of degrading proline by starting the reaction that converts it to pyrroline-5-carboxylate.  Hyperprolinemia type II is caused by a mutation in the ALDH4A1 gene, which provides instructions for producing the enzyme pyrroline-5-carboxylate dehydrogenase. This enzyme helps to break down the pyrroline-5-carboxylate produced in the previous reaction, converting it to the amino acid glutamate. The conversion between proline and glutamate, and the reverse reaction controlled by different enzymes, are important in maintaining a supply of the amino acids needed for protein production, and for energy transfer within the cell.  A deficiency of either proline oxidase or pyrroline-5-carboxylate dehydrogenase results in a buildup of proline in the body. A deficiency of the latter enzyme leads to higher levels of proline and a buildup of the intermediate breakdown product pyrroline-5-carboxylate, causing the signs and symptoms of hyperprolinemia type II.",hyperprolinemia,0000500,GHR,https://ghr.nlm.nih.gov/condition/hyperprolinemia,C0268529,T047,Disorders
Is hyperprolinemia inherited ?,0000500-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition. In about one-third of cases, individuals carrying one copy of an altered PRODH gene have moderately elevated levels of proline in their blood, but these levels do not cause any health problems. Individuals with one altered ALDH4A1 gene have normal levels of proline in their blood.",hyperprolinemia,0000500,GHR,https://ghr.nlm.nih.gov/condition/hyperprolinemia,C0268529,T047,Disorders
What are the treatments for hyperprolinemia ?,0000500-5,treatment,These resources address the diagnosis or management of hyperprolinemia:  - Baby's First Test  - Genetic Testing Registry: Deficiency of pyrroline-5-carboxylate reductase  - Genetic Testing Registry: Proline dehydrogenase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hyperprolinemia,0000500,GHR,https://ghr.nlm.nih.gov/condition/hyperprolinemia,C0268529,T047,Disorders
What is (are) hypochondrogenesis ?,0000501-1,information,"Hypochondrogenesis is a rare, severe disorder of bone growth. This condition is characterized by a small body, short limbs, and abnormal bone formation (ossification) in the spine and pelvis.  Affected infants have short arms and legs, a small chest with short ribs, and underdeveloped lungs. Bones in the skull develop normally, but the bones of the spine (vertebrae) and pelvis do not harden (ossify) properly. The face appears flat and oval-shaped, with widely spaced eyes, a small chin, and, in some cases, an opening in the roof of the mouth called a cleft palate. Individuals with hypochondrogenesis have an enlarged abdomen and may have a condition called hydrops fetalis in which excess fluid builds up in the body before birth.  As a result of these serious health problems, some affected fetuses do not survive to term. Infants born with hypochondrogenesis usually die at birth or shortly thereafter from respiratory failure. Babies who live past the newborn period are usually reclassified as having spondyloepiphyseal dysplasia congenita, a related but milder disorder that similarly affects bone development.",hypochondrogenesis,0000501,GHR,https://ghr.nlm.nih.gov/condition/hypochondrogenesis,C0542428,T019,Disorders
How many people are affected by hypochondrogenesis ?,0000501-2,frequency,"Hypochondrogenesis and achondrogenesis, type 2 (a similar skeletal disorder) together affect 1 in 40,000 to 60,000 newborns.",hypochondrogenesis,0000501,GHR,https://ghr.nlm.nih.gov/condition/hypochondrogenesis,C0542428,T019,Disorders
What are the genetic changes related to hypochondrogenesis ?,0000501-3,genetic changes,"Hypochondrogenesis is one of the most severe conditions in a spectrum of disorders caused by mutations in the COL2A1 gene. This gene provides instructions for making a protein that forms type II collagen. This type of collagen is found mostly in the clear gel that fills the eyeball (the vitreous) and in cartilage. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Type II collagen is essential for the normal development of bones and other connective tissues that form the body's supportive framework. Mutations in the COL2A1 gene interfere with the assembly of type II collagen molecules, which prevents bones and other connective tissues from developing properly.",hypochondrogenesis,0000501,GHR,https://ghr.nlm.nih.gov/condition/hypochondrogenesis,C0542428,T019,Disorders
Is hypochondrogenesis inherited ?,0000501-4,inheritance,Hypochondrogenesis is considered an autosomal dominant disorder because one copy of the altered gene in each cell is sufficient to cause the condition. It is caused by new mutations in the COL2A1 gene and occurs in people with no history of the disorder in their family. This condition is not passed on to the next generation because affected individuals do not live long enough to have children.,hypochondrogenesis,0000501,GHR,https://ghr.nlm.nih.gov/condition/hypochondrogenesis,C0542428,T019,Disorders
What are the treatments for hypochondrogenesis ?,0000501-5,treatment,These resources address the diagnosis or management of hypochondrogenesis:  - Genetic Testing Registry: Hypochondrogenesis  - MedlinePlus Encyclopedia: Achondrogenesis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hypochondrogenesis,0000501,GHR,https://ghr.nlm.nih.gov/condition/hypochondrogenesis,C0542428,T019,Disorders
What is (are) hypochondroplasia ?,0000502-1,information,"Hypochondroplasia is a form of short-limbed dwarfism. This condition affects the conversion of cartilage into bone (a process called ossification), particularly in the long bones of the arms and legs. Hypochondroplasia is similar to another skeletal disorder called achondroplasia, but the features tend to be milder.  All people with hypochondroplasia have short stature. The adult height for men with this condition ranges from 138 centimeters to 165 centimeters (4 feet, 6 inches to 5 feet, 5 inches). The height range for adult women is 128 centimeters to 151 centimeters (4 feet, 2 inches to 4 feet, 11 inches).  People with hypochondroplasia have short arms and legs and broad, short hands and feet. Other characteristic features include a large head, limited range of motion at the elbows, a sway of the lower back (lordosis), and bowed legs. These signs are generally less pronounced than those seen with achondroplasia and may not be noticeable until early or middle childhood. Some studies have reported that a small percentage of people with hypochondroplasia have mild to moderate intellectual disability or learning problems, but other studies have produced conflicting results.",hypochondroplasia,0000502,GHR,https://ghr.nlm.nih.gov/condition/hypochondroplasia,C0410529,T019,Disorders
How many people are affected by hypochondroplasia ?,0000502-2,frequency,"The incidence of hypochondroplasia is unknown. Researchers believe that it may be about as common as achondroplasia, which occurs in 1 in 15,000 to 40,000 newborns. More than 200 people worldwide have been diagnosed with hypochondroplasia.",hypochondroplasia,0000502,GHR,https://ghr.nlm.nih.gov/condition/hypochondroplasia,C0410529,T019,Disorders
What are the genetic changes related to hypochondroplasia ?,0000502-3,genetic changes,"About 70 percent of all cases of hypochondroplasia are caused by mutations in the FGFR3 gene. This gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. Although it remains unclear how FGFR3 mutations lead to the features of hypochondroplasia, researchers believe that these genetic changes cause the protein to be overly active. The overactive FGFR3 protein likely interferes with skeletal development and leads to the disturbances in bone growth that are characteristic of this disorder.  In the absence of a mutation in the FGFR3 gene, the cause of hypochondroplasia is unknown. Researchers suspect that mutations in other genes are involved, although these genes have not been identified.",hypochondroplasia,0000502,GHR,https://ghr.nlm.nih.gov/condition/hypochondroplasia,C0410529,T019,Disorders
Is hypochondroplasia inherited ?,0000502-4,inheritance,"Hypochondroplasia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most people with hypochondroplasia have average-size parents; these cases result from a new mutation in the FGFR3 gene. In the remaining cases, people with hypochondroplasia have inherited an altered FGFR3 gene from one or two affected parents. Individuals who inherit two altered copies of this gene typically have more severe problems with bone growth than those who inherit a single FGFR3 mutation.",hypochondroplasia,0000502,GHR,https://ghr.nlm.nih.gov/condition/hypochondroplasia,C0410529,T019,Disorders
What are the treatments for hypochondroplasia ?,0000502-5,treatment,These resources address the diagnosis or management of hypochondroplasia:  - Gene Review: Gene Review: Hypochondroplasia  - Genetic Testing Registry: Hypochondroplasia  - MedlinePlus Encyclopedia: Lordosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hypochondroplasia,0000502,GHR,https://ghr.nlm.nih.gov/condition/hypochondroplasia,C0410529,T019,Disorders
What is (are) hypochromic microcytic anemia with iron overload ?,0000503-1,information,"Hypochromic microcytic anemia with iron overload is a condition that impairs the normal transport of iron in cells. Iron is an essential component of hemoglobin, which is the substance that red blood cells use to carry oxygen to cells and tissues throughout the body. In this condition, red blood cells cannot access iron in the blood, so there is a decrease of red blood cell production (anemia) that is apparent at birth. The red blood cells that are produced are abnormally small (microcytic) and pale (hypochromic). Hypochromic microcytic anemia with iron overload can lead to pale skin (pallor), tiredness (fatigue), and slow growth.  In hypochromic microcytic anemia with iron overload, the iron that is not used by red blood cells accumulates in the liver, which can impair its function over time. The liver problems typically become apparent in adolescence or early adulthood.",hypochromic microcytic anemia with iron overload,0000503,GHR,https://ghr.nlm.nih.gov/condition/hypochromic-microcytic-anemia-with-iron-overload,C0271901,T047,Disorders
How many people are affected by hypochromic microcytic anemia with iron overload ?,0000503-2,frequency,Hypochromic microcytic anemia with iron overload is likely a rare disorder; at least five affected families have been reported in the scientific literature.,hypochromic microcytic anemia with iron overload,0000503,GHR,https://ghr.nlm.nih.gov/condition/hypochromic-microcytic-anemia-with-iron-overload,C0271901,T047,Disorders
What are the genetic changes related to hypochromic microcytic anemia with iron overload ?,0000503-3,genetic changes,"Mutations in the SLC11A2 gene cause hypochromic microcytic anemia with iron overload. The SLC11A2 gene provides instructions for making a protein called divalent metal transporter 1 (DMT1). The DMT1 protein is found in all tissues, where its primary role is to transport positively charged iron atoms (ions) within cells. In a section of the small intestine called the duodenum, the DMT1 protein is located within finger-like projections called microvilli. These projections absorb nutrients from food as it passes through the intestine and then release them into the bloodstream. In all other cells, including immature red blood cells called erythroblasts, DMT1 is located in the membrane of endosomes, which are specialized compartments that are formed at the cell surface to carry proteins and other molecules to their destinations within the cell. DMT1 transports iron from the endosomes to the cytoplasm so it can be used by the cell.  SLC11A2 gene mutations lead to reduced production of the DMT1 protein, decreased protein function, or impaired ability of the protein to get to the correct location in cells. In erythroblasts, a shortage of DMT1 protein diminishes the amount of iron transported within cells to attach to hemoglobin. As a result, the development of healthy red blood cells is impaired, leading to a shortage of these cells. In the duodenum, a shortage of DMT1 protein decreases iron absorption. To compensate, cells increase production of functional DMT1 protein, which increases iron absorption. Because the red blood cells cannot use the iron that is absorbed, it accumulates in the liver, eventually impairing liver function. The lack of involvement of other tissues in hypochromic microcytic anemia with iron overload is likely because these tissues have other ways to transport iron.",hypochromic microcytic anemia with iron overload,0000503,GHR,https://ghr.nlm.nih.gov/condition/hypochromic-microcytic-anemia-with-iron-overload,C0271901,T047,Disorders
Is hypochromic microcytic anemia with iron overload inherited ?,0000503-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",hypochromic microcytic anemia with iron overload,0000503,GHR,https://ghr.nlm.nih.gov/condition/hypochromic-microcytic-anemia-with-iron-overload,C0271901,T047,Disorders
What are the treatments for hypochromic microcytic anemia with iron overload ?,0000503-5,treatment,These resources address the diagnosis or management of hypochromic microcytic anemia with iron overload:  - Genetic Testing Registry: Hypochromic microcytic anemia with iron overload   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hypochromic microcytic anemia with iron overload,0000503,GHR,https://ghr.nlm.nih.gov/condition/hypochromic-microcytic-anemia-with-iron-overload,C0271901,T047,Disorders
What is (are) hypohidrotic ectodermal dysplasia ?,0000504-1,information,"Hypohidrotic ectodermal dysplasia is one of about 150 types of ectodermal dysplasia in humans. Before birth, these disorders result in the abnormal development of structures including the skin, hair, nails, teeth, and sweat glands.  Most people with hypohidrotic ectodermal dysplasia have a reduced ability to sweat (hypohidrosis) because they have fewer sweat glands than normal or their sweat glands do not function properly. Sweating is a major way that the body controls its temperature; as sweat evaporates from the skin, it cools the body. An inability to sweat can lead to a dangerously high body temperature (hyperthermia), particularly in hot weather. In some cases, hyperthermia can cause life-threatening medical problems.  Affected individuals tend to have sparse scalp and body hair (hypotrichosis). The hair is often light-colored, brittle, and slow-growing. This condition is also characterized by absent teeth (hypodontia) or teeth that are malformed. The teeth that are present are frequently small and pointed.  Hypohidrotic ectodermal dysplasia is associated with distinctive facial features including a prominent forehead, thick lips, and a flattened bridge of the nose. Additional features of this condition include thin, wrinkled, and dark-colored skin around the eyes; chronic skin problems such as eczema; and a bad-smelling discharge from the nose (ozena).",hypohidrotic ectodermal dysplasia,0000504,GHR,https://ghr.nlm.nih.gov/condition/hypohidrotic-ectodermal-dysplasia,C0162359,T019,Disorders
How many people are affected by hypohidrotic ectodermal dysplasia ?,0000504-2,frequency,"Hypohidrotic ectodermal dysplasia is the most common form of ectodermal dysplasia in humans. It is estimated to affect at least 1 in 17,000 people worldwide.",hypohidrotic ectodermal dysplasia,0000504,GHR,https://ghr.nlm.nih.gov/condition/hypohidrotic-ectodermal-dysplasia,C0162359,T019,Disorders
What are the genetic changes related to hypohidrotic ectodermal dysplasia ?,0000504-3,genetic changes,"Mutations in the EDA, EDAR, and EDARADD genes cause hypohidrotic ectodermal dysplasia.  The EDA, EDAR, and EDARADD genes provide instructions for making proteins that work together during embryonic development. These proteins form part of a signaling pathway that is critical for the interaction between two cell layers, the ectoderm and the mesoderm. In the early embryo, these cell layers form the basis for many of the body's organs and tissues. Ectoderm-mesoderm interactions are essential for the formation of several structures that arise from the ectoderm, including the skin, hair, nails, teeth, and sweat glands.  Mutations in the EDA, EDAR, or EDARADD gene prevent normal interactions between the ectoderm and the mesoderm and impair the normal development of hair, sweat glands, and teeth. The improper formation of these ectodermal structures leads to the characteristic features of hypohidrotic ectodermal dysplasia.",hypohidrotic ectodermal dysplasia,0000504,GHR,https://ghr.nlm.nih.gov/condition/hypohidrotic-ectodermal-dysplasia,C0162359,T019,Disorders
Is hypohidrotic ectodermal dysplasia inherited ?,0000504-4,inheritance,"Hypohidrotic ectodermal dysplasia has several different inheritance patterns. Most cases are caused by mutations in the EDA gene, which are inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In X-linked recessive inheritance, a female with one altered copy of the gene in each cell is called a carrier. In about 70 percent of cases, carriers of hypohidrotic ectodermal dysplasia experience some features of the condition. These signs and symptoms are usually mild and include a few missing or abnormal teeth, sparse hair, and some problems with sweat gland function. Some carriers, however, have more severe features of this disorder.  Less commonly, hypohidrotic ectodermal dysplasia results from mutations in the EDAR or EDARADD gene. EDAR mutations can have an autosomal dominant or autosomal recessive pattern of inheritance, and EDARADD mutations have an autosomal recessive pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. Autosomal recessive inheritance means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.",hypohidrotic ectodermal dysplasia,0000504,GHR,https://ghr.nlm.nih.gov/condition/hypohidrotic-ectodermal-dysplasia,C0162359,T019,Disorders
What are the treatments for hypohidrotic ectodermal dysplasia ?,0000504-5,treatment,These resources address the diagnosis or management of hypohidrotic ectodermal dysplasia:  - Gene Review: Gene Review: Hypohidrotic Ectodermal Dysplasia  - Genetic Testing Registry: Autosomal dominant hypohidrotic ectodermal dysplasia  - Genetic Testing Registry: Autosomal recessive hypohidrotic ectodermal dysplasia syndrome  - Genetic Testing Registry: Hypohidrotic X-linked ectodermal dysplasia  - MedlinePlus Encyclopedia: Ectodermal dysplasia  - MedlinePlus Encyclopedia: Ozena  - MedlinePlus Encyclopedia: Sweating - absent   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hypohidrotic ectodermal dysplasia,0000504,GHR,https://ghr.nlm.nih.gov/condition/hypohidrotic-ectodermal-dysplasia,C0162359,T019,Disorders
What is (are) hypokalemic periodic paralysis ?,0000505-1,information,"Hypokalemic periodic paralysis is a condition that causes episodes of extreme muscle weakness typically beginning in childhood or adolescence. Most often, these episodes involve a temporary inability to move muscles in the arms and legs. Attacks cause severe weakness or paralysis that usually lasts from hours to days. Some people may have episodes almost every day, while others experience them weekly, monthly, or only rarely. Attacks can occur without warning or can be triggered by factors such as rest after exercise, a viral illness, or certain medications. Often, a large, carbohydrate-rich meal or vigorous exercise in the evening can trigger an attack upon waking the following morning. Although affected individuals usually regain their muscle strength between attacks, repeated episodes can lead to persistent muscle weakness later in life.  People with hypokalemic periodic paralysis have reduced levels of potassium in their blood (hypokalemia) during episodes of muscle weakness. Researchers are investigating how low potassium levels may be related to the muscle abnormalities in this condition.",hypokalemic periodic paralysis,0000505,GHR,https://ghr.nlm.nih.gov/condition/hypokalemic-periodic-paralysis,C3714580,T047,Disorders
How many people are affected by hypokalemic periodic paralysis ?,0000505-2,frequency,"Although its exact prevalence is unknown, hypokalemic periodic paralysis is estimated to affect 1 in 100,000 people. Men tend to experience symptoms of this condition more often than women.",hypokalemic periodic paralysis,0000505,GHR,https://ghr.nlm.nih.gov/condition/hypokalemic-periodic-paralysis,C3714580,T047,Disorders
What are the genetic changes related to hypokalemic periodic paralysis ?,0000505-3,genetic changes,"Mutations in the CACNA1S and SCN4A genes cause hypokalemic periodic paralysis.  The CACNA1S and SCN4A genes provide instructions for making proteins that play an essential role in muscles used for movement (skeletal muscles). For the body to move normally, these muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of certain positively charged atoms (ions) into muscle cells. The CACNA1S and SCN4A proteins form channels that control the flow of these ions. The channel formed by the CACNA1S protein transports calcium ions into cells, while the channel formed by the SCN4A protein transports sodium ions.  Mutations in the CACNA1S or SCN4A gene alter the usual structure and function of calcium or sodium channels. The altered channels cannot properly regulate the flow of ions into muscle cells, which reduces the ability of skeletal muscles to contract. Because muscle contraction is needed for movement, a disruption in normal ion transport leads to episodes of severe muscle weakness or paralysis.  A small percentage of people with the characteristic features of hypokalemic periodic paralysis do not have identified mutations in the CACNA1S or SCN4A gene. In these cases, the cause of the condition is unknown.",hypokalemic periodic paralysis,0000505,GHR,https://ghr.nlm.nih.gov/condition/hypokalemic-periodic-paralysis,C3714580,T047,Disorders
Is hypokalemic periodic paralysis inherited ?,0000505-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",hypokalemic periodic paralysis,0000505,GHR,https://ghr.nlm.nih.gov/condition/hypokalemic-periodic-paralysis,C3714580,T047,Disorders
What are the treatments for hypokalemic periodic paralysis ?,0000505-5,treatment,These resources address the diagnosis or management of hypokalemic periodic paralysis:  - Gene Review: Gene Review: Hypokalemic Periodic Paralysis  - Genetic Testing Registry: Hypokalemic periodic paralysis  - MedlinePlus Encyclopedia: Hypokalemic periodic paralysis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hypokalemic periodic paralysis,0000505,GHR,https://ghr.nlm.nih.gov/condition/hypokalemic-periodic-paralysis,C3714580,T047,Disorders
What is (are) hypomagnesemia with secondary hypocalcemia ?,0000506-1,information,"Hypomagnesemia with secondary hypocalcemia is an inherited condition caused by the body's inability to absorb and retain magnesium that is taken in through the diet. As a result, magnesium levels in the blood are severely low (hypomagnesemia).  Hypomagnesemia impairs the function of the parathyroid glands, which are small hormone-producing glands located in the neck. Normally, the parathyroid glands release a hormone that increases blood calcium levels when they are low. Magnesium is required for the production and release of parathyroid hormone, so when magnesium is too low, insufficient parathyroid hormone is produced and blood calcium levels are also reduced (hypocalcemia). The hypocalcemia is described as ""secondary"" because it occurs as a consequence of hypomagnesemia.  Shortages of magnesium and calcium can cause neurological problems that begin in infancy, including painful muscle spasms (tetany) and seizures. If left untreated, hypomagnesemia with secondary hypocalcemia can lead to developmental delay, intellectual disability, a failure to gain weight and grow at the expected rate (failure to thrive), and heart failure.",hypomagnesemia with secondary hypocalcemia,0000506,GHR,https://ghr.nlm.nih.gov/condition/hypomagnesemia-with-secondary-hypocalcemia,C1865974,T191,Disorders
How many people are affected by hypomagnesemia with secondary hypocalcemia ?,0000506-2,frequency,"Hypomagnesemia with secondary hypocalcemia is thought to be a rare condition, but its prevalence is unknown.",hypomagnesemia with secondary hypocalcemia,0000506,GHR,https://ghr.nlm.nih.gov/condition/hypomagnesemia-with-secondary-hypocalcemia,C1865974,T191,Disorders
What are the genetic changes related to hypomagnesemia with secondary hypocalcemia ?,0000506-3,genetic changes,"Hypomagnesemia with secondary hypocalcemia is caused by mutations in the TRPM6 gene. This gene provides instructions for making a protein that acts as a channel, which allows charged atoms (ions) of magnesium (Mg2+) to flow into cells; the channel may also allow small amounts of calcium ions (Ca2+) to pass into cells. Magnesium is involved in many cell processes, including production of cellular energy, maintenance of DNA building blocks (nucleotides), protein production, and cell growth and death. Magnesium and calcium are also required for the normal functioning of nerve cells that control muscle movement (motor neurons).  The TRPM6 channel is embedded in the membrane of epithelial cells that line the large intestine, structures in the kidneys known as distal convoluted tubules, the lungs, and the testes in males. When the body needs additional Mg2+, the TRPM6 channel allows it to be absorbed in the intestine and filtered from the fluids that pass through the kidneys by the distal convoluted tubules. When the body has sufficient or too much Mg2+, the TRPM6 channel does not filter out the Mg2+ from fluids but allows the ion to be released from the kidney cells into the urine. The channel also helps to regulate Ca2+, but to a lesser degree.  Most TRPM6 gene mutations that cause hypomagnesemia with secondary hypocalcemia result in a lack of functional protein. A loss of functional TRPM6 channels prevent Mg2+ absorption in the intestine and cause excessive amounts of Mg2+ to be excreted by the kidneys and released in the urine. A lack of Mg2+ in the body impairs the production of parathyroid hormone, which likely reduces blood Ca2+ levels. Additionally, hypomagnesemia and hypocalcemia can disrupt many cell processes and impair the function of motor neurons, leading to neurological problems and movement disorders. If the condition is not effectively treated and low Mg2+ levels persist, signs and symptoms can worsen over time and may lead to early death.",hypomagnesemia with secondary hypocalcemia,0000506,GHR,https://ghr.nlm.nih.gov/condition/hypomagnesemia-with-secondary-hypocalcemia,C1865974,T191,Disorders
Is hypomagnesemia with secondary hypocalcemia inherited ?,0000506-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",hypomagnesemia with secondary hypocalcemia,0000506,GHR,https://ghr.nlm.nih.gov/condition/hypomagnesemia-with-secondary-hypocalcemia,C1865974,T191,Disorders
What are the treatments for hypomagnesemia with secondary hypocalcemia ?,0000506-5,treatment,"These resources address the diagnosis or management of hypomagnesemia with secondary hypocalcemia:  - Genetic Testing Registry: Hypomagnesemia 1, intestinal  - MedlinePlus Encyclopedia: Hypomagnesemia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",hypomagnesemia with secondary hypocalcemia,0000506,GHR,https://ghr.nlm.nih.gov/condition/hypomagnesemia-with-secondary-hypocalcemia,C1865974,T191,Disorders
What is (are) hypomyelination and congenital cataract ?,0000507-1,information,"Hypomyelination and congenital cataract is an inherited condition that affects the nervous system and the eyes. This disease is one of a group of genetic disorders called leukoencephalopathies. Leukoencephalopathies involve abnormalities of the brain's white matter. White matter consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses. Hypomyelination and congenital cataract is caused by a reduced ability to form myelin (hypomyelination). Additionally, people with this disorder are typically born with a clouding of the lens (cataract) in both eyes.  People with this condition usually have normal development throughout the first year of life. Development slows around the age of 1. Most affected children learn to walk between the ages of 1 and 2, although they usually need some type of support. Over time they experience muscle weakness and wasting (atrophy) in their legs, and many affected people eventually require wheelchair assistance. Weakness in the muscles of the trunk and a progressive abnormal curvature of the spine (scoliosis) further impair walking in some individuals. Most people with hypomyelination and congenital cataract have reduced sensation in their arms and legs (peripheral neuropathy). In addition, affected individuals typically have speech difficulties (dysarthria) and mild to moderate intellectual disability.",hypomyelination and congenital cataract,0000507,GHR,https://ghr.nlm.nih.gov/condition/hypomyelination-and-congenital-cataract,C1864663,T019,Disorders
How many people are affected by hypomyelination and congenital cataract ?,0000507-2,frequency,The prevalence of hypomyelination and congenital cataract is unknown.,hypomyelination and congenital cataract,0000507,GHR,https://ghr.nlm.nih.gov/condition/hypomyelination-and-congenital-cataract,C1864663,T019,Disorders
What are the genetic changes related to hypomyelination and congenital cataract ?,0000507-3,genetic changes,"Mutations in the FAM126A gene cause hypomyelination and congenital cataract. The FAM126A gene provides instructions for making a protein called hyccin, the function of which is not completely understood. Based on the features of hypomyelination and congenital cataract, researchers presume that hyccin is involved in the formation of myelin throughout the nervous system. Hyccin is also active in the lens of the eye, the heart, and the kidneys. It is unclear how mutations in the FAM126A gene cause cataracts.  Most FAM126A gene mutations that cause hypomyelination and congenital cataract prevent the production of hyccin. People who cannot produce any hyccin have problems forming myelin, leading to the signs and symptoms of this condition.  People who have mutations that allow some protein production tend to have milder symptoms than those who produce no protein. These individuals typically retain the ability to walk longer, although they still need support, and they usually do not have peripheral neuropathy.",hypomyelination and congenital cataract,0000507,GHR,https://ghr.nlm.nih.gov/condition/hypomyelination-and-congenital-cataract,C1864663,T019,Disorders
Is hypomyelination and congenital cataract inherited ?,0000507-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",hypomyelination and congenital cataract,0000507,GHR,https://ghr.nlm.nih.gov/condition/hypomyelination-and-congenital-cataract,C1864663,T019,Disorders
What are the treatments for hypomyelination and congenital cataract ?,0000507-5,treatment,These resources address the diagnosis or management of hypomyelination and congenital cataract:  - Gene Review: Gene Review: Hypomyelination and Congenital Cataract  - Genetic Testing Registry: Hypomyelination and Congenital Cataract  - MedlinePlus Encyclopedia: Congenital Cataract  - MedlinePlus Encyclopedia: Muscle Atrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hypomyelination and congenital cataract,0000507,GHR,https://ghr.nlm.nih.gov/condition/hypomyelination-and-congenital-cataract,C1864663,T019,Disorders
What is (are) hypophosphatasia ?,0000508-1,information,"Hypophosphatasia is an inherited disorder that affects the development of bones and teeth. This condition disrupts a process called mineralization, in which minerals such as calcium and phosphorus are deposited in developing bones and teeth. Mineralization is critical for the formation of bones that are strong and rigid and teeth that can withstand chewing and grinding.  The signs and symptoms of hypophosphatasia vary widely and can appear anywhere from before birth to adulthood. The most severe forms of the disorder tend to occur before birth and in early infancy. Hypophosphatasia weakens and softens the bones, causing skeletal abnormalities similar to another childhood bone disorder called rickets. Affected infants are born with short limbs, an abnormally shaped chest, and soft skull bones. Additional complications in infancy include poor feeding and a failure to gain weight, respiratory problems, and high levels of calcium in the blood (hypercalcemia), which can lead to recurrent vomiting and kidney problems. These complications are life-threatening in some cases.  The forms of hypophosphatasia that appear in childhood or adulthood are typically less severe than those that appear in infancy. Early loss of primary (baby) teeth is one of the first signs of the condition in children. Affected children may have short stature with bowed legs or knock knees, enlarged wrist and ankle joints, and an abnormal skull shape. Adult forms of hypophosphatasia are characterized by a softening of the bones known as osteomalacia. In adults, recurrent fractures in the foot and thigh bones can lead to chronic pain. Affected adults may lose their secondary (adult) teeth prematurely and are at increased risk for joint pain and inflammation.  The mildest form of this condition, called odontohypophosphatasia, only affects the teeth. People with this disorder typically experience abnormal tooth development and premature tooth loss, but do not have the skeletal abnormalities seen in other forms of hypophosphatasia.",hypophosphatasia,0000508,GHR,https://ghr.nlm.nih.gov/condition/hypophosphatasia,C0020630,T047,Disorders
How many people are affected by hypophosphatasia ?,0000508-2,frequency,"Severe forms of hypophosphatasia affect an estimated 1 in 100,000 newborns. Milder cases, such as those that appear in childhood or adulthood, probably occur more frequently.  Hypophosphatasia has been reported worldwide in people of various ethnic backgrounds. This condition appears to be most common in white populations. It is particularly frequent in a Mennonite population in Manitoba, Canada, where about 1 in 2,500 infants is born with severe features of the condition.",hypophosphatasia,0000508,GHR,https://ghr.nlm.nih.gov/condition/hypophosphatasia,C0020630,T047,Disorders
What are the genetic changes related to hypophosphatasia ?,0000508-3,genetic changes,"Mutations in the ALPL gene cause hypophosphatasia.  The ALPL gene provides instructions for making an enzyme called alkaline phosphatase. This enzyme plays an essential role in mineralization of the skeleton and teeth. Mutations in the ALPL gene lead to the production of an abnormal version of alkaline phosphatase that cannot participate effectively in the mineralization process. A shortage of alkaline phosphatase allows several other substances, which are normally processed by the enzyme, to build up abnormally in the body. Researchers believe that a buildup of one of these compounds, inorganic pyrophosphate (PPi), underlies the defective mineralization of bones and teeth in people with hypophosphatasia.  ALPL mutations that almost completely eliminate the activity of alkaline phosphatase usually result in the more severe forms of hypophosphatasia. Other mutations, which reduce but do not eliminate the activity of the enzyme, are often responsible for milder forms of the condition.",hypophosphatasia,0000508,GHR,https://ghr.nlm.nih.gov/condition/hypophosphatasia,C0020630,T047,Disorders
Is hypophosphatasia inherited ?,0000508-4,inheritance,"The severe forms of hypophosphatasia that appear early in life are inherited in an autosomal recessive pattern. Autosomal recessive inheritance means that two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene but do not show signs and symptoms of the disorder.  Milder forms of hypophosphatasia can have either an autosomal recessive or an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder.",hypophosphatasia,0000508,GHR,https://ghr.nlm.nih.gov/condition/hypophosphatasia,C0020630,T047,Disorders
What are the treatments for hypophosphatasia ?,0000508-5,treatment,These resources address the diagnosis or management of hypophosphatasia:  - Gene Review: Gene Review: Hypophosphatasia  - Genetic Testing Registry: Adult hypophosphatasia  - Genetic Testing Registry: Childhood hypophosphatasia  - Genetic Testing Registry: Hypophosphatasia  - Genetic Testing Registry: Infantile hypophosphatasia  - MedlinePlus Encyclopedia: Osteomalacia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hypophosphatasia,0000508,GHR,https://ghr.nlm.nih.gov/condition/hypophosphatasia,C0020630,T047,Disorders
What is (are) hystrix-like ichthyosis with deafness ?,0000509-1,information,"Hystrix-like ichthyosis with deafness (HID) is a disorder characterized by dry, scaly skin (ichthyosis) and hearing loss that is usually profound. Hystrix-like means resembling a porcupine; in this type of ichthyosis, the scales may be thick and spiky, giving the appearance of porcupine quills.  Newborns with HID typically develop reddened skin. The skin abnormalities worsen over time, and the ichthyosis eventually covers most of the body, although the palms of the hands and soles of the feet are usually only mildly affected. Breaks in the skin may occur and in severe cases can lead to life-threatening infections. Affected individuals have an increased risk of developing a type of skin cancer called squamous cell carcinoma, which can also affect mucous membranes such as the inner lining of the mouth. People with HID may also have patchy hair loss caused by scarring on particular areas of skin.",hystrix-like ichthyosis with deafness,0000509,GHR,https://ghr.nlm.nih.gov/condition/hystrix-like-ichthyosis-with-deafness,C0020758,T019,Disorders
How many people are affected by hystrix-like ichthyosis with deafness ?,0000509-2,frequency,HID is a rare disorder. Its prevalence is unknown.,hystrix-like ichthyosis with deafness,0000509,GHR,https://ghr.nlm.nih.gov/condition/hystrix-like-ichthyosis-with-deafness,C0020758,T019,Disorders
What are the genetic changes related to hystrix-like ichthyosis with deafness ?,0000509-3,genetic changes,"HID is caused by mutations in the GJB2 gene. This gene provides instructions for making a protein called gap junction beta 2, more commonly known as connexin 26. Connexin 26 is a member of the connexin protein family. Connexin proteins form channels called gap junctions that permit the transport of nutrients, charged atoms (ions), and signaling molecules between neighboring cells that are in contact with each other. Gap junctions made with connexin 26 transport potassium ions and certain small molecules.  Connexin 26 is found in cells throughout the body, including the inner ear and the skin. In the inner ear, channels made from connexin 26 are found in a snail-shaped structure called the cochlea. These channels may help to maintain the proper level of potassium ions required for the conversion of sound waves to electrical nerve impulses. This conversion is essential for normal hearing. In addition, connexin 26 may be involved in the maturation of certain cells in the cochlea. Connexin 26 also plays a role in the growth and maturation of the outermost layer of skin (the epidermis).  At least one GJB2 gene mutation has been identified in people with HID. This mutation changes a single protein building block (amino acid) in connexin 26. The mutation is thought to result in channels that constantly leak ions, which impairs the health of the cells and increases cell death. Death of cells in the skin and the inner ear may underlie the signs and symptoms of HID.  Because the GJB2 gene mutation identified in people with HID also occurs in keratitis-ichthyosis-deafness syndrome (KID syndrome), a disorder with similar features and the addition of eye abnormalities, many researchers categorize KID syndrome and HID as a single disorder, which they call KID/HID. It is not known why some people with this mutation have eye problems while others do not.",hystrix-like ichthyosis with deafness,0000509,GHR,https://ghr.nlm.nih.gov/condition/hystrix-like-ichthyosis-with-deafness,C0020758,T019,Disorders
Is hystrix-like ichthyosis with deafness inherited ?,0000509-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",hystrix-like ichthyosis with deafness,0000509,GHR,https://ghr.nlm.nih.gov/condition/hystrix-like-ichthyosis-with-deafness,C0020758,T019,Disorders
What are the treatments for hystrix-like ichthyosis with deafness ?,0000509-5,treatment,These resources address the diagnosis or management of hystrix-like ichthyosis with deafness:  - Foundation for Ichthyosis and Related Skin Types: Ichthyosis Hystrix  - Genetic Testing Registry: Hystrix-like ichthyosis with deafness   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,hystrix-like ichthyosis with deafness,0000509,GHR,https://ghr.nlm.nih.gov/condition/hystrix-like-ichthyosis-with-deafness,C0020758,T019,Disorders
What is (are) ichthyosis with confetti ?,0000510-1,information,"Ichthyosis with confetti is a disorder of the skin. Individuals with this condition are born with red, scaly skin all over the body, which can be itchy in some people. In childhood or adolescence, hundreds to thousands of small patches of normal skin appear, usually on the torso. The numerous pale spots surrounded by red skin look like confetti, giving the condition its name. The patches of normal skin increase in number and size over time.  In addition to red, scaly skin, people with ichthyosis with confetti typically have abnormally thick skin on the palms of the hands and soles of the feet (palmoplantar keratoderma). Many affected individuals have excess hair (hirsutism) on some parts of the body, particularly on the arms and legs. Because of their skin abnormalities, people with ichthyosis with confetti are at increased risk of developing skin infections.",ichthyosis with confetti,0000510,GHR,https://ghr.nlm.nih.gov/condition/ichthyosis-with-confetti,C3665704,T047,Disorders
How many people are affected by ichthyosis with confetti ?,0000510-2,frequency,Ichthyosis with confetti is a rare disorder. Fewer than 20 affected individuals have been described in the medical literature.,ichthyosis with confetti,0000510,GHR,https://ghr.nlm.nih.gov/condition/ichthyosis-with-confetti,C3665704,T047,Disorders
What are the genetic changes related to ichthyosis with confetti ?,0000510-3,genetic changes,"Mutations in the KRT10 gene cause ichthyosis with confetti. This gene provides instructions for making a protein called keratin 10, which is found in cells called keratinocytes in the outer layer of the skin (the epidermis). In the fluid-filled space inside these cells (the cytoplasm), this tough, fibrous protein attaches to another keratin protein (produced from a different gene) to form fibers called intermediate filaments. These filaments assemble into strong networks that provide strength and resiliency to the skin.  KRT10 gene mutations associated with ichthyosis with confetti alter the keratin 10 protein. The altered protein is abnormally transported to the nucleus of cells, where it cannot form networks of intermediate filaments. Loss of these networks disrupts the epidermis, contributing to the red, scaly skin. However, in some abnormal cells, the mutated gene corrects itself through a complex process by which genetic material is exchanged between chromosomes. As a result, normal keratin 10 protein is produced and remains in the cytoplasm. The cell becomes normal and, as it continues to grow and divide, forms small patches of normal skin that give ichthyosis with confetti its name.",ichthyosis with confetti,0000510,GHR,https://ghr.nlm.nih.gov/condition/ichthyosis-with-confetti,C3665704,T047,Disorders
Is ichthyosis with confetti inherited ?,0000510-4,inheritance,"Ichthyosis with confetti is considered to have an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Usually, the condition is caused by a new mutation that occurs very early in embryonic development (called a de novo mutation). In these cases, the affected individuals have no history of the disorder in their family. In some cases, an affected person inherits the mutation from one affected parent.",ichthyosis with confetti,0000510,GHR,https://ghr.nlm.nih.gov/condition/ichthyosis-with-confetti,C3665704,T047,Disorders
What are the treatments for ichthyosis with confetti ?,0000510-5,treatment,These resources address the diagnosis or management of ichthyosis with confetti:  - Foundation for Ichthyosis and Related Skin Types (FIRST): Skin Care Tips  - Foundation for Ichthyosis and Related Skin Types (FIRST): Treating Ichthyosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,ichthyosis with confetti,0000510,GHR,https://ghr.nlm.nih.gov/condition/ichthyosis-with-confetti,C3665704,T047,Disorders
What is (are) idiopathic inflammatory myopathy ?,0000511-1,information,"Idiopathic inflammatory myopathy is a group of disorders characterized by inflammation of the muscles used for movement (skeletal muscles). Idiopathic inflammatory myopathy usually appears in adults between ages 40 and 60 or in children between ages 5 and 15, though it can occur at any age.  The primary symptom of idiopathic inflammatory myopathy is muscle weakness, which develops gradually over a period of weeks to months or even years. Other symptoms include joint pain and general tiredness (fatigue).  There are several forms of idiopathic inflammatory myopathy, including polymyositis, dermatomyositis, and sporadic inclusion body myositis.  Polymyositis and dermatomyositis involve weakness of the muscles closest to the center of the body (proximal muscles), such as the muscles of the hips and thighs, upper arms, and neck. People with these forms of idiopathic inflammatory myopathy may find it difficult to climb stairs, get up from a seated position, or lift items above their head. In some cases, muscle weakness may make swallowing or breathing difficult.  Polymyositis and dermatomyositis have similar symptoms, but dermatomyositis is distinguished by a reddish or purplish rash on the eyelids, elbows, knees, or knuckles. Sometimes, abnormal calcium deposits form hard, painful bumps under the skin (calcinosis).  In sporadic inclusion body myositis, the muscles most affected are those of the wrists and fingers and the front of the thigh. Affected individuals may frequently stumble while walking and find it difficult to grasp items. As in dermatomyositis and polymyositis, swallowing can be difficult.",idiopathic inflammatory myopathy,0000511,GHR,https://ghr.nlm.nih.gov/condition/idiopathic-inflammatory-myopathy,C0751356,T047,Disorders
How many people are affected by idiopathic inflammatory myopathy ?,0000511-2,frequency,"The incidence of idiopathic inflammatory myopathy is approximately 2 to 8 cases per million people each year.  For unknown reasons, polymyositis and dermatomyositis are about twice as common in women as in men, while sporadic inclusion body myositis is more common in men.",idiopathic inflammatory myopathy,0000511,GHR,https://ghr.nlm.nih.gov/condition/idiopathic-inflammatory-myopathy,C0751356,T047,Disorders
What are the genetic changes related to idiopathic inflammatory myopathy ?,0000511-3,genetic changes,"Idiopathic inflammatory myopathy is thought to arise from a combination of genetic and environmental factors. The term ""idiopathic"" indicates that the specific cause of the disorder is unknown.  Researchers have identified variations in several genes that may influence the risk of developing idiopathic inflammatory myopathy. The most commonly associated genes belong to a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Each HLA gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. Specific variations of several HLA genes seem to affect the risk of developing idiopathic inflammatory myopathy. Researchers are studying variations in other genes related to the body's immune function to understand how they contribute to the risk of developing idiopathic inflammatory myopathy.  It is likely that specific genetic variations increase a person's risk of developing idiopathic inflammatory myopathy, and then exposure to certain environmental factors triggers the disorder. Infection, exposure to certain medications, and exposure to ultraviolet light (such as sunlight) have been identified as possible environmental triggers, but most risk factors for this condition remain unknown.",idiopathic inflammatory myopathy,0000511,GHR,https://ghr.nlm.nih.gov/condition/idiopathic-inflammatory-myopathy,C0751356,T047,Disorders
Is idiopathic inflammatory myopathy inherited ?,0000511-4,inheritance,"Most cases of idiopathic inflammatory myopathy are sporadic, which means they occur in people with no history of the disorder in their family. However, several people with idiopathic inflammatory myopathy have had close relatives with autoimmune disorders. Autoimmune diseases occur when the immune system malfunctions and attacks the body's tissues and organs.  A small percentage of all cases of idiopathic inflammatory myopathy have been reported to run in families; however, the condition does not have a clear pattern of inheritance. Multiple genetic and environmental factors likely play a part in determining the risk of developing this disorder. As a result, inheriting a genetic variation linked with idiopathic inflammatory myopathy does not mean that a person will develop the condition.",idiopathic inflammatory myopathy,0000511,GHR,https://ghr.nlm.nih.gov/condition/idiopathic-inflammatory-myopathy,C0751356,T047,Disorders
What are the treatments for idiopathic inflammatory myopathy ?,0000511-5,treatment,These resources address the diagnosis or management of idiopathic inflammatory myopathy:  - Genetic Testing Registry: Idiopathic myopathy  - Genetic Testing Registry: Inclusion body myositis  - Johns Hopkins Myositis Center: Diagnosis  - Johns Hopkins Myositis Center: Treatment  - Muscular Dystrophy Association: Facts about Inflammatory Myopathies (Myositis)   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,idiopathic inflammatory myopathy,0000511,GHR,https://ghr.nlm.nih.gov/condition/idiopathic-inflammatory-myopathy,C0751356,T047,Disorders
What is (are) idiopathic pulmonary fibrosis ?,0000512-1,information,"Idiopathic pulmonary fibrosis is a chronic, progressive lung disease. This condition causes scar tissue (fibrosis) to build up in the lungs, which makes the lungs unable to transport oxygen into the bloodstream effectively. The disease usually affects people between the ages of 50 and 70.  The most common signs and symptoms of idiopathic pulmonary fibrosis are shortness of breath and a persistent dry, hacking cough. Many affected individuals also experience a loss of appetite and gradual weight loss. Some people with idiopathic pulmonary fibrosis develop widened and rounded tips of the fingers and toes (clubbing) resulting from a shortage of oxygen. These features are relatively nonspecific; not everyone with these health problems has idiopathic pulmonary fibrosis. Other respiratory diseases, some of which are less serious, can cause similar signs and symptoms.  In people with idiopathic pulmonary fibrosis, scarring of the lungs increases over time until the lungs can no longer provide enough oxygen to the body's organs and tissues. Some people with idiopathic pulmonary fibrosis develop other serious lung conditions, including lung cancer, blood clots in the lungs (pulmonary emboli), pneumonia, or high blood pressure in the blood vessels that supply the lungs (pulmonary hypertension). Most affected individuals survive 3 to 5 years after their diagnosis. However, the course of the disease is highly variable; some affected people become seriously ill within a few months, while others may live with the disease for a decade or longer.  In most cases, idiopathic pulmonary fibrosis occurs in only one person in a family. These cases are described as sporadic. However, a small percentage of people with this disease have at least one other affected family member. When idiopathic pulmonary fibrosis occurs in multiple members of the same family, it is known as familial pulmonary fibrosis.",idiopathic pulmonary fibrosis,0000512,GHR,https://ghr.nlm.nih.gov/condition/idiopathic-pulmonary-fibrosis,C3812887,T047,Disorders
How many people are affected by idiopathic pulmonary fibrosis ?,0000512-2,frequency,"Idiopathic pulmonary fibrosis has an estimated prevalence of 13 to 20 per 100,000 people worldwide. About 100,000 people are affected in the United States, and 30,000 to 40,000 new cases are diagnosed each year.  Familial pulmonary fibrosis is less common than the sporadic form of the disease. Only a small percentage of cases of idiopathic pulmonary fibrosis appear to run in families.",idiopathic pulmonary fibrosis,0000512,GHR,https://ghr.nlm.nih.gov/condition/idiopathic-pulmonary-fibrosis,C3812887,T047,Disorders
What are the genetic changes related to idiopathic pulmonary fibrosis ?,0000512-3,genetic changes,"The cause of idiopathic pulmonary fibrosis is unknown, although the disease probably results from a combination of genetic and environmental factors. It is likely that genetic changes increase a person's risk of developing idiopathic pulmonary fibrosis, and then exposure to certain environmental factors triggers the disease.  Changes in several genes have been suggested as risk factors for idiopathic pulmonary fibrosis. Most of these genetic changes account for only a small proportion of cases. However, mutations in genes known as TERC and TERT have been found in about 15 percent of all cases of familial pulmonary fibrosis and a smaller percentage of cases of sporadic idiopathic pulmonary fibrosis. The TERC and TERT genes provide instructions for making components of an enzyme called telomerase, which maintains structures at the ends of chromosomes known as telomeres. It is not well understood how defects in telomerase are associated with the lung damage characteristic of idiopathic pulmonary fibrosis.  Researchers have also examined environmental risk factors that could contribute to idiopathic pulmonary fibrosis. These factors include exposure to wood or metal dust, viral infections, certain medications, and cigarette smoking. Some research suggests that gastroesophageal reflux disease (GERD) may also be a risk factor for idiopathic pulmonary fibrosis; affected individuals may breathe in (aspirate) stomach contents, which over time could damage the lungs.",idiopathic pulmonary fibrosis,0000512,GHR,https://ghr.nlm.nih.gov/condition/idiopathic-pulmonary-fibrosis,C3812887,T047,Disorders
Is idiopathic pulmonary fibrosis inherited ?,0000512-4,inheritance,"Most cases of idiopathic pulmonary fibrosis are sporadic; they occur in people with no history of the disorder in their family.  Familial pulmonary fibrosis appears to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of an altered gene in each cell is sufficient to cause the disorder. However, some people who inherit the altered gene never develop features of familial pulmonary fibrosis. (This situation is known as reduced penetrance.) It is unclear why some people with a mutated gene develop the disease and other people with the mutated gene do not.",idiopathic pulmonary fibrosis,0000512,GHR,https://ghr.nlm.nih.gov/condition/idiopathic-pulmonary-fibrosis,C3812887,T047,Disorders
What are the treatments for idiopathic pulmonary fibrosis ?,0000512-5,treatment,"These resources address the diagnosis or management of idiopathic pulmonary fibrosis:  - Gene Review: Gene Review: Pulmonary Fibrosis, Familial  - Genetic Testing Registry: Idiopathic fibrosing alveolitis, chronic form   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",idiopathic pulmonary fibrosis,0000512,GHR,https://ghr.nlm.nih.gov/condition/idiopathic-pulmonary-fibrosis,C3812887,T047,Disorders
What is (are) Imerslund-Grsbeck syndrome ?,0000513-1,information,"Imerslund-Grsbeck syndrome is a condition caused by low levels of vitamin B12 (also known as cobalamin). The primary feature of this condition is a blood disorder called megaloblastic anemia. In this form of anemia, which is a disorder characterized by the shortage of red blood cells, the red cells that are present are abnormally large. About half of people with Imerslund-Grsbeck syndrome also have high levels of protein in their urine (proteinuria). Although proteinuria can be an indication of kidney problems, people with Imerslund-Grsbeck syndrome appear to have normal kidney function.  Imerslund-Grsbeck syndrome typically begins in infancy or early childhood. The blood abnormality leads to many of the signs and symptoms of the condition, including an inability to grow and gain weight at the expected rate (failure to thrive), pale skin (pallor), excessive tiredness (fatigue), and recurring gastrointestinal or respiratory infections. Other features of Imerslund-Grsbeck syndrome include mild neurological problems, such as weak muscle tone (hypotonia), numbness or tingling in the hands or feet, movement problems, delayed development, or confusion. Rarely, affected individuals have abnormalities of organs or tissues that make up the urinary tract, such as the bladder or the tubes that carry fluid from the kidneys to the bladder (the ureters).",Imerslund-Grsbeck syndrome,0000513,GHR,https://ghr.nlm.nih.gov/condition/imerslund-grasbeck-syndrome,C0494218,T047,Disorders
How many people are affected by Imerslund-Grsbeck syndrome ?,0000513-2,frequency,"Imerslund-Grsbeck syndrome is a rare condition that was first described in Finland and Norway; in these regions, the condition is estimated to affect 1 in 200,000 people. The condition has also been reported in other countries worldwide; its prevalence in these countries is unknown.",Imerslund-Grsbeck syndrome,0000513,GHR,https://ghr.nlm.nih.gov/condition/imerslund-grasbeck-syndrome,C0494218,T047,Disorders
What are the genetic changes related to Imerslund-Grsbeck syndrome ?,0000513-3,genetic changes,"Mutations in the AMN or CUBN gene can cause Imerslund-Grsbeck syndrome. The AMN gene provides instructions for making a protein called amnionless, and the CUBN gene provides instructions for making a protein called cubilin. Together, these proteins play a role in the uptake of vitamin B12 from food. Vitamin B12, which cannot be made in the body and can only be obtained from food, is essential for the formation of DNA and proteins, the production of cellular energy, and the breakdown of fats. This vitamin is involved in the formation of red blood cells and maintenance of the brain and spinal cord (central nervous system).  The amnionless protein is embedded primarily in the membrane of kidney cells and cells that line the small intestine. Amnionless attaches (binds) to cubilin, anchoring cubilin to the cell membrane. Cubilin can interact with molecules and proteins passing through the intestine or kidneys. During digestion, vitamin B12 is released from food. As the vitamin passes through the small intestine, cubilin binds to it. Amnionless helps transfer the cubilin-vitamin B12 complex into the intestinal cell. From there, the vitamin is released into the blood and transported throughout the body. In the kidney, the amnionless and cubilin proteins are involved in the reabsorption of certain proteins that would otherwise be released in urine.  Mutations in the AMN gene prevent cubilin from attaching to the cells in the small intestine and kidneys. Without cubilin function in the small intestine, vitamin B12 is not taken into the body. A shortage of this essential vitamin impairs the proper development of red blood cells, leading to megaloblastic anemia. Low levels of vitamin B12 can also affect the central nervous system, causing neurological problems. In addition, without cubilin function in the kidneys, proteins are not reabsorbed and are instead released in urine, leading to proteinuria.  Like AMN gene mutations, some CUBN gene mutations impair cubilin's function in both the small intestine and the kidneys, leading to a shortage of vitamin B12 and proteinuria. Other CUBN gene mutations affect cubilin's function only in the small intestine, impairing uptake of vitamin B12 into the intestinal cells. Individuals with these mutations have a shortage of vitamin B12, which can lead to megaloblastic anemia and neurological problems, but not proteinuria.",Imerslund-Grsbeck syndrome,0000513,GHR,https://ghr.nlm.nih.gov/condition/imerslund-grasbeck-syndrome,C0494218,T047,Disorders
Is Imerslund-Grsbeck syndrome inherited ?,0000513-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Imerslund-Grsbeck syndrome,0000513,GHR,https://ghr.nlm.nih.gov/condition/imerslund-grasbeck-syndrome,C0494218,T047,Disorders
What are the treatments for Imerslund-Grsbeck syndrome ?,0000513-5,treatment,These resources address the diagnosis or management of Imerslund-Grsbeck syndrome:  - MedlinePlus Encyclopedia: Anemia - B12 deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Imerslund-Grsbeck syndrome,0000513,GHR,https://ghr.nlm.nih.gov/condition/imerslund-grasbeck-syndrome,C0494218,T047,Disorders
"What is (are) immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome ?",0000514-1,information,"Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is characterized by the development of multiple autoimmune disorders in affected individuals. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. Although IPEX syndrome can affect many different areas of the body, autoimmune disorders involving the intestines, skin, and hormone-producing (endocrine) glands occur most often. Most patients with IPEX syndrome are males, and the disease can be life-threatening in early childhood.  Almost all individuals with IPEX syndrome develop a disorder of the intestines called enteropathy. Enteropathy occurs when certain cells in the intestines are destroyed by a person's immune system. It causes severe diarrhea, which is usually the first symptom of IPEX syndrome. Enteropathy typically begins in the first few months of life. It can cause failure to gain weight and grow at the expected rate (failure to thrive) and general wasting and weight loss (cachexia).  People with IPEX syndrome frequently develop inflammation of the skin, called dermatitis. Eczema is the most common type of dermatitis that occurs in this syndrome, and it causes abnormal patches of red, irritated skin. Other skin disorders that cause similar symptoms are sometimes present in IPEX syndrome.  The term polyendocrinopathy is used in IPEX syndrome because individuals can develop multiple disorders of the endocrine glands. Type 1 diabetes mellitus is an autoimmune condition involving the pancreas and is the most common endocrine disorder present in people with IPEX syndrome. It usually develops within the first few months of life and prevents the body from properly controlling the amount of sugar in the blood. Autoimmune thyroid disease may also develop in people with IPEX syndrome. The thyroid gland is a butterfly-shaped organ in the lower neck that produces hormones. This gland is commonly underactive (hypothyroidism) in individuals with this disorder, but may become overactive (hyperthyroidism).  Individuals with IPEX syndrome typically develop other types of autoimmune disorders in addition to those that involve the intestines, skin, and endocrine glands. Autoimmune blood disorders are common; about half of affected individuals have low levels of red blood cells (anemia), platelets (thrombocytopenia), or white blood cells (neutropenia) because these cells are attacked by the immune system. In some individuals, IPEX syndrome involves the liver and kidneys.","immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome",0000514,GHR,https://ghr.nlm.nih.gov/condition/immune-dysregulation-polyendocrinopathy-enteropathy-x-linked-syndrome,C1844666,T047,Disorders
"How many people are affected by immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome ?",0000514-2,frequency,IPEX syndrome is a rare disorder; its prevalence is unknown.,"immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome",0000514,GHR,https://ghr.nlm.nih.gov/condition/immune-dysregulation-polyendocrinopathy-enteropathy-x-linked-syndrome,C1844666,T047,Disorders
"What are the genetic changes related to immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome ?",0000514-3,genetic changes,"Mutations in the FOXP3 gene cause some cases of IPEX syndrome. The protein produced from this gene is a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of particular genes. This protein is essential for the production and normal function of certain immune cells called regulatory T cells. Regulatory T cells play an important role in controlling the immune system and preventing autoimmune disorders. Mutations in the FOXP3 gene lead to reduced numbers or a complete absence of regulatory T cells. Without the proper number of regulatory T cells, the body cannot control immune responses. Normal body tissues and organs are attacked, causing the multiple autoimmune disorders present in people with IPEX syndrome.  About half of individuals diagnosed with IPEX syndrome do not have identified mutations in the FOXP3 gene. In these cases, the cause of the disorder is unknown.","immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome",0000514,GHR,https://ghr.nlm.nih.gov/condition/immune-dysregulation-polyendocrinopathy-enteropathy-x-linked-syndrome,C1844666,T047,Disorders
"Is immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome inherited ?",0000514-4,inheritance,"When IPEX syndrome is due to mutations in the FOXP3 gene, it is inherited in an X-linked recessive pattern. The FOXP3 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  Some people have a condition that appears identical to IPEX syndrome, but they do not have mutations in the FOXP3 gene. The inheritance pattern for this IPEX-like syndrome is unknown, but females can be affected.","immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome",0000514,GHR,https://ghr.nlm.nih.gov/condition/immune-dysregulation-polyendocrinopathy-enteropathy-x-linked-syndrome,C1844666,T047,Disorders
"What are the treatments for immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome ?",0000514-5,treatment,These resources address the diagnosis or management of IPEX syndrome:  - Gene Review: Gene Review: IPEX Syndrome  - Genetic Testing Registry: Insulin-dependent diabetes mellitus secretory diarrhea syndrome  - Seattle Children's Hospital   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,"immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome",0000514,GHR,https://ghr.nlm.nih.gov/condition/immune-dysregulation-polyendocrinopathy-enteropathy-x-linked-syndrome,C1844666,T047,Disorders
What is (are) inclusion body myopathy 2 ?,0000515-1,information,"Inclusion body myopathy 2 is a condition that primarily affects skeletal muscles, which are muscles that the body uses for movement. This disorder causes muscle weakness that appears in late adolescence or early adulthood and worsens over time.  The first sign of inclusion body myopathy 2 is weakness of a muscle in the lower leg called the tibialis anterior. This muscle helps control up-and-down movement of the foot. Weakness in the tibialis anterior alters the way a person walks and makes it difficult to run and climb stairs. As the disorder progresses, weakness also develops in muscles of the upper legs, hips, shoulders, and hands. Unlike most forms of myopathy, inclusion body myopathy 2 usually does not affect the quadriceps, which are a group of large muscles at the front of the thigh. This condition also does not affect muscles of the eye or heart, and it does not cause neurological problems. Weakness in leg muscles makes walking increasingly difficult, and most people with inclusion body myopathy 2 require wheelchair assistance within 20 years after signs and symptoms appear.  People with the characteristic features of inclusion body myopathy 2 have been described in several different populations. When the condition was first reported in Japanese families, researchers called it distal myopathy with rimmed vacuoles (DMRV) or Nonaka myopathy. When a similar disorder was discovered in Iranian Jewish families, researchers called it rimmed vacuole myopathy or hereditary inclusion body myopathy (HIBM). It has since become clear that these conditions are variations of a single disorder caused by mutations in the same gene.",inclusion body myopathy 2,0000515,GHR,https://ghr.nlm.nih.gov/condition/inclusion-body-myopathy-2,C1853926,T019,Disorders
How many people are affected by inclusion body myopathy 2 ?,0000515-2,frequency,"More than 200 people with inclusion body myopathy 2 have been reported. Most are of Iranian Jewish descent; the condition affects an estimated 1 in 1,500 people in this population. Additionally, at least 15 people in the Japanese population have been diagnosed with this disorder. Inclusion body myopathy 2 has also been found in several other ethnic groups worldwide.",inclusion body myopathy 2,0000515,GHR,https://ghr.nlm.nih.gov/condition/inclusion-body-myopathy-2,C1853926,T019,Disorders
What are the genetic changes related to inclusion body myopathy 2 ?,0000515-3,genetic changes,"Mutations in the GNE gene cause inclusion body myopathy 2. The GNE gene provides instructions for making an enzyme found in cells and tissues throughout the body. This enzyme is involved in a chemical pathway that produces sialic acid, which is a simple sugar that attaches to the ends of more complex molecules on the surface of cells. By modifying these molecules, sialic acid influences a wide variety of cellular functions including cell movement (migration), attaching cells to one another (adhesion), signaling between cells, and inflammation.  The mutations responsible for inclusion body myopathy 2 reduce the activity of the enzyme produced from the GNE gene, which decreases the production of sialic acid. As a result, less of this simple sugar is available to attach to cell surface molecules. Researchers are working to determine how a shortage of sialic acid leads to progressive muscle weakness in people with inclusion body myopathy 2. Sialic acid is important for the normal function of many different cells and tissues, so it is unclear why the signs and symptoms of this disorder appear to be limited to the skeletal muscles.",inclusion body myopathy 2,0000515,GHR,https://ghr.nlm.nih.gov/condition/inclusion-body-myopathy-2,C1853926,T019,Disorders
Is inclusion body myopathy 2 inherited ?,0000515-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",inclusion body myopathy 2,0000515,GHR,https://ghr.nlm.nih.gov/condition/inclusion-body-myopathy-2,C1853926,T019,Disorders
What are the treatments for inclusion body myopathy 2 ?,0000515-5,treatment,These resources address the diagnosis or management of inclusion body myopathy 2:  - Gene Review: Gene Review: GNE-Related Myopathy  - Genetic Testing Registry: Inclusion body myopathy 2  - Genetic Testing Registry: Nonaka myopathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,inclusion body myopathy 2,0000515,GHR,https://ghr.nlm.nih.gov/condition/inclusion-body-myopathy-2,C1853926,T019,Disorders
What is (are) inclusion body myopathy with early-onset Paget disease and frontotemporal dementia ?,0000516-1,information,"Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia (IBMPFD) is a condition that can affect the muscles, bones, and brain.  The first symptom of IBMPFD is often muscle weakness (myopathy), which typically appears in mid-adulthood. Weakness first occurs in muscles of the hips and shoulders, making it difficult to climb stairs and raise the arms above the shoulders. As the disorder progresses, weakness develops in other muscles in the arms and legs. Muscle weakness can also affect respiratory and heart (cardiac) muscles, leading to life-threatening breathing difficulties and heart failure.  About half of all adults with IBMPFD develop a disorder called Paget disease of bone. This disorder most often affects bones of the hips, spine, and skull, and the long bones of the arms and legs. Bone pain, particularly in the hips and spine, is usually the major symptom of Paget disease. Rarely, this condition can weaken bones so much that they break (fracture).  In about one-third of people with IBMPFD, the disorder also affects the brain. IBMPFD is associated with a brain condition called frontotemporal dementia, which becomes noticeable in a person's forties or fifties. Frontotemporal dementia progressively damages parts of the brain that control reasoning, personality, social skills, speech, and language. People with this condition initially may have trouble speaking, remembering words and names (dysnomia), and using numbers (dyscalculia). Personality changes, a loss of judgment, and inappropriate social behavior are also hallmarks of the disease. As the dementia worsens, affected people ultimately become unable to speak, read, or care for themselves.  People with IBMPFD usually live into their fifties or sixties.",inclusion body myopathy with early-onset Paget disease and frontotemporal dementia,0000516,GHR,https://ghr.nlm.nih.gov/condition/inclusion-body-myopathy-with-early-onset-paget-disease-and-frontotemporal-dementia,C1833672,T047,Disorders
How many people are affected by inclusion body myopathy with early-onset Paget disease and frontotemporal dementia ?,0000516-2,frequency,"Although the prevalence of IBMPFD is unknown, this condition is rare. It has been identified in about 26 families.",inclusion body myopathy with early-onset Paget disease and frontotemporal dementia,0000516,GHR,https://ghr.nlm.nih.gov/condition/inclusion-body-myopathy-with-early-onset-paget-disease-and-frontotemporal-dementia,C1833672,T047,Disorders
What are the genetic changes related to inclusion body myopathy with early-onset Paget disease and frontotemporal dementia ?,0000516-3,genetic changes,"Mutations in the VCP gene cause IBMPFD. The VCP gene provides instructions for making an enzyme called valosin-containing protein, which has a wide variety of functions within cells. One of its most critical jobs is to help break down (degrade) proteins that are abnormal or no longer needed.  Mutations in the VCP gene alter the structure of valosin-containing protein, disrupting its ability to break down other proteins. As a result, excess and abnormal proteins may build up in muscle, bone, and brain cells. The proteins form clumps that interfere with the normal functions of these cells. It remains unclear how damage to muscle, bone, and brain cells leads to the specific features of IBMPFD.",inclusion body myopathy with early-onset Paget disease and frontotemporal dementia,0000516,GHR,https://ghr.nlm.nih.gov/condition/inclusion-body-myopathy-with-early-onset-paget-disease-and-frontotemporal-dementia,C1833672,T047,Disorders
Is inclusion body myopathy with early-onset Paget disease and frontotemporal dementia inherited ?,0000516-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",inclusion body myopathy with early-onset Paget disease and frontotemporal dementia,0000516,GHR,https://ghr.nlm.nih.gov/condition/inclusion-body-myopathy-with-early-onset-paget-disease-and-frontotemporal-dementia,C1833672,T047,Disorders
What are the treatments for inclusion body myopathy with early-onset Paget disease and frontotemporal dementia ?,0000516-5,treatment,These resources address the diagnosis or management of IBMPFD:  - Gene Review: Gene Review: Inclusion Body Myopathy with Paget Disease of Bone and/or Frontotemporal Dementia  - Genetic Testing Registry: Inclusion body myopathy with early-onset paget disease and frontotemporal dementia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,inclusion body myopathy with early-onset Paget disease and frontotemporal dementia,0000516,GHR,https://ghr.nlm.nih.gov/condition/inclusion-body-myopathy-with-early-onset-paget-disease-and-frontotemporal-dementia,C1833672,T047,Disorders
What is (are) incontinentia pigmenti ?,0000517-1,information,"Incontinentia pigmenti is a condition that can affect many body systems, particularly the skin. This condition occurs much more often in females than in males.  Incontinentia pigmenti is characterized by skin abnormalities that evolve throughout childhood and young adulthood. Many affected infants have a blistering rash at birth and in early infancy, which heals and is followed by the development of wart-like skin growths. In early childhood, the skin develops grey or brown patches (hyperpigmentation) that occur in a swirled pattern. These patches fade with time, and adults with incontinentia pigmenti usually have lines of unusually light-colored skin (hypopigmentation) on their arms and legs.  Other signs and symptoms of incontinentia pigmenti can include hair loss (alopecia) affecting the scalp and other parts of the body, dental abnormalities (such as small teeth or few teeth), eye abnormalities that can lead to vision loss, and lined or pitted fingernails and toenails. Most people with incontinentia pigmenti have normal intelligence; however, this condition may affect the brain. Associated problems can include delayed development or intellectual disability, seizures, and other neurological problems.",incontinentia pigmenti,0000517,GHR,https://ghr.nlm.nih.gov/condition/incontinentia-pigmenti,C2930820,T019,Disorders
How many people are affected by incontinentia pigmenti ?,0000517-2,frequency,"Incontinentia pigmenti is an uncommon disorder. Between 900 and 1,200 affected individuals have been reported in the scientific literature. Most of these individuals are female, but several dozen males with incontinentia pigmenti have also been identified.",incontinentia pigmenti,0000517,GHR,https://ghr.nlm.nih.gov/condition/incontinentia-pigmenti,C2930820,T019,Disorders
What are the genetic changes related to incontinentia pigmenti ?,0000517-3,genetic changes,"Mutations in the IKBKG gene cause incontinentia pigmenti. The IKBKG gene provides instructions for making a protein that helps regulate nuclear factor-kappa-B. Nuclear factor-kappa-B is a group of related proteins that helps protect cells from self-destructing (undergoing apoptosis) in response to certain signals.  About 80 percent of affected individuals have a mutation that deletes some genetic material from the IKBKG gene. This deletion probably leads to the production of an abnormally small, nonfunctional version of the IKBKG protein. Other people with incontinentia pigmenti have mutations that prevent the production of any IKBKG protein. Without this protein, nuclear factor-kappa-B is not regulated properly, and cells are more sensitive to signals that trigger them to self-destruct. Researchers believe that this abnormal cell death leads to the signs and symptoms of incontinentia pigmenti.",incontinentia pigmenti,0000517,GHR,https://ghr.nlm.nih.gov/condition/incontinentia-pigmenti,C2930820,T019,Disorders
Is incontinentia pigmenti inherited ?,0000517-4,inheritance,"This condition is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. Some cells produce a normal amount of IKBKG protein and other cells produce none. The resulting imbalance in cells producing this protein leads to the signs and symptoms of incontinentia pigmenti.  In males (who have only one X chromosome), most IKBKG mutations result in a total loss of the IKBKG protein. A lack of this protein appears to be lethal early in development, so few males are born with incontinentia pigmenti. Affected males who survive may have an IKBKG mutation with relatively mild effects, an IKBKG mutation in only some of the body's cells (mosaicism), or an extra copy of the X chromosome in each cell.  Some people with incontinentia pigmenti inherit an IKBKG mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",incontinentia pigmenti,0000517,GHR,https://ghr.nlm.nih.gov/condition/incontinentia-pigmenti,C2930820,T019,Disorders
What are the treatments for incontinentia pigmenti ?,0000517-5,treatment,These resources address the diagnosis or management of incontinentia pigmenti:  - Gene Review: Gene Review: Incontinentia Pigmenti  - Genetic Testing Registry: Incontinentia pigmenti syndrome  - MedlinePlus Encyclopedia: Incontinentia Pigmenti Syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,incontinentia pigmenti,0000517,GHR,https://ghr.nlm.nih.gov/condition/incontinentia-pigmenti,C2930820,T019,Disorders
What is (are) infantile neuroaxonal dystrophy ?,0000518-1,information,"Infantile neuroaxonal dystrophy is a disorder that primarily affects the nervous system. Individuals with infantile neuroaxonal dystrophy typically do not have any symptoms at birth, but between the ages of about 6 and 18 months they begin to experience delays in acquiring new motor and intellectual skills, such as crawling or beginning to speak. Eventually they lose previously acquired skills (developmental regression). In some cases, signs and symptoms of infantile neuroaxonal dystrophy first appear later in childhood or during the teenage years and progress more slowly.  Children with infantile neuroaxonal dystrophy experience progressive difficulties with movement. They generally have muscles that are at first weak and ""floppy"" (hypotonic), and then gradually become very stiff (spastic). Eventually, affected children lose the ability to move independently. Lack of muscle strength causes difficulty with feeding. Muscle weakness can also result in breathing problems that can lead to frequent infections, such as pneumonia. Seizures occur in some affected children.  Rapid, involuntary eye movements (nystagmus), eyes that do not look in the same direction (strabismus), and vision loss due to deterioration (atrophy) of the nerve that carries information from the eye to the brain (the optic nerve) often occur in infantile neuroaxonal dystrophy. Hearing loss may also develop. Children with this disorder experience progressive deterioration of cognitive functions (dementia), and they eventually lose awareness of their surroundings.  Infantile neuroaxonal dystrophy is characterized by the development of swellings called spheroid bodies in the axons, the fibers that extend from nerve cells (neurons) and transmit impulses to muscles and other neurons. In some individuals with infantile neuroaxonal dystrophy, abnormal amounts of iron accumulate in a specific region of the brain called the basal ganglia. The relationship of these features to the symptoms of infantile neuroaxonal dystrophy is unknown.",infantile neuroaxonal dystrophy,0000518,GHR,https://ghr.nlm.nih.gov/condition/infantile-neuroaxonal-dystrophy,C0270724,T047,Disorders
How many people are affected by infantile neuroaxonal dystrophy ?,0000518-2,frequency,Infantile neuroaxonal dystrophy is a very rare disorder. Its specific incidence is unknown.,infantile neuroaxonal dystrophy,0000518,GHR,https://ghr.nlm.nih.gov/condition/infantile-neuroaxonal-dystrophy,C0270724,T047,Disorders
What are the genetic changes related to infantile neuroaxonal dystrophy ?,0000518-3,genetic changes,"Mutations in the PLA2G6 gene have been identified in most individuals with infantile neuroaxonal dystrophy. The PLA2G6 gene provides instructions for making a type of enzyme called an A2 phospholipase. This type of enzyme is involved in breaking down (metabolizing) fats called phospholipids. Phospholipid metabolism is important for many body processes, including helping to keep the cell membrane intact and functioning properly. Specifically, the A2 phospholipase produced from the PLA2G6 gene, sometimes called PLA2 group VI, helps to regulate the levels of a compound called phosphatidylcholine, which is abundant in the cell membrane.  Mutations in the PLA2G6 gene impair the function of the PLA2 group VI enzyme, which may disrupt cell membrane maintenance and contribute to the development of spheroid bodies in the nerve axons. Although it is unknown how changes in this enzyme's function lead to the signs and symptoms of infantile neuroaxonal dystrophy, phospholipid metabolism problems have been seen in both this disorder and a similar disorder called pantothenate kinase-associated neurodegeneration. These disorders, as well as the more common Alzheimer disease and Parkinson disease, also are associated with changes in brain iron metabolism. Researchers are studying the links between phospholipid defects, brain iron, and damage to nerve cells, but have not determined how the iron accumulation that occurs in some individuals with infantile neuroaxonal dystrophy may contribute to the features of this disorder.  A few individuals with infantile neuroaxonal dystrophy have not been found to have mutations in the PLA2G6 gene. The genetic cause of the condition in these cases is unknown; there is evidence that at least one other unidentified gene may be involved.",infantile neuroaxonal dystrophy,0000518,GHR,https://ghr.nlm.nih.gov/condition/infantile-neuroaxonal-dystrophy,C0270724,T047,Disorders
Is infantile neuroaxonal dystrophy inherited ?,0000518-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",infantile neuroaxonal dystrophy,0000518,GHR,https://ghr.nlm.nih.gov/condition/infantile-neuroaxonal-dystrophy,C0270724,T047,Disorders
What are the treatments for infantile neuroaxonal dystrophy ?,0000518-5,treatment,These resources address the diagnosis or management of infantile neuroaxonal dystrophy:  - Gene Review: Gene Review: PLA2G6-Associated Neurodegeneration  - Genetic Testing Registry: Infantile neuroaxonal dystrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,infantile neuroaxonal dystrophy,0000518,GHR,https://ghr.nlm.nih.gov/condition/infantile-neuroaxonal-dystrophy,C0270724,T047,Disorders
What is (are) infantile neuronal ceroid lipofuscinosis ?,0000519-1,information,"Infantile neuronal ceroid lipofuscinosis (NCL) is an inherited disorder that primarily affects the nervous system. Beginning in infancy, children with this condition have intellectual and motor disability, rarely developing the ability to speak or walk. Affected children often have muscle twitches (myoclonus), recurrent seizures (epilepsy), or vision impairment. An unusually small head (microcephaly) and progressive loss of nerve cells in the brain are also characteristic features of this disorder. Children with infantile NCL usually do not survive past childhood.  Infantile NCL is one of a group of NCLs (collectively called Batten disease) that affect the nervous system and typically cause progressive problems with vision, movement, and thinking ability. The different types of NCLs are distinguished by the age at which signs and symptoms first appear.",infantile neuronal ceroid lipofuscinosis,0000519,GHR,https://ghr.nlm.nih.gov/condition/infantile-neuronal-ceroid-lipofuscinosis,C0268281,T019,Disorders
How many people are affected by infantile neuronal ceroid lipofuscinosis ?,0000519-2,frequency,"The incidence of infantile NCL is unknown. Collectively, all forms of NCL affect an estimated 1 in 100,000 individuals worldwide. NCLs are more common in Finland, where approximately 1 in 12,500 individuals are affected.",infantile neuronal ceroid lipofuscinosis,0000519,GHR,https://ghr.nlm.nih.gov/condition/infantile-neuronal-ceroid-lipofuscinosis,C0268281,T019,Disorders
What are the genetic changes related to infantile neuronal ceroid lipofuscinosis ?,0000519-3,genetic changes,"Mutations in the PPT1 gene cause most cases of infantile NCL. The PPT1 gene provides instructions for making an enzyme called palmitoyl-protein thioesterase 1. This enzyme is active in cell compartments called lysosomes, which digest and recycle different types of molecules. Palmitoyl-protein thioesterase 1 removes certain fats called long-chain fatty acids from proteins, which probably helps break down the proteins. Palmitoyl-protein thioesterase 1 is also thought to be involved in a variety of other cell functions.  PPT1 gene mutations that cause infantile NCL decrease the production or function of palmitoyl-protein thioesterase 1. A shortage of functional enzyme impairs the removal of fatty acids from proteins. In the lysosomes, these fats and proteins accumulate as fatty substances called lipopigments. These accumulations occur in cells throughout the body, but nerve cells in the brain seem to be particularly vulnerable to the damage caused by buildup of lipopigments and the loss of enzyme function. The progressive death of cells, especially in the brain, leads to the signs and symptoms of infantile NCL.",infantile neuronal ceroid lipofuscinosis,0000519,GHR,https://ghr.nlm.nih.gov/condition/infantile-neuronal-ceroid-lipofuscinosis,C0268281,T019,Disorders
Is infantile neuronal ceroid lipofuscinosis inherited ?,0000519-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",infantile neuronal ceroid lipofuscinosis,0000519,GHR,https://ghr.nlm.nih.gov/condition/infantile-neuronal-ceroid-lipofuscinosis,C0268281,T019,Disorders
What are the treatments for infantile neuronal ceroid lipofuscinosis ?,0000519-5,treatment,These resources address the diagnosis or management of infantile neuronal ceroid lipofuscinosis:  - Genetic Testing Registry: Ceroid lipofuscinosis neuronal 1  - Genetic Testing Registry: Infantile neuronal ceroid lipofuscinosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,infantile neuronal ceroid lipofuscinosis,0000519,GHR,https://ghr.nlm.nih.gov/condition/infantile-neuronal-ceroid-lipofuscinosis,C0268281,T019,Disorders
What is (are) infantile systemic hyalinosis ?,0000520-1,information,"Infantile systemic hyalinosis is a disorder that severely affects many areas of the body, including the skin, joints, bones, and internal organs. Hyalinosis refers to the abnormal accumulation of a clear (hyaline) substance in body tissues. The signs and symptoms of this condition are present at birth or develop within the first few months of life. Infantile systemic hyalinosis is characterized by painful skin bumps that frequently appear on the hands, neck, scalp, ears, and nose. They also develop in joint creases and the genital region. These skin bumps may be large or small and often increase in number over time.  Lumps of noncancerous tissue also form in the muscles and internal organs of children with infantile systemic hyalinosis, causing pain and severe complications. Most affected individuals develop a condition called protein-losing enteropathy due to the formation of lumps in their intestines. This condition results in severe diarrhea, failure to gain weight and grow at the expected rate (failure to thrive), and general wasting and weight loss (cachexia).  Infantile systemic hyalinosis is also characterized by overgrowth of the gums (gingival hypertrophy). Additionally, people with this condition have joint deformities (contractures) that impair movement. Affected individuals may grow slowly and have bone abnormalities.  Although children with infantile systemic hyalinosis have severe physical limitations, mental development is typically normal. Affected individuals often do not survive beyond early childhood due to chronic diarrhea and recurrent infections.",infantile systemic hyalinosis,0000520,GHR,https://ghr.nlm.nih.gov/condition/infantile-systemic-hyalinosis,C2745948,T047,Disorders
How many people are affected by infantile systemic hyalinosis ?,0000520-2,frequency,The prevalence of infantile systemic hyalinosis is unknown. Fewer than 20 people with this disorder have been reported.,infantile systemic hyalinosis,0000520,GHR,https://ghr.nlm.nih.gov/condition/infantile-systemic-hyalinosis,C2745948,T047,Disorders
What are the genetic changes related to infantile systemic hyalinosis ?,0000520-3,genetic changes,"Mutations in the ANTXR2 gene (also known as the CMG2 gene) cause infantile systemic hyalinosis. The ANTXR2 gene provides instructions for making a protein involved in the formation of tiny blood vessels (capillaries). Researchers believe that the ANTXR2 protein is also important for maintaining the structure of basement membranes, which are thin, sheet-like structures that separate and support cells in many tissues.  The signs and symptoms of infantile systemic hyalinosis are caused by the accumulation of a hyaline substance in different parts of the body. The nature of this substance is not well known, but it is likely made up of protein and sugar molecules. Researchers suspect that mutations in the ANTXR2 gene disrupt the formation of basement membranes, allowing the hyaline substance to leak through and build up in various body tissues.",infantile systemic hyalinosis,0000520,GHR,https://ghr.nlm.nih.gov/condition/infantile-systemic-hyalinosis,C2745948,T047,Disorders
Is infantile systemic hyalinosis inherited ?,0000520-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",infantile systemic hyalinosis,0000520,GHR,https://ghr.nlm.nih.gov/condition/infantile-systemic-hyalinosis,C2745948,T047,Disorders
What are the treatments for infantile systemic hyalinosis ?,0000520-5,treatment,"These resources address the diagnosis or management of infantile systemic hyalinosis:  - Gene Review: Gene Review: Hyalinosis, Inherited Systemic  - Genetic Testing Registry: Hyaline fibromatosis syndrome  - MedlinePlus Encyclopedia: Protein-losing enteropathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",infantile systemic hyalinosis,0000520,GHR,https://ghr.nlm.nih.gov/condition/infantile-systemic-hyalinosis,C2745948,T047,Disorders
What is (are) infantile-onset ascending hereditary spastic paralysis ?,0000521-1,information,"Infantile-onset ascending hereditary spastic paralysis is one of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and eventual paralysis of the lower limbs (paraplegia). The spasticity and paraplegia result from degeneration (atrophy) of motor neurons, which are specialized nerve cells in the brain and spinal cord that control muscle movement. Hereditary spastic paraplegias are divided into two types: pure and complicated. The pure types involve only the lower limbs, while the complicated types involve additional areas of the nervous system, affecting the upper limbs and other areas of the body. Infantile-onset ascending hereditary spastic paralysis starts as a pure hereditary spastic paraplegia, with spasticity and weakness in the legs only, but as the disorder progresses, the muscles in the arms, neck, and head become involved and features of the disorder are more characteristic of the complicated type.  Affected infants are typically normal at birth, then within the first 2 years of life, the initial symptoms of infantile-onset ascending hereditary spastic paralysis appear. Early symptoms include exaggerated reflexes (hyperreflexia) and recurrent muscle spasms in the legs. As the condition progresses, affected children develop abnormal tightness and stiffness in the leg muscles and weakness in the legs and arms. Over time, muscle weakness and stiffness travels up (ascends) the body from the legs to the head and neck. Muscles in the head and neck usually weaken during adolescence; symptoms include slow eye movements and difficulty with speech and swallowing. Affected individuals may lose the ability to speak (anarthria). The leg and arm muscle weakness can become so severe as to lead to paralysis; as a result affected individuals require wheelchair assistance by late childhood or early adolescence. Intelligence is not affected in this condition.  A condition called juvenile primary lateral sclerosis shares many of the features of infantile-onset ascending hereditary spastic paralysis. Both conditions have the same genetic cause and significantly impair movement beginning in childhood; however, the pattern of nerve degeneration is different. Because of their similarities, these conditions are sometimes considered the same disorder.",infantile-onset ascending hereditary spastic paralysis,0000521,GHR,https://ghr.nlm.nih.gov/condition/infantile-onset-ascending-hereditary-spastic-paralysis,C0085621,T046,Disorders
How many people are affected by infantile-onset ascending hereditary spastic paralysis ?,0000521-2,frequency,"Infantile-onset ascending hereditary spastic paralysis is a rare disorder, with at least 30 cases reported in the scientific literature.",infantile-onset ascending hereditary spastic paralysis,0000521,GHR,https://ghr.nlm.nih.gov/condition/infantile-onset-ascending-hereditary-spastic-paralysis,C0085621,T046,Disorders
What are the genetic changes related to infantile-onset ascending hereditary spastic paralysis ?,0000521-3,genetic changes,"Infantile-onset ascending hereditary spastic paralysis is caused by mutations in the ALS2 gene. This gene provides instructions for making the alsin protein. Alsin is produced in a wide range of tissues, with highest amounts in the brain, particularly in motor neurons. Alsin turns on (activates) multiple proteins called GTPases that convert a molecule called GTP into another molecule called GDP. GTPases play important roles in several cell processes. The GTPases that are activated by alsin are involved in the proper placement of the various proteins and fats that make up the cell membrane, the transport of molecules from the cell membrane to the interior of the cell (endocytosis), and the development of specialized structures called axons and dendrites that project from neurons and are essential for the transmission of nerve impulses.  Mutations in the ALS2 gene alter the instructions for making alsin, often resulting in the production of an abnormally short alsin protein that is unstable and rapidly broken down. It is unclear exactly how ALS2 gene mutations cause infantile-onset ascending hereditary spastic paralysis. Research suggests that a lack of alsin and the subsequent loss of GTPase functions, such as endocytosis and the development of axons and dendrites, contribute to the progressive atrophy of motor neurons that is characteristic of this condition.",infantile-onset ascending hereditary spastic paralysis,0000521,GHR,https://ghr.nlm.nih.gov/condition/infantile-onset-ascending-hereditary-spastic-paralysis,C0085621,T046,Disorders
Is infantile-onset ascending hereditary spastic paralysis inherited ?,0000521-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",infantile-onset ascending hereditary spastic paralysis,0000521,GHR,https://ghr.nlm.nih.gov/condition/infantile-onset-ascending-hereditary-spastic-paralysis,C0085621,T046,Disorders
What are the treatments for infantile-onset ascending hereditary spastic paralysis ?,0000521-5,treatment,These resources address the diagnosis or management of infantile-onset ascending hereditary spastic paralysis:  - Gene Review: Gene Review: ALS2-Related Disorders  - Genetic Testing Registry: Infantile-onset ascending hereditary spastic paralysis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,infantile-onset ascending hereditary spastic paralysis,0000521,GHR,https://ghr.nlm.nih.gov/condition/infantile-onset-ascending-hereditary-spastic-paralysis,C0085621,T046,Disorders
What is (are) infantile-onset spinocerebellar ataxia ?,0000522-1,information,"Infantile-onset spinocerebellar ataxia (IOSCA) is a progressive disorder that affects the nervous system. Babies with IOSCA develop normally during the first year of life. During early childhood, however, they begin experiencing difficulty coordinating movements (ataxia); very weak muscle tone (hypotonia); involuntary writhing movements of the limbs (athetosis); and decreased reflexes. By their teenage years affected individuals require wheelchair assistance.  People with IOSCA often develop problems with the autonomic nervous system, which controls involuntary body functions. As a result, they may experience excessive sweating, difficulty controlling urination, and severe constipation.  IOSCA also leads to vision and hearing problems that begin by about age 7. Children with this disorder develop weakness in the muscles that control eye movement (ophthalmoplegia). In their teenage years they experience degeneration of the nerves that carry information from the eyes to the brain (optic atrophy), which can result in vision loss. Hearing loss caused by nerve damage (sensorineural hearing loss) typically occurs during childhood and progresses to profound deafness.  Individuals with IOSCA may have recurrent seizures (epilepsy). These seizures can lead to severe brain dysfunction (encephalopathy).  Most people with IOSCA survive into adulthood. However, a few individuals with IOSCA have an especially severe form of the disorder involving liver damage and encephalopathy that develops during early childhood. These children do not generally live past age 5.",infantile-onset spinocerebellar ataxia,0000522,GHR,https://ghr.nlm.nih.gov/condition/infantile-onset-spinocerebellar-ataxia,C1849096,T047,Disorders
How many people are affected by infantile-onset spinocerebellar ataxia ?,0000522-2,frequency,More than 20 individuals with IOSCA have been identified in Finland. A few individuals with similar symptoms have been reported elsewhere in Europe.,infantile-onset spinocerebellar ataxia,0000522,GHR,https://ghr.nlm.nih.gov/condition/infantile-onset-spinocerebellar-ataxia,C1849096,T047,Disorders
What are the genetic changes related to infantile-onset spinocerebellar ataxia ?,0000522-3,genetic changes,"Mutations in the C10orf2 gene cause IOSCA. The C10orf2 gene provides instructions for making two very similar proteins called Twinkle and Twinky. These proteins are found in the mitochondria, which are structures within cells that convert the energy from food into a form that cells can use.  Mitochondria each contain a small amount of DNA, known as mitochondrial DNA or mtDNA, which is essential for the normal function of these structures. The Twinkle protein is involved in the production and maintenance of mtDNA. The function of the Twinky protein is unknown.  The C10orf2 gene mutations that cause IOSCA interfere with the function of the Twinkle protein and result in reduced quantities of mtDNA (mtDNA depletion). Impaired mitochondrial function in the nervous system, muscles, and other tissues that require a large amount of energy leads to neurological dysfunction and the other problems associated with IOSCA.",infantile-onset spinocerebellar ataxia,0000522,GHR,https://ghr.nlm.nih.gov/condition/infantile-onset-spinocerebellar-ataxia,C1849096,T047,Disorders
Is infantile-onset spinocerebellar ataxia inherited ?,0000522-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",infantile-onset spinocerebellar ataxia,0000522,GHR,https://ghr.nlm.nih.gov/condition/infantile-onset-spinocerebellar-ataxia,C1849096,T047,Disorders
What are the treatments for infantile-onset spinocerebellar ataxia ?,0000522-5,treatment,These resources address the diagnosis or management of IOSCA:  - Gene Review: Gene Review: Infantile-Onset Spinocerebellar Ataxia  - Genetic Testing Registry: Mitochondrial DNA depletion syndrome 7 (hepatocerebral type)   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,infantile-onset spinocerebellar ataxia,0000522,GHR,https://ghr.nlm.nih.gov/condition/infantile-onset-spinocerebellar-ataxia,C1849096,T047,Disorders
What is (are) inherited thyroxine-binding globulin deficiency ?,0000523-1,information,"Inherited thyroxine-binding globulin deficiency is a genetic condition that typically does not cause any health problems.  Thyroxine-binding globulin is a protein that carries hormones made or used by the thyroid gland, which is a butterfly-shaped tissue in the lower neck. Thyroid hormones play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism). Most of the time, these hormones circulate in the bloodstream attached to thyroxine-binding globulin and similar proteins. If there is a shortage (deficiency) of thyroxine-binding globulin, the amount of circulating thyroid hormones is reduced.  Researchers have identified two forms of inherited thyroxine-binding globulin deficiency: the complete form (TBG-CD), which results in a total loss of thyroxine-binding globulin, and the partial form (TBG-PD), which reduces the amount of this protein or alters its structure. Neither of these conditions causes any problems with thyroid function. They are usually identified during routine blood tests that measure thyroid hormones.  Although inherited thyroxine-binding globulin deficiency does not cause any health problems, it can be mistaken for more serious thyroid disorders (such as hypothyroidism). Therefore, it is important to diagnose inherited thyroxine-binding globulin deficiency to avoid unnecessary treatments.",inherited thyroxine-binding globulin deficiency,0000523,GHR,https://ghr.nlm.nih.gov/condition/inherited-thyroxine-binding-globulin-deficiency,C1839141,T047,Disorders
How many people are affected by inherited thyroxine-binding globulin deficiency ?,0000523-2,frequency,"The complete form of inherited thyroxine-binding globulin deficiency, TBG-CD, affects about 1 in 15,000 newborns worldwide. The partial form, TBG-PD, affects about 1 in 4,000 newborns. These conditions appear to be more common in the Australian Aborigine population and in the Bedouin population of southern Israel.",inherited thyroxine-binding globulin deficiency,0000523,GHR,https://ghr.nlm.nih.gov/condition/inherited-thyroxine-binding-globulin-deficiency,C1839141,T047,Disorders
What are the genetic changes related to inherited thyroxine-binding globulin deficiency ?,0000523-3,genetic changes,"Inherited thyroxine-binding globulin deficiency results from mutations in the SERPINA7 gene. This gene provides instructions for making thyroxine-binding globulin. Some mutations in the SERPINA7 gene prevent the production of a functional protein, causing TBG-CD. Other mutations reduce the amount of this protein or alter its structure, resulting in TBG-PD.  Researchers have also described non-inherited forms of thyroxine-binding globulin deficiency, which are more common than the inherited form. Non-inherited thyroxine-binding globulin deficiency can occur with a variety of illnesses and is a side effect of some medications.",inherited thyroxine-binding globulin deficiency,0000523,GHR,https://ghr.nlm.nih.gov/condition/inherited-thyroxine-binding-globulin-deficiency,C1839141,T047,Disorders
Is inherited thyroxine-binding globulin deficiency inherited ?,0000523-4,inheritance,"Inherited thyroxine-binding globulin deficiency has an X-linked pattern of inheritance. The SERPINA7 gene is located on the X chromosome, which is one of the two sex chromosomes.  In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes partial or complete inherited thyroxine-binding globulin deficiency. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell reduces the amount of thyroxine-binding globulin. However, their levels of this protein are usually within the normal range.  A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",inherited thyroxine-binding globulin deficiency,0000523,GHR,https://ghr.nlm.nih.gov/condition/inherited-thyroxine-binding-globulin-deficiency,C1839141,T047,Disorders
What are the treatments for inherited thyroxine-binding globulin deficiency ?,0000523-5,treatment,These resources address the diagnosis or management of inherited thyroxine-binding globulin deficiency:  - American Thyroid Association: Thyroid Function Tests  - MedlinePlus Encyclopedia: Serum TBG Level   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,inherited thyroxine-binding globulin deficiency,0000523,GHR,https://ghr.nlm.nih.gov/condition/inherited-thyroxine-binding-globulin-deficiency,C1839141,T047,Disorders
What is (are) intestinal pseudo-obstruction ?,0000524-1,information,"Intestinal pseudo-obstruction is a condition characterized by impairment of the muscle contractions that move food through the digestive tract. The condition may arise from abnormalities of the gastrointestinal muscles themselves (myogenic) or from problems with the nerves that control the muscle contractions (neurogenic).  When intestinal pseudo-obstruction occurs by itself, it is called primary or idiopathic intestinal pseudo-obstruction. The disorder can also develop as a complication of another medical condition; in these cases, it is called secondary intestinal pseudo-obstruction.  Intestinal pseudo-obstruction leads to a buildup of partially digested food in the intestines. This buildup can cause abdominal swelling (distention) and pain, nausea, vomiting, and constipation or diarrhea. Affected individuals experience loss of appetite and impaired ability to absorb nutrients, which may lead to malnutrition. These symptoms resemble those of an intestinal blockage (obstruction), but in intestinal pseudo-obstruction no blockage is found.  Some people with intestinal pseudo-obstruction have bladder dysfunction such as an inability to pass urine. Other features of this condition may include decreased muscle tone (hypotonia) or stiffness (spasticity), weakness in the muscles that control eye movement (ophthalmoplegia), intellectual disability, seizures, unusual facial features, or recurrent infections.  Intestinal pseudo-obstruction can occur at any time of life. Its symptoms may range from mild to severe. Some affected individuals may require nutritional support. Depending on the severity of the condition, such support may include nutritional supplements, a feeding tube, or intravenous feedings (parenteral nutrition).",intestinal pseudo-obstruction,0000524,GHR,https://ghr.nlm.nih.gov/condition/intestinal-pseudo-obstruction,C0021847,T047,Disorders
How many people are affected by intestinal pseudo-obstruction ?,0000524-2,frequency,"Primary intestinal pseudo-obstruction is a rare disorder. Its prevalence is unknown. The prevalence of secondary intestinal pseudo-obstruction is also unknown, but it is believed to be more common than the primary form.",intestinal pseudo-obstruction,0000524,GHR,https://ghr.nlm.nih.gov/condition/intestinal-pseudo-obstruction,C0021847,T047,Disorders
What are the genetic changes related to intestinal pseudo-obstruction ?,0000524-3,genetic changes,"In some individuals with primary intestinal pseudo-obstruction, the condition is caused by mutations in the FLNA gene. This gene provides instructions for producing the protein filamin A, which helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. Filamin A attaches (binds) to another protein called actin and helps it form the branching network of filaments that make up the cytoskeleton.  Some individuals with primary intestinal pseudo-obstruction have FLNA gene mutations that result in an abnormally short filamin A protein. Others have duplications or deletions of genetic material in the FLNA gene. Researchers believe that these genetic changes may impair the function of the filamin A protein, causing abnormalities in the cytoskeleton of nerve cells (neurons) in the gastrointestinal tract. These abnormalities interfere with the nerves' ability to produce the coordinated waves of muscle contractions (peristalsis) that move food through the digestive tract.  Deletions or duplications of genetic material that affect the FLNA gene can also include adjacent genes on the X chromosome. Changes in adjacent genes may account for some of the other signs and symptoms that can occur with intestinal pseudo-obstruction.  Secondary intestinal pseudo-obstruction may result from other disorders that damage muscles or nerves, such as Parkinson disease, diabetes, or muscular dystrophy. Additionally, the condition is a feature of an inherited disease called mitochondrial neurogastrointestinal encephalopathy disease (MNGIE disease) that affects the energy-producing centers of cells (mitochondria). Infections, surgery, or certain drugs can also cause secondary intestinal pseudo-obstruction.  In some affected individuals, the cause of intestinal pseudo-obstruction is unknown. Studies suggest that in some cases the condition may result from mutations in other genes that have not been identified.",intestinal pseudo-obstruction,0000524,GHR,https://ghr.nlm.nih.gov/condition/intestinal-pseudo-obstruction,C0021847,T047,Disorders
Is intestinal pseudo-obstruction inherited ?,0000524-4,inheritance,"Intestinal pseudo-obstruction is often not inherited. When it does run in families, it can have different inheritance patterns.  Intestinal pseudo-obstruction caused by FLNA gene mutations is inherited in an X-linked recessive pattern. The FLNA gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  Intestinal pseudo-obstruction can also be inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In other families it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. When intestinal pseudo-obstruction is inherited in an autosomal dominant or autosomal recessive pattern, the genetic cause of the disorder is unknown.  When intestinal pseudo-obstruction is a feature of MNGIE disease, it is inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mitochondrial DNA (mtDNA). Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children.  In some cases, the inheritance pattern is unknown.",intestinal pseudo-obstruction,0000524,GHR,https://ghr.nlm.nih.gov/condition/intestinal-pseudo-obstruction,C0021847,T047,Disorders
What are the treatments for intestinal pseudo-obstruction ?,0000524-5,treatment,"These resources address the diagnosis or management of intestinal pseudo-obstruction:  - Children's Hospital of Pittsburgh  - Genetic Testing Registry: Intestinal pseudoobstruction neuronal chronic idiopathic X-linked  - Genetic Testing Registry: Natal teeth, intestinal pseudoobstruction and patent ductus  - Genetic Testing Registry: Visceral myopathy familial with external ophthalmoplegia  - Genetic Testing Registry: Visceral neuropathy familial  - Genetic Testing Registry: Visceral neuropathy, familial, autosomal dominant   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",intestinal pseudo-obstruction,0000524,GHR,https://ghr.nlm.nih.gov/condition/intestinal-pseudo-obstruction,C0021847,T047,Disorders
What is (are) intrahepatic cholestasis of pregnancy ?,0000525-1,information,"Intrahepatic cholestasis of pregnancy is a liver disorder that occurs in pregnant women. Cholestasis is a condition that impairs the release of a digestive fluid called bile from liver cells. As a result, bile builds up in the liver, impairing liver function. Because the problems with bile release occur within the liver (intrahepatic), the condition is described as intrahepatic cholestasis. Intrahepatic cholestasis of pregnancy usually becomes apparent in the third trimester of pregnancy. Bile flow returns to normal after delivery of the baby, and the signs and symptoms of the condition disappear. However, they can return during later pregnancies.  This condition causes severe itchiness (pruritus) in the expectant mother. The itchiness usually begins on the palms of the hands and the soles of the feet and then spreads to other parts of the body. Occasionally, affected women have yellowing of the skin and whites of the eyes (jaundice). Some studies have shown that women with intrahepatic cholestasis of pregnancy are more likely to develop gallstones sometime in their life than women who do not have the condition.  Intrahepatic cholestasis of pregnancy can cause problems for the unborn baby. This condition is associated with an increased risk of premature delivery and stillbirth. Additionally, some infants born to mothers with intrahepatic cholestasis of pregnancy have a slow heart rate and a lack of oxygen during delivery (fetal distress).",intrahepatic cholestasis of pregnancy,0000525,GHR,https://ghr.nlm.nih.gov/condition/intrahepatic-cholestasis-of-pregnancy,C0268318,T047,Disorders
How many people are affected by intrahepatic cholestasis of pregnancy ?,0000525-2,frequency,"Intrahepatic cholestasis of pregnancy is estimated to affect 1 percent of women of Northern European ancestry. The condition is more common in certain populations, such as women of Araucanian Indian ancestry in Chile or women of Scandinavian ancestry. This condition is found less frequently in other populations.",intrahepatic cholestasis of pregnancy,0000525,GHR,https://ghr.nlm.nih.gov/condition/intrahepatic-cholestasis-of-pregnancy,C0268318,T047,Disorders
What are the genetic changes related to intrahepatic cholestasis of pregnancy ?,0000525-3,genetic changes,"Genetic changes in the ABCB11 or the ABCB4 gene can increase a woman's likelihood of developing intrahepatic cholestasis of pregnancy.  The ABCB11 gene provides instructions for making a protein called the bile salt export pump (BSEP). This protein is found in the liver, and its main role is to move bile salts (a component of bile) out of liver cells, which is important for the normal release of bile. Changes in the ABCB11 gene associated with intrahepatic cholestasis of pregnancy reduce the amount or function of the BSEP protein, although enough function remains for sufficient bile secretion under most circumstances. Studies show that the hormones estrogen and progesterone (and products formed during their breakdown), which are elevated during pregnancy, further reduce the function of BSEP, resulting in impaired bile secretion and the features of intrahepatic cholestasis of pregnancy.  The ABCB4 gene provides instructions for making a protein that helps move certain fats called phospholipids across cell membranes and release them into bile. Phospholipids attach (bind) to bile acids (another component of bile). Large amounts of bile acids can be toxic when they are not bound to phospholipids. A mutation in one copy of the ABCB4 gene mildly reduces the production of ABCB4 protein. Under most circumstances, though, enough protein is available to move an adequate amount of phospholipids out of liver cells to bind to bile acids. Although the mechanism is unclear, the function of the remaining ABCB4 protein appears to be impaired during pregnancy, which may further reduce the movement of phospholipids into bile. The lack of phospholipids available to bind to bile acids leads to a buildup of toxic bile acids that can impair liver function, including the regulation of bile flow.  Most women with intrahepatic cholestasis of pregnancy do not have a genetic change in the ABCB11 or ABCB4 gene. Other genetic and environmental factors likely play a role in increasing susceptibility to this condition.",intrahepatic cholestasis of pregnancy,0000525,GHR,https://ghr.nlm.nih.gov/condition/intrahepatic-cholestasis-of-pregnancy,C0268318,T047,Disorders
Is intrahepatic cholestasis of pregnancy inherited ?,0000525-4,inheritance,"Susceptibility to intrahepatic cholestasis of pregnancy is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing the disorder. Some women with an altered gene do not develop intrahepatic cholestasis of pregnancy. Many other factors likely contribute to the risk of developing this complex disorder.",intrahepatic cholestasis of pregnancy,0000525,GHR,https://ghr.nlm.nih.gov/condition/intrahepatic-cholestasis-of-pregnancy,C0268318,T047,Disorders
What are the treatments for intrahepatic cholestasis of pregnancy ?,0000525-5,treatment,These resources address the diagnosis or management of intrahepatic cholestasis of pregnancy:  - Gene Review: Gene Review: ATP8B1 Deficiency  - Genetic Testing Registry: Cholestasis of pregnancy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,intrahepatic cholestasis of pregnancy,0000525,GHR,https://ghr.nlm.nih.gov/condition/intrahepatic-cholestasis-of-pregnancy,C0268318,T047,Disorders
What is (are) intranuclear rod myopathy ?,0000526-1,information,"Intranuclear rod myopathy is a disorder that primarily affects skeletal muscles, which are muscles that the body uses for movement. People with intranuclear rod myopathy have severe muscle weakness (myopathy) and poor muscle tone (hypotonia) throughout the body. Signs and symptoms of this condition are apparent in infancy and include feeding and swallowing difficulties, a weak cry, and difficulty with controlling head movements. Affected babies are sometimes described as ""floppy"" and may be unable to move on their own.  The severe muscle weakness that occurs in intranuclear rod myopathy also affects the muscles used for breathing. Individuals with this disorder may take shallow breaths (hypoventilate), especially during sleep, resulting in a shortage of oxygen and a buildup of carbon dioxide in the blood. Frequent respiratory infections and life-threatening breathing difficulties can occur. Because of the respiratory problems, most affected individuals do not survive past infancy. Those who do survive have delayed development of motor skills such as sitting, crawling, standing, and walking.  The name intranuclear rod myopathy comes from characteristic abnormal rod-shaped structures that can be seen in the nucleus of muscle cells when muscle tissue is viewed under a microscope.",intranuclear rod myopathy,0000526,GHR,https://ghr.nlm.nih.gov/condition/intranuclear-rod-myopathy,C3711377,T047,Disorders
How many people are affected by intranuclear rod myopathy ?,0000526-2,frequency,Intranuclear rod myopathy is a rare disorder that has been identified in only a small number of individuals. Its exact prevalence is unknown.,intranuclear rod myopathy,0000526,GHR,https://ghr.nlm.nih.gov/condition/intranuclear-rod-myopathy,C3711377,T047,Disorders
What are the genetic changes related to intranuclear rod myopathy ?,0000526-3,genetic changes,"Intranuclear rod myopathy is caused by a mutation in the ACTA1 gene. This gene provides instructions for making a protein called skeletal alpha ()-actin, which is part of the actin protein family. Actin proteins are important for cell movement and the tensing of muscle fibers (muscle contraction). Thin filaments made up of actin molecules and thick filaments made up of another protein called myosin are the primary components of muscle fibers and are important for muscle contraction. Attachment (binding) and release of the overlapping thick and thin filaments allows them to move relative to each other so that the muscles can contract.  ACTA1 gene mutations that cause intranuclear rod myopathy result in the accumulation of rods of skeletal -actin in the nucleus of muscle cells. Normally, most actin is found in the fluid surrounding the nucleus (the cytoplasm), with small amounts in the nucleus itself. Researchers suggest that the ACTA1 gene mutations that cause intranuclear rod myopathy may interfere with the normal transport of actin between the nucleus and the cytoplasm, resulting in the accumulation of actin in the nucleus and the formation of intranuclear rods. Abnormal accumulation of actin in the nucleus of muscle cells and a corresponding reduction of available actin in muscle fibers may impair muscle contraction and lead to the muscle weakness seen in intranuclear rod myopathy.  In some people with intranuclear rod myopathy, no ACTA1 gene mutations have been identified. The cause of the disorder in these individuals is unknown.",intranuclear rod myopathy,0000526,GHR,https://ghr.nlm.nih.gov/condition/intranuclear-rod-myopathy,C3711377,T047,Disorders
Is intranuclear rod myopathy inherited ?,0000526-4,inheritance,"Intranuclear rod myopathy is an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases are not inherited; they result from new mutations in the gene and occur in people with no history of the disorder in their family.",intranuclear rod myopathy,0000526,GHR,https://ghr.nlm.nih.gov/condition/intranuclear-rod-myopathy,C3711377,T047,Disorders
What are the treatments for intranuclear rod myopathy ?,0000526-5,treatment,These resources address the diagnosis or management of intranuclear rod myopathy:  - Genetic Testing Registry: Nemaline myopathy 3   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,intranuclear rod myopathy,0000526,GHR,https://ghr.nlm.nih.gov/condition/intranuclear-rod-myopathy,C3711377,T047,Disorders
"What is (are) intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies ?",0000527-1,information,"The combination of intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies is commonly known by the acronym IMAGe. This rare syndrome has signs and symptoms that affect many parts of the body.  Most affected individuals grow slowly before birth (intrauterine growth restriction) and are small in infancy. They have skeletal abnormalities that often become apparent in early childhood, although these abnormalities are usually mild and can be difficult to recognize on x-rays. The most common bone changes are metaphyseal dysplasia and epiphyseal dysplasia; these are malformations of the ends of long bones in the arms and legs. Some affected individuals also have an abnormal side-to-side curvature of the spine (scoliosis) or thinning of the bones (osteoporosis).  Adrenal hypoplasia congenita is the most severe feature of IMAGe syndrome. The adrenal glands are a pair of small glands on top of each kidney. They produce a variety of hormones that regulate many essential functions in the body. Underdevelopment (hypoplasia) of these glands prevents them from producing enough hormones, a condition known as adrenal insufficiency. The signs of adrenal insufficiency begin shortly after birth and include vomiting, difficulty with feeding, dehydration, extremely low blood sugar (hypoglycemia), and shock. If untreated, these complications can be life-threatening.  The genital abnormalities associated with IMAGe syndrome occur only in affected males. They include an unusually small penis (micropenis), undescended testes (cryptorchidism), and the opening of the urethra on the underside of the penis (hypospadias).  Several additional signs and symptoms have been reported in people with IMAGe syndrome. Some affected individuals have distinctive facial features, such as a prominent forehead, low-set ears, and a short nose with a flat nasal bridge. Less commonly, people with this condition have premature fusion of certain bones of the skull (craniosynostosis), a split in the soft flap of tissue that hangs from the back of the mouth (cleft or bifid uvula), a high-arched roof of the mouth (palate), and a small chin (micrognathia). Other possible features of IMAGe syndrome include high levels of calcium in the blood (hypercalcemia) or urine (hypercalcuria) and a shortage of growth hormone in childhood that results in short stature.","intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies",0000527,GHR,https://ghr.nlm.nih.gov/condition/intrauterine-growth-restriction-metaphyseal-dysplasia-adrenal-hypoplasia-congenita-and-genital-anomalies,C0265294,T019,Disorders
"How many people are affected by intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies ?",0000527-2,frequency,"IMAGe syndrome is very rare, with only about 20 cases reported in the medical literature. The condition has been diagnosed more often in males than in females, probably because females do not have associated genital abnormalities.","intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies",0000527,GHR,https://ghr.nlm.nih.gov/condition/intrauterine-growth-restriction-metaphyseal-dysplasia-adrenal-hypoplasia-congenita-and-genital-anomalies,C0265294,T019,Disorders
"What are the genetic changes related to intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies ?",0000527-3,genetic changes,"IMAGe syndrome is caused by mutations in the CDKN1C gene. This gene provides instructions for making a protein that helps control growth before birth. The mutations that cause IMAGe syndrome alter the structure and function of the CDKN1C protein, which inhibits normal growth starting in the early stages of development before birth. Researchers are working to determine how these genetic changes underlie the bone abnormalities, adrenal gland underdevelopment, and other signs and symptoms of this condition.  People inherit one copy of most genes from their mother and one copy from their father. For most genes, both copies are fully turned on (active) in cells. The CDKN1C gene, however, is most active when it is inherited from a person's mother. The copy of CDKN1C inherited from a person's father is active at much lower levels in most tissues. This sort of parent-specific difference in gene activation is caused by a phenomenon called genomic imprinting. When genomic imprinting reduces the activity of the copy of a gene inherited from the father, that gene is said to be paternally imprinted.","intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies",0000527,GHR,https://ghr.nlm.nih.gov/condition/intrauterine-growth-restriction-metaphyseal-dysplasia-adrenal-hypoplasia-congenita-and-genital-anomalies,C0265294,T019,Disorders
"Is intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies inherited ?",0000527-4,inheritance,"The inheritance of IMAGe syndrome is complex. The condition is described as having an autosomal dominant inheritance pattern because one copy of the altered CDKN1C gene in each cell is sufficient to cause the disorder. However, because this gene is paternally imprinted, IMAGe syndrome results only when the mutation is present on the maternally inherited copy of the gene. When a mutation affects the paternally inherited copy of the CDKN1C gene, it does not cause health problems. Therefore, IMAGe syndrome is passed only from mothers to their children.","intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies",0000527,GHR,https://ghr.nlm.nih.gov/condition/intrauterine-growth-restriction-metaphyseal-dysplasia-adrenal-hypoplasia-congenita-and-genital-anomalies,C0265294,T019,Disorders
"What are the treatments for intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies ?",0000527-5,treatment,"These resources address the diagnosis or management of IMAGe syndrome:  - Gene Review: Gene Review: IMAGe Syndrome  - Genetic Testing Registry: Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies  - National Institutes of Health Clinical Center: Managing Adrenal Insufficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies",0000527,GHR,https://ghr.nlm.nih.gov/condition/intrauterine-growth-restriction-metaphyseal-dysplasia-adrenal-hypoplasia-congenita-and-genital-anomalies,C0265294,T019,Disorders
What is (are) IRAK-4 deficiency ?,0000528-1,information,"IRAK-4 deficiency is an inherited disorder of the immune system (primary immunodeficiency). This immunodeficiency leads to recurrent infections by a subset of bacteria known as pyogenic bacteria but not by other infectious agents. (Infection with pyogenic bacteria causes the production of pus.) The most common infections in IRAK-4 deficiency are caused by the Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa bacteria. Most people with this condition have their first bacterial infection before age 2, and the infections can be life-threatening in infancy and childhood. Infections become less frequent with age.  Most people with IRAK-4 deficiency have invasive bacterial infections, which can involve the blood (septicemia), the membrane covering the brain and spinal cord (meningitis), or the joints (leading to inflammation and arthritis). Invasive infections can also cause areas of tissue breakdown and pus production (abscesses) on internal organs. In addition, affected individuals can have localized infections of the upper respiratory tract, skin, or eyes. Although fever is a common reaction to bacterial infections, many people with IRAK-4 deficiency do not at first develop a high fever in response to these infections, even if the infection is severe.",IRAK-4 deficiency,0000528,GHR,https://ghr.nlm.nih.gov/condition/irak-4-deficiency,C1843256,T047,Disorders
How many people are affected by IRAK-4 deficiency ?,0000528-2,frequency,"IRAK-4 deficiency is a very rare condition, although the exact prevalence is unknown. At least 49 individuals with this condition have been described in the scientific literature.",IRAK-4 deficiency,0000528,GHR,https://ghr.nlm.nih.gov/condition/irak-4-deficiency,C1843256,T047,Disorders
What are the genetic changes related to IRAK-4 deficiency ?,0000528-3,genetic changes,"IRAK-4 deficiency is caused by mutations in the IRAK4 gene, which provides instructions for making a protein that plays an important role in stimulating the immune system to respond to infection. The IRAK-4 protein is part of a signaling pathway that is involved in early recognition of foreign invaders (pathogens) and the initiation of inflammation to fight infection. This signaling pathway is part of the innate immune response, which is the body's early, nonspecific response to pathogens.  Mutations in the IRAK4 gene lead to the production of a nonfunctional protein or no protein at all. The loss of functional IRAK-4 protein prevents the immune system from triggering inflammation in response to pathogens that would normally help fight the infections. Because the early immune response is insufficient, bacterial infections occur often and become severe and invasive.",IRAK-4 deficiency,0000528,GHR,https://ghr.nlm.nih.gov/condition/irak-4-deficiency,C1843256,T047,Disorders
Is IRAK-4 deficiency inherited ?,0000528-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",IRAK-4 deficiency,0000528,GHR,https://ghr.nlm.nih.gov/condition/irak-4-deficiency,C1843256,T047,Disorders
What are the treatments for IRAK-4 deficiency ?,0000528-5,treatment,These resources address the diagnosis or management of IRAK-4 deficiency:  - Genetic Testing Registry: IRAK4 deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,IRAK-4 deficiency,0000528,GHR,https://ghr.nlm.nih.gov/condition/irak-4-deficiency,C1843256,T047,Disorders
What is (are) iron-refractory iron deficiency anemia ?,0000529-1,information,"Iron-refractory iron deficiency anemia is one of many types of anemia, which is a group of conditions characterized by a shortage of healthy red blood cells. This shortage prevents the blood from carrying an adequate supply of oxygen to the body's tissues.  Iron-refractory iron deficiency anemia results from an inadequate amount (deficiency) of iron in the bloodstream. It is described as ""iron-refractory"" because the condition is totally resistant (refractory) to treatment with iron given orally and partially resistant to iron given in other ways, such as intravenously (by IV). In people with this form of anemia, red blood cells are abnormally small (microcytic) and pale (hypochromic). The symptoms of iron-refractory iron deficiency anemia can include tiredness (fatigue), weakness, pale skin, and other complications. These symptoms are most pronounced during childhood, although they tend to be mild. Affected individuals usually have normal growth and development.",iron-refractory iron deficiency anemia,0000529,GHR,https://ghr.nlm.nih.gov/condition/iron-refractory-iron-deficiency-anemia,C0085576,T047,Disorders
How many people are affected by iron-refractory iron deficiency anemia ?,0000529-2,frequency,"Although iron deficiency anemia is relatively common, the prevalence of the iron-refractory form of the disease is unknown. At least 50 cases have been described in the medical literature. Researchers suspect that iron-refractory iron deficiency anemia is underdiagnosed because affected individuals with very mild symptoms may never come to medical attention.",iron-refractory iron deficiency anemia,0000529,GHR,https://ghr.nlm.nih.gov/condition/iron-refractory-iron-deficiency-anemia,C0085576,T047,Disorders
What are the genetic changes related to iron-refractory iron deficiency anemia ?,0000529-3,genetic changes,"Mutations in the TMPRSS6 gene cause iron-refractory iron deficiency anemia. This gene provides instructions for making a protein called matriptase-2, which helps regulate iron levels in the body. TMPRSS6 gene mutations reduce or eliminate functional matriptase-2, which disrupts iron regulation and leads to a shortage of iron in the bloodstream. Iron is an essential component of hemoglobin, which is the molecule in red blood cells that carries oxygen. When not enough iron is available in the bloodstream, less hemoglobin is produced, causing red blood cells to be abnormally small and pale. The abnormal cells cannot carry oxygen effectively to the body's cells and tissues, which leads to fatigue, weakness, and other symptoms of anemia.",iron-refractory iron deficiency anemia,0000529,GHR,https://ghr.nlm.nih.gov/condition/iron-refractory-iron-deficiency-anemia,C0085576,T047,Disorders
Is iron-refractory iron deficiency anemia inherited ?,0000529-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",iron-refractory iron deficiency anemia,0000529,GHR,https://ghr.nlm.nih.gov/condition/iron-refractory-iron-deficiency-anemia,C0085576,T047,Disorders
What are the treatments for iron-refractory iron deficiency anemia ?,0000529-5,treatment,"These resources address the diagnosis or management of iron-refractory iron deficiency anemia:  - National Heart, Lung, and Blood Institute: How is Anemia Diagnosed?  - National Heart, Lung, and Blood Institute: How is Anemia Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",iron-refractory iron deficiency anemia,0000529,GHR,https://ghr.nlm.nih.gov/condition/iron-refractory-iron-deficiency-anemia,C0085576,T047,Disorders
What is (are) isobutyryl-CoA dehydrogenase deficiency ?,0000530-1,information,"Isobutyryl-CoA dehydrogenase (IBD) deficiency is a condition that disrupts the breakdown of certain proteins. Normally, proteins from food are broken down into parts called amino acids. Amino acids can be further processed to provide energy for growth and development. People with IBD deficiency have inadequate levels of an enzyme that helps break down a particular amino acid called valine.  Most people with IBD deficiency are asymptomatic, which means they do not have any signs or symptoms of the condition. A few children with IBD deficiency have developed features such as a weakened and enlarged heart (dilated cardiomyopathy), weak muscle tone (hypotonia), and developmental delay. This condition may also cause low numbers of red blood cells (anemia) and very low blood levels of carnitine, which is a natural substance that helps convert certain foods into energy. The range of signs and symptoms associated with IBD deficiency remains unclear because very few affected individuals have been reported.",isobutyryl-CoA dehydrogenase deficiency,0000530,GHR,https://ghr.nlm.nih.gov/condition/isobutyryl-coa-dehydrogenase-deficiency,C1969809,T047,Disorders
How many people are affected by isobutyryl-CoA dehydrogenase deficiency ?,0000530-2,frequency,IBD deficiency is a rare disorder; approximately 22 cases have been reported in the medical literature.,isobutyryl-CoA dehydrogenase deficiency,0000530,GHR,https://ghr.nlm.nih.gov/condition/isobutyryl-coa-dehydrogenase-deficiency,C1969809,T047,Disorders
What are the genetic changes related to isobutyryl-CoA dehydrogenase deficiency ?,0000530-3,genetic changes,"Mutations in the ACAD8 gene cause IBD deficiency. This gene provides instructions for making the IBD enzyme, which is involved in breaking down valine. ACAD8 gene mutations reduce or eliminate the activity of the IBD enzyme. As a result, valine is not broken down properly. Impaired processing of valine may lead to reduced energy production and the features of IBD deficiency.",isobutyryl-CoA dehydrogenase deficiency,0000530,GHR,https://ghr.nlm.nih.gov/condition/isobutyryl-coa-dehydrogenase-deficiency,C1969809,T047,Disorders
Is isobutyryl-CoA dehydrogenase deficiency inherited ?,0000530-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",isobutyryl-CoA dehydrogenase deficiency,0000530,GHR,https://ghr.nlm.nih.gov/condition/isobutyryl-coa-dehydrogenase-deficiency,C1969809,T047,Disorders
What are the treatments for isobutyryl-CoA dehydrogenase deficiency ?,0000530-5,treatment,These resources address the diagnosis or management of isobutyryl-CoA dehydrogenase deficiency:  - Baby's First Test  - Genetic Testing Registry: Deficiency of isobutyryl-CoA dehydrogenase  - MedlinePlus Encyclopedia: Dilated Cardiomyopathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,isobutyryl-CoA dehydrogenase deficiency,0000530,GHR,https://ghr.nlm.nih.gov/condition/isobutyryl-coa-dehydrogenase-deficiency,C1969809,T047,Disorders
What is (are) isodicentric chromosome 15 syndrome ?,0000531-1,information,"Isodicentric chromosome 15 syndrome is a developmental disorder with a broad spectrum of features. The signs and symptoms vary among affected individuals.  Poor muscle tone is commonly seen in individuals with isodicentric chromosome 15 syndrome and contributes to delayed development and impairment of motor skills, including sitting and walking.  Babies with isodicentric chromosome 15 syndrome often have trouble feeding due to weak facial muscles that impair sucking and swallowing; many also have backflow of acidic stomach contents into the esophagus (gastroesophageal reflux). These feeding problems may make it difficult for them to gain weight.  Intellectual disability in isodicentric chromosome 15 syndrome can range from mild to profound. Speech is usually delayed and often remains absent or impaired. Behavioral difficulties often associated with isodicentric chromosome 15 syndrome include hyperactivity, anxiety, and frustration leading to tantrums. Other behaviors resemble features of autistic spectrum disorders, such as repeating the words of others (echolalia), difficulty with changes in routine, and problems with social interaction.  About two-thirds of people with isodicentric chromosome 15 syndrome have seizures. In more than half of affected individuals, the seizures begin in the first year of life.  About 40 percent of individuals with isodicentric chromosome 15 syndrome are born with eyes that do not look in the same direction (strabismus). Hearing loss in childhood is common and is usually caused by fluid buildup in the middle ear. This hearing loss is often temporary. However, if left untreated during early childhood, the hearing loss can interfere with language development and worsen the speech problems associated with this disorder.  Other problems associated with isodicentric chromosome 15 syndrome in some affected individuals include minor genital abnormalities in males such as undescended testes (cryptorchidism) and a spine that curves to the side (scoliosis).",isodicentric chromosome 15 syndrome,0000531,GHR,https://ghr.nlm.nih.gov/condition/isodicentric-chromosome-15-syndrome,C3711376,T047,Disorders
How many people are affected by isodicentric chromosome 15 syndrome ?,0000531-2,frequency,"Isodicentric chromosome 15 syndrome occurs in about 1 in 30,000 newborns.",isodicentric chromosome 15 syndrome,0000531,GHR,https://ghr.nlm.nih.gov/condition/isodicentric-chromosome-15-syndrome,C3711376,T047,Disorders
What are the genetic changes related to isodicentric chromosome 15 syndrome ?,0000531-3,genetic changes,"Isodicentric chromosome 15 syndrome results from the presence of an abnormal extra chromosome, called an isodicentric chromosome 15, in each cell. An isodicentric chromosome contains mirror-image segments of genetic material and has two constriction points (centromeres), rather than one centromere as in normal chromosomes. In isodicentric chromosome 15 syndrome, the isodicentric chromosome is made up of two extra copies of a segment of genetic material from chromosome 15, attached end-to-end. Typically this copied genetic material includes a region of the chromosome called 15q11-q13.  Cells normally have two copies of each chromosome, one inherited from each parent. In people with isodicentric chromosome 15 syndrome, cells have the usual two copies of chromosome 15 plus the two extra copies of the segment of genetic material in the isodicentric chromosome. The extra genetic material disrupts the normal course of development, causing the characteristic features of this disorder. Some individuals with isodicentric chromosome 15 whose copied genetic material does not include the 15q11-q13 region do not show signs or symptoms of the condition.",isodicentric chromosome 15 syndrome,0000531,GHR,https://ghr.nlm.nih.gov/condition/isodicentric-chromosome-15-syndrome,C3711376,T047,Disorders
Is isodicentric chromosome 15 syndrome inherited ?,0000531-4,inheritance,Isodicentric chromosome 15 syndrome is usually not inherited. The chromosomal change that causes the disorder typically occurs as a random event during the formation of reproductive cells (eggs or sperm) in a parent of the affected individual. Most affected individuals have no history of the disorder in their family.,isodicentric chromosome 15 syndrome,0000531,GHR,https://ghr.nlm.nih.gov/condition/isodicentric-chromosome-15-syndrome,C3711376,T047,Disorders
What are the treatments for isodicentric chromosome 15 syndrome ?,0000531-5,treatment,These resources address the diagnosis or management of isodicentric chromosome 15 syndrome:  - Autism Speaks: How is Autism Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,isodicentric chromosome 15 syndrome,0000531,GHR,https://ghr.nlm.nih.gov/condition/isodicentric-chromosome-15-syndrome,C3711376,T047,Disorders
What is (are) isolated Duane retraction syndrome ?,0000532-1,information,"Isolated Duane retraction syndrome is a disorder of eye movement. This condition prevents outward movement of the eye (toward the ear), and in some cases may also limit inward eye movement (toward the nose). As the eye moves inward, the eyelids partially close and the eyeball pulls back (retracts) into its socket. Most commonly, only one eye is affected. About 10 percent of people with isolated Duane retraction syndrome develop amblyopia (""lazy eye""), a condition that causes vision loss in the affected eye.  About 70 percent of all cases of Duane retraction syndrome are isolated, which means they occur without other signs and symptoms. Duane retraction syndrome can also occur as part of syndromes that affect other areas of the body. For example, Duane-radial ray syndrome is characterized by this eye disorder in conjunction with abnormalities of bones in the arms and hands.  Researchers have identified three forms of isolated Duane retraction syndrome, designated types I, II, and III. The types vary in which eye movements are most severely restricted (inward, outward, or both). All three types are characterized by retraction of the eyeball as the eye moves inward.",isolated Duane retraction syndrome,0000532,GHR,https://ghr.nlm.nih.gov/condition/isolated-duane-retraction-syndrome,C0013261,T047,Disorders
How many people are affected by isolated Duane retraction syndrome ?,0000532-2,frequency,"Isolated Duane retraction syndrome affects an estimated 1 in 1,000 people worldwide. This condition accounts for 1 percent to 5 percent of all cases of abnormal eye alignment (strabismus). For unknown reasons, isolated Duane syndrome affects females more often than males.",isolated Duane retraction syndrome,0000532,GHR,https://ghr.nlm.nih.gov/condition/isolated-duane-retraction-syndrome,C0013261,T047,Disorders
What are the genetic changes related to isolated Duane retraction syndrome ?,0000532-3,genetic changes,"In most people with isolated Duane retraction syndrome, the cause of the condition is unknown. However, researchers have identified mutations in one gene, CHN1, that cause the disorder in a small number of families. The CHN1 gene provides instructions for making a protein that is involved in the early development of the nervous system. Specifically, the protein appears to be critical for the formation of nerves that control several of the muscles surrounding the eyes (extraocular muscles). Mutations in the CHN1 gene disrupt the normal development of these nerves and the extraocular muscles needed for side-to-side eye movement. Abnormal function of these muscles leads to restricted eye movement and related problems with vision.",isolated Duane retraction syndrome,0000532,GHR,https://ghr.nlm.nih.gov/condition/isolated-duane-retraction-syndrome,C0013261,T047,Disorders
Is isolated Duane retraction syndrome inherited ?,0000532-4,inheritance,"Isolated Duane retraction syndrome usually occurs in people with no history of the disorder in their family. These cases are described as simplex, and their genetic cause is unknown.  Less commonly, isolated Duane retraction syndrome can run in families. Familial cases most often have an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder. When isolated Duane retraction syndrome is caused by CHN1 mutations, it has an autosomal dominant inheritance pattern.  In a few families with isolated Duane retraction syndrome, the pattern of affected family members suggests autosomal recessive inheritance. In these families, one or more children are affected, although the parents typically have no signs or symptoms of the condition. The parents of children with an autosomal recessive condition are called carriers, which means they carry one mutated copy of a gene in each cell. In affected children, both copies of the gene in each cell are mutated. However, researchers have not discovered the gene or genes responsible for autosomal recessive isolated Duane retraction syndrome.",isolated Duane retraction syndrome,0000532,GHR,https://ghr.nlm.nih.gov/condition/isolated-duane-retraction-syndrome,C0013261,T047,Disorders
What are the treatments for isolated Duane retraction syndrome ?,0000532-5,treatment,These resources address the diagnosis or management of isolated Duane retraction syndrome:  - Gene Review: Gene Review: Duane Syndrome  - Genetic Testing Registry: Duane's syndrome  - MedlinePlus Encyclopedia: Extraocular Muscle Function Testing   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,isolated Duane retraction syndrome,0000532,GHR,https://ghr.nlm.nih.gov/condition/isolated-duane-retraction-syndrome,C0013261,T047,Disorders
What is (are) isolated ectopia lentis ?,0000533-1,information,"Isolated ectopia lentis is a condition that affects the eyes, specifically the positioning of the lens. The lens is a clear structure at the front of the eye that helps focus light. In people with isolated ectopia lentis, the lens in one or both eyes is not centrally positioned as it should be but is off-center (displaced). Isolated ectopia lentis usually becomes apparent in childhood. The lens may drift further off-center over time.  Vision problems are common in isolated ectopia lentis. Affected individuals often have nearsightedness (myopia) and can have an irregular curvature of the lens or a structure that covers the front of the eye (the cornea), which causes blurred vision (astigmatism). They may also develop clouding of the lenses (cataracts) or increased pressure in the eyes (glaucoma) at an earlier age than other adults. In a small number of people with isolated ectopia lentis, tearing of the back lining of the eye (retinal detachment) occurs, which can lead to further vision problems and possible blindness.  In individuals with isolated ectopia lentis, each eye can be affected differently. In addition, the eye problems vary among affected individuals, even those within the same family.  Ectopia lentis is classified as isolated when it occurs alone without signs and symptoms affecting other body systems. Ectopia lentis can also be classified as syndromic, when it is part of a syndrome that affects multiple parts of the body. Ectopia lentis is a common feature of genetic syndromes such as Marfan syndrome and Weill-Marchesani syndrome.",isolated ectopia lentis,0000533,GHR,https://ghr.nlm.nih.gov/condition/isolated-ectopia-lentis,C0013581,T019,Disorders
How many people are affected by isolated ectopia lentis ?,0000533-2,frequency,"The prevalence of isolated ectopia lentis is unknown. In Denmark, an estimated 6.4 per 100,000 individuals have ectopia lentis, but a large proportion of these cases (about 75 percent) are syndromic.",isolated ectopia lentis,0000533,GHR,https://ghr.nlm.nih.gov/condition/isolated-ectopia-lentis,C0013581,T019,Disorders
What are the genetic changes related to isolated ectopia lentis ?,0000533-3,genetic changes,"Mutations in the FBN1 or ADAMTSL4 gene cause isolated ectopia lentis. These genes provide instructions for making proteins that are necessary for the formation of threadlike filaments called microfibrils. Microfibrils provide support to many tissues, including the lenses of the eyes, which are held in position by these filaments.  Mutations in the FBN1 or ADAMTSL4 gene impair protein function and lead to a decrease in microfibril formation or result in the formation of impaired microfibrils. Without functional microfibrils to anchor the lens in its central position at the front of the eye, the lens becomes displaced. The displaced lens cannot focus light correctly, contributing to the vision problems that are common in people with isolated ectopia lentis.",isolated ectopia lentis,0000533,GHR,https://ghr.nlm.nih.gov/condition/isolated-ectopia-lentis,C0013581,T019,Disorders
Is isolated ectopia lentis inherited ?,0000533-4,inheritance,"When isolated ectopia lentis is caused by mutations in the FBN1 gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  When isolated ectopia lentis is caused by mutations in the ADAMTSL4 gene, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",isolated ectopia lentis,0000533,GHR,https://ghr.nlm.nih.gov/condition/isolated-ectopia-lentis,C0013581,T019,Disorders
What are the treatments for isolated ectopia lentis ?,0000533-5,treatment,"These resources address the diagnosis or management of isolated ectopia lentis:  - Gene Review: Gene Review: ADAMTSL4-Related Eye Disorders  - Genetic Testing Registry: Ectopia lentis, isolated autosomal recessive  - Genetic Testing Registry: Ectopia lentis, isolated, autosomal dominant   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",isolated ectopia lentis,0000533,GHR,https://ghr.nlm.nih.gov/condition/isolated-ectopia-lentis,C0013581,T019,Disorders
What is (are) isolated growth hormone deficiency ?,0000534-1,information,"Isolated growth hormone deficiency is a condition caused by a severe shortage or absence of growth hormone. Growth hormone is a protein that is necessary for the normal growth of the body's bones and tissues. Because they do not have enough of this hormone, people with isolated growth hormone deficiency commonly experience a failure to grow at the expected rate and have unusually short stature. This condition is usually apparent by early childhood.  There are four types of isolated growth hormone deficiency differentiated by the severity of the condition, the gene involved, and the inheritance pattern.  Isolated growth hormone deficiency type IA is caused by an absence of growth hormone and is the most severe of all the types. In people with type IA, growth failure is evident in infancy as affected babies are shorter than normal at birth.  People with isolated growth hormone deficiency type IB produce very low levels of growth hormone. As a result, type IB is characterized by short stature, but this growth failure is typically not as severe as in type IA. Growth failure in people with type IB is usually apparent in early to mid-childhood.  Individuals with isolated growth hormone deficiency type II have very low levels of growth hormone and short stature that varies in severity. Growth failure in these individuals is usually evident in early to mid-childhood. It is estimated that nearly half of the individuals with type II have underdevelopment of the pituitary gland (pituitary hypoplasia). The pituitary gland is located at the base of the brain and produces many hormones, including growth hormone.  Isolated growth hormone deficiency type III is similar to type II in that affected individuals have very low levels of growth hormone and short stature that varies in severity. Growth failure in type III is usually evident in early to mid-childhood. People with type III may also have a weakened immune system and are prone to frequent infections. They produce very few B cells, which are specialized white blood cells that help protect the body against infection (agammaglobulinemia).",isolated growth hormone deficiency,0000534,GHR,https://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency,C3714796,T047,Disorders
How many people are affected by isolated growth hormone deficiency ?,0000534-2,frequency,"The incidence of isolated growth hormone deficiency is estimated to be 1 in 4,000 to 10,000 individuals worldwide.",isolated growth hormone deficiency,0000534,GHR,https://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency,C3714796,T047,Disorders
What are the genetic changes related to isolated growth hormone deficiency ?,0000534-3,genetic changes,"Isolated growth hormone deficiency is caused by mutations in one of at least three genes. Isolated growth hormone deficiency types IA and II are caused by mutations in the GH1 gene. Type IB is caused by mutations in either the GH1 or GHRHR gene. Type III is caused by mutations in the BTK gene.  The GH1 gene provides instructions for making the growth hormone protein. Growth hormone is produced in the pituitary gland and plays a major role in promoting the body's growth. Growth hormone also plays a role in various chemical reactions (metabolic processes) in the body. Mutations in the GH1 gene prevent or impair the production of growth hormone. Without sufficient growth hormone, the body fails to grow at its normal rate, resulting in slow growth and short stature as seen in isolated growth hormone deficiency types IA, IB, and II.  The GHRHR gene provides instructions for making a protein called the growth hormone releasing hormone receptor. This receptor attaches (binds) to a molecule called growth hormone releasing hormone. The binding of growth hormone releasing hormone to the receptor triggers the production of growth hormone and its release from the pituitary gland. Mutations in the GHRHR gene impair the production or release of growth hormone. The resulting shortage of growth hormone prevents the body from growing at the expected rate. Decreased growth hormone activity due to GHRHR gene mutations is responsible for many cases of isolated growth hormone deficiency type IB.  The BTK gene provides instructions for making a protein called Bruton tyrosine kinase (BTK), which is essential for the development and maturation of immune system cells called B cells. The BTK protein transmits important chemical signals that instruct B cells to mature and produce special proteins called antibodies. Antibodies attach to specific foreign particles and germs, marking them for destruction. It is unknown how mutations in the BTK gene contribute to short stature in people with isolated growth hormone deficiency type III.  Some people with isolated growth hormone deficiency do not have mutations in the GH1, GHRHR, or BTK genes. In these individuals, the cause of the condition is unknown. When this condition does not have an identified genetic cause, it is known as idiopathic isolated growth hormone deficiency.",isolated growth hormone deficiency,0000534,GHR,https://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency,C3714796,T047,Disorders
Is isolated growth hormone deficiency inherited ?,0000534-4,inheritance,"Isolated growth hormone deficiency can have different inheritance patterns depending on the type of the condition.  Isolated growth hormone deficiency types IA and IB are inherited in an autosomal recessive pattern, which means both copies of the GH1 or GHRHR gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Isolated growth hormone deficiency type II can be inherited in an autosomal dominant pattern, which means a mutation in one copy of the GH1 gene in each cell is sufficient to cause the disorder. This condition can also result from new mutations in the GH1 gene and occur in people with no history of the disorder in their family.  Isolated growth hormone deficiency type III, caused by mutations in the BTK gene, is inherited in an X-linked recessive pattern. The BTK gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",isolated growth hormone deficiency,0000534,GHR,https://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency,C3714796,T047,Disorders
What are the treatments for isolated growth hormone deficiency ?,0000534-5,treatment,These resources address the diagnosis or management of isolated growth hormone deficiency:  - Genetic Testing Registry: Ateleiotic dwarfism  - Genetic Testing Registry: Autosomal dominant isolated somatotropin deficiency  - Genetic Testing Registry: Isolated growth hormone deficiency type 1B  - Genetic Testing Registry: X-linked agammaglobulinemia with growth hormone deficiency  - MedlinePlus Encyclopedia: Growth Hormone Test   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,isolated growth hormone deficiency,0000534,GHR,https://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency,C3714796,T047,Disorders
What is (are) isolated lissencephaly sequence ?,0000537-1,information,"Isolated lissencephaly sequence (ILS) is a condition that affects brain development before birth. Normally, the cells that make up the exterior of the brain (cerebral cortex) are well-organized, multi-layered, and arranged into many folds and grooves (gyri). In people with ILS, the cells of the cerebral cortex are disorganized, and the brain surface is abnormally smooth with an absence (agyria) or reduction (pachygyria) of folds and grooves. In most cases, these abnormalities impair brain growth, causing the brain to be smaller than normal (microcephaly). This underdevelopment of the brain causes severe intellectual disability, delayed development, and recurrent seizures (epilepsy) in individuals with ILS.  More than 90 percent of individuals with ILS develop epilepsy, often within the first year of life. Up to 80 percent of infants with ILS have a type of seizure called infantile spasms, these seizures can be severe enough to cause brain dysfunction (epileptic encephalopathy). After the first months of life, most children with ILS develop a variety of seizure types, including persisting infantile spasms, short periods of loss of consciousness (absence seizures); sudden episodes of weak muscle tone (drop attacks); rapid, uncontrolled muscle jerks (myoclonic seizures); and episodes of muscle rigidity, convulsions, and loss of consciousness (tonic-clonic seizures).  Infants with ILS may have poor muscle tone (hypotonia) and difficulty feeding, which leads to poor growth overall. Hypotonia also affects the muscles used for breathing, which often causes breathing problems that can lead to a life-threatening bacterial lung infection known as aspiration pneumonia. Children with ILS often develop muscle stiffness (spasticity) in their arms and legs and an abnormal side-to-side curvature of the spine (scoliosis). Rarely, the muscle stiffness will progress to paralysis (spastic paraplegia). Individuals with ILS cannot walk and rarely crawl. Most children with ILS do not develop communication skills.",isolated lissencephaly sequence,0000537,GHR,https://ghr.nlm.nih.gov/condition/isolated-lissencephaly-sequence,C0266463,T019,Disorders
How many people are affected by isolated lissencephaly sequence ?,0000537-2,frequency,"ILS affects approximately 1 in 100,000 newborns.",isolated lissencephaly sequence,0000537,GHR,https://ghr.nlm.nih.gov/condition/isolated-lissencephaly-sequence,C0266463,T019,Disorders
What are the genetic changes related to isolated lissencephaly sequence ?,0000537-3,genetic changes,"Mutations in the PAFAH1B1, DCX, or TUBA1A gene can cause ILS. PAFAH1B1 gene mutations are responsible for over half of ILS cases; DCX gene mutations cause about 10 percent of cases; and TUBA1A gene mutations cause a small percentage of ILS. These genes provide instructions for making proteins that are involved in the movement (migration) of nerve cells (neurons) to their proper locations in the developing brain. Neuronal migration is dependent on cell structures called microtubules. Microtubules are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). Microtubules form scaffolding within the cell that elongates in a specific direction, altering the cytoskeleton and moving the neuron. The protein produced from the TUBA1A gene is a component of microtubules. The proteins produced from the DCX and PAFAH1B1 genes promote neuronal migration by interacting with microtubules.  Mutations in any of these three genes impair the function of microtubules and the normal migration of neurons during fetal development. As a result, the layers of the cerebral cortex are disorganized and the normal folds and grooves of the brain do not form. This impairment of brain development leads to the smooth brain appearance and the resulting neurological problems characteristic of ILS.  Some individuals with ILS do not have an identified mutation in any of these three genes; the cause of the condition in these individuals may be unidentified mutations in other genes that affect neuronal migration or other unknown factors.",isolated lissencephaly sequence,0000537,GHR,https://ghr.nlm.nih.gov/condition/isolated-lissencephaly-sequence,C0266463,T019,Disorders
Is isolated lissencephaly sequence inherited ?,0000537-4,inheritance,"The inheritance pattern of ILS depends on the gene involved.  When ILS is caused by mutations in the PAFAH1B1 or TUBA1A gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  When mutations in the DCX gene cause ILS, it is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), one altered copy of the DCX gene in each cell is sufficient to cause the condition. In females, who have two copies of the X chromosome, one altered copy of the DCX gene in each cell can lead to a less severe condition in females called subcortical band heterotopia, or may cause no symptoms at all. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",isolated lissencephaly sequence,0000537,GHR,https://ghr.nlm.nih.gov/condition/isolated-lissencephaly-sequence,C0266463,T019,Disorders
What are the treatments for isolated lissencephaly sequence ?,0000537-5,treatment,"These resources address the diagnosis or management of isolated lissencephaly sequence:  - Gene Review: Gene Review: DCX-Related Disorders  - Gene Review: Gene Review: LIS1-Associated Lissencephaly/Subcortical Band Heterotopia  - Gene Review: Gene Review: Tubulinopathies Overview  - Genetic Testing Registry: Lissencephaly 1  - Genetic Testing Registry: Lissencephaly 3  - Genetic Testing Registry: Lissencephaly, X-linked   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",isolated lissencephaly sequence,0000537,GHR,https://ghr.nlm.nih.gov/condition/isolated-lissencephaly-sequence,C0266463,T019,Disorders
What is (are) isolated Pierre Robin sequence ?,0000538-1,information,"Pierre Robin sequence is a set of abnormalities affecting the head and face, consisting of a small lower jaw (micrognathia), a tongue that is placed further back than normal (glossoptosis), and an opening in the roof of the mouth (a cleft palate). This condition is described as a ""sequence"" because one of its features, an underdeveloped lower jaw (mandible), sets off a sequence of events before birth that cause the other signs and symptoms. Specifically, having an abnormally small jaw affects placement of the tongue and formation of the palate, leading to glossoptosis and cleft palate.  The combination of features characteristic of Pierre Robin sequence can lead to difficulty breathing and problems eating early in life. As a result, some affected babies have an inability to grow and gain weight at the expected rate (failure to thrive). In some children with Pierre Robin sequence, growth of the mandible catches up, and these individuals have normal-sized chins.  Some people have Pierre Robin sequence as part of a syndrome that affects other organs and tissues in the body, such as campomelic dysplasia or Stickler syndrome. These instances are described as syndromic. When Pierre Robin sequence occurs by itself, it is described as nonsyndromic or isolated. Approximately 20 to 40 percent of cases of Pierre Robin sequence are isolated.",isolated Pierre Robin sequence,0000538,GHR,https://ghr.nlm.nih.gov/condition/isolated-pierre-robin-sequence,C0031900,T019,Disorders
How many people are affected by isolated Pierre Robin sequence ?,0000538-2,frequency,"Isolated Pierre Robin sequence affects an estimated 1 in 8,500 to 14,000 people.",isolated Pierre Robin sequence,0000538,GHR,https://ghr.nlm.nih.gov/condition/isolated-pierre-robin-sequence,C0031900,T019,Disorders
What are the genetic changes related to isolated Pierre Robin sequence ?,0000538-3,genetic changes,"Changes in the DNA near the SOX9 gene are the most common genetic cause of isolated Pierre Robin sequence. It is likely that changes in other genes, some of which have not been identified, also cause isolated Pierre Robin sequence.  The SOX9 gene provides instructions for making a protein that plays a critical role in the formation of many different tissues and organs during embryonic development. The SOX9 protein regulates the activity of other genes, especially those that are important for development of the skeleton, including the mandible.  The genetic changes associated with isolated Pierre Robin sequence occur near the SOX9 gene. These abnormalities are thought to disrupt regions of DNA called enhancers that normally regulate the activity of the SOX9 gene, reducing SOX9 gene activity. As a result, the SOX9 protein cannot properly control the genes essential for normal development of the lower jaw, causing micrognathia, and consequently, glossoptosis and cleft palate.",isolated Pierre Robin sequence,0000538,GHR,https://ghr.nlm.nih.gov/condition/isolated-pierre-robin-sequence,C0031900,T019,Disorders
Is isolated Pierre Robin sequence inherited ?,0000538-4,inheritance,"Isolated Pierre Robin sequence is usually not inherited. It typically results from new genetic changes and occurs in people with no history of the disorder in their family. When the condition is inherited, it follows an autosomal dominant pattern, which means one copy of the altered DNA in each cell is sufficient to cause the disorder.",isolated Pierre Robin sequence,0000538,GHR,https://ghr.nlm.nih.gov/condition/isolated-pierre-robin-sequence,C0031900,T019,Disorders
What are the treatments for isolated Pierre Robin sequence ?,0000538-5,treatment,These resources address the diagnosis or management of isolated Pierre Robin sequence:  - Boston Children's Hospital: Cleft Lip and Cleft Palate Treatment and Care  - Genetic Testing Registry: Robin sequence  - Seattle Children's Hospital: Robin Sequence Treatments   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,isolated Pierre Robin sequence,0000538,GHR,https://ghr.nlm.nih.gov/condition/isolated-pierre-robin-sequence,C0031900,T019,Disorders
What is (are) isovaleric acidemia ?,0000539-1,information,"Isovaleric acidemia is a rare disorder in which the body is unable to process certain proteins properly. It is classified as an organic acid disorder, which is a condition that leads to an abnormal buildup of particular acids known as organic acids. Abnormal levels of organic acids in the blood (organic acidemia), urine (organic aciduria), and tissues can be toxic and can cause serious health problems.  Normally, the body breaks down proteins from food into smaller parts called amino acids. Amino acids can be further processed to provide energy for growth and development. People with isovaleric acidemia have inadequate levels of an enzyme that helps break down a particular amino acid called leucine.  Health problems related to isovaleric acidemia range from very mild to life-threatening. In severe cases, the features of isovaleric acidemia become apparent within a few days after birth. The initial symptoms include poor feeding, vomiting, seizures, and lack of energy (lethargy). These symptoms sometimes progress to more serious medical problems, including seizures, coma, and possibly death. A characteristic sign of isovaleric acidemia is a distinctive odor of sweaty feet during acute illness. This odor is caused by the buildup of a compound called isovaleric acid in affected individuals.  In other cases, the signs and symptoms of isovaleric acidemia appear during childhood and may come and go over time. Children with this condition may fail to gain weight and grow at the expected rate (failure to thrive) and often have delayed development. In these children, episodes of more serious health problems can be triggered by prolonged periods without food (fasting), infections, or eating an increased amount of protein-rich foods.  Some people with gene mutations that cause isovaleric acidemia are asymptomatic, which means they never experience any signs or symptoms of the condition.",isovaleric acidemia,0000539,GHR,https://ghr.nlm.nih.gov/condition/isovaleric-acidemia,C0268575,T047,Disorders
How many people are affected by isovaleric acidemia ?,0000539-2,frequency,"Isovaleric acidemia is estimated to affect at least 1 in 250,000 people in the United States.",isovaleric acidemia,0000539,GHR,https://ghr.nlm.nih.gov/condition/isovaleric-acidemia,C0268575,T047,Disorders
What are the genetic changes related to isovaleric acidemia ?,0000539-3,genetic changes,"Mutations in the IVD gene cause isovaleric acidemia.  The IVD gene provides instructions for making an enzyme that plays an essential role in breaking down proteins from the diet. Specifically, this enzyme helps process the amino acid leucine, which is part of many proteins. If a mutation in the IVD gene reduces or eliminates the activity of this enzyme, the body is unable to break down leucine properly. As a result, an organic acid called isovaleric acid and related compounds build up to harmful levels in the body. This buildup damages the brain and nervous system, causing serious health problems.",isovaleric acidemia,0000539,GHR,https://ghr.nlm.nih.gov/condition/isovaleric-acidemia,C0268575,T047,Disorders
Is isovaleric acidemia inherited ?,0000539-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",isovaleric acidemia,0000539,GHR,https://ghr.nlm.nih.gov/condition/isovaleric-acidemia,C0268575,T047,Disorders
What are the treatments for isovaleric acidemia ?,0000539-5,treatment,These resources address the diagnosis or management of isovaleric acidemia:  - Baby's First Test  - Genetic Testing Registry: Isovaleryl-CoA dehydrogenase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,isovaleric acidemia,0000539,GHR,https://ghr.nlm.nih.gov/condition/isovaleric-acidemia,C0268575,T047,Disorders
What is (are) Jackson-Weiss syndrome ?,0000540-1,information,"Jackson-Weiss syndrome is a genetic disorder characterized by foot abnormalities and the premature fusion of certain skull bones (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face.  Many of the characteristic facial features of Jackson-Weiss syndrome result from premature fusion of the skull bones. Abnormal growth of these bones leads to a misshapen skull, widely spaced eyes, and a bulging forehead.  Foot abnormalities are the most consistent features of Jackson-Weiss syndrome. The first (big) toes are short and wide, and they bend away from the other toes. Additionally, the bones of some toes may be fused together (syndactyly) or abnormally shaped. The hands are almost always normal.  People with Jackson-Weiss syndrome usually have normal intelligence and a normal life span.",Jackson-Weiss syndrome,0000540,GHR,https://ghr.nlm.nih.gov/condition/jackson-weiss-syndrome,C0795998,T047,Disorders
How many people are affected by Jackson-Weiss syndrome ?,0000540-2,frequency,Jackson-Weiss syndrome is a rare genetic disorder; its incidence is unknown.,Jackson-Weiss syndrome,0000540,GHR,https://ghr.nlm.nih.gov/condition/jackson-weiss-syndrome,C0795998,T047,Disorders
What are the genetic changes related to Jackson-Weiss syndrome ?,0000540-3,genetic changes,"Mutations in the FGFR2 gene cause Jackson-Weiss syndrome. This gene provides instructions for making a protein called fibroblast growth factor receptor 2. Among its multiple functions, this protein signals immature cells to become bone cells during embryonic development. A mutation in a specific part of the FGFR2 gene overstimulates signaling by the FGFR2 protein, which promotes the premature fusion of skull bones and affects the development of bones in the feet.",Jackson-Weiss syndrome,0000540,GHR,https://ghr.nlm.nih.gov/condition/jackson-weiss-syndrome,C0795998,T047,Disorders
Is Jackson-Weiss syndrome inherited ?,0000540-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Jackson-Weiss syndrome,0000540,GHR,https://ghr.nlm.nih.gov/condition/jackson-weiss-syndrome,C0795998,T047,Disorders
What are the treatments for Jackson-Weiss syndrome ?,0000540-5,treatment,These resources address the diagnosis or management of Jackson-Weiss syndrome:  - Gene Review: Gene Review: FGFR-Related Craniosynostosis Syndromes  - Genetic Testing Registry: Jackson-Weiss syndrome  - MedlinePlus Encyclopedia: Craniosynostosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Jackson-Weiss syndrome,0000540,GHR,https://ghr.nlm.nih.gov/condition/jackson-weiss-syndrome,C0795998,T047,Disorders
What is (are) Jacobsen syndrome ?,0000541-1,information,"Jacobsen syndrome is a condition caused by a loss of genetic material from chromosome 11. Because this deletion occurs at the end (terminus) of the long (q) arm of chromosome 11, Jacobsen syndrome is also known as 11q terminal deletion disorder.  The signs and symptoms of Jacobsen syndrome vary considerably. Most affected individuals have delayed development, including the development of speech and motor skills (such as sitting, standing, and walking). Most also have cognitive impairment and learning difficulties. Behavioral problems have been reported, including compulsive behavior (such as shredding paper), a short attention span, and easy distractibility. Many people with Jacobsen syndrome have been diagnosed with attention deficit-hyperactivity disorder (ADHD). Jacobsen syndrome is also associated with an increased likelihood of autism spectrum disorders, which are characterized by impaired communication and socialization skills.  Jacobsen syndrome is also characterized by distinctive facial features. These include small and low-set ears, widely set eyes (hypertelorism) with droopy eyelids (ptosis), skin folds covering the inner corner of the eyes (epicanthal folds), a broad nasal bridge, downturned corners of the mouth, a thin upper lip, and a small lower jaw. Affected individuals often have a large head size (macrocephaly) and a skull abnormality called trigonocephaly, which gives the forehead a pointed appearance.  More than 90 percent of people with Jacobsen syndrome have a bleeding disorder called Paris-Trousseau syndrome. This condition causes a lifelong risk of abnormal bleeding and easy bruising. Paris-Trousseau syndrome is a disorder of platelets, which are blood cell fragments that are necessary for blood clotting.  Other features of Jacobsen syndrome can include heart defects, feeding difficulties in infancy, short stature, frequent ear and sinus infections, and skeletal abnormalities. The disorder can also affect the digestive system, kidneys, and genitalia. The life expectancy of people with Jacobsen syndrome is unknown, although affected individuals have lived into adulthood.",Jacobsen syndrome,0000541,GHR,https://ghr.nlm.nih.gov/condition/jacobsen-syndrome,C0795841,T047,Disorders
How many people are affected by Jacobsen syndrome ?,0000541-2,frequency,"The estimated incidence of Jacobsen syndrome is 1 in 100,000 newborns. More than 200 affected individuals have been reported.",Jacobsen syndrome,0000541,GHR,https://ghr.nlm.nih.gov/condition/jacobsen-syndrome,C0795841,T047,Disorders
What are the genetic changes related to Jacobsen syndrome ?,0000541-3,genetic changes,"Jacobsen syndrome is caused by a deletion of genetic material at the end of the long (q) arm of chromosome 11. The size of the deletion varies among affected individuals, with most affected people missing 5 million to 16 million DNA building blocks (also written as 5 Mb to 16 Mb). In almost all affected people, the deletion includes the tip of chromosome 11. Larger deletions tend to cause more severe signs and symptoms than smaller deletions.  The features of Jacobsen syndrome are likely related to the loss of multiple genes on chromosome 11. Depending on its size, the deleted region can contain from about 170 to more than 340 genes. Many of these genes have not been well characterized. However, genes in this region appear to be critical for the normal development of many parts of the body, including the brain, facial features, and heart. Only a few genes have been studied as possible contributors to the specific features of Jacobsen syndrome; researchers are working to determine which additional genes may be associated with this condition.",Jacobsen syndrome,0000541,GHR,https://ghr.nlm.nih.gov/condition/jacobsen-syndrome,C0795841,T047,Disorders
Is Jacobsen syndrome inherited ?,0000541-4,inheritance,"Most cases of Jacobsen syndrome are not inherited. They result from a chromosomal deletion that occurs as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family, although they can pass the chromosome deletion to their children.  Between 5 and 10 percent of people with Jacobsen syndrome inherit the chromosome abnormality from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which a segment from chromosome 11 has traded places with a segment from another chromosome. In a balanced translocation, no genetic material is gained or lost. Balanced translocations usually do not cause any health problems; however, they can become unbalanced as they are passed to the next generation.  Children who inherit an unbalanced translocation can have a chromosomal rearrangement with some missing genetic material and some extra genetic material. Individuals with Jacobsen syndrome who inherit an unbalanced translocation are missing genetic material from the end of the long arm of chromosome 11 and have extra genetic material from another chromosome. These chromosomal changes result in the health problems characteristic of this disorder.",Jacobsen syndrome,0000541,GHR,https://ghr.nlm.nih.gov/condition/jacobsen-syndrome,C0795841,T047,Disorders
What are the treatments for Jacobsen syndrome ?,0000541-5,treatment,These resources address the diagnosis or management of Jacobsen syndrome:  - 11q Research & Resource Group: Concerns and Recommendations  - Genetic Testing Registry: 11q partial monosomy syndrome  - Unique: Chromosome 11q Deletion Disorder: Jacobsen Syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Jacobsen syndrome,0000541,GHR,https://ghr.nlm.nih.gov/condition/jacobsen-syndrome,C0795841,T047,Disorders
What is (are) Jervell and Lange-Nielsen syndrome ?,0000542-1,information,"Jervell and Lange-Nielsen syndrome is a condition that causes profound hearing loss from birth and a disruption of the heart's normal rhythm (arrhythmia). This disorder is a form of long QT syndrome, which is a heart condition that causes the heart (cardiac) muscle to take longer than usual to recharge between beats. Beginning in early childhood, the irregular heartbeats increase the risk of fainting (syncope) and sudden death.",Jervell and Lange-Nielsen syndrome,0000542,GHR,https://ghr.nlm.nih.gov/condition/jervell-and-lange-nielsen-syndrome,C0022387,T047,Disorders
How many people are affected by Jervell and Lange-Nielsen syndrome ?,0000542-2,frequency,"Jervell and Lange-Nielsen syndrome is uncommon; it affects an estimated 1.6 to 6 per 1 million people worldwide. This condition has a higher prevalence in Denmark, where it affects at least 1 in 200,000 people.",Jervell and Lange-Nielsen syndrome,0000542,GHR,https://ghr.nlm.nih.gov/condition/jervell-and-lange-nielsen-syndrome,C0022387,T047,Disorders
What are the genetic changes related to Jervell and Lange-Nielsen syndrome ?,0000542-3,genetic changes,"Mutations in the KCNE1 and KCNQ1 genes cause Jervell and Lange-Nielsen syndrome.  The KCNE1 and KCNQ1 genes provide instructions for making proteins that work together to form a channel across cell membranes. These channels transport positively charged potassium atoms (ions) out of cells. The movement of potassium ions through these channels is critical for maintaining the normal functions of inner ear structures and cardiac muscle.  About 90 percent of cases of Jervell and Lange-Nielsen syndrome are caused by mutations in the KCNQ1 gene; KCNE1 mutations are responsible for the remaining cases. Mutations in these genes alter the usual structure and function of potassium channels or prevent the assembly of normal channels. These changes disrupt the flow of potassium ions in the inner ear and in cardiac muscle, leading to hearing loss and an irregular heart rhythm characteristic of Jervell and Lange-Nielsen syndrome.",Jervell and Lange-Nielsen syndrome,0000542,GHR,https://ghr.nlm.nih.gov/condition/jervell-and-lange-nielsen-syndrome,C0022387,T047,Disorders
Is Jervell and Lange-Nielsen syndrome inherited ?,0000542-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of a child with an autosomal recessive disorder are not affected, but are carriers of one copy of the mutated gene. Some carriers of a KCNQ1 or KCNE1 mutation have signs and symptoms affecting the heart, but their hearing is usually normal.",Jervell and Lange-Nielsen syndrome,0000542,GHR,https://ghr.nlm.nih.gov/condition/jervell-and-lange-nielsen-syndrome,C0022387,T047,Disorders
What are the treatments for Jervell and Lange-Nielsen syndrome ?,0000542-5,treatment,These resources address the diagnosis or management of Jervell and Lange-Nielsen syndrome:  - Gene Review: Gene Review: Jervell and Lange-Nielsen Syndrome  - Genetic Testing Registry: Jervell and Lange-Nielsen syndrome  - MedlinePlus Encyclopedia: Arrhythmias   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Jervell and Lange-Nielsen syndrome,0000542,GHR,https://ghr.nlm.nih.gov/condition/jervell-and-lange-nielsen-syndrome,C0022387,T047,Disorders
What is (are) Joubert syndrome ?,0000543-1,information,"Joubert syndrome is a disorder that affects many parts of the body. The signs and symptoms of this condition vary among affected individuals, even among members of the same family.  The hallmark feature of Joubert syndrome is a brain abnormality called the molar tooth sign, which can be seen on brain imaging studies such as magnetic resonance imaging (MRI). This sign results from the abnormal development of regions near the back of the brain called the cerebellar vermis and the brainstem. The molar tooth sign got its name because the characteristic brain abnormalities resemble the cross-section of a molar tooth when seen on an MRI.  Most infants with Joubert syndrome have weak muscle tone (hypotonia) in infancy, which evolves into difficulty coordinating movements (ataxia) in early childhood. Other characteristic features of the condition include episodes of unusually fast or slow breathing in infancy and abnormal eye movements. Most affected individuals have delayed development and intellectual disability, which range from mild to severe. Distinctive facial features are also characteristic of Joubert syndrome; these include a broad forehead, arched eyebrows, droopy eyelids (ptosis), widely spaced eyes, low-set ears, and a triangle-shaped mouth.  Joubert syndrome can include a broad range of additional signs and symptoms. The condition is sometimes associated with other eye abnormalities (such as retinal dystrophy, which can cause vision loss), kidney disease, liver disease, skeletal abnormalities (such as the presence of extra fingers and toes), and hormone (endocrine) problems. When the characteristic features of Joubert syndrome occur in combination with one or more of these additional signs and symptoms, researchers refer to the condition as ""Joubert syndrome and related disorders (JSRD).""",Joubert syndrome,0000543,GHR,https://ghr.nlm.nih.gov/condition/joubert-syndrome,C0431399,T047,Disorders
How many people are affected by Joubert syndrome ?,0000543-2,frequency,"Joubert syndrome is estimated to affect between 1 in 80,000 and 1 in 100,000 newborns. However, this estimate may be too low because Joubert syndrome has such a large range of possible features and is likely underdiagnosed.",Joubert syndrome,0000543,GHR,https://ghr.nlm.nih.gov/condition/joubert-syndrome,C0431399,T047,Disorders
What are the genetic changes related to Joubert syndrome ?,0000543-3,genetic changes,"Joubert syndrome and related disorders can be caused by mutations in at least 10 genes. The proteins produced from these genes are known or suspected to play roles in cell structures called cilia. Cilia are microscopic, finger-like projections that stick out from the surface of cells and are involved in chemical signaling. Cilia are important for the structure and function of many types of cells, including brain cells (neurons) and certain cells in the kidneys and liver. Cilia are also necessary for the perception of sensory input (such as sight, hearing, and smell).  Mutations in the genes associated with Joubert syndrome and related disorders lead to problems with the structure and function of cilia. Defects in these cell structures probably disrupt important chemical signaling pathways during development. Although researchers believe that defective cilia are responsible for most of the features of these disorders, it remains unclear how they lead to specific developmental abnormalities.  Mutations in the 10 genes known to be associated with Joubert syndrome and related disorders only account for about half of all cases of these conditions. In the remaining cases, the genetic cause is unknown.",Joubert syndrome,0000543,GHR,https://ghr.nlm.nih.gov/condition/joubert-syndrome,C0431399,T047,Disorders
Is Joubert syndrome inherited ?,0000543-4,inheritance,"Joubert syndrome typically has an autosomal recessive pattern of inheritance, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they usually do not show signs and symptoms of the condition.  Rare cases of Joubert syndrome are inherited in an X-linked recessive pattern. In these cases, the causative gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",Joubert syndrome,0000543,GHR,https://ghr.nlm.nih.gov/condition/joubert-syndrome,C0431399,T047,Disorders
What are the treatments for Joubert syndrome ?,0000543-5,treatment,These resources address the diagnosis or management of Joubert syndrome:  - Gene Review: Gene Review: Joubert Syndrome and Related Disorders  - Genetic Testing Registry: Familial aplasia of the vermis  - Genetic Testing Registry: Joubert syndrome 10  - Genetic Testing Registry: Joubert syndrome 2  - Genetic Testing Registry: Joubert syndrome 3  - Genetic Testing Registry: Joubert syndrome 4  - Genetic Testing Registry: Joubert syndrome 5  - Genetic Testing Registry: Joubert syndrome 6  - Genetic Testing Registry: Joubert syndrome 7  - Genetic Testing Registry: Joubert syndrome 8  - Genetic Testing Registry: Joubert syndrome 9   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Joubert syndrome,0000543,GHR,https://ghr.nlm.nih.gov/condition/joubert-syndrome,C0431399,T047,Disorders
What is (are) junctional epidermolysis bullosa ?,0000544-1,information,"Junctional epidermolysis bullosa (JEB) is one of the major forms of epidermolysis bullosa, a group of genetic conditions that cause the skin to be very fragile and to blister easily. Blisters and skin erosions form in response to minor injury or friction, such as rubbing or scratching. Researchers classify junctional epidermolysis bullosa into two main types: Herlitz JEB and non-Herlitz JEB. Although the types differ in severity, their features overlap significantly, and they can be caused by mutations in the same genes.  Herlitz JEB is the more severe form of the condition. From birth or early infancy, affected individuals have blistering over large regions of the body. Blistering also affects the mucous membranes, such as the moist lining of the mouth and digestive tract, which can make it difficult to eat and digest food. As a result, many affected children have chronic malnutrition and slow growth. The extensive blistering leads to scarring and the formation of red, bumpy patches called granulation tissue. Granulation tissue bleeds easily and profusely, making affected infants susceptible to serious infections and loss of necessary proteins, minerals, and fluids. Additionally, a buildup of granulation tissue in the airway can lead to a weak, hoarse cry and difficulty breathing.  Other complications of Herlitz JEB can include fusion of the fingers and toes, abnormalities of the fingernails and toenails, joint deformities (contractures) that restrict movement, and hair loss (alopecia). Because the signs and symptoms of Herlitz JEB are so severe, infants with this condition usually do not survive beyond the first year of life.  The milder form of junctional epidermolysis bullosa is called non-Herlitz JEB. The blistering associated with non-Herlitz JEB may be limited to the hands, feet, knees, and elbows, and it often improves after the newborn period. Other characteristic features of this condition include alopecia, malformed fingernails and toenails, and irregular tooth enamel. Most affected individuals do not have extensive scarring or granulation tissue formation, so breathing difficulties and other severe complications are rare. Non-Herlitz JEB is typically associated with a normal lifespan.",junctional epidermolysis bullosa,0000544,GHR,https://ghr.nlm.nih.gov/condition/junctional-epidermolysis-bullosa,C0079301,T047,Disorders
How many people are affected by junctional epidermolysis bullosa ?,0000544-2,frequency,"Both types of junctional epidermolysis bullosa are rare, affecting fewer than 1 per million people in the United States.",junctional epidermolysis bullosa,0000544,GHR,https://ghr.nlm.nih.gov/condition/junctional-epidermolysis-bullosa,C0079301,T047,Disorders
What are the genetic changes related to junctional epidermolysis bullosa ?,0000544-3,genetic changes,"Junctional epidermolysis bullosa results from mutations in the LAMA3, LAMB3, LAMC2, and COL17A1 genes. Mutations in each of these genes can cause Herlitz JEB or non-Herlitz JEB. LAMB3 gene mutations are the most common, causing about 70 percent of all cases of junctional epidermolysis bullosa.  The LAMA3, LAMB3, and LAMC2 genes each provide instructions for making one part (subunit) of a protein called laminin 332. This protein plays an important role in strengthening and stabilizing the skin by helping to attach the top layer of skin (the epidermis) to underlying layers. Mutations in any of the three laminin 332 genes lead to the production of a defective or nonfunctional version of this protein. Without functional laminin 332, cells in the epidermis are fragile and easily damaged. Friction or other minor trauma can cause the skin layers to separate, leading to the formation of blisters.  The COL17A1 gene provides instructions for making a protein that is used to assemble type XVII collagen. Collagens are molecules that give structure and strength to connective tissues, such as skin, tendons, and ligaments, throughout the body. Type XVII collagen helps attach the epidermis to underlying layers of skin, making the skin strong and flexible. Mutations in the COL17A1 gene prevent the normal formation of collagen XVII. As a result, the skin is less resistant to friction and minor trauma and blisters easily. Most COL17A1 gene mutations cause non-Herlitz JEB, although a few individuals with mutations in this gene have had the more severe Herlitz JEB.",junctional epidermolysis bullosa,0000544,GHR,https://ghr.nlm.nih.gov/condition/junctional-epidermolysis-bullosa,C0079301,T047,Disorders
Is junctional epidermolysis bullosa inherited ?,0000544-4,inheritance,"Both types of junctional epidermolysis bullosa are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",junctional epidermolysis bullosa,0000544,GHR,https://ghr.nlm.nih.gov/condition/junctional-epidermolysis-bullosa,C0079301,T047,Disorders
What are the treatments for junctional epidermolysis bullosa ?,0000544-5,treatment,"These resources address the diagnosis or management of junctional epidermolysis bullosa:  - Epidermolysis Bullosa Center, Cincinnati Children's Hospital Medical Center  - Gene Review: Gene Review: Junctional Epidermolysis Bullosa  - Genetic Testing Registry: Adult junctional epidermolysis bullosa  - Genetic Testing Registry: Epidermolysis bullosa, junctional  - Genetic Testing Registry: Junctional epidermolysis bullosa gravis of Herlitz  - MedlinePlus Encyclopedia: Epidermolysis Bullosa   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",junctional epidermolysis bullosa,0000544,GHR,https://ghr.nlm.nih.gov/condition/junctional-epidermolysis-bullosa,C0079301,T047,Disorders
What is (are) juvenile Batten disease ?,0000545-1,information,"Juvenile Batten disease is an inherited disorder that primarily affects the nervous system. After a few years of normal development, children with this condition develop progressive vision loss, intellectual and motor disability, speech difficulties, and seizures.  Vision impairment is often the first noticeable sign of juvenile Batten disease, beginning between the ages of 4 and 8 years. Vision loss tends to progress rapidly, eventually resulting in blindness.  After vision impairment has begun, children with juvenile Batten disease experience the loss of previously acquired skills (developmental regression), usually beginning with the ability to speak in complete sentences. Affected children also have difficulty learning new information. In addition to the intellectual decline, affected children lose motor skills such as the ability to walk or sit. They also develop movement abnormalities that include rigidity or stiffness, slow or diminished movements (hypokinesia), and stooped posture. Affected children may have recurrent seizures (epilepsy), heart problems, behavioral problems, difficulty sleeping, and problems with attention that begin in mid- to late childhood. Most people with juvenile Batten disease live into their twenties or thirties.  Juvenile Batten disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs). These disorders all affect the nervous system and typically cause progressive problems with vision, movement, and thinking ability. The different types of NCLs are distinguished by the age at which signs and symptoms first appear. Some people refer to the entire group of NCLs as Batten disease, while others limit that designation to the juvenile form of the disorder.",juvenile Batten disease,0000545,GHR,https://ghr.nlm.nih.gov/condition/juvenile-batten-disease,C0751383,T047,Disorders
How many people are affected by juvenile Batten disease ?,0000545-2,frequency,"Juvenile Batten disease is the most common type of NCL, but its exact prevalence is unknown. Collectively, all forms of NCL affect an estimated 1 in 100,000 individuals worldwide. NCLs are more common in Finland, where approximately 1 in 12,500 individuals are affected.",juvenile Batten disease,0000545,GHR,https://ghr.nlm.nih.gov/condition/juvenile-batten-disease,C0751383,T047,Disorders
What are the genetic changes related to juvenile Batten disease ?,0000545-3,genetic changes,"Most cases of juvenile Batten disease are caused by mutations in the CLN3 gene. This gene provides instructions for making a protein whose function is unknown.  It is unclear how mutations in the CLN3 gene lead to the characteristic features of juvenile Batten disease. These mutations somehow disrupt the function of cellular structures called lysosomes. Lysosomes are compartments in the cell that normally digest and recycle different types of molecules. Lysosome malfunction leads to a buildup of fatty substances called lipopigments within these cell structures. These accumulations occur in cells throughout the body, but neurons in the brain seem to be particularly vulnerable to the damage caused by lipopigments. The progressive death of cells, especially in the brain, leads to vision loss, seizures, and intellectual decline in people with juvenile Batten disease.  A small percentage of cases of juvenile Batten disease are caused by mutations in other genes. Many of these genes are involved in lysosomal function, and when mutated, can cause this or other forms of NCL.",juvenile Batten disease,0000545,GHR,https://ghr.nlm.nih.gov/condition/juvenile-batten-disease,C0751383,T047,Disorders
Is juvenile Batten disease inherited ?,0000545-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",juvenile Batten disease,0000545,GHR,https://ghr.nlm.nih.gov/condition/juvenile-batten-disease,C0751383,T047,Disorders
What are the treatments for juvenile Batten disease ?,0000545-5,treatment,These resources address the diagnosis or management of juvenile Batten disease:  - Batten Disease Diagnostic and Clinical Research Center at the University of Rochester Medical Center  - Batten Disease Support and Research Association: Centers of Excellence  - Gene Review: Gene Review: Neuronal Ceroid-Lipofuscinoses  - Genetic Testing Registry: Juvenile neuronal ceroid lipofuscinosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,juvenile Batten disease,0000545,GHR,https://ghr.nlm.nih.gov/condition/juvenile-batten-disease,C0751383,T047,Disorders
What is (are) juvenile hyaline fibromatosis ?,0000546-1,information,"Juvenile hyaline fibromatosis is a disorder that affects the skin, joints, and bones. Individuals with this condition typically begin to develop signs and symptoms within the first few years of life. Juvenile hyaline fibromatosis is characterized by skin bumps that frequently appear on the hands, neck, scalp, ears, and nose. These skin bumps can also develop in joint creases and the genital region. They vary in size and are sometimes painful. Affected individuals usually develop more skin bumps over time.  Juvenile hyaline fibromatosis is also characterized by overgrowth of the gums (gingival hypertrophy) and joint deformities (contractures) that can impair movement. In addition, affected individuals may grow slowly and have bone abnormalities. People with juvenile hyaline fibromatosis typically have severe physical limitations, but most individuals have normal intelligence and live into adulthood.",juvenile hyaline fibromatosis,0000546,GHR,https://ghr.nlm.nih.gov/condition/juvenile-hyaline-fibromatosis,C2745948,T047,Disorders
How many people are affected by juvenile hyaline fibromatosis ?,0000546-2,frequency,The prevalence of juvenile hyaline fibromatosis is unknown. About 70 people with this disorder have been reported.,juvenile hyaline fibromatosis,0000546,GHR,https://ghr.nlm.nih.gov/condition/juvenile-hyaline-fibromatosis,C2745948,T047,Disorders
What are the genetic changes related to juvenile hyaline fibromatosis ?,0000546-3,genetic changes,"Mutations in the ANTXR2 gene (also known as the CMG2 gene) cause juvenile hyaline fibromatosis. The ANTXR2 gene provides instructions for making a protein involved in the formation of tiny blood vessels (capillaries). Researchers believe that the ANTXR2 protein is also important for maintaining the structure of basement membranes, which are thin, sheet-like structures that separate and support cells in many tissues.  The signs and symptoms of juvenile hyaline fibromatosis are caused by the accumulation of a clear (hyaline) substance in different parts of the body. The nature of this substance is not well known, but it is likely made up of protein and sugar molecules. Researchers suspect that mutations in the ANTXR2 gene disrupt the formation of basement membranes, allowing the hyaline substance to leak through and build up in various body tissues.",juvenile hyaline fibromatosis,0000546,GHR,https://ghr.nlm.nih.gov/condition/juvenile-hyaline-fibromatosis,C2745948,T047,Disorders
Is juvenile hyaline fibromatosis inherited ?,0000546-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",juvenile hyaline fibromatosis,0000546,GHR,https://ghr.nlm.nih.gov/condition/juvenile-hyaline-fibromatosis,C2745948,T047,Disorders
What are the treatments for juvenile hyaline fibromatosis ?,0000546-5,treatment,"These resources address the diagnosis or management of juvenile hyaline fibromatosis:  - Gene Review: Gene Review: Hyalinosis, Inherited Systemic  - Genetic Testing Registry: Hyaline fibromatosis syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",juvenile hyaline fibromatosis,0000546,GHR,https://ghr.nlm.nih.gov/condition/juvenile-hyaline-fibromatosis,C2745948,T047,Disorders
What is (are) juvenile idiopathic arthritis ?,0000547-1,information,"Juvenile idiopathic arthritis refers to a group of conditions involving joint inflammation (arthritis) that first appears before the age of 16. This condition is an autoimmune disorder, which means that the immune system malfunctions and attacks the body's organs and tissues, in this case the joints.  Researchers have described seven types of juvenile idiopathic arthritis. The types are distinguished by their signs and symptoms, the number of joints affected, the results of laboratory tests, and the family history.  Systemic juvenile idiopathic arthritis causes inflammation in one or more joints. A high daily fever that lasts at least 2 weeks either precedes or accompanies the arthritis. Individuals with systemic arthritis may also have a skin rash or enlargement of the lymph nodes (lymphadenopathy), liver (hepatomegaly), or spleen (splenomegaly).  Oligoarticular juvenile idiopathic arthritis (also known as oligoarthritis) has no features other than joint inflammation. Oligoarthritis is marked by the occurrence of arthritis in four or fewer joints in the first 6 months of the disease. It is divided into two subtypes depending on the course of disease. If the arthritis is confined to four or fewer joints after 6 months, then the condition is classified as persistent oligoarthritis. If more than four joints are affected after 6 months, this condition is classified as extended oligoarthritis.  Rheumatoid factor positive polyarticular juvenile idiopathic arthritis (also known as polyarthritis, rheumatoid factor positive) causes inflammation in five or more joints within the first 6 months of the disease. Individuals with this condition also have a positive blood test for proteins called rheumatoid factors. This type of arthritis closely resembles rheumatoid arthritis as seen in adults.  Rheumatoid factor negative polyarticular juvenile idiopathic arthritis (also known as polyarthritis, rheumatoid factor negative) is also characterized by arthritis in five or more joints within the first 6 months of the disease. Individuals with this type, however, test negative for rheumatoid factor in the blood.  Psoriatic juvenile idiopathic arthritis involves arthritis that usually occurs in combination with a skin disorder called psoriasis. Psoriasis is a condition characterized by patches of red, irritated skin that are often covered by flaky white scales. Some affected individuals develop psoriasis before arthritis while others first develop arthritis. Other features of psoriatic arthritis include abnormalities of the fingers and nails or eye problems.  Enthesitis-related juvenile idiopathic arthritis is characterized by tenderness where the bone meets a tendon, ligament or other connective tissue. This tenderness, known as enthesitis, accompanies the joint inflammation of arthritis. Enthesitis-related arthritis may also involve inflammation in parts of the body other than the joints.  The last type of juvenile idiopathic arthritis is called undifferentiated arthritis. This classification is given to affected individuals who do not fit into any of the above types or who fulfill the criteria for more than one type of juvenile idiopathic arthritis.",juvenile idiopathic arthritis,0000547,GHR,https://ghr.nlm.nih.gov/condition/juvenile-idiopathic-arthritis,C3495559,T047,Disorders
How many people are affected by juvenile idiopathic arthritis ?,0000547-2,frequency,"The incidence of juvenile idiopathic arthritis in North America and Europe is estimated to be 4 to 16 in 10,000 children. One in 1,000, or approximately 294,000, children in the United States are affected. The most common type of juvenile idiopathic arthritis in the United States is oligoarticular juvenile idiopathic arthritis, which accounts for about half of all cases. For reasons that are unclear, females seem to be affected with juvenile idiopathic arthritis somewhat more frequently than males. However, in enthesitis-related juvenile idiopathic arthritis males are affected more often than females. The incidence of juvenile idiopathic arthritis varies across different populations and ethnic groups.",juvenile idiopathic arthritis,0000547,GHR,https://ghr.nlm.nih.gov/condition/juvenile-idiopathic-arthritis,C3495559,T047,Disorders
What are the genetic changes related to juvenile idiopathic arthritis ?,0000547-3,genetic changes,"Juvenile idiopathic arthritis is thought to arise from a combination of genetic and environmental factors. The term ""idiopathic"" indicates that the specific cause of the disorder is unknown. Its signs and symptoms result from excessive inflammation in and around the joints. Inflammation occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight microbial invaders and facilitate tissue repair. Normally, the body stops the inflammatory response after healing is complete to prevent damage to its own cells and tissues. In people with juvenile idiopathic arthritis, the inflammatory response is prolonged, particularly during movement of the joints. The reasons for this excessive inflammatory response are unclear.  Researchers have identified changes in several genes that may influence the risk of developing juvenile idiopathic arthritis. Many of these genes belong to a family of genes that provide instructions for making a group of related proteins called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Each HLA gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. Certain normal variations of several HLA genes seem to affect the risk of developing juvenile idiopathic arthritis, and the specific type of the condition that a person may have.  Normal variations in several other genes have also been associated with juvenile idiopathic arthritis. Many of these genes are thought to play roles in immune system function. Additional unknown genetic influences and environmental factors, such as infection and other issues that affect immune health, are also likely to influence a person's chances of developing this complex disorder.",juvenile idiopathic arthritis,0000547,GHR,https://ghr.nlm.nih.gov/condition/juvenile-idiopathic-arthritis,C3495559,T047,Disorders
Is juvenile idiopathic arthritis inherited ?,0000547-4,inheritance,"Most cases of juvenile idiopathic arthritis are sporadic, which means they occur in people with no history of the disorder in their family. A small percentage of cases of juvenile idiopathic arthritis have been reported to run in families, although the inheritance pattern of the condition is unclear. A sibling of a person with juvenile idiopathic arthritis has an estimated risk of developing the condition that is about 12 times that of the general population.",juvenile idiopathic arthritis,0000547,GHR,https://ghr.nlm.nih.gov/condition/juvenile-idiopathic-arthritis,C3495559,T047,Disorders
What are the treatments for juvenile idiopathic arthritis ?,0000547-5,treatment,"These resources address the diagnosis or management of juvenile idiopathic arthritis:  - American College of Rheumatology: Arthritis in Children  - Genetic Testing Registry: Rheumatoid arthritis, systemic juvenile   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",juvenile idiopathic arthritis,0000547,GHR,https://ghr.nlm.nih.gov/condition/juvenile-idiopathic-arthritis,C3495559,T047,Disorders
What is (are) juvenile myoclonic epilepsy ?,0000548-1,information,"Juvenile myoclonic epilepsy is a condition characterized by recurrent seizures (epilepsy). This condition begins in childhood or adolescence, usually between ages 12 and 18, and lasts into adulthood. The most common type of seizure in people with this condition is myoclonic seizures, which cause rapid, uncontrolled muscle jerks. People with this condition may also have generalized tonic-clonic seizures (also known as grand mal seizures), which cause muscle rigidity, convulsions, and loss of consciousness. Sometimes, affected individuals have absence seizures, which cause loss of consciousness for a short period that appears as a staring spell. Typically, people with juvenile myoclonic epilepsy develop the characteristic myoclonic seizures in adolescence, then develop generalized tonic-clonic seizures a few years later. Although seizures can happen at any time, they occur most commonly in the morning, shortly after awakening. Seizures can be triggered by a lack of sleep, extreme tiredness, stress, or alcohol consumption.",juvenile myoclonic epilepsy,0000548,GHR,https://ghr.nlm.nih.gov/condition/juvenile-myoclonic-epilepsy,C0270853,T047,Disorders
How many people are affected by juvenile myoclonic epilepsy ?,0000548-2,frequency,"Juvenile myoclonic epilepsy affects an estimated 1 in 1,000 people worldwide. Approximately 5 percent of people with epilepsy have juvenile myoclonic epilepsy.",juvenile myoclonic epilepsy,0000548,GHR,https://ghr.nlm.nih.gov/condition/juvenile-myoclonic-epilepsy,C0270853,T047,Disorders
What are the genetic changes related to juvenile myoclonic epilepsy ?,0000548-3,genetic changes,"The genetics of juvenile myoclonic epilepsy are complex and not completely understood. Mutations in one of several genes can cause or increase susceptibility to this condition. The most studied of these genes are the GABRA1 gene and the EFHC1 gene, although mutations in at least three other genes have been identified in people with this condition. Many people with juvenile myoclonic epilepsy do not have mutations in any of these genes. Changes in other, unidentified genes are likely involved in this condition.  A mutation in the GABRA1 gene has been identified in several members of a large family with juvenile myoclonic epilepsy. The GABRA1 gene provides instructions for making one piece, the alpha-1 (1) subunit, of the GABAA receptor protein. The GABAA receptor acts as a channel that allows negatively charged chlorine atoms (chloride ions) to cross the cell membrane. After infancy, the influx of chloride ions creates an environment in the cell that inhibits signaling between nerve cells (neurons) and prevents the brain from being overloaded with too many signals. Mutations in the GABRA1 gene lead to an altered 1 subunit and a decrease in the number of GABAA receptors available. As a result, the signaling between neurons is not controlled, which can lead to overstimulation of neurons. Researchers believe that the overstimulation of certain neurons in the brain triggers the abnormal brain activity associated with seizures.  Mutations in the EFHC1 gene have been associated with juvenile myoclonic epilepsy in a small number of people. The EFHC1 gene provides instructions for making a protein that also plays a role in neuron activity, although its function is not completely understood. The EFHC1 protein is attached to another protein that acts as a calcium channel. This protein allows positively charged calcium ions to cross the cell membrane. The movement of these ions is critical for normal signaling between neurons. The EFHC1 protein is thought to help regulate the balance of calcium ions inside the cell, although the mechanism is unclear. In addition, studies show that the EFHC1 protein may be involved in the self-destruction of cells. EFHC1 gene mutations reduce the function of the EFHC1 protein. Researchers suggest that this reduction causes an increase in the number of neurons and disrupts the calcium balance. Together, these effects may lead to overstimulation of neurons and trigger seizures.",juvenile myoclonic epilepsy,0000548,GHR,https://ghr.nlm.nih.gov/condition/juvenile-myoclonic-epilepsy,C0270853,T047,Disorders
Is juvenile myoclonic epilepsy inherited ?,0000548-4,inheritance,"The inheritance pattern of juvenile myoclonic epilepsy is not completely understood. When the condition is caused by mutations in the GABRA1 gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. The inheritance pattern of juvenile myoclonic epilepsy caused by mutations in the EFHC1 gene is not known.  Although juvenile myoclonic epilepsy can run in families, many cases occur in people with no family history of the disorder.",juvenile myoclonic epilepsy,0000548,GHR,https://ghr.nlm.nih.gov/condition/juvenile-myoclonic-epilepsy,C0270853,T047,Disorders
What are the treatments for juvenile myoclonic epilepsy ?,0000548-5,treatment,"These resources address the diagnosis or management of juvenile myoclonic epilepsy:  - Genetic Testing Registry: Epilepsy with grand mal seizures on awakening  - Genetic Testing Registry: Epilepsy, idiopathic generalized 10  - Genetic Testing Registry: Epilepsy, idiopathic generalized 9  - Genetic Testing Registry: Epilepsy, juvenile myoclonic 5  - Genetic Testing Registry: Epilepsy, juvenile myoclonic 9  - Genetic Testing Registry: Juvenile myoclonic epilepsy  - Merck Manual Consumer Version: Seizure Disorders   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",juvenile myoclonic epilepsy,0000548,GHR,https://ghr.nlm.nih.gov/condition/juvenile-myoclonic-epilepsy,C0270853,T047,Disorders
What is (are) juvenile Paget disease ?,0000549-1,information,"Juvenile Paget disease is a disorder that affects bone growth. This disease causes bones to be abnormally large, misshapen, and easily broken (fractured).  The signs of juvenile Paget disease appear in infancy or early childhood. As bones grow, they become progressively weaker and more deformed. These abnormalities usually become more severe during the adolescent growth spurt, when bones grow very quickly.  Juvenile Paget disease affects the entire skeleton, resulting in widespread bone and joint pain. The bones of the skull tend to grow unusually large and thick, which can lead to hearing loss. The disease also affects bones of the spine (vertebrae). The deformed vertebrae can collapse, leading to abnormal curvature of the spine. Additionally, weight-bearing long bones in the legs tend to bow and fracture easily, which can interfere with standing and walking.",juvenile Paget disease,0000549,GHR,https://ghr.nlm.nih.gov/condition/juvenile-paget-disease,C0268414,T047,Disorders
How many people are affected by juvenile Paget disease ?,0000549-2,frequency,Juvenile Paget disease is rare; about 50 affected individuals have been identified worldwide.,juvenile Paget disease,0000549,GHR,https://ghr.nlm.nih.gov/condition/juvenile-paget-disease,C0268414,T047,Disorders
What are the genetic changes related to juvenile Paget disease ?,0000549-3,genetic changes,"Juvenile Paget disease is caused by mutations in the TNFRSF11B gene. This gene provides instructions for making a protein that is involved in bone remodeling, a normal process in which old bone is broken down and new bone is created to replace it.  Bones are constantly being remodeled, and the process is carefully controlled to ensure that bones stay strong and healthy. Mutations in the TNFRSF11B gene lead to a much faster rate of bone remodeling starting early in life. Bone tissue is broken down more quickly than usual, and when new bone tissue grows it is larger, weaker, and less organized than normal bone. This abnormally fast bone remodeling underlies the problems with bone growth characteristic of juvenile Paget disease.",juvenile Paget disease,0000549,GHR,https://ghr.nlm.nih.gov/condition/juvenile-paget-disease,C0268414,T047,Disorders
Is juvenile Paget disease inherited ?,0000549-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",juvenile Paget disease,0000549,GHR,https://ghr.nlm.nih.gov/condition/juvenile-paget-disease,C0268414,T047,Disorders
What are the treatments for juvenile Paget disease ?,0000549-5,treatment,These resources address the diagnosis or management of juvenile Paget disease:  - Genetic Testing Registry: Hyperphosphatasemia with bone disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,juvenile Paget disease,0000549,GHR,https://ghr.nlm.nih.gov/condition/juvenile-paget-disease,C0268414,T047,Disorders
What is (are) juvenile polyposis syndrome ?,0000550-1,information,"Juvenile polyposis syndrome is a disorder characterized by multiple noncancerous (benign) growths called juvenile polyps. People with juvenile polyposis syndrome typically develop polyps before age 20; however, in the name of this condition ""juvenile"" refers to the characteristics of the tissues that make up the polyp, not the age of the affected individual. These growths occur in the gastrointestinal tract, typically in the large intestine (colon). The number of polyps varies from only a few to hundreds, even among affected members of the same family. Polyps may cause gastrointestinal bleeding, a shortage of red blood cells (anemia), abdominal pain, and diarrhea. Approximately 15 percent of people with juvenile polyposis syndrome have other abnormalities, such as a twisting of the intestines (intestinal malrotation), heart or brain abnormalities, an opening in the roof of the mouth (cleft palate), extra fingers or toes (polydactyly), and abnormalities of the genitalia or urinary tract.  Juvenile polyposis syndrome is diagnosed when a person has any one of the following: (1) more than five juvenile polyps of the colon or rectum; (2) juvenile polyps in other parts of the gastrointestinal tract; or (3) any number of juvenile polyps and one or more affected family members. Single juvenile polyps are relatively common in children and are not characteristic of juvenile polyposis syndrome.  Three types of juvenile polyposis syndrome have been described, based on the signs and symptoms of the disorder. Juvenile polyposis of infancy is characterized by polyps that occur throughout the gastrointestinal tract during infancy. Juvenile polyposis of infancy is the most severe form of the disorder and is associated with the poorest outcome. Children with this type may develop a condition called protein-losing enteropathy. This condition results in severe diarrhea, failure to gain weight and grow at the expected rate (failure to thrive), and general wasting and weight loss (cachexia). Another type called generalized juvenile polyposis is diagnosed when polyps develop throughout the gastrointestinal tract. In the third type, known as juvenile polyposis coli, affected individuals develop polyps only in their colon. People with generalized juvenile polyposis and juvenile polyposis coli typically develop polyps during childhood.  Most juvenile polyps are benign, but there is a chance that polyps can become cancerous (malignant). It is estimated that people with juvenile polyposis syndrome have a 10 to 50 percent risk of developing a cancer of the gastrointestinal tract. The most common type of cancer seen in people with juvenile polyposis syndrome is colorectal cancer.",juvenile polyposis syndrome,0000550,GHR,https://ghr.nlm.nih.gov/condition/juvenile-polyposis-syndrome,C0334108,T191,Disorders
How many people are affected by juvenile polyposis syndrome ?,0000550-2,frequency,"Juvenile polyposis syndrome occurs in approximately 1 in 100,000 individuals worldwide.",juvenile polyposis syndrome,0000550,GHR,https://ghr.nlm.nih.gov/condition/juvenile-polyposis-syndrome,C0334108,T191,Disorders
What are the genetic changes related to juvenile polyposis syndrome ?,0000550-3,genetic changes,"Mutations in the BMPR1A and SMAD4 genes cause juvenile polyposis syndrome. These genes provide instructions for making proteins that are involved in transmitting chemical signals from the cell membrane to the nucleus. This type of signaling pathway allows the environment outside the cell to affect how the cell produces other proteins. The BMPR1A and SMAD4 proteins work together to help regulate the activity of particular genes and the growth and division (proliferation) of cells.  Mutations in the BMPR1A gene or the SMAD4 gene disrupt cell signaling and interfere with their roles in regulating gene activity and cell proliferation. This lack of regulation causes cells to grow and divide in an uncontrolled way, which can lead to polyp formation.",juvenile polyposis syndrome,0000550,GHR,https://ghr.nlm.nih.gov/condition/juvenile-polyposis-syndrome,C0334108,T191,Disorders
Is juvenile polyposis syndrome inherited ?,0000550-4,inheritance,"Juvenile polyposis syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In approximately 75 percent of cases, an affected person inherits the mutation from one affected parent. The remaining 25 percent of cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",juvenile polyposis syndrome,0000550,GHR,https://ghr.nlm.nih.gov/condition/juvenile-polyposis-syndrome,C0334108,T191,Disorders
What are the treatments for juvenile polyposis syndrome ?,0000550-5,treatment,These resources address the diagnosis or management of juvenile polyposis syndrome:  - Gene Review: Gene Review: Juvenile Polyposis Syndrome  - Genetic Testing Registry: Juvenile polyposis syndrome  - MedlinePlus Encyclopedia: Colorectal Polyps   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,juvenile polyposis syndrome,0000550,GHR,https://ghr.nlm.nih.gov/condition/juvenile-polyposis-syndrome,C0334108,T191,Disorders
What is (are) juvenile primary lateral sclerosis ?,0000551-1,information,"Juvenile primary lateral sclerosis is a rare disorder characterized by progressive weakness and tightness (spasticity) of muscles in the arms, legs, and face. The features of this disorder are caused by damage to motor neurons, which are specialized nerve cells in the brain and spinal cord that control muscle movement.  Symptoms of juvenile primary lateral sclerosis begin in early childhood and progress slowly over many years. Early symptoms include clumsiness, muscle weakness and spasticity in the legs, and difficulty with balance. As symptoms progress, the spasticity spreads to the arms and hands and individuals develop slurred speech, drooling, difficulty swallowing, and an inability to walk.",juvenile primary lateral sclerosis,0000551,GHR,https://ghr.nlm.nih.gov/condition/juvenile-primary-lateral-sclerosis,C1853396,T047,Disorders
How many people are affected by juvenile primary lateral sclerosis ?,0000551-2,frequency,"Juvenile primary lateral sclerosis is a rare disorder, with few reported cases.",juvenile primary lateral sclerosis,0000551,GHR,https://ghr.nlm.nih.gov/condition/juvenile-primary-lateral-sclerosis,C1853396,T047,Disorders
What are the genetic changes related to juvenile primary lateral sclerosis ?,0000551-3,genetic changes,"Mutations in the ALS2 gene cause most cases of juvenile primary lateral sclerosis. This gene provides instructions for making a protein called alsin. Alsin is abundant in motor neurons, but its function is not fully understood. Mutations in the ALS2 gene alter the instructions for producing alsin. As a result, alsin is unstable and is quickly broken down, or it cannot function properly. It is unclear how the loss of functional alsin protein damages motor neurons and causes juvenile primary lateral sclerosis.",juvenile primary lateral sclerosis,0000551,GHR,https://ghr.nlm.nih.gov/condition/juvenile-primary-lateral-sclerosis,C1853396,T047,Disorders
Is juvenile primary lateral sclerosis inherited ?,0000551-4,inheritance,"When caused by mutations in the ALS2 gene, juvenile primary lateral sclerosis is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",juvenile primary lateral sclerosis,0000551,GHR,https://ghr.nlm.nih.gov/condition/juvenile-primary-lateral-sclerosis,C1853396,T047,Disorders
What are the treatments for juvenile primary lateral sclerosis ?,0000551-5,treatment,These resources address the diagnosis or management of juvenile primary lateral sclerosis:  - Gene Review: Gene Review: ALS2-Related Disorders  - Genetic Testing Registry: Juvenile primary lateral sclerosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,juvenile primary lateral sclerosis,0000551,GHR,https://ghr.nlm.nih.gov/condition/juvenile-primary-lateral-sclerosis,C1853396,T047,Disorders
What is (are) juvenile primary osteoporosis ?,0000552-1,information,"Juvenile primary osteoporosis is a skeletal disorder characterized by thinning of the bones (osteoporosis) that begins in childhood. Osteoporosis is caused by a shortage of calcium and other minerals in bones (decreased bone mineral density), which makes the bones brittle and prone to fracture. Affected individuals often have multiple fractures in the long bones of the arms and legs, especially in the regions where new bone forms (metaphyses). They also have fractures in the bones that form the spine (vertebrae), which can cause collapse of the affected vertebrae (compressed vertebrae). Multiple fractures can cause bone pain and lead to movement problems.",juvenile primary osteoporosis,0000552,GHR,https://ghr.nlm.nih.gov/condition/juvenile-primary-osteoporosis,C3711559,T047,Disorders
How many people are affected by juvenile primary osteoporosis ?,0000552-2,frequency,"The prevalence of juvenile primary osteoporosis is unknown. Nearly 1 in 10 adults over age 50 have osteoporosis, but the condition is uncommon in children. Osteoporosis can occur at a young age as a feature of other conditions but rarely occurs without other signs and symptoms (primary osteoporosis).",juvenile primary osteoporosis,0000552,GHR,https://ghr.nlm.nih.gov/condition/juvenile-primary-osteoporosis,C3711559,T047,Disorders
What are the genetic changes related to juvenile primary osteoporosis ?,0000552-3,genetic changes,"Mutations in the LRP5 gene can cause juvenile primary osteoporosis. This gene provides instructions for making a protein that participates in a chemical signaling pathway that affects the way cells and tissues develop. In particular, the LRP5 protein is involved in the regulation of bone mineral density.  LRP5 gene mutations that cause juvenile primary osteoporosis result in an LRP5 protein that cannot transmit signals along the pathway. The resulting reduction in signaling impairs proper bone development, causing decreased bone mineral density and osteoporosis at a young age.  Many people with childhood-onset osteoporosis do not have a mutation in the LRP5 gene. (When its cause is unknown, the condition is often called idiopathic juvenile osteoporosis). It is likely that mutations in other genes that have not been identified are involved in this condition.",juvenile primary osteoporosis,0000552,GHR,https://ghr.nlm.nih.gov/condition/juvenile-primary-osteoporosis,C3711559,T047,Disorders
Is juvenile primary osteoporosis inherited ?,0000552-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",juvenile primary osteoporosis,0000552,GHR,https://ghr.nlm.nih.gov/condition/juvenile-primary-osteoporosis,C3711559,T047,Disorders
What are the treatments for juvenile primary osteoporosis ?,0000552-5,treatment,These resources address the diagnosis or management of juvenile primary osteoporosis:  - Lucile Packard Children's Hospital at Stanford: Juvenile Osteoporosis  - MedlinePlus Encyclopedia: Bone Mineral Density Test  - Merck Manual Home Health Edition: Osteoporosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,juvenile primary osteoporosis,0000552,GHR,https://ghr.nlm.nih.gov/condition/juvenile-primary-osteoporosis,C3711559,T047,Disorders
What is (are) Kabuki syndrome ?,0000553-1,information,"Kabuki syndrome is a disorder that affects many parts of the body. It is characterized by distinctive facial features including arched eyebrows; long eyelashes; long openings of the eyelids (long palpebral fissures) with the lower lids turned out (everted) at the outside edges; a flat, broadened tip of the nose; and large protruding earlobes. The name of this disorder comes from the resemblance of its characteristic facial appearance to stage makeup used in traditional Japanese theater called Kabuki.  People with Kabuki syndrome have developmental delay and intellectual disability that range from mild to severe. Affected individuals may also have seizures, an unusually small head size (microcephaly), or weak muscle tone (hypotonia). Some have eye problems such as rapid, involuntary eye movements (nystagmus) or eyes that do not look in the same direction (strabismus).  Other characteristic features of Kabuki syndrome include short stature and skeletal abnormalities such as abnormal side-to-side curvature of the spine (scoliosis), short fifth fingers, or problems with the hip and knee joints. The roof of the mouth may have an abnormal opening (cleft palate) or be high and arched, and dental problems are common in affected individuals. People with Kabuki syndrome may also have fingerprints with unusual features and fleshy pads at the tips of the fingers. These prominent finger pads are called fetal finger pads because they normally occur in human fetuses; in most people they disappear before birth.  A wide variety of other health problems occur in some people with Kabuki syndrome. Among the most commonly reported are heart abnormalities, frequent ear infections (otitis media), hearing loss, and early puberty.",Kabuki syndrome,0000553,GHR,https://ghr.nlm.nih.gov/condition/kabuki-syndrome,C0039082,T019,Disorders
How many people are affected by Kabuki syndrome ?,0000553-2,frequency,"Kabuki syndrome occurs in approximately 1 in 32,000 newborns.",Kabuki syndrome,0000553,GHR,https://ghr.nlm.nih.gov/condition/kabuki-syndrome,C0039082,T019,Disorders
What are the genetic changes related to Kabuki syndrome ?,0000553-3,genetic changes,"Kabuki syndrome is caused by mutations in the KMT2D gene (also known as MLL2) or the KDM6A gene.  Between 55 and 80 percent of cases of Kabuki syndrome are caused by mutations in the KMT2D gene. This gene provides instructions for making an enzyme called lysine-specific methyltransferase 2D that is found in many organs and tissues of the body. Lysine-specific methyltransferase 2D functions as a histone methyltransferase. Histone methyltransferases are enzymes that modify proteins called histones. Histones are structural proteins that attach (bind) to DNA and give chromosomes their shape. By adding a molecule called a methyl group to histones (a process called methylation), histone methyltransferases control (regulate) the activity of certain genes. Lysine-specific methyltransferase 2D appears to activate certain genes that are important for development.  About 6 percent of cases of Kabuki syndrome are caused by mutations in the KDM6A gene. This gene provides instructions for making an enzyme called lysine-specific demethylase 6A. This enzyme is a histone demethylase, which means that it helps to remove methyl groups from certain histones. Like lysine-specific methyltransferase 2D, lysine-specific demethylase 6A regulates the activity of certain genes, and research suggests that the two enzymes work together to control certain developmental processes.  The KMT2D and KDM6A gene mutations associated with Kabuki syndrome lead to the absence of the corresponding functional enzyme. A lack of the enzymes produced from these genes disrupts normal histone methylation and impairs proper activation of certain genes in many of the body's organs and tissues, resulting in the abnormalities of development and function characteristic of Kabuki syndrome.  Some people with Kabuki syndrome have no identified KMT2D or KDM6A gene mutation. The cause of the disorder in these individuals is unknown.",Kabuki syndrome,0000553,GHR,https://ghr.nlm.nih.gov/condition/kabuki-syndrome,C0039082,T019,Disorders
Is Kabuki syndrome inherited ?,0000553-4,inheritance,"When Kabuki syndrome is caused by mutations in the KMT2D gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  When Kabuki syndrome is caused by mutations in the KDM6A gene, it is inherited in an X-linked dominant pattern. The KDM6A gene is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  Most cases of Kabuki syndrome result from a new mutation in one of these genes and occur in people with no history of the disorder in their family. In a few cases, an affected person is believed to have inherited the mutation from one affected parent.",Kabuki syndrome,0000553,GHR,https://ghr.nlm.nih.gov/condition/kabuki-syndrome,C0039082,T019,Disorders
What are the treatments for Kabuki syndrome ?,0000553-5,treatment,These resources address the diagnosis or management of Kabuki syndrome:  - Boston Children's Hospital  - Gene Review: Gene Review: Kabuki Syndrome  - Genetic Testing Registry: Kabuki make-up syndrome  - Genetic Testing Registry: Kabuki syndrome 2   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Kabuki syndrome,0000553,GHR,https://ghr.nlm.nih.gov/condition/kabuki-syndrome,C0039082,T019,Disorders
What is (are) Kallmann syndrome ?,0000554-1,information,"Kallmann syndrome is a condition characterized by delayed or absent puberty and an impaired sense of smell.  This disorder is a form of hypogonadotropic hypogonadism (HH), which is a condition affecting the production of hormones that direct sexual development. Males with hypogonadotropic hypogonadism are often born with an unusually small penis (micropenis) and undescended testes (cryptorchidism). At puberty, most affected individuals do not develop secondary sex characteristics, such as the growth of facial hair and deepening of the voice in males. Affected females usually do not begin menstruating at puberty and have little or no breast development. In some people, puberty is incomplete or delayed.  In Kallmann syndrome, the sense of smell is either diminished (hyposmia) or completely absent (anosmia). This feature distinguishes Kallmann syndrome from most other forms of hypogonadotropic hypogonadism, which do not affect the sense of smell. Many people with Kallmann syndrome are not aware that they are unable to detect odors until the impairment is discovered through testing.  The features of Kallmann syndrome vary, even among affected people in the same family. Additional signs and symptoms can include a failure of one kidney to develop (unilateral renal agenesis), a cleft lip with or without an opening in the roof of the mouth (a cleft palate), abnormal eye movements, hearing loss, and abnormalities of tooth development. Some affected individuals have a condition called bimanual synkinesis, in which the movements of one hand are mirrored by the other hand. Bimanual synkinesis can make it difficult to do tasks that require the hands to move separately, such as playing a musical instrument.  Researchers have identified four forms of Kallmann syndrome, designated types 1 through 4, which are distinguished by their genetic cause. The four types are each characterized by hypogonadotropic hypogonadism and an impaired sense of smell. Additional features, such as a cleft palate, seem to occur only in types 1 and 2.",Kallmann syndrome,0000554,GHR,https://ghr.nlm.nih.gov/condition/kallmann-syndrome,C0162809,T047,Disorders
How many people are affected by Kallmann syndrome ?,0000554-2,frequency,"Kallmann syndrome is estimated to affect 1 in 10,000 to 86,000 people and occurs more often in males than in females. Kallmann syndrome 1 is the most common form of the disorder.",Kallmann syndrome,0000554,GHR,https://ghr.nlm.nih.gov/condition/kallmann-syndrome,C0162809,T047,Disorders
What are the genetic changes related to Kallmann syndrome ?,0000554-3,genetic changes,"Mutations in the ANOS1, FGFR1, PROKR2, and PROK2 genes cause Kallmann syndrome. ANOS1 gene mutations are responsible for Kallmann syndrome 1. Kallmann syndrome 2 results from mutations in the FGFR1 gene. Mutations in the PROKR2 and PROK2 genes cause Kallmann syndrome types 3 and 4, respectively.  The genes associated with Kallmann syndrome play a role in the development of certain areas of the brain before birth. Although some of their specific functions are unclear, these genes appear to be involved in the formation and movement (migration) of a group of nerve cells that are specialized to process smells (olfactory neurons). These nerve cells come together into a bundle called the olfactory bulb, which is critical for the perception of odors. The ANOS1, FGFR1, PROKR2, and PROK2 genes also play a role in the migration of neurons that produce a hormone called gonadotropin-releasing hormone (GnRH). GnRH controls the production of several other hormones that direct sexual development before birth and during puberty. These hormones are important for the normal function of the gonads (ovaries in women and testes in men).  Studies suggest that mutations in the ANOS1, FGFR1, PROKR2, or PROK2 gene disrupt the migration of olfactory nerve cells and GnRH-producing nerve cells in the developing brain. If olfactory nerve cells do not extend to the olfactory bulb, a person's sense of smell will be impaired or absent. Misplacement of GnRH-producing neurons prevents the production of certain sex hormones, which interferes with normal sexual development and causes the characteristic features of hypogonadotropic hypogonadism. It is unclear how gene mutations lead to the other possible signs and symptoms of Kallmann syndrome. Because the features of this condition vary among individuals, researchers suspect that additional genetic and environmental factors may be involved.  Together, mutations in the ANOS1, FGFR1, PROKR2, and PROK2 genes account for 25 percent to 30 percent of all cases of Kallmann syndrome. In cases without an identified mutation in one of these genes, the cause of the condition is unknown. Researchers are looking for other genes that can cause this disorder.",Kallmann syndrome,0000554,GHR,https://ghr.nlm.nih.gov/condition/kallmann-syndrome,C0162809,T047,Disorders
Is Kallmann syndrome inherited ?,0000554-4,inheritance,"Kallmann syndrome 1 (caused by ANOS1 gene mutations) has an X-linked recessive pattern of inheritance. The ANOS1 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  Most cases of Kallmann syndrome 1 are described as simplex, which means only one person in a family is affected. Some affected people inherit a ANOS1 gene mutation from their mothers, who carry a single mutated copy of the gene in each cell. Other people have the condition as a result of a new mutation in the ANOS1 gene.  Other forms of Kallmann syndrome can be inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  In several families, Kallmann syndrome has shown an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Kallmann syndrome,0000554,GHR,https://ghr.nlm.nih.gov/condition/kallmann-syndrome,C0162809,T047,Disorders
What are the treatments for Kallmann syndrome ?,0000554-5,treatment,These resources address the diagnosis or management of Kallmann syndrome:  - Gene Review: Gene Review: Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency  - Genetic Testing Registry: Hypogonadism with anosmia  - Genetic Testing Registry: Kallmann syndrome 1  - Genetic Testing Registry: Kallmann syndrome 2  - Genetic Testing Registry: Kallmann syndrome 3  - Genetic Testing Registry: Kallmann syndrome 4  - MedlinePlus Encyclopedia: Hypogonadotropic Hypogonadism  - MedlinePlus Encyclopedia: Smell - Impaired   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Kallmann syndrome,0000554,GHR,https://ghr.nlm.nih.gov/condition/kallmann-syndrome,C0162809,T047,Disorders
What is (are) Kawasaki disease ?,0000555-1,information,"Kawasaki disease is a sudden and time-limited (acute) illness that affects infants and young children. Affected children develop a prolonged fever lasting several days, a skin rash, and swollen lymph nodes in the neck (cervical lymphadenopathy). They also develop redness in the whites of the eyes (conjunctivitis) and redness (erythema) of the lips, lining of the mouth (oral mucosa), tongue, palms of the hands, and soles of the feet.  Without treatment, 15 to 25 percent of individuals with Kawasaki disease develop bulging and thinning of the walls of the arteries that supply blood to the heart muscle (coronary artery aneurysms) or other damage to the coronary arteries, which can be life-threatening.",Kawasaki disease,0000555,GHR,https://ghr.nlm.nih.gov/condition/kawasaki-disease,C0026691,T047,Disorders
How many people are affected by Kawasaki disease ?,0000555-2,frequency,"In the United States and other Western countries, Kawasaki disease occurs in approximately 1 in 10,000 children under 5 each year. The condition is 10 to 20 times more common in East Asia, including Japan, Korea, and Taiwan.",Kawasaki disease,0000555,GHR,https://ghr.nlm.nih.gov/condition/kawasaki-disease,C0026691,T047,Disorders
What are the genetic changes related to Kawasaki disease ?,0000555-3,genetic changes,"The causes of Kawasaki disease are not well understood. The disorder is generally regarded as being the result of an abnormal immune system activation, but the triggers of this abnormal response are unknown. Because cases of the disorder tend to cluster geographically and by season, researchers have suggested that an infection may be involved. However, no infectious agent (such as a virus or bacteria) has been identified.  A variation in the ITPKC gene has been associated with an increased risk of Kawasaki disease. The ITPKC gene provides instructions for making an enzyme called inositol 1,4,5-trisphosphate 3-kinase C. This enzyme helps limit the activity of immune system cells called T cells. T cells identify foreign substances and defend the body against infection. Reducing the activity of T cells when appropriate prevents the overproduction of immune proteins called cytokines that lead to inflammation and which, in excess, cause tissue damage. Researchers suggest that the ITPKC gene variation may interfere with the body's ability to reduce T cell activity, leading to inflammation that damages blood vessels and results in the signs and symptoms of Kawasaki disease.  It appears likely that other factors, including changes in other genes, also influence the development of this complex disorder.",Kawasaki disease,0000555,GHR,https://ghr.nlm.nih.gov/condition/kawasaki-disease,C0026691,T047,Disorders
Is Kawasaki disease inherited ?,0000555-4,inheritance,"A predisposition to Kawasaki disease appears to be passed through generations in families, but the inheritance pattern is unknown. Children of parents who have had Kawasaki disease have twice the risk of developing the disorder compared to the general population. Children with affected siblings have a tenfold higher risk.",Kawasaki disease,0000555,GHR,https://ghr.nlm.nih.gov/condition/kawasaki-disease,C0026691,T047,Disorders
What are the treatments for Kawasaki disease ?,0000555-5,treatment,"These resources address the diagnosis or management of Kawasaki disease:  - Cincinnati Children's Hospital Medical Center  - Genetic Testing Registry: Acute febrile mucocutaneous lymph node syndrome  - National Heart, Lung, and Blood Institute: How is Kawasaki Disease Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Kawasaki disease,0000555,GHR,https://ghr.nlm.nih.gov/condition/kawasaki-disease,C0026691,T047,Disorders
What is (are) KBG syndrome ?,0000556-1,information,"KBG syndrome is a rare disorder that affects several body systems. ""KBG"" represents the surname initials of the first families diagnosed with the disorder. Common signs and symptoms in individuals with this condition include unusual facial features, skeletal abnormalities, and intellectual disability.  A characteristic feature of KBG syndrome is unusually large upper front teeth (macrodontia). Other distinctive facial features include a wide, short skull (brachycephaly), a triangular face shape, widely spaced eyes (hypertelorism), wide eyebrows that may grow together in the middle (synophrys), a prominent nasal bridge, a long space between the nose and upper lip (philtrum), and a thin upper lip.  A common skeletal abnormality in people with KBG syndrome is slowed mineralization of bones (delayed bone age); for example, an affected 3-year-old child may have bones more typical of a child of 2. In addition, affected individuals can have abnormalities of the bones of the spine (vertebrae) and ribs. They can also have abnormalities of the bones of the hands, including unusually short or curved fifth (pinky) fingers (brachydactyly or clinodactyly, respectively). Most affected individuals are shorter than average from birth.  Development of mental and movement abilities is also delayed in KBG syndrome. Most affected individuals learn to speak and walk later than normal and have mild to moderate intellectual disability. Some people with this condition have behavioral or emotional problems, such as hyperactivity or anxiety.  Less common features of KBG syndrome include hearing loss, seizures, and heart defects.",KBG syndrome,0000556,GHR,https://ghr.nlm.nih.gov/condition/kbg-syndrome,C0220687,T047,Disorders
How many people are affected by KBG syndrome ?,0000556-2,frequency,"KBG syndrome is a rare disorder that has been reported in around 60 individuals. For unknown reasons, males are affected more often than females. Doctors think the disorder is underdiagnosed because the signs and symptoms can be mild and may be attributed to other disorders.",KBG syndrome,0000556,GHR,https://ghr.nlm.nih.gov/condition/kbg-syndrome,C0220687,T047,Disorders
What are the genetic changes related to KBG syndrome ?,0000556-3,genetic changes,"KBG syndrome is caused by mutations in the ANKRD11 gene. The protein produced from this gene enables other proteins to interact with each other and helps control gene activity. The ANKRD11 protein is found in nerve cells (neurons) in the brain. It plays a role in the proper development of the brain and may be involved in the ability of neurons to change and adapt over time (plasticity), which is important for learning and memory. ANKRD11 may function in other cells in the body and appears to be involved in normal bone development.  Most of the ANKRD11 gene mutations involved in KBG syndrome lead to an abnormally short ANKRD11 protein, which likely has little or no function. Reduction of this protein's function is thought to underlie the signs and symptoms of the condition. Because ANKRD11 is thought to play an important role in neurons and brain development, researchers speculate that a partial loss of its function may lead to developmental delay and intellectual disability in KBG syndrome. However, the mechanism is not fully known. It is also unclear how loss of ANKRD11 function leads to the skeletal features of the condition.",KBG syndrome,0000556,GHR,https://ghr.nlm.nih.gov/condition/kbg-syndrome,C0220687,T047,Disorders
Is KBG syndrome inherited ?,0000556-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",KBG syndrome,0000556,GHR,https://ghr.nlm.nih.gov/condition/kbg-syndrome,C0220687,T047,Disorders
What are the treatments for KBG syndrome ?,0000556-5,treatment,These resources address the diagnosis or management of KBG syndrome:  - Genetic Testing Registry: KBG syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,KBG syndrome,0000556,GHR,https://ghr.nlm.nih.gov/condition/kbg-syndrome,C0220687,T047,Disorders
What is (are) Kearns-Sayre syndrome ?,0000557-1,information,"Kearns-Sayre syndrome is a condition that affects many parts of the body, especially the eyes. The features of Kearns-Sayre syndrome usually appear before age 20, and the condition is diagnosed by a few characteristic signs and symptoms. People with Kearns-Sayre syndrome have progressive external ophthalmoplegia, which is weakness or paralysis of the eye muscles that impairs eye movement and causes drooping eyelids (ptosis). Affected individuals also have an eye condition called pigmentary retinopathy, which results from breakdown (degeneration) of the light-sensing tissue at the back of the eye (the retina) that gives it a speckled and streaked appearance. The retinopathy may cause loss of vision. In addition, people with Kearns-Sayre syndrome have at least one of the following signs or symptoms: abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects), problems with coordination and balance that cause unsteadiness while walking (ataxia), or abnormally high levels of protein in the fluid that surrounds and protects the brain and spinal cord (the cerebrospinal fluid or CSF).  People with Kearns-Sayre syndrome may also experience muscle weakness in their limbs, deafness, kidney problems, or a deterioration of cognitive functions (dementia). Affected individuals often have short stature. In addition, diabetes mellitus is occasionally seen in people with Kearns-Sayre syndrome.  When the muscle cells of affected individuals are stained and viewed under a microscope, these cells usually appear abnormal. The abnormal muscle cells contain an excess of structures called mitochondria and are known as ragged-red fibers.  A related condition called ophthalmoplegia-plus may be diagnosed if an individual has many of the signs and symptoms of Kearns-Sayre syndrome but not all the criteria are met.",Kearns-Sayre syndrome,0000557,GHR,https://ghr.nlm.nih.gov/condition/kearns-sayre-syndrome,C0022541,T047,Disorders
How many people are affected by Kearns-Sayre syndrome ?,0000557-2,frequency,"The prevalence of Kearns-Sayre syndrome is approximately 1 to 3 per 100,000 individuals.",Kearns-Sayre syndrome,0000557,GHR,https://ghr.nlm.nih.gov/condition/kearns-sayre-syndrome,C0022541,T047,Disorders
What are the genetic changes related to Kearns-Sayre syndrome ?,0000557-3,genetic changes,"Kearns-Sayre syndrome is a condition caused by defects in mitochondria, which are structures within cells that use oxygen to convert the energy from food into a form cells can use. This process is called oxidative phosphorylation. Although most DNA is packaged in chromosomes within the nucleus (nuclear DNA), mitochondria also have a small amount of their own DNA, called mitochondrial DNA (mtDNA). This type of DNA contains many genes essential for normal mitochondrial function. People with Kearns-Sayre syndrome have a single, large deletion of mtDNA, ranging from 1,000 to 10,000 DNA building blocks (nucleotides). The cause of the deletion in affected individuals is unknown.  The mtDNA deletions that cause Kearns-Sayre syndrome result in the loss of genes important for mitochondrial protein formation and oxidative phosphorylation. The most common deletion removes 4,997 nucleotides, which includes twelve mitochondrial genes. Deletions of mtDNA result in impairment of oxidative phosphorylation and a decrease in cellular energy production. Regardless of which genes are deleted, all steps of oxidative phosphorylation are affected. Researchers have not determined how these deletions lead to the specific signs and symptoms of Kearns-Sayre syndrome, although the features of the condition are probably related to a lack of cellular energy. It has been suggested that eyes are commonly affected by mitochondrial defects because they are especially dependent on mitochondria for energy.",Kearns-Sayre syndrome,0000557,GHR,https://ghr.nlm.nih.gov/condition/kearns-sayre-syndrome,C0022541,T047,Disorders
Is Kearns-Sayre syndrome inherited ?,0000557-4,inheritance,"This condition is generally not inherited but arises from mutations in the body's cells that occur after conception. This alteration is called a somatic mutation and is present only in certain cells.  Rarely, this condition is inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mtDNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children.",Kearns-Sayre syndrome,0000557,GHR,https://ghr.nlm.nih.gov/condition/kearns-sayre-syndrome,C0022541,T047,Disorders
What are the treatments for Kearns-Sayre syndrome ?,0000557-5,treatment,These resources address the diagnosis or management of Kearns-Sayre syndrome:  - Gene Review: Gene Review: Mitochondrial DNA Deletion Syndromes  - Genetic Testing Registry: Kearns Sayre syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Kearns-Sayre syndrome,0000557,GHR,https://ghr.nlm.nih.gov/condition/kearns-sayre-syndrome,C0022541,T047,Disorders
What is (are) keratitis-ichthyosis-deafness syndrome ?,0000558-1,information,"Keratitis-ichthyosis-deafness (KID) syndrome is characterized by eye problems, skin abnormalities, and hearing loss.  People with KID syndrome usually have keratitis, which is inflammation of the front surface of the eye (the cornea). The keratitis may cause pain, increased sensitivity to light (photophobia), abnormal blood vessel growth over the cornea (neovascularization), and scarring. Over time, affected individuals experience a loss of sharp vision (reduced visual acuity); in severe cases the keratitis can lead to blindness.  Most people with KID syndrome have thick, hard skin on the palms of the hands and soles of the feet (palmoplantar keratoderma). Affected individuals also have thick, reddened patches of skin (erythrokeratoderma) that are dry and scaly (ichthyosis). These dry patches can occur anywhere on the body, although they most commonly affect the neck, groin, and armpits. Breaks in the skin often occur and may lead to infections. In severe cases these infections can be life-threatening, especially in infancy. Approximately 12 percent of people with KID syndrome develop a type of skin cancer called squamous cell carcinoma, which may also affect mucous membranes such as the lining of the mouth.  Partial hair loss is a common feature of KID syndrome, and often affects the eyebrows and eyelashes. Affected individuals may also have small, abnormally formed nails.  Hearing loss in this condition is usually profound, but occasionally is less severe.",keratitis-ichthyosis-deafness syndrome,0000558,GHR,https://ghr.nlm.nih.gov/condition/keratitis-ichthyosis-deafness-syndrome,C0011053,T019,Disorders
How many people are affected by keratitis-ichthyosis-deafness syndrome ?,0000558-2,frequency,KID syndrome is a rare disorder. Its prevalence is unknown. Approximately 100 cases have been reported.,keratitis-ichthyosis-deafness syndrome,0000558,GHR,https://ghr.nlm.nih.gov/condition/keratitis-ichthyosis-deafness-syndrome,C0011053,T019,Disorders
What are the genetic changes related to keratitis-ichthyosis-deafness syndrome ?,0000558-3,genetic changes,"KID syndrome is caused by mutations in the GJB2 gene. This gene provides instructions for making a protein called gap junction beta 2, more commonly known as connexin 26. Connexin 26 is a member of the connexin protein family. Connexin proteins form channels called gap junctions that permit the transport of nutrients, charged atoms (ions), and signaling molecules between neighboring cells that are in contact with each other. Gap junctions made with connexin 26 transport potassium ions and certain small molecules.  Connexin 26 is found in cells throughout the body, including the inner ear and the skin. In the inner ear, channels made from connexin 26 are found in a snail-shaped structure called the cochlea. These channels may help to maintain the proper level of potassium ions required for the conversion of sound waves to electrical nerve impulses. This conversion is essential for normal hearing. In addition, connexin 26 may be involved in the maturation of certain cells in the cochlea. Connexin 26 also plays a role in the growth and maturation of the outermost layer of skin (the epidermis).  The GJB2 gene mutations that cause KID syndrome change single protein building blocks (amino acids) in connexin 26. The mutations are thought to result in channels that constantly leak ions, which impairs the health of the cells and increases cell death. Death of cells in the skin and the inner ear may underlie the ichthyosis and deafness that occur in KID syndrome. It is unclear how GJB2 gene mutations affect the eye.  Because at least one of the GJB2 gene mutations identified in people with KID syndrome also occurs in hystrix-like ichthyosis with deafness (HID), a disorder with similar features but without keratitis, many researchers categorize KID syndrome and HID as a single disorder, which they call KID/HID. It is not known why some people with this mutation have eye problems while others do not.",keratitis-ichthyosis-deafness syndrome,0000558,GHR,https://ghr.nlm.nih.gov/condition/keratitis-ichthyosis-deafness-syndrome,C0011053,T019,Disorders
Is keratitis-ichthyosis-deafness syndrome inherited ?,0000558-4,inheritance,"KID syndrome is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. However, most cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  A few families have had a condition resembling KID syndrome with an autosomal recessive pattern of inheritance. In autosomal recessive inheritance, both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Affected individuals in these families have liver disease, which is not a feature of the autosomal dominant form. The autosomal recessive condition is sometimes called Desmons syndrome. It is unknown whether it is also caused by GJB2 gene mutations.",keratitis-ichthyosis-deafness syndrome,0000558,GHR,https://ghr.nlm.nih.gov/condition/keratitis-ichthyosis-deafness-syndrome,C0011053,T019,Disorders
What are the treatments for keratitis-ichthyosis-deafness syndrome ?,0000558-5,treatment,"These resources address the diagnosis or management of keratitis-ichthyosis-deafness syndrome:  - Genetic Testing Registry: Autosomal recessive keratitis-ichthyosis-deafness syndrome  - Genetic Testing Registry: Keratitis-ichthyosis-deafness syndrome, autosomal dominant   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",keratitis-ichthyosis-deafness syndrome,0000558,GHR,https://ghr.nlm.nih.gov/condition/keratitis-ichthyosis-deafness-syndrome,C0011053,T019,Disorders
What is (are) keratoderma with woolly hair ?,0000559-1,information,"Keratoderma with woolly hair is a group of related conditions that affect the skin and hair and in many cases increase the risk of potentially life-threatening heart problems. People with these conditions have hair that is unusually coarse, dry, fine, and tightly curled. In some cases, the hair is also sparse. The woolly hair texture typically affects only scalp hair and is present from birth. Starting early in life, affected individuals also develop palmoplantar keratoderma, a condition that causes skin on the palms of the hands and the soles of the feet to become thick, scaly, and calloused.  Cardiomyopathy, which is a disease of the heart muscle, is a life-threatening health problem that can develop in people with keratoderma with woolly hair. Unlike the other features of this condition, signs and symptoms of cardiomyopathy may not appear until adolescence or later. Complications of cardiomyopathy can include an abnormal heartbeat (arrhythmia), heart failure, and sudden death.  Keratoderma with woolly hair comprises several related conditions with overlapping signs and symptoms. Researchers have recently proposed classifying keratoderma with woolly hair into four types, based on the underlying genetic cause. Type I, also known as Naxos disease, is characterized by palmoplantar keratoderma, woolly hair, and a form of cardiomyopathy called arrhythmogenic right ventricular cardiomyopathy (ARVC). Type II, also known as Carvajal syndrome, has hair and skin abnormalities similar to type I but features a different form of cardiomyopathy, called dilated left ventricular cardiomyopathy. Type III also has signs and symptoms similar to those of type I, including ARVC, although the hair and skin abnormalities are often milder. Type IV is characterized by palmoplantar keratoderma and woolly and sparse hair, as well as abnormal fingernails and toenails. Type IV does not appear to cause cardiomyopathy.",keratoderma with woolly hair,0000559,GHR,https://ghr.nlm.nih.gov/condition/keratoderma-with-woolly-hair,C0343073,T047,Disorders
How many people are affected by keratoderma with woolly hair ?,0000559-2,frequency,"Keratoderma with woolly hair is rare; its prevalence worldwide is unknown.  Type I (Naxos disease) was first described in families from the Greek island of Naxos. Since then, affected families have been found in other Greek islands, Turkey, and the Middle East. This form of the condition may affect up to 1 in 1,000 people from the Greek islands.  Type II (Carvajal syndrome), type III, and type IV have each been identified in only a small number of families worldwide.",keratoderma with woolly hair,0000559,GHR,https://ghr.nlm.nih.gov/condition/keratoderma-with-woolly-hair,C0343073,T047,Disorders
What are the genetic changes related to keratoderma with woolly hair ?,0000559-3,genetic changes,"Mutations in the JUP, DSP, DSC2, and KANK2 genes cause keratoderma with woolly hair types I through IV, respectively. The JUP, DSP, and DSC2 genes provide instructions for making components of specialized cell structures called desmosomes. Desmosomes are located in the membrane surrounding certain cells, including skin and heart muscle cells. Desmosomes help attach cells to one another, which provides strength and stability to tissues. They also play a role in signaling between cells.  Mutations in the JUP, DSP, or DSC2 gene alter the structure and impair the function of desmosomes. Abnormal or missing desmosomes prevent cells from sticking to one another effectively, which likely makes the hair, skin, and heart muscle more fragile. Over time, as these tissues are exposed to mechanical stress (for example, friction on the surface of the skin or the constant contraction and relaxation of the heart muscle), they become damaged and can no longer function normally. This mechanism probably underlies the skin, hair, and heart problems that occur in keratoderma with woolly hair. Some studies suggest that abnormal cell signaling may also contribute to cardiomyopathy in people with this group of conditions.  Unlike the other genes associated with keratoderma with woolly hair, the KANK2 gene provides instructions for making a protein that is not part of desmosomes. Instead, it regulates other proteins called steroid receptor coactivators (SRCs), whose function is to help turn on (activate) certain genes. SRCs play important roles in tissues throughout the body, including the skin. Studies suggest that mutations in the KANK2 gene disrupt the regulation of SRCs, which leads to abnormal gene activity. However, it is unclear how these changes underlie the skin and hair abnormalities in keratoderma with woolly hair type IV.",keratoderma with woolly hair,0000559,GHR,https://ghr.nlm.nih.gov/condition/keratoderma-with-woolly-hair,C0343073,T047,Disorders
Is keratoderma with woolly hair inherited ?,0000559-4,inheritance,"Most cases of keratoderma with woolly hair have an autosomal recessive pattern of inheritance, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they usually do not show signs and symptoms of the condition.",keratoderma with woolly hair,0000559,GHR,https://ghr.nlm.nih.gov/condition/keratoderma-with-woolly-hair,C0343073,T047,Disorders
What are the treatments for keratoderma with woolly hair ?,0000559-5,treatment,"These resources address the diagnosis or management of keratoderma with woolly hair:  - Gene Review: Gene Review: Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy  - Gene Review: Gene Review: Dilated Cardiomyopathy Overview  - Genetic Testing Registry: Arrhythmogenic right ventricular cardiomyopathy, type 11  - Genetic Testing Registry: Cardiomyopathy, dilated, with woolly hair, keratoderma, and tooth agenesis  - Genetic Testing Registry: Naxos disease  - Genetic Testing Registry: Palmoplantar keratoderma and woolly hair  - National Heart, Lung, and Blood Institute: How is Cardiomyopathy Diagnosed?  - National Heart, Lung, and Blood Institute: How is Cardiomyopathy Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",keratoderma with woolly hair,0000559,GHR,https://ghr.nlm.nih.gov/condition/keratoderma-with-woolly-hair,C0343073,T047,Disorders
What is (are) Kleefstra syndrome ?,0000560-1,information,"Kleefstra syndrome is a disorder that involves many parts of the body. Characteristic features of Kleefstra syndrome include developmental delay and intellectual disability, severely limited or absent speech, and weak muscle tone (hypotonia). Affected individuals also have an unusually small head size (microcephaly) and a wide, short skull (brachycephaly). Distinctive facial features include eyebrows that grow together in the middle (synophrys), widely spaced eyes (hypertelorism), a sunken appearance of the middle of the face (midface hypoplasia), nostrils that open to the front rather than downward (anteverted nares), a protruding jaw (prognathism), rolled out (everted) lips, and a large tongue (macroglossia). Affected individuals may have a high birth weight and childhood obesity.  People with Kleefstra syndrome may also have structural brain abnormalities, congenital heart defects, genitourinary abnormalities, seizures, and a tendency to develop severe respiratory infections. During childhood they may exhibit features of autism or related developmental disorders affecting communication and social interaction. In adolescence, they may develop a general loss of interest and enthusiasm (apathy) or unresponsiveness (catatonia).",Kleefstra syndrome,0000560,GHR,https://ghr.nlm.nih.gov/condition/kleefstra-syndrome,C0795833,T047,Disorders
How many people are affected by Kleefstra syndrome ?,0000560-2,frequency,The prevalence of Kleefstra syndrome is unknown. Only recently has testing become available to distinguish it from other disorders with similar features.,Kleefstra syndrome,0000560,GHR,https://ghr.nlm.nih.gov/condition/kleefstra-syndrome,C0795833,T047,Disorders
What are the genetic changes related to Kleefstra syndrome ?,0000560-3,genetic changes,"Kleefstra syndrome is caused by the loss of the EHMT1 gene or by mutations that disable its function. The EHMT1 gene provides instructions for making an enzyme called euchromatic histone methyltransferase 1. Histone methyltransferases are enzymes that modify proteins called histones. Histones are structural proteins that attach (bind) to DNA and give chromosomes their shape. By adding a molecule called a methyl group to histones, histone methyltransferases can turn off (suppress) the activity of certain genes, which is essential for normal development and function.  Most people with Kleefstra syndrome are missing a sequence of about 1 million DNA building blocks (base pairs) on one copy of chromosome 9 in each cell. The deletion occurs near the end of the long (q) arm of the chromosome at a location designated q34.3, a region containing the EHMT1 gene. Some affected individuals have shorter or longer deletions in the same region.  The loss of the EHMT1 gene from one copy of chromosome 9 in each cell is believed to be responsible for the characteristic features of Kleefstra syndrome in people with the 9q34.3 deletion. However, the loss of other genes in the same region may lead to additional health problems in some affected individuals.  About 25 percent of individuals with Kleefstra syndrome do not have a deletion of genetic material from chromosome 9; instead, these individuals have mutations in the EHMT1 gene. Some of these mutations change single protein building blocks (amino acids) in euchromatic histone methyltransferase 1. Others create a premature stop signal in the instructions for making the enzyme or alter the way the gene's instructions are pieced together to produce the enzyme. These changes generally result in an enzyme that is unstable and decays rapidly, or that is disabled and cannot function properly.  Either a deletion or a mutation affecting the EHMT1 gene results in a lack of functional euchromatic histone methyltransferase 1 enzyme. A lack of this enzyme impairs proper control of the activity of certain genes in many of the body's organs and tissues, resulting in the abnormalities of development and function characteristic of Kleefstra syndrome.",Kleefstra syndrome,0000560,GHR,https://ghr.nlm.nih.gov/condition/kleefstra-syndrome,C0795833,T047,Disorders
Is Kleefstra syndrome inherited ?,0000560-4,inheritance,"The inheritance of Kleefstra syndrome is considered to be autosomal dominant because a deletion in one copy of chromosome 9 in each cell or a mutation in one copy of the EHMT1 gene is sufficient to cause the condition. Most cases of Kleefstra syndrome are not inherited, however. The genetic change occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family, though they can pass the disorder on to their children. Only a few people with Kleefstra syndrome have been known to reproduce.  Rarely, affected individuals inherit a chromosome 9 with a deleted segment from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which no genetic material is gained or lost. Balanced translocations usually do not cause any health problems; however, they can become unbalanced as they are passed to the next generation. Children who inherit an unbalanced translocation can have a chromosomal rearrangement with extra or missing genetic material. Individuals with Kleefstra syndrome who inherit an unbalanced translocation are missing genetic material from the long arm of chromosome 9.  A few individuals with Kleefstra syndrome have inherited the chromosome 9q34.3 deletion from an unaffected parent who is mosaic for the deletion. Mosaic means that an individual has the deletion in some cells (including some sperm or egg cells), but not in others.",Kleefstra syndrome,0000560,GHR,https://ghr.nlm.nih.gov/condition/kleefstra-syndrome,C0795833,T047,Disorders
What are the treatments for Kleefstra syndrome ?,0000560-5,treatment,These resources address the diagnosis or management of Kleefstra syndrome:  - Gene Review: Gene Review: Kleefstra Syndrome  - Genetic Testing Registry: Chromosome 9q deletion syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Kleefstra syndrome,0000560,GHR,https://ghr.nlm.nih.gov/condition/kleefstra-syndrome,C0795833,T047,Disorders
What is (are) Klinefelter syndrome ?,0000561-1,information,"Klinefelter syndrome is a chromosomal condition that affects male physical and cognitive development. Its signs and symptoms vary among affected individuals.  Affected individuals typically have small testes that do not produce as much testosterone as usual. Testosterone is the hormone that directs male sexual development before birth and during puberty. A shortage of testosterone can lead to delayed or incomplete puberty, breast enlargement (gynecomastia), reduced facial and body hair, and an inability to have biological children (infertility). Some affected individuals also have genital differences including undescended testes (cryptorchidism), the opening of the urethra on the underside of the penis (hypospadias), or an unusually small penis (micropenis).  Older children and adults with Klinefelter syndrome tend to be taller than their peers. Compared with unaffected men, adults with Klinefelter syndrome have an increased risk of developing breast cancer and a chronic inflammatory disease called systemic lupus erythematosus. Their chance of developing these disorders is similar to that of women in the general population.  Children with Klinefelter syndrome may have learning disabilities and delayed speech and language development. They tend to be quiet, sensitive, and unassertive, but personality characteristics vary among affected individuals.",Klinefelter syndrome,0000561,GHR,https://ghr.nlm.nih.gov/condition/klinefelter-syndrome,C0432474,T019,Disorders
How many people are affected by Klinefelter syndrome ?,0000561-2,frequency,"Klinefelter syndrome affects 1 in 500 to 1,000 newborn males. Most variants of Klinefelter syndrome are much rarer, occurring in 1 in 50,000 or fewer newborns.  Researchers suspect that Klinefelter syndrome is underdiagnosed because the condition may not be identified in people with mild signs and symptoms. Additionally, the features of the condition vary and overlap significantly with those of other conditions.",Klinefelter syndrome,0000561,GHR,https://ghr.nlm.nih.gov/condition/klinefelter-syndrome,C0432474,T019,Disorders
What are the genetic changes related to Klinefelter syndrome ?,0000561-3,genetic changes,"Klinefelter syndrome is a condition related to the X and Y chromosomes (the sex chromosomes). People typically have two sex chromosomes in each cell: females have two X chromosomes (46,XX), and males have one X and one Y chromosome (46,XY). Most often, Klinefelter syndrome results from the presence of one extra copy of the X chromosome in each cell (47,XXY). Extra copies of genes on the X chromosome interfere with male sexual development, often preventing the testes from functioning normally and reducing the levels of testosterone. Most people with an extra X chromosome have the features described above, although some have few or no associated signs and symptoms.  Some people with features of Klinefelter syndrome have more than one extra sex chromosome in each cell (for example, 48,XXXY or 49,XXXXY). These conditions, which are often called variants of Klinefelter syndrome, tend to cause more severe signs and symptoms than classic Klinefelter syndrome. In addition to affecting male sexual development, variants of Klinefelter syndrome are associated with intellectual disability, distinctive facial features, skeletal abnormalities, poor coordination, and severe problems with speech. As the number of extra sex chromosomes increases, so does the risk of these health problems.  Some people with features of Klinefelter syndrome have the extra X chromosome in only some of their cells; in these individuals, the condition is described as mosaic Klinefelter syndrome (46,XY/47,XXY). Individuals with mosaic Klinefelter syndrome may have milder signs and symptoms, depending on how many cells have an additional X chromosome.",Klinefelter syndrome,0000561,GHR,https://ghr.nlm.nih.gov/condition/klinefelter-syndrome,C0432474,T019,Disorders
Is Klinefelter syndrome inherited ?,0000561-4,inheritance,"Klinefelter syndrome and its variants are not inherited; these chromosomal changes usually occur as random events during the formation of reproductive cells (eggs and sperm) in a parent. An error in cell division called nondisjunction results in a reproductive cell with an abnormal number of chromosomes. For example, an egg or sperm cell may gain one or more extra copies of the X chromosome as a result of nondisjunction. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have one or more extra X chromosomes in each of the body's cells.  Mosaic 46,XY/47,XXY is also not inherited. It occurs as a random event during cell division early in fetal development. As a result, some of the body's cells have one X chromosome and one Y chromosome (46,XY), and other cells have an extra copy of the X chromosome (47,XXY).",Klinefelter syndrome,0000561,GHR,https://ghr.nlm.nih.gov/condition/klinefelter-syndrome,C0432474,T019,Disorders
What are the treatments for Klinefelter syndrome ?,0000561-5,treatment,"These resources address the diagnosis or management of Klinefelter syndrome:  - Genetic Testing Registry: Klinefelter's syndrome, XXY  - MedlinePlus Encyclopedia: Klinefelter Syndrome  - MedlinePlus Encyclopedia: Testicular Failure   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Klinefelter syndrome,0000561,GHR,https://ghr.nlm.nih.gov/condition/klinefelter-syndrome,C0432474,T019,Disorders
What is (are) Klippel-Feil syndrome ?,0000562-1,information,"Klippel-Feil syndrome is a bone disorder characterized by the abnormal joining (fusion) of two or more spinal bones in the neck (cervical vertebrae). The vertebral fusion is present from birth. Three major features result from this vertebral fusion: a short neck, the resulting appearance of a low hairline at the back of the head, and a limited range of motion in the neck. Most affected people have one or two of these characteristic features. Less than half of all individuals with Klippel-Feil syndrome have all three classic features of this condition.  In people with Klippel-Feil syndrome, the fused vertebrae can limit the range of movement of the neck and back as well as lead to chronic headaches and muscle pain in the neck and back that range in severity. People with minimal bone involvement often have fewer problems compared to individuals with several vertebrae affected. The shortened neck can cause a slight difference in the size and shape of the right and left sides of the face (facial asymmetry). Trauma to the spine, such as a fall or car accident, can aggravate problems in the fused area. Fusion of the vertebrae can lead to nerve damage in the head, neck, or back. Over time, individuals with Klippel-Feil syndrome can develop a narrowing of the spinal canal (spinal stenosis) in the neck, which can compress and damage the spinal cord. Rarely, spinal nerve abnormalities may cause abnormal sensations or involuntary movements in people with Klippel-Feil syndrome. Affected individuals may develop a painful joint disorder called osteoarthritis around the areas of fused bone or experience painful involuntary tensing of the neck muscles (cervical dystonia). In addition to the fused cervical bones, people with this condition may have abnormalities in other vertebrae. Many people with Klippel-Feil syndrome have abnormal side-to-side curvature of the spine (scoliosis) due to malformation of the vertebrae; fusion of additional vertebrae below the neck may also occur.  People with Klippel-Feil syndrome may have a wide variety of other features in addition to their spine abnormalities. Some people with this condition have hearing difficulties, eye abnormalities, an opening in the roof of the mouth (cleft palate), genitourinary problems such as abnormal kidneys or reproductive organs, heart abnormalities, or lung defects that can cause breathing problems. Affected individuals may have other skeletal defects including arms or legs of unequal length (limb length discrepancy), which can result in misalignment of the hips or knees. Additionally, the shoulder blades may be underdeveloped so that they sit abnormally high on the back, a condition called Sprengel deformity. Rarely, structural brain abnormalities or a type of birth defect that occurs during the development of the brain and spinal cord (neural tube defect) can occur in people with Klippel-Feil syndrome.  In some cases, Klippel-Feil syndrome occurs as a feature of another disorder or syndrome, such as Wildervanck syndrome or hemifacial microsomia. In these instances, affected individuals have the signs and symptoms of both Klippel-Feil syndrome and the additional disorder.",Klippel-Feil syndrome,0000562,GHR,https://ghr.nlm.nih.gov/condition/klippel-feil-syndrome,C0022738,T019,Disorders
How many people are affected by Klippel-Feil syndrome ?,0000562-2,frequency,"Klippel-Feil syndrome is estimated to occur in 1 in 40,000 to 42,000 newborns worldwide. Females seem to be affected slightly more often than males.",Klippel-Feil syndrome,0000562,GHR,https://ghr.nlm.nih.gov/condition/klippel-feil-syndrome,C0022738,T019,Disorders
What are the genetic changes related to Klippel-Feil syndrome ?,0000562-3,genetic changes,"Mutations in the GDF6, GDF3, or MEOX1 gene can cause Klippel-Feil syndrome. These genes are involved in proper bone development. The protein produced from the GDF6 gene is necessary for the formation of bones and joints, including those in the spine. While the protein produced from the GDF3 gene is known to be involved in bone development, its exact role is unclear. The protein produced from the MEOX1 gene, called homeobox protein MOX-1, regulates the process that begins separating vertebrae from one another during early development.  GDF6 and GDF3 gene mutations that cause Klippel-Feil syndrome likely lead to reduced function of the respective proteins. MEOX1 gene mutations lead to a complete lack of homeobox protein MOX-1. Although the GDF6, GDF3, and homeobox protein MOX-1 proteins are involved in bone development, particularly formation of vertebrae, it is unclear how a shortage of one of these proteins leads to incomplete separation of the cervical vertebrae in people with Klippel-Feil syndrome.  When Klippel-Feil syndrome is a feature of another disorder, it is caused by mutations in genes involved in the other disorder.",Klippel-Feil syndrome,0000562,GHR,https://ghr.nlm.nih.gov/condition/klippel-feil-syndrome,C0022738,T019,Disorders
Is Klippel-Feil syndrome inherited ?,0000562-4,inheritance,"When Klippel-Feil syndrome is caused by mutations in the GDF6 or GDF3 genes, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  When caused by mutations in the MEOX1 gene, Klippel-Feil syndrome is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  As a feature of another disorder, Klippel-Feil syndrome is inherited in whatever pattern the other disorder follows.",Klippel-Feil syndrome,0000562,GHR,https://ghr.nlm.nih.gov/condition/klippel-feil-syndrome,C0022738,T019,Disorders
What are the treatments for Klippel-Feil syndrome ?,0000562-5,treatment,"These resources address the diagnosis or management of Klippel-Feil syndrome:  - Genetic Testing Registry: Klippel Feil syndrome  - Genetic Testing Registry: Klippel-Feil syndrome 1, autosomal dominant  - Genetic Testing Registry: Klippel-Feil syndrome 2, autosomal recessive  - Genetic Testing Registry: Klippel-Feil syndrome 3, autosomal dominant   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Klippel-Feil syndrome,0000562,GHR,https://ghr.nlm.nih.gov/condition/klippel-feil-syndrome,C0022738,T019,Disorders
What is (are) Klippel-Trenaunay syndrome ?,0000563-1,information,"Klippel-Trenaunay syndrome is a condition that affects the development of blood vessels, soft tissues, and bones. The disorder has three characteristic features: a red birthmark called a port-wine stain, abnormal overgrowth of soft tissues and bones, and vein malformations.  Most people with Klippel-Trenaunay syndrome are born with a port-wine stain. This type of birthmark is caused by swelling of small blood vessels near the surface of the skin. Port-wine stains are typically flat and can vary from pale pink to deep maroon in color. In people with Klippel-Trenaunay syndrome, the port-wine stain usually covers part of one limb. The affected area may become lighter or darker with age. Occasionally, port-wine stains develop small red blisters that break open and bleed easily.  Klippel-Trenaunay syndrome is also associated with overgrowth of bones and soft tissues beginning in infancy. Usually this abnormal growth is limited to one limb, most often one leg. However, overgrowth can also affect the arms or, rarely, the trunk. The abnormal growth can cause pain, a feeling of heaviness, and reduced movement in the affected area. If the overgrowth causes one leg to be longer than the other, it can also lead to problems with walking.  Malformations of veins are the third major feature of Klippel-Trenaunay syndrome. These abnormalities include varicose veins, which are swollen and twisted veins near the surface of the skin that often cause pain. Varicose veins usually occur on the sides of the upper legs and calves. Veins deep in the limbs can also be abnormal in people with Klippel-Trenaunay syndrome. Malformations of deep veins increase the risk of a type of clot called a deep vein thrombosis (DVT). If a DVT travels through the bloodstream and lodges in the lungs, it can cause a life-threatening clot known as a pulmonary embolism (PE).  Complications of Klippel-Trenaunay syndrome can include a type of skin infection called cellulitis, swelling caused by a buildup of fluid (lymphedema), and internal bleeding from abnormal blood vessels. Less commonly, this condition is also associated with fusion of certain fingers or toes (syndactyly) or the presence of extra digits (polydactyly).",Klippel-Trenaunay syndrome,0000563,GHR,https://ghr.nlm.nih.gov/condition/klippel-trenaunay-syndrome,C0022739,T019,Disorders
How many people are affected by Klippel-Trenaunay syndrome ?,0000563-2,frequency,"Klippel-Trenaunay syndrome is estimated to affect at least 1 in 100,000 people worldwide.",Klippel-Trenaunay syndrome,0000563,GHR,https://ghr.nlm.nih.gov/condition/klippel-trenaunay-syndrome,C0022739,T019,Disorders
What are the genetic changes related to Klippel-Trenaunay syndrome ?,0000563-3,genetic changes,"The cause of Klippel-Trenaunay syndrome is unknown. Researchers suspect that the condition may result from changes in one or more genes that regulate the growth of blood vessels during embryonic development. However, no associated genes have been identified. It is also unclear how blood vessel malformations are related to the overgrowth of bones and soft tissues.",Klippel-Trenaunay syndrome,0000563,GHR,https://ghr.nlm.nih.gov/condition/klippel-trenaunay-syndrome,C0022739,T019,Disorders
Is Klippel-Trenaunay syndrome inherited ?,0000563-4,inheritance,"Klippel-Trenaunay syndrome is almost always sporadic, which means that it occurs in people with no history of the disorder in their family. Studies suggest that the condition may result from gene mutations that are not inherited. These genetic changes, which are called somatic mutations, probably occur very early in development and are present only in certain cells. Somatic mutations could explain why the signs and symptoms of Klippel-Trenaunay syndrome are often limited to specific areas of the body. However, it is unclear whether somatic mutations are responsible for this condition because no associated genes have been found.",Klippel-Trenaunay syndrome,0000563,GHR,https://ghr.nlm.nih.gov/condition/klippel-trenaunay-syndrome,C0022739,T019,Disorders
What are the treatments for Klippel-Trenaunay syndrome ?,0000563-5,treatment,These resources address the diagnosis or management of Klippel-Trenaunay syndrome:  - Cincinnati Children's Hospital Medical Center  - Cleveland Clinic  - Genetic Testing Registry: Klippel Trenaunay syndrome  - Seattle Children's Hospital   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Klippel-Trenaunay syndrome,0000563,GHR,https://ghr.nlm.nih.gov/condition/klippel-trenaunay-syndrome,C0022739,T019,Disorders
What is (are) Kniest dysplasia ?,0000564-1,information,"Kniest dysplasia is a disorder of bone growth characterized by short stature (dwarfism) with other skeletal abnormalities and problems with vision and hearing.  People with Kniest dysplasia are born with a short trunk and shortened arms and legs. Adult height ranges from 42 inches to 58 inches. Affected individuals have abnormally large joints that can cause pain and restrict movement, limiting physical activity. These joint problems can also lead to arthritis. Other skeletal features may include a rounded upper back that also curves to the side (kyphoscoliosis), severely flattened bones of the spine (platyspondyly), dumbbell-shaped bones in the arms and legs, long and knobby fingers, and an inward- and upward-turning foot (clubfoot).  Individuals with Kniest dysplasia have a round, flat face with bulging and wide-set eyes. Some affected infants are born with an opening in the roof of the mouth called a cleft palate. Infants may also have breathing problems due to weakness of the windpipe. Severe nearsightedness (myopia) and other eye problems are common in Kniest dysplasia. Some eye problems, such as tearing of the back lining of the eye (retinal detachment), can lead to blindness. Hearing loss resulting from recurrent ear infections is also possible.",Kniest dysplasia,0000564,GHR,https://ghr.nlm.nih.gov/condition/kniest-dysplasia,C0265279,T019,Disorders
How many people are affected by Kniest dysplasia ?,0000564-2,frequency,Kniest dysplasia is a rare condition; the exact incidence is unknown.,Kniest dysplasia,0000564,GHR,https://ghr.nlm.nih.gov/condition/kniest-dysplasia,C0265279,T019,Disorders
What are the genetic changes related to Kniest dysplasia ?,0000564-3,genetic changes,"Kniest dysplasia is one of a spectrum of skeletal disorders caused by mutations in the COL2A1 gene. This gene provides instructions for making a protein that forms type II collagen. This type of collagen is found mostly in the clear gel that fills the eyeball (the vitreous) and in cartilage. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Type II collagen is essential for the normal development of bones and other connective tissues that form the body's supportive framework.  Most mutations in the COL2A1 gene that cause Kniest dysplasia interfere with the assembly of type II collagen molecules. Abnormal collagen prevents bones and other connective tissues from developing properly, which leads to the signs and symptoms of Kniest dysplasia.",Kniest dysplasia,0000564,GHR,https://ghr.nlm.nih.gov/condition/kniest-dysplasia,C0265279,T019,Disorders
Is Kniest dysplasia inherited ?,0000564-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Kniest dysplasia,0000564,GHR,https://ghr.nlm.nih.gov/condition/kniest-dysplasia,C0265279,T019,Disorders
What are the treatments for Kniest dysplasia ?,0000564-5,treatment,These resources address the diagnosis or management of Kniest dysplasia:  - Genetic Testing Registry: Kniest dysplasia  - MedlinePlus Encyclopedia: Clubfoot  - MedlinePlus Encyclopedia: Retinal Detachment  - MedlinePlus Encyclopedia: Scoliosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Kniest dysplasia,0000564,GHR,https://ghr.nlm.nih.gov/condition/kniest-dysplasia,C0265279,T019,Disorders
What is (are) Knobloch syndrome ?,0000565-1,information,"Knobloch syndrome is a rare condition characterized by severe vision problems and a skull defect.  A characteristic feature of Knobloch syndrome is extreme nearsightedness (high myopia). In addition, several other eye abnormalities are common in people with this condition. Most affected individuals have vitreoretinal degeneration, which is breakdown (degeneration) of two structures in the eye called the vitreous and the retina. The vitreous is the gelatin-like substance that fills the eye, and the retina is the light-sensitive tissue at the back of the eye. Vitreoretinal degeneration often leads to separation of the retina from the back of the eye (retinal detachment). Affected individuals may also have abnormalities in the central area of the retina, called the macula. The macula is responsible for sharp central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. Due to abnormalities in the vitreous, retina, and macula, people with Knobloch syndrome often develop blindness in one or both eyes.  Another characteristic feature of Knobloch syndrome is a skull defect called an occipital encephalocele, which is a sac-like protrusion of the brain (encephalocele) through a defect in the bone at the base of the skull (occipital bone). Some affected individuals have been diagnosed with a different skull defect in the occipital region, and it is unclear whether the defect is always a true encephalocele. In other conditions, encephaloceles may be associated with intellectual disability; however, most people with Knobloch syndrome have normal intelligence.",Knobloch syndrome,0000565,GHR,https://ghr.nlm.nih.gov/condition/knobloch-syndrome,C1849409,T019,Disorders
How many people are affected by Knobloch syndrome ?,0000565-2,frequency,"Knobloch syndrome is a rare condition. However, the exact prevalence of the condition is unknown.",Knobloch syndrome,0000565,GHR,https://ghr.nlm.nih.gov/condition/knobloch-syndrome,C1849409,T019,Disorders
What are the genetic changes related to Knobloch syndrome ?,0000565-3,genetic changes,"Mutations in the COL18A1 gene can cause Knobloch syndrome. The COL18A1 gene provides instructions for making a protein that forms collagen XVIII, which is found in the basement membranes of tissues throughout the body. Basement membranes are thin, sheet-like structures that separate and support cells in these tissues. Collagen XVIII is found in the basement membranes of several parts of the eye, including the vitreous and retina, among other tissues. Little is known about the function of this protein, but it appears to be involved in normal development of the eye.  Several mutations in the COL18A1 gene have been identified in people with Knobloch syndrome. Most COL18A1 gene mutations lead to an abnormally short version of the genetic blueprint used to make the collagen XVIII protein. Although the process is unclear, the COL18A1 gene mutations result in the loss of collagen XVIII protein, which likely causes the signs and symptoms of Knobloch syndrome.  When the condition is caused by COL18A1 gene mutations, it is sometimes referred to as Knobloch syndrome type I. Research indicates that mutations in at least two other genes that have not been identified may cause Knobloch syndrome types II and III. Although they are caused by alterations in different genes, the three types of the condition have similar signs and symptoms.",Knobloch syndrome,0000565,GHR,https://ghr.nlm.nih.gov/condition/knobloch-syndrome,C1849409,T019,Disorders
Is Knobloch syndrome inherited ?,0000565-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Knobloch syndrome,0000565,GHR,https://ghr.nlm.nih.gov/condition/knobloch-syndrome,C1849409,T019,Disorders
What are the treatments for Knobloch syndrome ?,0000565-5,treatment,These resources address the diagnosis or management of Knobloch syndrome:  - American Academy of Ophthalmology: Eye Smart  - Genetic Testing Registry: Knobloch syndrome 1  - JAMA Patient Page: Retinal Detachment  - National Eye Institute: Facts About Retinal Detachment  - Prevent Blindness America: Retinal Tears and Detachments   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Knobloch syndrome,0000565,GHR,https://ghr.nlm.nih.gov/condition/knobloch-syndrome,C1849409,T019,Disorders
What is (are) Koolen-de Vries syndrome ?,0000566-1,information,"Koolen-de Vries syndrome is a disorder characterized by developmental delay and mild to moderate intellectual disability. People with this disorder typically have a disposition that is described as cheerful, sociable, and cooperative. They usually have weak muscle tone (hypotonia) in childhood. About half have recurrent seizures (epilepsy).  Affected individuals often have distinctive facial features including a high, broad forehead; droopy eyelids (ptosis); a narrowing of the eye openings (blepharophimosis); outer corners of the eyes that point upward (upward-slanting palpebral fissures); skin folds covering the inner corner of the eyes (epicanthal folds); a bulbous nose; and prominent ears. Males with Koolen-de Vries syndrome often have undescended testes (cryptorchidism). Defects in the walls between the chambers of the heart (septal defects) or other cardiac abnormalities, kidney problems, and skeletal anomalies such as foot deformities occur in some affected individuals.",Koolen-de Vries syndrome,0000566,GHR,https://ghr.nlm.nih.gov/condition/koolen-de-vries-syndrome,C0039082,T047,Disorders
How many people are affected by Koolen-de Vries syndrome ?,0000566-2,frequency,"The prevalence of Koolen-de Vries syndrome is estimated to be 1 in 16,000. However, the underlying genetic cause is often not identified in people with intellectual disability, so this condition is likely underdiagnosed.",Koolen-de Vries syndrome,0000566,GHR,https://ghr.nlm.nih.gov/condition/koolen-de-vries-syndrome,C0039082,T047,Disorders
What are the genetic changes related to Koolen-de Vries syndrome ?,0000566-3,genetic changes,"Koolen-de Vries syndrome is caused by genetic changes that eliminate the function of one copy of the KANSL1 gene in each cell. Most affected individuals are missing a small amount of genetic material, including the KANSL1 gene, from one copy of chromosome 17. This type of genetic abnormality is called a microdeletion. A small number of individuals with Koolen-de Vries syndrome do not have a chromosome 17 microdeletion but instead have a mutation within the KANSL1 gene that causes one copy of the gene to be nonfunctional.  The microdeletion that causes Koolen-de Vries syndrome occurs on the long (q) arm of chromosome 17 at a location designated q21.31. While the exact size of the deletion varies among affected individuals, most are missing a sequence of about 500,000 DNA building blocks (base pairs) containing several genes. However, because individuals with KANSL1 gene mutations have the same signs and symptoms as those with the microdeletion, researchers have concluded that the loss of this gene accounts for the features of this disorder.  The KANSL1 gene provides instructions for making a protein that helps regulate gene activity (expression) by modifying chromatin. Chromatin is the complex of DNA and protein that packages DNA into chromosomes. The protein produced from the KANSL1 gene is found in most organs and tissues of the body before birth and throughout life. By its involvement in controlling the activity of other genes, this protein plays an important role in the development and function of many parts of the body. Loss of one copy of this gene impairs normal development and function, but the relationship of KANSL1 gene loss to the specific signs and symptoms of Koolen-de Vries syndrome is unclear.",Koolen-de Vries syndrome,0000566,GHR,https://ghr.nlm.nih.gov/condition/koolen-de-vries-syndrome,C0039082,T047,Disorders
Is Koolen-de Vries syndrome inherited ?,0000566-4,inheritance,"Koolen-de Vries syndrome is considered an autosomal dominant condition because a deletion or mutation affecting one copy of the KANSL1 gene in each cell is sufficient to cause the disorder. In most cases, the disorder is not inherited. The genetic change occurs most often as a random event during the formation of reproductive cells (eggs and sperm) or in early fetal development. Affected people typically have no history of the disorder in their family. While it is possible for them to pass the condition on to their children, no individuals with Koolen-de Vries syndrome have been known to reproduce.  Most people with Koolen-de Vries syndrome caused by a deletion have had at least one parent with a common variant of the 17q21.31 region of chromosome 17 called the H2 lineage. This variant is found in 20 percent of people of European and Middle Eastern descent, although it is rare in other populations. In the H2 lineage, a 900 kb segment of DNA, which includes the region deleted in most cases of Koolen-de Vries syndrome, has undergone an inversion. An inversion involves two breaks in a chromosome; the resulting piece of DNA is reversed and reinserted into the chromosome.  People with the H2 lineage have no health problems related to the inversion. However, genetic material can be lost or duplicated when the inversion is passed to the next generation. Other, unknown factors are thought to play a role in this process. So while the inversion is very common, only an extremely small percentage of parents with the inversion have a child affected by Koolen-de Vries syndrome.",Koolen-de Vries syndrome,0000566,GHR,https://ghr.nlm.nih.gov/condition/koolen-de-vries-syndrome,C0039082,T047,Disorders
What are the treatments for Koolen-de Vries syndrome ?,0000566-5,treatment,These resources address the diagnosis or management of Koolen-de Vries syndrome:  - Gene Review: Gene Review: KANSL1-Related Intellectual Disability Syndrome  - Genetic Testing Registry: Koolen-de Vries syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Koolen-de Vries syndrome,0000566,GHR,https://ghr.nlm.nih.gov/condition/koolen-de-vries-syndrome,C0039082,T047,Disorders
What is (are) Krabbe disease ?,0000567-1,information,"Krabbe disease (also called globoid cell leukodystrophy) is a degenerative disorder that affects the nervous system. It is caused by the shortage (deficiency) of an enzyme called galactosylceramidase. This enzyme deficiency impairs the growth and maintenance of myelin, the protective covering around certain nerve cells that ensures the rapid transmission of nerve impulses. Krabbe disease is part of a group of disorders known as leukodystrophies, which result from the loss of myelin (demyelination). This disorder is also characterized by the abnormal presence of globoid cells, which are globe-shaped cells that usually have more than one nucleus.  The symptoms of Krabbe disease usually begin before the age of 1 year (the infantile form). Initial signs and symptoms typically include irritability, muscle weakness, feeding difficulties, episodes of fever without any sign of infection, stiff posture, and slowed mental and physical development. As the disease progresses, muscles continue to weaken, affecting the infant's ability to move, chew, swallow, and breathe. Affected infants also experience vision loss and seizures.  Less commonly, onset of Krabbe disease can occur in childhood, adolescence, or adulthood (late-onset forms). Visual problems and walking difficulties are the most common initial symptoms in this form of the disorder, however, signs and symptoms vary considerably among affected individuals.",Krabbe disease,0000567,GHR,https://ghr.nlm.nih.gov/condition/krabbe-disease,C0023521,T047,Disorders
How many people are affected by Krabbe disease ?,0000567-2,frequency,"In the United States, Krabbe disease affects about 1 in 100,000 individuals. A higher incidence (6 cases per 1,000 people) has been reported in a few isolated communities in Israel.",Krabbe disease,0000567,GHR,https://ghr.nlm.nih.gov/condition/krabbe-disease,C0023521,T047,Disorders
What are the genetic changes related to Krabbe disease ?,0000567-3,genetic changes,"Mutations in the GALC gene cause Krabbe disease. These mutations cause a deficiency of the enzyme galactosylceramidase. This deficiency leads to a progressive loss of myelin that covers many nerves. Without myelin, nerves in the brain and other parts of the body cannot function properly, leading to the signs and symptoms of Krabbe disease.",Krabbe disease,0000567,GHR,https://ghr.nlm.nih.gov/condition/krabbe-disease,C0023521,T047,Disorders
Is Krabbe disease inherited ?,0000567-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Krabbe disease,0000567,GHR,https://ghr.nlm.nih.gov/condition/krabbe-disease,C0023521,T047,Disorders
What are the treatments for Krabbe disease ?,0000567-5,treatment,These resources address the diagnosis or management of Krabbe disease:  - Baby's First Test  - Gene Review: Gene Review: Krabbe Disease  - Genetic Testing Registry: Galactosylceramide beta-galactosidase deficiency  - MedlinePlus Encyclopedia: Krabbe disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Krabbe disease,0000567,GHR,https://ghr.nlm.nih.gov/condition/krabbe-disease,C0023521,T047,Disorders
What is (are) Kufs disease ?,0000568-1,information,"Kufs disease is a condition that primarily affects the nervous system, causing problems with movement and intellectual function that worsen over time. The signs and symptoms of Kufs disease typically appear around age 30, but they can develop anytime between adolescence and late adulthood.  Two types of Kufs disease have been described: type A and type B. The two types are differentiated by their genetic cause, pattern of inheritance, and certain signs and symptoms. Type A is characterized by a combination of seizures and uncontrollable muscle jerks (myoclonic epilepsy), a decline in intellectual function (dementia), impaired muscle coordination (ataxia), involuntary movements such as tremors or tics, and speech difficulties (dysarthria). Kufs disease type B shares many features with type A, but it is distinguished by changes in personality and is not associated with myoclonic epilepsy or dysarthria.  The signs and symptoms of Kufs disease worsen over time, and affected individuals usually survive about 15 years after the disorder begins.  Kufs disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which are also known as Batten disease. These disorders affect the nervous system and typically cause progressive problems with vision, movement, and thinking ability. Kufs disease, however, does not affect vision. The different types of NCLs are distinguished by the age at which signs and symptoms first appear.",Kufs disease,0000568,GHR,https://ghr.nlm.nih.gov/condition/kufs-disease,C0022797,T047,Disorders
How many people are affected by Kufs disease ?,0000568-2,frequency,"Collectively, all forms of NCL affect an estimated 1 in 100,000 individuals worldwide. NCLs are more common in Finland, where approximately 1 in 12,500 individuals have the condition. Kufs disease is thought to represent 1.3 to 10 percent of all NCLs.",Kufs disease,0000568,GHR,https://ghr.nlm.nih.gov/condition/kufs-disease,C0022797,T047,Disorders
What are the genetic changes related to Kufs disease ?,0000568-3,genetic changes,"Mutations in the CLN6 or PPT1 gene cause Kufs disease type A, and mutations in the DNAJC5 or CTSF gene cause Kufs disease type B. Most of the proteins or enzymes produced from these genes are involved in breaking down proteins or clearing unneeded materials from cells.  The CLN6 gene provides instructions for making a protein that likely regulates the transport of certain proteins and fats within the cell. Based on this function, the CLN6 protein appears to help in the process of ridding cells of materials they no longer need.  The PPT1 gene provides instructions for making an enzyme called palmitoyl-protein thioesterase 1. This enzyme is found in structures called lysosomes, which are compartments within cells that break down and recycle different types of molecules. Palmitoyl-protein thioesterase 1 removes certain fats from proteins, which probably helps break down the proteins.  The protein produced from the DNAJC5 gene is called cysteine string protein alpha (CSP). This protein is found in the brain and plays a role in the transmission of nerve impulses by ensuring that nerve cells receive signals.  The enzyme produced from the CTSF gene is called cathepsin F. Cathepsin F acts as a protease, which modifies proteins by cutting them apart. Cathepsin F is found in many types of cells and is active in lysosomes. By cutting proteins apart, cathepsin F can break proteins down, turn on (activate) proteins, and regulate self-destruction of the cell (apoptosis).  Mutations in the CLN6, PPT1, DNAJC5, or CTSF gene usually reduce the activity of the gene or impair the function of the protein or enzyme produced from the gene. In many cases, these mutations cause incomplete breakdown of certain proteins and other materials. These materials accumulate in the lysosome, forming fatty substances called lipopigments. In other cases, it is unclear what causes the buildup of lipopigments. In Kufs disease, these accumulations occur in nerve cells (neurons) in the brain, resulting in cell dysfunction and eventually cell death. The progressive death of neurons leads to the signs and symptoms of Kufs disease.  Some people with either type of Kufs disease do not have an identified mutation in any of these four genes. In these individuals, the cause of the condition is unknown.",Kufs disease,0000568,GHR,https://ghr.nlm.nih.gov/condition/kufs-disease,C0022797,T047,Disorders
Is Kufs disease inherited ?,0000568-4,inheritance,"Kufs disease type A, caused by mutations in the CLN6 or PPT1 gene, has an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Kufs disease type B, caused by mutations in the DNAJC5 or CTSF gene, has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases of Kufs disease type B occur in people with no history of the disorder in their family.",Kufs disease,0000568,GHR,https://ghr.nlm.nih.gov/condition/kufs-disease,C0022797,T047,Disorders
What are the treatments for Kufs disease ?,0000568-5,treatment,These resources address the diagnosis or management of Kufs disease:  - Gene Review: Gene Review: Neuronal Ceroid-Lipofuscinoses  - Genetic Testing Registry: Adult neuronal ceroid lipofuscinosis  - Genetic Testing Registry: Ceroid lipofuscinosis neuronal 4B autosomal dominant   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Kufs disease,0000568,GHR,https://ghr.nlm.nih.gov/condition/kufs-disease,C0022797,T047,Disorders
What is (are) Kuskokwim syndrome ?,0000569-1,information,"Kuskokwim syndrome is characterized by joint deformities called contractures that restrict the movement of affected joints. This condition has been found only in a population of native Alaskans known as Yup'ik Eskimos, who live in and around a region of southwest Alaska known as the Kuskokwim River Delta.  In Kuskokwim syndrome, contractures most commonly affect the knees, ankles, and elbows, although other joints, particularly of the lower body, can be affected. The contractures are usually present at birth and worsen during childhood. They tend to stabilize after childhood, and they remain throughout life.  Some individuals with this condition have other bone abnormalities, most commonly affecting the spine, pelvis, and feet. Affected individuals can develop an inward curve of the lower back (lordosis), a spine that curves to the side (scoliosis), wedge-shaped spinal bones, or an abnormality of the collarbones (clavicles) described as clubbing. Affected individuals are typically shorter than their peers and they may have an abnormally large head (macrocephaly).",Kuskokwim syndrome,0000569,GHR,https://ghr.nlm.nih.gov/condition/kuskokwim-syndrome,C3839326,T047,Disorders
How many people are affected by Kuskokwim syndrome ?,0000569-2,frequency,Kuskokwim syndrome is extremely rare. It affects a small number of people from the Yup'ik Eskimo population in southwest Alaska.,Kuskokwim syndrome,0000569,GHR,https://ghr.nlm.nih.gov/condition/kuskokwim-syndrome,C3839326,T047,Disorders
What are the genetic changes related to Kuskokwim syndrome ?,0000569-3,genetic changes,"Kuskokwim syndrome is caused by mutations in the FKBP10 gene, which provides instructions for making the FKBP10 protein (formerly known as FKBP65). This protein is important for the correct processing of complex molecules called collagens, which provide structure and strength to connective tissues that support the body's bones, joints, and organs. Collagen molecules are cross-linked to one another to form long, thin fibrils, which are found in the spaces around cells (the extracellular matrix). The formation of cross-links results in very strong collagen fibrils. The FKBP10 protein attaches to collagens and plays a role in their cross-linking.  A mutation in the FKBP10 gene alters the FKBP10 protein, making it unstable and easily broken down. As a result, people with Kuskokwim syndrome have only about 5 percent of the normal amount of FKBP10 protein. This reduction in protein levels impairs collagen cross-linking and leads to a disorganized network of collagen molecules. It is unclear how these changes in the collagen matrix are involved in the development of joint contractures and other abnormalities in people with Kuskokwim syndrome.",Kuskokwim syndrome,0000569,GHR,https://ghr.nlm.nih.gov/condition/kuskokwim-syndrome,C3839326,T047,Disorders
Is Kuskokwim syndrome inherited ?,0000569-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Kuskokwim syndrome,0000569,GHR,https://ghr.nlm.nih.gov/condition/kuskokwim-syndrome,C3839326,T047,Disorders
What are the treatments for Kuskokwim syndrome ?,0000569-5,treatment,These resources address the diagnosis or management of Kuskokwim syndrome:  - Genetic Testing Registry: Kuskokwim disease  - Mount Sinai Hospital: Contractures Information   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Kuskokwim syndrome,0000569,GHR,https://ghr.nlm.nih.gov/condition/kuskokwim-syndrome,C3839326,T047,Disorders
What is (are) L1 syndrome ?,0000570-1,information,"L1 syndrome is an inherited disorder that primarily affects the nervous system. L1 syndrome involves a variety of features that were once thought to be distinct disorders, but are now considered to be part of the same syndrome. The most common characteristics of L1 syndrome are muscle stiffness (spasticity) of the lower limbs, intellectual disability, increased fluid in the center of the brain (hydrocephalus), and thumbs bent toward the palm (adducted thumbs). People with L1 syndrome can also have difficulty speaking (aphasia), seizures, and underdeveloped or absent tissue connecting the left and right halves of the brain (agenesis of the corpus callosum). The symptoms of L1 syndrome vary widely among affected individuals, even among members of the same family. Because this disorder involves spasticity of the lower limbs, L1 syndrome is sometimes referred to as spastic paraplegia type 1 (SPG1).",L1 syndrome,0000570,GHR,https://ghr.nlm.nih.gov/condition/l1-syndrome,C0795953,T047,Disorders
How many people are affected by L1 syndrome ?,0000570-2,frequency,"L1 syndrome is estimated to occur in 1 in 25,000 to 60,000 males. Females are rarely affected by this condition.",L1 syndrome,0000570,GHR,https://ghr.nlm.nih.gov/condition/l1-syndrome,C0795953,T047,Disorders
What are the genetic changes related to L1 syndrome ?,0000570-3,genetic changes,"L1 syndrome is caused by mutations in the L1CAM gene. The L1CAM gene provides instructions for producing the L1 protein, which is found throughout the nervous system on the surface of nerve cells (neurons). The L1 protein plays a role in the development and organization of neurons, the formation of the protective sheath (myelin) that surrounds certain neurons, and the formation of junctions between nerve cells (synapses), where cell-to-cell communication occurs. Mutations in the L1 protein can interfere with these developmental processes. Research suggests that a disruption in the development and function of neurons causes the signs and symptoms of L1 syndrome.",L1 syndrome,0000570,GHR,https://ghr.nlm.nih.gov/condition/l1-syndrome,C0795953,T047,Disorders
Is L1 syndrome inherited ?,0000570-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",L1 syndrome,0000570,GHR,https://ghr.nlm.nih.gov/condition/l1-syndrome,C0795953,T047,Disorders
What are the treatments for L1 syndrome ?,0000570-5,treatment,"These resources address the diagnosis or management of L1 syndrome:  - Gene Review: Gene Review: Hereditary Spastic Paraplegia Overview  - Gene Review: Gene Review: L1 Syndrome  - Genetic Testing Registry: Corpus callosum, partial agenesis of, X-linked  - Genetic Testing Registry: L1 Syndrome  - Genetic Testing Registry: Spastic paraplegia 1  - Genetic Testing Registry: X-linked hydrocephalus syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",L1 syndrome,0000570,GHR,https://ghr.nlm.nih.gov/condition/l1-syndrome,C0795953,T047,Disorders
What is (are) lacrimo-auriculo-dento-digital syndrome ?,0000571-1,information,"Lacrimo-auriculo-dento-digital (LADD) syndrome is a genetic disorder that mainly affects the eyes, ears, mouth, and hands. LADD syndrome is characterized by defects in the tear-producing lacrimal system (lacrimo-), ear problems (auriculo-), dental abnormalities (dento-), and deformities of the fingers (digital).  The lacrimal system consists of structures in the eye that produce and secrete tears. Lacrimal system malformations that can occur with LADD syndrome include an underdeveloped or absent opening to the tear duct at the edge of the eyelid (lacrimal puncta) and blockage of the channel (nasolacrimal duct) that connects the inside corner of the eye where tears gather (tear sac) to the nasal cavity. These malformations of the lacrimal system can lead to chronic tearing (epiphora), inflammation of the tear sac (dacryocystitis), inflammation of the front surface of the eye (keratoconjunctivitis), or an inability to produce tears.  Ears that are low-set and described as cup-shaped, often accompanied by hearing loss, are a common feature of LADD syndrome. The hearing loss may be mild to severe and can be caused by changes in the inner ear (sensorineural deafness), changes in the middle ear (conductive hearing loss), or both (mixed hearing loss).  People with LADD syndrome may have underdeveloped or absent salivary glands, which impairs saliva production. A decrease in saliva leads to dry mouth (xerostomia) and a greater susceptibility to cavities. Individuals with LADD syndrome often have small, underdeveloped teeth with thin enamel and peg-shaped front teeth (incisors).  Hand deformities are also a frequent feature of LADD syndrome. Affected individuals may have abnormally small or missing thumbs. Alternatively, the thumb might be duplicated, fused with the index finger (syndactyly), abnormally placed, or have three bones instead of the normal two and resemble a finger. Abnormalities of the fingers include syndactyly of the second and third fingers, extra or missing fingers, and curved pinky fingers (fifth finger clinodactyly). Sometimes, the forearm is also affected. It can be shorter than normal with abnormal wrist and elbow joint development that limits movement.  People with LADD syndrome may also experience other signs and symptoms. They can have kidney problems that include hardening of the kidneys (nephrosclerosis) and urine accumulation in the kidneys (hydronephrosis), which can impair kidney function. Recurrent urinary tract infections and abnormalities of the genitourinary system can also occur. Some people with LADD syndrome have an opening in the roof of the mouth (cleft palate) with or without a split in the upper lip (cleft lip). The signs and symptoms of this condition vary widely, even among affected family members.",lacrimo-auriculo-dento-digital syndrome,0000571,GHR,https://ghr.nlm.nih.gov/condition/lacrimo-auriculo-dento-digital-syndrome,C0265269,T047,Disorders
How many people are affected by lacrimo-auriculo-dento-digital syndrome ?,0000571-2,frequency,LADD syndrome appears to be a rare condition; at least 60 cases have been described in the scientific literature.,lacrimo-auriculo-dento-digital syndrome,0000571,GHR,https://ghr.nlm.nih.gov/condition/lacrimo-auriculo-dento-digital-syndrome,C0265269,T047,Disorders
What are the genetic changes related to lacrimo-auriculo-dento-digital syndrome ?,0000571-3,genetic changes,"Mutations in the FGFR2, FGFR3, or FGF10 gene can cause LADD syndrome.  The FGFR2 and FGFR3 genes provide instructions for making proteins that are part of a family called fibroblast growth factor receptors. The FGF10 gene provides instructions for making a protein called a fibroblast growth factor, which is a family of proteins that attaches (binds) to fibroblast growth factor receptors. The receptors are located within the membranes of cells, where they receive signals that control growth and development from growth factors outside the cell. The signals triggered by the FGFR2, FGFR3, and FGF10 genes appear to stimulate cells to form the structures that make up the lacrimal glands, salivary glands, ears, skeleton, and many other organs.  Mutations in the FGFR2, FGFR3, or FGF10 gene alter the proteins produced from these genes and disrupt the signaling within cells. As a result, cell maturation and development is impaired and the formation of many tissues is affected, leading to the signs and symptoms of LADD syndrome.",lacrimo-auriculo-dento-digital syndrome,0000571,GHR,https://ghr.nlm.nih.gov/condition/lacrimo-auriculo-dento-digital-syndrome,C0265269,T047,Disorders
Is lacrimo-auriculo-dento-digital syndrome inherited ?,0000571-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means a mutation in one copy of the FGFR2, FGFR3, or FGF10 gene in each cell is sufficient to cause the disorder.  In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",lacrimo-auriculo-dento-digital syndrome,0000571,GHR,https://ghr.nlm.nih.gov/condition/lacrimo-auriculo-dento-digital-syndrome,C0265269,T047,Disorders
What are the treatments for lacrimo-auriculo-dento-digital syndrome ?,0000571-5,treatment,These resources address the diagnosis or management of lacrimo-auriculo-dento-digital syndrome:  - American Academy of Ophthalmology: The Tearing Patient  - Cincinnati Children's Hospital: Tear Duct Probing and Irrigation  - Cleveland Clinic: Dry Eyes  - Cleveland Clinic: Dry Mouth Treatment  - Genetic Testing Registry: Levy-Hollister syndrome  - Monroe Carell Jr. Children's Hospital at Vanderbilt: Blocked Tear Duct (Dacryostenosis)   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,lacrimo-auriculo-dento-digital syndrome,0000571,GHR,https://ghr.nlm.nih.gov/condition/lacrimo-auriculo-dento-digital-syndrome,C0265269,T047,Disorders
What is (are) lactate dehydrogenase deficiency ?,0000572-1,information,"Lactate dehydrogenase deficiency is a condition that affects how the body breaks down sugar to use as energy in cells, primarily muscle cells.  There are two types of this condition: lactate dehydrogenase-A deficiency (sometimes called glycogen storage disease XI) and lactate dehydrogenase-B deficiency.  People with lactate dehydrogenase-A deficiency experience fatigue, muscle pain, and cramps during exercise (exercise intolerance). In some people with lactate dehydrogenase-A deficiency, high-intensity exercise or other strenuous activity leads to the breakdown of muscle tissue (rhabdomyolysis). The destruction of muscle tissue releases a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria). Myoglobin causes the urine to be red or brown. This protein can also damage the kidneys, in some cases leading to life-threatening kidney failure. Some people with lactate dehydrogenase-A deficiency develop skin rashes. The severity of the signs and symptoms among individuals with lactate dehydrogenase-A deficiency varies greatly.  People with lactate dehydrogenase-B deficiency typically do not have any signs or symptoms of the condition. They do not have difficulty with physical activity or any specific physical features related to the condition. Affected individuals are usually discovered only when routine blood tests reveal reduced lactate dehydrogenase activity.",lactate dehydrogenase deficiency,0000572,GHR,https://ghr.nlm.nih.gov/condition/lactate-dehydrogenase-deficiency,C0342769,T047,Disorders
How many people are affected by lactate dehydrogenase deficiency ?,0000572-2,frequency,"Lactate dehydrogenase deficiency is a rare disorder. In Japan, this condition affects 1 in 1 million individuals; the prevalence of lactate dehydrogenase deficiency in other countries is unknown.",lactate dehydrogenase deficiency,0000572,GHR,https://ghr.nlm.nih.gov/condition/lactate-dehydrogenase-deficiency,C0342769,T047,Disorders
What are the genetic changes related to lactate dehydrogenase deficiency ?,0000572-3,genetic changes,"Mutations in the LDHA gene cause lactate dehydrogenase-A deficiency, and mutations in the LDHB gene cause lactate dehydrogenase-B deficiency. These genes provide instructions for making the lactate dehydrogenase-A and lactate dehydrogenase-B pieces (subunits) of the lactate dehydrogenase enzyme. This enzyme is found throughout the body and is important for creating energy for cells. There are five different forms of this enzyme, each made up of four protein subunits. Various combinations of the lactate dehydrogenase-A and lactate dehydrogenase-B subunits make up the different forms of the enzyme.  The version of lactate dehydrogenase made of four lactate dehydrogenase-A subunits is found primarily in skeletal muscles, which are muscles used for movement. Skeletal muscles need large amounts of energy during high-intensity physical activity when the body's oxygen intake is not sufficient for the amount of energy required (anaerobic exercise). During anaerobic exercise, the lactate dehydrogenase enzyme is involved in the breakdown of sugar stored in the muscles (in the form of glycogen) to create additional energy. During the final stage of glycogen breakdown, lactate dehydrogenase converts a molecule called pyruvate to a similar molecule called lactate.  Mutations in the LDHA gene result in the production of an abnormal lactate dehydrogenase-A subunit that cannot attach (bind) to other subunits to form the lactate dehydrogenase enzyme. A lack of functional subunit reduces the amount of enzyme that is formed, mostly affecting skeletal muscles. As a result, glycogen is not broken down efficiently, leading to decreased energy in muscle cells. When muscle cells do not get sufficient energy during exercise or strenuous activity, the muscles become weak and muscle tissue can break down, as experienced by people with lactate dehydrogenase-A deficiency.  The version of lactate dehydrogenase made of four lactate dehydrogenase-B subunits is found primarily in heart (cardiac) muscle. In cardiac muscle, lactate dehydrogenase converts lactate to pyruvate, which can participate in other chemical reactions to create energy. LDHB gene mutations lead to the production of an abnormal lactate dehydrogenase-B subunit that cannot form the lactate dehydrogenase enzyme. Even though lactate dehydrogenase activity is decreased in the cardiac muscle of people with lactate dehydrogenase-B deficiency, they do not appear to have any signs or symptoms related to their condition. It is unclear why this type of enzyme deficiency does not cause any health problems.",lactate dehydrogenase deficiency,0000572,GHR,https://ghr.nlm.nih.gov/condition/lactate-dehydrogenase-deficiency,C0342769,T047,Disorders
Is lactate dehydrogenase deficiency inherited ?,0000572-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",lactate dehydrogenase deficiency,0000572,GHR,https://ghr.nlm.nih.gov/condition/lactate-dehydrogenase-deficiency,C0342769,T047,Disorders
What are the treatments for lactate dehydrogenase deficiency ?,0000572-5,treatment,These resources address the diagnosis or management of lactate dehydrogenase deficiency:  - Genetic Testing Registry: Glycogen storage disease XI  - Genetic Testing Registry: Lactate dehydrogenase B deficiency  - MedlinePlus Encyclopedia: LDH Isoenzymes  - MedlinePlus Encyclopedia: Lactate Dehydrogenase Test   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,lactate dehydrogenase deficiency,0000572,GHR,https://ghr.nlm.nih.gov/condition/lactate-dehydrogenase-deficiency,C0342769,T047,Disorders
What is (are) lactose intolerance ?,0000573-1,information,"Lactose intolerance is an impaired ability to digest lactose, a sugar found in milk and other dairy products. Lactose is normally broken down by an enzyme called lactase, which is produced by cells in the lining of the small intestine.  Congenital lactase deficiency, also called congenital alactasia, is a disorder in which infants are unable to break down lactose in breast milk or formula. This form of lactose intolerance results in severe diarrhea. If affected infants are not given a lactose-free infant formula, they may develop severe dehydration and weight loss.  Lactose intolerance in adulthood is caused by reduced production of lactase after infancy (lactase nonpersistence). If individuals with lactose intolerance consume lactose-containing dairy products, they may experience abdominal pain, bloating, flatulence, nausea, and diarrhea beginning 30 minutes to 2 hours later.  Most people with lactase nonpersistence retain some lactase activity and can include varying amounts of lactose in their diets without experiencing symptoms. Often, affected individuals have difficulty digesting fresh milk but can eat certain dairy products such as cheese or yogurt without discomfort. These foods are made using fermentation processes that break down much of the lactose in milk.",lactose intolerance,0000573,GHR,https://ghr.nlm.nih.gov/condition/lactose-intolerance,C0022951,T047,Disorders
How many people are affected by lactose intolerance ?,0000573-2,frequency,"Lactose intolerance in infancy resulting from congenital lactase deficiency is a rare disorder. Its incidence is unknown. This condition is most common in Finland, where it affects an estimated 1 in 60,000 newborns.  Approximately 65 percent of the human population has a reduced ability to digest lactose after infancy. Lactose intolerance in adulthood is most prevalent in people of East Asian descent, affecting more than 90 percent of adults in some of these communities. Lactose intolerance is also very common in people of West African, Arab, Jewish, Greek, and Italian descent.  The prevalence of lactose intolerance is lowest in populations with a long history of dependence on unfermented milk products as an important food source. For example, only about 5 percent of people of Northern European descent are lactose intolerant.",lactose intolerance,0000573,GHR,https://ghr.nlm.nih.gov/condition/lactose-intolerance,C0022951,T047,Disorders
What are the genetic changes related to lactose intolerance ?,0000573-3,genetic changes,"Lactose intolerance in infants (congenital lactase deficiency) is caused by mutations in the LCT gene. The LCT gene provides instructions for making the lactase enzyme. Mutations that cause congenital lactase deficiency are believed to interfere with the function of lactase, causing affected infants to have a severely impaired ability to digest lactose in breast milk or formula.  Lactose intolerance in adulthood is caused by gradually decreasing activity (expression) of the LCT gene after infancy, which occurs in most humans. LCT gene expression is controlled by a DNA sequence called a regulatory element, which is located within a nearby gene called MCM6. Some individuals have inherited changes in this element that lead to sustained lactase production in the small intestine and the ability to digest lactose throughout life. People without these changes have a reduced ability to digest lactose as they get older, resulting in the signs and symptoms of lactose intolerance.",lactose intolerance,0000573,GHR,https://ghr.nlm.nih.gov/condition/lactose-intolerance,C0022951,T047,Disorders
Is lactose intolerance inherited ?,0000573-4,inheritance,"The type of lactose intolerance that occurs in infants (congenital lactase deficiency) is inherited in an autosomal recessive pattern, which means both copies of the LCT gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  The ability to digest lactose into adulthood depends on which variations in the regulatory element within the MCM6 gene individuals have inherited from their parents. The variations that promote continued lactase production are considered autosomal dominant, which means one copy of the altered regulatory element in each cell is sufficient to sustain lactase production. People who have not inherited these variations from either parent will have some degree of lactose intolerance.",lactose intolerance,0000573,GHR,https://ghr.nlm.nih.gov/condition/lactose-intolerance,C0022951,T047,Disorders
What are the treatments for lactose intolerance ?,0000573-5,treatment,These resources address the diagnosis or management of lactose intolerance:  - Genetic Testing Registry: Congenital lactase deficiency  - Genetic Testing Registry: Nonpersistence of intestinal lactase  - MedlinePlus Encyclopedia: Lactose Intolerance  - MedlinePlus Encyclopedia: Lactose Tolerance Tests   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,lactose intolerance,0000573,GHR,https://ghr.nlm.nih.gov/condition/lactose-intolerance,C0022951,T047,Disorders
What is (are) Lafora progressive myoclonus epilepsy ?,0000574-1,information,"Lafora progressive myoclonus epilepsy is a brain disorder characterized by recurrent seizures (epilepsy) and a decline in intellectual function. The signs and symptoms of the disorder usually appear in late childhood or adolescence and worsen with time.  Myoclonus is a term used to describe episodes of sudden, involuntary muscle jerking or twitching that can affect part of the body or the entire body. Myoclonus can occur when an affected person is at rest, and it is made worse by motion, excitement, or flashing light (photic stimulation). In the later stages of Lafora progressive myoclonus epilepsy, myoclonus often occurs continuously and affects the entire body.  Several types of seizures commonly occur in people with Lafora progressive myoclonus epilepsy. Generalized tonic-clonic seizures (also known as grand mal seizures) affect the entire body, causing muscle rigidity, convulsions, and loss of consciousness. Affected individuals may also experience occipital seizures, which can cause temporary blindness and visual hallucinations. Over time, the seizures worsen and become more difficult to treat. A life-threatening seizure condition called status epilepticus may also develop. Status epilepticus is a continuous state of seizure activity lasting longer than several minutes.  About the same time seizures begin, intellectual function starts to decline. Behavioral changes, depression, confusion, and speech difficulties (dysarthria) are among the early signs and symptoms of this disorder. As the condition progresses, a continued loss of intellectual function (dementia) impairs memory, judgment, and thought. Affected people lose the ability to perform the activities of daily living by their mid-twenties, and they ultimately require comprehensive care. People with Lafora progressive myoclonus epilepsy generally survive up to 10 years after symptoms first appear.",Lafora progressive myoclonus epilepsy,0000574,GHR,https://ghr.nlm.nih.gov/condition/lafora-progressive-myoclonus-epilepsy,C0751783,T047,Disorders
How many people are affected by Lafora progressive myoclonus epilepsy ?,0000574-2,frequency,"The prevalence of Lafora progressive myoclonus epilepsy is unknown. Although the condition occurs worldwide, it appears to be most common in Mediterranean countries (including Spain, France, and Italy), parts of Central Asia, India, Pakistan, North Africa, and the Middle East.",Lafora progressive myoclonus epilepsy,0000574,GHR,https://ghr.nlm.nih.gov/condition/lafora-progressive-myoclonus-epilepsy,C0751783,T047,Disorders
What are the genetic changes related to Lafora progressive myoclonus epilepsy ?,0000574-3,genetic changes,"Lafora progressive myoclonus epilepsy can be caused by mutations in either the EPM2A gene or the NHLRC1 gene. These genes provide instructions for making proteins called laforin and malin, respectively. Laforin and malin play a critical role in the survival of nerve cells (neurons) in the brain.  Studies suggest that laforin and malin work together and may have several functions. One of these is to help regulate the production of a complex sugar called glycogen, which is a major source of stored energy in the body. The body stores this sugar in the liver and muscles, breaking it down when it is needed for fuel. Laforin and malin may prevent a potentially damaging buildup of glycogen in tissues that do not normally store this molecule, such as those of the nervous system.  Researchers have discovered that people with Lafora progressive myoclonus epilepsy have distinctive clumps called Lafora bodies within their cells. Lafora bodies are made up of an abnormal form of glycogen that cannot be broken down and used for fuel. Instead, it builds up to form clumps that can damage cells. Neurons appear to be particularly vulnerable to this type of damage. Although Lafora bodies are found in many of the body's tissues, the signs and symptoms of Lafora progressive myoclonus epilepsy are limited to the nervous system.  Mutations in the EPM2A gene prevent cells from making functional laforin, while NHLRC1 gene mutations prevent the production of functional malin. It is unclear how a loss of either of these proteins leads to the formation of Lafora bodies. However, a loss of laforin or malin ultimately results in the death of neurons, which interferes with the brain's normal functions. The condition tends to progress more slowly in some people with NHLRC1 gene mutations than in those with EPM2A gene mutations.  Mutations in the EPM2A and NHLRC1 genes account for 80 percent to 90 percent of all cases of Lafora progressive myoclonus epilepsy. In the remaining cases, the cause of the condition is unknown. Researchers are searching for other genetic changes that may underlie this disease.",Lafora progressive myoclonus epilepsy,0000574,GHR,https://ghr.nlm.nih.gov/condition/lafora-progressive-myoclonus-epilepsy,C0751783,T047,Disorders
Is Lafora progressive myoclonus epilepsy inherited ?,0000574-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Lafora progressive myoclonus epilepsy,0000574,GHR,https://ghr.nlm.nih.gov/condition/lafora-progressive-myoclonus-epilepsy,C0751783,T047,Disorders
What are the treatments for Lafora progressive myoclonus epilepsy ?,0000574-5,treatment,"These resources address the diagnosis or management of Lafora progressive myoclonus epilepsy:  - Gene Review: Gene Review: Progressive Myoclonus Epilepsy, Lafora Type  - Genetic Testing Registry: Lafora disease  - MedlinePlus Encyclopedia: Epilepsy  - MedlinePlus Encyclopedia:Generalized Tonic-Clonic Seizure   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Lafora progressive myoclonus epilepsy,0000574,GHR,https://ghr.nlm.nih.gov/condition/lafora-progressive-myoclonus-epilepsy,C0751783,T047,Disorders
What is (are) Laing distal myopathy ?,0000575-1,information,"Laing distal myopathy is a condition that affects skeletal muscles, which are muscles that the body uses for movement. This disorder causes progressive muscle weakness that appears in childhood. The first sign of Laing distal myopathy is usually weakness in certain muscles in the feet and ankles. This weakness leads to tightening of the Achilles tendon (the band that connects the heel of the foot to the calf muscles), an inability to lift the first (big) toe, and a high-stepping walk. Months to years later, muscle weakness develops in the hands and wrists. Weakness in these muscles makes it difficult to lift the fingers, particularly the third and fourth fingers. Many affected people also experience hand tremors.  In addition to muscle weakness in the hands and feet, Laing distal myopathy causes weakness in several muscles of the neck and face. A decade or more after the onset of symptoms, mild weakness also spreads to muscles in the legs, hips, and shoulders. Laing distal myopathy progresses very gradually, and most affected people remain mobile throughout life. Life expectancy is normal in people with this condition.",Laing distal myopathy,0000575,GHR,https://ghr.nlm.nih.gov/condition/laing-distal-myopathy,C0751336,T047,Disorders
How many people are affected by Laing distal myopathy ?,0000575-2,frequency,"Although Laing distal myopathy is thought to be rare, its prevalence is unknown. Several families with the condition have been identified worldwide.",Laing distal myopathy,0000575,GHR,https://ghr.nlm.nih.gov/condition/laing-distal-myopathy,C0751336,T047,Disorders
What are the genetic changes related to Laing distal myopathy ?,0000575-3,genetic changes,"Mutations in the MYH7 gene cause Laing distal myopathy. The MYH7 gene provides instructions for making a protein that is found in heart (cardiac) muscle and in type I skeletal muscle fibers. Type I fibers, which are also known as slow-twitch fibers, are one of two types of fibers that make up skeletal muscles. Type I fibers are the primary component of skeletal muscles that are resistant to fatigue. For example, muscles involved in posture, such as the neck muscles that hold the head steady, are made predominantly of type I fibers.  In cardiac and skeletal muscle cells, the protein produced from the MYH7 gene forms part of a larger protein called type II myosin. This type of myosin generates the mechanical force that is needed for muscles to contract. In the heart, regular contractions of cardiac muscle pump blood to the rest of the body. The coordinated contraction and relaxation of skeletal muscles allow the body to move.  It is unknown how mutations in the MYH7 gene cause progressive muscle weakness in people with Laing distal myopathy. Researchers have proposed that these mutations alter the structure of myosin in skeletal muscles, which prevents it from interacting with other proteins. The abnormal myosin gradually impairs the function of type I skeletal muscle fibers.  In most people with Laing distal myopathy, the signs and symptoms of the disorder are limited to weakness of skeletal muscles. Although myosin made with the MYH7 protein is also found in cardiac muscle, it is unclear why heart problems are not a typical feature of this condition.",Laing distal myopathy,0000575,GHR,https://ghr.nlm.nih.gov/condition/laing-distal-myopathy,C0751336,T047,Disorders
Is Laing distal myopathy inherited ?,0000575-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In most cases, an affected person inherits the mutation from one affected parent. A small percentage of cases result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.",Laing distal myopathy,0000575,GHR,https://ghr.nlm.nih.gov/condition/laing-distal-myopathy,C0751336,T047,Disorders
What are the treatments for Laing distal myopathy ?,0000575-5,treatment,"These resources address the diagnosis or management of Laing distal myopathy:  - Gene Review: Gene Review: Laing Distal Myopathy  - Genetic Testing Registry: Myopathy, distal, 1   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Laing distal myopathy,0000575,GHR,https://ghr.nlm.nih.gov/condition/laing-distal-myopathy,C0751336,T047,Disorders
What is (are) LAMA2-related muscular dystrophy ?,0000576-1,information,"LAMA2-related muscular dystrophy is a disorder that causes weakness and wasting (atrophy) of muscles used for movement (skeletal muscles). This condition generally appears in one of two ways: as a severe, early-onset type or a milder, late-onset form.  Early-onset LAMA2-related muscular dystrophy is apparent at birth or within the first few months of life. It is considered part of a class of muscle disorders called congenital muscular dystrophies and is sometimes called congenital muscular dystrophy type 1A. Affected infants have severe muscle weakness, lack of muscle tone (hypotonia), little spontaneous movement, and joint deformities (contractures). Weakness of the muscles in the face and throat can result in feeding difficulties and an inability to grow and gain weight at the expected rate (failure to thrive). Hypotonia also affects the muscles used for breathing, which causes a weak cry and breathing problems that can lead to frequent, potentially life-threatening lung infections.  As affected children grow, they often develop an abnormal, gradually worsening side-to-side curvature of the spine (scoliosis) and inward curvature of the back (lordosis). Children with early-onset LAMA2-related muscular dystrophy usually do not learn to walk unassisted. Speech problems may result from weakness of the facial muscles and tongue, but intelligence is usually normal. Heart problems and seizures occasionally occur in early-onset LAMA2-related muscular dystrophy. Because of the serious health problems that occur in this form of the disorder, many affected individuals do not survive past adolescence.  Late-onset LAMA2-related muscular dystrophy occurs later in childhood or in adulthood. Signs and symptoms of this form of the disorder are milder than in the early-onset type and are similar to those of a group of muscle disorders classified as limb-girdle muscular dystrophies. In late-onset LAMA2-related muscular dystrophy, the muscles most affected are those closest to the body (proximal muscles), specifically the muscles of the shoulders, upper arms, pelvic area, and thighs. Children with late-onset LAMA2-related muscular dystrophy sometimes have delayed development of motor skills such as walking, but generally achieve the ability to walk without assistance. Over time, they may develop rigidity of the back, joint contractures, scoliosis, and breathing problems. However, most affected individuals retain the ability to walk and climb stairs, and life expectancy and intelligence are usually not affected in late-onset LAMA2-related muscular dystrophy.",LAMA2-related muscular dystrophy,0000576,GHR,https://ghr.nlm.nih.gov/condition/lama2-related-muscular-dystrophy,C0445223,T019,Disorders
How many people are affected by LAMA2-related muscular dystrophy ?,0000576-2,frequency,"The prevalence of early-onset LAMA2-related muscular dystrophy is estimated at 1 in 30,000 individuals. This condition accounts for between 30 and 40 percent of total cases of congenital muscular dystrophy, although its contribution may be higher or lower than this range in specific populations. Late-onset LAMA2-related muscular dystrophy is rare; its prevalence is unknown.",LAMA2-related muscular dystrophy,0000576,GHR,https://ghr.nlm.nih.gov/condition/lama2-related-muscular-dystrophy,C0445223,T019,Disorders
What are the genetic changes related to LAMA2-related muscular dystrophy ?,0000576-3,genetic changes,"As its name suggests, LAMA2-related muscular dystrophy is caused by mutations in the LAMA2 gene. This gene provides instructions for making a part (subunit) of certain members of a protein family called laminins. Laminin proteins are made of three different subunits called alpha, beta, and gamma. There are several forms of each subunit, and each form is produced from instructions carried by a different gene. The LAMA2 gene provides instructions for the alpha-2 subunit. This subunit is found in the laminin 2 protein, also known as merosin; it is also part of another laminin protein called laminin 4.  Laminins are found in an intricate lattice of proteins and other molecules that forms in the spaces between cells (the extracellular matrix). Laminin 2 and laminin 4 play a particularly important role in the muscles used for movement (skeletal muscles). The laminins attach (bind) to other proteins in the extracellular matrix and in the membrane of muscle cells, which helps maintain the stability of muscle fibers.  Most LAMA2 gene mutations that cause the severe, early-onset form of LAMA2-related muscular dystrophy result in the absence of functional laminin alpha-2 subunit. Mutations that cause the milder, later-onset form usually result in a reduction (deficiency) of functional laminin alpha-2 subunit. Deficiency or absence of the laminin alpha-2 subunit results in a corresponding lack of laminin 2 and laminin 4, reducing the strength and stability of muscle tissue and leading to the signs and symptoms of LAMA2-related muscular dystrophy.",LAMA2-related muscular dystrophy,0000576,GHR,https://ghr.nlm.nih.gov/condition/lama2-related-muscular-dystrophy,C0445223,T019,Disorders
Is LAMA2-related muscular dystrophy inherited ?,0000576-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",LAMA2-related muscular dystrophy,0000576,GHR,https://ghr.nlm.nih.gov/condition/lama2-related-muscular-dystrophy,C0445223,T019,Disorders
What are the treatments for LAMA2-related muscular dystrophy ?,0000576-5,treatment,These resources address the diagnosis or management of LAMA2-related muscular dystrophy:  - Boston Children's Hospital: Treatment and Care for Muscular Dystrophy  - Gene Review: Gene Review: LAMA2-Related Muscular Dystrophy  - Genetic Testing Registry: Congenital muscular dystrophy due to partial LAMA2 deficiency  - Genetic Testing Registry: Merosin deficient congenital muscular dystrophy  - Kennedy Krieger Institute: Center for Genetic Muscle Disorders   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,LAMA2-related muscular dystrophy,0000576,GHR,https://ghr.nlm.nih.gov/condition/lama2-related-muscular-dystrophy,C0445223,T019,Disorders
What is (are) lamellar ichthyosis ?,0000577-1,information,"Lamellar ichthyosis is a condition that mainly affects the skin. Infants with this condition are typically born with a tight, clear sheath covering their skin called a collodion membrane. This membrane usually dries and peels off during the first few weeks of life, and then it becomes obvious that affected babies have scaly skin, and eyelids and lips that are turned outward. People with lamellar ichthyosis typically have large, dark, plate-like scales covering their skin on most of their body. Infants with lamellar ichthyosis may develop infections, an excessive loss of fluids (dehydration), and respiratory problems. Affected individuals may also have hair loss (alopecia), abnormally formed fingernails and toenails (nail dystrophy), a decreased ability to sweat (hypohidrosis), an increased sensitivity to heat, and a thickening of the skin on the palms of the hands and soles of the feet (keratoderma). Less frequently, affected individuals have reddened skin (erythema) and joint deformities (contractures).",lamellar ichthyosis,0000577,GHR,https://ghr.nlm.nih.gov/condition/lamellar-ichthyosis,C0079154,T019,Disorders
How many people are affected by lamellar ichthyosis ?,0000577-2,frequency,"Lamellar ichthyosis is estimated to affect 1 in 100,000 individuals in the United States. This condition is more common in Norway, where an estimated 1 in 91,000 individuals are affected.",lamellar ichthyosis,0000577,GHR,https://ghr.nlm.nih.gov/condition/lamellar-ichthyosis,C0079154,T019,Disorders
What are the genetic changes related to lamellar ichthyosis ?,0000577-3,genetic changes,"Mutations in one of many genes can cause lamellar ichthyosis. These genes provide instructions for making proteins that are found in the outermost layer of the skin (the epidermis). The skin abnormalities associated with lamellar ichthyosis disrupt the normal formation of the epidermis, resulting in impaired regulation of body temperature, water retention, and resistance to infections.  Mutations in the TGM1 gene are responsible for approximately 90 percent of cases of lamellar ichthyosis. The TGM1 gene provides instructions for making an enzyme called transglutaminase 1. This enzyme is involved in the formation of the cornified cell envelope, which is a structure that surrounds skin cells and helps form a protective barrier between the body and its environment. TGM1 gene mutations lead to severely reduced or absent enzyme production, which prevents the formation of the cornified cell envelope.  Mutations in other genes associated with lamellar ichthyosis are each responsible for only a small percentage of cases. In some people with lamellar ichthyosis, the cause of the disorder is unknown. Researchers have identified multiple chromosome regions that contain genes that may be associated with lamellar ichthyosis, although the specific genes have not been identified.",lamellar ichthyosis,0000577,GHR,https://ghr.nlm.nih.gov/condition/lamellar-ichthyosis,C0079154,T019,Disorders
Is lamellar ichthyosis inherited ?,0000577-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",lamellar ichthyosis,0000577,GHR,https://ghr.nlm.nih.gov/condition/lamellar-ichthyosis,C0079154,T019,Disorders
What are the treatments for lamellar ichthyosis ?,0000577-5,treatment,These resources address the diagnosis or management of lamellar ichthyosis:  - Foundation for Ichthyosis and Related Skin Types (FIRST): Skin Care Tips  - Gene Review: Gene Review: Autosomal Recessive Congenital Ichthyosis  - Genetic Testing Registry: Autosomal recessive congenital ichthyosis 3  - Genetic Testing Registry: Autosomal recessive congenital ichthyosis 4A  - Genetic Testing Registry: Autosomal recessive congenital ichthyosis 5  - Genetic Testing Registry: Autosomal recessive congenital ichthyosis 8  - Genetic Testing Registry: Congenital ichthyosis of skin   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,lamellar ichthyosis,0000577,GHR,https://ghr.nlm.nih.gov/condition/lamellar-ichthyosis,C0079154,T019,Disorders
What is (are) Langer mesomelic dysplasia ?,0000578-1,information,"Langer mesomelic dysplasia is a disorder of bone growth. Affected individuals typically have extreme shortening of the long bones in the arms and legs (mesomelia). As a result of the shortened leg bones, people with Langer mesomelic dysplasia have very short stature. A bone in the forearm called the ulna and a bone in the lower leg called the fibula are often underdeveloped or absent, while other bones in the forearm (the radius) and lower leg (the tibia) are unusually short, thick, and curved. Some people with Langer mesomelic dysplasia also have an abnormality of the wrist and forearm bones called Madelung deformity, which may cause pain and limit wrist movement. Additionally, some affected individuals have mild underdevelopment of the lower jaw bone (mandible).",Langer mesomelic dysplasia,0000578,GHR,https://ghr.nlm.nih.gov/condition/langer-mesomelic-dysplasia,C0432230,T019,Disorders
How many people are affected by Langer mesomelic dysplasia ?,0000578-2,frequency,"The prevalence of Langer mesomelic dysplasia is unknown, although the condition appears to be rare. Several dozen affected individuals have been reported in the scientific literature.",Langer mesomelic dysplasia,0000578,GHR,https://ghr.nlm.nih.gov/condition/langer-mesomelic-dysplasia,C0432230,T019,Disorders
What are the genetic changes related to Langer mesomelic dysplasia ?,0000578-3,genetic changes,"Langer mesomelic dysplasia results from changes involving the SHOX gene. The protein produced from this gene plays a role in bone development and is particularly important for the growth and maturation of bones in the arms and legs. The most common cause of Langer mesomelic dysplasia is a deletion of the entire SHOX gene. Other genetic changes that can cause the disorder include mutations in the SHOX gene or deletions of nearby genetic material that normally helps regulate the gene's activity. These changes greatly reduce or eliminate the amount of SHOX protein that is produced. A lack of this protein disrupts normal bone development and growth, which underlies the severe skeletal abnormalities associated with Langer mesomelic dysplasia.",Langer mesomelic dysplasia,0000578,GHR,https://ghr.nlm.nih.gov/condition/langer-mesomelic-dysplasia,C0432230,T019,Disorders
Is Langer mesomelic dysplasia inherited ?,0000578-4,inheritance,"Langer mesomelic dysplasia has a pseudoautosomal recessive pattern of inheritance. The SHOX gene is located on both the X and Y chromosomes (sex chromosomes) in an area known as the pseudoautosomal region. Although many genes are unique to either the X or Y chromosome, genes in the pseudoautosomal region are present on both sex chromosomes. As a result, both females (who have two X chromosomes) and males (who have one X and one Y chromosome) normally have two functional copies of the SHOX gene in each cell. The inheritance pattern of Langer mesomelic dysplasia is described as recessive because both copies of the SHOX gene in each cell must be missing or altered to cause the disorder. In females, the condition results when the gene is missing or altered on both copies of the X chromosome; in males, it results when the gene is missing or altered on the X chromosome and the Y chromosome.  A related skeletal disorder called Lri-Weill dyschondrosteosis occurs when one copy of the SHOX gene is mutated in each cell. This disorder has signs and symptoms that are similar to, but typically less severe than, those of Langer mesomelic dysplasia.",Langer mesomelic dysplasia,0000578,GHR,https://ghr.nlm.nih.gov/condition/langer-mesomelic-dysplasia,C0432230,T019,Disorders
What are the treatments for Langer mesomelic dysplasia ?,0000578-5,treatment,These resources address the diagnosis or management of Langer mesomelic dysplasia:  - Genetic Testing Registry: Langer mesomelic dysplasia syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Langer mesomelic dysplasia,0000578,GHR,https://ghr.nlm.nih.gov/condition/langer-mesomelic-dysplasia,C0432230,T019,Disorders
What is (are) Langer-Giedion syndrome ?,0000579-1,information,"Langer-Giedion syndrome is a condition that causes bone abnormalities and distinctive facial features. People with this condition have multiple noncancerous (benign) bone tumors called osteochondromas. Multiple osteochondromas may result in pain, limited range of joint movement, and pressure on nerves, blood vessels, the spinal cord, and tissues surrounding the osteochondromas. Affected individuals also have short stature and cone-shaped ends of the long bones (epiphyses). The characteristic appearance of individuals with Langer-Giedion syndrome includes sparse scalp hair, a rounded nose, a long flat area between the nose and the upper lip (philtrum), and a thin upper lip. Some people with this condition have loose skin in childhood, which typically resolves with age. Affected individuals may have some intellectual disability.",Langer-Giedion syndrome,0000579,GHR,https://ghr.nlm.nih.gov/condition/langer-giedion-syndrome,C0023003,T047,Disorders
How many people are affected by Langer-Giedion syndrome ?,0000579-2,frequency,Langer-Giedion syndrome is a rare condition; its incidence is unknown.,Langer-Giedion syndrome,0000579,GHR,https://ghr.nlm.nih.gov/condition/langer-giedion-syndrome,C0023003,T047,Disorders
What are the genetic changes related to Langer-Giedion syndrome ?,0000579-3,genetic changes,"Langer-Giedion syndrome is caused by the deletion or mutation of at least two genes on chromosome 8. Researchers have determined that the loss of a functional EXT1 gene is responsible for the multiple osteochondromas seen in people with Langer-Giedion syndrome. Loss of a functional TRPS1 gene may cause the other bone and facial abnormalities. The EXT1 gene and the TRPS1 gene are always missing or mutated in affected individuals, but other neighboring genes may also be involved. The loss of additional genes from this region of chromosome 8 likely contributes to the varied features of this condition.  Langer-Giedion syndrome is often described as a contiguous gene deletion syndrome because it results from the loss of several neighboring genes.",Langer-Giedion syndrome,0000579,GHR,https://ghr.nlm.nih.gov/condition/langer-giedion-syndrome,C0023003,T047,Disorders
Is Langer-Giedion syndrome inherited ?,0000579-4,inheritance,"Most cases of Langer-Giedion syndrome are not inherited, but occur as random events during the formation of reproductive cells (eggs or sperm) in a parent of an affected individual. These cases occur in people with no history of the disorder in their family. There have been very few instances in which people with Langer-Giedion syndrome have inherited the chromosomal deletion from a parent with the condition.  Langer-Giedion syndrome is considered an autosomal dominant condition because one copy of the altered chromosome 8 in each cell is sufficient to cause the disorder.",Langer-Giedion syndrome,0000579,GHR,https://ghr.nlm.nih.gov/condition/langer-giedion-syndrome,C0023003,T047,Disorders
What are the treatments for Langer-Giedion syndrome ?,0000579-5,treatment,These resources address the diagnosis or management of Langer-Giedion syndrome:  - Genetic Testing Registry: Langer-Giedion syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Langer-Giedion syndrome,0000579,GHR,https://ghr.nlm.nih.gov/condition/langer-giedion-syndrome,C0023003,T047,Disorders
What is (are) Langerhans cell histiocytosis ?,0000580-1,information,"Langerhans cell histiocytosis is a disorder in which excess immune system cells called Langerhans cells build up in the body. Langerhans cells, which help regulate the immune system, are normally found throughout the body, especially in the skin, lymph nodes, spleen, lungs, liver, and bone marrow. In Langerhans cell histiocytosis, excess immature Langerhans cells usually form tumors called granulomas. However, Langerhans cell histiocytosis is not generally considered to be a form of cancer.  In approximately 80 percent of affected individuals, one or more granulomas develop in the bones, causing pain and swelling. The granulomas, which usually occur in the skull or the long bones of the arms or legs, may cause the bone to fracture.  Granulomas also frequently occur in the skin, appearing as blisters, reddish bumps, or rashes which can be mild to severe. The pituitary gland may also be affected; this gland is located at the base of the brain and produces hormones that control many important body functions. Without hormone supplementation, affected individuals may experience delayed or absent puberty or an inability to have children (infertility). In addition, pituitary gland damage may result in the production of excessive amounts of urine (diabetes insipidus) and dysfunction of another gland called the thyroid. Thyroid dysfunction can affect the rate of chemical reactions in the body (metabolism), body temperature, skin and hair texture, and behavior.  In 15 to 20 percent of cases, Langerhans cell histiocytosis affects the lungs, liver, or blood-forming (hematopoietic) system; damage to these organs and tissues may be life-threatening. Lung involvement, which appears as swelling of the small airways (bronchioles) and blood vessels of the lungs, results in stiffening of the lung tissue, breathing problems, and increased risk of infection. Hematopoietic involvement, which occurs when the Langerhans cells crowd out blood-forming cells in the bone marrow, leads to a general reduction in the number of blood cells (pancytopenia). Pancytopenia results in fatigue due to low numbers of red blood cells (anemia), frequent infections due to low numbers of white blood cells (neutropenia), and clotting problems due to low numbers of platelets (thrombocytopenia).  Other signs and symptoms that may occur in Langerhans cell histiocytosis, depending on which organs and tissues have Langerhans cell deposits, include swollen lymph nodes, abdominal pain, yellowing of the skin and whites of the eyes (jaundice), delayed puberty, protruding eyes, dizziness, irritability, and seizures. About 1 in 50 affected individuals experience deterioration of neurological function (neurodegeneration).  Langerhans cell histiocytosis is often diagnosed in childhood, usually between ages 2 and 3, but can appear at any age. Most individuals with adult-onset Langerhans cell histiocytosis are current or past smokers; in about two-thirds of adult-onset cases the disorder affects only the lungs.  The severity of Langerhans cell histiocytosis, and its signs and symptoms, vary widely among affected individuals. Certain presentations or forms of the disorder were formerly considered to be separate diseases. Older names that were sometimes used for forms of Langerhans cell histiocytosis include eosinophilic granuloma, Hand-Schller-Christian disease, and Letterer-Siwe disease.  In many people with Langerhans cell histiocytosis, the disorder eventually goes away with appropriate treatment. It may even disappear on its own, especially if the disease occurs only in the skin. However, some complications of the condition, such as diabetes insipidus or other effects of tissue and organ damage, may be permanent.",Langerhans cell histiocytosis,0000580,GHR,https://ghr.nlm.nih.gov/condition/langerhans-cell-histiocytosis,C0019621,T191,Disorders
How many people are affected by Langerhans cell histiocytosis ?,0000580-2,frequency,"Langerhans cell histiocytosis is a rare disorder. Its prevalence is estimated at 1 to 2 in 100,000 people.",Langerhans cell histiocytosis,0000580,GHR,https://ghr.nlm.nih.gov/condition/langerhans-cell-histiocytosis,C0019621,T191,Disorders
What are the genetic changes related to Langerhans cell histiocytosis ?,0000580-3,genetic changes,"Somatic mutations in the BRAF gene have been identified in the Langerhans cells of about half of individuals with Langerhans cell histiocytosis. Somatic gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes are not inherited.  The BRAF gene provides instructions for making a protein that is normally switched on and off in response to signals that control cell growth and development. Somatic mutations cause the BRAF protein in affected cells to be continuously active and to transmit messages to the nucleus even in the absence of these chemical signals. The overactive protein may contribute to the development of Langerhans cell histiocytosis by allowing the Langerhans cells to grow and divide uncontrollably.  Changes in other genes have also been identified in the Langerhans cells of some individuals with Langerhans cell histiocytosis. Some researchers believe that additional factors, such as viral infections and environmental toxins, may also influence the development of this complex disorder.",Langerhans cell histiocytosis,0000580,GHR,https://ghr.nlm.nih.gov/condition/langerhans-cell-histiocytosis,C0019621,T191,Disorders
Is Langerhans cell histiocytosis inherited ?,0000580-4,inheritance,"Langerhans cell histiocytosis is usually not inherited and typically occurs in people with no history of the disorder in their family.  A few families with multiple cases of Langerhans cell histiocytosis have been identified, but the inheritance pattern is unknown.",Langerhans cell histiocytosis,0000580,GHR,https://ghr.nlm.nih.gov/condition/langerhans-cell-histiocytosis,C0019621,T191,Disorders
What are the treatments for Langerhans cell histiocytosis ?,0000580-5,treatment,"These resources address the diagnosis or management of Langerhans cell histiocytosis:  - Cincinnati Children's Hospital Medical Center  - Cleveland Clinic  - Genetic Testing Registry: Langerhans cell histiocytosis, multifocal  - National Cancer Institute: Langerhans Cell Histiocytosis Treatment  - Seattle Children's Hospital  - St. Jude Children's Research Hospital  - Sydney Children's Hospital   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Langerhans cell histiocytosis,0000580,GHR,https://ghr.nlm.nih.gov/condition/langerhans-cell-histiocytosis,C0019621,T191,Disorders
What is (are) Laron syndrome ?,0000581-1,information,"Laron syndrome is a rare form of short stature that results from the body's inability to use growth hormone, a substance produced by the brain's pituitary gland that helps promote growth. Affected individuals are close to normal size at birth, but they experience slow growth from early childhood that results in very short stature. If the condition is not treated, adult males typically reach a maximum height of about 4.5 feet; adult females may be just over 4 feet tall.  Other features of untreated Laron syndrome include reduced muscle strength and endurance, low blood sugar levels (hypoglycemia) in infancy, small genitals and delayed puberty, hair that is thin and fragile, and dental abnormalities. Many affected individuals have a distinctive facial appearance, including a protruding forehead, a sunken bridge of the nose (saddle nose), and a blue tint to the whites of the eyes (blue sclerae). Affected individuals have short limbs compared to the size of their torso, as well as small hands and feet. Adults with this condition tend to develop obesity. However, the signs and symptoms of Laron syndrome vary, even among affected members of the same family.  Studies suggest that people with Laron syndrome have a significantly reduced risk of cancer and type 2 diabetes. Affected individuals appear to develop these common diseases much less frequently than their unaffected relatives, despite having obesity (a risk factor for both cancer and type 2 diabetes). However, people with Laron syndrome do not seem to have an increased lifespan compared with their unaffected relatives.",Laron syndrome,0000581,GHR,https://ghr.nlm.nih.gov/condition/laron-syndrome,C0271568,T047,Disorders
How many people are affected by Laron syndrome ?,0000581-2,frequency,Laron syndrome is a rare disorder. About 350 people have been diagnosed with the condition worldwide. The largest single group of affected individuals (about 100 people) lives in an area of southern Ecuador.,Laron syndrome,0000581,GHR,https://ghr.nlm.nih.gov/condition/laron-syndrome,C0271568,T047,Disorders
What are the genetic changes related to Laron syndrome ?,0000581-3,genetic changes,"Laron syndrome is caused by mutations in the GHR gene. This gene provides instructions for making a protein called the growth hormone receptor. The receptor is present on the outer membrane of cells throughout the body, particularly liver cells. As its name suggests, the growth hormone receptor attaches (binds) to growth hormone; the two proteins fit together like a key in a lock. When growth hormone is bound to its receptor, it triggers signaling that stimulates the growth and division of cells. This signaling also leads to the production, primarily by liver cells, of another important growth-promoting hormone called insulin-like growth factor I (IGF-I).  Growth hormone and IGF-I have a wide variety of effects on the growth and function of many parts of the body. For example, these hormones stimulate the growth and division of cells called chondrocytes, which play a critical role in producing new bone tissue. Growth hormone and IGF-I also influence metabolism, including how the body uses and stores carbohydrates, proteins, and fats from food.  Mutations in the GHR gene impair the receptor's ability to bind to growth hormone or to trigger signaling within cells. As a result, even when growth hormone is available, cells are unable to respond by producing IGF-I and stimulating growth and division. The cells' inability to react to growth hormone, which is described as growth hormone insensitivity, disrupts the normal growth and function of many different tissues. Short stature results when growth hormone cannot adequately stimulate the growth of bones. Changes in metabolism caused by insensitivity to growth hormone and the resulting shortage of IGF-I cause many of the other features of the condition, including obesity.  Researchers are working to determine how mutations in the GHR gene may protect people with Laron syndrome from developing cancer and type 2 diabetes. Studies suggest that insensitivity to growth hormone may help prevent the uncontrolled growth and division of cells that can lead to the development of cancerous tumors. Growth hormone insensitivity also appears to alter how the body responds to insulin, which is a hormone that regulates blood sugar levels. Resistance to the effects of insulin is a major risk factor for type 2 diabetes. People with Laron syndrome have the opposite situation, an increased sensitivity to insulin, which likely helps explain their reduced risk of this common disease.",Laron syndrome,0000581,GHR,https://ghr.nlm.nih.gov/condition/laron-syndrome,C0271568,T047,Disorders
Is Laron syndrome inherited ?,0000581-4,inheritance,"Most cases of Laron syndrome are inherited in an autosomal recessive pattern, which means both copies of the GHR gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Much less commonly, the condition has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most of these cases, an affected person has one parent with the condition.",Laron syndrome,0000581,GHR,https://ghr.nlm.nih.gov/condition/laron-syndrome,C0271568,T047,Disorders
What are the treatments for Laron syndrome ?,0000581-5,treatment,These resources address the diagnosis or management of Laron syndrome:  - Children's Hospital of Pittsburgh: Growth Hormone Treatment  - Cinncinati Children's Hospital Medical Center: Growth Hormone Therapy  - Genetic Testing Registry: Laron-type isolated somatotropin defect   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Laron syndrome,0000581,GHR,https://ghr.nlm.nih.gov/condition/laron-syndrome,C0271568,T047,Disorders
What is (are) Larsen syndrome ?,0000582-1,information,"Larsen syndrome is a disorder that affects the development of bones throughout the body. The signs and symptoms of Larsen syndrome vary widely even within the same family. Affected individuals are usually born with inward- and upward-turning feet (clubfeet) and dislocations of the hips, knees, and elbows. They generally have small extra bones in their wrists and ankles that are visible on x-ray images. The tips of their fingers, especially the thumbs, are typically blunt and square-shaped (spatulate).  People with Larsen syndrome may also have an unusually large range of joint movement (hypermobility) and short stature. They can also have abnormal curvature of the spine (kyphosis or scoliosis) that may compress the spinal cord and lead to weakness of the limbs.  Characteristic facial features include a prominent forehead (frontal bossing), flattening of the bridge of the nose and of the middle of the face (midface hypoplasia), and wide-set eyes (ocular hypertelorism). Some people with Larsen syndrome have an opening in the roof of the mouth (a cleft palate) or hearing loss caused by malformations in the tiny bones in the ears (ossicles). Some affected individuals experience respiratory problems as a result of weakness of the airways that can lead to partial closing, short pauses in breathing (apnea), and frequent respiratory infections. People with Larsen syndrome can survive into adulthood and intelligence is unaffected.",Larsen syndrome,0000582,GHR,https://ghr.nlm.nih.gov/condition/larsen-syndrome,C1835564,T019,Disorders
How many people are affected by Larsen syndrome ?,0000582-2,frequency,"Larsen syndrome occurs in approximately 1 in 100,000 newborns.",Larsen syndrome,0000582,GHR,https://ghr.nlm.nih.gov/condition/larsen-syndrome,C1835564,T019,Disorders
What are the genetic changes related to Larsen syndrome ?,0000582-3,genetic changes,"Mutations in the FLNB gene cause Larsen syndrome. The FLNB gene provides instructions for making a protein called filamin B. This protein helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. Filamin B attaches (binds) to another protein called actin and helps the actin to form the branching network of filaments that makes up the cytoskeleton. It also links actin to many other proteins to perform various functions within the cell, including the cell signaling that helps determine how the cytoskeleton will change as tissues grow and take shape during development.  Filamin B is especially important in the development of the skeleton before birth. It is active (expressed) in the cell membranes of cartilage-forming cells (chondrocytes). Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone (a process called ossification), except for the cartilage that continues to cover and protect the ends of bones and is present in the nose, airways (trachea and bronchi), and external ears. Filamin B appears to be important for normal cell growth and division (proliferation) and maturation (differentiation) of chondrocytes and for the ossification of cartilage.  FLNB gene mutations that cause Larsen syndrome change single protein building blocks (amino acids) in the filamin B protein or delete a small section of the protein sequence, resulting in an abnormal protein. This abnormal protein appears to have a new, atypical function that interferes with the proliferation or differentiation of chondrocytes, impairing ossification and leading to the signs and symptoms of Larsen syndrome.",Larsen syndrome,0000582,GHR,https://ghr.nlm.nih.gov/condition/larsen-syndrome,C1835564,T019,Disorders
Is Larsen syndrome inherited ?,0000582-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  Autosomal recessive inheritance of Larsen syndrome has been reported in a small number of families. Autosomal recessive means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. In some of these cases, the appearance of autosomal recessive inheritance may actually result from multiple siblings in a family each inheriting a single altered gene from an unaffected parent who has an FLNB mutation only in some or all of their sperm or egg cells. When a mutation is present only in reproductive cells, it is known as germline mosaicism.  A few rarer conditions with overlapping signs and symptoms and autosomal recessive inheritance have sometimes been diagnosed as Larsen syndrome, but they are now generally considered to be different disorders because they are typically more severe and are not caused by FLNB gene mutations.",Larsen syndrome,0000582,GHR,https://ghr.nlm.nih.gov/condition/larsen-syndrome,C1835564,T019,Disorders
What are the treatments for Larsen syndrome ?,0000582-5,treatment,"These resources address the diagnosis or management of Larsen syndrome:  - Gene Review: Gene Review: FLNB-Related Disorders  - Genetic Testing Registry: Larsen syndrome  - Genetic Testing Registry: Larsen syndrome, dominant type   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Larsen syndrome,0000582,GHR,https://ghr.nlm.nih.gov/condition/larsen-syndrome,C1835564,T019,Disorders
What is (are) laryngo-onycho-cutaneous syndrome ?,0000583-1,information,"Laryngo-onycho-cutaneous (LOC) syndrome is a disorder that leads to abnormalities of the voicebox (laryngo-), finger- and toenails (onycho-), and skin (cutaneous). Many of the condition's signs and symptoms are related to the abnormal growth of granulation tissue in different parts of the body. This red, bumpy tissue is normally produced during wound healing and is usually replaced by skin cells as healing continues. However, in people with LOC syndrome, this tissue grows even when there is no major injury.  One of the first symptoms in infants with LOC syndrome is a hoarse cry due to ulcers or overgrowth of granulation tissue in the voicebox (the larynx). Excess granulation tissue can also block the airways, leading to life-threatening breathing problems; as a result many affected individuals do not survive past childhood.  In LOC syndrome, granulation tissue also grows in the eyes, specifically the conjunctiva, which are the moist tissues that line the eyelids and the white part of the eyes. Affected individuals often have impairment or complete loss of vision due to the tissue overgrowth.  Another common feature of LOC syndrome is missing patches of skin (cutaneous erosions). The erosions heal slowly and may become infected. People with LOC syndrome can also have malformed nails and small, abnormal teeth. The hard, white material that forms the protective outer layer of each tooth (enamel) is thin, which contributes to frequent cavities.  LOC syndrome is typically considered a subtype of another skin condition called junctional epidermolysis bullosa, which is characterized by fragile skin that blisters easily. While individuals with junctional epidermolysis bullosa can have some of the features of LOC syndrome, they do not usually have overgrowth of granulation tissue in the conjunctiva.",laryngo-onycho-cutaneous syndrome,0000583,GHR,https://ghr.nlm.nih.gov/condition/laryngo-onycho-cutaneous-syndrome,C0039082,T047,Disorders
How many people are affected by laryngo-onycho-cutaneous syndrome ?,0000583-2,frequency,"LOC syndrome is a rare disorder that primarily affects families of Punjabi background from India and Pakistan, although the condition has also been reported in one family from Iran.",laryngo-onycho-cutaneous syndrome,0000583,GHR,https://ghr.nlm.nih.gov/condition/laryngo-onycho-cutaneous-syndrome,C0039082,T047,Disorders
What are the genetic changes related to laryngo-onycho-cutaneous syndrome ?,0000583-3,genetic changes,"LOC syndrome is caused by mutations in the LAMA3 gene, which provides instructions for making one part (subunit) of a protein called laminin 332. This protein is made up of three subunits, called alpha, beta, and gamma. The LAMA3 gene carries instructions for the alpha subunit; the beta and gamma subunits are produced from other genes.  The laminin 332 protein plays an important role in strengthening and stabilizing the skin by helping to attach the top layer of skin (the epidermis) to underlying layers. Studies suggest that laminin 332 is also involved in wound healing. Additionally, researchers have proposed roles for laminin 332 in the clear outer covering of the eye (the cornea) and in the development of tooth enamel.  The mutations involved in LOC syndrome alter the structure of one version of the alpha subunit of laminin 332 (called alpha-3a). Laminins made with the altered subunit cannot effectively attach the epidermis to underlying layers of skin or regulate wound healing. These abnormalities of laminin 332 cause the cutaneous erosions and overgrowth of granulation tissue that are characteristic of LOC syndrome. The inability of laminin 332 to perform its other functions leads to the nail and tooth abnormalities that occur in this condition.",laryngo-onycho-cutaneous syndrome,0000583,GHR,https://ghr.nlm.nih.gov/condition/laryngo-onycho-cutaneous-syndrome,C0039082,T047,Disorders
Is laryngo-onycho-cutaneous syndrome inherited ?,0000583-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",laryngo-onycho-cutaneous syndrome,0000583,GHR,https://ghr.nlm.nih.gov/condition/laryngo-onycho-cutaneous-syndrome,C0039082,T047,Disorders
What are the treatments for laryngo-onycho-cutaneous syndrome ?,0000583-5,treatment,These resources address the diagnosis or management of laryngo-onycho-cutaneous syndrome:  - Genetic Testing Registry: Laryngoonychocutaneous syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,laryngo-onycho-cutaneous syndrome,0000583,GHR,https://ghr.nlm.nih.gov/condition/laryngo-onycho-cutaneous-syndrome,C0039082,T047,Disorders
What is (are) late-infantile neuronal ceroid lipofuscinosis ?,0000584-1,information,"Late-infantile neuronal ceroid lipofuscinosis (NCL) is an inherited disorder that primarily affects the nervous system. The signs and symptoms of this condition typically begin in late infancy or early childhood. The initial features usually include recurrent seizures (epilepsy) and difficulty coordinating movements (ataxia). Affected children also develop muscle twitches (myoclonus) and vision impairment. Late-infantile NCL affects motor skills, such as sitting and walking, and speech development. This condition also causes the loss of previously acquired skills (developmental regression), progressive intellectual disability, and behavioral problems. Individuals with this condition often require the use of a wheelchair by late childhood and typically do not survive past their teens.  Late-infantile NCL is one of a group of NCLs (collectively called Batten disease) that affect the nervous system and typically cause progressive problems with vision, movement, and thinking ability. The different types of NCLs are distinguished by the age at which signs and symptoms first appear.",late-infantile neuronal ceroid lipofuscinosis,0000584,GHR,https://ghr.nlm.nih.gov/condition/late-infantile-neuronal-ceroid-lipofuscinosis,C0022340,T047,Disorders
How many people are affected by late-infantile neuronal ceroid lipofuscinosis ?,0000584-2,frequency,"The prevalence of late-infantile NCL is unknown. Collectively, all forms of NCL affect an estimated 1 in 100,000 individuals worldwide. NCLs are more common in Finland, where approximately 1 in 12,500 individuals are affected.",late-infantile neuronal ceroid lipofuscinosis,0000584,GHR,https://ghr.nlm.nih.gov/condition/late-infantile-neuronal-ceroid-lipofuscinosis,C0022340,T047,Disorders
What are the genetic changes related to late-infantile neuronal ceroid lipofuscinosis ?,0000584-3,genetic changes,"Mutations in the TPP1 gene cause most cases of late-infantile NCL. Mutations in the CLN5, CLN6, CLN8, MFSD8, and PPT1 genes each account for a small percentage of cases.  The TPP1 gene produces an enzyme called tripeptidyl peptidase 1. This enzyme is found in cell structures called lysosomes, which digest and recycle different types of molecules. Tripeptidyl peptidase 1 breaks down protein fragments, known as peptides, into their individual building blocks (amino acids).  The proteins produced from the other genes involved in this condition are active either in lysosomes or in another cell compartment called the endoplasmic reticulum. The endoplasmic reticulum is involved in protein production, processing, and transport. Within these cell structures, the proteins largely play roles in the breakdown of other proteins or substances.  Mutations in the TPP1, CLN5, CLN6, CLN8, MFSD8, or PPT1 gene usually reduce the production or activity of the particular protein or enzyme made from the gene. In many cases, a reduction in functional protein or enzyme results in incomplete breakdown of certain proteins and other materials. These materials accumulate in the lysosome forming fatty substances called lipopigments. In some cases, it is unclear what causes the buildup of lipopigments. In late-infantile NCL, these accumulations occur in cells throughout the body, but neurons seem particularly vulnerable to damage caused by lipopigments and a decrease in specific protein function. The progressive death of cells in the brain and other tissues leads to the signs and symptoms of late-infantile NCL.",late-infantile neuronal ceroid lipofuscinosis,0000584,GHR,https://ghr.nlm.nih.gov/condition/late-infantile-neuronal-ceroid-lipofuscinosis,C0022340,T047,Disorders
Is late-infantile neuronal ceroid lipofuscinosis inherited ?,0000584-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",late-infantile neuronal ceroid lipofuscinosis,0000584,GHR,https://ghr.nlm.nih.gov/condition/late-infantile-neuronal-ceroid-lipofuscinosis,C0022340,T047,Disorders
What are the treatments for late-infantile neuronal ceroid lipofuscinosis ?,0000584-5,treatment,These resources address the diagnosis or management of late-infantile neuronal ceroid lipofuscinosis:  - Gene Review: Gene Review: Neuronal Ceroid-Lipofuscinoses  - Genetic Testing Registry: Ceroid lipofuscinosis neuronal 5  - Genetic Testing Registry: Ceroid lipofuscinosis neuronal 6  - Genetic Testing Registry: Ceroid lipofuscinosis neuronal 7  - Genetic Testing Registry: Ceroid lipofuscinosis neuronal 8  - Genetic Testing Registry: Late-infantile neuronal ceroid lipofuscinosis  - Genetic Testing Registry: Neuronal ceroid lipofuscinosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,late-infantile neuronal ceroid lipofuscinosis,0000584,GHR,https://ghr.nlm.nih.gov/condition/late-infantile-neuronal-ceroid-lipofuscinosis,C0022340,T047,Disorders
What is (are) lattice corneal dystrophy type I ?,0000585-1,information,"Lattice corneal dystrophy type I is an eye disorder that affects the clear, outer covering of the eye called the cornea. The cornea must remain clear for an individual to see properly; however, in lattice corneal dystrophy type I, protein clumps known as amyloid deposits cloud the cornea, which leads to vision impairment. The cornea is made up of several layers of tissue, and in lattice corneal dystrophy type I, the deposits form in the stromal layer. The amyloid deposits form as delicate, branching fibers that create a lattice pattern.  Affected individuals often have recurrent corneal erosions, which are caused by separation of particular layers of the cornea from one another. Corneal erosions are very painful and can cause sensitivity to bright light (photophobia). Lattice corneal dystrophy type I is usually bilateral, which means it affects both eyes. The condition becomes apparent in childhood or adolescence and leads to vision problems by early adulthood.",lattice corneal dystrophy type I,0000585,GHR,https://ghr.nlm.nih.gov/condition/lattice-corneal-dystrophy-type-i,C1690006,T047,Disorders
How many people are affected by lattice corneal dystrophy type I ?,0000585-2,frequency,"Lattice corneal dystrophy type I is one of the most common disorders in a group of conditions that are characterized by protein deposits in the cornea (corneal dystrophies); however, it is still a rare condition. The prevalence of lattice corneal dystrophy type I is unknown.",lattice corneal dystrophy type I,0000585,GHR,https://ghr.nlm.nih.gov/condition/lattice-corneal-dystrophy-type-i,C1690006,T047,Disorders
What are the genetic changes related to lattice corneal dystrophy type I ?,0000585-3,genetic changes,"Lattice corneal dystrophy type I is caused by mutations in the TGFBI gene. This gene provides instructions for making a protein that is found in many tissues throughout the body, including the cornea. The TGFBI protein is part of the extracellular matrix, an intricate network that forms in the spaces between cells and provides structural support to tissues. The protein is thought to play a role in the attachment of cells to one another (cell adhesion) and cell movement (migration).  The TGFBI gene mutations involved in lattice corneal dystrophy type I change single protein building blocks (amino acids) in the TGFBI protein. Mutated TGFBI proteins abnormally clump together and form amyloid deposits. However, it is unclear how the changes caused by the gene mutations induce the protein to form deposits.",lattice corneal dystrophy type I,0000585,GHR,https://ghr.nlm.nih.gov/condition/lattice-corneal-dystrophy-type-i,C1690006,T047,Disorders
Is lattice corneal dystrophy type I inherited ?,0000585-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.",lattice corneal dystrophy type I,0000585,GHR,https://ghr.nlm.nih.gov/condition/lattice-corneal-dystrophy-type-i,C1690006,T047,Disorders
What are the treatments for lattice corneal dystrophy type I ?,0000585-5,treatment,These resources address the diagnosis or management of lattice corneal dystrophy type I:  - American Foundation for the Blind: Living with Vision Loss  - Genetic Testing Registry: Lattice corneal dystrophy Type I  - Merck Manual Home Health Edition: Diagnosis of Eye Disorders: Slit-Lamp Examination   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,lattice corneal dystrophy type I,0000585,GHR,https://ghr.nlm.nih.gov/condition/lattice-corneal-dystrophy-type-i,C1690006,T047,Disorders
What is (are) lattice corneal dystrophy type II ?,0000586-1,information,"Lattice corneal dystrophy type II is characterized by an accumulation of protein clumps called amyloid deposits in tissues throughout the body. The deposits frequently occur in blood vessel walls and basement membranes, which are thin, sheet-like structures that separate and support cells in many tissues. Amyloid deposits lead to characteristic signs and symptoms involving the eyes, nerves, and skin that worsen with age.  The earliest sign of this condition, which is usually identified in a person's twenties, is accumulation of amyloid deposits in the cornea (lattice corneal dystrophy). The cornea is the clear, outer covering of the eye. It is made up of several layers of tissue, and in lattice corneal dystrophy type II, the amyloid deposits form in the stromal layer. The amyloid deposits form as delicate, branching fibers that create a lattice pattern. Because these protein deposits cloud the cornea, they often lead to vision impairment. In addition, affected individuals can have recurrent corneal erosions, which are caused by separation of particular layers of the cornea from one another. Corneal erosions are very painful and can cause sensitivity to bright light (photophobia). Amyloid deposits and corneal erosions are usually bilateral, which means they affect both eyes.  As lattice corneal dystrophy type II progresses, the nerves become involved, typically starting in a person's forties. It is thought that the amyloid deposits disrupt nerve function. Dysfunction of the nerves in the head and face (cranial nerves) can cause paralysis of facial muscles (facial palsy); decreased sensations in the face (facial hypoesthesia); and difficulty speaking, chewing, and swallowing. Dysfunction of the nerves that connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, and heat (peripheral nerves) can cause loss of sensation and weakness in the limbs (peripheral neuropathy). Peripheral neuropathy usually occurs in the lower legs and arms, leading to muscle weakness, clumsiness, and difficulty sensing vibrations.  The skin is also commonly affected in people with lattice corneal dystrophy type II, typically beginning in a person's forties. People with this condition may have thickened, sagging skin, especially on the scalp and forehead, and a condition called cutis laxa, which is characterized by loose skin that lacks elasticity. The skin can also be dry and itchy. Because of loose skin and muscle paralysis in the face, individuals with lattice corneal dystrophy type II can have a facial expression that appears sad.",lattice corneal dystrophy type II,0000586,GHR,https://ghr.nlm.nih.gov/condition/lattice-corneal-dystrophy-type-ii,C0010036,T047,Disorders
How many people are affected by lattice corneal dystrophy type II ?,0000586-2,frequency,"Lattice corneal dystrophy type II is a rare condition; however, the prevalence is unknown. While this condition can be found in populations worldwide, it was first described in Finland and is more common there.",lattice corneal dystrophy type II,0000586,GHR,https://ghr.nlm.nih.gov/condition/lattice-corneal-dystrophy-type-ii,C0010036,T047,Disorders
What are the genetic changes related to lattice corneal dystrophy type II ?,0000586-3,genetic changes,"Lattice corneal dystrophy type II is caused by mutations in the GSN gene. This gene provides instructions for making a protein called gelsolin. This protein is found throughout the body and helps regulate the formation of the network of protein filaments that gives structure to cells (the cytoskeleton). Mutations that cause lattice corneal dystrophy type II change a single protein building block (amino acid) in the gelsolin protein. The altered gelsolin protein is broken down differently than the normal protein, which results in an abnormal gelsolin protein fragment that is released from the cell. These protein fragments clump together and form amyloid deposits, which lead to the signs and symptoms of lattice corneal dystrophy type II.",lattice corneal dystrophy type II,0000586,GHR,https://ghr.nlm.nih.gov/condition/lattice-corneal-dystrophy-type-ii,C0010036,T047,Disorders
Is lattice corneal dystrophy type II inherited ?,0000586-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Although a mutation in one copy of the gene can cause the disorder, people with mutations in both copies of the gene have more severe signs and symptoms.",lattice corneal dystrophy type II,0000586,GHR,https://ghr.nlm.nih.gov/condition/lattice-corneal-dystrophy-type-ii,C0010036,T047,Disorders
What are the treatments for lattice corneal dystrophy type II ?,0000586-5,treatment,These resources address the diagnosis or management of lattice corneal dystrophy type II:  - American Foundation for the Blind: Living with Vision Loss  - Genetic Testing Registry: Meretoja syndrome  - Merck Manual Home Health Edition: Diagnosis of Eye Disorders: Slit-Lamp Examination   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,lattice corneal dystrophy type II,0000586,GHR,https://ghr.nlm.nih.gov/condition/lattice-corneal-dystrophy-type-ii,C0010036,T047,Disorders
What is (are) Leber congenital amaurosis ?,0000587-1,information,"Leber congenital amaurosis is an eye disorder that primarily affects the retina, which is the specialized tissue at the back of the eye that detects light and color. People with this disorder typically have severe visual impairment beginning in infancy. The visual impairment tends to be stable, although it may worsen very slowly over time.  Leber congenital amaurosis is also associated with other vision problems, including an increased sensitivity to light (photophobia), involuntary movements of the eyes (nystagmus), and extreme farsightedness (hyperopia). The pupils, which usually expand and contract in response to the amount of light entering the eye, do not react normally to light. Instead, they expand and contract more slowly than normal, or they may not respond to light at all. Additionally, the clear front covering of the eye (the cornea) may be cone-shaped and abnormally thin, a condition known as keratoconus.  A specific behavior called Franceschetti's oculo-digital sign is characteristic of Leber congenital amaurosis. This sign consists of poking, pressing, and rubbing the eyes with a knuckle or finger. Researchers suspect that this behavior may contribute to deep-set eyes and keratoconus in affected children.  In rare cases, delayed development and intellectual disability have been reported in people with the features of Leber congenital amaurosis. However, researchers are uncertain whether these individuals actually have Leber congenital amaurosis or another syndrome with similar signs and symptoms.  At least 13 types of Leber congenital amaurosis have been described. The types are distinguished by their genetic cause, patterns of vision loss, and related eye abnormalities.",Leber congenital amaurosis,0000587,GHR,https://ghr.nlm.nih.gov/condition/leber-congenital-amaurosis,C0339527,T047,Disorders
How many people are affected by Leber congenital amaurosis ?,0000587-2,frequency,"Leber congenital amaurosis occurs in 2 to 3 per 100,000 newborns. It is one of the most common causes of blindness in children.",Leber congenital amaurosis,0000587,GHR,https://ghr.nlm.nih.gov/condition/leber-congenital-amaurosis,C0339527,T047,Disorders
What are the genetic changes related to Leber congenital amaurosis ?,0000587-3,genetic changes,"Leber congenital amaurosis can result from mutations in at least 14 genes, all of which are necessary for normal vision. These genes play a variety of roles in the development and function of the retina. For example, some of the genes associated with this disorder are necessary for the normal development of light-detecting cells called photoreceptors. Other genes are involved in phototransduction, the process by which light entering the eye is converted into electrical signals that are transmitted to the brain. Still other genes play a role in the function of cilia, which are microscopic finger-like projections that stick out from the surface of many types of cells. Cilia are necessary for the perception of several types of sensory input, including vision.  Mutations in any of the genes associated with Leber congenital amaurosis disrupt the development and function of the retina, resulting in early vision loss. Mutations in the CEP290, CRB1, GUCY2D, and RPE65 genes are the most common causes of the disorder, while mutations in the other genes generally account for a smaller percentage of cases. In about 30 percent of all people with Leber congenital amaurosis, the cause of the disorder is unknown.",Leber congenital amaurosis,0000587,GHR,https://ghr.nlm.nih.gov/condition/leber-congenital-amaurosis,C0339527,T047,Disorders
Is Leber congenital amaurosis inherited ?,0000587-4,inheritance,"Leber congenital amaurosis usually has an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  When Leber congenital amaurosis is caused by mutations in the CRX or IMPDH1 genes, the disorder has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. In most of these cases, an affected person inherits a gene mutation from one affected parent. Other cases result from new mutations and occur in people with no history of the disorder in their family.",Leber congenital amaurosis,0000587,GHR,https://ghr.nlm.nih.gov/condition/leber-congenital-amaurosis,C0339527,T047,Disorders
What are the treatments for Leber congenital amaurosis ?,0000587-5,treatment,These resources address the diagnosis or management of Leber congenital amaurosis:  - Gene Review: Gene Review: Leber Congenital Amaurosis  - Genetic Testing Registry: Leber congenital amaurosis 1  - Genetic Testing Registry: Leber congenital amaurosis 10  - Genetic Testing Registry: Leber congenital amaurosis 12  - Genetic Testing Registry: Leber congenital amaurosis 13  - Genetic Testing Registry: Leber congenital amaurosis 14  - Genetic Testing Registry: Leber congenital amaurosis 2  - Genetic Testing Registry: Leber congenital amaurosis 3  - Genetic Testing Registry: Leber congenital amaurosis 4  - Genetic Testing Registry: Leber congenital amaurosis 5  - Genetic Testing Registry: Leber congenital amaurosis 9  - Genetic Testing Registry: Leber's amaurosis  - National Eye Institute: Gene Therapy for Leber Congenital Amaurosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Leber congenital amaurosis,0000587,GHR,https://ghr.nlm.nih.gov/condition/leber-congenital-amaurosis,C0339527,T047,Disorders
What is (are) Leber hereditary optic neuropathy ?,0000588-1,information,"Leber hereditary optic neuropathy (LHON) is an inherited form of vision loss. Although this condition usually begins in a person's teens or twenties, rare cases may appear in early childhood or later in adulthood. For unknown reasons, males are affected much more often than females.  Blurring and clouding of vision are usually the first symptoms of LHON. These vision problems may begin in one eye or simultaneously in both eyes; if vision loss starts in one eye, the other eye is usually affected within several weeks or months. Over time, vision in both eyes worsens with a severe loss of sharpness (visual acuity) and color vision. This condition mainly affects central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. Vision loss results from the death of cells in the nerve that relays visual information from the eyes to the brain (the optic nerve). Although central vision gradually improves in a small percentage of cases, in most cases the vision loss is profound and permanent.  Vision loss is typically the only symptom of LHON; however, some families with additional signs and symptoms have been reported. In these individuals, the condition is described as ""LHON plus."" In addition to vision loss, the features of LHON plus can include movement disorders, tremors, and abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects). Some affected individuals develop features similar to multiple sclerosis, which is a chronic disorder characterized by muscle weakness, poor coordination, numbness, and a variety of other health problems.",Leber hereditary optic neuropathy,0000588,GHR,https://ghr.nlm.nih.gov/condition/leber-hereditary-optic-neuropathy,C0917796,T047,Disorders
How many people are affected by Leber hereditary optic neuropathy ?,0000588-2,frequency,"The prevalence of LHON in most populations is unknown. It affects 1 in 30,000 to 50,000 people in northeast England and Finland.",Leber hereditary optic neuropathy,0000588,GHR,https://ghr.nlm.nih.gov/condition/leber-hereditary-optic-neuropathy,C0917796,T047,Disorders
What are the genetic changes related to Leber hereditary optic neuropathy ?,0000588-3,genetic changes,"Mutations in the MT-ND1, MT-ND4, MT-ND4L, or MT-ND6 gene can cause LHON. These genes are found in the DNA of cellular structures called mitochondria, which convert the energy from food into a form that cells can use. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA, known as mitochondrial DNA or mtDNA.  The genes associated with LHON each provide instructions for making a protein involved in normal mitochondrial function. These proteins are part of a large enzyme complex in mitochondria that helps convert oxygen, fats, and simple sugars to energy. Mutations in any of the genes disrupt this process. It remains unclear how these genetic changes cause the death of cells in the optic nerve and lead to the specific features of LHON.  A significant percentage of people with a mutation that causes LHON do not develop any features of the disorder. Specifically, more than 50 percent of males with a mutation and more than 85 percent of females with a mutation never experience vision loss or related health problems. Additional factors may determine whether a person develops the signs and symptoms of this disorder. Environmental factors such as smoking and alcohol use may be involved, although studies have produced conflicting results. Researchers are also investigating whether changes in additional genes contribute to the development of signs and symptoms.",Leber hereditary optic neuropathy,0000588,GHR,https://ghr.nlm.nih.gov/condition/leber-hereditary-optic-neuropathy,C0917796,T047,Disorders
Is Leber hereditary optic neuropathy inherited ?,0000588-4,inheritance,"LHON has a mitochondrial pattern of inheritance, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mtDNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children.  Often, people who develop the features of LHON have no family history of the condition. Because a person may carry an mtDNA mutation without experiencing any signs or symptoms, it is hard to predict which members of a family who carry a mutation will eventually develop vision loss or other problems associated with LHON. It is important to note that all females with an mtDNA mutation, even those who do not have any signs or symptoms, will pass the genetic change to their children.",Leber hereditary optic neuropathy,0000588,GHR,https://ghr.nlm.nih.gov/condition/leber-hereditary-optic-neuropathy,C0917796,T047,Disorders
What are the treatments for Leber hereditary optic neuropathy ?,0000588-5,treatment,These resources address the diagnosis or management of Leber hereditary optic neuropathy:  - Gene Review: Gene Review: Leber Hereditary Optic Neuropathy  - Gene Review: Gene Review: Mitochondrial Disorders Overview  - Genetic Testing Registry: Leber's optic atrophy  - MedlinePlus Encyclopedia: Blindness  - MedlinePlus Encyclopedia: Blindness - Resources   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Leber hereditary optic neuropathy,0000588,GHR,https://ghr.nlm.nih.gov/condition/leber-hereditary-optic-neuropathy,C0917796,T047,Disorders
What is (are) Legg-Calv-Perthes disease ?,0000589-1,information,"Legg-Calv-Perthes disease is a bone disorder that affects the hips. Usually, only one hip is involved, but in about 10 percent of cases, both hips are affected. Legg-Calv-Perthes disease begins in childhood, typically between ages 4 and 8, and affects boys more frequently than girls.  In this condition, the upper end of the thigh bone, known as the femoral head, breaks down. As a result, the femoral head is no longer round and does not move easily in the hip socket, which leads to hip pain, limping, and restricted leg movement. The bone eventually begins to heal itself through a normal process called bone remodeling, by which old bone is removed and new bone is created to replace it. This cycle of breakdown and healing can recur multiple times. Affected individuals are often shorter than their peers due to the bone abnormalities. Many people with Legg-Calv-Perthes disease go on to develop a painful joint disorder called osteoarthritis in the hips at an early age.",Legg-Calv-Perthes disease,0000589,GHR,https://ghr.nlm.nih.gov/condition/legg-calve-perthes-disease,C0023234,T047,Disorders
How many people are affected by Legg-Calv-Perthes disease ?,0000589-2,frequency,"The incidence of Legg-Calv-Perthes disease varies by population. The condition is most common in white populations, in which it affects an estimated 1 to 3 in 20,000 children under age 15.",Legg-Calv-Perthes disease,0000589,GHR,https://ghr.nlm.nih.gov/condition/legg-calve-perthes-disease,C0023234,T047,Disorders
What are the genetic changes related to Legg-Calv-Perthes disease ?,0000589-3,genetic changes,"Legg-Calv-Perthes disease is usually not caused by genetic factors. The cause in these cases is unknown. In a small percentage of cases, mutations in the COL2A1 gene cause the bone abnormalities characteristic of Legg-Calv-Perthes disease. The COL2A1 gene provides instructions for making a protein that forms type II collagen. This type of collagen is found mostly in cartilage, a tough but flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Type II collagen is essential for the normal development of bones and other connective tissues that form the body's supportive framework.  COL2A1 gene mutations involved in Legg-Calv-Perthes disease lead to production of an altered protein; collagen that contains this protein may be less stable than normal. Researchers speculate that the breakdown of bone characteristic of Legg-Calv-Perthes disease is caused by impaired blood flow to the femoral head, which leads to death of the bone tissue (osteonecrosis); however it is unclear how abnormal type II collagen is involved in this process or why the hips are specifically affected.",Legg-Calv-Perthes disease,0000589,GHR,https://ghr.nlm.nih.gov/condition/legg-calve-perthes-disease,C0023234,T047,Disorders
Is Legg-Calv-Perthes disease inherited ?,0000589-4,inheritance,"When associated with COL2A1 gene mutations, the condition is inherited in an autosomal dominant pattern, which means one copy of the altered COL2A1 gene in each cell is sufficient to cause the disorder.  Most COL2A1-associated cases result from new mutations in the gene and occur in people with no history of the disorder in their family. These cases are referred to as sporadic. In other cases, the condition is passed through families. In these cases, referred to as familial, an affected person inherits the mutation from one affected parent.",Legg-Calv-Perthes disease,0000589,GHR,https://ghr.nlm.nih.gov/condition/legg-calve-perthes-disease,C0023234,T047,Disorders
What are the treatments for Legg-Calv-Perthes disease ?,0000589-5,treatment,These resources address the diagnosis or management of Legg-Calv-Perthes disease:  - National Osteonecrosis Foundation  - Seattle Children's Hospital   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Legg-Calv-Perthes disease,0000589,GHR,https://ghr.nlm.nih.gov/condition/legg-calve-perthes-disease,C0023234,T047,Disorders
What is (are) Legius syndrome ?,0000590-1,information,"Legius syndrome is a condition characterized by changes in skin coloring (pigmentation). Almost all affected individuals have multiple caf-au-lait spots, which are flat patches on the skin that are darker than the surrounding area. Another pigmentation change, freckles in the armpits and groin, may occur in some affected individuals.  Other signs and symptoms of Legius syndrome may include an abnormally large head (macrocephaly) and unusual facial characteristics. Although most people with Legius syndrome have normal intelligence, some affected individuals have been diagnosed with learning disabilities, attention deficit disorder (ADD), or attention deficit hyperactivity disorder (ADHD).  Many of the signs and symptoms of Legius syndrome also occur in a similar disorder called neurofibromatosis type 1. It can be difficult to tell the two disorders apart in early childhood. However, the features of the two disorders differ later in life.",Legius syndrome,0000590,GHR,https://ghr.nlm.nih.gov/condition/legius-syndrome,C1969623,T047,Disorders
How many people are affected by Legius syndrome ?,0000590-2,frequency,The prevalence of Legius syndrome is unknown. Many individuals with this disorder are likely misdiagnosed because the signs and symptoms of Legius syndrome are similar to those of neurofibromatosis type 1.,Legius syndrome,0000590,GHR,https://ghr.nlm.nih.gov/condition/legius-syndrome,C1969623,T047,Disorders
What are the genetic changes related to Legius syndrome ?,0000590-3,genetic changes,"Mutations in the SPRED1 gene cause Legius syndrome. The SPRED1 gene provides instructions for making the Spred-1 protein. This protein controls (regulates) an important cell signaling pathway that is involved in the growth and division of cells (proliferation), the process by which cells mature to carry out specific functions (differentiation), cell movement, and the self-destruction of cells (apoptosis). Mutations in the SPRED1 gene lead to a nonfunctional protein that can no longer regulate the pathway, resulting in overactive signaling. It is unclear how mutations in the SPRED1 gene cause the signs and symptoms of Legius syndrome.",Legius syndrome,0000590,GHR,https://ghr.nlm.nih.gov/condition/legius-syndrome,C1969623,T047,Disorders
Is Legius syndrome inherited ?,0000590-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Legius syndrome,0000590,GHR,https://ghr.nlm.nih.gov/condition/legius-syndrome,C1969623,T047,Disorders
What are the treatments for Legius syndrome ?,0000590-5,treatment,These resources address the diagnosis or management of Legius syndrome:  - Children's Tumor Foundation: NF1 or Legius Syndrome--An Emerging Challenge of Clinical Diagnosis  - Gene Review: Gene Review: Legius Syndrome  - Genetic Testing Registry: Legius syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Legius syndrome,0000590,GHR,https://ghr.nlm.nih.gov/condition/legius-syndrome,C1969623,T047,Disorders
What is (are) Leigh syndrome ?,0000591-1,information,"Leigh syndrome is a severe neurological disorder that typically arises in the first year of life. This condition is characterized by progressive loss of mental and movement abilities (psychomotor regression) and typically results in death within a couple of years, usually due to respiratory failure. A small number of individuals develop symptoms in adulthood or have symptoms that worsen more slowly.  The first signs of Leigh syndrome seen in infancy are usually vomiting, diarrhea, and difficulty swallowing (dysphagia) that leads to eating problems. These problems often result in an inability to grow and gain weight at the expected rate (failure to thrive). Severe muscle and movement problems are common in Leigh syndrome. Affected individuals may develop weak muscle tone (hypotonia), involuntary muscle contractions (dystonia), and problems with movement and balance (ataxia). Loss of sensation and weakness in the limbs (peripheral neuropathy), common in people with Leigh syndrome, may also make movement difficult.  Several other features may occur in people with Leigh syndrome. Many affected individuals develop weakness or paralysis of the muscles that move the eyes (ophthalmoparesis); rapid, involuntary eye movements (nystagmus); or degeneration of the nerves that carry information from the eyes to the brain (optic atrophy). Severe breathing problems are common in people with Leigh syndrome, and these problems can worsen until they cause acute respiratory failure. Some affected individuals develop hypertrophic cardiomyopathy, which is a thickening of the heart muscle that forces the heart to work harder to pump blood. In addition, a substance called lactate can build up in the body, and excessive amounts are often found in the blood, cerebrospinal fluid, or urine of people with Leigh syndrome.  The signs and symptoms of Leigh syndrome are caused in part by patches of damaged tissue (lesions) that develop in the brains of people with this condition. A procedure called magnetic resonance imaging (MRI) reveals characteristic lesions in certain regions of the brain and the brainstem (the part of the brain that is connected to the spinal cord). These regions include the basal ganglia, which help control movement; the cerebellum, which controls the ability to balance and coordinates movement; and the brainstem, which controls functions such as swallowing, breathing, hearing, and seeing. The brain lesions are often accompanied by loss of the myelin coating around nerves (demyelination), which reduces the ability of the nerves to activate muscles used for movement or relay sensory information back to the brain.",Leigh syndrome,0000591,GHR,https://ghr.nlm.nih.gov/condition/leigh-syndrome,C0023264,T047,Disorders
How many people are affected by Leigh syndrome ?,0000591-2,frequency,"Leigh syndrome affects at least 1 in 40,000 newborns. The condition is more common in certain populations. For example, the condition occurs in approximately 1 in 2,000 newborns in the Saguenay Lac-Saint-Jean region of Quebec, Canada.",Leigh syndrome,0000591,GHR,https://ghr.nlm.nih.gov/condition/leigh-syndrome,C0023264,T047,Disorders
What are the genetic changes related to Leigh syndrome ?,0000591-3,genetic changes,"Leigh syndrome can be caused by mutations in one of over 30 different genes. In humans, most genes are found in DNA in the cell's nucleus, called nuclear DNA. However, some genes are found in DNA in specialized structures in the cell called mitochondria. This type of DNA is known as mitochondrial DNA (mtDNA). While most people with Leigh syndrome have a mutation in nuclear DNA, about 20 to 25 percent have a mutation in mtDNA.  Most genes associated with Leigh syndrome are involved in the process of energy production in mitochondria. Mitochondria use oxygen to convert the energy from food into a form cells can use. Five protein complexes, made up of several proteins each, are involved in this process, called oxidative phosphorylation. The complexes are named complex I, complex II, complex III, complex IV, and complex V. During oxidative phosphorylation, the protein complexes drive the production of ATP, the cell's main energy source, through a step-by-step transfer of negatively charged particles called electrons. Many of the gene mutations associated with Leigh syndrome affect proteins in complexes I, II, IV, or V or disrupt the assembly of these complexes. These mutations reduce or eliminate the activity of one or more of these complexes, which can lead to Leigh syndrome.  Disruption of complex IV, also called cytochrome c oxidase or COX, is the most common cause of Leigh syndrome. The most frequently mutated gene in COX-deficient Leigh syndrome is called SURF1. This gene, which is found in nuclear DNA, provides instructions for making a protein that helps assemble the COX protein complex (complex IV). The COX protein complex, which is involved in the last step of electron transfer in oxidative phosphorylation, provides the energy that will be used in the next step of the process to generate ATP. Mutations in the SURF1 gene typically lead to an abnormally short SURF1 protein that is broken down in cells, resulting in the absence of functional SURF1 protein. The loss of this protein reduces the formation of normal COX complexes, which impairs mitochondrial energy production.  Other nuclear DNA mutations associated with Leigh syndrome decrease the activity of other oxidative phosphorylation protein complexes or affect additional steps related to energy production. For example, Leigh syndrome can be caused by mutations in genes that form the pyruvate dehydrogenase complex. These mutations lead to a shortage of pyruvate dehydrogenase, an enzyme involved in mitochondrial energy production.  The most common mtDNA mutation in Leigh syndrome affects the MT-ATP6 gene, which provides instructions for making a piece of complex V, also known as the ATP synthase protein complex. Using the energy provided by the other protein complexes, the ATP synthase complex generates ATP. MT-ATP6 gene mutations, found in 10 to 20 percent of people with Leigh syndrome, block the generation of ATP. Other mtDNA mutations associated with Leigh syndrome decrease the activity of other oxidative phosphorylation protein complexes or lead to reduced mitochondrial protein synthesis, all of which impair mitochondrial energy production.  Although the exact mechanism is unclear, researchers believe that impaired oxidative phosphorylation can lead to cell death because of decreased energy available in the cell. Certain tissues that require large amounts of energy, such as the brain, muscles, and heart, seem especially sensitive to decreases in cellular energy. Cell death in the brain likely causes the characteristic lesions seen in Leigh syndrome, which contribute to the signs and symptoms of the condition. Cell death in other sensitive tissues may also contribute to the features of Leigh syndrome.",Leigh syndrome,0000591,GHR,https://ghr.nlm.nih.gov/condition/leigh-syndrome,C0023264,T047,Disorders
Is Leigh syndrome inherited ?,0000591-4,inheritance,"Leigh syndrome can have different inheritance patterns. It is most commonly inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. This pattern of inheritance applies to genes contained in nuclear DNA. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  In about 20 to 25 percent of people with Leigh syndrome, the condition is inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mtDNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children. Occasionally, mutations in mtDNA occur spontaneously, and there is no history of Leigh syndrome in the family.  In a small number of affected individuals with mutations in nuclear DNA, Leigh syndrome is inherited in an X-linked recessive pattern. The condition has this pattern of inheritance when the mutated gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",Leigh syndrome,0000591,GHR,https://ghr.nlm.nih.gov/condition/leigh-syndrome,C0023264,T047,Disorders
What are the treatments for Leigh syndrome ?,0000591-5,treatment,"These resources address the diagnosis or management of Leigh syndrome:  - Gene Review: Gene Review: Mitochondrial DNA-Associated Leigh Syndrome and NARP  - Gene Review: Gene Review: Nuclear Gene-Encoded Leigh Syndrome Overview  - Genetic Testing Registry: Leigh Syndrome (mtDNA mutation)  - Genetic Testing Registry: Leigh Syndrome (nuclear DNA mutation)  - Genetic Testing Registry: Leigh syndrome  - Genetic Testing Registry: Leigh syndrome, French Canadian type   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Leigh syndrome,0000591,GHR,https://ghr.nlm.nih.gov/condition/leigh-syndrome,C0023264,T047,Disorders
What is (are) Lennox-Gastaut syndrome ?,0000592-1,information,"Lennox-Gastaut syndrome is a form of severe epilepsy that begins in childhood. It is characterized by multiple types of seizures and intellectual disability.  People with Lennox-Gastaut syndrome begin having frequent seizures in early childhood, usually between ages 3 and 5. More than three-quarters of affected individuals have tonic seizures, which cause the muscles to stiffen (contract) uncontrollably. These seizures occur most often during sleep. Also common are atypical absence seizures, which cause a partial or complete loss of consciousness. Additionally, many affected individuals have drop attacks, which are sudden episodes of weak muscle tone. Drop attacks can result in falls that cause serious or life-threatening injuries. Other types of seizures have been reported less frequently in people with Lennox-Gastaut syndrome.  Most of the seizures associated with Lennox-Gastaut syndrome are very brief. However, more than two-thirds of affected individuals experience at least one prolonged period of seizure activity known as nonconvulsive status epilepticus. These episodes can cause confusion and a loss of alertness lasting from hours to weeks.  Almost all children with Lennox-Gastaut syndrome develop learning problems and intellectual disability associated with their frequent seizures. Because the seizures associated with this condition are difficult to control with medication, the intellectual disability tends to worsen with time. Some affected children develop additional neurological abnormalities and behavioral problems. Many also have delayed development of motor skills such as sitting and crawling. As a result of their seizures and progressive intellectual disability, most people with Lennox-Gastaut syndrome require help with some or all of the usual activities of daily living. However, a small percentage of affected adults live independently.  People with Lennox-Gastaut syndrome have an increased risk of death compared to their peers of the same age. Although the increased risk is not fully understood, it is partly due to poorly controlled seizures and injuries from falls.",Lennox-Gastaut syndrome,0000592,GHR,https://ghr.nlm.nih.gov/condition/lennox-gastaut-syndrome,C0238111,T047,Disorders
How many people are affected by Lennox-Gastaut syndrome ?,0000592-2,frequency,"Lennox-Gastaut syndrome affects an estimated 1 in 50,000 to 1 in 100,000 children. This condition accounts for about 4 percent of all cases of childhood epilepsy. For unknown reasons, it appears to be more common in males than in females.",Lennox-Gastaut syndrome,0000592,GHR,https://ghr.nlm.nih.gov/condition/lennox-gastaut-syndrome,C0238111,T047,Disorders
What are the genetic changes related to Lennox-Gastaut syndrome ?,0000592-3,genetic changes,"Researchers have not identified any genes specific to Lennox-Gastaut syndrome, although the disorder likely has a genetic component. About two-thirds of cases are described as symptomatic, which means that they are related to an existing neurological problem. Symptomatic Lennox-Gastaut syndrome can be associated with brain injuries that occur before or during birth, problems with blood flow in the developing brain, brain infections, or other disorders affecting the nervous system. The condition can also result from a brain malformation known as cortical dysplasia or occur as part of a genetic disorder called tuberous sclerosis complex. Many people with Lennox-Gastaut syndrome have a history of recurrent seizures beginning in infancy (infantile spasms) or a related condition called West syndrome.  In about one-third of cases, the cause of Lennox-Gastaut syndrome is unknown. When the disorder occurs without an apparent underlying reason, it is described as cryptogenic. Individuals with cryptogenic Lennox-Gastaut syndrome have no history of epilepsy, neurological problems, or delayed development prior to the onset of the disorder.",Lennox-Gastaut syndrome,0000592,GHR,https://ghr.nlm.nih.gov/condition/lennox-gastaut-syndrome,C0238111,T047,Disorders
Is Lennox-Gastaut syndrome inherited ?,0000592-4,inheritance,"Most cases of Lennox-Gastaut syndrome are sporadic, which means they occur in people with no history of the disorder in their family. However, 3 to 30 percent of people with this condition have a family history of some type of epilepsy. People with the cryptogenic form of Lennox-Gastaut syndrome are more likely than people with the symptomatic form to have a family history of epilepsy.",Lennox-Gastaut syndrome,0000592,GHR,https://ghr.nlm.nih.gov/condition/lennox-gastaut-syndrome,C0238111,T047,Disorders
What are the treatments for Lennox-Gastaut syndrome ?,0000592-5,treatment,"These resources address the diagnosis or management of Lennox-Gastaut syndrome:  - Cleveland Clinic  - Genetic Testing Registry: Epileptic encephalopathy Lennox-Gastaut type  - National Institute of Neurological Disorders and Stroke: Diagnosis and Treatment of Epilepsy  - News Release: FDA Approves New Drug to Treat Severe Form of Epilepsy (U.S. Food and Drug Administration, November 20, 2008)   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Lennox-Gastaut syndrome,0000592,GHR,https://ghr.nlm.nih.gov/condition/lennox-gastaut-syndrome,C0238111,T047,Disorders
What is (are) Lenz microphthalmia syndrome ?,0000593-1,information,"Lenz microphthalmia syndrome is a condition characterized by abnormal development of the eyes and several other parts of the body. It occurs almost exclusively in males.  The eye abnormalities associated with Lenz microphthalmia syndrome can affect one or both eyes. People with this condition are born with eyeballs that are abnormally small (microphthalmia) or absent (anophthalmia), leading to vision loss or blindness. Other eye problems can include clouding of the lens (cataract), involuntary eye movements (nystagmus), a gap or split in structures that make up the eye (coloboma), and a higher risk of an eye disease called glaucoma.  Abnormalities of the ears, teeth, hands, skeleton, and urinary system are also frequently seen in Lenz microphthalmia syndrome. Less commonly, heart defects have been reported in affected individuals. Many people with this condition have delayed development or intellectual disability ranging from mild to severe.",Lenz microphthalmia syndrome,0000593,GHR,https://ghr.nlm.nih.gov/condition/lenz-microphthalmia-syndrome,C0026010,T019,Disorders
How many people are affected by Lenz microphthalmia syndrome ?,0000593-2,frequency,Lenz microphthalmia syndrome is a very rare condition; its incidence is unknown. It has been identified in only a few families worldwide.,Lenz microphthalmia syndrome,0000593,GHR,https://ghr.nlm.nih.gov/condition/lenz-microphthalmia-syndrome,C0026010,T019,Disorders
What are the genetic changes related to Lenz microphthalmia syndrome ?,0000593-3,genetic changes,"Mutations in at least two genes on the X chromosome are thought to be responsible for Lenz microphthalmia syndrome. Only one of these genes, BCOR, has been identified.  The BCOR gene provides instructions for making a protein called the BCL6 corepressor. This protein helps regulate the activity of other genes. Little is known about the protein's function, although it appears to play an important role in early embryonic development. A mutation in the BCOR gene has been found in one family with Lenz microphthalmia syndrome. This mutation changes the structure of the BCL6 corepressor protein, which disrupts the normal development of the eyes and several other organs and tissues before birth.  Researchers are working to determine whether Lenz microphthalmia syndrome is a single disorder with different genetic causes or two very similar disorders, each caused by mutations in a different gene. They are searching for a second gene on the X chromosome that may underlie additional cases of the disorder.",Lenz microphthalmia syndrome,0000593,GHR,https://ghr.nlm.nih.gov/condition/lenz-microphthalmia-syndrome,C0026010,T019,Disorders
Is Lenz microphthalmia syndrome inherited ?,0000593-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",Lenz microphthalmia syndrome,0000593,GHR,https://ghr.nlm.nih.gov/condition/lenz-microphthalmia-syndrome,C0026010,T019,Disorders
What are the treatments for Lenz microphthalmia syndrome ?,0000593-5,treatment,These resources address the diagnosis or management of Lenz microphthalmia syndrome:  - Gene Review: Gene Review: Lenz Microphthalmia Syndrome  - Genetic Testing Registry: Lenz microphthalmia syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Lenz microphthalmia syndrome,0000593,GHR,https://ghr.nlm.nih.gov/condition/lenz-microphthalmia-syndrome,C0026010,T019,Disorders
What is (are) leptin receptor deficiency ?,0000594-1,information,"Leptin receptor deficiency is a condition that causes severe obesity beginning in the first few months of life. Affected individuals are of normal weight at birth, but they are constantly hungry and quickly gain weight. The extreme hunger leads to chronic excessive eating (hyperphagia) and obesity. Beginning in early childhood, affected individuals develop abnormal eating behaviors such as fighting with other children over food, hoarding food, and eating in secret.  People with leptin receptor deficiency also have hypogonadotropic hypogonadism, which is a condition caused by reduced production of hormones that direct sexual development. Affected individuals experience delayed puberty or do not go through puberty, and may be unable to conceive children (infertile).",leptin receptor deficiency,0000594,GHR,https://ghr.nlm.nih.gov/condition/leptin-receptor-deficiency,C3554225,T047,Disorders
How many people are affected by leptin receptor deficiency ?,0000594-2,frequency,The prevalence of leptin receptor deficiency is unknown. It has been estimated to account for up to 3 percent of individuals with severe obesity and hyperphagia that begins in early childhood.,leptin receptor deficiency,0000594,GHR,https://ghr.nlm.nih.gov/condition/leptin-receptor-deficiency,C3554225,T047,Disorders
What are the genetic changes related to leptin receptor deficiency ?,0000594-3,genetic changes,"Leptin receptor deficiency is caused by mutations in the LEPR gene. This gene provides instructions for making a protein called the leptin receptor, which is involved in the regulation of body weight. The leptin receptor protein is found on the surface of cells in many organs and tissues of the body including a part of the brain called the hypothalamus. The hypothalamus controls hunger and thirst as well as other functions such as sleep, moods, and body temperature. It also regulates the release of many hormones that have functions throughout the body.  The leptin receptor is turned on (activated) by a hormone called leptin that attaches (binds) to the receptor, fitting into it like a key into a lock. Normally, the body's fat cells release leptin in proportion to their size. As fat cells become larger, they produce more leptin. This rise in leptin indicates that fat stores are increasing. In the hypothalamus, the binding of leptin to its receptor triggers a series of chemical signals that affect hunger and help produce a feeling of fullness (satiety).  LEPR gene mutations that cause leptin receptor deficiency prevent the receptor from responding to leptin, leading to the excessive hunger and weight gain associated with this disorder. Because hypogonadotropic hypogonadism occurs in leptin receptor deficiency, researchers suggest that leptin receptor signaling is also involved in regulating the body's response to hormones that control sexual development, and that this response is affected by LEPR gene mutations. However, the mechanism of this effect is unknown.  Leptin receptor deficiency is a rare cause of obesity. Researchers are studying the factors involved in more common forms of obesity.",leptin receptor deficiency,0000594,GHR,https://ghr.nlm.nih.gov/condition/leptin-receptor-deficiency,C3554225,T047,Disorders
Is leptin receptor deficiency inherited ?,0000594-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",leptin receptor deficiency,0000594,GHR,https://ghr.nlm.nih.gov/condition/leptin-receptor-deficiency,C3554225,T047,Disorders
What are the treatments for leptin receptor deficiency ?,0000594-5,treatment,"These resources address the diagnosis or management of leptin receptor deficiency:  - Eunice Kennedy Shriver National Institute of Child Health and Human Development: How Are Obesity and Overweight Diagnosed?  - Genetic Testing Registry: Leptin receptor deficiency  - Genetics of Obesity Study  - National Heart, Lung, and Blood Institute: How Are Overweight and Obesity Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",leptin receptor deficiency,0000594,GHR,https://ghr.nlm.nih.gov/condition/leptin-receptor-deficiency,C3554225,T047,Disorders
What is (are) Lesch-Nyhan syndrome ?,0000595-1,information,"Lesch-Nyhan syndrome is a condition that occurs almost exclusively in males. It is characterized by neurological and behavioral abnormalities and the overproduction of uric acid. Uric acid is a waste product of normal chemical processes and is found in blood and urine. Excess uric acid can be released from the blood and build up under the skin and cause gouty arthritis (arthritis caused by an accumulation of uric acid in the joints). Uric acid accumulation can also cause kidney and bladder stones.  The nervous system and behavioral disturbances experienced by people with Lesch-Nyhan syndrome include abnormal involuntary muscle movements, such as tensing of various muscles (dystonia), jerking movements (chorea), and flailing of the limbs (ballismus). People with Lesch-Nyhan syndrome usually cannot walk, require assistance sitting, and generally use a wheelchair. Self-injury (including biting and head banging) is the most common and distinctive behavioral problem in individuals with Lesch-Nyhan syndrome.",Lesch-Nyhan syndrome,0000595,GHR,https://ghr.nlm.nih.gov/condition/lesch-nyhan-syndrome,C0023374,T047,Disorders
How many people are affected by Lesch-Nyhan syndrome ?,0000595-2,frequency,"The prevalence of Lesch-Nyhan syndrome is approximately 1 in 380,000 individuals. This condition occurs with a similar frequency in all populations.",Lesch-Nyhan syndrome,0000595,GHR,https://ghr.nlm.nih.gov/condition/lesch-nyhan-syndrome,C0023374,T047,Disorders
What are the genetic changes related to Lesch-Nyhan syndrome ?,0000595-3,genetic changes,"Mutations in the HPRT1 gene cause Lesch-Nyhan syndrome. The HPRT1 gene provides instructions for making an enzyme called hypoxanthine phosphoribosyltransferase 1. This enzyme is responsible for recycling purines, a type of building block of DNA and its chemical cousin RNA. Recycling purines ensures that cells have a plentiful supply of building blocks for the production of DNA and RNA.  HPRT1 gene mutations that cause Lesch-Nyhan syndrome result in a severe shortage (deficiency) or complete absence of hypoxanthine phosphoribosyltransferase 1. When this enzyme is lacking, purines are broken down but not recycled, producing abnormally high levels of uric acid. For unknown reasons, a deficiency of hypoxanthine phosphoribosyltransferase 1 is associated with low levels of a chemical messenger in the brain called dopamine. Dopamine transmits messages that help the brain control physical movement and emotional behavior, and its shortage may play a role in the movement problems and other features of this disorder. However, it is unclear how a shortage of hypoxanthine phosphoribosyltransferase 1 causes the neurological and behavioral problems characteristic of Lesch-Nyhan syndrome.  Some people with HPRT1 gene mutations produce some functional enzyme. These individuals are said to have Lesch-Nyhan variant. The signs and symptoms of Lesch-Nyhan variant are often milder than those of Lesch-Nyhan syndrome and do not include self-injury.",Lesch-Nyhan syndrome,0000595,GHR,https://ghr.nlm.nih.gov/condition/lesch-nyhan-syndrome,C0023374,T047,Disorders
Is Lesch-Nyhan syndrome inherited ?,0000595-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",Lesch-Nyhan syndrome,0000595,GHR,https://ghr.nlm.nih.gov/condition/lesch-nyhan-syndrome,C0023374,T047,Disorders
What are the treatments for Lesch-Nyhan syndrome ?,0000595-5,treatment,These resources address the diagnosis or management of Lesch-Nyhan syndrome:  - Gene Review: Gene Review: Lesch-Nyhan Syndrome  - Genetic Testing Registry: Lesch-Nyhan syndrome  - MedlinePlus Encyclopedia: Lesch-Nyhan Syndrome  - MedlinePlus Encyclopedia: Uric Acid Crystals   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Lesch-Nyhan syndrome,0000595,GHR,https://ghr.nlm.nih.gov/condition/lesch-nyhan-syndrome,C0023374,T047,Disorders
What is (are) leukocyte adhesion deficiency type 1 ?,0000596-1,information,"Leukocyte adhesion deficiency type 1 is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. Immunodeficiencies are conditions in which the immune system is not able to protect the body effectively from foreign invaders such as viruses, bacteria, and fungi. Starting from birth, people with leukocyte adhesion deficiency type 1 develop serious bacterial and fungal infections.  One of the first signs of leukocyte adhesion deficiency type 1 is a delay in the detachment of the umbilical cord stump after birth. In newborns, the stump normally falls off within the first two weeks of life; but, in infants with leukocyte adhesion deficiency type 1, this separation usually occurs at three weeks or later. In addition, affected infants often have inflammation of the umbilical cord stump (omphalitis) due to a bacterial infection.  In leukocyte adhesion deficiency type 1, bacterial and fungal infections most commonly occur on the skin and mucous membranes such as the moist lining of the nose and mouth. In childhood, people with this condition develop severe inflammation of the gums (gingivitis) and other tissue around the teeth (periodontitis), which often results in the loss of both primary and permanent teeth. These infections often spread to cover a large area. A hallmark of leukocyte adhesion deficiency type 1 is the lack of pus formation at the sites of infection. In people with this condition, wounds are slow to heal, which can lead to additional infection.  Life expectancy in individuals with leukocyte adhesion deficiency type 1 is often severely shortened. Due to repeat infections, affected individuals may not survive past infancy.",leukocyte adhesion deficiency type 1,0000596,GHR,https://ghr.nlm.nih.gov/condition/leukocyte-adhesion-deficiency-type-1,C0398738,T046,Disorders
How many people are affected by leukocyte adhesion deficiency type 1 ?,0000596-2,frequency,Leukocyte adhesion deficiency type 1 is estimated to occur in 1 per million people worldwide. At least 300 cases of this condition have been reported in the scientific literature.,leukocyte adhesion deficiency type 1,0000596,GHR,https://ghr.nlm.nih.gov/condition/leukocyte-adhesion-deficiency-type-1,C0398738,T046,Disorders
What are the genetic changes related to leukocyte adhesion deficiency type 1 ?,0000596-3,genetic changes,"Mutations in the ITGB2 gene cause leukocyte adhesion deficiency type 1. This gene provides instructions for making one part (the 2 subunit) of at least four different proteins known as 2 integrins. Integrins that contain the 2 subunit are found embedded in the membrane that surrounds white blood cells (leukocytes). These integrins help leukocytes gather at sites of infection or injury, where they contribute to the immune response. 2 integrins recognize signs of inflammation and attach (bind) to proteins called ligands on the lining of blood vessels. This binding leads to linkage (adhesion) of the leukocyte to the blood vessel wall. Signaling through the 2 integrins triggers the transport of the attached leukocyte across the blood vessel wall to the site of infection or injury.  ITGB2 gene mutations that cause leukocyte adhesion deficiency type 1 lead to the production of a 2 subunit that cannot bind with other subunits to form 2 integrins. Leukocytes that lack these integrins cannot attach to the blood vessel wall or cross the vessel wall to contribute to the immune response. As a result, there is a decreased response to injury and foreign invaders, such as bacteria and fungi, resulting in frequent infections, delayed wound healing, and other signs and symptoms of this condition.",leukocyte adhesion deficiency type 1,0000596,GHR,https://ghr.nlm.nih.gov/condition/leukocyte-adhesion-deficiency-type-1,C0398738,T046,Disorders
Is leukocyte adhesion deficiency type 1 inherited ?,0000596-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",leukocyte adhesion deficiency type 1,0000596,GHR,https://ghr.nlm.nih.gov/condition/leukocyte-adhesion-deficiency-type-1,C0398738,T046,Disorders
What are the treatments for leukocyte adhesion deficiency type 1 ?,0000596-5,treatment,These resources address the diagnosis or management of leukocyte adhesion deficiency type 1:  - Genetic Testing Registry: Leukocyte adhesion deficiency type 1  - MedlinePlus Encyclopedia: Gingivitis  - MedlinePlus Encyclopedia: Immunodeficiency Disorders  - Primary Immune Deficiency Treatment Consortium   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,leukocyte adhesion deficiency type 1,0000596,GHR,https://ghr.nlm.nih.gov/condition/leukocyte-adhesion-deficiency-type-1,C0398738,T046,Disorders
What is (are) leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation ?,0000597-1,information,"Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (commonly referred to as LBSL) is a progressive disorder that affects the brain and spinal cord. Leukoencephalopathy refers to abnormalities in the white matter of the brain, which is tissue containing nerve cell fibers (axons) that transmit nerve impulses.  Most affected individuals begin to develop movement problems during childhood or adolescence. However, in some individuals, these problems do not develop until adulthood. People with LBSL have abnormal muscle stiffness (spasticity) and difficulty with coordinating movements (ataxia). In addition, affected individuals lose the ability to sense the position of their limbs or vibrations with their limbs. These movement and sensation problems affect the legs more than the arms, making walking difficult. Most affected individuals eventually require wheelchair assistance, sometimes as early as their teens, although the age varies.  People with LBSL can have other signs and symptoms of the condition. Some affected individuals develop recurrent seizures (epilepsy), speech difficulties (dysarthria), learning problems, or mild deterioration of mental functioning. Some people with this disorder are particularly vulnerable to severe complications following minor head trauma, which may trigger a loss of consciousness, other reversible neurological problems, or fever.  Distinct changes in the brains of people with LBSL can be seen using magnetic resonance imaging (MRI). These characteristic abnormalities typically involve particular parts of the white matter of the brain and specific regions (called tracts) within the brain stem and spinal cord, especially the pyramidal tract and the dorsal column. In addition, most affected individuals have a high level of a substance called lactate in the white matter of the brain, which is identified using another test called magnetic resonance spectroscopy (MRS).",leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation,0000597,GHR,https://ghr.nlm.nih.gov/condition/leukoencephalopathy-with-brainstem-and-spinal-cord-involvement-and-lactate-elevation,C0270612,T047,Disorders
How many people are affected by leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation ?,0000597-2,frequency,LBSL is a rare condition. Its exact prevalence is not known.,leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation,0000597,GHR,https://ghr.nlm.nih.gov/condition/leukoencephalopathy-with-brainstem-and-spinal-cord-involvement-and-lactate-elevation,C0270612,T047,Disorders
What are the genetic changes related to leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation ?,0000597-3,genetic changes,"LBSL is caused by mutations in the DARS2 gene, which provides instructions for making an enzyme called mitochondrial aspartyl-tRNA synthetase. This enzyme is important in the production (synthesis) of proteins in cellular structures called mitochondria, the energy-producing centers in cells. While most protein synthesis occurs in the fluid surrounding the nucleus (cytoplasm), some proteins are synthesized in the mitochondria.  During protein synthesis, in either the mitochondria or the cytoplasm, building blocks (amino acids) are connected together in a specific order, creating a chain of amino acids that forms the protein. Mitochondrial aspartyl-tRNA synthetase plays a role in adding the amino acid aspartic acid at the proper place in mitochondrial proteins.  Mutations in the DARS2 gene result in decreased mitochondrial aspartyl-tRNA synthetase enzyme activity, which hinders the addition of aspartic acid to mitochondrial proteins. It is unclear how the gene mutations lead to the signs and symptoms of LBSL. Researchers do not understand why reduced activity of mitochondrial aspartyl-tRNA synthetase specifically affects certain parts of the brain and spinal cord.",leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation,0000597,GHR,https://ghr.nlm.nih.gov/condition/leukoencephalopathy-with-brainstem-and-spinal-cord-involvement-and-lactate-elevation,C0270612,T047,Disorders
Is leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation inherited ?,0000597-4,inheritance,"LBSL is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. In this condition, each copy of the gene carries a different mutation (compound heterozygous mutations). An affected individual never has the same mutation in both copies of the gene (a homozygous mutation). The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation,0000597,GHR,https://ghr.nlm.nih.gov/condition/leukoencephalopathy-with-brainstem-and-spinal-cord-involvement-and-lactate-elevation,C0270612,T047,Disorders
What are the treatments for leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation ?,0000597-5,treatment,These resources address the diagnosis or management of LBSL:  - Gene Review: Gene Review: Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation  - Genetic Testing Registry: Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation,0000597,GHR,https://ghr.nlm.nih.gov/condition/leukoencephalopathy-with-brainstem-and-spinal-cord-involvement-and-lactate-elevation,C0270612,T047,Disorders
What is (are) leukoencephalopathy with vanishing white matter ?,0000598-1,information,"Leukoencephalopathy with vanishing white matter is a progressive disorder that mainly affects the brain and spinal cord (central nervous system). This disorder causes deterioration of the central nervous system's white matter, which consists of nerve fibers covered by myelin. Myelin is the fatty substance that insulates and protects nerves.  In most cases, people with leukoencephalopathy with vanishing white matter show no signs or symptoms of the disorder at birth. Affected children may have slightly delayed development of motor skills such as crawling or walking. During early childhood, most affected individuals begin to develop motor symptoms, including abnormal muscle stiffness (spasticity) and difficulty with coordinating movements (ataxia). There may also be some deterioration of mental functioning, but this is not usually as pronounced as the motor symptoms. Some affected females may have abnormal development of the ovaries (ovarian dysgenesis). Specific changes in the brain as seen using magnetic resonance imaging (MRI) are characteristic of leukoencephalopathy with vanishing white matter, and may be visible before the onset of symptoms.  While childhood onset is the most common form of leukoencephalopathy with vanishing white matter, some severe forms are apparent at birth. A severe, early-onset form seen among the Cree and Chippewayan populations of Quebec and Manitoba is called Cree leukoencephalopathy. Milder forms may not become evident until adolescence or adulthood, when behavioral or psychiatric problems may be the first signs of the disease. Some females with milder forms of leukoencephalopathy with vanishing white matter who survive to adolescence exhibit ovarian dysfunction. This variant of the disorder is called ovarioleukodystrophy.  Progression of leukoencephalopathy with vanishing white matter is generally uneven, with periods of relative stability interrupted by episodes of rapid decline. People with this disorder are particularly vulnerable to stresses such as infection, mild head trauma or other injury, or even extreme fright. These stresses may trigger the first symptoms of the condition or worsen existing symptoms, and can cause affected individuals to become lethargic or comatose.",leukoencephalopathy with vanishing white matter,0000598,GHR,https://ghr.nlm.nih.gov/condition/leukoencephalopathy-with-vanishing-white-matter,C1858991,T047,Disorders
How many people are affected by leukoencephalopathy with vanishing white matter ?,0000598-2,frequency,"The prevalence of leukoencephalopathy with vanishing white matter is unknown. Although it is a rare disorder, it is believed to be one of the most common inherited diseases that affect the white matter.",leukoencephalopathy with vanishing white matter,0000598,GHR,https://ghr.nlm.nih.gov/condition/leukoencephalopathy-with-vanishing-white-matter,C1858991,T047,Disorders
What are the genetic changes related to leukoencephalopathy with vanishing white matter ?,0000598-3,genetic changes,"Mutations in the EIF2B1, EIF2B2, EIF2B3, EIF2B4, and EIF2B5 genes cause leukoencephalopathy with vanishing white matter.  The EIF2B1, EIF2B2, EIF2B3, EIF2B4 and EIF2B5 genes provide instructions for making the five parts (subunits) of a protein called eIF2B. The eIF2B protein helps regulate overall protein production (synthesis) in the cell by interacting with another protein, eIF2. The eIF2 protein is called an initiation factor because it is involved in starting (initiating) protein synthesis. Proper regulation of protein synthesis is vital for ensuring that the correct levels of protein are available for the cell to cope with changing conditions. For example, cells must synthesize protein much faster if they are multiplying than if they are in a resting state.  Mutations have been identified in all five of the genes from which the eIF2B protein is produced, although most of these mutations (about 65 percent) occur in the EIF2B5 gene. These mutations cause partial loss of eIF2B function in various ways. For example, they may impair the ability of one of the protein subunits to form a complex with the others, or make it more difficult for the protein to attach to the initiation factor.  Partial loss of eIF2B function makes it more difficult for the body's cells to regulate protein synthesis and deal with changing conditions and stress. Researchers believe that cells in the white matter may be particularly affected by an abnormal response to stress, resulting in the signs and symptoms of leukoencephalopathy with vanishing white matter.",leukoencephalopathy with vanishing white matter,0000598,GHR,https://ghr.nlm.nih.gov/condition/leukoencephalopathy-with-vanishing-white-matter,C1858991,T047,Disorders
Is leukoencephalopathy with vanishing white matter inherited ?,0000598-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",leukoencephalopathy with vanishing white matter,0000598,GHR,https://ghr.nlm.nih.gov/condition/leukoencephalopathy-with-vanishing-white-matter,C1858991,T047,Disorders
What are the treatments for leukoencephalopathy with vanishing white matter ?,0000598-5,treatment,These resources address the diagnosis or management of leukoencephalopathy with vanishing white matter:  - Gene Review: Gene Review: Childhood Ataxia with Central Nervous System Hypomelination/Vanishing White Matter  - Genetic Testing Registry: Leukoencephalopathy with vanishing white matter   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,leukoencephalopathy with vanishing white matter,0000598,GHR,https://ghr.nlm.nih.gov/condition/leukoencephalopathy-with-vanishing-white-matter,C1858991,T047,Disorders
What is (are) Leydig cell hypoplasia ?,0000599-1,information,"Leydig cell hypoplasia is a condition that affects male sexual development. It is characterized by underdevelopment (hypoplasia) of Leydig cells in the testes. Leydig cells secrete male sex hormones (androgens) that are important for normal male sexual development before birth and during puberty.  In Leydig cell hypoplasia, affected individuals with a typical male chromosomal pattern (46,XY) may have a range of genital abnormalities. Affected males may have a small penis (micropenis), the opening of the urethra on the underside of the penis (hypospadias), or a scrotum divided into two lobes (bifid scrotum). Because of these abnormalities, the external genitalia may not look clearly male or clearly female (ambiguous genitalia).  In more severe cases of Leydig cell hypoplasia, people with a typical male chromosomal pattern (46,XY) have female external genitalia. They have small testes that are undescended, which means they are abnormally located in the pelvis, abdomen, or groin. People with this form of the disorder do not develop secondary sex characteristics, such as increased body hair, at puberty. Some researchers refer to this form of Leydig cell hypoplasia as type 1 and designate less severe cases as type 2.",Leydig cell hypoplasia,0000599,GHR,https://ghr.nlm.nih.gov/condition/leydig-cell-hypoplasia,C0860158,T019,Disorders
How many people are affected by Leydig cell hypoplasia ?,0000599-2,frequency,Leydig cell hypoplasia is a rare disorder; its prevalence is unknown.,Leydig cell hypoplasia,0000599,GHR,https://ghr.nlm.nih.gov/condition/leydig-cell-hypoplasia,C0860158,T019,Disorders
What are the genetic changes related to Leydig cell hypoplasia ?,0000599-3,genetic changes,"Mutations in the LHCGR gene cause Leydig cell hypoplasia. The LHCGR gene provides instructions for making a protein called the luteinizing hormone/chorionic gonadotropin receptor. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. Together, ligands and their receptors trigger signals that affect cell development and function.  The protein produced from the LHCGR gene acts as a receptor for two ligands: luteinizing hormone and a similar hormone called chorionic gonadotropin. The receptor allows the body to respond appropriately to these hormones. In males, chorionic gonadotropin stimulates the development of cells in the testes called Leydig cells, and luteinizing hormone triggers these cells to produce androgens. Androgens, including testosterone, are the hormones that control male sexual development and reproduction. In females, luteinizing hormone triggers the release of egg cells from the ovary (ovulation). Chorionic gonadotropin is produced during pregnancy and helps maintain conditions necessary for the pregnancy to continue.  The LHCGR gene mutations that cause Leydig cell hypoplasia disrupt luteinizing hormone/chorionic gonadotropin receptor function, impeding the body's ability to react to these hormones. In males, the mutations result in poorly developed or absent Leydig cells and impaired production of testosterone. A lack of testosterone interferes with the development of male reproductive organs before birth and the changes that appear at puberty. Mutations that prevent the production of any functional receptor protein cause the more severe features of Leydig cell hypoplasia, and mutations that allow some receptor protein function cause milder signs and symptoms.",Leydig cell hypoplasia,0000599,GHR,https://ghr.nlm.nih.gov/condition/leydig-cell-hypoplasia,C0860158,T019,Disorders
Is Leydig cell hypoplasia inherited ?,0000599-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Only people who have mutations in both copies of the LHCGR gene and are genetically male (with one X and one Y chromosome in each cell) have the characteristic signs of Leydig cell hypoplasia. Although people who are genetically female (with two X chromosomes in each cell) may inherit mutations in both copies of the LHCGR gene, they do not have Leydig cell hypoplasia because they do not have Leydig cells. They have normal female genitalia and normal breast and pubic hair development, but they may begin menstruation later than usual (after age 16) and have irregular menstrual periods. LHCGR gene mutations in females also prevent ovulation, leading to inability to have children (infertility).",Leydig cell hypoplasia,0000599,GHR,https://ghr.nlm.nih.gov/condition/leydig-cell-hypoplasia,C0860158,T019,Disorders
What are the treatments for Leydig cell hypoplasia ?,0000599-5,treatment,These resources address the diagnosis or management of Leydig cell hypoplasia:  - Genetic Testing Registry: Leydig cell agenesis  - MedlinePlus Encyclopedia: Ambiguous Genitalia  - MedlinePlus Encyclopedia: Hypospadias  - MedlinePlus Encyclopedia: Intersex   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Leydig cell hypoplasia,0000599,GHR,https://ghr.nlm.nih.gov/condition/leydig-cell-hypoplasia,C0860158,T019,Disorders
What is (are) Li-Fraumeni syndrome ?,0000600-1,information,"Li-Fraumeni syndrome is a rare disorder that greatly increases the risk of developing several types of cancer, particularly in children and young adults.  The cancers most often associated with Li-Fraumeni syndrome include breast cancer, a form of bone cancer called osteosarcoma, and cancers of soft tissues (such as muscle) called soft tissue sarcomas. Other cancers commonly seen in this syndrome include brain tumors, cancers of blood-forming tissues (leukemias), and a cancer called adrenocortical carcinoma that affects the outer layer of the adrenal glands (small hormone-producing glands on top of each kidney). Several other types of cancer also occur more frequently in people with Li-Fraumeni syndrome.  A very similar condition called Li-Fraumeni-like syndrome shares many of the features of classic Li-Fraumeni syndrome. Both conditions significantly increase the chances of developing multiple cancers beginning in childhood; however, the pattern of specific cancers seen in affected family members is different.",Li-Fraumeni syndrome,0000600,GHR,https://ghr.nlm.nih.gov/condition/li-fraumeni-syndrome,C0085390,T191,Disorders
How many people are affected by Li-Fraumeni syndrome ?,0000600-2,frequency,The exact prevalence of Li-Fraumeni is unknown. One U.S. registry of Li-Fraumeni syndrome patients suggests that about 400 people from 64 families have this disorder.,Li-Fraumeni syndrome,0000600,GHR,https://ghr.nlm.nih.gov/condition/li-fraumeni-syndrome,C0085390,T191,Disorders
What are the genetic changes related to Li-Fraumeni syndrome ?,0000600-3,genetic changes,"The CHEK2 and TP53 genes are associated with Li-Fraumeni syndrome.  More than half of all families with Li-Fraumeni syndrome have inherited mutations in the TP53 gene. TP53 is a tumor suppressor gene, which means that it normally helps control the growth and division of cells. Mutations in this gene can allow cells to divide in an uncontrolled way and form tumors. Other genetic and environmental factors are also likely to affect the risk of cancer in people with TP53 mutations.  A few families with cancers characteristic of Li-Fraumeni syndrome and Li-Fraumeni-like syndrome do not have TP53 mutations, but have mutations in the CHEK2 gene. Like the TP53 gene, CHEK2 is a tumor suppressor gene. Researchers are uncertain whether CHEK2 mutations actually cause these conditions or are merely associated with an increased risk of certain cancers (including breast cancer).",Li-Fraumeni syndrome,0000600,GHR,https://ghr.nlm.nih.gov/condition/li-fraumeni-syndrome,C0085390,T191,Disorders
Is Li-Fraumeni syndrome inherited ?,0000600-4,inheritance,"Li-Fraumeni syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing cancer. In most cases, an affected person has a parent and other family members with cancers characteristic of the condition.",Li-Fraumeni syndrome,0000600,GHR,https://ghr.nlm.nih.gov/condition/li-fraumeni-syndrome,C0085390,T191,Disorders
What are the treatments for Li-Fraumeni syndrome ?,0000600-5,treatment,These resources address the diagnosis or management of Li-Fraumeni syndrome:  - Gene Review: Gene Review: Li-Fraumeni Syndrome  - Genetic Testing Registry: Li-Fraumeni syndrome  - Genetic Testing Registry: Li-Fraumeni syndrome 1  - Genetic Testing Registry: Li-Fraumeni syndrome 2  - MedlinePlus Encyclopedia: Cancer  - National Cancer Institute: Genetic Testing for Hereditary Cancer Syndromes   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Li-Fraumeni syndrome,0000600,GHR,https://ghr.nlm.nih.gov/condition/li-fraumeni-syndrome,C0085390,T191,Disorders
What is (are) Liddle syndrome ?,0000601-1,information,"Liddle syndrome is an inherited form of high blood pressure (hypertension). This condition is characterized by severe hypertension that begins unusually early in life, often in childhood, although some affected individuals are not diagnosed until adulthood. Some people with Liddle syndrome have no additional signs or symptoms, especially in childhood. Over time, however, untreated hypertension can lead to heart disease or stroke, which may be fatal.  In addition to hypertension, affected individuals can have low levels of potassium in the blood (hypokalemia). Signs and symptoms of hypokalemia include muscle weakness or pain, fatigue, constipation, or heart palpitations. The shortage of potassium can also raise the pH of the blood, a condition known as metabolic alkalosis.",Liddle syndrome,0000601,GHR,https://ghr.nlm.nih.gov/condition/liddle-syndrome,C0221043,T047,Disorders
How many people are affected by Liddle syndrome ?,0000601-2,frequency,"Liddle syndrome is a rare condition, although its prevalence is unknown. The condition has been found in populations worldwide.",Liddle syndrome,0000601,GHR,https://ghr.nlm.nih.gov/condition/liddle-syndrome,C0221043,T047,Disorders
What are the genetic changes related to Liddle syndrome ?,0000601-3,genetic changes,"Liddle syndrome is caused by mutations in the SCNN1B or SCNN1G gene. Each of these genes provides instructions for making a piece (subunit) of a protein complex called the epithelial sodium channel (ENaC). These channels are found at the surface of certain cells called epithelial cells in many tissues of the body, including the kidneys, where the channels transport sodium into cells.  In the kidney, ENaC channels open in response to signals that sodium levels in the blood are too low, which allows sodium to flow into cells. From the kidney cells, this sodium is returned to the bloodstream (a process called reabsorption) rather than being removed from the body in urine.  Mutations in the SCNN1B or SCNN1G gene change the structure of the respective ENaC subunit. The changes alter a region of the subunit that is involved in signaling for its breakdown (degradation) when it is no longer needed. As a result of the mutations, the subunit proteins are not degraded, and more ENaC channels remain at the cell surface. The increase in channels at the cell surface abnormally increases the reabsorption of sodium (followed by water), which leads to hypertension. Reabsorption of sodium into the blood is linked with removal of potassium from the blood, so excess sodium reabsorption leads to hypokalemia.",Liddle syndrome,0000601,GHR,https://ghr.nlm.nih.gov/condition/liddle-syndrome,C0221043,T047,Disorders
Is Liddle syndrome inherited ?,0000601-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Liddle syndrome,0000601,GHR,https://ghr.nlm.nih.gov/condition/liddle-syndrome,C0221043,T047,Disorders
What are the treatments for Liddle syndrome ?,0000601-5,treatment,These resources address the diagnosis or management of Liddle syndrome:  - Genetic Testing Registry: Pseudoprimary hyperaldosteronism  - Merck Manual for Health Care Professionals   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Liddle syndrome,0000601,GHR,https://ghr.nlm.nih.gov/condition/liddle-syndrome,C0221043,T047,Disorders
What is (are) limb-girdle muscular dystrophy ?,0000602-1,information,"Limb-girdle muscular dystrophy is a term for a group of diseases that cause weakness and wasting of the muscles in the arms and legs. The muscles most affected are those closest to the body (proximal muscles), specifically the muscles of the shoulders, upper arms, pelvic area, and thighs.  The severity, age of onset, and features of limb-girdle muscle dystrophy vary among the many subtypes of this condition and may be inconsistent even within the same family. Signs and symptoms may first appear at any age and generally worsen with time, although in some cases they remain mild.  In the early stages of limb-girdle muscular dystrophy, affected individuals may have an unusual walking gait, such as waddling or walking on the balls of their feet, and may also have difficulty running. They may need to use their arms to press themselves up from a squatting position because of their weak thigh muscles. As the condition progresses, people with limb-girdle muscular dystrophy may eventually require wheelchair assistance.  Muscle wasting may cause changes in posture or in the appearance of the shoulder, back, and arm. In particular, weak shoulder muscles tend to make the shoulder blades (scapulae) ""stick out"" from the back, a sign known as scapular winging. Affected individuals may also have an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). Some develop joint stiffness (contractures) that can restrict movement in their hips, knees, ankles, or elbows. Overgrowth (hypertrophy) of the calf muscles occurs in some people with limb-girdle muscular dystrophy.  Weakening of the heart muscle (cardiomyopathy) occurs in some forms of limb-girdle muscular dystrophy. Some affected individuals experience mild to severe breathing problems related to the weakness of muscles needed for breathing.  Intelligence is generally unaffected in limb-girdle muscular dystrophy; however, developmental delay and intellectual disability have been reported in rare forms of the disorder.",limb-girdle muscular dystrophy,0000602,GHR,https://ghr.nlm.nih.gov/condition/limb-girdle-muscular-dystrophy,C0026850,T019,Disorders
How many people are affected by limb-girdle muscular dystrophy ?,0000602-2,frequency,"It is difficult to determine the prevalence of limb-girdle muscular dystrophy because its features vary and overlap with those of other muscle disorders. Prevalence estimates range from 1 in 14,500 to 1 in 123,000 individuals.",limb-girdle muscular dystrophy,0000602,GHR,https://ghr.nlm.nih.gov/condition/limb-girdle-muscular-dystrophy,C0026850,T019,Disorders
What are the genetic changes related to limb-girdle muscular dystrophy ?,0000602-3,genetic changes,"The various forms of limb-girdle muscular dystrophy are caused by mutations in many different genes. These genes provide instructions for making proteins that are involved in muscle maintenance and repair.  Some of the proteins produced from these genes assemble with other proteins into larger protein complexes. These complexes maintain the physical integrity of muscle tissue and allow the muscles to contract. Other proteins participate in cell signaling, cell membrane repair, or the removal of potentially toxic wastes from muscle cells.  Limb-girdle muscular dystrophy is classified based on its inheritance pattern and genetic cause. Limb-girdle muscular dystrophy type 1 includes forms of the disorder that have an inheritance pattern called autosomal dominant. Mutations in the LMNA gene cause limb-girdle muscular dystrophy type 1B. Limb-girdle muscular dystrophy type 1C is one of a group of muscle disorders called caveolinopathies caused by mutations in the CAV3 gene.  Limb-girdle muscular dystrophy type 2 includes forms of the disorder that have an inheritance pattern called autosomal recessive. Calpainopathy, or limb-girdle muscular dystrophy type 2A, is caused by mutations in the CAPN3 gene. Type 2A is the most common form of limb-girdle muscular dystrophy, accounting for about 30 percent of cases. Dysferlinopathy, also called limb-girdle muscular dystrophy type 2B, is caused by mutations in the DYSF gene.  Sarcoglycanopathies are forms of limb-girdle muscular dystrophy caused by mutations in the SGCA, SGCB, SGCG, and SGCD genes. These sarcoglycanopathies are known as limb-girdle muscular dystrophy types 2D, 2E, 2C, and 2F respectively.  A TTN gene mutation causes limb-girdle muscular dystrophy type 2J, which has been identified only in the Finnish population. Mutations in the ANO5 gene cause limb-girdle muscular dystrophy type 2L. Mutations in several other genes cause forms of limb-girdle muscular dystrophy called dystroglycanopathies, including limb-girdle muscular dystrophy types 2I, 2K, 2M, and 2N.  Other rare forms of limb-girdle muscular dystrophy are caused by mutations in several other genes, some of which have not been identified.",limb-girdle muscular dystrophy,0000602,GHR,https://ghr.nlm.nih.gov/condition/limb-girdle-muscular-dystrophy,C0026850,T019,Disorders
Is limb-girdle muscular dystrophy inherited ?,0000602-4,inheritance,"Limb-girdle muscular dystrophy can have different inheritance patterns.  Most forms of this condition are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Several rare forms of limb-girdle muscular dystrophy are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",limb-girdle muscular dystrophy,0000602,GHR,https://ghr.nlm.nih.gov/condition/limb-girdle-muscular-dystrophy,C0026850,T019,Disorders
What are the treatments for limb-girdle muscular dystrophy ?,0000602-5,treatment,"These resources address the diagnosis or management of limb-girdle muscular dystrophy:  - Cleveland Clinic  - Gene Review: Gene Review: Limb-Girdle Muscular Dystrophy Overview  - Genetic Testing Registry: Limb-girdle muscular dystrophy  - Genetic Testing Registry: Limb-girdle muscular dystrophy, type 1A  - Genetic Testing Registry: Limb-girdle muscular dystrophy, type 1B  - Genetic Testing Registry: Limb-girdle muscular dystrophy, type 1C  - Genetic Testing Registry: Limb-girdle muscular dystrophy, type 1E  - Genetic Testing Registry: Limb-girdle muscular dystrophy, type 1F  - Genetic Testing Registry: Limb-girdle muscular dystrophy, type 1G  - Genetic Testing Registry: Limb-girdle muscular dystrophy, type 1H  - Genetic Testing Registry: Limb-girdle muscular dystrophy, type 2A  - Genetic Testing Registry: Limb-girdle muscular dystrophy, type 2B  - Genetic Testing Registry: Limb-girdle muscular dystrophy, type 2D  - Genetic Testing Registry: Limb-girdle muscular dystrophy, type 2E  - Genetic Testing Registry: Limb-girdle muscular dystrophy, type 2F  - Genetic Testing Registry: Limb-girdle muscular dystrophy, type 2G  - Genetic Testing Registry: Limb-girdle muscular dystrophy, type 2J  - Genetic Testing Registry: Limb-girdle muscular dystrophy, type 2L  - Genetic Testing Registry: Limb-girdle muscular dystrophy-dystroglycanopathy, type C1  - Genetic Testing Registry: Limb-girdle muscular dystrophy-dystroglycanopathy, type C2  - Genetic Testing Registry: Limb-girdle muscular dystrophy-dystroglycanopathy, type C3  - Genetic Testing Registry: Limb-girdle muscular dystrophy-dystroglycanopathy, type C4  - Genetic Testing Registry: Limb-girdle muscular dystrophy-dystroglycanopathy, type C5  - Johns Hopkins Medicine  - LGMD-Diagnosis.org   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",limb-girdle muscular dystrophy,0000602,GHR,https://ghr.nlm.nih.gov/condition/limb-girdle-muscular-dystrophy,C0026850,T019,Disorders
What is (are) lissencephaly with cerebellar hypoplasia ?,0000603-1,information,"Lissencephaly with cerebellar hypoplasia (LCH) affects brain development, resulting in the brain having a smooth appearance (lissencephaly) instead of its normal folds and grooves. In addition, the part of the brain that coordinates movement is unusually small and underdeveloped (cerebellar hypoplasia). Other parts of the brain are also often underdeveloped in LCH, including the hippocampus, which plays a role in learning and memory, and the part of the brain that is connected to the spinal cord (the brainstem).  Individuals with LCH have moderate to severe intellectual disability and delayed development. They have few or no communication skills, extremely poor muscle tone (hypotonia), problems with coordination and balance (ataxia), and difficulty sitting or standing without support. Most affected children experience recurrent seizures (epilepsy) that begin within the first months of life. Some affected individuals have nearsightedness (myopia), involuntary eye movements (nystagmus), or puffiness or swelling caused by a buildup of fluids in the body's tissues (lymphedema).",lissencephaly with cerebellar hypoplasia,0000603,GHR,https://ghr.nlm.nih.gov/condition/lissencephaly-with-cerebellar-hypoplasia,C0266463,T019,Disorders
How many people are affected by lissencephaly with cerebellar hypoplasia ?,0000603-2,frequency,"LCH is a rare condition, although its prevalence is unknown.",lissencephaly with cerebellar hypoplasia,0000603,GHR,https://ghr.nlm.nih.gov/condition/lissencephaly-with-cerebellar-hypoplasia,C0266463,T019,Disorders
What are the genetic changes related to lissencephaly with cerebellar hypoplasia ?,0000603-3,genetic changes,"LCH can be caused by mutations in the RELN or TUBA1A gene. The RELN gene provides instructions for making a protein called reelin. In the developing brain, reelin turns on (activates) a signaling pathway that triggers nerve cells (neurons) to migrate to their proper locations. The protein produced from the TUBA1A gene is also involved in neuronal migration as a component of cell structures called microtubules. Microtubules are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). Microtubules form scaffolding within the cell that elongates in a specific direction, altering the cytoskeleton and moving neurons.  Mutations in either the RELN or TUBA1A gene impair the normal migration of neurons during fetal development. As a result, neurons are disorganized, the normal folds and grooves of the brain do not form, and brain structures do not develop properly. This impairment of brain development leads to the neurological problems characteristic of LCH.",lissencephaly with cerebellar hypoplasia,0000603,GHR,https://ghr.nlm.nih.gov/condition/lissencephaly-with-cerebellar-hypoplasia,C0266463,T019,Disorders
Is lissencephaly with cerebellar hypoplasia inherited ?,0000603-4,inheritance,"When LCH is caused by mutations in the RELN gene, the condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  When LCH is caused by mutations in the TUBA1A gene, the condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most of these cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",lissencephaly with cerebellar hypoplasia,0000603,GHR,https://ghr.nlm.nih.gov/condition/lissencephaly-with-cerebellar-hypoplasia,C0266463,T019,Disorders
What are the treatments for lissencephaly with cerebellar hypoplasia ?,0000603-5,treatment,These resources address the diagnosis or management of lissencephaly with cerebellar hypoplasia:  - Genetic Testing Registry: Lissencephaly 2  - Genetic Testing Registry: Lissencephaly 3   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,lissencephaly with cerebellar hypoplasia,0000603,GHR,https://ghr.nlm.nih.gov/condition/lissencephaly-with-cerebellar-hypoplasia,C0266463,T019,Disorders
What is (are) Loeys-Dietz syndrome ?,0000604-1,information,"Loeys-Dietz syndrome is a disorder that affects the connective tissue in many parts of the body. Connective tissue provides strength and flexibility to structures such as bones, ligaments, muscles, and blood vessels.  There are four types of Loeys-Dietz syndrome, labelled types I through IV, which are distinguished by their genetic cause. Regardless of the type, signs and symptoms of Loeys-Dietz syndrome can become apparent anytime in childhood or adulthood, and the severity is variable.  Loeys-Dietz syndrome is characterized by enlargement of the aorta, which is the large blood vessel that distributes blood from the heart to the rest of the body. The aorta can weaken and stretch, causing a bulge in the blood vessel wall (an aneurysm). Stretching of the aorta may also lead to a sudden tearing of the layers in the aorta wall (aortic dissection). People with Loeys-Dietz syndrome can also have aneurysms or dissections in arteries throughout the body and have arteries with abnormal twists and turns (arterial tortuosity).  Individuals with Loeys-Dietz syndrome often have skeletal problems including premature fusion of the skull bones (craniosynostosis), an abnormal side-to-side curvature of the spine (scoliosis), either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum), an inward- and upward-turning foot (clubfoot), flat feet (pes planus), or elongated limbs with joint deformities called contractures that restrict the movement of certain joints. Degeneration of the discs that separate the bones of the spine (vertebrae), often affecting the neck, is a common finding. Some affected individuals have prominent joint inflammation (osteoarthritis) that commonly affects the knees and the joints of the hands, wrists, and spine.  People with Loeys-Dietz syndrome may bruise easily and develop abnormal scars after wound healing. The skin is frequently described as translucent, often with stretch marks (striae) and visible underlying veins. Other characteristic features include widely spaced eyes (hypertelorism), a split in the soft flap of tissue that hangs from the back of the mouth (bifid uvula), and an opening in the roof of the mouth (cleft palate).  Individuals with Loeys-Dietz syndrome frequently develop immune system-related problems such as food allergies, asthma, or inflammatory disorders such as eczema or inflammatory bowel disease.",Loeys-Dietz syndrome,0000604,GHR,https://ghr.nlm.nih.gov/condition/loeys-dietz-syndrome,C2697932,T019,Disorders
How many people are affected by Loeys-Dietz syndrome ?,0000604-2,frequency,The prevalence of Loeys-Dietz syndrome is unknown. Loeys-Dietz syndrome types I and II appear to be the most common forms.,Loeys-Dietz syndrome,0000604,GHR,https://ghr.nlm.nih.gov/condition/loeys-dietz-syndrome,C2697932,T019,Disorders
What are the genetic changes related to Loeys-Dietz syndrome ?,0000604-3,genetic changes,"The four types of Loeys-Dietz syndrome are distinguished by their genetic cause: mutations in the TGFBR1 gene cause type I, mutations in the TGFBR2 gene cause type II, mutations in the SMAD3 gene cause type III, and mutations in the TGFB2 gene cause type IV. These four genes play a role in cell signaling that promotes growth and development of the body's tissues. This signaling pathway also helps with bone and blood vessel development and plays a part in the formation of the extracellular matrix, an intricate lattice of proteins and other molecules that forms in the spaces between cells.  Mutations in the TGFBR1, TGFBR2, TGFB2, and SMAD3 genes result in the production of proteins with little or no function. Even though these proteins have severely reduced function, cell signaling occurs at an even greater intensity than normal. Researchers speculate that the activity of proteins in this signaling pathway is increased to compensate for the protein whose function is reduced; however, the exact mechanism responsible for the increase in signaling is unclear. The overactive signaling pathway disrupts the development of connective tissue, the extracellular matrix, and various body systems, leading to the varied signs and symptoms of Loeys-Dietz syndrome.",Loeys-Dietz syndrome,0000604,GHR,https://ghr.nlm.nih.gov/condition/loeys-dietz-syndrome,C2697932,T019,Disorders
Is Loeys-Dietz syndrome inherited ?,0000604-4,inheritance,"Loeys-Dietz syndrome is considered to have an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In about 75 percent of cases, this disorder results from a new gene mutation and occurs in people with no history of the disorder in their family. In other cases, an affected person inherits the mutation from one affected parent.",Loeys-Dietz syndrome,0000604,GHR,https://ghr.nlm.nih.gov/condition/loeys-dietz-syndrome,C2697932,T019,Disorders
What are the treatments for Loeys-Dietz syndrome ?,0000604-5,treatment,These resources address the diagnosis or management of Loeys-Dietz syndrome:  - Gene Review: Gene Review: Loeys-Dietz Syndrome  - Genetic Testing Registry: Loeys-Dietz syndrome  - Genetic Testing Registry: Loeys-Dietz syndrome 1  - Genetic Testing Registry: Loeys-Dietz syndrome 2  - Genetic Testing Registry: Loeys-Dietz syndrome 3  - Genetic Testing Registry: Loeys-Dietz syndrome 4  - Johns Hopkins Medicine: Diagnosis of Craniosynostosis  - MedlinePlus Encyclopedia: Aortic Dissection  - National Heart Lung and Blood Institute: How Is an Aneurysm Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Loeys-Dietz syndrome,0000604,GHR,https://ghr.nlm.nih.gov/condition/loeys-dietz-syndrome,C2697932,T019,Disorders
What is (are) long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency ?,0000605-1,information,"Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is a rare condition that prevents the body from converting certain fats to energy, particularly during periods without food (fasting).  Signs and symptoms of LCHAD deficiency typically appear during infancy or early childhood and can include feeding difficulties, lack of energy (lethargy), low blood sugar (hypoglycemia), weak muscle tone (hypotonia), liver problems, and abnormalities in the light-sensitive tissue at the back of the eye (retina). Later in childhood, people with this condition may experience muscle pain, breakdown of muscle tissue, and a loss of sensation in their arms and legs (peripheral neuropathy). Individuals with LCHAD deficiency are also at risk for serious heart problems, breathing difficulties, coma, and sudden death.  Problems related to LCHAD deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.",long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency,0000605,GHR,https://ghr.nlm.nih.gov/condition/long-chain-3-hydroxyacyl-coa-dehydrogenase-deficiency,C1969443,T047,Disorders
How many people are affected by long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency ?,0000605-2,frequency,"The incidence of LCHAD deficiency is unknown. One estimate, based on a Finnish population, indicates that 1 in 62,000 pregnancies is affected by this disorder. In the United States, the incidence is probably much lower.",long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency,0000605,GHR,https://ghr.nlm.nih.gov/condition/long-chain-3-hydroxyacyl-coa-dehydrogenase-deficiency,C1969443,T047,Disorders
What are the genetic changes related to long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency ?,0000605-3,genetic changes,"Mutations in the HADHA gene cause LCHAD deficiency. The HADHA gene provides instructions for making part of an enzyme complex called mitochondrial trifunctional protein. This enzyme complex functions in mitochondria, the energy-producing centers within cells. As the name suggests, mitochondrial trifunctional protein contains three enzymes that each perform a different function. This enzyme complex is required to break down (metabolize) a group of fats called long-chain fatty acids. Long-chain fatty acids are found in foods such as milk and certain oils. These fatty acids are stored in the body's fat tissues. Fatty acids are a major source of energy for the heart and muscles. During periods of fasting, fatty acids are also an important energy source for the liver and other tissues.  Mutations in the HADHA gene that cause LCHAD deficiency disrupt one of the functions of this enzyme complex. These mutations prevent the normal processing of long-chain fatty acids from food and body fat. As a result, these fatty acids are not converted to energy, which can lead to some features of this disorder, such as lethargy and hypoglycemia. Long-chain fatty acids or partially metabolized fatty acids may also build up and damage the liver, heart, muscles, and retina. This abnormal buildup causes the other signs and symptoms of LCHAD deficiency.",long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency,0000605,GHR,https://ghr.nlm.nih.gov/condition/long-chain-3-hydroxyacyl-coa-dehydrogenase-deficiency,C1969443,T047,Disorders
Is long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency inherited ?,0000605-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency,0000605,GHR,https://ghr.nlm.nih.gov/condition/long-chain-3-hydroxyacyl-coa-dehydrogenase-deficiency,C1969443,T047,Disorders
What are the treatments for long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency ?,0000605-5,treatment,These resources address the diagnosis or management of LCHAD deficiency:  - Baby's First Test  - Genetic Testing Registry: Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency  - MedlinePlus Encyclopedia: Hypoglycemia  - MedlinePlus Encyclopedia: Peripheral Neuropathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency,0000605,GHR,https://ghr.nlm.nih.gov/condition/long-chain-3-hydroxyacyl-coa-dehydrogenase-deficiency,C1969443,T047,Disorders
What is (are) Lowe syndrome ?,0000606-1,information,"Lowe syndrome is a condition that primarily affects the eyes, brain, and kidneys. This disorder occurs almost exclusively in males.  Infants with Lowe syndrome are born with thick clouding of the lenses in both eyes (congenital cataracts), often with other eye abnormalities that can impair vision. About half of affected infants develop an eye disease called infantile glaucoma, which is characterized by increased pressure within the eyes.  Many individuals with Lowe syndrome have delayed development, and intellectual ability ranges from normal to severely impaired. Behavioral problems and seizures have also been reported in children with this condition. Most affected children have weak muscle tone from birth (neonatal hypotonia), which can contribute to feeding difficulties, problems with breathing, and delayed development of motor skills such as sitting, standing, and walking.  Kidney (renal) abnormalities, most commonly a condition known as renal Fanconi syndrome, frequently develop in individuals with Lowe syndrome. The kidneys play an essential role in maintaining the right amounts of minerals, salts, water, and other substances in the body. In individuals with renal Fanconi syndrome, the kidneys are unable to reabsorb important nutrients into the bloodstream. Instead, the nutrients are excreted in the urine. These kidney problems lead to increased urination, dehydration, and abnormally acidic blood (metabolic acidosis). A loss of salts and nutrients may also impair growth and result in soft, bowed bones (hypophosphatemic rickets), especially in the legs. Progressive kidney problems in older children and adults with Lowe syndrome can lead to life-threatening renal failure and end-stage renal disease (ESRD).",Lowe syndrome,0000606,GHR,https://ghr.nlm.nih.gov/condition/lowe-syndrome,C0028860,T047,Disorders
How many people are affected by Lowe syndrome ?,0000606-2,frequency,"Lowe syndrome is an uncommon condition. It has an estimated prevalence of 1 in 500,000 people.",Lowe syndrome,0000606,GHR,https://ghr.nlm.nih.gov/condition/lowe-syndrome,C0028860,T047,Disorders
What are the genetic changes related to Lowe syndrome ?,0000606-3,genetic changes,"Mutations in the OCRL gene cause Lowe syndrome. The OCRL gene provides instructions for making an enzyme that helps modify fat (lipid) molecules called membrane phospholipids. By controlling the levels of specific membrane phospholipids, the OCRL enzyme helps regulate the transport of certain substances to and from the cell membrane. This enzyme is also involved in the regulation of the actin cytoskeleton, which is a network of fibers that make up the cell's structural framework. The actin cytoskeleton has several critical functions, including determining cell shape and allowing cells to move.  Some mutations in the OCRL gene prevent the production of any OCRL enzyme. Other mutations reduce or eliminate the activity of the enzyme or prevent it from interacting with other proteins within the cell. Researchers are working to determine how OCRL mutations cause the characteristic features of Lowe syndrome. Because the OCRL enzyme is present throughout the body, it is unclear why the medical problems associated with this condition are mostly limited to the brain, kidneys, and eyes. It is possible that other enzymes may be able to compensate for the defective OCRL enzyme in unaffected tissues.",Lowe syndrome,0000606,GHR,https://ghr.nlm.nih.gov/condition/lowe-syndrome,C0028860,T047,Disorders
Is Lowe syndrome inherited ?,0000606-4,inheritance,"This condition is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Most X-linked disorders affect males much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In some cases of Lowe syndrome, an affected male inherits the mutation from a mother who carries one altered copy of the OCRL gene. Other cases result from new mutations in the gene and occur in males with no history of the disorder in their family.  Females who carry one mutated copy of the OCRL gene do not have the characteristic features of Lowe syndrome. Most female carriers, however, have changes in the lens of the eye that can be observed with a thorough eye examination. These changes typically do not impair vision.",Lowe syndrome,0000606,GHR,https://ghr.nlm.nih.gov/condition/lowe-syndrome,C0028860,T047,Disorders
What are the treatments for Lowe syndrome ?,0000606-5,treatment,These resources address the diagnosis or management of Lowe syndrome:  - Gene Review: Gene Review: Lowe Syndrome  - Genetic Testing Registry: Lowe syndrome  - MedlinePlus Encyclopedia: Congenital Cataract  - MedlinePlus Encyclopedia: Fanconi Syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Lowe syndrome,0000606,GHR,https://ghr.nlm.nih.gov/condition/lowe-syndrome,C0028860,T047,Disorders
What is (are) Lujan syndrome ?,0000607-1,information,"Lujan syndrome is a condition characterized by intellectual disability, behavioral problems, and certain physical features. It occurs almost exclusively in males.  The intellectual disability associated with Lujan syndrome is usually mild to moderate. Behavioral problems can include hyperactivity, aggressiveness, extreme shyness, and excessive attention-seeking. Some affected individuals have features of autism or related developmental disorders affecting communication and social interaction. A few have been diagnosed with psychiatric problems such as delusions and hallucinations.  Characteristic physical features of Lujan syndrome include a tall, thin body and an unusually large head (macrocephaly). Affected individuals also have a long, thin face with distinctive facial features such as a prominent top of the nose (high nasal root); a short space between the nose and the upper lip (philtrum); a narrow roof of the mouth (palate); crowded teeth; and a small chin (micrognathia). Almost all people with this condition have weak muscle tone (hypotonia).  Additional signs and symptoms of Lujan syndrome can include abnormal speech, heart defects, and abnormalities of the genitourinary system. Many affected individuals have long fingers and toes with an unusually large range of joint movement (hyperextensibility). Seizures and abnormalities of the tissue that connects the left and right halves of the brain (corpus callosum) have also been reported in people with this condition.",Lujan syndrome,0000607,GHR,https://ghr.nlm.nih.gov/condition/lujan-syndrome,C0796022,T019,Disorders
How many people are affected by Lujan syndrome ?,0000607-2,frequency,"Lujan syndrome appears to be an uncommon condition, but its prevalence is unknown.",Lujan syndrome,0000607,GHR,https://ghr.nlm.nih.gov/condition/lujan-syndrome,C0796022,T019,Disorders
What are the genetic changes related to Lujan syndrome ?,0000607-3,genetic changes,"Lujan syndrome is caused by at least one mutation in the MED12 gene. This gene provides instructions for making a protein that helps regulate gene activity; it is involved in many aspects of early development. The MED12 gene mutation that causes Lujan syndrome changes a single protein building block (amino acid) in the MED12 protein. This genetic change alters the structure, and presumably the function, of the MED12 protein. However, it is unclear how the mutation affects development and leads to the cognitive and physical features of Lujan syndrome.",Lujan syndrome,0000607,GHR,https://ghr.nlm.nih.gov/condition/lujan-syndrome,C0796022,T019,Disorders
Is Lujan syndrome inherited ?,0000607-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",Lujan syndrome,0000607,GHR,https://ghr.nlm.nih.gov/condition/lujan-syndrome,C0796022,T019,Disorders
What are the treatments for Lujan syndrome ?,0000607-5,treatment,These resources address the diagnosis or management of Lujan syndrome:  - Gene Review: Gene Review: MED12-Related Disorders  - Genetic Testing Registry: X-linked mental retardation with marfanoid habitus syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Lujan syndrome,0000607,GHR,https://ghr.nlm.nih.gov/condition/lujan-syndrome,C0796022,T019,Disorders
What is (are) lung cancer ?,0000608-1,information,"Lung cancer is a disease in which certain cells in the lungs become abnormal and multiply uncontrollably to form a tumor. Lung cancer may or may not cause signs or symptoms in its early stages. Some people with lung cancer have chest pain, frequent coughing, breathing problems, trouble swallowing or speaking, blood in the mucus, loss of appetite and weight loss, fatigue, or swelling in the face or neck. Lung cancer occurs most often in adults in their sixties or seventies. Most people who develop lung cancer have a history of long-term tobacco smoking; however, the condition can occur in people who have never smoked.  Lung cancer is generally divided into two types, small cell lung cancer and non-small cell lung cancer, based on the size of the affected cells when viewed under a microscope. Non-small cell lung cancer accounts for 85 percent of lung cancer, while small cell lung cancer accounts for the remaining 15 percent.  Small cell lung cancer grows quickly and often spreads to other tissues (metastasizes), most commonly to the adrenal glands (small hormone-producing glands located on top of each kidney), liver, brain, and bones. In more than half of cases, the small cell lung cancer has spread beyond the lung at the time of diagnosis. After diagnosis, most people with small cell lung cancer survive for about one year; less than seven percent survive 5 years.  Non-small cell lung cancer is divided into three main subtypes: adenocarcinoma, squamous cell carcinoma, and large cell lung carcinoma. Adenocarcinoma arises from the cells that line the small air sacs (alveoli) located throughout the lungs. Squamous cell carcinoma arises from the squamous cells that line the passages leading from the windpipe to the lungs (bronchi). Large cell carcinoma describes non-small cell lung cancers that do not appear to be adenocarcinomas or squamous cell carcinomas. As the name suggests, the tumor cells are large when viewed under a microscope. The 5-year survival rate for people with non-small cell lung cancer is usually between 11 and 17 percent; it can be lower or higher depending on the subtype and stage of the cancer.",lung cancer,0000608,GHR,https://ghr.nlm.nih.gov/condition/lung-cancer,C0242379,T191,Disorders
How many people are affected by lung cancer ?,0000608-2,frequency,"In the United States, it is estimated that more than 221,000 people develop lung cancer each year. An estimated 72 to 80 percent of lung cancer cases occur in tobacco smokers.  Approximately 6.6 percent of individuals will develop lung cancer during their lifetime. It is the leading cause of cancer deaths, accounting for an estimated 27 percent of all cancer deaths in the United States.",lung cancer,0000608,GHR,https://ghr.nlm.nih.gov/condition/lung-cancer,C0242379,T191,Disorders
What are the genetic changes related to lung cancer ?,0000608-3,genetic changes,"Cancers occur when genetic mutations build up in critical genes, specifically those that control cell growth and division or the repair of damaged DNA. These changes allow cells to grow and divide uncontrollably to form a tumor. In nearly all cases of lung cancer, these genetic changes are acquired during a person's lifetime and are present only in certain cells in the lung. These changes, which are called somatic mutations, are not inherited. Somatic mutations in many different genes have been found in lung cancer cells.  Mutations in the EGFR and KRAS genes are estimated to be present in up to half of all lung cancer cases. These genes each provide instructions for making a protein that is embedded within the cell membrane. When these proteins are turned on (activated) by binding to other molecules, signaling pathways are triggered within cells that promote cell growth and division (proliferation).  Mutations in either the EGFR or KRAS gene lead to the production of a protein that is constantly turned on (constitutively activated). As a result, cells are signaled to constantly proliferate, leading to tumor formation. When these gene changes occur in cells in the lungs, lung cancer develops.  Mutations in many other genes have each been found in a small proportion of cases.  In addition to genetic changes, researchers have identified many personal and environmental factors that expose individuals to cancer-causing compounds (carcinogens) and increase the rate at which somatic mutations occur, contributing to a person's risk of developing lung cancer. The greatest risk factor is long-term tobacco smoking, which increases a person's risk of developing lung cancer 20-fold. Other risk factors include exposure to air pollution, radon, asbestos, or secondhand smoke; long-term use of hormone replacement therapy for menopause; and a history of lung disease such as tuberculosis, emphysema, or chronic bronchitis. A history of lung cancer in closely related family members is also an important risk factor; however, because relatives with lung cancer were likely smokers, it is unclear whether the increased risk of lung cancer is the result of genetic factors or exposure to secondhand smoke.",lung cancer,0000608,GHR,https://ghr.nlm.nih.gov/condition/lung-cancer,C0242379,T191,Disorders
Is lung cancer inherited ?,0000608-4,inheritance,"Most cases of lung cancer are not related to inherited gene changes. These cancers are associated with somatic mutations that occur only in certain cells in the lung.  When lung cancer is related to inherited gene changes, the cancer risk is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase a person's chance of developing cancer. It is important to note that people inherit an increased risk of cancer, not the disease itself. Not all people who inherit mutations in these genes will develop lung cancer.",lung cancer,0000608,GHR,https://ghr.nlm.nih.gov/condition/lung-cancer,C0242379,T191,Disorders
What are the treatments for lung cancer ?,0000608-5,treatment,These resources address the diagnosis or management of lung cancer:  - Genetic Testing Registry: Lung cancer  - Genetic Testing Registry: Non-small cell lung cancer  - Lung Cancer Mutation Consortium: About Mutation Testing  - MedlinePlus Encyclopedia: Lung Cancer--Non-Small Cell  - MedlinePlus Encyclopedia: Lung Cancer--Small Cell  - National Cancer Institute: Drugs Approved for Lung Cancer  - National Cancer Institute: Non-Small Cell Lung Cancer Treatment  - National Cancer Institute: Small Cell Lung Cancer Treatment   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,lung cancer,0000608,GHR,https://ghr.nlm.nih.gov/condition/lung-cancer,C0242379,T191,Disorders
What is (are) lymphangioleiomyomatosis ?,0000609-1,information,"Lymphangioleiomyomatosis (LAM) is a condition that affects the lungs, the kidneys, and the lymphatic system. The lymphatic system consists of a network of vessels that transport lymph fluid and immune cells throughout the body.  LAM is found almost exclusively in women. It usually occurs as a feature of an inherited syndrome called tuberous sclerosis complex. When LAM occurs alone it is called isolated or sporadic LAM.  Signs and symptoms of LAM most often appear during a woman's thirties. Affected women have an overgrowth of abnormal smooth muscle-like cells (LAM cells) in the lungs, resulting in the formation of lung cysts and the destruction of normal lung tissue. They may also have an accumulation of fluid in the cavity around the lungs (chylothorax).  The lung abnormalities resulting from LAM may cause difficulty breathing (dyspnea), chest pain, and coughing, which may bring up blood (hemoptysis). Many women with this disorder have recurrent episodes of collapsed lung (spontaneous pneumothorax). The lung problems may be progressive and, without lung transplantation, may eventually lead to limitations in activities of daily living, the need for oxygen therapy, and respiratory failure. Although LAM cells are not considered cancerous, they may spread between tissues (metastasize). As a result, the condition may recur even after lung transplantation.  Women with LAM may develop cysts in the lymphatic vessels of the chest and abdomen. These cysts are called lymphangioleiomyomas. Affected women may also develop tumors called angiomyolipomas made up of LAM cells, fat cells, and blood vessels. Angiomyolipomas usually develop in the kidneys. Internal bleeding is a common complication of angiomyolipomas.",lymphangioleiomyomatosis,0000609,GHR,https://ghr.nlm.nih.gov/condition/lymphangioleiomyomatosis,C0751674,T191,Disorders
How many people are affected by lymphangioleiomyomatosis ?,0000609-2,frequency,"Sporadic LAM is estimated to occur in 2 to 5 per million women worldwide. This condition may be underdiagnosed because its symptoms are similar to those of other lung disorders such as asthma, bronchitis, and chronic obstructive pulmonary disease.",lymphangioleiomyomatosis,0000609,GHR,https://ghr.nlm.nih.gov/condition/lymphangioleiomyomatosis,C0751674,T191,Disorders
What are the genetic changes related to lymphangioleiomyomatosis ?,0000609-3,genetic changes,"Mutations in the TSC1 gene or, more commonly, the TSC2 gene, cause LAM. The TSC1 and TSC2 genes provide instructions for making the proteins hamartin and tuberin, respectively. Within cells, these two proteins likely help regulate cell growth and size. The proteins act as tumor suppressors, which normally prevent cells from growing and dividing too fast or in an uncontrolled way.  When both copies of the TSC1 gene are mutated in a particular cell, that cell cannot produce any functional hamartin; cells with two altered copies of the TSC2 gene are unable to produce any functional tuberin. The loss of these proteins allows the cell to grow and divide in an uncontrolled way, resulting in the tumors and cysts associated with LAM.  It is not well understood why LAM occurs predominantly in women. Researchers believe that the female sex hormone estrogen may be involved in the development of the disorder.",lymphangioleiomyomatosis,0000609,GHR,https://ghr.nlm.nih.gov/condition/lymphangioleiomyomatosis,C0751674,T191,Disorders
Is lymphangioleiomyomatosis inherited ?,0000609-4,inheritance,"Sporadic LAM is not inherited. Instead, researchers suggest that it is caused by a random mutation in the TSC1 or TSC2 gene that occurs very early in development. As a result, some of the body's cells have a normal version of the gene, while others have the mutated version. This situation is called mosaicism. When a mutation occurs in the other copy of the TSC1 or TSC2 gene in certain cells during a woman's lifetime (a somatic mutation), she may develop LAM. These women typically have no history of this disorder in their family.",lymphangioleiomyomatosis,0000609,GHR,https://ghr.nlm.nih.gov/condition/lymphangioleiomyomatosis,C0751674,T191,Disorders
What are the treatments for lymphangioleiomyomatosis ?,0000609-5,treatment,"These resources address the diagnosis or management of LAM:  - Canadian Lung Association  - Genetic Testing Registry: Lymphangiomyomatosis  - Merck Manual for Healthcare Professionals  - National Heart, Lung, and Blood Institute: How is LAM Diagnosed?  - National Heart, Lung, and Blood Institute: How is LAM Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",lymphangioleiomyomatosis,0000609,GHR,https://ghr.nlm.nih.gov/condition/lymphangioleiomyomatosis,C0751674,T191,Disorders
What is (are) lymphedema-distichiasis syndrome ?,0000610-1,information,"Lymphedema-distichiasis syndrome is a condition that affects the normal function of the lymphatic system, which is a part of the circulatory and immune systems. The lymphatic system produces and transports fluids and immune cells throughout the body. People with lymphedema-distichiasis syndrome develop puffiness or swelling (lymphedema) of the limbs, typically the legs and feet. Another characteristic of this syndrome is the growth of extra eyelashes (distichiasis), ranging from a few extra eyelashes to a full extra set on both the upper and lower lids. These eyelashes do not grow along the edge of the eyelid, but out of its inner lining. When the abnormal eyelashes touch the eyeball, they can cause damage to the clear covering of the eye (cornea). Related eye problems can include an irregular curvature of the cornea causing blurred vision (astigmatism) or scarring of the cornea. Other health problems associated with this disorder include swollen and knotted (varicose) veins, droopy eyelids (ptosis), heart abnormalities, and an opening in the roof of the mouth (a cleft palate).  All people with lymphedema-distichiasis syndrome have extra eyelashes present at birth. The age of onset of lymphedema varies, but it most often begins during puberty. Males usually develop lymphedema earlier than females, but all affected individuals will develop lymphedema by the time they are in their forties.",lymphedema-distichiasis syndrome,0000610,GHR,https://ghr.nlm.nih.gov/condition/lymphedema-distichiasis-syndrome,C0423848,T019,Disorders
How many people are affected by lymphedema-distichiasis syndrome ?,0000610-2,frequency,"The prevalence of lymphedema-distichiasis syndrome is unknown. Because the extra eyelashes can be overlooked during a medical examination, researchers believe that some people with this condition may be misdiagnosed as having lymphedema only.",lymphedema-distichiasis syndrome,0000610,GHR,https://ghr.nlm.nih.gov/condition/lymphedema-distichiasis-syndrome,C0423848,T019,Disorders
What are the genetic changes related to lymphedema-distichiasis syndrome ?,0000610-3,genetic changes,"Lymphedema-distichiasis syndrome is caused by mutations in the FOXC2 gene. The FOXC2 gene provides instructions for making a protein that plays a critical role in the formation of many organs and tissues before birth. The FOXC2 protein is a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of many other genes. Researchers believe that the FOXC2 protein has a role in a variety of developmental processes, such as the formation of veins and the development of the lungs, eyes, kidneys and urinary tract, cardiovascular system, and the transport system for immune cells (lymphatic vessels).",lymphedema-distichiasis syndrome,0000610,GHR,https://ghr.nlm.nih.gov/condition/lymphedema-distichiasis-syndrome,C0423848,T019,Disorders
Is lymphedema-distichiasis syndrome inherited ?,0000610-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",lymphedema-distichiasis syndrome,0000610,GHR,https://ghr.nlm.nih.gov/condition/lymphedema-distichiasis-syndrome,C0423848,T019,Disorders
What are the treatments for lymphedema-distichiasis syndrome ?,0000610-5,treatment,These resources address the diagnosis or management of lymphedema-distichiasis syndrome:  - Gene Review: Gene Review: Lymphedema-Distichiasis Syndrome  - Genetic Testing Registry: Distichiasis-lymphedema syndrome  - MedlinePlus Encyclopedia: Lymph System   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,lymphedema-distichiasis syndrome,0000610,GHR,https://ghr.nlm.nih.gov/condition/lymphedema-distichiasis-syndrome,C0423848,T019,Disorders
What is (are) Lynch syndrome ?,0000611-1,information,"Lynch syndrome, often called hereditary nonpolyposis colorectal cancer (HNPCC), is an inherited disorder that increases the risk of many types of cancer, particularly cancers of the colon (large intestine) and rectum, which are collectively referred to as colorectal cancer. People with Lynch syndrome also have an increased risk of cancers of the stomach, small intestine, liver, gallbladder ducts, upper urinary tract, brain, and skin. Additionally, women with this disorder have a high risk of cancer of the ovaries and lining of the uterus (the endometrium). People with Lynch syndrome may occasionally have noncancerous (benign) growths (polyps) in the colon, called colon polyps. In individuals with this disorder, colon polyps occur earlier but not in greater numbers than they do in the general population.",Lynch syndrome,0000611,GHR,https://ghr.nlm.nih.gov/condition/lynch-syndrome,C1333990,T191,Disorders
How many people are affected by Lynch syndrome ?,0000611-2,frequency,"In the United States, about 140,000 new cases of colorectal cancer are diagnosed each year. Approximately 3 to 5 percent of these cancers are caused by Lynch syndrome.",Lynch syndrome,0000611,GHR,https://ghr.nlm.nih.gov/condition/lynch-syndrome,C1333990,T191,Disorders
What are the genetic changes related to Lynch syndrome ?,0000611-3,genetic changes,"Variations in the MLH1, MSH2, MSH6, PMS2, or EPCAM gene increase the risk of developing Lynch syndrome.  The MLH1, MSH2, MSH6, and PMS2 genes are involved in the repair of mistakes that occur when DNA is copied in preparation for cell division (a process called DNA replication). Mutations in any of these genes prevent the proper repair of DNA replication mistakes. As the abnormal cells continue to divide, the accumulated mistakes can lead to uncontrolled cell growth and possibly cancer.  Mutations in the EPCAM gene also lead to impaired DNA repair, although the gene is not itself involved in this process. The EPCAM gene lies next to the MSH2 gene on chromosome 2; certain EPCAM gene mutations cause the MSH2 gene to be turned off (inactivated), interrupting DNA repair and leading to accumulated DNA mistakes.  Although mutations in these genes predispose individuals to cancer, not all people who carry these mutations develop cancerous tumors.",Lynch syndrome,0000611,GHR,https://ghr.nlm.nih.gov/condition/lynch-syndrome,C1333990,T191,Disorders
Is Lynch syndrome inherited ?,0000611-4,inheritance,"Lynch syndrome cancer risk is inherited in an autosomal dominant pattern, which means one inherited copy of the altered gene in each cell is sufficient to increase cancer risk. It is important to note that people inherit an increased risk of cancer, not the disease itself. Not all people who inherit mutations in these genes will develop cancer.",Lynch syndrome,0000611,GHR,https://ghr.nlm.nih.gov/condition/lynch-syndrome,C1333990,T191,Disorders
What are the treatments for Lynch syndrome ?,0000611-5,treatment,These resources address the diagnosis or management of Lynch syndrome:  - American Medical Association and National Coalition for Health Professional Education in Genetics: Understand the Basics of Genetic Testing for Hereditary Colorectal Cancer  - Gene Review: Gene Review: Lynch Syndrome  - GeneFacts: Lynch Syndrome: Management  - Genetic Testing Registry: Hereditary nonpolyposis colorectal cancer type 3  - Genetic Testing Registry: Hereditary nonpolyposis colorectal cancer type 4  - Genetic Testing Registry: Hereditary nonpolyposis colorectal cancer type 5  - Genetic Testing Registry: Hereditary nonpolyposis colorectal cancer type 8  - Genetic Testing Registry: Lynch syndrome  - Genetic Testing Registry: Lynch syndrome I  - Genetic Testing Registry: Lynch syndrome II  - Genomics Education Programme (UK)  - MedlinePlus Encyclopedia: Colon Cancer  - National Cancer Institute: Genetic Testing for Hereditary Cancer Syndromes   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Lynch syndrome,0000611,GHR,https://ghr.nlm.nih.gov/condition/lynch-syndrome,C1333990,T191,Disorders
What is (are) lysinuric protein intolerance ?,0000612-1,information,"Lysinuric protein intolerance is a disorder caused by the body's inability to digest and use certain protein building blocks (amino acids), namely lysine, arginine, and ornithine. Because the body cannot effectively break down these amino acids, which are found in many protein-rich foods, nausea and vomiting are typically experienced after ingesting protein.  People with lysinuric protein intolerance have features associated with protein intolerance, including an enlarged liver and spleen (hepatosplenomegaly), short stature, muscle weakness, impaired immune function, and progressively brittle bones that are prone to fracture (osteoporosis). A lung disorder called pulmonary alveolar proteinosis may also develop. This disorder is characterized by protein deposits in the lungs, which interfere with lung function and can be life-threatening. An accumulation of amino acids in the kidneys can cause end-stage renal disease (ESRD) in which the kidneys become unable to filter fluids and waste products from the body effectively. A lack of certain amino acids can cause elevated levels of ammonia in the blood. If ammonia levels are too high for too long, they can cause coma and intellectual disability.  The signs and symptoms of lysinuric protein intolerance typically appear after infants are weaned and receive greater amounts of protein from solid foods.",lysinuric protein intolerance,0000612,GHR,https://ghr.nlm.nih.gov/condition/lysinuric-protein-intolerance,C0268647,T046,Disorders
How many people are affected by lysinuric protein intolerance ?,0000612-2,frequency,"Lysinuric protein intolerance is estimated to occur in 1 in 60,000 newborns in Finland and 1 in 57,000 newborns in Japan. Outside these populations this condition occurs less frequently, but the exact incidence is unknown.",lysinuric protein intolerance,0000612,GHR,https://ghr.nlm.nih.gov/condition/lysinuric-protein-intolerance,C0268647,T046,Disorders
What are the genetic changes related to lysinuric protein intolerance ?,0000612-3,genetic changes,"Mutations in the SLC7A7 gene cause lysinuric protein intolerance. The SLC7A7 gene provides instructions for producing a protein called y+L amino acid transporter 1 (y+LAT-1), which is involved in transporting lysine, arginine, and ornithine between cells in the body. The transportation of amino acids from the small intestines and kidneys to the rest of the body is necessary for the body to be able to use proteins. Mutations in the y+LAT-1 protein disrupt the transportation of amino acids, leading to a shortage of lysine, arginine, and ornithine in the body and an abnormally large amount of these amino acids in urine.  A shortage of lysine, arginine, and ornithine disrupts many vital functions. Arginine and ornithine are involved in a cellular process called the urea cycle, which processes excess nitrogen (in the form of ammonia) that is generated when protein is used by the body. The lack of arginine and ornithine in the urea cycle causes elevated levels of ammonia in the blood. Lysine is particularly abundant in collagen molecules that give structure and strength to connective tissues such as skin, tendons, and ligaments. A deficiency of lysine contributes to the short stature and osteoporosis seen in people with lysinuric protein intolerance. Other features of lysinuric protein intolerance are thought to result from abnormal protein transport (such as protein deposits in the lungs) or a lack of protein that can be used by the body (protein malnutrition).",lysinuric protein intolerance,0000612,GHR,https://ghr.nlm.nih.gov/condition/lysinuric-protein-intolerance,C0268647,T046,Disorders
Is lysinuric protein intolerance inherited ?,0000612-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",lysinuric protein intolerance,0000612,GHR,https://ghr.nlm.nih.gov/condition/lysinuric-protein-intolerance,C0268647,T046,Disorders
What are the treatments for lysinuric protein intolerance ?,0000612-5,treatment,These resources address the diagnosis or management of lysinuric protein intolerance:  - Gene Review: Gene Review: Lysinuric Protein Intolerance  - Genetic Testing Registry: Lysinuric protein intolerance  - MedlinePlus Encyclopedia: Aminoaciduria  - MedlinePlus Encyclopedia: Malabsorption   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,lysinuric protein intolerance,0000612,GHR,https://ghr.nlm.nih.gov/condition/lysinuric-protein-intolerance,C0268647,T046,Disorders
What is (are) Mabry syndrome ?,0000613-1,information,"Mabry syndrome is a condition characterized by intellectual disability, distinctive facial features, increased levels of an enzyme called alkaline phosphatase in the blood (hyperphosphatasia), and other signs and symptoms.  People with Mabry syndrome have intellectual disability that is often moderate to severe. They typically have little to no speech development and are delayed in the development of motor skills (such as sitting, crawling, and walking). Many affected individuals have low muscle tone (hypotonia) and develop recurrent seizures (epilepsy) in early childhood. Seizures are usually the generalized tonic-clonic type, which involve muscle rigidity, convulsions, and loss of consciousness.  Individuals with Mabry syndrome have distinctive facial features that include wide-set eyes (hypertelorism), long openings of the eyelids (long palpebral fissures), a nose with a broad bridge and a rounded tip, downturned corners of the mouth, and a thin upper lip. These facial features usually become less pronounced over time.  Hyperphosphatasia begins within the first year of life in people with Mabry syndrome. There are many different types of alkaline phosphatase found in tissues; the type that is increased in Mabry syndrome is called the tissue non-specific type and is found throughout the body. In affected individuals, alkaline phosphatase levels in the blood are usually increased by one to two times the normal amount, but can be up to 20 times higher than normal. The elevated enzyme levels remain relatively stable over a person's lifetime. Hyperphosphatasia appears to cause no negative health effects, but this finding can help health professionals diagnose Mabry syndrome.  Another common feature of Mabry syndrome is shortened bones at the ends of fingers (brachytelephalangy), which can be seen on x-ray imaging. Underdeveloped fingernails (nail hypoplasia) may also occur. Sometimes, individuals with Mabry syndrome have abnormalities of the digestive system, including narrowing or blockage of the anus (anal stenosis or anal atresia) or Hirschsprung disease, a disorder that causes severe constipation or blockage of the intestine. Rarely, affected individuals experience hearing loss.  The signs and symptoms of Mabry syndrome vary among affected individuals. Those who are least severely affected have only intellectual disability and hyperphosphatasia, without distinctive facial features or the other health problems listed above.",Mabry syndrome,0000613,GHR,https://ghr.nlm.nih.gov/condition/mabry-syndrome,C1855923,T047,Disorders
How many people are affected by Mabry syndrome ?,0000613-2,frequency,"Mabry syndrome is likely a rare condition, but its prevalence is unknown. More than 20 cases have been described in the scientific literature.",Mabry syndrome,0000613,GHR,https://ghr.nlm.nih.gov/condition/mabry-syndrome,C1855923,T047,Disorders
What are the genetic changes related to Mabry syndrome ?,0000613-3,genetic changes,"Mutations in the PIGV, PIGO, or PGAP2 gene cause Mabry syndrome. These genes are all involved in the production (synthesis) of a molecule called a glycosylphosphosphatidylinositol (GPI) anchor. This molecule is synthesized in a series of steps. It then attaches (binds) to various proteins and binds them to the outer surface of the cell membrane, ensuring that they are available when needed. Alkaline phosphatase is an example of a protein that is bound to the cell membrane by a GPI anchor.  The proteins produced from the PIGV and PIGO genes are involved in piecing together the GPI anchor. After the complete GPI anchor is attached to a protein, the protein produced from the PGAP2 gene adjusts the anchor to enhance the anchor's ability to bind to the cell membrane.  Mutations in the PIGV, PIGO, or PGAP2 gene result in the production of an incomplete GPI anchor that cannot attach to proteins or to cell membranes. Proteins lacking a functional GPI anchor cannot bind to the cell membrane and are instead released from the cell. The release of non-GPI anchored alkaline phosphatase elevates the amount of this protein in the blood, causing hyperphosphatasia in people with Mabry syndrome. It is unclear how gene mutations lead to the other features of Mabry syndrome, but these signs and symptoms are likely due to a lack of proper GPI anchoring of proteins.  PIGV gene mutations are the most frequent cause of Mabry syndrome, accounting for approximately half of all cases. Mutations in the PIGO and PGAP2 genes are responsible for a small proportion of Mabry syndrome. The remaining affected individuals do not have an identified mutation in any of these three genes; the cause of the condition in these individuals is unknown.",Mabry syndrome,0000613,GHR,https://ghr.nlm.nih.gov/condition/mabry-syndrome,C1855923,T047,Disorders
Is Mabry syndrome inherited ?,0000613-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Mabry syndrome,0000613,GHR,https://ghr.nlm.nih.gov/condition/mabry-syndrome,C1855923,T047,Disorders
What are the treatments for Mabry syndrome ?,0000613-5,treatment,These resources address the diagnosis or management of Mabry syndrome:  - Genetic Testing Registry: Hyperphosphatasia with mental retardation syndrome  - Genetic Testing Registry: Hyperphosphatasia with mental retardation syndrome 1  - Genetic Testing Registry: Hyperphosphatasia with mental retardation syndrome 2  - Genetic Testing Registry: Hyperphosphatasia with mental retardation syndrome 3  - MedlinePlus Encyclopedia: ALP Isoenzyme Test  - MedlinePlus Encyclopedia: ALP--Blood Test  - Seattle Children's Hospital: Hirschsprung's Disease--Treatments   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Mabry syndrome,0000613,GHR,https://ghr.nlm.nih.gov/condition/mabry-syndrome,C1855923,T047,Disorders
What is (are) Maffucci syndrome ?,0000615-1,information,"Maffucci syndrome is a disorder that primarily affects the bones and skin. It is characterized by multiple enchondromas, which are noncancerous (benign) growths of cartilage that develop within the bones. These growths most commonly occur in the limb bones, especially in the bones of the hands and feet; however, they may also occur in the skull, ribs, and bones of the spine (vertebrae). Enchondromas may result in severe bone deformities, shortening of the limbs, and fractures.  The signs and symptoms of Maffucci syndrome may be detectable at birth, although they generally do not become apparent until around the age of 5. Enchondromas develop near the ends of bones, where normal growth occurs, and they frequently stop forming after affected individuals stop growing in early adulthood. As a result of the bone deformities associated with Maffucci syndrome, people with this disorder generally have short stature and underdeveloped muscles.  Maffucci syndrome is distinguished from a similar disorder that involves enchondromas (Ollier disease) by the presence of red or purplish growths in the skin consisting of tangles of abnormal blood vessels (hemangiomas). In addition to hemangiomas, individuals with Maffucci syndrome occasionally also have lymphangiomas, which are masses made up of the thin tubes that carry lymph fluid (lymphatic vessels). These growths may appear anywhere on the body.  Although the enchondromas associated with Maffucci syndrome start out as benign, they may become cancerous (malignant). In particular, affected individuals may develop bone cancers called chondrosarcomas, especially in the skull. People with Maffucci syndrome also have an increased risk of other cancers, such as ovarian or liver cancer.  People with Maffucci syndrome usually have a normal lifespan, and intelligence is unaffected. The extent of their physical impairment depends on their individual skeletal deformities, but in most cases they have no major limitations in their activities.",Maffucci syndrome,0000615,GHR,https://ghr.nlm.nih.gov/condition/maffucci-syndrome,C0024454,T019,Disorders
How many people are affected by Maffucci syndrome ?,0000615-2,frequency,"Maffucci syndrome is very rare. Since it was first described in 1881, fewer than 200 cases have been reported worldwide.",Maffucci syndrome,0000615,GHR,https://ghr.nlm.nih.gov/condition/maffucci-syndrome,C0024454,T019,Disorders
What are the genetic changes related to Maffucci syndrome ?,0000615-3,genetic changes,"In most people with Maffucci syndrome, the disorder is caused by mutations in the IDH1 or IDH2 gene. These genes provide instructions for making enzymes called isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2, respectively. These enzymes convert a compound called isocitrate to another compound called 2-ketoglutarate. This reaction also produces a molecule called NADPH, which is necessary for many cellular processes. IDH1 or IDH2 gene mutations cause the enzyme produced from the respective gene to take on a new, abnormal function. Although these mutations have been found in some cells of enchondromas and hemangiomas in people with Maffucci syndrome, the relationship between the mutations and the signs and symptoms of the disorder is not well understood.  Mutations in other genes may also account for some cases of Maffucci syndrome.",Maffucci syndrome,0000615,GHR,https://ghr.nlm.nih.gov/condition/maffucci-syndrome,C0024454,T019,Disorders
Is Maffucci syndrome inherited ?,0000615-4,inheritance,"Maffucci syndrome is not inherited. The mutations that cause this disorder are somatic, which means they occur during a person's lifetime. A somatic mutation occurs in a single cell. As that cell continues to grow and divide, the cells derived from it also have the same mutation. In Maffucci syndrome, the mutation is thought to occur in a cell during early development before birth; cells that arise from that abnormal cell have the mutation, while the body's other cells do not. This situation is called mosaicism.",Maffucci syndrome,0000615,GHR,https://ghr.nlm.nih.gov/condition/maffucci-syndrome,C0024454,T019,Disorders
What are the treatments for Maffucci syndrome ?,0000615-5,treatment,These resources address the diagnosis or management of Maffucci syndrome:  - Genetic Testing Registry: Maffucci syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Maffucci syndrome,0000615,GHR,https://ghr.nlm.nih.gov/condition/maffucci-syndrome,C0024454,T019,Disorders
What is (are) Mainzer-Saldino syndrome ?,0000616-1,information,"Mainzer-Saldino syndrome is a disorder characterized by kidney disease, eye problems, and skeletal abnormalities.  People with Mainzer-Saldino syndrome have chronic kidney disease that begins in childhood and gets worse over time. The rate at which the kidney disease worsens is variable, but the condition eventually leads to kidney failure in most affected individuals.  Degeneration of the light-sensitive tissue at the back of the eye (the retina) almost always occurs in this disorder, but the age at which this feature develops varies. Some affected individuals are blind or have severe vision impairment beginning in infancy, with the pattern of vision loss resembling a condition called Leber congenital amaurosis. In other people with Mainzer-Saldino syndrome, the retinal degeneration begins in childhood, but some vision is retained into early adulthood. The vision loss in these affected individuals resembles a category of retinal disorders called rod-cone dystrophies. The most common rod-cone dystrophy is called retinitis pigmentosa, and the vision problems in Mainzer-Saldino syndrome are sometimes referred to as such. However, the abnormal deposits of pigment in the retina from which retinitis pigmentosa gets its name are often not found in Mainzer-Saldino syndrome. As a result, some researchers use terms such as ""atypical retinitis pigmentosa without pigment"" to describe the retinal degeneration that occurs in Mainzer-Saldino syndrome.  The skeletal abnormality most characteristic of Mainzer-Saldino syndrome consists of cone-shaped ends of the bones (epiphyses) in the fingers (phalanges) that can be seen on x-ray images after the first year of life. Affected individuals may also have abnormalities of the thigh bones that occur in the epiphyses and adjacent areas where bone growth occurs (the metaphyses). Occasionally, other skeletal abnormalities occur, including short stature and premature fusion of certain skull bones (craniosynostosis) that affects the shape of the head and face. Affected individuals may also have a small rib cage, which sometimes causes breathing problems in infancy, but the breathing problems are usually mild.  A small number of individuals with this disorder have additional problems affecting other organs. These can include liver disease resulting in a buildup of scar tissue in the liver (hepatic fibrosis); cerebellar ataxia, which is difficulty with coordination and balance arising from problems with a part of the brain called the cerebellum; and mild intellectual disability.",Mainzer-Saldino syndrome,0000616,GHR,https://ghr.nlm.nih.gov/condition/mainzer-saldino-syndrome,C1849437,T047,Disorders
How many people are affected by Mainzer-Saldino syndrome ?,0000616-2,frequency,Mainzer-Saldino syndrome is a rare disorder; its prevalence is unknown. At least 20 cases have been reported.,Mainzer-Saldino syndrome,0000616,GHR,https://ghr.nlm.nih.gov/condition/mainzer-saldino-syndrome,C1849437,T047,Disorders
What are the genetic changes related to Mainzer-Saldino syndrome ?,0000616-3,genetic changes,"Mainzer-Saldino syndrome is usually caused by mutations in the IFT140 gene. This gene provides instructions for making a protein that is involved in the formation and maintenance of cilia, which are microscopic, finger-like projections that stick out from the surface of cells and participate in signaling pathways that transmit information within and between cells. Cilia are important for the structure and function of many types of cells, including cells in the kidneys, liver, and brain. Light-sensing cells (photoreceptors) in the retina also contain cilia, which are essential for normal vision. Cilia also play a role in the development of the bones, although the mechanism is not well understood.  The movement of substances within cilia and similar structures called flagella is known as intraflagellar transport (IFT). This process is essential for the assembly and maintenance of these cell structures. During intraflagellar transport, cells use molecules called IFT particles to carry materials to and from the tips of cilia. IFT particles are made of proteins produced from related genes that belong to the IFT gene family. Each IFT particle is made up of two groups of IFT proteins: complex A, which includes at least six proteins, and complex B, which includes at least 15 proteins. The protein produced from the IFT140 gene forms part of IFT complex A (IFT-A).  Mutations in the IFT140 gene that cause Mainzer-Saldino syndrome may change the shape of the IFT140 protein or affect its interactions with other IFT proteins, likely impairing the assembly of IFT-A and the development or maintenance of cilia. As a result, fewer cilia may be present or functional, affecting many organs and tissues in the body and resulting in the signs and symptoms of Mainzer-Saldino syndrome. Disorders such as Mainzer-Saldino syndrome that are caused by problems with cilia and involve bone abnormalities are called skeletal ciliopathies.  While IFT140 gene mutations are believed to account for most cases of Mainzer-Saldino syndrome, mutations in additional genes that have not been identified may also cause this disorder.",Mainzer-Saldino syndrome,0000616,GHR,https://ghr.nlm.nih.gov/condition/mainzer-saldino-syndrome,C1849437,T047,Disorders
Is Mainzer-Saldino syndrome inherited ?,0000616-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Mainzer-Saldino syndrome,0000616,GHR,https://ghr.nlm.nih.gov/condition/mainzer-saldino-syndrome,C1849437,T047,Disorders
What are the treatments for Mainzer-Saldino syndrome ?,0000616-5,treatment,These resources address the diagnosis or management of Mainzer-Saldino syndrome:  - MedlinePlus Encyclopedia: Electroretinography  - National Institutes of Diabetes and Digestive and Kidney Diseases: Treatment Methods for Kidney Failure in Children   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Mainzer-Saldino syndrome,0000616,GHR,https://ghr.nlm.nih.gov/condition/mainzer-saldino-syndrome,C1849437,T047,Disorders
What is (are) Majeed syndrome ?,0000617-1,information,"Majeed syndrome is a rare condition characterized by recurrent episodes of fever and inflammation in the bones and skin.  One of the major features of Majeed syndrome is an inflammatory bone condition known as chronic recurrent multifocal osteomyelitis (CRMO). This condition causes recurrent episodes of pain and joint swelling beginning in infancy or early childhood. These symptoms persist into adulthood, although they may improve for short periods. CRMO can lead to complications such as slow growth and the development of joint deformities called contractures, which restrict the movement of certain joints.  Another feature of Majeed syndrome is a blood disorder called congenital dyserythropoietic anemia. This disorder is one of many types of anemia, all of which involve a shortage of red blood cells. Without enough of these cells, the blood cannot carry an adequate supply of oxygen to the body's tissues. The resulting symptoms can include tiredness (fatigue), weakness, pale skin, and shortness of breath. Complications of congenital dyserythropoietic anemia can range from mild to severe.  Most people with Majeed syndrome also develop inflammatory disorders of the skin, most often a condition known as Sweet syndrome. The symptoms of Sweet syndrome include fever and the development of painful bumps or blisters on the face, neck, back, and arms.",Majeed syndrome,0000617,GHR,https://ghr.nlm.nih.gov/condition/majeed-syndrome,C1864997,T047,Disorders
How many people are affected by Majeed syndrome ?,0000617-2,frequency,"Majeed syndrome appears to be very rare; it has been reported in three families, all from the Middle East.",Majeed syndrome,0000617,GHR,https://ghr.nlm.nih.gov/condition/majeed-syndrome,C1864997,T047,Disorders
What are the genetic changes related to Majeed syndrome ?,0000617-3,genetic changes,"Majeed syndrome results from mutations in the LPIN2 gene. This gene provides instructions for making a protein called lipin-2. Researchers believe that this protein may play a role in the processing of fats (lipid metabolism). However, no lipid abnormalities have been found with Majeed syndrome. Lipin-2 also may be involved in controlling inflammation and in cell division.  Mutations in the LPIN2 gene alter the structure and function of lipin-2. It is unclear how these genetic changes lead to bone disease, anemia, and inflammation of the skin in people with Majeed syndrome.",Majeed syndrome,0000617,GHR,https://ghr.nlm.nih.gov/condition/majeed-syndrome,C1864997,T047,Disorders
Is Majeed syndrome inherited ?,0000617-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene. Although carriers typically do not show signs and symptoms of the condition, some parents of children with Majeed syndrome have had an inflammatory skin disorder called psoriasis.",Majeed syndrome,0000617,GHR,https://ghr.nlm.nih.gov/condition/majeed-syndrome,C1864997,T047,Disorders
What are the treatments for Majeed syndrome ?,0000617-5,treatment,These resources address the diagnosis or management of Majeed syndrome:  - Gene Review: Gene Review: Majeed Syndrome  - Genetic Testing Registry: Majeed syndrome  - MedlinePlus Encyclopedia: Osteomyelitis  - MedlinePlus Encyclopedia: Psoriasis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Majeed syndrome,0000617,GHR,https://ghr.nlm.nih.gov/condition/majeed-syndrome,C1864997,T047,Disorders
What is (are) mal de Meleda ?,0000618-1,information,"Mal de Meleda is a rare skin disorder that begins in early infancy. Affected individuals have a condition known as palmoplantar keratoderma, in which the skin of the palms of the hands and soles of the feet becomes thick, hard, and callused. In mal de Meleda, the thickened skin is also found on the back of the hands and feet and on the wrists and ankles. In addition, affected individuals may have rough, thick pads on the joints of the fingers and toes and on the elbows and knees. Some people with mal de Meleda have recurrent fungal infections in the thickened skin, which can lead to a strong odor. Other features of this disorder can include short fingers and toes (brachydactyly), nail abnormalities, red skin around the mouth, and excessive sweating (hyperhidrosis).",mal de Meleda,0000618,GHR,https://ghr.nlm.nih.gov/condition/mal-de-meleda,C0025221,T019,Disorders
How many people are affected by mal de Meleda ?,0000618-2,frequency,Mal de Meleda is a rare disorder; its prevalence is unknown. The disorder was first identified on the Croatian island of Mjlet (called Meleda in Italian) and has since been found in populations worldwide.,mal de Meleda,0000618,GHR,https://ghr.nlm.nih.gov/condition/mal-de-meleda,C0025221,T019,Disorders
What are the genetic changes related to mal de Meleda ?,0000618-3,genetic changes,"Mal de Meleda is caused by mutations in the SLURP1 gene. This gene provides instructions for making a protein that interacts with other proteins, called receptors, and is likely involved in signaling within cells. Studies show that the SLURP-1 protein can attach (bind) to nicotinic acetylcholine receptors (nAChRs) in the skin. Through interaction with these receptors, the SLURP-1 protein is thought to be involved in controlling the growth and division (proliferation), maturation (differentiation), and survival of skin cells.  Mutations in the SLURP1 gene lead to little or no SLURP-1 protein in the body. It is unclear how a lack of this protein leads to the skin problems that occur in mal de Meleda. Researchers speculate that without SLURP-1, the activity of genes controlled by nAChR signaling is altered, leading to overgrowth of skin cells or survival of cells that normally would have died. The excess of cells can result in skin thickening. It is unclear why skin on the hands and feet is particularly affected.",mal de Meleda,0000618,GHR,https://ghr.nlm.nih.gov/condition/mal-de-meleda,C0025221,T019,Disorders
Is mal de Meleda inherited ?,0000618-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",mal de Meleda,0000618,GHR,https://ghr.nlm.nih.gov/condition/mal-de-meleda,C0025221,T019,Disorders
What are the treatments for mal de Meleda ?,0000618-5,treatment,These resources address the diagnosis or management of mal de Meleda:  - Foundation for Ichthyosis and Related Skin Types: Palmoplantar Keratodermas  - Genetic Testing Registry: Acroerythrokeratoderma   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,mal de Meleda,0000618,GHR,https://ghr.nlm.nih.gov/condition/mal-de-meleda,C0025221,T019,Disorders
What is (are) malignant hyperthermia ?,0000619-1,information,"Malignant hyperthermia is a severe reaction to particular drugs that are often used during surgery and other invasive procedures. Specifically, this reaction occurs in response to some anesthetic gases, which are used to block the sensation of pain, and with a muscle relaxant that is used to temporarily paralyze a person during a surgical procedure. If given these drugs, people at risk for malignant hyperthermia may experience muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), a high fever, increased acid levels in the blood and other tissues (acidosis), and a rapid heart rate. Without prompt treatment, the complications of malignant hyperthermia can be life-threatening.  People at increased risk for this disorder are said to have malignant hyperthermia susceptibility. Affected individuals may never know they have the condition unless they undergo testing or have a severe reaction to anesthesia during a surgical procedure. While this condition often occurs in people without other serious medical problems, certain inherited muscle diseases (including central core disease and multiminicore disease) are associated with malignant hyperthermia susceptibility.",malignant hyperthermia,0000619,GHR,https://ghr.nlm.nih.gov/condition/malignant-hyperthermia,C0024591,T047,Disorders
How many people are affected by malignant hyperthermia ?,0000619-2,frequency,"Malignant hyperthermia occurs in 1 in 5,000 to 50,000 instances in which people are given anesthetic gases. Susceptibility to malignant hyperthermia is probably more frequent, because many people with an increased risk of this condition are never exposed to drugs that trigger a reaction.",malignant hyperthermia,0000619,GHR,https://ghr.nlm.nih.gov/condition/malignant-hyperthermia,C0024591,T047,Disorders
What are the genetic changes related to malignant hyperthermia ?,0000619-3,genetic changes,"Variations of the CACNA1S and RYR1 genes increase the risk of developing malignant hyperthermia.  Researchers have described at least six forms of malignant hyperthermia susceptibility, which are caused by mutations in different genes. Mutations in the RYR1 gene are responsible for a form of the condition known as MHS1. These mutations account for most cases of malignant hyperthermia susceptibility. Another form of the condition, MHS5, results from mutations in the CACNA1S gene. These mutations are less common, causing less than 1 percent of all cases of malignant hyperthermia susceptibility.  The RYR1 and CACNA1S genes provide instructions for making proteins that play essential roles in muscles used for movement (skeletal muscles). For the body to move normally, these muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of certain charged atoms (ions) into muscle cells. The proteins produced from the RYR1 and CACNA1S genes are involved in the movement of calcium ions within muscle cells. In response to certain signals, the CACNA1S protein helps activate the RYR1 channel, which releases stored calcium ions within muscle cells. The resulting increase in calcium ion concentration inside muscle cells stimulates muscle fibers to contract.  Mutations in the RYR1 or CACNA1S gene cause the RYR1 channel to open more easily and close more slowly in response to certain drugs. As a result, large amounts of calcium ions are released from storage within muscle cells. An overabundance of available calcium ions causes skeletal muscles to contract abnormally, which leads to muscle rigidity in people with malignant hyperthermia. An increase in calcium ion concentration within muscle cells also activates processes that generate heat (leading to increased body temperature) and produce excess acid (leading to acidosis).  The genetic causes of several other types of malignant hyperthermia (MHS2, MHS4, and MHS6) are still under study. A form of the condition known as MHS3 has been linked to the CACNA2D1 gene. This gene provides instructions for making a protein that plays an essential role in activating the RYR1 channel to release calcium ions into muscle cells. Although this gene is thought to be related to malignant hyperthermia in a few families, no causative mutations have been identified.",malignant hyperthermia,0000619,GHR,https://ghr.nlm.nih.gov/condition/malignant-hyperthermia,C0024591,T047,Disorders
Is malignant hyperthermia inherited ?,0000619-4,inheritance,"Malignant hyperthermia susceptibility is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of a severe reaction to certain drugs used during surgery. In most cases, an affected person inherits the altered gene from a parent who is also at risk for the condition.",malignant hyperthermia,0000619,GHR,https://ghr.nlm.nih.gov/condition/malignant-hyperthermia,C0024591,T047,Disorders
What are the treatments for malignant hyperthermia ?,0000619-5,treatment,These resources address the diagnosis or management of malignant hyperthermia:  - Gene Review: Gene Review: Malignant Hyperthermia Susceptibility  - Genetic Testing Registry: Malignant hyperthermia susceptibility type 1  - Genetic Testing Registry: Malignant hyperthermia susceptibility type 2  - Genetic Testing Registry: Malignant hyperthermia susceptibility type 3  - Genetic Testing Registry: Malignant hyperthermia susceptibility type 4  - Genetic Testing Registry: Malignant hyperthermia susceptibility type 5  - Genetic Testing Registry: Malignant hyperthermia susceptibility type 6  - MedlinePlus Encyclopedia: Malignant Hyperthermia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,malignant hyperthermia,0000619,GHR,https://ghr.nlm.nih.gov/condition/malignant-hyperthermia,C0024591,T047,Disorders
What is (are) malignant migrating partial seizures of infancy ?,0000620-1,information,"Malignant migrating partial seizures of infancy (MMPSI) is a severe form of epilepsy that begins very early in life. Recurrent seizures begin before the age of 6 months but commonly start within a few weeks of birth. The seizures do not respond well to treatment. Although affected individuals may develop normally at first, progression stalls and skills decline when seizures begin; as a result, affected individuals have profound developmental delay.  The seizures in MMPSI are described as partial (or focal) because the seizure activity occurs in regions of the brain rather than affecting the entire brain. Seizure activity can appear in multiple locations in the brain or move (migrate) from one region to another during an episode. Depending on the region affected, seizures can involve sudden redness and warmth (flushing) of the face; drooling; short pauses in breathing (apnea); movement of the head or eyes to one side; twitches in the eyelids or tongue; chewing motions; or jerking of an arm, leg, or both on one side of the body. If seizure activity spreads to affect the entire brain, it causes a loss of consciousness, muscle stiffening, and rhythmic jerking (tonic-clonic seizure). Episodes that begin as partial seizures and spread throughout the brain are known as secondarily generalized seizures.  Initially, the seizures associated with MMPSI are relatively infrequent, occurring every few weeks. Within a few months of the seizures starting, though, the frequency increases. Affected individuals can have clusters of five to 30 seizures several times a day. Each seizure typically lasts seconds to a couple of minutes, but they can be prolonged (classified as status epilepticus). In some cases, the seizure activity may be almost continuous for several days. After a year or more of persistent seizures, the episodes become less frequent.  Seizures can affect growth of the brain and lead to a small head size (microcephaly). The problems with brain development can also cause profound developmental delay and intellectual impairment. Affected babies often lose the mental and motor skills they developed after birth, such as the ability to make eye contact and control their head movement. Many have weak muscle tone (hypotonia) and become ""floppy."" If seizures can be controlled for a short period, development may improve. Some affected children learn to reach for objects or walk. However, most children with this condition do not develop language skills.  Because of the serious health problems caused by MMPSI, many affected individuals do not survive past infancy or early childhood.",malignant migrating partial seizures of infancy,0000620,GHR,https://ghr.nlm.nih.gov/condition/malignant-migrating-partial-seizures-of-infancy,C0751495,T184,Disorders
How many people are affected by malignant migrating partial seizures of infancy ?,0000620-2,frequency,"MMPSI is a rare condition. Although its prevalence is unknown, approximately 100 cases have been described in the medical literature.",malignant migrating partial seizures of infancy,0000620,GHR,https://ghr.nlm.nih.gov/condition/malignant-migrating-partial-seizures-of-infancy,C0751495,T184,Disorders
What are the genetic changes related to malignant migrating partial seizures of infancy ?,0000620-3,genetic changes,"The genetic cause of MMPSI is not fully known. Mutations in the KCNT1 gene have been found in several individuals with this condition and are the most common known cause of MMPSI. Mutations in other genes are also thought to be involved in the condition.  The KCNT1 gene provides instructions for making a protein that forms potassium channels. Potassium channels, which transport positively charged atoms (ions) of potassium into and out of cells, play a key role in a cell's ability to generate and transmit electrical signals. Channels made with the KCNT1 protein are active in nerve cells (neurons) in the brain, where they transport potassium ions out of cells. This flow of ions is involved in generating currents to activate (excite) neurons and send signals in the brain.  KCNT1 gene mutations alter the KCNT1 protein. Electrical currents generated by potassium channels made with the altered KCNT1 protein are abnormally increased, which allows unregulated excitation of neurons in the brain. Seizures develop when neurons in the brain are abnormally excited. It is unclear why seizure activity can migrate in MMPSI. Repeated seizures in affected individuals contribute to the developmental delay that is characteristic of this condition.",malignant migrating partial seizures of infancy,0000620,GHR,https://ghr.nlm.nih.gov/condition/malignant-migrating-partial-seizures-of-infancy,C0751495,T184,Disorders
Is malignant migrating partial seizures of infancy inherited ?,0000620-4,inheritance,MMPSI is not inherited from a parent and does not run in families. This condition is caused by a new mutation that occurs very early in embryonic development (called a de novo mutation).,malignant migrating partial seizures of infancy,0000620,GHR,https://ghr.nlm.nih.gov/condition/malignant-migrating-partial-seizures-of-infancy,C0751495,T184,Disorders
What are the treatments for malignant migrating partial seizures of infancy ?,0000620-5,treatment,These resources address the diagnosis or management of malignant migrating partial seizures of infancy:  - Genetic Testing Registry: Early infantile epileptic encephalopathy 14  - MedlinePlus Encyclopedia: EEG   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,malignant migrating partial seizures of infancy,0000620,GHR,https://ghr.nlm.nih.gov/condition/malignant-migrating-partial-seizures-of-infancy,C0751495,T184,Disorders
What is (are) malonyl-CoA decarboxylase deficiency ?,0000621-1,information,"Malonyl-CoA decarboxylase deficiency is a condition that prevents the body from converting certain fats to energy. The signs and symptoms of this disorder typically appear in early childhood. Almost all affected children have delayed development. Additional signs and symptoms can include weak muscle tone (hypotonia), seizures, diarrhea, vomiting, and low blood sugar (hypoglycemia). A heart condition called cardiomyopathy, which weakens and enlarges the heart muscle, is another common feature of malonyl-CoA decarboxylase deficiency.",malonyl-CoA decarboxylase deficiency,0000621,GHR,https://ghr.nlm.nih.gov/condition/malonyl-coa-decarboxylase-deficiency,C0342793,T047,Disorders
How many people are affected by malonyl-CoA decarboxylase deficiency ?,0000621-2,frequency,This condition is very rare; fewer than 30 cases have been reported.,malonyl-CoA decarboxylase deficiency,0000621,GHR,https://ghr.nlm.nih.gov/condition/malonyl-coa-decarboxylase-deficiency,C0342793,T047,Disorders
What are the genetic changes related to malonyl-CoA decarboxylase deficiency ?,0000621-3,genetic changes,"Mutations in the MLYCD gene cause malonyl-CoA decarboxylase deficiency. The MLYCD gene provides instructions for making an enzyme called malonyl-CoA decarboxylase. Within cells, this enzyme helps regulate the formation and breakdown of a group of fats called fatty acids. Many tissues, including the heart muscle, use fatty acids as a major source of energy.  Mutations in the MLYCD gene reduce or eliminate the function of malonyl-CoA decarboxylase. A shortage of this enzyme disrupts the normal balance of fatty acid formation and breakdown in the body. As a result, fatty acids cannot be converted to energy, which can lead to characteristic features of this disorder including low blood sugar and cardiomyopathy. Byproducts of fatty acid processing build up in tissues, which also contributes to the signs and symptoms of malonyl-CoA decarboxylase deficiency.",malonyl-CoA decarboxylase deficiency,0000621,GHR,https://ghr.nlm.nih.gov/condition/malonyl-coa-decarboxylase-deficiency,C0342793,T047,Disorders
Is malonyl-CoA decarboxylase deficiency inherited ?,0000621-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",malonyl-CoA decarboxylase deficiency,0000621,GHR,https://ghr.nlm.nih.gov/condition/malonyl-coa-decarboxylase-deficiency,C0342793,T047,Disorders
What are the treatments for malonyl-CoA decarboxylase deficiency ?,0000621-5,treatment,These resources address the diagnosis or management of malonyl-CoA decarboxylase deficiency:  - Baby's First Test  - Genetic Testing Registry: Deficiency of malonyl-CoA decarboxylase   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,malonyl-CoA decarboxylase deficiency,0000621,GHR,https://ghr.nlm.nih.gov/condition/malonyl-coa-decarboxylase-deficiency,C0342793,T047,Disorders
What is (are) mandibuloacral dysplasia ?,0000622-1,information,"Mandibuloacral dysplasia is a condition that causes a variety of abnormalities involving bone development, skin coloring (pigmentation), and fat distribution. People with this condition may grow slowly after birth. Most affected individuals are born with an underdeveloped lower jaw bone (mandible) and small collar bones (clavicles), leading to the characteristic features of a small chin and sloped shoulders. Other bone problems include loss of bone from the tips of the fingers (acroosteolysis), which causes bulbous finger tips; delayed closure of certain skull bones; and joint deformities (contractures).  People with mandibuloacral dysplasia can have mottled or patchy skin pigmentation or other skin abnormalities. Some people with this condition have features of premature aging (a condition called progeria), such as thin skin, loss of teeth, loss of hair, and a beaked nose. Some individuals with mandibuloacral dysplasia have metabolic problems, such as diabetes.  A common feature of mandibuloacral dysplasia is a lack of fatty tissue under the skin (lipodystrophy) in certain regions of the body. The two types of this disorder, mandibuloacral dysplasia with type A lipodystrophy (MADA) and mandibuloacral dysplasia with type B lipodystrophy (MADB) are distinguished by the pattern of fat distribution throughout the body. Type A is described as partial lipodystrophy; affected individuals have a loss of fatty tissue from the torso and limbs, but it may build up around the neck and shoulders. Type B is a generalized lipodystrophy, with loss of fatty tissue in the face, torso, and limbs.  MADA usually begins in adulthood, although children can be affected. MADB begins earlier, often just after birth. Many babies with MADB are born prematurely.",mandibuloacral dysplasia,0000622,GHR,https://ghr.nlm.nih.gov/condition/mandibuloacral-dysplasia,C0432291,T019,Disorders
How many people are affected by mandibuloacral dysplasia ?,0000622-2,frequency,Mandibuloacral dysplasia is a rare condition; its prevalence is unknown.,mandibuloacral dysplasia,0000622,GHR,https://ghr.nlm.nih.gov/condition/mandibuloacral-dysplasia,C0432291,T019,Disorders
What are the genetic changes related to mandibuloacral dysplasia ?,0000622-3,genetic changes,"The two forms of mandibuloacral dysplasia are caused by mutations in different genes. Mutations in the LMNA gene cause MADA, and mutations in the ZMPSTE24 gene cause MADB. Within cells, these genes are involved in maintaining the structure of the nucleus and may play a role in many cellular processes.  The LMNA gene provides instructions for making two related proteins, lamin A and lamin C. These proteins act as scaffolding (supporting) components of the nuclear envelope, which is the membrane that surrounds the nucleus in cells. The nuclear envelope regulates the movement of molecules into and out of the nucleus and may help regulate the activity of certain genes. Mutations in this gene likely change the structure of lamin A and lamin C.  The lamin A protein (but not lamin C) must be processed within the cell before becoming part of the nuclear envelope. The protein produced from the ZMPSTE24 gene is involved in this processing; it cuts the immature lamin A protein (prelamin A) at a particular location, forming mature lamin A. Mutations in the ZMPSTE24 gene lead to a buildup of prelamin A and a shortage of the mature protein.  Mutations in the LMNA or ZMPSTE24 gene likely disrupt the structure of the nuclear envelope. Researchers are working to understand how these genetic changes result in the signs and symptoms of mandibuloacral dysplasia.",mandibuloacral dysplasia,0000622,GHR,https://ghr.nlm.nih.gov/condition/mandibuloacral-dysplasia,C0432291,T019,Disorders
Is mandibuloacral dysplasia inherited ?,0000622-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",mandibuloacral dysplasia,0000622,GHR,https://ghr.nlm.nih.gov/condition/mandibuloacral-dysplasia,C0432291,T019,Disorders
What are the treatments for mandibuloacral dysplasia ?,0000622-5,treatment,These resources address the diagnosis or management of mandibuloacral dysplasia:  - Genetic Testing Registry: Mandibuloacral dysostosis  - Genetic Testing Registry: Mandibuloacral dysplasia with type B lipodystrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,mandibuloacral dysplasia,0000622,GHR,https://ghr.nlm.nih.gov/condition/mandibuloacral-dysplasia,C0432291,T019,Disorders
What is (are) mandibulofacial dysostosis with microcephaly ?,0000623-1,information,"Mandibulofacial dysostosis with microcephaly (MFDM) is a disorder that causes abnormalities of the head and face. People with this disorder often have an unusually small head at birth, and the head does not grow at the same rate as the rest of the body, so it appears that the head is getting smaller as the body grows (progressive microcephaly). Affected individuals have developmental delay and intellectual disability that can range from mild to severe. Speech and language problems are also common in this disorder.  Facial abnormalities that occur in MFDM include underdevelopment of the middle of the face and the cheekbones (midface and malar hypoplasia) and an unusually small lower jaw (mandibular hypoplasia, also called micrognathia). The external ears are small and abnormally shaped, and they may have skin growths in front of them called preauricular tags. There may also be abnormalities of the ear canal, the tiny bones in the ears (ossicles), or a part of the inner ear called the semicircular canals. These ear abnormalities lead to hearing loss in most affected individuals. Some people with MFDM have an opening in the roof of the mouth (cleft palate), which may also contribute to hearing loss by increasing the risk of ear infections. Affected individuals can also have a blockage of the nasal passages (choanal atresia) that can cause respiratory problems.  Heart problems, abnormalities of the thumbs, and short stature are other features that can occur in MFDM. Some people with this disorder also have blockage of the esophagus (esophageal atresia). In esophageal atresia, the upper esophagus does not connect to the lower esophagus and stomach. Most babies born with esophageal atresia (EA) also have a tracheoesophageal fistula (TEF), in which the esophagus and the trachea are abnormally connected, allowing fluids from the esophagus to get into the airways and interfere with breathing. Esophageal atresia/tracheoesophageal fistula (EA/TEF) is a life-threatening condition; without treatment, it prevents normal feeding and can cause lung damage from repeated exposure to esophageal fluids.",mandibulofacial dysostosis with microcephaly,0000623,GHR,https://ghr.nlm.nih.gov/condition/mandibulofacial-dysostosis-with-microcephaly,C0013393,T047,Disorders
How many people are affected by mandibulofacial dysostosis with microcephaly ?,0000623-2,frequency,MFDM is a rare disorder; its exact prevalence is unknown. More than 60 affected individuals have been described in the medical literature.,mandibulofacial dysostosis with microcephaly,0000623,GHR,https://ghr.nlm.nih.gov/condition/mandibulofacial-dysostosis-with-microcephaly,C0013393,T047,Disorders
What are the genetic changes related to mandibulofacial dysostosis with microcephaly ?,0000623-3,genetic changes,"MFDM is caused by mutations in the EFTUD2 gene. This gene provides instructions for making one part (subunit) of two complexes called the major and minor spliceosomes. Spliceosomes help process messenger RNA (mRNA), which is a chemical cousin of DNA that serves as a genetic blueprint for making proteins. The spliceosomes recognize and then remove regions called introns to help produce mature mRNA molecules.  EFTUD2 gene mutations that cause MFDM result in the production of little or no functional enzyme from one copy of the gene in each cell. A shortage of this enzyme likely impairs mRNA processing. The relationship between these mutations and the specific symptoms of MFDM is not well understood.",mandibulofacial dysostosis with microcephaly,0000623,GHR,https://ghr.nlm.nih.gov/condition/mandibulofacial-dysostosis-with-microcephaly,C0013393,T047,Disorders
Is mandibulofacial dysostosis with microcephaly inherited ?,0000623-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family. In other cases, an affected person inherits the mutation from a parent. The parent may be mildly affected or may be unaffected. Sometimes the parent has the gene mutation only in some or all of their sperm or egg cells, which is known as germline mosaicism. In these cases, the parent has no signs or symptoms of the condition.",mandibulofacial dysostosis with microcephaly,0000623,GHR,https://ghr.nlm.nih.gov/condition/mandibulofacial-dysostosis-with-microcephaly,C0013393,T047,Disorders
What are the treatments for mandibulofacial dysostosis with microcephaly ?,0000623-5,treatment,"These resources address the diagnosis or management of MFDM:  - Gene Review: Gene Review: Mandibulofacial Dysostosis with Microcephaly  - Genetic Testing Registry: Growth and mental retardation, mandibulofacial dysostosis, microcephaly, and cleft palate   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",mandibulofacial dysostosis with microcephaly,0000623,GHR,https://ghr.nlm.nih.gov/condition/mandibulofacial-dysostosis-with-microcephaly,C0013393,T047,Disorders
What is (are) Manitoba oculotrichoanal syndrome ?,0000624-1,information,"Manitoba oculotrichoanal syndrome is a condition involving several characteristic physical features, particularly affecting the eyes (oculo-), hair (tricho-), and anus (-anal).  People with Manitoba oculotrichoanal syndrome have widely spaced eyes (hypertelorism). They may also have other eye abnormalities including small eyes (microphthalmia), a notched or partially absent upper eyelid (upper eyelid coloboma), eyelids that are attached to the front surface of the eye (corneopalpebral synechiae), or eyes that are completely covered by skin and usually malformed (cryptophthalmos). These abnormalities may affect one or both eyes.  Individuals with Manitoba oculotrichoanal syndrome usually have abnormalities of the front hairline, such as hair growth extending from the temple to the eye on one or both sides of the face. One or both eyebrows may be completely or partially missing. Most people with this disorder also have a wide nose with a notched tip; in some cases this notch extends up from the tip so that the nose appears to be divided into two halves (bifid nose).  About 20 percent of people with Manitoba oculotrichoanal syndrome have defects in the abdominal wall, such as a soft out-pouching around the belly-button (an umbilical hernia) or an opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the navel. Another characteristic feature of Manitoba oculotrichoanal syndrome is a narrow anus (anal stenosis) or an anal opening farther forward than usual. Umbilical wall defects or anal malformations may require surgical correction. Some affected individuals also have malformations of the kidneys.  The severity of the features of Manitoba oculotrichoanal syndrome may vary even within the same family. With appropriate treatment, affected individuals generally have normal growth and development, intelligence, and life expectancy.",Manitoba oculotrichoanal syndrome,0000624,GHR,https://ghr.nlm.nih.gov/condition/manitoba-oculotrichoanal-syndrome,C0039082,T047,Disorders
How many people are affected by Manitoba oculotrichoanal syndrome ?,0000624-2,frequency,"Manitoba oculotrichoanal syndrome is estimated to occur in 2 to 6 in 1,000 people in a small isolated Ojibway-Cree community in northern Manitoba, Canada. Although this region has the highest incidence of the condition, it has also been diagnosed in a few people from other parts of the world.",Manitoba oculotrichoanal syndrome,0000624,GHR,https://ghr.nlm.nih.gov/condition/manitoba-oculotrichoanal-syndrome,C0039082,T047,Disorders
What are the genetic changes related to Manitoba oculotrichoanal syndrome ?,0000624-3,genetic changes,"Manitoba oculotrichoanal syndrome is caused by mutations in the FREM1 gene. The FREM1 gene provides instructions for making a protein that is involved in the formation and organization of basement membranes, which are thin, sheet-like structures that separate and support cells in many tissues.  The FREM1 protein is one of a group of proteins, including proteins called FRAS1 and FREM2, that interact during embryonic development as components of basement membranes. Basement membranes help anchor layers of cells lining the surfaces and cavities of the body (epithelial cells) to other embryonic tissues, including those that give rise to connective tissues such as skin and cartilage.  The FREM1 gene mutations that have been identified in people with Manitoba oculotrichoanal syndrome delete genetic material from the FREM1 gene or result in a premature stop signal that leads to an abnormally short FREM1 protein. These mutations most likely result in a nonfunctional protein.  Absence of functional FREM1 protein interferes with its role in embryonic basement membrane development and may also affect the location, stability, or function of the FRAS1 and FREM2 proteins. The features of Manitoba oculotrichoanal syndrome may result from the failure of neighboring embryonic tissues to fuse properly due to impairment of the basement membranes' anchoring function.",Manitoba oculotrichoanal syndrome,0000624,GHR,https://ghr.nlm.nih.gov/condition/manitoba-oculotrichoanal-syndrome,C0039082,T047,Disorders
Is Manitoba oculotrichoanal syndrome inherited ?,0000624-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Manitoba oculotrichoanal syndrome,0000624,GHR,https://ghr.nlm.nih.gov/condition/manitoba-oculotrichoanal-syndrome,C0039082,T047,Disorders
What are the treatments for Manitoba oculotrichoanal syndrome ?,0000624-5,treatment,These resources address the diagnosis or management of Manitoba oculotrichoanal syndrome:  - Gene Review: Gene Review: Manitoba Oculotrichoanal Syndrome  - Genetic Testing Registry: Marles Greenberg Persaud syndrome  - MedlinePlus Encyclopedia: Omphalocele Repair   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Manitoba oculotrichoanal syndrome,0000624,GHR,https://ghr.nlm.nih.gov/condition/manitoba-oculotrichoanal-syndrome,C0039082,T047,Disorders
What is (are) mannose-binding lectin deficiency ?,0000625-1,information,"Mannose-binding lectin deficiency is a condition that affects the immune system. People with this condition have low levels of an immune system protein called mannose-binding lectin in their blood. These individuals are prone to recurrent infections, including infections of the upper respiratory tract and other body systems. People with this condition may also contract more serious infections such as pneumonia and meningitis. Depending on the type of infection, the symptoms caused by the infections vary in frequency and severity.  Infants and young children with mannose-binding lectin deficiency seem to be more susceptible to infections, but adults can also develop recurrent infections. In addition, affected individuals undergoing chemotherapy or taking drugs that suppress the immune system are especially prone to infections.",mannose-binding lectin deficiency,0000625,GHR,https://ghr.nlm.nih.gov/condition/mannose-binding-lectin-deficiency,C3280586,T047,Disorders
How many people are affected by mannose-binding lectin deficiency ?,0000625-2,frequency,"Mannose-binding lectin deficiency is thought to affect approximately 5 to 10 percent of people worldwide; however, many affected individuals have no signs or symptoms related to low mannose-binding lectin levels. The condition is more common in certain populations, such as sub-Saharan Africans.",mannose-binding lectin deficiency,0000625,GHR,https://ghr.nlm.nih.gov/condition/mannose-binding-lectin-deficiency,C3280586,T047,Disorders
What are the genetic changes related to mannose-binding lectin deficiency ?,0000625-3,genetic changes,"Relatively common mutations in the MBL2 gene can lead to mannose-binding lectin deficiency. This gene provides instructions for making a protein that assembles into a complex called mannose-binding lectin. Functional mannose-binding lectins are made up of two to six protein groups called trimers, which are each composed of three of the protein pieces (subunits) produced from the MBL2 gene.  Mannose-binding lectin plays an important role in the body's immune response by attaching to foreign invaders such as bacteria, viruses, or yeast and turning on (activating) the complement system. The complement system is a group of immune system proteins that work together to destroy foreign invaders (pathogens), trigger inflammation, and remove debris from cells and tissues. Mannose-binding lectin can also stimulate special immune cells to engulf and break down the attached pathogen.  Disease-associated mutations in the MBL2 gene can reduce the production of the mannose-binding lectin subunit or eliminate the subunit's ability to assemble into functional mannose-binding lectin. A decrease in the availability of the normal subunit protein may lead to a reduction of the functional mannose-binding lectin in blood. With decreased levels of mannose-binding lectin, the body does not recognize and fight foreign invaders efficiently. Consequently, infections can be more common in people with this condition.  However, not everyone with a change in the MBL2 gene has decreased levels of mannose-binding lectin, and not everyone with decreased protein levels is prone to infection. Researchers believe that a number of factors, including other genetic and environmental factors, are involved in the development of mannose-binding lectin deficiency and susceptibility to infection.",mannose-binding lectin deficiency,0000625,GHR,https://ghr.nlm.nih.gov/condition/mannose-binding-lectin-deficiency,C3280586,T047,Disorders
Is mannose-binding lectin deficiency inherited ?,0000625-4,inheritance,"The inheritance pattern of mannose-binding lectin deficiency is unclear. Some reports show that having a disease-associated mutation in one copy of the MBL2 gene in each cell can lead to the condition, while other reports state that a mutation in both copies of the gene is necessary. It is important to note that people inherit an increased risk of developing mannose-binding lectin deficiency, not the condition itself. Not all people who inherit mutations in this gene will develop the condition.",mannose-binding lectin deficiency,0000625,GHR,https://ghr.nlm.nih.gov/condition/mannose-binding-lectin-deficiency,C3280586,T047,Disorders
What are the treatments for mannose-binding lectin deficiency ?,0000625-5,treatment,These resources address the diagnosis or management of mannose-binding lectin deficiency:  - Genetic Testing Registry: Mannose-binding protein deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,mannose-binding lectin deficiency,0000625,GHR,https://ghr.nlm.nih.gov/condition/mannose-binding-lectin-deficiency,C3280586,T047,Disorders
What is (are) maple syrup urine disease ?,0000626-1,information,"Maple syrup urine disease is an inherited disorder in which the body is unable to process certain protein building blocks (amino acids) properly. The condition gets its name from the distinctive sweet odor of affected infants' urine and is also characterized by poor feeding, vomiting, lack of energy (lethargy), and developmental delay. If untreated, maple syrup urine disease can lead to seizures, coma, and death.  Maple syrup urine disease is often classified by its pattern of signs and symptoms. The most common and severe form of the disease is the classic type, which becomes apparent soon after birth. Variant forms of the disorder become apparent later in infancy or childhood and are typically milder, but they still involve developmental delay and other health problems if not treated.",maple syrup urine disease,0000626,GHR,https://ghr.nlm.nih.gov/condition/maple-syrup-urine-disease,C0024776,T047,Disorders
How many people are affected by maple syrup urine disease ?,0000626-2,frequency,"Maple syrup urine disease affects an estimated 1 in 185,000 infants worldwide. The disorder occurs much more frequently in the Old Order Mennonite population, with an estimated incidence of about 1 in 380 newborns.",maple syrup urine disease,0000626,GHR,https://ghr.nlm.nih.gov/condition/maple-syrup-urine-disease,C0024776,T047,Disorders
What are the genetic changes related to maple syrup urine disease ?,0000626-3,genetic changes,"Mutations in the BCKDHA, BCKDHB, and DBT genes can cause maple syrup urine disease. These three genes provide instructions for making proteins that work together as a complex. The protein complex is essential for breaking down the amino acids leucine, isoleucine, and valine, which are present in many kinds of food, particularly protein-rich foods such as milk, meat, and eggs.  Mutations in any of these three genes reduce or eliminate the function of the protein complex, preventing the normal breakdown of leucine, isoleucine, and valine. As a result, these amino acids and their byproducts build up in the body. Because high levels of these substances are toxic to the brain and other organs, their accumulation leads to the serious health problems associated with maple syrup urine disease.",maple syrup urine disease,0000626,GHR,https://ghr.nlm.nih.gov/condition/maple-syrup-urine-disease,C0024776,T047,Disorders
Is maple syrup urine disease inherited ?,0000626-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",maple syrup urine disease,0000626,GHR,https://ghr.nlm.nih.gov/condition/maple-syrup-urine-disease,C0024776,T047,Disorders
What are the treatments for maple syrup urine disease ?,0000626-5,treatment,These resources address the diagnosis or management of maple syrup urine disease:  - Baby's First Test  - Gene Review: Gene Review: Maple Syrup Urine Disease  - Genetic Testing Registry: Maple syrup urine disease  - MedlinePlus Encyclopedia: Maple Syrup Urine Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,maple syrup urine disease,0000626,GHR,https://ghr.nlm.nih.gov/condition/maple-syrup-urine-disease,C0024776,T047,Disorders
What is (are) Marfan syndrome ?,0000627-1,information,"Marfan syndrome is a disorder that affects the connective tissue in many parts of the body. Connective tissue provides strength and flexibility to structures such as bones, ligaments, muscles, blood vessels, and heart valves. The signs and symptoms of Marfan syndrome vary widely in severity, timing of onset, and rate of progression.  The two primary features of Marfan syndrome are vision problems caused by a dislocated lens (ectopia lentis) in one or both eyes and defects in the large blood vessel that distributes blood from the heart to the rest of the body (the aorta). The aorta can weaken and stretch, which may lead to a bulge in the blood vessel wall (an aneurysm). Stretching of the aorta may cause the aortic valve to leak, which can lead to a sudden tearing of the layers in the aorta wall (aortic dissection). Aortic aneurysm and dissection can be life threatening.  Many people with Marfan syndrome have additional heart problems including a leak in the valve that connects two of the four chambers of the heart (mitral valve prolapse) or the valve that regulates blood flow from the heart into the aorta (aortic valve regurgitation). Leaks in these valves can cause shortness of breath, fatigue, and an irregular heartbeat felt as skipped or extra beats (palpitations).  Individuals with Marfan syndrome are usually tall and slender, have elongated fingers and toes (arachnodactyly), and have an arm span that exceeds their body height. Other common features include a long and narrow face, crowded teeth, an abnormal curvature of the spine (scoliosis or kyphosis), and either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum). Some individuals develop an abnormal accumulation of air in the chest cavity that can result in the collapse of a lung (spontaneous pneumothorax). A membrane called the dura, which surrounds the brain and spinal cord, can be abnormally enlarged (dural ectasia) in people with Marfan syndrome. Dural ectasia can cause pain in the back, abdomen, legs, or head. Most individuals with Marfan syndrome have some degree of nearsightedness (myopia). Clouding of the lens (cataract) may occur in mid-adulthood, and increased pressure within the eye (glaucoma) occurs more frequently in people with Marfan syndrome than in those without the condition.  The features of Marfan syndrome can become apparent anytime between infancy and adulthood. Depending on the onset and severity of signs and symptoms, Marfan can be fatal early in life; however, the majority of affected individuals survive into mid- to late adulthood.",Marfan syndrome,0000627,GHR,https://ghr.nlm.nih.gov/condition/marfan-syndrome,C0024796,T047,Disorders
How many people are affected by Marfan syndrome ?,0000627-2,frequency,"The incidence of Marfan syndrome is approximately 1 in 5,000 worldwide.",Marfan syndrome,0000627,GHR,https://ghr.nlm.nih.gov/condition/marfan-syndrome,C0024796,T047,Disorders
What are the genetic changes related to Marfan syndrome ?,0000627-3,genetic changes,"Mutations in the FBN1 gene cause Marfan syndrome. The FBN1 gene provides instructions for making a protein called fibrillin-1. Fibrillin-1 attaches (binds) to other fibrillin-1 proteins and other molecules to form threadlike filaments called microfibrils. Microfibrils become part of the fibers that provide strength and flexibility to connective tissue. Additionally, microfibrils store molecules called growth factors and release them at various times to control the growth and repair of tissues and organs throughout the body. A mutation in the FBN1 gene can reduce the amount of functional fibrillin-1 that is available to form microfibrils, which leads to decreased microfibril formation. As a result, excess growth factors are released and elasticity in many tissues is decreased, leading to overgrowth and instability of tissues.",Marfan syndrome,0000627,GHR,https://ghr.nlm.nih.gov/condition/marfan-syndrome,C0024796,T047,Disorders
Is Marfan syndrome inherited ?,0000627-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  At least 25 percent of Marfan syndrome cases result from a new mutation in the FBN1 gene. These cases occur in people with no history of the disorder in their family.",Marfan syndrome,0000627,GHR,https://ghr.nlm.nih.gov/condition/marfan-syndrome,C0024796,T047,Disorders
What are the treatments for Marfan syndrome ?,0000627-5,treatment,These resources address the diagnosis or management of Marfan syndrome:  - Gene Review: Gene Review: Marfan Syndrome  - Genetic Testing Registry: Marfan syndrome  - MarfanDX  - MedlinePlus Encyclopedia: Aortic Dissection  - MedlinePlus Encyclopedia: Marfan Syndrome  - MedlinePlus Encyclopedia: Thoracic Aortic Aneurysm  - National Marfan Foundation: Diagnosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Marfan syndrome,0000627,GHR,https://ghr.nlm.nih.gov/condition/marfan-syndrome,C0024796,T047,Disorders
What is (are) Marinesco-Sjgren syndrome ?,0000628-1,information,"Marinesco-Sjgren syndrome is a condition that has a variety of signs and symptoms affecting many tissues. People with Marinesco-Sjgren syndrome have clouding of the lens of the eyes (cataracts) that usually develops soon after birth or in early childhood. Affected individuals also have muscle weakness (myopathy) and difficulty coordinating movements (ataxia), which may impair their ability to walk. People with Marinesco-Sjgren syndrome may experience further decline in muscle function later in life.  Most people with Marinesco-Sjgren syndrome have mild to moderate intellectual disability. They also have skeletal abnormalities including short stature and a spine that curves to the side (scoliosis). Other features of Marinesco-Sjgren syndrome include eyes that do not look in the same direction (strabismus), involuntary eye movements (nystagmus), and impaired speech (dysarthria).  Affected individuals may have hypergonadotropic hypogonadism, which affects the production of hormones that direct sexual development. As a result, puberty is either delayed or absent.",Marinesco-Sjgren syndrome,0000628,GHR,https://ghr.nlm.nih.gov/condition/marinesco-sjogren-syndrome,C0039082,T047,Disorders
How many people are affected by Marinesco-Sjgren syndrome ?,0000628-2,frequency,Marinesco-Sjgren syndrome appears to be a rare condition. More than 100 cases have been reported worldwide.,Marinesco-Sjgren syndrome,0000628,GHR,https://ghr.nlm.nih.gov/condition/marinesco-sjogren-syndrome,C0039082,T047,Disorders
What are the genetic changes related to Marinesco-Sjgren syndrome ?,0000628-3,genetic changes,"Mutations in the SIL1 gene cause Marinesco-Sjgren syndrome. The SIL1 gene provides instructions for producing a protein located in a cell structure called the endoplasmic reticulum. Among its many functions, the endoplasmic reticulum folds and modifies newly formed proteins so they have the correct 3-dimensional shape. The SIL1 protein plays a role in the process of protein folding.  SIL1 gene mutations result in the production of a protein that has little or no activity. A lack of SIL1 protein is thought to impair protein folding, which could disrupt protein transport and cause proteins to accumulate in the endoplasmic reticulum. This accumulation likely damages and destroys cells in many different tissues, leading to ataxia, myopathy, and the other features of Marinesco-Sjgren syndrome.  Approximately one-third of people with Marinesco-Sjgren syndrome do not have identified mutations in the SIL1 gene. In these cases, the cause of the condition is unknown.",Marinesco-Sjgren syndrome,0000628,GHR,https://ghr.nlm.nih.gov/condition/marinesco-sjogren-syndrome,C0039082,T047,Disorders
Is Marinesco-Sjgren syndrome inherited ?,0000628-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Marinesco-Sjgren syndrome,0000628,GHR,https://ghr.nlm.nih.gov/condition/marinesco-sjogren-syndrome,C0039082,T047,Disorders
What are the treatments for Marinesco-Sjgren syndrome ?,0000628-5,treatment,These resources address the diagnosis or management of Marinesco-Sjgren syndrome:  - Gene Review: Gene Review: Marinesco-Sjogren Syndrome  - Genetic Testing Registry: Marinesco-Sjgren syndrome  - MedlinePlus Encyclopedia: Congenital Cataract  - MedlinePlus Encyclopedia: Hypogonadism  - MedlinePlus Encyclopedia: Muscle Atrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Marinesco-Sjgren syndrome,0000628,GHR,https://ghr.nlm.nih.gov/condition/marinesco-sjogren-syndrome,C0039082,T047,Disorders
What is (are) maternally inherited diabetes and deafness ?,0000629-1,information,"Maternally inherited diabetes and deafness (MIDD) is a form of diabetes that is often accompanied by hearing loss, especially of high tones. The diabetes in MIDD is characterized by high blood sugar levels (hyperglycemia) resulting from a shortage of the hormone insulin, which regulates the amount of sugar in the blood. In MIDD, the diabetes and hearing loss usually develop in mid-adulthood, although the age that they occur varies from childhood to late adulthood. Typically, hearing loss occurs before diabetes.  Some people with MIDD develop an eye disorder called macular retinal dystrophy, which is characterized by colored patches in the light-sensitive tissue that lines the back of the eye (the retina). This disorder does not usually cause vision problems in people with MIDD. Individuals with MIDD also may experience muscle cramps or weakness, particularly during exercise; heart problems; kidney disease; and constipation. Individuals with MIDD are often shorter than their peers.",maternally inherited diabetes and deafness,0000629,GHR,https://ghr.nlm.nih.gov/condition/maternally-inherited-diabetes-and-deafness,C0011053,T047,Disorders
How many people are affected by maternally inherited diabetes and deafness ?,0000629-2,frequency,About 1 percent of people with diabetes have MIDD. The condition is most common in the Japanese population and has been found in populations worldwide.,maternally inherited diabetes and deafness,0000629,GHR,https://ghr.nlm.nih.gov/condition/maternally-inherited-diabetes-and-deafness,C0011053,T047,Disorders
What are the genetic changes related to maternally inherited diabetes and deafness ?,0000629-3,genetic changes,"Mutations in the MT-TL1, MT-TK, or MT-TE gene cause MIDD. These genes are found in mitochondrial DNA, which is part of cellular structures called mitochondria. Although most DNA is packaged in chromosomes within the cell nucleus, mitochondria also have a small amount of their own DNA (known as mitochondrial DNA or mtDNA).  The MT-TL1, MT-TK, and MT-TE genes provide instructions for making molecules called transfer RNAs (tRNAs), which are chemical cousins of DNA. These molecules help assemble protein building blocks (amino acids) into functioning proteins. The MT-TL1 gene provides instructions for making a specific form of tRNA that is designated as tRNALeu(UUR). During protein assembly, this molecule attaches to the amino acid leucine (Leu) and inserts it into the appropriate locations in the growing protein. Similarly, the protein produced from the MT-TK gene, called tRNALys, attaches to the amino acid lysine (Lys) and inserts it into proteins being assembled. Also, the protein produced from the MT-TE gene, called tRNAGlu, attaches to the amino acid glutamic acid (Glu) and adds it to growing proteins.  These tRNA molecules are present only in mitochondria, and they help assemble proteins that are involved in producing energy for cells. In certain cells in the pancreas called beta cells, mitochondria also play a role in controlling the amount of sugar (glucose) in the bloodstream. In response to high glucose levels, mitochondria help trigger the release of insulin, which stimulates cells to take up glucose from the blood.  Mutations in the MT-TL1, MT-TK, or MT-TE gene reduce the ability of tRNA to add amino acids to growing proteins, which slows protein production in mitochondria and impairs their functioning. Researchers believe that the disruption of mitochondrial function lessens the ability of mitochondria to help trigger insulin release. In people with this condition, diabetes results when the beta cells do not produce enough insulin to regulate blood sugar effectively. Researchers have not determined how the mutations lead to hearing loss or the other features of MIDD.",maternally inherited diabetes and deafness,0000629,GHR,https://ghr.nlm.nih.gov/condition/maternally-inherited-diabetes-and-deafness,C0011053,T047,Disorders
Is maternally inherited diabetes and deafness inherited ?,0000629-4,inheritance,"MIDD is inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mtDNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children.  Most of the body's cells contain thousands of mitochondria, each with one or more copies of mtDNA. These cells can have a mix of mitochondria containing mutated and unmutated DNA (heteroplasmy). The severity of MIDD is thought to be associated with the percentage of mitochondria with the mtDNA mutation.",maternally inherited diabetes and deafness,0000629,GHR,https://ghr.nlm.nih.gov/condition/maternally-inherited-diabetes-and-deafness,C0011053,T047,Disorders
What are the treatments for maternally inherited diabetes and deafness ?,0000629-5,treatment,These resources address the diagnosis or management of MIDD:  - Genetic Testing Registry: Diabetes-deafness syndrome maternally transmitted   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,maternally inherited diabetes and deafness,0000629,GHR,https://ghr.nlm.nih.gov/condition/maternally-inherited-diabetes-and-deafness,C0011053,T047,Disorders
What is (are) Mayer-Rokitansky-Kster-Hauser syndrome ?,0000630-1,information,"Mayer-Rokitansky-Kster-Hauser (MRKH) syndrome is a disorder that occurs in females and mainly affects the reproductive system. This condition causes the vagina and uterus to be underdeveloped or absent. Affected women usually do not have menstrual periods due to the absent uterus. Often, the first noticeable sign of MRKH syndrome is that menstruation does not begin by age 16 (primary amenorrhea). Women with MRKH syndrome have a female chromosome pattern (46,XX) and normally functioning ovaries. They also have normal female external genitalia and normal breast and pubic hair development. Although women with this condition are usually unable to carry a pregnancy, they may be able to have children through assisted reproduction.  Women with MRKH syndrome may also have abnormalities in other parts of the body. The kidneys may be abnormally formed or positioned, or one kidney may fail to develop (unilateral renal agenesis). Affected individuals commonly develop skeletal abnormalities, particularly of the spinal bones (vertebrae). Females with MRKH syndrome may also have hearing loss or heart defects.",Mayer-Rokitansky-Kster-Hauser syndrome,0000630,GHR,https://ghr.nlm.nih.gov/condition/mayer-rokitansky-kuster-hauser-syndrome,C0039082,T047,Disorders
How many people are affected by Mayer-Rokitansky-Kster-Hauser syndrome ?,0000630-2,frequency,"MRKH syndrome affects approximately 1 in 4,500 newborn girls.",Mayer-Rokitansky-Kster-Hauser syndrome,0000630,GHR,https://ghr.nlm.nih.gov/condition/mayer-rokitansky-kuster-hauser-syndrome,C0039082,T047,Disorders
What are the genetic changes related to Mayer-Rokitansky-Kster-Hauser syndrome ?,0000630-3,genetic changes,"The cause of MRKH syndrome is unknown, although it probably results from a combination of genetic and environmental factors. Researchers have not identified any genes associated with MRKH syndrome.  The reproductive abnormalities of MRKH syndrome are due to incomplete development of the Mllerian duct. This structure in the embryo develops into the uterus, fallopian tubes, cervix, and the upper part of the vagina. The cause of the abnormal development of the Mllerian duct in affected individuals is unknown. Originally, researchers believed that MRKH syndrome was caused by something the fetus was exposed to during pregnancy, such as a medication or maternal illness. However, studies have not identified an association with maternal drug use, illness, or other factors. It is also unclear why some affected individuals have abnormalities in parts of the body other than the reproductive system.",Mayer-Rokitansky-Kster-Hauser syndrome,0000630,GHR,https://ghr.nlm.nih.gov/condition/mayer-rokitansky-kuster-hauser-syndrome,C0039082,T047,Disorders
Is Mayer-Rokitansky-Kster-Hauser syndrome inherited ?,0000630-4,inheritance,"Most cases of MRKH syndrome occur in people with no history of the disorder in their family.  Less often, MRKH syndrome is passed through generations in families. Its inheritance pattern is usually unclear because the signs and symptoms of the condition frequently vary among affected individuals in the same family. However, in some families, the condition appears to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of the altered gene in each cell is typically sufficient to cause the disorder, although no genes have been associated with MRKH syndrome.",Mayer-Rokitansky-Kster-Hauser syndrome,0000630,GHR,https://ghr.nlm.nih.gov/condition/mayer-rokitansky-kuster-hauser-syndrome,C0039082,T047,Disorders
What are the treatments for Mayer-Rokitansky-Kster-Hauser syndrome ?,0000630-5,treatment,These resources address the diagnosis or management of Mayer-Rokitansky-Kster-Hauser syndrome:  - American Urological Association Foundation: Vaginal Agenesis  - Children's Hospital Boston: Center for Young Women's Health  - Genetic Testing Registry: Rokitansky Kuster Hauser syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Mayer-Rokitansky-Kster-Hauser syndrome,0000630,GHR,https://ghr.nlm.nih.gov/condition/mayer-rokitansky-kuster-hauser-syndrome,C0039082,T047,Disorders
What is (are) McCune-Albright syndrome ?,0000631-1,information,"McCune-Albright syndrome is a disorder that affects the bones, skin, and several hormone-producing (endocrine) tissues.  People with McCune-Albright syndrome develop areas of abnormal scar-like (fibrous) tissue in their bones, a condition called polyostotic fibrous dysplasia. Polyostotic means the abnormal areas (lesions) may occur in many bones; often they are confined to one side of the body. Replacement of bone with fibrous tissue may lead to fractures, uneven growth, and deformity. When lesions occur in the bones of the skull and jaw it can result in uneven (asymmetric) growth of the face. Asymmetry may also occur in the long bones; uneven growth of leg bones may cause limping. Abnormal curvature of the spine (scoliosis) may also occur. Bone lesions may become cancerous, but this happens in fewer than 1 percent of people with McCune-Albright syndrome.  In addition to bone abnormalities, affected individuals usually have light brown patches of skin called caf-au-lait spots, which may be present from birth. The irregular borders of the caf-au-lait spots in McCune-Albright syndrome are often compared to a map of the coast of Maine. By contrast, caf-au-lait spots in other disorders have smooth borders, which are compared to the coast of California. Like the bone lesions, the caf-au-lait spots in McCune-Albright syndrome often appear on only one side of the body.  Girls with McCune-Albright syndrome usually reach puberty early. These girls usually have menstrual bleeding by age two, many years before secondary sex characteristics such as breast enlargement and pubic hair are evident. This early onset of menstruation is believed to be caused by excess estrogen, a female sex hormone, produced by cysts that develop in one of the ovaries. Less commonly, boys with McCune-Albright syndrome may also experience early puberty.  Other endocrine problems may also occur in people with McCune-Albright syndrome. The thyroid gland, a butterfly-shaped organ at the base of the neck, may become enlarged (a condition called a goiter) or develop masses called nodules. About 50 percent of affected individuals produce excessive amounts of thyroid hormone (hyperthyroidism), resulting in a fast heart rate, high blood pressure, weight loss, tremors, sweating, and other symptoms. The pituitary gland (a structure at the base of the brain that makes several hormones) may produce too much growth hormone. Excess growth hormone can result in acromegaly, a condition characterized by large hands and feet, arthritis, and distinctive facial features that are often described as ""coarse."" Rarely, affected individuals develop Cushing's syndrome, an excess of the hormone cortisol produced by the adrenal glands, which are small glands located on top of each kidney. Cushing's syndrome causes weight gain in the face and upper body, slowed growth in children, fragile skin, fatigue, and other health problems.",McCune-Albright syndrome,0000631,GHR,https://ghr.nlm.nih.gov/condition/mccune-albright-syndrome,C0242292,T047,Disorders
How many people are affected by McCune-Albright syndrome ?,0000631-2,frequency,"McCune-Albright syndrome occurs in between 1 in 100,000 and 1 in 1,000,000 people worldwide.",McCune-Albright syndrome,0000631,GHR,https://ghr.nlm.nih.gov/condition/mccune-albright-syndrome,C0242292,T047,Disorders
What are the genetic changes related to McCune-Albright syndrome ?,0000631-3,genetic changes,"McCune-Albright syndrome is caused by a mutation in the GNAS gene. The GNAS gene provides instructions for making one part of a protein complex called a guanine nucleotide-binding protein, or a G protein.  In a process called signal transduction, G proteins trigger a complex network of signaling pathways that ultimately influence many cell functions by regulating the activity of hormones. The protein produced from the GNAS gene helps stimulate the activity of an enzyme called adenylate cyclase. GNAS gene mutations that cause McCune-Albright syndrome result in a G protein that causes the adenylate cyclase enzyme to be constantly turned on (constitutively activated). Constitutive activation of the adenylate cyclase enzyme leads to over-production of several hormones, resulting in the signs and symptoms of McCune-Albright syndrome.",McCune-Albright syndrome,0000631,GHR,https://ghr.nlm.nih.gov/condition/mccune-albright-syndrome,C0242292,T047,Disorders
Is McCune-Albright syndrome inherited ?,0000631-4,inheritance,"McCune-Albright syndrome is not inherited. Instead, it is caused by a random mutation in the GNAS gene that occurs very early in development. As a result, some of the body's cells have a normal version of the GNAS gene, while other cells have the mutated version. This phenomenon is called mosaicism. The severity of this disorder and its specific features depend on the number and location of cells that have the mutated GNAS gene.",McCune-Albright syndrome,0000631,GHR,https://ghr.nlm.nih.gov/condition/mccune-albright-syndrome,C0242292,T047,Disorders
What are the treatments for McCune-Albright syndrome ?,0000631-5,treatment,These resources address the diagnosis or management of McCune-Albright syndrome:  - Gene Review: Gene Review: Fibrous Dysplasia/McCune-Albright Syndrome  - Genetic Testing Registry: McCune-Albright syndrome  - MedlinePlus Encyclopedia: McCune-Albright syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,McCune-Albright syndrome,0000631,GHR,https://ghr.nlm.nih.gov/condition/mccune-albright-syndrome,C0242292,T047,Disorders
What is (are) McKusick-Kaufman syndrome ?,0000632-1,information,"McKusick-Kaufman syndrome is a condition that affects the development of the hands and feet, heart, and reproductive system. It is characterized by a combination of three features: extra fingers and/or toes (polydactyly), heart defects, and genital abnormalities.  Most females with McKusick-Kaufman syndrome are born with a genital abnormality called hydrometrocolpos, which is a large accumulation of fluid in the pelvis. Hydrometrocolpos results from a blockage of the vagina before birth, which can occur if part of the vagina fails to develop (vaginal agenesis) or if a membrane blocks the opening of the vagina. This blockage allows fluid to build up in the vagina and uterus, stretching these organs and leading to a fluid-filled mass. Genital abnormalities in males with McKusick-Kaufman syndrome can include placement of the urethral opening on the underside of the penis (hypospadias), a downward-curving penis (chordee), and undescended testes (cryptorchidism).  The signs and symptoms of McKusick-Kaufman syndrome overlap significantly with those of another genetic disorder, Bardet-Biedl syndrome. Bardet-Biedl syndrome has several features that are not seen in McKusick-Kaufman syndrome, however. These include vision loss, delayed development, obesity, and kidney (renal) failure. Because some of these features are not apparent at birth, the two conditions can be difficult to tell apart in infancy and early childhood.",McKusick-Kaufman syndrome,0000632,GHR,https://ghr.nlm.nih.gov/condition/mckusick-kaufman-syndrome,C0948368,T019,Disorders
How many people are affected by McKusick-Kaufman syndrome ?,0000632-2,frequency,"This condition was first described in the Old Order Amish population, where it affects an estimated 1 in 10,000 people. The incidence of McKusick-Kaufman syndrome in non-Amish populations is unknown.",McKusick-Kaufman syndrome,0000632,GHR,https://ghr.nlm.nih.gov/condition/mckusick-kaufman-syndrome,C0948368,T019,Disorders
What are the genetic changes related to McKusick-Kaufman syndrome ?,0000632-3,genetic changes,"Mutations in the MKKS gene cause McKusick-Kaufman syndrome. This gene provides instructions for making a protein that plays an important role in the formation of the limbs, heart, and reproductive system. The protein's structure suggests that it may act as a chaperonin, which is a type of protein that helps fold other proteins. Proteins must be folded into the correct 3-dimensional shape to perform their usual functions in the body. Although the structure of the MKKS protein is similar to that of a chaperonin, some recent studies have suggested that protein folding may not be this protein's primary function. Researchers speculate that the MKKS protein also may be involved in transporting other proteins within the cell.  The mutations that underlie McKusick-Kaufman syndrome alter the structure of the MKKS protein. Although the altered protein disrupts the development of several parts of the body before birth, it is unclear how MKKS mutations lead to the specific features of this disorder.",McKusick-Kaufman syndrome,0000632,GHR,https://ghr.nlm.nih.gov/condition/mckusick-kaufman-syndrome,C0948368,T019,Disorders
Is McKusick-Kaufman syndrome inherited ?,0000632-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",McKusick-Kaufman syndrome,0000632,GHR,https://ghr.nlm.nih.gov/condition/mckusick-kaufman-syndrome,C0948368,T019,Disorders
What are the treatments for McKusick-Kaufman syndrome ?,0000632-5,treatment,These resources address the diagnosis or management of McKusick-Kaufman syndrome:  - Gene Review: Gene Review: McKusick-Kaufman Syndrome  - Genetic Testing Registry: McKusick Kaufman syndrome  - MedlinePlus Encyclopedia: Polydactyly   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,McKusick-Kaufman syndrome,0000632,GHR,https://ghr.nlm.nih.gov/condition/mckusick-kaufman-syndrome,C0948368,T019,Disorders
What is (are) McLeod neuroacanthocytosis syndrome ?,0000633-1,information,"McLeod neuroacanthocytosis syndrome is primarily a neurological disorder that occurs almost exclusively in boys and men. This disorder affects movement in many parts of the body. People with McLeod neuroacanthocytosis syndrome also have abnormal star-shaped red blood cells (acanthocytosis). This condition is one of a group of disorders called neuroacanthocytoses that involve neurological problems and abnormal red blood cells.  McLeod neuroacanthocytosis syndrome affects the brain and spinal cord (central nervous system). Affected individuals have involuntary movements, including jerking motions (chorea), particularly of the arms and legs, and muscle tensing (dystonia) in the face and throat, which can cause grimacing and vocal tics (such as grunting and clicking noises). Dystonia of the tongue can lead to swallowing difficulties. Seizures occur in approximately half of all people with McLeod neuroacanthocytosis syndrome. Individuals with this condition may develop difficulty processing, learning, and remembering information (cognitive impairment). They may also develop psychiatric disorders, such as depression, bipolar disorder, psychosis, or obsessive-compulsive disorder.  People with McLeod neuroacanthocytosis syndrome also have problems with their muscles, including muscle weakness (myopathy) and muscle degeneration (atrophy). Sometimes, nerves that connect to muscles atrophy (neurogenic atrophy), leading to loss of muscle mass and impaired movement. Individuals with McLeod neuroacanthocytosis syndrome may also have reduced sensation and weakness in their arms and legs (peripheral neuropathy). Life-threatening heart problems such as irregular heartbeats (arrhythmia) and a weakened and enlarged heart (dilated cardiomyopathy) are common in individuals with this disorder.  The signs and symptoms of McLeod neuroacanthocytosis syndrome usually begin in mid-adulthood. Behavioral changes, such as lack of self-restraint, the inability to take care of oneself, anxiety, depression, and changes in personality may be the first signs of this condition. While these behavioral changes are typically not progressive, the movement and muscle problems and intellectual impairments tend to worsen with age.",McLeod neuroacanthocytosis syndrome,0000633,GHR,https://ghr.nlm.nih.gov/condition/mcleod-neuroacanthocytosis-syndrome,C0393576,T047,Disorders
How many people are affected by McLeod neuroacanthocytosis syndrome ?,0000633-2,frequency,McLeod neuroacanthocytosis syndrome is rare; approximately 150 cases have been reported worldwide.,McLeod neuroacanthocytosis syndrome,0000633,GHR,https://ghr.nlm.nih.gov/condition/mcleod-neuroacanthocytosis-syndrome,C0393576,T047,Disorders
What are the genetic changes related to McLeod neuroacanthocytosis syndrome ?,0000633-3,genetic changes,"Mutations in the XK gene cause McLeod neuroacanthocytosis syndrome. The XK gene provides instructions for producing the XK protein, which carries the blood antigen Kx. Blood antigens are found on the surface of red blood cells and determine blood type. The XK protein is found in various tissues, particularly the brain, muscle, and heart. The function of the XK protein is unclear; researchers believe that it might play a role in transporting substances into and out of cells. On red blood cells, the XK protein attaches to another blood group protein, the Kell protein. The function of this blood group complex is unknown.  XK gene mutations typically lead to the production of an abnormally short, nonfunctional protein or cause no protein to be produced at all. A lack of XK protein leads to an absence of Kx antigens on red blood cells; the Kell antigen is also less prevalent. The absence of Kx antigen and reduction of Kell antigen is known as the ""McLeod phenotype,"" and refers only to the red blood cells. It is not known how the lack of XK protein leads to the movement problems and other features of McLeod neuroacanthocytosis syndrome.",McLeod neuroacanthocytosis syndrome,0000633,GHR,https://ghr.nlm.nih.gov/condition/mcleod-neuroacanthocytosis-syndrome,C0393576,T047,Disorders
Is McLeod neuroacanthocytosis syndrome inherited ?,0000633-4,inheritance,"McLeod neuroacanthocytosis syndrome is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. Rarely, females with a mutation in one copy of the XK gene can have the characteristic misshapen blood cells and movement problems associated with McLeod neuroacanthocytosis syndrome. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",McLeod neuroacanthocytosis syndrome,0000633,GHR,https://ghr.nlm.nih.gov/condition/mcleod-neuroacanthocytosis-syndrome,C0393576,T047,Disorders
What are the treatments for McLeod neuroacanthocytosis syndrome ?,0000633-5,treatment,These resources address the diagnosis or management of McLeod neuroacanthocytosis syndrome:  - Gene Review: Gene Review: McLeod Neuroacanthocytosis Syndrome  - Genetic Testing Registry: McLeod neuroacanthocytosis syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,McLeod neuroacanthocytosis syndrome,0000633,GHR,https://ghr.nlm.nih.gov/condition/mcleod-neuroacanthocytosis-syndrome,C0393576,T047,Disorders
What is (are) Meckel syndrome ?,0000634-1,information,"Meckel syndrome is a disorder with severe signs and symptoms that affect many parts of the body. The most common features are enlarged kidneys with numerous fluid-filled cysts; an occipital encephalocele, which is a sac-like protrusion of the brain through an opening at the back of the skull; and the presence of extra fingers and toes (polydactyly). Most affected individuals also have a buildup of scar tissue (fibrosis) in the liver.  Other signs and symptoms of Meckel syndrome vary widely among affected individuals. Numerous abnormalities of the brain and spinal cord (central nervous system) have been reported in people with Meckel syndrome, including a group of birth defects known as neural tube defects. These defects occur when a structure called the neural tube, a layer of cells that ultimately develops into the brain and spinal cord, fails to close completely during the first few weeks of embryonic development. Meckel syndrome can also cause problems with development of the eyes and other facial features, heart, bones, urinary system, and genitalia.  Because of their serious health problems, most individuals with Meckel syndrome die before or shortly after birth. Most often, affected infants die of respiratory problems or kidney failure.",Meckel syndrome,0000634,GHR,https://ghr.nlm.nih.gov/condition/meckel-syndrome,C3714506,T047,Disorders
How many people are affected by Meckel syndrome ?,0000634-2,frequency,"Meckel syndrome affects 1 in 13,250 to 1 in 140,000 people worldwide. It is more common in certain populations; for example, the condition affects about 1 in 9,000 people of Finnish ancestry and about 1 in 3,000 people of Belgian ancestry.",Meckel syndrome,0000634,GHR,https://ghr.nlm.nih.gov/condition/meckel-syndrome,C3714506,T047,Disorders
What are the genetic changes related to Meckel syndrome ?,0000634-3,genetic changes,"Meckel syndrome can be caused by mutations in one of at least eight genes. The proteins produced from these genes are known or suspected to play roles in cell structures called cilia. Cilia are microscopic, finger-like projections that stick out from the surface of cells and are involved in signaling pathways that transmit information between cells. Cilia are important for the structure and function of many types of cells, including brain cells and certain cells in the kidneys and liver.  Mutations in the genes associated with Meckel syndrome lead to problems with the structure and function of cilia. Defects in these cell structures probably disrupt important chemical signaling pathways during early development. Although researchers believe that defective cilia are responsible for most of the features of this disorder, it remains unclear how they lead to specific developmental abnormalities of the brain, kidneys, and other parts of the body.  Mutations in the eight genes known to be associated with Meckel syndrome account for about 75 percent of all cases of the condition. In the remaining cases, the genetic cause is unknown. Mutations in several other genes have been identified in people with features similar to those of Meckel syndrome, although it is unclear whether these individuals actually have Meckel syndrome or a related disorder (often described as a ""Meckel-like phenotype"").",Meckel syndrome,0000634,GHR,https://ghr.nlm.nih.gov/condition/meckel-syndrome,C3714506,T047,Disorders
Is Meckel syndrome inherited ?,0000634-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Meckel syndrome,0000634,GHR,https://ghr.nlm.nih.gov/condition/meckel-syndrome,C3714506,T047,Disorders
What are the treatments for Meckel syndrome ?,0000634-5,treatment,"These resources address the diagnosis or management of Meckel syndrome:  - Genetic Testing Registry: Meckel syndrome type 1  - Genetic Testing Registry: Meckel syndrome type 2  - Genetic Testing Registry: Meckel syndrome type 3  - Genetic Testing Registry: Meckel syndrome type 4  - Genetic Testing Registry: Meckel syndrome type 5  - Genetic Testing Registry: Meckel syndrome type 6  - Genetic Testing Registry: Meckel syndrome type 7  - Genetic Testing Registry: Meckel syndrome type 8  - Genetic Testing Registry: Meckel syndrome, type 10  - Genetic Testing Registry: Meckel syndrome, type 9   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Meckel syndrome,0000634,GHR,https://ghr.nlm.nih.gov/condition/meckel-syndrome,C3714506,T047,Disorders
What is (are) MECP2 duplication syndrome ?,0000635-1,information,"MECP2 duplication syndrome is a condition that occurs almost exclusively in males and is characterized by moderate to severe intellectual disability. Most people with this condition also have weak muscle tone in infancy, feeding difficulties, poor or absent speech, seizures that may not improve with treatment, or muscle stiffness (spasticity). Individuals with MECP2 duplication syndrome have delayed development of motor skills such as sitting and walking. Some affected individuals experience the loss of previously acquired skills (developmental regression). Approximately one third of people with this condition cannot walk without assistance. Many individuals with MECP2 duplication syndrome have recurrent respiratory tract infections. These respiratory infections are a major cause of death in affected individuals, with almost half succumbing by age 25.",MECP2 duplication syndrome,0000635,GHR,https://ghr.nlm.nih.gov/condition/mecp2-duplication-syndrome,C1846058,T048,Disorders
How many people are affected by MECP2 duplication syndrome ?,0000635-2,frequency,The prevalence of MECP2 duplication syndrome is unknown; approximately 120 affected individuals have been reported in the scientific literature. It is estimated that this condition is responsible for 1 to 2 percent of all cases of intellectual disability caused by changes in the X chromosome.,MECP2 duplication syndrome,0000635,GHR,https://ghr.nlm.nih.gov/condition/mecp2-duplication-syndrome,C1846058,T048,Disorders
What are the genetic changes related to MECP2 duplication syndrome ?,0000635-3,genetic changes,"MECP2 duplication syndrome is caused by a genetic change in which there is an extra copy of the MECP2 gene in each cell. This extra copy of the MECP2 gene is caused by a duplication of genetic material on the long (q) arm of the X chromosome. The size of the duplication varies from 100,000 to 900,000 DNA building blocks (base pairs), also written as 100 to 900 kilobases (kb). The MECP2 gene is always included in this duplication, and other genes may be involved, depending on the size of the duplicated segment. Extra copies of these other genes do not seem to affect the severity of the condition, because people with larger duplications have signs and symptoms that are similar to people with smaller duplications.  The MECP2 gene provides instructions for making a protein called MeCP2 that is critical for normal brain function. Researchers believe that this protein has several functions, including regulating other genes in the brain by switching them off when they are not needed. An extra copy of the MECP2 gene leads to the production of excess MeCP2 protein, which is unable to properly regulate the expression of other genes. The misregulation of gene expression in the brain results in abnormal nerve cell (neuronal) function. These neuronal abnormalities cause irregular brain activity, leading to the signs and symptoms of MECP2 duplication syndrome.",MECP2 duplication syndrome,0000635,GHR,https://ghr.nlm.nih.gov/condition/mecp2-duplication-syndrome,C1846058,T048,Disorders
Is MECP2 duplication syndrome inherited ?,0000635-4,inheritance,"MECP2 duplication syndrome is inherited in an X-linked pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), a duplication of the only copy of the MECP2 gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a duplication of one of the two copies of the gene typically does not cause the disorder. Females usually do not have signs and symptoms of MECP2 duplication syndrome because the X chromosome that contains the duplication may be turned off (inactive) due to a process called X-inactivation.  Early in embryonic development in females, one of the two X chromosomes is permanently inactivated in somatic cells (cells other than egg and sperm cells). X-inactivation ensures that females, like males, have only one active copy of the X chromosome in each body cell. Usually X-inactivation occurs randomly, such that each X chromosome is active in about half of the body cells. Sometimes X-inactivation is not random, and one X chromosome is active in more than half of cells. When X-inactivation does not occur randomly, it is called skewed X-inactivation.  Research shows that females with an MECP2 gene duplication have skewed X-inactivation, which results in the inactivation of the X chromosome containing the duplication in most cells of the body. This skewed X inactivation ensures that only the chromosome with the normal MECP2 gene is expressed. This skewed X-inactivation is why females with an MECP2 gene duplication typically do not have any features related to the additional genetic material.",MECP2 duplication syndrome,0000635,GHR,https://ghr.nlm.nih.gov/condition/mecp2-duplication-syndrome,C1846058,T048,Disorders
What are the treatments for MECP2 duplication syndrome ?,0000635-5,treatment,These resources address the diagnosis or management of MECP2 duplication syndrome:  - Cincinnati Children's Hospital: MECP2-Related Disorders  - Cleveland Clinic: Spasticity  - Gene Review: Gene Review: MECP2 Duplication Syndrome  - Genetic Testing Registry: MECP2 duplication syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,MECP2 duplication syndrome,0000635,GHR,https://ghr.nlm.nih.gov/condition/mecp2-duplication-syndrome,C1846058,T048,Disorders
What is (are) MECP2-related severe neonatal encephalopathy ?,0000636-1,information,"MECP2-related severe neonatal encephalopathy is a neurological disorder that primarily affects males and causes brain dysfunction (encephalopathy). Affected males have a small head size (microcephaly), poor muscle tone (hypotonia) in infancy, movement disorders, rigidity, and seizures. Infants with this condition appear normal at birth but then develop severe encephalopathy within the first week of life. These babies experience poor feeding, leading to a failure to gain weight and grow at the expected rate (failure to thrive). Individuals with MECP2-related severe neonatal encephalopathy have severe to profound intellectual disability. Affected males have breathing problems, with some having episodes in which breathing slows or stops for short periods (apnea). As the child ages, the apnea episodes tend to last longer, especially during sleep, and affected babies often require use of a machine to help regulate their breathing (mechanical ventilation). Most males with MECP2-related severe neonatal encephalopathy do not live past the age of 2 because of respiratory failure.  MECP2-related severe neonatal encephalopathy is the most severe condition in a spectrum of disorders with the same genetic cause. The mildest is PPM-X syndrome, followed by MECP2 duplication syndrome, then Rett syndrome (which exclusively affects females), and finally MECP2-related severe neonatal encephalopathy.",MECP2-related severe neonatal encephalopathy,0000636,GHR,https://ghr.nlm.nih.gov/condition/mecp2-related-severe-neonatal-encephalopathy,C0235820,T047,Disorders
How many people are affected by MECP2-related severe neonatal encephalopathy ?,0000636-2,frequency,MECP2-related severe neonatal encephalopathy is likely a rare condition. Twenty to 30 affected males have been reported in the scientific literature.,MECP2-related severe neonatal encephalopathy,0000636,GHR,https://ghr.nlm.nih.gov/condition/mecp2-related-severe-neonatal-encephalopathy,C0235820,T047,Disorders
What are the genetic changes related to MECP2-related severe neonatal encephalopathy ?,0000636-3,genetic changes,"Mutations in the MECP2 gene cause MECP2-related severe neonatal encephalopathy. The MECP2 gene provides instructions for making a protein called MeCP2 that is critical for normal brain function. Researchers believe that this protein has several functions, including regulating other genes in the brain by switching them on or off as they are needed. The MeCP2 protein likely plays a role in maintaining the normal function of nerve cells, which ensures that connections (synapses) between these cells form properly. The MeCP2 protein may also control the production of different versions of certain proteins in nerve cells. Although mutations in the MECP2 gene disrupt the normal function of nerve cells, it is unclear how these mutations lead to the signs and symptoms of MECP2-related severe neonatal encephalopathy.",MECP2-related severe neonatal encephalopathy,0000636,GHR,https://ghr.nlm.nih.gov/condition/mecp2-related-severe-neonatal-encephalopathy,C0235820,T047,Disorders
Is MECP2-related severe neonatal encephalopathy inherited ?,0000636-4,inheritance,"MECP2-related severe neonatal encephalopathy has an X-linked pattern of inheritance. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males, who have only one X chromosome, a mutation in the only copy of the gene in each cell is sufficient to cause the condition. In females, who have two X chromosomes, a mutation in one of the two copies of the gene in each cell is usually sufficient to cause the condition. However, females with a mutation in the MECP2 gene do not develop MECP2-related severe neonatal encephalopathy. Instead, they typically develop Rett syndrome, which has signs and symptoms that include intellectual disability, seizures, and movement problems.  In some cases, males with MECP2-related severe neonatal encephalopathy inherit the mutation from a mother with mild neurological problems or from a mother with no features related to the mutation. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",MECP2-related severe neonatal encephalopathy,0000636,GHR,https://ghr.nlm.nih.gov/condition/mecp2-related-severe-neonatal-encephalopathy,C0235820,T047,Disorders
What are the treatments for MECP2-related severe neonatal encephalopathy ?,0000636-5,treatment,These resources address the diagnosis or management of MECP2-related severe neonatal encephalopathy:  - Cincinnati Children's Hospital: MECP2-Related Disorders  - Gene Review: Gene Review: MECP2-Related Disorders  - Genetic Testing Registry: Severe neonatal-onset encephalopathy with microcephaly  - Johns Hopkins Children's Center: Failure to Thrive   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,MECP2-related severe neonatal encephalopathy,0000636,GHR,https://ghr.nlm.nih.gov/condition/mecp2-related-severe-neonatal-encephalopathy,C0235820,T047,Disorders
What is (are) medium-chain acyl-CoA dehydrogenase deficiency ?,0000637-1,information,"Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a condition that prevents the body from converting certain fats to energy, particularly during periods without food (fasting).  Signs and symptoms of MCAD deficiency typically appear during infancy or early childhood and can include vomiting, lack of energy (lethargy), and low blood sugar (hypoglycemia). In rare cases, symptoms of this disorder are not recognized early in life, and the condition is not diagnosed until adulthood. People with MCAD deficiency are at risk of serious complications such as seizures, breathing difficulties, liver problems, brain damage, coma, and sudden death.  Problems related to MCAD deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.",medium-chain acyl-CoA dehydrogenase deficiency,0000637,GHR,https://ghr.nlm.nih.gov/condition/medium-chain-acyl-coa-dehydrogenase-deficiency,C0220710,T047,Disorders
How many people are affected by medium-chain acyl-CoA dehydrogenase deficiency ?,0000637-2,frequency,"In the United States, the estimated incidence of MCAD deficiency is 1 in 17,000 people. The condition is more common in people of northern European ancestry than in other ethnic groups.",medium-chain acyl-CoA dehydrogenase deficiency,0000637,GHR,https://ghr.nlm.nih.gov/condition/medium-chain-acyl-coa-dehydrogenase-deficiency,C0220710,T047,Disorders
What are the genetic changes related to medium-chain acyl-CoA dehydrogenase deficiency ?,0000637-3,genetic changes,"Mutations in the ACADM gene cause MCAD deficiency. This gene provides instructions for making an enzyme called medium-chain acyl-CoA dehydrogenase, which is required to break down (metabolize) a group of fats called medium-chain fatty acids. These fatty acids are found in foods and the body's fat tissues. Fatty acids are a major source of energy for the heart and muscles. During periods of fasting, fatty acids are also an important energy source for the liver and other tissues.  Mutations in the ACADM gene lead to a shortage (deficiency) of the MCAD enzyme within cells. Without sufficient amounts of this enzyme, medium-chain fatty acids are not metabolized properly. As a result, these fats are not converted to energy, which can lead to the characteristic signs and symptoms of this disorder such as lethargy and hypoglycemia. Medium-chain fatty acids or partially metabolized fatty acids may also build up in tissues and damage the liver and brain. This abnormal buildup causes the other signs and symptoms of MCAD deficiency.",medium-chain acyl-CoA dehydrogenase deficiency,0000637,GHR,https://ghr.nlm.nih.gov/condition/medium-chain-acyl-coa-dehydrogenase-deficiency,C0220710,T047,Disorders
Is medium-chain acyl-CoA dehydrogenase deficiency inherited ?,0000637-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",medium-chain acyl-CoA dehydrogenase deficiency,0000637,GHR,https://ghr.nlm.nih.gov/condition/medium-chain-acyl-coa-dehydrogenase-deficiency,C0220710,T047,Disorders
What are the treatments for medium-chain acyl-CoA dehydrogenase deficiency ?,0000637-5,treatment,These resources address the diagnosis or management of MCAD deficiency:  - Baby's First Test  - Gene Review: Gene Review: Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency  - Genetic Testing Registry: Medium-chain acyl-coenzyme A dehydrogenase deficiency  - MedlinePlus Encyclopedia: Newborn Screening Tests   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,medium-chain acyl-CoA dehydrogenase deficiency,0000637,GHR,https://ghr.nlm.nih.gov/condition/medium-chain-acyl-coa-dehydrogenase-deficiency,C0220710,T047,Disorders
What is (are) medullary cystic kidney disease type 1 ?,0000638-1,information,"Medullary cystic kidney disease type 1 (MCKD1) is an inherited condition that affects the kidneys. It leads to scarring (fibrosis) and impaired function of the kidneys, usually beginning in adulthood. The kidneys filter fluid and waste products from the body. They also reabsorb needed nutrients and release them back into the blood. As MCKD1 progresses, the kidneys are less able to function, resulting in kidney failure.  Declining kidney function in people with MCKD1 leads to the signs and symptoms of the condition. The features are variable, even among members of the same family. Many individuals with MCKD1 develop high blood pressure (hypertension), especially as kidney function worsens. Some develop high levels of a waste product called uric acid in the blood (hyperuricemia) because the damaged kidneys are unable to remove uric acid effectively. In a small number of affected individuals, the buildup of this waste product can cause gout, which is a form of arthritis resulting from uric acid crystals in the joints.  Although the condition is named medullary cystic kidney disease, only about 40 percent of affected individuals have medullary cysts, which are fluid filled pockets found in a particular region of the kidney. When present, the cysts are usually found in the inner part of the kidney (the medullary region) or the border between the inner and outer parts (corticomedullary region). These cysts are visible by tests such as ultrasound or CT scan.",medullary cystic kidney disease type 1,0000638,GHR,https://ghr.nlm.nih.gov/condition/medullary-cystic-kidney-disease-type-1,C2919861,T047,Disorders
How many people are affected by medullary cystic kidney disease type 1 ?,0000638-2,frequency,"MCKD1 is a rare disorder, although its prevalence is unknown.",medullary cystic kidney disease type 1,0000638,GHR,https://ghr.nlm.nih.gov/condition/medullary-cystic-kidney-disease-type-1,C2919861,T047,Disorders
What are the genetic changes related to medullary cystic kidney disease type 1 ?,0000638-3,genetic changes,"MCKD1 is caused by mutations in the MUC1 gene. This gene provides instructions for making a protein called mucin 1, which is one of several mucin proteins that make up mucus. Mucus is a slippery substance that lubricates the lining of the airways, digestive system, reproductive system, and other organs and tissues and protects them from foreign invaders and other particles.  In addition to its role in mucus, mucin 1 relays signals from outside the cell to the cell's nucleus. Through this cellular signaling, mucin 1 is thought to be involved in the growth, movement, and survival of cells. Research suggests that mucin 1 plays a role in the normal development of the kidneys.  MCKD1 is caused by the insertion of a single DNA building block (nucleotide) called cytosine into the MUC1 gene. These mutations have been found in one particular region of the gene. They lead to the production of an altered protein. It is unclear how this change causes kidney disease.",medullary cystic kidney disease type 1,0000638,GHR,https://ghr.nlm.nih.gov/condition/medullary-cystic-kidney-disease-type-1,C2919861,T047,Disorders
Is medullary cystic kidney disease type 1 inherited ?,0000638-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",medullary cystic kidney disease type 1,0000638,GHR,https://ghr.nlm.nih.gov/condition/medullary-cystic-kidney-disease-type-1,C2919861,T047,Disorders
What are the treatments for medullary cystic kidney disease type 1 ?,0000638-5,treatment,These resources address the diagnosis or management of medullary cystic kidney disease type 1:  - MedlinePlus Encyclopedia: Medullary Cystic Kidney Disease  - Merck Manual for Health Care Professionals: Nephronophthisis and Medullary Cystic Kidney Disease Complex   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,medullary cystic kidney disease type 1,0000638,GHR,https://ghr.nlm.nih.gov/condition/medullary-cystic-kidney-disease-type-1,C2919861,T047,Disorders
What is (are) Meesmann corneal dystrophy ?,0000639-1,information,"Meesmann corneal dystrophy is an eye disease that affects the cornea, which is the clear front covering of the eye. This condition is characterized by the formation of tiny round cysts in the outermost layer of the cornea, called the corneal epithelium. This part of the cornea acts as a barrier to help prevent foreign materials, such as dust and bacteria, from entering the eye.  In people with Meesmann corneal dystrophy, cysts can appear as early as the first year of life. They usually affect both eyes and increase in number over time. The cysts usually do not cause any symptoms until late adolescence or adulthood, when they start to break open (rupture) on the surface of the cornea and cause irritation. The resulting symptoms typically include increased sensitivity to light (photophobia), twitching of the eyelids (blepharospasm), increased tear production, the sensation of having a foreign object in the eye, and an inability to tolerate wearing contact lenses. Some affected individuals also have temporary episodes of blurred vision.",Meesmann corneal dystrophy,0000639,GHR,https://ghr.nlm.nih.gov/condition/meesmann-corneal-dystrophy,C0339277,T019,Disorders
How many people are affected by Meesmann corneal dystrophy ?,0000639-2,frequency,"Meesmann corneal dystrophy is a rare disorder whose prevalence is unknown. It was first described in a large, multi-generational German family with more than 100 affected members. Since then, the condition has been reported in individuals and families worldwide.",Meesmann corneal dystrophy,0000639,GHR,https://ghr.nlm.nih.gov/condition/meesmann-corneal-dystrophy,C0339277,T019,Disorders
What are the genetic changes related to Meesmann corneal dystrophy ?,0000639-3,genetic changes,"Meesmann corneal dystrophy can result from mutations in either the KRT12 gene or the KRT3 gene. These genes provide instructions for making proteins called keratin 12 and keratin 3, which are found in the corneal epithelium. The two proteins interact to form the structural framework of this layer of the cornea. Mutations in either the KRT12 or KRT3 gene weaken this framework, causing the corneal epithelium to become fragile and to develop the cysts that characterize the disorder. The cysts likely contain clumps of abnormal keratin proteins and other cellular debris. When the cysts rupture, they cause eye irritation and the other symptoms of Meesmann corneal dystrophy.",Meesmann corneal dystrophy,0000639,GHR,https://ghr.nlm.nih.gov/condition/meesmann-corneal-dystrophy,C0339277,T019,Disorders
Is Meesmann corneal dystrophy inherited ?,0000639-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of an altered KRT12 or KRT3 gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the condition from an affected parent.",Meesmann corneal dystrophy,0000639,GHR,https://ghr.nlm.nih.gov/condition/meesmann-corneal-dystrophy,C0339277,T019,Disorders
What are the treatments for Meesmann corneal dystrophy ?,0000639-5,treatment,These resources address the diagnosis or management of Meesmann corneal dystrophy:  - Genetic Testing Registry: Meesman's corneal dystrophy  - Merck Manual Home Health Handbook: Tests for Eye Disorders: The Eye Examination   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Meesmann corneal dystrophy,0000639,GHR,https://ghr.nlm.nih.gov/condition/meesmann-corneal-dystrophy,C0339277,T019,Disorders
What is (are) megalencephalic leukoencephalopathy with subcortical cysts ?,0000640-1,information,"Megalencephalic leukoencephalopathy with subcortical cysts is a progressive condition that affects brain development and function. Individuals with this condition typically have an enlarged brain (megalencephaly) that is evident at birth or within the first year of life. Megalencephaly leads to an increase in the size of the head (macrocephaly). Affected people also have leukoencephalopathy, an abnormality of the brain's white matter. White matter consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses. In megalencephalic leukoencephalopathy with subcortical cysts, the myelin is swollen and contains numerous fluid-filled pockets (vacuoles). Over time, the swelling decreases and the myelin begins to waste away (atrophy). Individuals affected with this condition may develop cysts in the brain; because these cysts form below an area of the brain called the cerebral cortex, they are called subcortical cysts. These cysts can grow in size and number.  The brain abnormalities in people with megalencephalic leukoencephalopathy with subcortical cysts affect the use of muscles and lead to movement problems. Affected individuals typically experience muscle stiffness (spasticity) and difficulty coordinating movements (ataxia). Walking ability varies greatly among those affected. Some people lose the ability to walk early in life and need wheelchair assistance, while others are able to walk unassisted well into adulthood. Minor head trauma can further impair movements and may lead to coma. Affected individuals may also develop uncontrolled muscle tensing (dystonia), involuntary writhing movements of the limbs (athetosis), difficulty swallowing (dysphagia), and impaired speech (dysarthria). More than half of all people with this condition have recurrent seizures (epilepsy). Despite the widespread brain abnormalities, people with this condition typically have only mild to moderate intellectual disability.  There are three types of megalencephalic leukoencephalopathy with subcortical cysts, which are distinguished by their signs and symptoms and genetic cause. Types 1 and 2A have different genetic causes but are nearly identical in signs and symptoms. Types 2A and 2B have the same genetic cause but the signs and symptoms of type 2B often begin to improve after one year. After improvement, individuals with type 2B usually have macrocephaly and may have intellectual disability.",megalencephalic leukoencephalopathy with subcortical cysts,0000640,GHR,https://ghr.nlm.nih.gov/condition/megalencephalic-leukoencephalopathy-with-subcortical-cysts,C0270612,T019,Disorders
How many people are affected by megalencephalic leukoencephalopathy with subcortical cysts ?,0000640-2,frequency,Megalencephalic leukoencephalopathy with subcortical cysts is a rare condition; its exact prevalence is unknown. More than 150 cases have been reported in the scientific literature.,megalencephalic leukoencephalopathy with subcortical cysts,0000640,GHR,https://ghr.nlm.nih.gov/condition/megalencephalic-leukoencephalopathy-with-subcortical-cysts,C0270612,T019,Disorders
What are the genetic changes related to megalencephalic leukoencephalopathy with subcortical cysts ?,0000640-3,genetic changes,"Mutations in the MLC1 gene cause megalencephalic leukoencephalopathy with subcortical cysts type 1; this type accounts for 75 percent of all cases. The MLC1 gene provides instructions for producing a protein that is made primarily in the brain. The MLC1 protein is found in astroglial cells, which are a specialized form of brain cells called glial cells. Glial cells protect and maintain other nerve cells (neurons). The MLC1 protein functions at junctions that connect neighboring astroglial cells. The role of the MLC1 protein at the cell junction is unknown, but research suggests that it may control the flow of fluids into cells or the strength of cells' attachment to one another (cell adhesion).  Mutations in the HEPACAM gene cause megalencephalic leukoencephalopathy with subcortical cysts types 2A and 2B; together, these types account for 20 percent of all cases. The HEPACAM gene provides instructions for making a protein called GlialCAM. This protein primarily functions in the brain, particularly in glial cells. GlialCAM attaches (binds) to other GlialCAM proteins or to the MLC1 protein and guides them to cell junctions. The function of GlialCAM at the cell junction is unclear.  Most MLC1 gene mutations alter the structure of the MLC1 protein or prevent the cell from producing any of this protein, leading to a lack of functional MLC1 protein at the astroglial cell junctions. HEPACAM gene mutations lead to a protein that is unable to correctly transport GlialCAM and MLC1 proteins to cell junctions. It is unknown how a lack of functional MLC1 or GlialCAM protein at cell junctions in the brain impairs brain development and function, causing the signs and symptoms of megalencephalic leukoencephalopathy with subcortical cysts.  Approximately 5 percent of people with megalencephalic leukoencephalopathy with subcortical cysts do not have identified mutations in the MLC1 or HEPACAM gene. In these individuals, the cause of the disorder is unknown.",megalencephalic leukoencephalopathy with subcortical cysts,0000640,GHR,https://ghr.nlm.nih.gov/condition/megalencephalic-leukoencephalopathy-with-subcortical-cysts,C0270612,T019,Disorders
Is megalencephalic leukoencephalopathy with subcortical cysts inherited ?,0000640-4,inheritance,"All cases of megalencephalic leukoencephalopathy with subcortical cysts caused by mutations in the MLC1 gene (type 1) and some cases caused by mutations in the HEPACAM gene (type 2A) are inherited in an autosomal recessive pattern. Autosomal recessive inheritance means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Megalencephalic leukoencephalopathy with subcortical cysts type 2B is inherited in an autosomal dominant pattern, which means one copy of the altered HEPACAM gene in each cell is sufficient to cause the disorder. Most cases of type 2B result from new (de novo) mutations in the HEPACAM gene that occur during the formation of reproductive cells (eggs or sperm) or in early embryonic development. These cases occur in people with no history of the disorder in their family.",megalencephalic leukoencephalopathy with subcortical cysts,0000640,GHR,https://ghr.nlm.nih.gov/condition/megalencephalic-leukoencephalopathy-with-subcortical-cysts,C0270612,T019,Disorders
What are the treatments for megalencephalic leukoencephalopathy with subcortical cysts ?,0000640-5,treatment,"These resources address the diagnosis or management of megalencephalic leukoencephalopathy with subcortical cysts:  - Gene Review: Gene Review: Megalencephalic Leukoencephalopathy with Subcortical Cysts  - Genetic Testing Registry: Megalencephalic leukoencephalopathy with subcortical cysts  - Genetic Testing Registry: Megalencephalic leukoencephalopathy with subcortical cysts 1  - Genetic Testing Registry: Megalencephalic leukoencephalopathy with subcortical cysts 2a  - Genetic Testing Registry: Megalencephalic leukoencephalopathy with subcortical cysts 2b, remitting, with or without mental retardation  - MedlinePlus Encyclopedia: Myelin   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",megalencephalic leukoencephalopathy with subcortical cysts,0000640,GHR,https://ghr.nlm.nih.gov/condition/megalencephalic-leukoencephalopathy-with-subcortical-cysts,C0270612,T019,Disorders
What is (are) megalencephaly-capillary malformation syndrome ?,0000641-1,information,"Megalencephaly-capillary malformation syndrome (MCAP) is a disorder characterized by overgrowth of several tissues in the body. Its primary features are a large brain (megalencephaly) and abnormalities of small blood vessels in the skin called capillaries (capillary malformations).  In individuals with MCAP, megalencephaly leads to an unusually large head size (macrocephaly), which is typically evident at birth. After birth, the brain and head continue to grow at a fast rate for the first few years of life; then, the growth slows to a normal rate, although the head remains larger than average. Additional brain abnormalities are common in people with MCAP; these can include excess fluid within the brain (hydrocephalus) and abnormalities in the brain's structure, such as those known as Chiari malformation and polymicrogyria. Abnormal brain development leads to intellectual disability in most affected individuals and can also cause seizures or weak muscle tone (hypotonia). In particular, polymicrogyria is associated with speech delays and difficulty chewing and swallowing.  The capillary malformations characteristic of MCAP are composed of enlarged capillaries that increase blood flow near the surface of the skin. These malformations usually look like pink or red spots on the skin. In most affected individuals, capillary malformations occur on the face, particularly the nose, the upper lip, and the area between the nose and upper lip (the philtrum). In other people with MCAP, the malformations appear as patches spread over the body or as a reddish net-like pattern on the skin (cutis marmorata).  In some people with MCAP, excessive growth affects not only the brain but other individual parts of the body, which is known as segmental overgrowth. This can lead to one arm or leg that is bigger or longer than the other or a few oversized fingers or toes. Some affected individuals have fusion of the skin between two or more fingers or toes (cutaneous syndactyly).  Additional features of MCAP can include flexible joints and skin that stretches easily. Some affected individuals are said to have doughy skin because the tissue under the skin is unusually thick and soft.  The gene involved in MCAP is also associated with several types of cancer. Although a small number of individuals with MCAP have developed tumors (in particular, a childhood form of kidney cancer known as Wilms tumor and noncancerous tumors in the nervous system known as meningiomas), people with MCAP do not appear to have a greater risk of developing cancer than the general population.",megalencephaly-capillary malformation syndrome,0000641,GHR,https://ghr.nlm.nih.gov/condition/megalencephaly-capillary-malformation-syndrome,C3813729,T019,Disorders
How many people are affected by megalencephaly-capillary malformation syndrome ?,0000641-2,frequency,"The prevalence of MCAP is unknown. At least 150 affected individuals have been reported in the medical literature. Because the condition is often thought to be misdiagnosed or underdiagnosed, it may be more common than reported.",megalencephaly-capillary malformation syndrome,0000641,GHR,https://ghr.nlm.nih.gov/condition/megalencephaly-capillary-malformation-syndrome,C3813729,T019,Disorders
What are the genetic changes related to megalencephaly-capillary malformation syndrome ?,0000641-3,genetic changes,"MCAP is caused by mutations in the PIK3CA gene, which provides instructions for making the p110 alpha (p110) protein. This protein is one piece (subunit) of an enzyme called phosphatidylinositol 3-kinase (PI3K), which plays a role in chemical signaling within cells. PI3K signaling is important for many cell activities, including cell growth and division (proliferation), movement (migration) of cells, and cell survival. These functions make PI3K important for the development of tissues throughout the body, including the brain and blood vessels.  PIK3CA gene mutations involved in MCAP alter the p110 protein. The altered subunit makes PI3K abnormally active, which allows cells to grow and divide continuously. Increased cell proliferation leads to the overgrowth of the brain, blood vessels, and other organs and tissues characteristic of MCAP.",megalencephaly-capillary malformation syndrome,0000641,GHR,https://ghr.nlm.nih.gov/condition/megalencephaly-capillary-malformation-syndrome,C3813729,T019,Disorders
Is megalencephaly-capillary malformation syndrome inherited ?,0000641-4,inheritance,"MCAP is not inherited from a parent and does not run in families. In people with MCAP, a PIK3CA gene mutation arises randomly in one cell during the early stages of development before birth. As cells continue to divide, some cells will have the mutation and other cells will not. This mixture of cells with and without a genetic mutation is known as mosaicism.",megalencephaly-capillary malformation syndrome,0000641,GHR,https://ghr.nlm.nih.gov/condition/megalencephaly-capillary-malformation-syndrome,C3813729,T019,Disorders
What are the treatments for megalencephaly-capillary malformation syndrome ?,0000641-5,treatment,These resources address the diagnosis or management of megalencephaly-capillary malformation syndrome:  - Contact a Family  - Gene Review: Gene Review: PIK3CA-Related Segmental Overgrowth  - Genetic Testing Registry: Megalencephaly cutis marmorata telangiectatica congenita  - M-CM Network: How is M-CM Diagnosed?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,megalencephaly-capillary malformation syndrome,0000641,GHR,https://ghr.nlm.nih.gov/condition/megalencephaly-capillary-malformation-syndrome,C3813729,T019,Disorders
What is (are) MEGDEL syndrome ?,0000642-1,information,"MEGDEL syndrome is an inherited disorder that affects multiple body systems. It is named for several of its features: 3-methylglutaconic aciduria (MEG), deafness (D), encephalopathy (E), and Leigh-like disease (L).  MEGDEL syndrome is characterized by abnormally high levels of an acid, called 3-methylglutaconic acid, in the urine (3-methylglutaconic aciduria). MEGDEL syndrome is one of a group of metabolic disorders that can be diagnosed by presence of this feature. People with MEGDEL syndrome also have high urine levels of another acid called 3-methylglutaric acid.  In infancy, individuals with MEGDEL syndrome develop hearing loss caused by changes in the inner ear (sensorineural deafness); the hearing problems gradually worsen over time.  Another feature of MEGDEL syndrome is brain dysfunction (encephalopathy). In infancy, encephalopathy leads to difficulty feeding, an inability to grow and gain weight at the expected rate (failure to thrive), and weak muscle tone (hypotonia). Infants with MEGDEL syndrome later develop involuntary muscle tensing (dystonia) and muscle stiffness (spasticity), which worsen over time. Because of these brain and muscle problems, affected babies have delayed development of mental and movement abilities (psychomotor delay), or they may lose skills they already developed. Individuals with MEGDEL syndrome have intellectual disability and never learn to speak.  People with MEGDEL syndrome have changes in the brain that resemble those in another condition called Leigh syndrome. These changes, which can be seen with medical imaging, are referred to as Leigh-like disease.  Other features that occur commonly in MEGDEL syndrome include low blood sugar (hypoglycemia) in affected newborns; liver problems (hepatopathy) in infancy, which can be serious but improve by early childhood; and episodes of abnormally high amounts of lactic acid in the blood (lactic acidosis).  The life expectancy of individuals with MEGDEL syndrome is unknown. Because of the severe health problems caused by the disorder, some affected individuals do not survive past infancy.",MEGDEL syndrome,0000642,GHR,https://ghr.nlm.nih.gov/condition/megdel-syndrome,C3553597,T047,Disorders
How many people are affected by MEGDEL syndrome ?,0000642-2,frequency,MEGDEL syndrome is a rare disorder; its prevalence is unknown. At least 40 affected individuals have been mentioned in the medical literature.,MEGDEL syndrome,0000642,GHR,https://ghr.nlm.nih.gov/condition/megdel-syndrome,C3553597,T047,Disorders
What are the genetic changes related to MEGDEL syndrome ?,0000642-3,genetic changes,"MEGDEL syndrome is caused by mutations in the SERAC1 gene. The function of the protein produced from this gene is not completely understood, although research suggests that it is involved in altering (remodeling) certain fats called phospholipids, particularly a phospholipid known as phosphatidylglycerol. Another phospholipid called cardiolipin is made from phosphatidylglycerol. Cardiolipin is a component of the membrane that surrounds cellular structures called mitochondria, which convert the energy from food into a form that cells can use, and is important for the proper functioning of these structures.  SERAC1 gene mutations involved in MEGDEL syndrome lead to little or no SERAC1 protein function. As a result, phosphatidylglycerol remodeling is impaired, which likely alters the composition of cardiolipin. Researchers speculate that the abnormal cardiolipin affects mitochondrial function, reducing cellular energy production and leading to the neurological and hearing problems characteristic of MEGDEL syndrome. It is unclear how SERAC1 gene mutations lead to abnormal release of 3-methylglutaconic acid in the urine, although it is thought to be related to mitochondrial dysfunction.",MEGDEL syndrome,0000642,GHR,https://ghr.nlm.nih.gov/condition/megdel-syndrome,C3553597,T047,Disorders
Is MEGDEL syndrome inherited ?,0000642-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",MEGDEL syndrome,0000642,GHR,https://ghr.nlm.nih.gov/condition/megdel-syndrome,C3553597,T047,Disorders
What are the treatments for MEGDEL syndrome ?,0000642-5,treatment,"These resources address the diagnosis or management of MEGDEL syndrome:  - Baby's First Test: 3-Methylglutaconic Aciduria  - Gene Review: Gene Review: MEGDEL Syndrome  - Genetic Testing Registry: 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",MEGDEL syndrome,0000642,GHR,https://ghr.nlm.nih.gov/condition/megdel-syndrome,C3553597,T047,Disorders
What is (are) Meier-Gorlin syndrome ?,0000643-1,information,"Meier-Gorlin syndrome is a condition primarily characterized by short stature. It is considered a form of primordial dwarfism because the growth problems begin before birth (intrauterine growth retardation). After birth, affected individuals continue to grow at a slow rate. Other characteristic features of this condition are underdeveloped or missing kneecaps (patellae), small ears, and, often, an abnormally small head (microcephaly). Despite a small head size, most people with Meier-Gorlin syndrome have normal intellect.  Some people with Meier-Gorlin syndrome have other skeletal abnormalities, such as unusually narrow long bones in the arms and legs, a deformity of the knee joint that allows the knee to bend backwards (genu recurvatum), and slowed mineralization of bones (delayed bone age).  Most people with Meier-Gorlin syndrome have distinctive facial features. In addition to being abnormally small, the ears may be low-set or rotated backward. Additional features can include a small mouth (microstomia), an underdeveloped lower jaw (micrognathia), full lips, and a narrow nose with a high nasal bridge.  Abnormalities in sexual development may also occur in Meier-Gorlin syndrome. In some males with this condition, the testes are small or undescended (cryptorchidism). Affected females may have unusually small external genital folds (hypoplasia of the labia majora) and small breasts. Both males and females with this condition can have sparse or absent underarm (axillary) hair.  Additional features of Meier-Gorlin syndrome can include difficulty feeding and a lung condition known as pulmonary emphysema or other breathing problems.",Meier-Gorlin syndrome,0000643,GHR,https://ghr.nlm.nih.gov/condition/meier-gorlin-syndrome,C1868684,T019,Disorders
How many people are affected by Meier-Gorlin syndrome ?,0000643-2,frequency,"Meier-Gorlin syndrome is a rare condition; however, its prevalence is unknown.",Meier-Gorlin syndrome,0000643,GHR,https://ghr.nlm.nih.gov/condition/meier-gorlin-syndrome,C1868684,T019,Disorders
What are the genetic changes related to Meier-Gorlin syndrome ?,0000643-3,genetic changes,"Meier-Gorlin syndrome can be caused by mutations in one of several genes. Each of these genes, ORC1, ORC4, ORC6, CDT1, and CDC6, provides instructions for making one of a group of proteins known as the pre-replication complex. This complex regulates initiation of the copying (replication) of DNA before cells divide. Specifically, the pre-replication complex attaches (binds) to certain regions of DNA known as origins of replication, allowing copying of the DNA to begin at that location. This tightly controlled process, called replication licensing, helps ensure that DNA replication occurs only once per cell division and is required for cells to divide.  Mutations in any one of these genes impair formation of the pre-replication complex and disrupt replication licensing; however, it is not clear how a reduction in replication licensing leads to Meier-Gorlin syndrome. Researchers speculate that such a reduction delays the cell division process, which impairs growth of the bones and other tissues during development. Some research suggests that some of the pre-replication complex proteins have additional functions, impairment of which may contribute to features of Meier-Gorlin syndrome, such as delayed development of the kneecaps and ears.",Meier-Gorlin syndrome,0000643,GHR,https://ghr.nlm.nih.gov/condition/meier-gorlin-syndrome,C1868684,T019,Disorders
Is Meier-Gorlin syndrome inherited ?,0000643-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Meier-Gorlin syndrome,0000643,GHR,https://ghr.nlm.nih.gov/condition/meier-gorlin-syndrome,C1868684,T019,Disorders
What are the treatments for Meier-Gorlin syndrome ?,0000643-5,treatment,These resources address the diagnosis or management of Meier-Gorlin syndrome:  - Genetic Testing Registry: Meier-Gorlin syndrome  - Genetic Testing Registry: Meier-Gorlin syndrome 2  - Genetic Testing Registry: Meier-Gorlin syndrome 3  - Genetic Testing Registry: Meier-Gorlin syndrome 4  - Genetic Testing Registry: Meier-Gorlin syndrome 5   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Meier-Gorlin syndrome,0000643,GHR,https://ghr.nlm.nih.gov/condition/meier-gorlin-syndrome,C1868684,T019,Disorders
What is (are) Meige disease ?,0000644-1,information,"Meige disease is a condition that affects the normal function of the lymphatic system. The lymphatic system consists of a network of vessels that transport lymphatic fluid and immune cells throughout the body. Meige disease is characterized by the abnormal transport of lymphatic fluid. When this fluid builds up abnormally, it causes swelling (lymphedema) in the lower limbs.  Meige disease is classified as a primary lymphedema, which means it is a form of lymphedema that is not caused by other health conditions. In Meige disease, the lymphatic system abnormalities are present from birth (congenital), although the swelling is not usually apparent until puberty. The swelling often begins in the feet and ankles and progresses up the legs to the knees. Some affected individuals develop non-contagious skin infections called cellulitis or erysipelas in the legs, which can further damage the vessels that carry lymphatic fluid.",Meige disease,0000644,GHR,https://ghr.nlm.nih.gov/condition/meige-disease,C0238261,T047,Disorders
How many people are affected by Meige disease ?,0000644-2,frequency,"The prevalence of Meige disease is unknown. Collectively, the many types of primary lymphedema affect an estimated 1 in 100,000 people younger than 20; Meige disease is the most common type of primary lymphedema.  For unknown reasons, this condition affects females about three times as often as males.",Meige disease,0000644,GHR,https://ghr.nlm.nih.gov/condition/meige-disease,C0238261,T047,Disorders
What are the genetic changes related to Meige disease ?,0000644-3,genetic changes,"The cause of Meige disease is unknown. The condition is thought to be genetic because it tends to run in families, and other forms of primary lymphedema have been found to have a genetic cause. Researchers have studied many genes associated with the lymphatic system; however, no genetic change has been definitively found to cause the signs and symptoms of Meige disease.",Meige disease,0000644,GHR,https://ghr.nlm.nih.gov/condition/meige-disease,C0238261,T047,Disorders
Is Meige disease inherited ?,0000644-4,inheritance,"Meige disease appears to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of an altered gene in each cell is sufficient to cause the disorder, although no genes have been associated with Meige disease.  People with Meige disease usually have at least one other affected family member. In most cases, an affected person has one parent with the condition. When the condition occurs in only one person in a family, the condition is described as Meige-like disease.",Meige disease,0000644,GHR,https://ghr.nlm.nih.gov/condition/meige-disease,C0238261,T047,Disorders
What are the treatments for Meige disease ?,0000644-5,treatment,These resources address the diagnosis or management of Meige disease:  - Genetic Testing Registry: Lymphedema praecox  - Johns Hopkins Medicine: Lymphedema Management   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Meige disease,0000644,GHR,https://ghr.nlm.nih.gov/condition/meige-disease,C0238261,T047,Disorders
What is (are) Melnick-Needles syndrome ?,0000645-1,information,"Melnick-Needles syndrome is a disorder involving abnormalities in skeletal development and other health problems. It is a member of a group of related conditions called otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 1, otopalatodigital syndrome type 2, and frontometaphyseal dysplasia. In general, these disorders involve hearing loss caused by malformations in the tiny bones in the ears (ossicles), problems in the development of the roof of the mouth (palate), and skeletal abnormalities involving the fingers and/or toes (digits).  Melnick-Needles syndrome is usually the most severe of the otopalatodigital spectrum disorders. People with this condition are usually of short stature, have an abnormal curvature of the spine (scoliosis), partial dislocation (subluxation) of certain joints, and unusually long fingers and toes. They may have bowed limbs; underdeveloped, irregular ribs that can cause problems with breathing; and other abnormal or absent bones.  Characteristic facial features may include bulging eyes with prominent brow ridges, excess hair growth on the forehead, round cheeks, a very small lower jaw and chin (micrognathia), and misaligned teeth. One side of the face may appear noticeably different from the other (facial asymmetry). Some individuals with this disorder have hearing loss.  In addition to skeletal abnormalities, individuals with Melnick-Needles syndrome may have obstruction of the ducts between the kidneys and bladder (ureters) or heart defects.  Males with Melnick-Needles syndrome generally have much more severe signs and symptoms than do females, and in almost all cases die before or soon after birth.",Melnick-Needles syndrome,0000645,GHR,https://ghr.nlm.nih.gov/condition/melnick-needles-syndrome,C0025237,T047,Disorders
How many people are affected by Melnick-Needles syndrome ?,0000645-2,frequency,Melnick-Needles syndrome is a rare disorder; fewer than 100 cases have been reported worldwide.,Melnick-Needles syndrome,0000645,GHR,https://ghr.nlm.nih.gov/condition/melnick-needles-syndrome,C0025237,T047,Disorders
What are the genetic changes related to Melnick-Needles syndrome ?,0000645-3,genetic changes,"Mutations in the FLNA gene cause Melnick-Needles syndrome.  The FLNA gene provides instructions for producing the protein filamin A, which helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. Filamin A binds to another protein called actin, and helps the actin to form the branching network of filaments that make up the cytoskeleton. Filamin A also links actin to many other proteins to perform various functions within the cell.  A small number of mutations in the FLNA gene have been identified in people with Melnick-Needles syndrome. These mutations are described as ""gain-of-function"" because they appear to enhance the activity of the filamin A protein or give the protein a new, atypical function. Researchers believe that the mutations may change the way the filamin A protein helps regulate processes involved in skeletal development, but it is not known how changes in the protein relate to the specific signs and symptoms of Melnick-Needles syndrome.",Melnick-Needles syndrome,0000645,GHR,https://ghr.nlm.nih.gov/condition/melnick-needles-syndrome,C0025237,T047,Disorders
Is Melnick-Needles syndrome inherited ?,0000645-4,inheritance,"This condition is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In most cases, males experience more severe symptoms of the disorder than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",Melnick-Needles syndrome,0000645,GHR,https://ghr.nlm.nih.gov/condition/melnick-needles-syndrome,C0025237,T047,Disorders
What are the treatments for Melnick-Needles syndrome ?,0000645-5,treatment,These resources address the diagnosis or management of Melnick-Needles syndrome:  - Gene Review: Gene Review: Otopalatodigital Spectrum Disorders  - Genetic Testing Registry: Melnick-Needles syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Melnick-Needles syndrome,0000645,GHR,https://ghr.nlm.nih.gov/condition/melnick-needles-syndrome,C0025237,T047,Disorders
What is (are) Menkes syndrome ?,0000646-1,information,"Menkes syndrome is a disorder that affects copper levels in the body. It is characterized by sparse, kinky hair; failure to gain weight and grow at the expected rate (failure to thrive); and deterioration of the nervous system. Additional signs and symptoms include weak muscle tone (hypotonia), sagging facial features, seizures, developmental delay, and intellectual disability. Children with Menkes syndrome typically begin to develop symptoms during infancy and often do not live past age 3. Early treatment with copper may improve the prognosis in some affected individuals. In rare cases, symptoms begin later in childhood.  Occipital horn syndrome (sometimes called X-linked cutis laxa) is a less severe form of Menkes syndrome that begins in early to middle childhood. It is characterized by wedge-shaped calcium deposits in a bone at the base of the skull (the occipital bone), coarse hair, and loose skin and joints.",Menkes syndrome,0000646,GHR,https://ghr.nlm.nih.gov/condition/menkes-syndrome,C0022716,T047,Disorders
How many people are affected by Menkes syndrome ?,0000646-2,frequency,"The incidence of Menkes syndrome and occipital horn syndrome is estimated to be 1 in 100,000 newborns.",Menkes syndrome,0000646,GHR,https://ghr.nlm.nih.gov/condition/menkes-syndrome,C0022716,T047,Disorders
What are the genetic changes related to Menkes syndrome ?,0000646-3,genetic changes,"Mutations in the ATP7A gene cause Menkes syndrome. The ATP7A gene provides instructions for making a protein that is important for regulating copper levels in the body. Copper is necessary for many cellular functions, but it is toxic when present in excessive amounts. Mutations in the ATP7A gene result in poor distribution of copper to the body's cells. Copper accumulates in some tissues, such as the small intestine and kidneys, while the brain and other tissues have unusually low levels of copper. The decreased supply of copper can reduce the activity of numerous copper-containing enzymes that are necessary for the structure and function of bone, skin, hair, blood vessels, and the nervous system. The signs and symptoms of Menkes syndrome and occipital horn syndrome are caused by the reduced activity of these copper-containing enzymes.",Menkes syndrome,0000646,GHR,https://ghr.nlm.nih.gov/condition/menkes-syndrome,C0022716,T047,Disorders
Is Menkes syndrome inherited ?,0000646-4,inheritance,"Menkes syndrome is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In about one-third of cases, Menkes syndrome is caused by new mutations in the ATP7A gene. People with a new mutation do not have a history of the disorder in their family.",Menkes syndrome,0000646,GHR,https://ghr.nlm.nih.gov/condition/menkes-syndrome,C0022716,T047,Disorders
What are the treatments for Menkes syndrome ?,0000646-5,treatment,These resources address the diagnosis or management of Menkes syndrome:  - Gene Review: Gene Review: ATP7A-Related Copper Transport Disorders  - Genetic Testing Registry: Menkes kinky-hair syndrome  - MedlinePlus Encyclopedia: Copper in diet  - MedlinePlus Encyclopedia: Menkes syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Menkes syndrome,0000646,GHR,https://ghr.nlm.nih.gov/condition/menkes-syndrome,C0022716,T047,Disorders
What is (are) metachromatic leukodystrophy ?,0000647-1,information,"Metachromatic leukodystrophy is an inherited disorder characterized by the accumulation of fats called sulfatides in cells. This accumulation especially affects cells in the nervous system that produce myelin, the substance that insulates and protects nerves. Nerve cells covered by myelin make up a tissue called white matter. Sulfatide accumulation in myelin-producing cells causes progressive destruction of white matter (leukodystrophy) throughout the nervous system, including in the brain and spinal cord (the central nervous system) and the nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound (the peripheral nervous system).  In people with metachromatic leukodystrophy, white matter damage causes progressive deterioration of intellectual functions and motor skills, such as the ability to walk. Affected individuals also develop loss of sensation in the extremities (peripheral neuropathy), incontinence, seizures, paralysis, an inability to speak, blindness, and hearing loss. Eventually they lose awareness of their surroundings and become unresponsive. While neurological problems are the primary feature of metachromatic leukodystrophy, effects of sulfatide accumulation on other organs and tissues have been reported, most often involving the gallbladder.  The most common form of metachromatic leukodystrophy, affecting about 50 to 60 percent of all individuals with this disorder, is called the late infantile form. This form of the disorder usually appears in the second year of life. Affected children lose any speech they have developed, become weak, and develop problems with walking (gait disturbance). As the disorder worsens, muscle tone generally first decreases, and then increases to the point of rigidity. Individuals with the late infantile form of metachromatic leukodystrophy typically do not survive past childhood.  In 20 to 30 percent of individuals with metachromatic leukodystrophy, onset occurs between the age of 4 and adolescence. In this juvenile form, the first signs of the disorder may be behavioral problems and increasing difficulty with schoolwork. Progression of the disorder is slower than in the late infantile form, and affected individuals may survive for about 20 years after diagnosis.  The adult form of metachromatic leukodystrophy affects approximately 15 to 20 percent of individuals with the disorder. In this form, the first symptoms appear during the teenage years or later. Often behavioral problems such as alcoholism, drug abuse, or difficulties at school or work are the first symptoms to appear. The affected individual may experience psychiatric symptoms such as delusions or hallucinations. People with the adult form of metachromatic leukodystrophy may survive for 20 to 30 years after diagnosis. During this time there may be some periods of relative stability and other periods of more rapid decline.  Metachromatic leukodystrophy gets its name from the way cells with an accumulation of sulfatides appear when viewed under a microscope. The sulfatides form granules that are described as metachromatic, which means they pick up color differently than surrounding cellular material when stained for examination.",metachromatic leukodystrophy,0000647,GHR,https://ghr.nlm.nih.gov/condition/metachromatic-leukodystrophy,C0023522,T047,Disorders
How many people are affected by metachromatic leukodystrophy ?,0000647-2,frequency,"Metachromatic leukodystrophy is reported to occur in 1 in 40,000 to 160,000 individuals worldwide. The condition is more common in certain genetically isolated populations: 1 in 75 in a small group of Jews who immigrated to Israel from southern Arabia (Habbanites), 1 in 2,500 in the western portion of the Navajo Nation, and 1 in 8,000 among Arab groups in Israel.",metachromatic leukodystrophy,0000647,GHR,https://ghr.nlm.nih.gov/condition/metachromatic-leukodystrophy,C0023522,T047,Disorders
What are the genetic changes related to metachromatic leukodystrophy ?,0000647-3,genetic changes,"Most individuals with metachromatic leukodystrophy have mutations in the ARSA gene, which provides instructions for making the enzyme arylsulfatase A. This enzyme is located in cellular structures called lysosomes, which are the cell's recycling centers. Within lysosomes, arylsulfatase A helps break down sulfatides. A few individuals with metachromatic leukodystrophy have mutations in the PSAP gene. This gene provides instructions for making a protein that is broken up (cleaved) into smaller proteins that assist enzymes in breaking down various fats. One of these smaller proteins is called saposin B; this protein works with arylsulfatase A to break down sulfatides.  Mutations in the ARSA or PSAP genes result in a decreased ability to break down sulfatides, resulting in the accumulation of these substances in cells. Excess sulfatides are toxic to the nervous system. The accumulation gradually destroys myelin-producing cells, leading to the impairment of nervous system function that occurs in metachromatic leukodystrophy.  In some cases, individuals with very low arylsulfatase A activity show no symptoms of metachromatic leukodystrophy. This condition is called pseudoarylsulfatase deficiency.",metachromatic leukodystrophy,0000647,GHR,https://ghr.nlm.nih.gov/condition/metachromatic-leukodystrophy,C0023522,T047,Disorders
Is metachromatic leukodystrophy inherited ?,0000647-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",metachromatic leukodystrophy,0000647,GHR,https://ghr.nlm.nih.gov/condition/metachromatic-leukodystrophy,C0023522,T047,Disorders
What are the treatments for metachromatic leukodystrophy ?,0000647-5,treatment,These resources address the diagnosis or management of metachromatic leukodystrophy:  - Gene Review: Gene Review: Arylsulfatase A Deficiency  - Genetic Testing Registry: Metachromatic leukodystrophy  - Genetic Testing Registry: Sphingolipid activator protein 1 deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,metachromatic leukodystrophy,0000647,GHR,https://ghr.nlm.nih.gov/condition/metachromatic-leukodystrophy,C0023522,T047,Disorders
What is (are) metatropic dysplasia ?,0000648-1,information,"Metatropic dysplasia is a skeletal disorder characterized by short stature (dwarfism) with other skeletal abnormalities. The term ""metatropic"" is derived from the Greek word ""metatropos,"" which means ""changing patterns."" This name reflects the fact that the skeletal abnormalities associated with the condition change over time.  Affected infants are born with a narrow chest and unusually short arms and legs with dumbbell-shaped long bones. Beginning in early childhood, people with this condition develop abnormal side-to-side and front-to-back curvature of the spine (scoliosis and kyphosis, often called kyphoscoliosis when they occur together). The curvature worsens with time and tends to be resistant to treatment. Because of the severe kyphoscoliosis, affected individuals may ultimately have a very short torso in relation to the length of their arms and legs.  Some people with metatropic dysplasia are born with an elongated tailbone known as a coccygeal tail; it is made of a tough but flexible tissue called cartilage. The coccygeal tail usually shrinks over time. Other skeletal problems associated with metatropic dysplasia include flattened bones of the spine (platyspondyly); excessive movement of spinal bones in the neck that can damage the spinal cord; either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum); and joint deformities called contractures that restrict the movement of joints in the shoulders, elbows, hips, and knees. Beginning early in life, affected individuals can also develop a degenerative form of arthritis that causes joint pain and further restricts movement.  The signs and symptoms of metatropic dysplasia can vary from relatively mild to life-threatening. In the most severe cases, the narrow chest and spinal abnormalities prevent the lungs from expanding fully, which restricts breathing. Researchers formerly recognized several distinct forms of metatropic dysplasia based on the severity of the condition's features. The forms included a mild type, a classic type, and a lethal type. However, all of these forms are now considered to be part of a single condition with a spectrum of overlapping signs and symptoms.",metatropic dysplasia,0000648,GHR,https://ghr.nlm.nih.gov/condition/metatropic-dysplasia,C0265281,T019,Disorders
How many people are affected by metatropic dysplasia ?,0000648-2,frequency,Metatropic dysplasia is a rare disease; its exact prevalence is unknown. More than 80 affected individuals have been reported in the scientific literature.,metatropic dysplasia,0000648,GHR,https://ghr.nlm.nih.gov/condition/metatropic-dysplasia,C0265281,T019,Disorders
What are the genetic changes related to metatropic dysplasia ?,0000648-3,genetic changes,"Metatropic dysplasia is caused by mutations in the TRPV4 gene, which provides instructions for making a protein that acts as a calcium channel. The TRPV4 channel transports positively charged calcium atoms (calcium ions) across cell membranes and into cells. The channel is found in many types of cells, but little is known about its function. Studies suggest that it plays a role in the normal development of cartilage and bone. This role would help explain why TRPV4 gene mutations cause the skeletal abnormalities characteristic of metatropic dysplasia. Mutations in the TRPV4 gene appear to overactivate the channel, increasing the flow of calcium ions into cells. However, it remains unclear how changes in the activity of the calcium channel lead to the specific features of the condition.",metatropic dysplasia,0000648,GHR,https://ghr.nlm.nih.gov/condition/metatropic-dysplasia,C0265281,T019,Disorders
Is metatropic dysplasia inherited ?,0000648-4,inheritance,"Metatropic dysplasia is considered an autosomal dominant disorder because one mutated copy of the TRPV4 gene in each cell is sufficient to cause the condition. Most cases of metatropic dysplasia are caused by new mutations in the gene and occur in people with no history of the disorder in their family. In a few reported cases, an affected person has inherited the condition from an affected parent.  In the past, it was thought that the lethal type of metatropic dysplasia had an autosomal recessive pattern of inheritance, in which both copies of the gene in each cell have mutations. However, more recent research has confirmed that all metatropic dysplasia has an autosomal dominant pattern of inheritance.",metatropic dysplasia,0000648,GHR,https://ghr.nlm.nih.gov/condition/metatropic-dysplasia,C0265281,T019,Disorders
What are the treatments for metatropic dysplasia ?,0000648-5,treatment,These resources address the diagnosis or management of metatropic dysplasia:  - Gene Review: Gene Review: TRPV4-Associated Disorders  - Genetic Testing Registry: Metatrophic dysplasia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,metatropic dysplasia,0000648,GHR,https://ghr.nlm.nih.gov/condition/metatropic-dysplasia,C0265281,T019,Disorders
"What is (are) methemoglobinemia, beta-globin type ?",0000649-1,information,"Methemoglobinemia, beta-globin type is a condition that affects the function of red blood cells. Specifically, it alters a molecule called hemoglobin within these cells. Hemoglobin within red blood cells attaches (binds) to oxygen molecules in the lungs, which it carries through the bloodstream, then releases in tissues throughout the body. Instead of normal hemoglobin, people with methemoglobinemia, beta-globin type have an abnormal form called methemoglobin, which is unable to efficiently deliver oxygen to the body's tissues. In methemoglobinemia, beta-globin type, the abnormal hemoglobin gives the blood a brown color. It also causes a bluish appearance of the skin, lips, and nails (cyanosis), which usually first appears around the age of 6 months. The signs and symptoms of methemoglobinemia, beta-globin type are generally limited to cyanosis, which does not cause any health problems. However, in rare cases, severe methemoglobinemia, beta-globin type can cause headaches, weakness, and fatigue.","methemoglobinemia, beta-globin type",0000649,GHR,https://ghr.nlm.nih.gov/condition/methemoglobinemia-beta-globin-type,C1840779,T047,Disorders
"How many people are affected by methemoglobinemia, beta-globin type ?",0000649-2,frequency,"The incidence of methemoglobinemia, beta-globin type is unknown.","methemoglobinemia, beta-globin type",0000649,GHR,https://ghr.nlm.nih.gov/condition/methemoglobinemia-beta-globin-type,C1840779,T047,Disorders
"What are the genetic changes related to methemoglobinemia, beta-globin type ?",0000649-3,genetic changes,"Methemoglobinemia, beta-globin type is caused by mutations in the HBB gene. This gene provides instructions for making a protein called beta-globin. Beta-globin is one of four components (subunits) that make up hemoglobin. In adults, hemoglobin normally contains two subunits of beta-globin and two subunits of another protein called alpha-globin. Each of these protein subunits is bound to an iron-containing molecule called heme; each heme contains an iron molecule in its center that can bind to one oxygen molecule. For hemoglobin to bind to oxygen, the iron within the heme molecule needs to be in a form called ferrous iron (Fe2+). The iron within the heme can change to another form of iron called ferric iron (Fe3+), which cannot bind oxygen. Hemoglobin that contains ferric iron is known as methemoglobin.  HBB gene mutations that cause methemoglobinemia, beta-globin type change the structure of beta-globin and promote the heme iron to change from ferrous to ferric. The ferric iron cannot bind oxygen and causes cyanosis and the brown appearance of blood.","methemoglobinemia, beta-globin type",0000649,GHR,https://ghr.nlm.nih.gov/condition/methemoglobinemia-beta-globin-type,C1840779,T047,Disorders
"Is methemoglobinemia, beta-globin type inherited ?",0000649-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.","methemoglobinemia, beta-globin type",0000649,GHR,https://ghr.nlm.nih.gov/condition/methemoglobinemia-beta-globin-type,C1840779,T047,Disorders
"What are the treatments for methemoglobinemia, beta-globin type ?",0000649-5,treatment,"These resources address the diagnosis or management of methemoglobinemia, beta-globin type:  - Genetic Testing Registry: Methemoglobinemia, beta-globin type  - KidsHealth from Nemours: Blood Test: Hemoglobin  - MedlinePlus Encyclopedia: Hemoglobin  - MedlinePlus Encyclopedia: Methemoglobinemia  - MedlinePlus Encyclopedia: Skin Discoloration--Bluish   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","methemoglobinemia, beta-globin type",0000649,GHR,https://ghr.nlm.nih.gov/condition/methemoglobinemia-beta-globin-type,C1840779,T047,Disorders
What is (are) methylmalonic acidemia ?,0000650-1,information,"Methylmalonic acidemia is an inherited disorder in which the body is unable to process certain proteins and fats (lipids) properly. The effects of methylmalonic acidemia, which usually appear in early infancy, vary from mild to life-threatening. Affected infants can experience vomiting, dehydration, weak muscle tone (hypotonia), developmental delay, excessive tiredness (lethargy), an enlarged liver (hepatomegaly), and failure to gain weight and grow at the expected rate (failure to thrive). Long-term complications can include feeding problems, intellectual disability, chronic kidney disease, and inflammation of the pancreas (pancreatitis). Without treatment, this disorder can lead to coma and death in some cases.",methylmalonic acidemia,0000650,GHR,https://ghr.nlm.nih.gov/condition/methylmalonic-acidemia,C0268583,T047,Disorders
How many people are affected by methylmalonic acidemia ?,0000650-2,frequency,"This condition occurs in an estimated 1 in 50,000 to 100,000 people.",methylmalonic acidemia,0000650,GHR,https://ghr.nlm.nih.gov/condition/methylmalonic-acidemia,C0268583,T047,Disorders
What are the genetic changes related to methylmalonic acidemia ?,0000650-3,genetic changes,"Mutations in the MUT, MMAA, MMAB, MMADHC, and MCEE genes cause methylmalonic acidemia. The long term effects of methylmalonic acidemia depend on which gene is mutated and the severity of the mutation.  About 60 percent of methylmalonic acidemia cases are caused by mutations in the MUT gene. This gene provides instructions for making an enzyme called methylmalonyl CoA mutase. This enzyme works with vitamin B12 (also called cobalamin) to break down several protein building blocks (amino acids), certain lipids, and cholesterol. Mutations in the MUT gene alter the enzyme's structure or reduce the amount of the enzyme, which prevents these molecules from being broken down properly. As a result, a substance called methylmalonyl CoA and other potentially toxic compounds can accumulate in the body's organs and tissues, causing the signs and symptoms of methylmalonic acidemia.  Mutations in the MUT gene that prevent the production of any functional enzyme result in a form of the condition designated mut0. Mut0 is the most severe form of methylmalonic acidemia and has the poorest outcome. Mutations that change the structure of methylmalonyl CoA mutase but do not eliminate its activity cause a form of the condition designated mut-. The mut- form is typically less severe, with more variable symptoms than the mut0 form.  Some cases of methylmalonic acidemia are caused by mutations in the MMAA, MMAB, or MMADHC gene. Proteins produced from the MMAA, MMAB, and MMADHC genes are needed for the proper function of methylmalonyl CoA mutase. Mutations that affect proteins produced from these three genes can impair the activity of methylmalonyl CoA mutase, leading to methylmalonic acidemia.  A few other cases of methylmalonic acidemia are caused by mutations in the MCEE gene. This gene provides instructions for producing an enzyme called methylmalonyl CoA epimerase. Like methylmalonyl CoA mutase, this enzyme also plays a role in the breakdown of amino acids, certain lipids, and cholesterol. Disruption in the function of methylmalonyl CoA epimerase leads to a mild form of methylmalonic acidemia.  It is likely that mutations in other, unidentified genes also cause methylmalonic acidemia.",methylmalonic acidemia,0000650,GHR,https://ghr.nlm.nih.gov/condition/methylmalonic-acidemia,C0268583,T047,Disorders
Is methylmalonic acidemia inherited ?,0000650-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the MUT, MMAA, MMAB, MMADHC, or MCEE gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition are carriers of one copy of the mutated gene but do not show signs and symptoms of the condition.",methylmalonic acidemia,0000650,GHR,https://ghr.nlm.nih.gov/condition/methylmalonic-acidemia,C0268583,T047,Disorders
What are the treatments for methylmalonic acidemia ?,0000650-5,treatment,These resources address the diagnosis or management of methylmalonic acidemia:  - Baby's First Test: Methylmalonic Acidemia (Cobalamin Disorders)  - Baby's First Test: Methylmalonic Acidemia (Methymalonyl-CoA Mutase Deficiency)  - Gene Review: Gene Review: Isolated Methylmalonic Acidemia  - Genetic Testing Registry: Methylmalonic acidemia  - Genetic Testing Registry: Methylmalonic acidemia with homocystinuria cblD  - Genetic Testing Registry: Methylmalonic aciduria cblA type  - Genetic Testing Registry: Methylmalonic aciduria cblB type  - Genetic Testing Registry: Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency  - Genetic Testing Registry: Methylmalonyl-CoA epimerase deficiency  - MedlinePlus Encyclopedia: Methylmalonic acid  - MedlinePlus Encyclopedia: Methylmalonic acidemia  - New England Consortium of Metabolic Programs   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,methylmalonic acidemia,0000650,GHR,https://ghr.nlm.nih.gov/condition/methylmalonic-acidemia,C0268583,T047,Disorders
What is (are) methylmalonic acidemia with homocystinuria ?,0000651-1,information,"Methylmalonic acidemia with homocystinuria is an inherited disorder in which the body is unable to properly process protein building blocks (amino acids), certain fats (lipids), and a waxy fat-like substance called cholesterol. Individuals with this disorder have a combination of features from two separate conditions, methylmalonic acidemia and homocystinuria. The signs and symptoms of the combined condition, methylmalonic acidemia with homocystinuria, usually develop in infancy, although they can begin at any age.  When the condition begins early in life, affected individuals typically have an inability to grow and gain weight at the expected rate (failure to thrive), which is sometimes recognized before birth (intrauterine growth retardation). These infants can also have difficulty feeding and an abnormally pale appearance (pallor). Neurological problems are also common in methylmalonic acidemia with homocystinuria, including weak muscle tone (hypotonia) and seizures. Most infants and children with this condition have an unusually small head size (microcephaly), delayed development, and intellectual disability. Less common features of the condition include eye problems and a blood disorder called megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number of red blood cells (anemia), and the remaining red blood cells are larger than normal (megaloblastic). The signs and symptoms of methylmalonic acidemia with homocystinuria worsen over time, and the condition can be life-threatening if not treated.  When methylmalonic acidemia with homocystinuria begins in adolescence or adulthood, the signs and symptoms usually include psychiatric changes and cognitive problems. Affected individuals can exhibit changes in their behavior and personality; they may become less social and may experience hallucinations, delirium, and psychosis. In addition, these individuals can begin to lose previously acquired mental and movement abilities, resulting in a decline in school or work performance, difficulty controlling movements, memory problems, speech difficulties, a decline in intellectual function (dementia), or an extreme lack of energy (lethargy). Some people with methylmalonic acidemia with homocystinuria whose signs and symptoms begin later in life develop a condition called subacute combined degeneration of the spinal cord, which leads to numbness and weakness in the lower limbs, difficulty walking, and frequent falls.",methylmalonic acidemia with homocystinuria,0000651,GHR,https://ghr.nlm.nih.gov/condition/methylmalonic-acidemia-with-homocystinuria,C1848561,T046,Disorders
How many people are affected by methylmalonic acidemia with homocystinuria ?,0000651-2,frequency,"The most common form of the condition, called methylmalonic acidemia with homocystinuria, cblC type, is estimated to affect 1 in 200,000 newborns worldwide. Studies indicate that this form of the condition may be even more common in particular populations. These studies estimate the condition occurs in 1 in 100,000 people in New York and 1 in 60,000 people in California. Other types of methylmalonic acidemia with homocystinuria are much less common. Fewer than 20 cases of each of the other types have been reported in the medical literature.",methylmalonic acidemia with homocystinuria,0000651,GHR,https://ghr.nlm.nih.gov/condition/methylmalonic-acidemia-with-homocystinuria,C1848561,T046,Disorders
What are the genetic changes related to methylmalonic acidemia with homocystinuria ?,0000651-3,genetic changes,"Methylmalonic acidemia with homocystinuria can be caused by mutations in one of several genes: MMACHC, MMADHC, LMBRD1, ABCD4, or HCFC1. Mutations in these genes account for the different types of the disorder, which are known as complementation groups: cblC, cblD, cblF, cblJ, and cblX, respectively.  Each of the above-mentioned genes is involved in the processing of vitamin B12, also known as cobalamin or Cbl. Processing of the vitamin converts it to one of two molecules, adenosylcobalamin (AdoCbl) or methylcobalamin (MeCbl). AdoCbl is required for the normal function of an enzyme that helps break down certain amino acids, lipids, and cholesterol. AdoCbl is called a cofactor because it helps the enzyme carry out its function. MeCbl is also a cofactor, but for another enzyme that converts the amino acid homocysteine to another amino acid, methionine. The body uses methionine to make proteins and other important compounds.  Mutations in the MMACHC, MMADHC, LMBRD1, ABCD4, or HCFC1 gene affect early steps of vitamin B12 processing, resulting in a shortage of both AdoCbl and MeCbl. Without AdoCbl, proteins and lipids are not broken down properly. This defect allows potentially toxic compounds to build up in the body's organs and tissues, causing methylmalonic acidemia. Without MeCbl, homocysteine is not converted to methionine. As a result, homocysteine builds up in the bloodstream and methionine is depleted. Some of the excess homocysteine is excreted in urine (homocystinuria). Researchers have not determined how altered levels of homocysteine and methionine lead to the health problems associated with homocystinuria.  Mutations in other genes involved in vitamin B12 processing can cause related conditions. Those mutations that impair only AdoCbl production lead to methylmalonic acidemia, and those that impair only MeCbl production cause homocystinuria.",methylmalonic acidemia with homocystinuria,0000651,GHR,https://ghr.nlm.nih.gov/condition/methylmalonic-acidemia-with-homocystinuria,C1848561,T046,Disorders
Is methylmalonic acidemia with homocystinuria inherited ?,0000651-4,inheritance,"Methylmalonic acidemia with homocystinuria is usually inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  When caused by mutations in the HCFC1 gene, the condition is inherited in an X-linked recessive pattern. The HCFC1 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",methylmalonic acidemia with homocystinuria,0000651,GHR,https://ghr.nlm.nih.gov/condition/methylmalonic-acidemia-with-homocystinuria,C1848561,T046,Disorders
What are the treatments for methylmalonic acidemia with homocystinuria ?,0000651-5,treatment,"These resources address the diagnosis or management of methylmalonic acidemia with homocystinuria:  - Baby's First Test: Methylmalonic Acidemia with Homocystinuria  - Gene Review: Gene Review: Disorders of Intracellular Cobalamin Metabolism  - Genetic Testing Registry: METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, cblF TYPE  - Genetic Testing Registry: METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, cblJ TYPE  - Genetic Testing Registry: Methylmalonic acidemia with homocystinuria  - Genetic Testing Registry: Methylmalonic acidemia with homocystinuria cblD   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",methylmalonic acidemia with homocystinuria,0000651,GHR,https://ghr.nlm.nih.gov/condition/methylmalonic-acidemia-with-homocystinuria,C1848561,T046,Disorders
What is (are) mevalonate kinase deficiency ?,0000652-1,information,"Mevalonate kinase deficiency is a condition characterized by recurrent episodes of fever, which typically begin during infancy. Each episode of fever lasts about 3 to 6 days, and the frequency of the episodes varies among affected individuals. In childhood the fevers seem to be more frequent, occurring as often as 25 times a year, but as the individual gets older the episodes occur less often.  Mevalonate kinase deficiency has additional signs and symptoms, and the severity depends on the type of the condition. There are two types of mevalonate kinase deficiency: a less severe type called hyperimmunoglobulinemia D syndrome (HIDS) and a more severe type called mevalonic aciduria (MVA).  During episodes of fever, people with HIDS typically have enlargement of the lymph nodes (lymphadenopathy), abdominal pain, joint pain, diarrhea, skin rashes, and headache. Occasionally they will have painful sores called aphthous ulcers around their mouth. In females, these may also occur around the vagina. A small number of people with HIDS have intellectual disability, problems with movement and balance (ataxia), eye problems, and recurrent seizures (epilepsy). Rarely, people with HIDS develop a buildup of protein deposits (amyloidosis) in the kidneys that can lead to kidney failure. Fever episodes in individuals with HIDS can be triggered by vaccinations, surgery, injury, or stress. Most people with HIDS have abnormally high levels of immune system proteins called immunoglobulin D (IgD) and immunoglobulin A (IgA) in the blood. It is unclear why people with HIDS have high levels of IgD and IgA. Elevated levels of these immunoglobulins do not appear to cause any signs or symptoms. Individuals with HIDS do not have any signs and symptoms of the condition between fever episodes and typically have a normal life expectancy.  People with MVA have signs and symptoms of the condition at all times, not just during episodes of fever. Affected children have developmental delay, progressive ataxia, progressive problems with vision, and failure to gain weight and grow at the expected rate (failure to thrive). Individuals with MVA typically have an unusually small, elongated head. In childhood or adolescence, affected individuals may develop eye problems such as inflammation of the eye (uveitis), a blue tint in the white part of the eye (blue sclera), an eye disorder called retinitis pigmentosa that causes vision loss, or clouding of the lens of the eye (cataracts). Affected adults may have short stature and may develop muscle weakness (myopathy) later in life. During fever episodes, people with MVA may have an enlarged liver and spleen (hepatosplenomegaly), lymphadenopathy, abdominal pain, diarrhea, and skin rashes. Children with MVA who are severely affected with multiple problems may live only into early childhood; mildly affected individuals may have a normal life expectancy.",mevalonate kinase deficiency,0000652,GHR,https://ghr.nlm.nih.gov/condition/mevalonate-kinase-deficiency,C0342731,T047,Disorders
How many people are affected by mevalonate kinase deficiency ?,0000652-2,frequency,More than 200 people with mevalonate kinase deficiency have been reported worldwide; the majority of these individuals have HIDS.,mevalonate kinase deficiency,0000652,GHR,https://ghr.nlm.nih.gov/condition/mevalonate-kinase-deficiency,C0342731,T047,Disorders
What are the genetic changes related to mevalonate kinase deficiency ?,0000652-3,genetic changes,"Mutations in the MVK gene cause mevalonate kinase deficiency. The MVK gene provides instructions for making the mevalonate kinase enzyme. This enzyme is involved in the production of cholesterol, which is later converted into steroid hormones and bile acids. Steroid hormones are needed for normal development and reproduction, and bile acids are used to digest fats. Mevalonate kinase also helps to produce other substances that are necessary for certain cellular functions, such as cell growth, cell maturation (differentiation), formation of the cell's structural framework (the cytoskeleton), gene activity (expression), and protein production and modification.  Most MVK gene mutations that cause mevalonate kinase deficiency result in an enzyme that is unstable and folded into an incorrect 3-dimensional shape, leading to a reduction of mevalonate kinase enzyme activity. Despite this shortage (deficiency) of mevalonate kinase activity, people with mevalonate kinase deficiency typically have normal production of cholesterol, steroid hormones, and bile acids.  It is unclear how a lack of mevalonate kinase activity causes the signs and symptoms of this condition. Some researchers believe the features may be due to a buildup of mevalonic acid, the substance that mevalonate kinase normally acts on. Other researchers think that a shortage of the substances produced from mevalonic acid, such as those substances necessary for certain cellular functions, causes the fever episodes and other features of this condition.  The severity of the enzyme deficiency determines the severity of the condition. People who have approximately 1 to 20 percent of normal mevalonate kinase activity typically develop HIDS. Individuals who have less than 1 percent of normal enzyme activity usually develop MVA.",mevalonate kinase deficiency,0000652,GHR,https://ghr.nlm.nih.gov/condition/mevalonate-kinase-deficiency,C0342731,T047,Disorders
Is mevalonate kinase deficiency inherited ?,0000652-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",mevalonate kinase deficiency,0000652,GHR,https://ghr.nlm.nih.gov/condition/mevalonate-kinase-deficiency,C0342731,T047,Disorders
What are the treatments for mevalonate kinase deficiency ?,0000652-5,treatment,These resources address the diagnosis or management of mevalonate kinase deficiency:  - Genetic Testing Registry: Hyperimmunoglobulin D with periodic fever  - Genetic Testing Registry: Mevalonic aciduria   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,mevalonate kinase deficiency,0000652,GHR,https://ghr.nlm.nih.gov/condition/mevalonate-kinase-deficiency,C0342731,T047,Disorders
What is (are) microcephalic osteodysplastic primordial dwarfism type II ?,0000653-1,information,"Microcephalic osteodysplastic primordial dwarfism type II (MOPDII) is a condition characterized by short stature (dwarfism) with other skeletal abnormalities (osteodysplasia) and an unusually small head size (microcephaly). The growth problems in MOPDII are primordial, meaning they begin before birth, with affected individuals showing slow prenatal growth (intrauterine growth retardation). After birth, affected individuals continue to grow at a very slow rate. The final adult height of people with this condition ranges from 20 inches to 40 inches. Other skeletal abnormalities in MOPDII include abnormal development of the hip joints (hip dysplasia), thinning of the bones in the arms and legs, an abnormal side-to-side curvature of the spine (scoliosis), and shortened wrist bones. In people with MOPDII head growth slows over time; affected individuals have an adult brain size comparable to that of a 3-month-old infant. However, intellectual development is typically normal.  People with this condition typically have a high-pitched, nasal voice that results from a narrowing of the voicebox (subglottic stenosis). Facial features characteristic of MOPDII include a prominent nose, full cheeks, a long midface, and a small jaw. Other signs and symptoms seen in some people with MOPDII include small teeth (microdontia) and farsightedness. Over time, affected individuals may develop areas of abnormally light or dark skin coloring (pigmentation).  Many individuals with MOPDII have blood vessel abnormalities. For example, some affected individuals develop a bulge in one of the blood vessels at the center of the brain (intracranial aneurysm). These aneurysms are dangerous because they can burst, causing bleeding within the brain. Some affected individuals have Moyamoya disease, in which arteries at the base of the brain are narrowed, leading to restricted blood flow. These vascular abnormalities are often treatable, though they increase the risk of stroke and reduce the life expectancy of affected individuals.",microcephalic osteodysplastic primordial dwarfism type II,0000653,GHR,https://ghr.nlm.nih.gov/condition/microcephalic-osteodysplastic-primordial-dwarfism-type-ii,C0432246,T019,Disorders
How many people are affected by microcephalic osteodysplastic primordial dwarfism type II ?,0000653-2,frequency,"MOPDII appears to be a rare condition, although its prevalence is unknown.",microcephalic osteodysplastic primordial dwarfism type II,0000653,GHR,https://ghr.nlm.nih.gov/condition/microcephalic-osteodysplastic-primordial-dwarfism-type-ii,C0432246,T019,Disorders
What are the genetic changes related to microcephalic osteodysplastic primordial dwarfism type II ?,0000653-3,genetic changes,"Mutations in the PCNT gene cause MOPDII. The PCNT gene provides instructions for making a protein called pericentrin. Within cells, this protein is located in structures called centrosomes. Centrosomes play a role in cell division and the assembly of microtubules. Microtubules are fibers that help cells maintain their shape, assist in the process of cell division, and are essential for the transport of materials within cells. Pericentrin acts as an anchoring protein, securing other proteins to the centrosome. Through its interactions with these proteins, pericentrin plays a role in regulation of the cell cycle, which is the cell's way of replicating itself in an organized, step-by-step fashion.  PCNT gene mutations lead to the production of a nonfunctional pericentrin protein that cannot anchor other proteins to the centrosome. As a result, centrosomes cannot properly assemble microtubules, leading to disruption of the cell cycle and cell division. Impaired cell division causes a reduction in cell production, while disruption of the cell cycle can lead to cell death. This overall reduction in the number of cells leads to short bones, microcephaly, and the other signs and symptoms of MOPDII.",microcephalic osteodysplastic primordial dwarfism type II,0000653,GHR,https://ghr.nlm.nih.gov/condition/microcephalic-osteodysplastic-primordial-dwarfism-type-ii,C0432246,T019,Disorders
Is microcephalic osteodysplastic primordial dwarfism type II inherited ?,0000653-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",microcephalic osteodysplastic primordial dwarfism type II,0000653,GHR,https://ghr.nlm.nih.gov/condition/microcephalic-osteodysplastic-primordial-dwarfism-type-ii,C0432246,T019,Disorders
What are the treatments for microcephalic osteodysplastic primordial dwarfism type II ?,0000653-5,treatment,These resources address the diagnosis or management of MOPDII:  - Genetic Testing Registry: Microcephalic osteodysplastic primordial dwarfism type 2   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,microcephalic osteodysplastic primordial dwarfism type II,0000653,GHR,https://ghr.nlm.nih.gov/condition/microcephalic-osteodysplastic-primordial-dwarfism-type-ii,C0432246,T019,Disorders
What is (are) microcephaly-capillary malformation syndrome ?,0000654-1,information,"Microcephaly-capillary malformation syndrome is an inherited disorder characterized by an abnormally small head size (microcephaly) and abnormalities of small blood vessels in the skin called capillaries (capillary malformations).  In people with microcephaly-capillary malformation syndrome, microcephaly begins before birth and is associated with an unusually small brain and multiple brain abnormalities. Affected individuals develop seizures that can occur many times per day and are difficult to treat (intractable epilepsy). The problems with brain development and epilepsy lead to profound developmental delay and intellectual impairment. Most affected individuals do not develop skills beyond those of a 1- or 2-month-old infant. For example, most children with this condition are never able to control their head movements or sit unassisted.  Capillary malformations are composed of enlarged capillaries that increase blood flow near the surface of the skin. These malformations look like pink or red spots on the skin. People with microcephaly-capillary malformation syndrome are born with anywhere from a few to hundreds of these spots, which can occur anywhere on the body. The spots are usually round or oval-shaped and range in size from the head of a pin to a large coin.  Other signs and symptoms of microcephaly-capillary malformation syndrome include abnormal movements, feeding difficulties, slow growth, and short stature. Most affected individuals have abnormalities of the fingers and toes, including digits with tapered ends and abnormally small or missing fingernails and toenails. Some affected children also have distinctive facial features and an unusual pattern of hair growth on the scalp.",microcephaly-capillary malformation syndrome,0000654,GHR,https://ghr.nlm.nih.gov/condition/microcephaly-capillary-malformation-syndrome,C0340803,T019,Disorders
How many people are affected by microcephaly-capillary malformation syndrome ?,0000654-2,frequency,Microcephaly-capillary malformation syndrome is rare. About a dozen people have been diagnosed with the disorder.,microcephaly-capillary malformation syndrome,0000654,GHR,https://ghr.nlm.nih.gov/condition/microcephaly-capillary-malformation-syndrome,C0340803,T019,Disorders
What are the genetic changes related to microcephaly-capillary malformation syndrome ?,0000654-3,genetic changes,"Microcephaly-capillary malformation syndrome results from mutations in the STAMBP gene. This gene provides instructions for making a protein called STAM binding protein. This protein plays a role in sorting damaged or unneeded proteins so they can be transported from the cell surface to specialized cell compartments that break down (degrade) or recycle them. This process helps to maintain the proper balance of protein production and breakdown (protein homeostasis) that cells need to function and survive. Studies suggest that STAM binding protein is also involved in multiple chemical signaling pathways within cells, including pathways needed for overall growth and the formation of new blood vessels (angiogenesis).  Mutations in the STAMBP gene reduce or eliminate the production of STAM binding protein. This shortage allows damaged or unneeded proteins to build up inside cells instead of being degraded or recycled, which may damage cells and cause them to self-destruct (undergo apoptosis). Researchers suspect that abnormal apoptosis of brain cells starting before birth may cause microcephaly and the underlying brain abnormalities found in people with microcephaly-capillary malformation syndrome. A lack of STAM binding protein also alters multiple signaling pathways that are necessary for normal development, which may underlie the capillary malformations and other signs and symptoms of the condition.",microcephaly-capillary malformation syndrome,0000654,GHR,https://ghr.nlm.nih.gov/condition/microcephaly-capillary-malformation-syndrome,C0340803,T019,Disorders
Is microcephaly-capillary malformation syndrome inherited ?,0000654-4,inheritance,"This condition has an autosomal recessive pattern of inheritance, which means both copies of the STAMBP gene in each cell have mutations. An affected individual usually inherits one altered copy of the gene from each parent. Parents of an individual with an autosomal recessive condition typically do not show signs and symptoms of the condition.  At least one individual with microcephaly-capillary malformation syndrome inherited two mutated copies of the STAMBP gene through a mechanism called uniparental isodisomy. In this case, an error occurred during the formation of egg or sperm cells, and the child received two copies of the mutated gene from one parent instead of one copy from each parent.",microcephaly-capillary malformation syndrome,0000654,GHR,https://ghr.nlm.nih.gov/condition/microcephaly-capillary-malformation-syndrome,C0340803,T019,Disorders
What are the treatments for microcephaly-capillary malformation syndrome ?,0000654-5,treatment,These resources address the diagnosis or management of microcephaly-capillary malformation syndrome:  - Gene Review: Gene Review: Microcephaly-Capillary Malformation Syndrome  - Genetic Testing Registry: Microcephaly-capillary malformation syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,microcephaly-capillary malformation syndrome,0000654,GHR,https://ghr.nlm.nih.gov/condition/microcephaly-capillary-malformation-syndrome,C0340803,T019,Disorders
What is (are) microphthalmia ?,0000655-1,information,"Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.  People with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.  People with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.  Between one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.",microphthalmia,0000655,GHR,https://ghr.nlm.nih.gov/condition/microphthalmia,C0026010,T019,Disorders
How many people are affected by microphthalmia ?,0000655-2,frequency,"Microphthalmia occurs in approximately 1 in 10,000 individuals.",microphthalmia,0000655,GHR,https://ghr.nlm.nih.gov/condition/microphthalmia,C0026010,T019,Disorders
What are the genetic changes related to microphthalmia ?,0000655-3,genetic changes,"Microphthalmia may be caused by changes in many genes involved in the early development of the eye, most of which have not been identified. The condition may also result from a chromosomal abnormality affecting one or more genes. Most genetic changes associated with isolated microphthalmia have been identified only in very small numbers of affected individuals.  Microphthalmia may also be caused by environmental factors that affect early development, such as a shortage of certain vitamins during pregnancy, radiation, infections such as rubella, or exposure to substances that cause birth defects (teratogens).",microphthalmia,0000655,GHR,https://ghr.nlm.nih.gov/condition/microphthalmia,C0026010,T019,Disorders
Is microphthalmia inherited ?,0000655-4,inheritance,"Isolated microphthalmia is sometimes inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. In some cases, parents of affected individuals have less severe eye abnormalities.  When microphthalmia occurs as a feature of a genetic syndrome or chromosomal abnormality, it may cluster in families according to the inheritance pattern for that condition, which may be autosomal recessive or other patterns.  Often microphthalmia is not inherited, and there is only one affected individual in a family.",microphthalmia,0000655,GHR,https://ghr.nlm.nih.gov/condition/microphthalmia,C0026010,T019,Disorders
What are the treatments for microphthalmia ?,0000655-5,treatment,"These resources address the diagnosis or management of microphthalmia:  - Gene Review: Gene Review: Microphthalmia/Anophthalmia/Coloboma Spectrum  - Genetic Testing Registry: Cataract, congenital, with microphthalmia  - Genetic Testing Registry: Cataract, microphthalmia and nystagmus  - Genetic Testing Registry: Microphthalmia, isolated 1  - Genetic Testing Registry: Microphthalmia, isolated 2  - Genetic Testing Registry: Microphthalmia, isolated 3  - Genetic Testing Registry: Microphthalmia, isolated 4  - Genetic Testing Registry: Microphthalmia, isolated 5  - Genetic Testing Registry: Microphthalmia, isolated 6  - Genetic Testing Registry: Microphthalmia, isolated 7  - Genetic Testing Registry: Microphthalmia, isolated 8  - Genetic Testing Registry: Microphthalmia, isolated, with coloboma 1  - Genetic Testing Registry: Microphthalmia, isolated, with coloboma 2  - Genetic Testing Registry: Microphthalmia, isolated, with coloboma 3  - Genetic Testing Registry: Microphthalmia, isolated, with coloboma 4  - Genetic Testing Registry: Microphthalmia, isolated, with coloboma 5  - Genetic Testing Registry: Microphthalmia, isolated, with coloboma 6  - Genetic Testing Registry: Microphthalmia, isolated, with corectopia  - Genetic Testing Registry: Microphthalmos   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",microphthalmia,0000655,GHR,https://ghr.nlm.nih.gov/condition/microphthalmia,C0026010,T019,Disorders
What is (are) microphthalmia with linear skin defects syndrome ?,0000656-1,information,"Microphthalmia with linear skin defects syndrome is a disorder that mainly affects females. In people with this condition, one or both eyes may be very small or poorly developed (microphthalmia). Affected individuals also typically have unusual linear skin markings on the head and neck. These markings follow the paths along which cells migrate as the skin develops before birth (lines of Blaschko). The skin defects generally improve over time and leave variable degrees of scarring.  The signs and symptoms of microphthalmia with linear skin defects syndrome vary widely, even among affected individuals within the same family. In addition to the characteristic eye problems and skin markings, this condition can cause abnormalities in the brain, heart, and genitourinary system. A hole in the muscle that separates the abdomen from the chest cavity (the diaphragm), which is called a diaphragmatic hernia, may occur in people with this disorder. Affected individuals may also have short stature and fingernails and toenails that do not grow normally (nail dystrophy).",microphthalmia with linear skin defects syndrome,0000656,GHR,https://ghr.nlm.nih.gov/condition/microphthalmia-with-linear-skin-defects-syndrome,C0796070,T047,Disorders
How many people are affected by microphthalmia with linear skin defects syndrome ?,0000656-2,frequency,The prevalence of microphthalmia with linear skin defects syndrome is unknown. More than 50 affected individuals have been identified.,microphthalmia with linear skin defects syndrome,0000656,GHR,https://ghr.nlm.nih.gov/condition/microphthalmia-with-linear-skin-defects-syndrome,C0796070,T047,Disorders
What are the genetic changes related to microphthalmia with linear skin defects syndrome ?,0000656-3,genetic changes,"Mutations in the HCCS gene or a deletion of genetic material that includes the HCCS gene cause microphthalmia with linear skin defects syndrome. The HCCS gene carries instructions for producing an enzyme called holocytochrome c-type synthase. This enzyme is active in many tissues of the body and is found in the mitochondria, the energy-producing centers within cells.  Within the mitochondria, the holocytochrome c-type synthase enzyme helps produce a molecule called cytochrome c. Cytochrome c is involved in a process called oxidative phosphorylation, by which mitochondria generate adenosine triphosphate (ATP), the cell's main energy source. It also plays a role in the self-destruction of cells (apoptosis).  HCCS gene mutations result in a holocytochrome c-type synthase enzyme that cannot perform its function. A deletion of genetic material that includes the HCCS gene prevents the production of the enzyme. A lack of functional holocytochrome c-type synthase enzyme can damage cells by impairing their ability to generate energy. In addition, without the holocytochrome c-type synthase enzyme, the damaged cells may not be able to undergo apoptosis. These cells may instead die in a process called necrosis that causes inflammation and damages neighboring cells. During early development this spreading cell damage may lead to the eye abnormalities and other signs and symptoms of microphthalmia with linear skin defects syndrome.",microphthalmia with linear skin defects syndrome,0000656,GHR,https://ghr.nlm.nih.gov/condition/microphthalmia-with-linear-skin-defects-syndrome,C0796070,T047,Disorders
Is microphthalmia with linear skin defects syndrome inherited ?,0000656-4,inheritance,"This condition is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. Some cells produce a normal amount of the holocytochrome c-type synthase enzyme and other cells produce none. The resulting overall reduction in the amount of this enzyme leads to the signs and symptoms of microphthalmia with linear skin defects syndrome.  In males (who have only one X chromosome), mutations result in a total loss of the holocytochrome c-type synthase enzyme. A lack of this enzyme appears to be lethal very early in development, so almost no males are born with microphthalmia with linear skin defects syndrome. A few affected individuals with male appearance but who have two X chromosomes have been identified.  Most cases of microphthalmia with linear skin defects syndrome occur in people with no history of the disorder in their family. These cases usually result from the deletion of a segment of the X chromosome during the formation of reproductive cells (eggs and sperm) or in early fetal development. They may also result from a new mutation in the HCCS gene.",microphthalmia with linear skin defects syndrome,0000656,GHR,https://ghr.nlm.nih.gov/condition/microphthalmia-with-linear-skin-defects-syndrome,C0796070,T047,Disorders
What are the treatments for microphthalmia with linear skin defects syndrome ?,0000656-5,treatment,"These resources address the diagnosis or management of microphthalmia with linear skin defects syndrome:  - Gene Review: Gene Review: Microphthalmia with Linear Skin Defects Syndrome  - Genetic Testing Registry: Microphthalmia, syndromic, 7   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",microphthalmia with linear skin defects syndrome,0000656,GHR,https://ghr.nlm.nih.gov/condition/microphthalmia-with-linear-skin-defects-syndrome,C0796070,T047,Disorders
What is (are) microvillus inclusion disease ?,0000657-1,information,"Microvillus inclusion disease is a condition characterized by chronic, watery, life-threatening diarrhea typically beginning in the first hours to days of life. Rarely, the diarrhea starts around age 3 or 4 months. Food intake increases the frequency of diarrhea.  Microvillus inclusion disease prevents the absorption of nutrients from food during digestion, resulting in malnutrition and dehydration. Affected infants often have difficulty gaining weight and growing at the expected rate (failure to thrive), developmental delay, liver and kidney problems, and thinning of the bones (osteoporosis). Some affected individuals develop cholestasis, which is a reduced ability to produce and release a digestive fluid called bile. Cholestasis leads to irreversible liver disease (cirrhosis).  In individuals with microvillus inclusion disease, lifelong nutritional support is needed and given through intravenous feedings (parenteral nutrition). Even with nutritional supplementation, most children with microvillus inclusion disease do not survive beyond childhood.  A variant of microvillus inclusion disease with milder diarrhea often does not require full-time parenteral nutrition. Individuals with the variant type frequently live past childhood.",microvillus inclusion disease,0000657,GHR,https://ghr.nlm.nih.gov/condition/microvillus-inclusion-disease,C0341306,T047,Disorders
How many people are affected by microvillus inclusion disease ?,0000657-2,frequency,"The prevalence of microvillus inclusion disease is unknown. At least 200 cases have been reported in Europe, although this condition occurs worldwide.",microvillus inclusion disease,0000657,GHR,https://ghr.nlm.nih.gov/condition/microvillus-inclusion-disease,C0341306,T047,Disorders
What are the genetic changes related to microvillus inclusion disease ?,0000657-3,genetic changes,"Mutations in the MYO5B gene cause microvillus inclusion disease. The MYO5B gene provides instructions for making a protein called myosin Vb. This protein helps to determine the position of various components within cells (cell polarity). Myosin Vb also plays a role in moving components from the cell membrane to the interior of the cell for recycling.  MYO5B gene mutations that cause microvillus inclusion disease result in a decrease or absence of myosin Vb function. In cells that line the small intestine (enterocytes), a lack of myosin Vb function changes the cell polarity. As a result, enterocytes cannot properly form structures called microvilli, which normally project like small fingers from the surface of the cells and absorb nutrients and fluids from food as it passes through the intestine. Inside affected enterocytes, small clumps of abnormal microvilli mix with misplaced digestive proteins to form microvillus inclusions, which contribute to the dysfunction of enterocytes. Disorganized enterocytes with poorly formed microvilli reduce the intestine's ability to take in nutrients. The inability to absorb nutrients and fluids during digestion leads to recurrent diarrhea, malnutrition, and dehydration in individuals with microvillus inclusion disease.  Some people with the signs and symptoms of microvillus inclusion disease do not have mutations in the MYO5B gene. These cases may be variants of microvillus inclusion disease. Studies suggest that mutations in other genes can cause these cases, but the causes are usually unknown.",microvillus inclusion disease,0000657,GHR,https://ghr.nlm.nih.gov/condition/microvillus-inclusion-disease,C0341306,T047,Disorders
Is microvillus inclusion disease inherited ?,0000657-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",microvillus inclusion disease,0000657,GHR,https://ghr.nlm.nih.gov/condition/microvillus-inclusion-disease,C0341306,T047,Disorders
What are the treatments for microvillus inclusion disease ?,0000657-5,treatment,These resources address the diagnosis or management of microvillus inclusion disease:  - Children's Hospital of Pittsburgh  - Genetic Testing Registry: Congenital microvillous atrophy  - Great Ormond Street Hospital for Children (UK): Intestinal Assessment  - International Microvillus Inclusion Disease Patient Registry   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,microvillus inclusion disease,0000657,GHR,https://ghr.nlm.nih.gov/condition/microvillus-inclusion-disease,C0341306,T047,Disorders
What is (are) Miller syndrome ?,0000658-1,information,"Miller syndrome is a rare condition that mainly affects the development of the face and limbs. The severity of this disorder varies among affected individuals.  Children with Miller syndrome are born with underdeveloped cheek bones (malar hypoplasia) and a very small lower jaw (micrognathia). They often have an opening in the roof of the mouth (cleft palate) and/or a split in the upper lip (cleft lip). These abnormalities frequently cause feeding problems in infants with Miller syndrome. The airway is usually restricted due to the micrognathia, which can lead to life-threatening breathing problems.  People with Miller syndrome often have eyes that slant downward, eyelids that turn out so the inner surface is exposed (ectropion), and a notch in the lower eyelids called an eyelid coloboma. Many affected individuals have small, cup-shaped ears, and some have hearing loss caused by defects in the middle ear (conductive hearing loss). Another feature of this condition is the presence of extra nipples. Miller syndrome does not affect a person's intelligence, although speech development may be delayed due to hearing impairment.  Individuals with Miller syndrome have various bone abnormalities in their arms and legs. The most common problem is absent fifth (pinky) fingers and toes. Affected individuals may also have webbed or fused fingers or toes (syndactyly) and abnormally formed bones in the forearms and lower legs. People with Miller syndrome sometimes have defects in other bones, such as the ribs or spine.  Less commonly, affected individuals have abnormalities of the heart, kidneys, genitalia, or gastrointestinal tract.",Miller syndrome,0000658,GHR,https://ghr.nlm.nih.gov/condition/miller-syndrome,C0812435,T019,Disorders
How many people are affected by Miller syndrome ?,0000658-2,frequency,Miller syndrome is a rare disorder; it is estimated to affect fewer than 1 in 1 million newborns. At least 30 cases have been reported in the medical literature.,Miller syndrome,0000658,GHR,https://ghr.nlm.nih.gov/condition/miller-syndrome,C0812435,T019,Disorders
What are the genetic changes related to Miller syndrome ?,0000658-3,genetic changes,"Mutations in the DHODH gene cause Miller syndrome. This gene provides instructions for making an enzyme called dihydroorotate dehydrogenase. This enzyme is involved in producing pyrimidines, which are building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in the cell. Specifically, dihydroorotate dehydrogenase converts a molecule called dihydroorotate to a molecule called orotic acid. In subsequent steps, other enzymes modify orotic acid to produce pyrimidines.  Miller syndrome disrupts the development of structures called the first and second pharyngeal arches. The pharyngeal arches are five paired structures that form on each side of the head and neck during embryonic development. These structures develop into the bones, skin, nerves, and muscles of the head and neck. In particular, the first and second pharyngeal arches develop into the jaw, the nerves and muscles for chewing and facial expressions, the bones in the middle ear, and the outer ear. It remains unclear exactly how DHODH gene mutations lead to abnormal development of the pharyngeal arches in people with Miller syndrome.  Development of the arms and legs is also affected by Miller syndrome. Each limb starts out as a small mound of tissue called a limb bud, which grows outward. Many different proteins are involved in the normal shaping (patterning) of each limb. Once the overall pattern of a limb is formed, detailed shaping can take place. For example, to create individual fingers and toes, certain cells self-destruct (undergo apoptosis) to remove the webbing between each digit. The role dihydroorotate dehydrogenase plays in limb development is not known. It is also unknown how mutations in the DHODH gene cause bone abnormalities in the arms and legs of people with Miller syndrome.",Miller syndrome,0000658,GHR,https://ghr.nlm.nih.gov/condition/miller-syndrome,C0812435,T019,Disorders
Is Miller syndrome inherited ?,0000658-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Miller syndrome,0000658,GHR,https://ghr.nlm.nih.gov/condition/miller-syndrome,C0812435,T019,Disorders
What are the treatments for Miller syndrome ?,0000658-5,treatment,These resources address the diagnosis or management of Miller syndrome:  - Genetic Testing Registry: Miller syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Miller syndrome,0000658,GHR,https://ghr.nlm.nih.gov/condition/miller-syndrome,C0812435,T019,Disorders
What is (are) Miller-Dieker syndrome ?,0000659-1,information,"Miller-Dieker syndrome is a condition characterized by a pattern of abnormal brain development known as lissencephaly. Normally the exterior of the brain (cerebral cortex) is multi-layered with folds and grooves. People with lissencephaly have an abnormally smooth brain with fewer folds and grooves. These brain malformations cause severe intellectual disability, developmental delay, seizures, abnormal muscle stiffness (spasticity), weak muscle tone (hypotonia), and feeding difficulties. Seizures usually begin before six months of age, and some occur from birth. Typically, the smoother the surface of the brain is, the more severe the associated symptoms are.  In addition to lissencephaly, people with Miller-Dieker syndrome tend to have distinctive facial features that include a prominent forehead; a sunken appearance in the middle of the face (midface hypoplasia); a small, upturned nose; low-set and abnormally shaped ears; a small jaw; and a thick upper lip. Some individuals with this condition also grow more slowly than other children. Rarely, affected individuals will have heart or kidney malformations or an opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the navel. People with Miller-Dieker syndrome may also have life-threatening breathing problems. Most individuals with this condition do not survive beyond childhood.",Miller-Dieker syndrome,0000659,GHR,https://ghr.nlm.nih.gov/condition/miller-dieker-syndrome,C0039082,T047,Disorders
How many people are affected by Miller-Dieker syndrome ?,0000659-2,frequency,"Miller-Dieker syndrome appears to be a rare disorder, although its prevalence is unknown.",Miller-Dieker syndrome,0000659,GHR,https://ghr.nlm.nih.gov/condition/miller-dieker-syndrome,C0039082,T047,Disorders
What are the genetic changes related to Miller-Dieker syndrome ?,0000659-3,genetic changes,"Miller-Dieker syndrome is caused by a deletion of genetic material near the end of the short (p) arm of chromosome 17. The signs and symptoms of Miller-Dieker syndrome are probably related to the loss of multiple genes in this region. The size of the deletion varies among affected individuals.  Researchers are working to identify all of the genes that contribute to the features of Miller-Dieker syndrome. They have determined that the loss of a particular gene on chromosome 17, PAFAH1B1, is responsible for the syndrome's characteristic sign of lissencephaly. The loss of another gene, YWHAE, in the same region of chromosome 17 increases the severity of the lissencephaly in people with Miller-Dieker syndrome. Additional genes in the deleted region probably contribute to the varied features of Miller-Dieker syndrome.",Miller-Dieker syndrome,0000659,GHR,https://ghr.nlm.nih.gov/condition/miller-dieker-syndrome,C0039082,T047,Disorders
Is Miller-Dieker syndrome inherited ?,0000659-4,inheritance,"Most cases of Miller-Dieker syndrome are not inherited. The deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family.  When Miller-Dieker syndrome is inherited, its inheritance pattern is considered autosomal dominant because a deletion in one copy of chromosome 17 in each cell is sufficient to cause the condition. About 12 percent of people with Miller-Dieker syndrome inherit a chromosome abnormality from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which no genetic material is gained or lost. Balanced translocations usually do not cause any health problems; however, they can become unbalanced as they are passed to the next generation. Children who inherit an unbalanced translocation can have a chromosomal rearrangement with extra or missing genetic material. Individuals with Miller-Dieker syndrome who inherit an unbalanced translocation are missing genetic material from the short arm of chromosome 17, which results in the health problems characteristic of this disorder.",Miller-Dieker syndrome,0000659,GHR,https://ghr.nlm.nih.gov/condition/miller-dieker-syndrome,C0039082,T047,Disorders
What are the treatments for Miller-Dieker syndrome ?,0000659-5,treatment,These resources address the diagnosis or management of Miller-Dieker syndrome:  - Gene Review: Gene Review: LIS1-Associated Lissencephaly/Subcortical Band Heterotopia  - Genetic Testing Registry: Miller Dieker syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Miller-Dieker syndrome,0000659,GHR,https://ghr.nlm.nih.gov/condition/miller-dieker-syndrome,C0039082,T047,Disorders
What is (are) Milroy disease ?,0000660-1,information,"Milroy disease is a condition that affects the normal function of the lymphatic system. The lymphatic system produces and transports fluids and immune cells throughout the body. Impaired transport with accumulation of lymph fluid can cause swelling (lymphedema). Individuals with Milroy disease typically have lymphedema in their lower legs and feet at birth or develop it in infancy. The lymphedema typically occurs on both sides of the body and may worsen over time.  Milroy disease is associated with other features in addition to lymphedema. Males with Milroy disease are sometimes born with an accumulation of fluid in the scrotum (hydrocele). Males and females may have upslanting toenails, deep creases in the toes, wart-like growths (papillomas), and prominent leg veins. Some individuals develop non-contagious skin infections called cellulitis that can damage the thin tubes that carry lymph fluid (lymphatic vessels). Episodes of cellulitis can cause further swelling in the lower limbs.",Milroy disease,0000660,GHR,https://ghr.nlm.nih.gov/condition/milroy-disease,C1704423,T019,Disorders
How many people are affected by Milroy disease ?,0000660-2,frequency,Milroy disease is a rare disorder; its incidence is unknown.,Milroy disease,0000660,GHR,https://ghr.nlm.nih.gov/condition/milroy-disease,C1704423,T019,Disorders
What are the genetic changes related to Milroy disease ?,0000660-3,genetic changes,"Mutations in the FLT4 gene cause some cases of Milroy disease. The FLT4 gene provides instructions for producing a protein called vascular endothelial growth factor receptor 3 (VEGFR-3), which regulates the development and maintenance of the lymphatic system. Mutations in the FLT4 gene interfere with the growth, movement, and survival of cells that line the lymphatic vessels (lymphatic endothelial cells). These mutations lead to the development of small or absent lymphatic vessels. If lymph fluid is not properly transported, it builds up in the body's tissues and causes lymphedema. It is not known how mutations in the FLT4 gene lead to the other features of this disorder.  Many individuals with Milroy disease do not have a mutation in the FLT4 gene. In these individuals, the cause of the disorder is unknown.",Milroy disease,0000660,GHR,https://ghr.nlm.nih.gov/condition/milroy-disease,C1704423,T019,Disorders
Is Milroy disease inherited ?,0000660-4,inheritance,"Milroy disease is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In many cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the FLT4 gene. These cases occur in people with no history of the disorder in their family. About 10 percent to 15 percent of people with a mutation in the FLT4 gene do not develop the features of Milroy disease.",Milroy disease,0000660,GHR,https://ghr.nlm.nih.gov/condition/milroy-disease,C1704423,T019,Disorders
What are the treatments for Milroy disease ?,0000660-5,treatment,These resources address the diagnosis or management of Milroy disease:  - Gene Review: Gene Review: Milroy Disease  - Genetic Testing Registry: Hereditary lymphedema type I  - MedlinePlus Encyclopedia: Lymphatic Obstruction   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Milroy disease,0000660,GHR,https://ghr.nlm.nih.gov/condition/milroy-disease,C1704423,T019,Disorders
What is (are) mitochondrial complex III deficiency ?,0000661-1,information,"Mitochondrial complex III deficiency is a genetic condition that can affect several parts of the body, including the brain, kidneys, liver, heart, and the muscles used for movement (skeletal muscles). Signs and symptoms of mitochondrial complex III deficiency usually begin in infancy but can appear later.  The severity of mitochondrial complex III deficiency varies widely among affected individuals. People who are mildly affected tend to have muscle weakness (myopathy) and extreme tiredness (fatigue), particularly during exercise (exercise intolerance). More severely affected individuals have problems with multiple body systems, such as liver disease that can lead to liver failure, kidney abnormalities (tubulopathy), and brain dysfunction (encephalopathy). Encephalopathy can cause delayed development of mental and motor skills (psychomotor delay), movement problems, weak muscle tone (hypotonia), and difficulty with communication. Some affected individuals have a form of heart disease called cardiomyopathy, which can lead to heart failure. Most people with mitochondrial complex III deficiency have a buildup of a chemical called lactic acid in the body (lactic acidosis). Some affected individuals also have buildup of molecules called ketones (ketoacidosis) or high blood sugar levels (hyperglycemia). Abnormally high levels of these chemicals in the body can be life-threatening.  Mitochondrial complex III deficiency can be fatal in childhood, although individuals with mild signs and symptoms can survive into adolescence or adulthood.",mitochondrial complex III deficiency,0000661,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-complex-iii-deficiency,C1852372,T047,Disorders
How many people are affected by mitochondrial complex III deficiency ?,0000661-2,frequency,"The prevalence of mitochondrial complex III deficiency is unknown, although the condition is thought to be rare.",mitochondrial complex III deficiency,0000661,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-complex-iii-deficiency,C1852372,T047,Disorders
What are the genetic changes related to mitochondrial complex III deficiency ?,0000661-3,genetic changes,"Mitochondrial complex III deficiency can be caused by mutations in one of several genes. The proteins produced from these genes either are a part of or help assemble a group of proteins called complex III. The two most commonly mutated genes involved in mitochondrial complex III deficiency are MT-CYB and BCS1L. It is likely that genes that have not been identified are also involved in this condition.  Cytochrome b, produced from the MT-CYB gene, is one component of complex III, and the protein produced from the BCS1L gene is critical for the formation of the complex. Complex III is found in cell structures called mitochondria, which convert the energy from food into a form that cells can use. Complex III is one of several complexes that carry out a multistep process called oxidative phosphorylation, through which cells derive much of their energy. As a byproduct of its action in oxidative phosphorylation, complex III produces reactive oxygen species, which are harmful molecules that can damage DNA and tissues.  MT-CYB and BCS1L gene mutations impair the formation of complex III molecules. As a result, complex III activity and oxidative phosphorylation are reduced. Researchers believe that impaired oxidative phosphorylation can lead to cell death by reducing the amount of energy available in the cell. It is thought that tissues and organs that require a lot of energy, such as the brain, liver, kidneys, and skeletal muscles, are most affected by a reduction in oxidative phosphorylation. In addition, for unknown reasons, BCS1L gene mutations lead to increased overall production of reactive oxygen species, although production by complex III is reduced. Damage from reduced energy and from reactive oxygen species likely contributes to the signs and symptoms of mitochondrial complex III deficiency.  Unlike most genes, the MT-CYB gene is found in DNA located in mitochondria, called mitochondrial DNA (mtDNA). This location may help explain why some people have more severe features of the condition than others. Most of the body's cells contain thousands of mitochondria, each with one or more copies of mtDNA. These cells can have a mix of mitochondria containing mutated and unmutated DNA (heteroplasmy). When caused by MT-CYB gene mutations, the severity of mitochondrial complex III deficiency is thought to be associated with the percentage of mitochondria with the gene mutation. The other genes known to be involved in this condition are found in DNA packaged in chromosomes within the cell nucleus (nuclear DNA). It is not clear why the severity of the condition varies in people with mutations in these other genes.",mitochondrial complex III deficiency,0000661,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-complex-iii-deficiency,C1852372,T047,Disorders
Is mitochondrial complex III deficiency inherited ?,0000661-4,inheritance,"Mitochondrial complex III deficiency is usually inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  In some cases caused by mutations in the MT-CYB gene, the condition is not inherited; it is caused by new mutations in the gene that occur in people with no history of the condition in their family. Other cases caused by mutations in the MT-CYB gene are inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mtDNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children.",mitochondrial complex III deficiency,0000661,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-complex-iii-deficiency,C1852372,T047,Disorders
What are the treatments for mitochondrial complex III deficiency ?,0000661-5,treatment,"These resources address the diagnosis or management of mitochondrial complex III deficiency:  - Gene Review: Gene Review: Mitochondrial Disorders Overview  - Genetic Testing Registry: MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 6  - Genetic Testing Registry: MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 7  - Genetic Testing Registry: MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 8  - Genetic Testing Registry: Mitochondrial complex III deficiency  - Genetic Testing Registry: Mitochondrial complex III deficiency, nuclear type 2  - Genetic Testing Registry: Mitochondrial complex III deficiency, nuclear type 3  - Genetic Testing Registry: Mitochondrial complex III deficiency, nuclear type 4  - Genetic Testing Registry: Mitochondrial complex III deficiency, nuclear type 5   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",mitochondrial complex III deficiency,0000661,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-complex-iii-deficiency,C1852372,T047,Disorders
"What is (are) mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes ?",0000662-1,information,"Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a condition that affects many of the body's systems, particularly the brain and nervous system (encephalo-) and muscles (myopathy). The signs and symptoms of this disorder most often appear in childhood following a period of normal development, although they can begin at any age. Early symptoms may include muscle weakness and pain, recurrent headaches, loss of appetite, vomiting, and seizures. Most affected individuals experience stroke-like episodes beginning before age 40. These episodes often involve temporary muscle weakness on one side of the body (hemiparesis), altered consciousness, vision abnormalities, seizures, and severe headaches resembling migraines. Repeated stroke-like episodes can progressively damage the brain, leading to vision loss, problems with movement, and a loss of intellectual function (dementia).  Most people with MELAS have a buildup of lactic acid in their bodies, a condition called lactic acidosis. Increased acidity in the blood can lead to vomiting, abdominal pain, extreme tiredness (fatigue), muscle weakness, and difficulty breathing. Less commonly, people with MELAS may experience involuntary muscle spasms (myoclonus), impaired muscle coordination (ataxia), hearing loss, heart and kidney problems, diabetes, and hormonal imbalances.","mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes",0000662,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-encephalomyopathy-lactic-acidosis-and-stroke-like-episodes,C0162666,T047,Disorders
"How many people are affected by mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes ?",0000662-2,frequency,"The exact incidence of MELAS is unknown. It is one of the more common conditions in a group known as mitochondrial diseases. Together, mitochondrial diseases occur in about 1 in 4,000 people.","mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes",0000662,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-encephalomyopathy-lactic-acidosis-and-stroke-like-episodes,C0162666,T047,Disorders
"What are the genetic changes related to mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes ?",0000662-3,genetic changes,"MELAS can result from mutations in one of several genes, including MT-ND1, MT-ND5, MT-TH, MT-TL1, and MT-TV. These genes are found in the DNA of cellular structures called mitochondria, which convert the energy from food into a form that cells can use. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA, known as mitochondrial DNA or mtDNA.  Some of the genes related to MELAS provide instructions for making proteins involved in normal mitochondrial function. These proteins are part of a large enzyme complex in mitochondria that helps convert oxygen, fats, and simple sugars to energy. Other genes associated with this disorder provide instructions for making molecules called transfer RNAs (tRNAs), which are chemical cousins of DNA. These molecules help assemble protein building blocks called amino acids into full-length, functioning proteins within mitochondria.  Mutations in a particular transfer RNA gene, MT-TL1, cause more than 80 percent of all cases of MELAS. These mutations impair the ability of mitochondria to make proteins, use oxygen, and produce energy. Researchers have not determined how changes in mtDNA lead to the specific signs and symptoms of MELAS. They continue to investigate the effects of mitochondrial gene mutations in different tissues, particularly in the brain.","mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes",0000662,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-encephalomyopathy-lactic-acidosis-and-stroke-like-episodes,C0162666,T047,Disorders
"Is mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes inherited ?",0000662-4,inheritance,"This condition is inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mtDNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children.  In most cases, people with MELAS inherit an altered mitochondrial gene from their mother. Less commonly, the disorder results from a new mutation in a mitochondrial gene and occurs in people with no family history of MELAS.","mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes",0000662,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-encephalomyopathy-lactic-acidosis-and-stroke-like-episodes,C0162666,T047,Disorders
"What are the treatments for mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes ?",0000662-5,treatment,"These resources address the diagnosis or management of MELAS:  - Gene Review: Gene Review: MELAS  - Gene Review: Gene Review: Mitochondrial Disorders Overview  - Genetic Testing Registry: Juvenile myopathy, encephalopathy, lactic acidosis AND stroke  - MedlinePlus Encyclopedia: Lactic acidosis  - MedlinePlus Encyclopedia: Stroke   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes",0000662,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-encephalomyopathy-lactic-acidosis-and-stroke-like-episodes,C0162666,T047,Disorders
What is (are) mitochondrial membrane protein-associated neurodegeneration ?,0000663-1,information,"Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a disorder of the nervous system. The condition typically begins in childhood or early adulthood and worsens (progresses) over time.  MPAN commonly begins with difficulty walking. As the condition progresses, affected individuals usually develop other movement problems, including muscle stiffness (spasticity) and involuntary muscle cramping (dystonia). Many people with MPAN have a pattern of movement abnormalities known as parkinsonism. These abnormalities include unusually slow movement (bradykinesia), muscle rigidity, involuntary trembling (tremors), and an inability to hold the body upright and balanced (postural instability).  Other neurological problems that occur in individuals with MPAN include degeneration of the nerve cells that carry visual information from the eyes to the brain (optic atrophy), which can impair vision; problems with speech (dysarthria); difficulty swallowing (dysphagia); and, in later stages of the condition, an inability to control the bowels or the flow of urine (incontinence). Additionally, affected individuals may experience a loss of intellectual function (dementia) and psychiatric symptoms such as behavioral problems, mood swings, hyperactivity, and depression.  MPAN is characterized by an abnormal buildup of iron in certain regions of the brain. Because of these deposits, MPAN is considered part of a group of conditions known as neurodegeneration with brain iron accumulation (NBIA).",mitochondrial membrane protein-associated neurodegeneration,0000663,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-membrane-protein-associated-neurodegeneration,C0027746,T049,Disorders
How many people are affected by mitochondrial membrane protein-associated neurodegeneration ?,0000663-2,frequency,MPAN is a rare condition that is estimated to affect less than 1 in 1 million people.,mitochondrial membrane protein-associated neurodegeneration,0000663,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-membrane-protein-associated-neurodegeneration,C0027746,T049,Disorders
What are the genetic changes related to mitochondrial membrane protein-associated neurodegeneration ?,0000663-3,genetic changes,"Mutations in the C19orf12 gene cause MPAN. The protein produced from this gene is found in the membrane of cellular structures called mitochondria, which are the energy-producing centers of the cell. Although its function is unknown, researchers suggest that the C19orf12 protein plays a role in the maintenance of fat (lipid) molecules, a process known as lipid homeostasis.  The gene mutations that cause this condition lead to an altered C19orf12 protein that likely has little or no function. It is unclear how these genetic changes lead to the neurological problems associated with MPAN. Researchers are working to determine whether there is a link between problems with lipid homeostasis and brain iron accumulation and how these abnormalities might contribute to the features of this disorder.",mitochondrial membrane protein-associated neurodegeneration,0000663,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-membrane-protein-associated-neurodegeneration,C0027746,T049,Disorders
Is mitochondrial membrane protein-associated neurodegeneration inherited ?,0000663-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",mitochondrial membrane protein-associated neurodegeneration,0000663,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-membrane-protein-associated-neurodegeneration,C0027746,T049,Disorders
What are the treatments for mitochondrial membrane protein-associated neurodegeneration ?,0000663-5,treatment,These resources address the diagnosis or management of mitochondrial membrane protein-associated neurodegeneration:  - Gene Review: Gene Review: Mitochondrial Membrane Protein-Associated Neurodegeneration  - Gene Review: Gene Review: Neurodegeneration with Brain Iron Accumulation Disorders Overview  - Genetic Testing Registry: Neurodegeneration with brain iron accumulation 4  - Spastic Paraplegia Foundation: Treatments and Therapies   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,mitochondrial membrane protein-associated neurodegeneration,0000663,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-membrane-protein-associated-neurodegeneration,C0027746,T049,Disorders
What is (are) mitochondrial neurogastrointestinal encephalopathy disease ?,0000664-1,information,"Mitochondrial neurogastrointestinal encephalopathy (MNGIE) disease is a condition that affects several parts of the body, particularly the digestive system and nervous system. The major features of MNGIE disease can appear anytime from infancy to adulthood, but signs and symptoms most often begin by age 20. The medical problems associated with this disorder worsen with time.  Abnormalities of the digestive system are among the most common and severe features of MNGIE disease. Almost all affected people have a condition known as gastrointestinal dysmotility, in which the muscles and nerves of the digestive system do not move food through the digestive tract efficiently. The resulting digestive problems include feelings of fullness (satiety) after eating only a small amount, trouble swallowing (dysphagia), nausea and vomiting after eating, episodes of abdominal pain, diarrhea, and intestinal blockage. These gastrointestinal problems lead to extreme weight loss and reduced muscle mass (cachexia).  MNGIE disease is also characterized by abnormalities of the nervous system, although these tend to be milder than the gastrointestinal problems. Affected individuals experience tingling, numbness, and weakness in their limbs (peripheral neuropathy), particularly in the hands and feet. Additional neurological signs and symptoms can include droopy eyelids (ptosis), weakness of the muscles that control eye movement (ophthalmoplegia), and hearing loss. Leukoencephalopathy, which is the deterioration of a type of brain tissue known as white matter, is a hallmark of MNGIE disease. These changes in the brain can be seen with magnetic resonance imaging (MRI), though they usually do not cause symptoms in people with this disorder.",mitochondrial neurogastrointestinal encephalopathy disease,0000664,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-neurogastrointestinal-encephalopathy-disease,C0085584,T047,Disorders
How many people are affected by mitochondrial neurogastrointestinal encephalopathy disease ?,0000664-2,frequency,The prevalence of MNGIE disease is unknown. About 70 people with this disorder have been reported.,mitochondrial neurogastrointestinal encephalopathy disease,0000664,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-neurogastrointestinal-encephalopathy-disease,C0085584,T047,Disorders
What are the genetic changes related to mitochondrial neurogastrointestinal encephalopathy disease ?,0000664-3,genetic changes,"Mutations in the TYMP gene (previously known as ECGF1) cause MNGIE disease. This gene provides instructions for making an enzyme called thymidine phosphorylase. Thymidine is a molecule known as a nucleoside, which (after a chemical modification) is used as a building block of DNA. Thymidine phosphorylase breaks down thymidine into smaller molecules, which helps regulate the level of nucleosides in cells.  TYMP mutations greatly reduce or eliminate the activity of thymidine phosphorylase. A shortage of this enzyme allows thymidine to build up to very high levels in the body. Researchers believe that an excess of this molecule is damaging to a particular kind of DNA known as mitochondrial DNA or mtDNA. Mitochondria are structures within cells that convert the energy from food into a form that cells can use. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA.  Mitochondria use nucleosides, including thymidine, to build new molecules of mtDNA as needed. A loss of thymidine phosphorylase activity and the resulting buildup of thymidine disrupt the usual maintenance and repair of mtDNA. As a result, mutations can accumulate in mtDNA, causing it to become unstable. Additionally, mitochondria may have less mtDNA than usual (mtDNA depletion). These genetic changes impair the normal function of mitochondria. Although mtDNA abnormalities underlie the digestive and neurological problems characteristic of MNGIE disease, it is unclear how defective mitochondria cause the specific features of the disorder.",mitochondrial neurogastrointestinal encephalopathy disease,0000664,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-neurogastrointestinal-encephalopathy-disease,C0085584,T047,Disorders
Is mitochondrial neurogastrointestinal encephalopathy disease inherited ?,0000664-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the TYMP gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",mitochondrial neurogastrointestinal encephalopathy disease,0000664,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-neurogastrointestinal-encephalopathy-disease,C0085584,T047,Disorders
What are the treatments for mitochondrial neurogastrointestinal encephalopathy disease ?,0000664-5,treatment,These resources address the diagnosis or management of MNGIE disease:  - Gene Review: Gene Review: Mitochondrial Neurogastrointestinal Encephalopathy Disease  - Genetic Testing Registry: Myoneural gastrointestinal encephalopathy syndrome  - MedlinePlus Encyclopedia: Leukoencephalopathy (image)   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,mitochondrial neurogastrointestinal encephalopathy disease,0000664,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-neurogastrointestinal-encephalopathy-disease,C0085584,T047,Disorders
What is (are) mitochondrial trifunctional protein deficiency ?,0000665-1,information,"Mitochondrial trifunctional protein deficiency is a rare condition that prevents the body from converting certain fats to energy, particularly during periods without food (fasting).  Signs and symptoms of mitochondrial trifunctional protein deficiency may begin during infancy or later in life. Features that occur during infancy include feeding difficulties, lack of energy (lethargy), low blood sugar (hypoglycemia), weak muscle tone (hypotonia), and liver problems. Infants with this disorder are also at high risk for serious heart problems, breathing difficulties, coma, and sudden death. Signs and symptoms of mitochondrial trifunctional protein deficiency that may begin after infancy include hypotonia, muscle pain, a breakdown of muscle tissue, and a loss of sensation in the extremities (peripheral neuropathy).  Problems related to mitochondrial trifunctional protein deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.",mitochondrial trifunctional protein deficiency,0000665,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-trifunctional-protein-deficiency,C1969443,T047,Disorders
How many people are affected by mitochondrial trifunctional protein deficiency ?,0000665-2,frequency,Mitochondrial trifunctional protein deficiency is a rare disorder; its incidence is unknown.,mitochondrial trifunctional protein deficiency,0000665,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-trifunctional-protein-deficiency,C1969443,T047,Disorders
What are the genetic changes related to mitochondrial trifunctional protein deficiency ?,0000665-3,genetic changes,"Mutations in the HADHA and HADHB genes cause mitochondrial trifunctional protein deficiency. These genes each provide instructions for making part of an enzyme complex called mitochondrial trifunctional protein. This enzyme complex functions in mitochondria, the energy-producing centers within cells. As the name suggests, mitochondrial trifunctional protein contains three enzymes that each perform a different function. This enzyme complex is required to break down (metabolize) a group of fats called long-chain fatty acids. Long-chain fatty acids are found in foods such as milk and certain oils. These fatty acids are stored in the body's fat tissues. Fatty acids are a major source of energy for the heart and muscles. During periods of fasting, fatty acids are also an important energy source for the liver and other tissues.  Mutations in the HADHA or HADHB genes that cause mitochondrial trifunctional protein deficiency disrupt all three functions of this enzyme complex. Without enough of this enzyme complex, long-chain fatty acids from food and body fat cannot be metabolized and processed. As a result, these fatty acids are not converted to energy, which can lead to some features of this disorder, such as lethargy and hypoglycemia. Long-chain fatty acids or partially metabolized fatty acids may also build up and damage the liver, heart, and muscles. This abnormal buildup causes the other signs and symptoms of mitochondrial trifunctional protein deficiency.",mitochondrial trifunctional protein deficiency,0000665,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-trifunctional-protein-deficiency,C1969443,T047,Disorders
Is mitochondrial trifunctional protein deficiency inherited ?,0000665-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",mitochondrial trifunctional protein deficiency,0000665,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-trifunctional-protein-deficiency,C1969443,T047,Disorders
What are the treatments for mitochondrial trifunctional protein deficiency ?,0000665-5,treatment,These resources address the diagnosis or management of mitochondrial trifunctional protein deficiency:  - Baby's First Test  - Genetic Testing Registry: Mitochondrial trifunctional protein deficiency  - MedlinePlus Encyclopedia: Hypoglycemia  - MedlinePlus Encyclopedia: Peripheral Neuropathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,mitochondrial trifunctional protein deficiency,0000665,GHR,https://ghr.nlm.nih.gov/condition/mitochondrial-trifunctional-protein-deficiency,C1969443,T047,Disorders
What is (are) Miyoshi myopathy ?,0000666-1,information,"Miyoshi myopathy is a muscle disorder that primarily affects muscles away from the center of the body (distal muscles), such as those in the legs. During early to mid-adulthood, affected individuals typically begin to experience muscle weakness and wasting (atrophy) in one or both calves. If only one leg is affected, the calves appear different in size (asymmetrical). Calf weakness can make it difficult to stand on tiptoe.  As Miyoshi myopathy slowly progresses, the muscle weakness and atrophy spread up the leg to the muscles in the thigh and buttock. Eventually, affected individuals may have difficulty climbing stairs or walking for an extended period of time. Some people with Miyoshi myopathy may eventually need wheelchair assistance.  Rarely, the upper arm or shoulder muscles are mildly affected in Miyoshi myopathy. In a few cases, abnormal heart rhythms (arrhythmias) have developed. Individuals with Miyoshi myopathy have highly elevated levels of an enzyme called creatine kinase (CK) in their blood, which often indicates muscle disease.",Miyoshi myopathy,0000666,GHR,https://ghr.nlm.nih.gov/condition/miyoshi-myopathy,C1850808,T047,Disorders
How many people are affected by Miyoshi myopathy ?,0000666-2,frequency,"The exact prevalence of Miyoshi myopathy is unknown. In Japan, where the condition was first described, it is estimated to affect 1 in 440,000 individuals.",Miyoshi myopathy,0000666,GHR,https://ghr.nlm.nih.gov/condition/miyoshi-myopathy,C1850808,T047,Disorders
What are the genetic changes related to Miyoshi myopathy ?,0000666-3,genetic changes,"Miyoshi myopathy is caused by mutations in the DYSF or ANO5 gene. When this condition is caused by ANO5 gene mutations it is sometimes referred to as distal anoctaminopathy. The DYSF and ANO5 genes provide instructions for making proteins primarily found in muscles that are used for movement (skeletal muscles). The protein produced from the DYSF gene, called dysferlin, is found in the thin membrane called the sarcolemma that surrounds muscle fibers. Dysferlin is thought to aid in repairing the sarcolemma when it becomes damaged or torn due to muscle strain.  The ANO5 gene provides instructions for making a protein called anoctamin-5. This protein is located within the membrane of a cell structure called the endoplasmic reticulum, which is involved in protein production, processing, and transport. Anoctamin-5 is thought to act as a channel, allowing charged chlorine atoms (chloride ions) to flow in and out of the endoplasmic reticulum. The regulation of chloride flow within muscle cells plays a role in controlling muscle tensing (contraction) and relaxation.  DYSF or ANO5 gene mutations often result in a decrease or elimination of the corresponding protein. A lack of dysferlin leads to a reduced ability to repair damage done to the sarcolemma of muscle fibers. As a result, damage accumulates and leads to atrophy of the muscle fiber. It is unclear why this damage leads to the specific pattern of weakness and atrophy that is characteristic of Miyoshi myopathy. The effects of the loss of anoctamin-5 are also unclear. While chloride is necessary for normal muscle function, it is unknown how a lack of this chloride channel causes the signs and symptoms of Miyoshi myopathy.",Miyoshi myopathy,0000666,GHR,https://ghr.nlm.nih.gov/condition/miyoshi-myopathy,C1850808,T047,Disorders
Is Miyoshi myopathy inherited ?,0000666-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Miyoshi myopathy,0000666,GHR,https://ghr.nlm.nih.gov/condition/miyoshi-myopathy,C1850808,T047,Disorders
What are the treatments for Miyoshi myopathy ?,0000666-5,treatment,These resources address the diagnosis or management of Miyoshi myopathy:  - Gene Review: Gene Review: ANO5-Related Muscle Diseases  - Gene Review: Gene Review: Dysferlinopathy  - Genetic Testing Registry: Miyoshi muscular dystrophy 1  - Genetic Testing Registry: Miyoshi muscular dystrophy 3   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Miyoshi myopathy,0000666,GHR,https://ghr.nlm.nih.gov/condition/miyoshi-myopathy,C1850808,T047,Disorders
What is (are) Moebius syndrome ?,0000667-1,information,"Moebius syndrome is a rare neurological condition that primarily affects the muscles that control facial expression and eye movement. The signs and symptoms of this condition are present from birth.  Weakness or paralysis of the facial muscles is one of the most common features of Moebius syndrome. Affected individuals lack facial expressions; they cannot smile, frown, or raise their eyebrows. The muscle weakness also causes problems with feeding that become apparent in early infancy.  Many people with Moebius syndrome are born with a small chin (micrognathia) and a small mouth (microstomia) with a short or unusually shaped tongue. The roof of the mouth may have an abnormal opening (cleft palate) or be high and arched. These abnormalities contribute to problems with speech, which occur in many children with Moebius syndrome. Dental abnormalities, including missing and misaligned teeth, are also common.  Moebius syndrome also affects muscles that control back-and-forth eye movement. Affected individuals must move their head from side to side to read or follow the movement of objects. People with this disorder have difficulty making eye contact, and their eyes may not look in the same direction (strabismus). Additionally, the eyelids may not close completely when blinking or sleeping, which can result in dry or irritated eyes.  Other features of Moebius syndrome can include bone abnormalities in the hands and feet, weak muscle tone (hypotonia), and hearing loss. Affected children often experience delayed development of motor skills (such as crawling and walking), although most eventually acquire these skills.  Some research studies have suggested that children with Moebius syndrome are more likely than unaffected children to have characteristics of autism spectrum disorders, which are a group of conditions characterized by impaired communication and social interaction. However, recent studies have questioned this association. Because people with Moebius syndrome have difficulty with eye contact and speech due to their physical differences, autism spectrum disorders can be difficult to diagnose in these individuals. Moebius syndrome may also be associated with a somewhat increased risk of intellectual disability; however, most affected individuals have normal intelligence.",Moebius syndrome,0000667,GHR,https://ghr.nlm.nih.gov/condition/moebius-syndrome,C0221060,T019,Disorders
How many people are affected by Moebius syndrome ?,0000667-2,frequency,"The exact incidence of Moebius syndrome is unknown. Researchers estimate that the condition affects 1 in 50,000 to 1 in 500,000 newborns.",Moebius syndrome,0000667,GHR,https://ghr.nlm.nih.gov/condition/moebius-syndrome,C0221060,T019,Disorders
What are the genetic changes related to Moebius syndrome ?,0000667-3,genetic changes,"The causes of Moebius syndrome are unknown, although the condition probably results from a combination of environmental and genetic factors. Researchers are working to identify and describe specific genes related to this condition. The disorder appears to be associated with changes in particular regions of chromosomes 3, 10, or 13 in some families. Certain medications taken during pregnancy and abuse of drugs such as cocaine may also be risk factors for Moebius syndrome.  Many of the signs and symptoms of Moebius syndrome result from the absence or underdevelopment of cranial nerves VI and VII. These nerves, which emerge from the brainstem at the back of the brain, control back-and-forth eye movement and facial expressions. The disorder can also affect other cranial nerves that are important for speech, chewing, and swallowing. Abnormal development of cranial nerves leads to the facial muscle weakness or paralysis that is characteristic of Moebius syndrome.  Researchers speculate that Moebius syndrome may result from changes in blood flow to the brainstem during early stages of embryonic development. However, it is unclear what causes these changes to occur and why they specifically disrupt the development of cranial nerves VI and VII. Even less is known about the causes of some other signs and symptoms of this condition, including hand and foot abnormalities.",Moebius syndrome,0000667,GHR,https://ghr.nlm.nih.gov/condition/moebius-syndrome,C0221060,T019,Disorders
Is Moebius syndrome inherited ?,0000667-4,inheritance,"Most cases of Moebius syndrome are sporadic, which means they occur in people with no history of the disorder in their family. A small percentage of all cases have been reported to run in families; however, the condition does not have a single clear pattern of inheritance.",Moebius syndrome,0000667,GHR,https://ghr.nlm.nih.gov/condition/moebius-syndrome,C0221060,T019,Disorders
What are the treatments for Moebius syndrome ?,0000667-5,treatment,These resources address the diagnosis or management of Moebius syndrome:  - Boston Children's Hospital  - Cleveland Clinic  - Genetic Testing Registry: Oromandibular-limb hypogenesis spectrum  - Swedish Information Centre for Rare Diseases: Diagnosis and Treatment   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Moebius syndrome,0000667,GHR,https://ghr.nlm.nih.gov/condition/moebius-syndrome,C0221060,T019,Disorders
What is (are) molybdenum cofactor deficiency ?,0000668-1,information,"Molybdenum cofactor deficiency is a rare condition characterized by brain dysfunction (encephalopathy) that worsens over time. Babies with this condition appear normal at birth, but within a week they have difficulty feeding and develop seizures that do not improve with treatment (intractable seizures). Brain abnormalities, including deterioration (atrophy) of brain tissue, lead to severe developmental delay; affected individuals usually do not learn to sit unassisted or to speak. A small percentage of affected individuals have an exaggerated startle reaction (hyperekplexia) to unexpected stimuli such as loud noises. Other features of molybdenum cofactor deficiency can include a small head size (microcephaly) and facial features that are described as ""coarse.""  Tests reveal that affected individuals have high levels of chemicals called sulfite, S-sulfocysteine, xanthine, and hypoxanthine in the urine and low levels of a chemical called uric acid in the blood.  Because of the serious health problems caused by molybdenum cofactor deficiency, affected individuals usually do not survive past early childhood.",molybdenum cofactor deficiency,0000668,GHR,https://ghr.nlm.nih.gov/condition/molybdenum-cofactor-deficiency,C0268119,T047,Disorders
How many people are affected by molybdenum cofactor deficiency ?,0000668-2,frequency,"Molybdenum cofactor deficiency is a rare condition that is estimated to occur in 1 in 100,000 to 200,000 newborns worldwide. More than 100 cases have been reported in the medical literature, although it is thought that the condition is underdiagnosed, so the number of affected individuals may be higher.",molybdenum cofactor deficiency,0000668,GHR,https://ghr.nlm.nih.gov/condition/molybdenum-cofactor-deficiency,C0268119,T047,Disorders
What are the genetic changes related to molybdenum cofactor deficiency ?,0000668-3,genetic changes,"Molybdenum cofactor deficiency is caused by mutations in the MOCS1, MOCS2, or GPHN gene. There are three forms of the disorder, named types A, B, and C (or complementation groups A, B, and C). The forms have the same signs and symptoms but are distinguished by their genetic cause: MOCS1 gene mutations cause type A, MOCS2 gene mutations cause type B, and GPHN gene mutations cause type C. The proteins produced from each of these genes are involved in the formation (biosynthesis) of a molecule called molybdenum cofactor. Molybdenum cofactor, which contains the element molybdenum, is essential to the function of several enzymes. These enzymes help break down (metabolize) different substances in the body, some of which are toxic if not metabolized.  Mutations in the MOCS1, MOCS2, or GPHN gene reduce or eliminate the function of the associated protein, which impairs molybdenum cofactor biosynthesis. Without the cofactor, the metabolic enzymes that rely on it cannot function.  The resulting loss of enzyme activity leads to buildup of certain chemicals, including sulfite, S-sulfocysteine, xanthine, and hypoxanthine (which can be identified in urine), and low levels of uric acid in the blood. Sulfite, which is normally broken down by one of the molybdenum cofactor-dependent enzymes, is toxic, especially to the brain. Researchers suggest that damage caused by the abnormally high levels of sulfite (and possibly other chemicals) leads to encephalopathy, seizures, and the other features of molybdenum cofactor deficiency.",molybdenum cofactor deficiency,0000668,GHR,https://ghr.nlm.nih.gov/condition/molybdenum-cofactor-deficiency,C0268119,T047,Disorders
Is molybdenum cofactor deficiency inherited ?,0000668-4,inheritance,"Molybdenum cofactor deficiency has an autosomal recessive pattern of inheritance, which means both copies of the gene in each cell have mutations. An affected individual usually inherits one altered copy of the gene from each parent. Parents of an individual with an autosomal recessive condition typically do not show signs and symptoms of the condition.  At least one individual with molybdenum cofactor deficiency inherited two mutated copies of the MOCS1 gene through a mechanism called uniparental isodisomy. In this case, an error occurred during the formation of egg or sperm cells, and the child received two copies of the mutated gene from one parent instead of one copy from each parent.",molybdenum cofactor deficiency,0000668,GHR,https://ghr.nlm.nih.gov/condition/molybdenum-cofactor-deficiency,C0268119,T047,Disorders
What are the treatments for molybdenum cofactor deficiency ?,0000668-5,treatment,"These resources address the diagnosis or management of molybdenum cofactor deficiency:  - Genetic Testing Registry: Combined molybdoflavoprotein enzyme deficiency  - Genetic Testing Registry: Molybdenum cofactor deficiency, complementation group A  - Genetic Testing Registry: Molybdenum cofactor deficiency, complementation group B  - Genetic Testing Registry: Molybdenum cofactor deficiency, complementation group C   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",molybdenum cofactor deficiency,0000668,GHR,https://ghr.nlm.nih.gov/condition/molybdenum-cofactor-deficiency,C0268119,T047,Disorders
What is (are) monilethrix ?,0000669-1,information,"Monilethrix is a condition that affects hair growth. Its most characteristic feature is that individual strands of hair have a beaded appearance like the beads of a necklace. The name monilethrix comes from the Latin word for necklace (monile) and the Greek word for hair (thrix). Noticeable when viewed under a microscope, the beaded appearance is due to periodic narrowing of the hair shaft. People with monilethrix also have sparse hair growth (hypotrichosis) and short, brittle hair that breaks easily.  Affected individuals usually have normal hair at birth, but the hair abnormalities develop within the first few months of life. In mild cases of monilethrix, only hair on the back of the head (occiput) or nape of the neck is affected. In more severe cases, hair over the whole scalp can be affected, as well as pubic hair, underarm hair, eyebrows, eyelashes, or hair on the arms and legs.  Occasionally, the skin and nails are involved in monilethrix. Some affected individuals have a skin condition called keratosis pilaris, which causes small bumps on the skin, especially on the scalp, neck, and arms. Affected individuals may also have abnormal fingernails or toenails.",monilethrix,0000669,GHR,https://ghr.nlm.nih.gov/condition/monilethrix,C0546966,T019,Disorders
How many people are affected by monilethrix ?,0000669-2,frequency,The prevalence of monilethrix is unknown.,monilethrix,0000669,GHR,https://ghr.nlm.nih.gov/condition/monilethrix,C0546966,T019,Disorders
What are the genetic changes related to monilethrix ?,0000669-3,genetic changes,"Monilethrix is caused by mutations in one of several genes. Mutations in the KRT81 gene, the KRT83 gene, the KRT86 gene, or the DSG4 gene account for most cases of monilethrix. These genes provide instructions for making proteins that give structure and strength to strands of hair.  Hair growth occurs in the hair follicle, a specialized structure in the skin. As the cells of the hair follicle mature to take on specialized functions (differentiate), they produce particular proteins and form the different compartments of the hair follicle and the hair shaft. As the cells in the hair follicle divide, the hair shaft is pushed upward and extends beyond the skin.  The KRT81, KRT83, and KRT86 genes provide instructions for making proteins known as keratins. Keratins are a group of tough, fibrous proteins that form the structural framework of cells that make up the hair, skin, and nails. The KRT81 gene provides instructions for making the type II hair keratin K81 protein (K81); the KRT83 gene provides instruction for making the type II hair keratin K83 protein (K83); and the KRT86 gene provides instructions for making the type II hair keratin K86 protein (K86). The K81, K83, and K86 proteins are found in cells of the inner compartment of the hair shaft known as the cortex. These proteins give hair its strength and elasticity.  The DSG4 gene provides instructions for making a protein called desmoglein 4 (DSG4). This protein is found in specialized structures called desmosomes that are located in the membrane surrounding certain cells. These structures help attach cells to one another and play a role in communication between cells. The DSG4 protein is found in particular regions of the hair follicle, including the hair shaft cortex. Desmosomes in these regions provide strength to the hair and are thought to play a role in communicating the signals for cells to differentiate to form the hair shaft.  In people with monilethrix, the cortex of the affected hair shaft appears abnormal. However, it is unclear how mutations in the KRT81, KRT83, KRT86, or DSG4 genes are related to the abnormality in the cortex or the beaded appearance of the hair.  Some people with monilethrix do not have a mutation in one of these genes. These individuals may have a genetic change in another gene, or the cause of the condition may be unknown.",monilethrix,0000669,GHR,https://ghr.nlm.nih.gov/condition/monilethrix,C0546966,T019,Disorders
Is monilethrix inherited ?,0000669-4,inheritance,"Monilethrix can have multiple patterns of inheritance. When the condition is caused by a mutation in one of the keratin genes, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In rare cases, the condition results from a new mutation in the gene and is not inherited.  When the condition is caused by mutations in the DSG4 gene, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",monilethrix,0000669,GHR,https://ghr.nlm.nih.gov/condition/monilethrix,C0546966,T019,Disorders
What are the treatments for monilethrix ?,0000669-5,treatment,These resources address the diagnosis or management of monilethrix:  - Genetic Testing Registry: Beaded hair   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,monilethrix,0000669,GHR,https://ghr.nlm.nih.gov/condition/monilethrix,C0546966,T019,Disorders
What is (are) Mowat-Wilson syndrome ?,0000670-1,information,"Mowat-Wilson syndrome is a genetic condition that affects many parts of the body. Major signs of this disorder frequently include distinctive facial features, intellectual disability, delayed development, an intestinal disorder called Hirschsprung disease, and other birth defects.  Children with Mowat-Wilson syndrome have a square-shaped face with deep-set, widely spaced eyes. They also have a broad nasal bridge with a rounded nasal tip; a prominent and pointed chin; large, flaring eyebrows; and uplifted earlobes with a dimple in the middle. These facial features become more distinctive with age, and adults with Mowat-Wilson syndrome have an elongated face with heavy eyebrows and a pronounced chin and jaw. Affected people tend to have a smiling, open-mouthed expression, and they typically have friendly and happy personalities.  Mowat-Wilson syndrome is often associated with an unusually small head (microcephaly), structural brain abnormalities, and intellectual disability ranging from moderate to severe. Speech is absent or severely impaired, and affected people may learn to speak only a few words. Many people with this condition can understand others' speech, however, and some use sign language to communicate. If speech develops, it is delayed until mid-childhood or later. Children with Mowat-Wilson syndrome also have delayed development of motor skills such as sitting, standing, and walking.  More than half of people with Mowat-Wilson syndrome are born with an intestinal disorder called Hirschsprung disease that causes severe constipation, intestinal blockage, and enlargement of the colon. Chronic constipation also occurs frequently in people with Mowat-Wilson syndrome who have not been diagnosed with Hirschsprung disease.  Other features of Mowat-Wilson syndrome include short stature, seizures, heart defects, and abnormalities of the urinary tract and genitalia. Less commonly, this condition also affects the eyes, teeth, hands, and skin coloring (pigmentation). Although many different medical issues have been associated with Mowat-Wilson syndrome, not every individual with this condition has all of these features.",Mowat-Wilson syndrome,0000670,GHR,https://ghr.nlm.nih.gov/condition/mowat-wilson-syndrome,C1856113,T047,Disorders
How many people are affected by Mowat-Wilson syndrome ?,0000670-2,frequency,The prevalence of Mowat-Wilson syndrome is unknown. More than 200 people with this condition have been reported in the medical literature.,Mowat-Wilson syndrome,0000670,GHR,https://ghr.nlm.nih.gov/condition/mowat-wilson-syndrome,C1856113,T047,Disorders
What are the genetic changes related to Mowat-Wilson syndrome ?,0000670-3,genetic changes,"Mutations in the ZEB2 gene cause Mowat-Wilson syndrome. The ZEB2 gene provides instructions for making a protein that plays a critical role in the formation of many organs and tissues before birth. This protein is a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of particular genes. Researchers believe that the ZEB2 protein is involved in the development of tissues that give rise to the nervous system, digestive tract, facial features, heart, and other organs.  Mowat-Wilson syndrome almost always results from a loss of one working copy of the ZEB2 gene in each cell. In some cases, the entire gene is deleted. In other cases, mutations within the gene lead to the production of an abnormally short, nonfunctional version of the ZEB2 protein. A shortage of this protein disrupts the normal development of many organs and tissues, which causes the varied signs and symptoms of Mowat-Wilson syndrome.",Mowat-Wilson syndrome,0000670,GHR,https://ghr.nlm.nih.gov/condition/mowat-wilson-syndrome,C1856113,T047,Disorders
Is Mowat-Wilson syndrome inherited ?,0000670-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Mowat-Wilson syndrome,0000670,GHR,https://ghr.nlm.nih.gov/condition/mowat-wilson-syndrome,C1856113,T047,Disorders
What are the treatments for Mowat-Wilson syndrome ?,0000670-5,treatment,These resources address the diagnosis or management of Mowat-Wilson syndrome:  - Gene Review: Gene Review: Mowat-Wilson Syndrome  - Genetic Testing Registry: Mowat-Wilson syndrome  - MedlinePlus Encyclopedia: Hirschsprung's Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Mowat-Wilson syndrome,0000670,GHR,https://ghr.nlm.nih.gov/condition/mowat-wilson-syndrome,C1856113,T047,Disorders
What is (are) moyamoya disease ?,0000671-1,information,"Moyamoya disease is a disorder of blood vessels in the brain, specifically the internal carotid arteries and the arteries that branch from them. These vessels, which provide oxygen-rich blood to the brain, narrow over time. Narrowing of these vessels reduces blood flow in the brain. In an attempt to compensate, new networks of small, fragile blood vessels form. These networks, visualized by a particular test called an angiogram, resemble puffs of smoke, which is how the condition got its name: ""moyamoya"" is an expression meaning ""something hazy like a puff of smoke"" in Japanese.  Moyamoya disease commonly begins either around age 5 or in a person's thirties or forties. A lack of blood supply to the brain leads to several symptoms of the disorder, including temporary stroke-like episodes (transient ischemic attacks), strokes, and seizures. In addition, the fragile blood vessels that grow can develop bulges (aneurysms), or they can break open, leading to bleeding (hemorrhage) in the brain. Affected individuals may develop recurrent headaches, involuntary jerking movements (chorea), or a decline in thinking ability. The symptoms of moyamoya disease often worsen over time if the condition is not treated.  Some people have the blood vessel changes characteristic of moyamoya disease in addition to features of another disorder, such as neurofibromatosis type 1, sickle cell disease, or Graves disease. These individuals are said to have moyamoya syndrome.",moyamoya disease,0000671,GHR,https://ghr.nlm.nih.gov/condition/moyamoya-disease,C0026654,T047,Disorders
How many people are affected by moyamoya disease ?,0000671-2,frequency,"Moyamoya disease was first identified in Japan, where it is most prevalent, affecting about 5 in 100,000 individuals. The condition is also relatively common in other Asian populations. It is ten times less common in Europe. In the United States, Asian Americans are four times more commonly affected than whites. For unknown reasons, moyamoya disease occurs twice as often in females as in males.",moyamoya disease,0000671,GHR,https://ghr.nlm.nih.gov/condition/moyamoya-disease,C0026654,T047,Disorders
What are the genetic changes related to moyamoya disease ?,0000671-3,genetic changes,"The genetics of moyamoya disease are not well understood. Research suggests that the condition can be passed through families, and changes in one gene, RNF213, have been associated with the condition. Other genes that have not been identified may be involved in moyamoya disease. It is also likely that other factors (such as infection or inflammation) in combination with genetic factors play a role in the condition's development.  The RNF213 gene provides instructions for making a protein whose function is unknown. However, research suggests that the RNF213 protein is involved in the proper development of blood vessels.  Changes in the RNF213 gene involved in moyamoya disease replace single protein building blocks (amino acids) in the RNF213 protein. The effect of these changes on the function of the RNF213 protein is unknown, and researchers are unsure how the changes contribute to the narrowing of blood vessels or the characteristic blood vessel growth of moyamoya disease. For unknown reasons, people with moyamoya disease have elevated levels of proteins involved in cell and tissue growth, including the growth of blood vessels (angiogenesis). An excess of these proteins could account for the growth of new blood vessels characteristic of moyamoya disease. It is not clear if changes in the RNF213 gene are involved in the overproduction of these proteins.",moyamoya disease,0000671,GHR,https://ghr.nlm.nih.gov/condition/moyamoya-disease,C0026654,T047,Disorders
Is moyamoya disease inherited ?,0000671-4,inheritance,"Up to 15 percent of Japanese people with moyamoya disease have one or more family members with the condition, indicating that the condition can be passed through generations in families; however, the inheritance pattern is unknown. Research suggests that the condition follows an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. However, some people who have a copy of the altered gene never develop the condition, which is a situation known as reduced penetrance.",moyamoya disease,0000671,GHR,https://ghr.nlm.nih.gov/condition/moyamoya-disease,C0026654,T047,Disorders
What are the treatments for moyamoya disease ?,0000671-5,treatment,These resources address the diagnosis or management of moyamoya disease:  - Barrow Neurological Institute: What Medical Therapies Are Used To Treat Moyamoya Disease?  - Boston Children's Hospital: Learn More About Treatment for Moyamoya Disease  - Genetic Testing Registry: Moyamoya disease  - Genetic Testing Registry: Moyamoya disease 2  - Genetic Testing Registry: Moyamoya disease 3  - Genetic Testing Registry: Moyamoya disease 5  - National Institute of Neurological Disorders and Stroke: Moyamoya Disease Information Page   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,moyamoya disease,0000671,GHR,https://ghr.nlm.nih.gov/condition/moyamoya-disease,C0026654,T047,Disorders
What is (are) MPV17-related hepatocerebral mitochondrial DNA depletion syndrome ?,0000672-1,information,"MPV17-related hepatocerebral mitochondrial DNA depletion syndrome is an inherited disorder that can cause liver disease and neurological problems. The signs and symptoms of this condition begin in infancy and typically include vomiting, diarrhea, and an inability to grow or gain weight at the expected rate (failure to thrive). Many affected infants have a buildup of a chemical called lactic acid in the body (lactic acidosis) and low blood sugar (hypoglycemia). Within the first weeks of life, infants develop liver disease that quickly progresses to liver failure. The liver is frequently enlarged (hepatomegaly) and liver cells often have a reduced ability to release a digestive fluid called bile (cholestasis). Rarely, affected children develop liver cancer. After the onset of liver disease, many affected infants develop neurological problems, which can include developmental delay, weak muscle tone (hypotonia), and reduced sensation in the limbs (peripheral neuropathy). Individuals with MPV17-related hepatocerebral mitochondrial DNA depletion syndrome typically survive only into infancy or early childhood.  MPV17-related hepatocerebral mitochondrial DNA depletion syndrome is most frequently seen in the Navajo population of the southwestern United States. In this population, the condition is known as Navajo neurohepatopathy. People with Navajo neurohepatopathy tend to have a longer life expectancy than those with MPV17-related hepatocerebral mitochondrial DNA depletion syndrome. In addition to the signs and symptoms described above, people with Navajo neurohepatopathy may have problems with sensing pain that can lead to painless bone fractures and self-mutilation of the fingers or toes. Individuals with Navajo neurohepatopathy may lack feeling in the clear front covering of the eye (corneal anesthesia), which can lead to open sores and scarring on the cornea, resulting in impaired vision. The cause of these additional features is unknown.",MPV17-related hepatocerebral mitochondrial DNA depletion syndrome,0000672,GHR,https://ghr.nlm.nih.gov/condition/mpv17-related-hepatocerebral-mitochondrial-dna-depletion-syndrome,C0342782,T047,Disorders
How many people are affected by MPV17-related hepatocerebral mitochondrial DNA depletion syndrome ?,0000672-2,frequency,"MPV17-related hepatocerebral mitochondrial DNA depletion syndrome is thought to be a rare condition. Approximately 30 cases have been described in the scientific literature, including seven families with Navajo neurohepatopathy. Within the Navajo Nation of the southwestern United States, Navajo neurohepatopathy is estimated to occur in 1 in 1,600 newborns.",MPV17-related hepatocerebral mitochondrial DNA depletion syndrome,0000672,GHR,https://ghr.nlm.nih.gov/condition/mpv17-related-hepatocerebral-mitochondrial-dna-depletion-syndrome,C0342782,T047,Disorders
What are the genetic changes related to MPV17-related hepatocerebral mitochondrial DNA depletion syndrome ?,0000672-3,genetic changes,"As the condition name suggests, mutations in the MPV17 gene cause MPV17-related hepatocerebral mitochondrial DNA depletion syndrome. The protein produced from the MPV17 gene is located in the inner membrane of cell structures called mitochondria. Mitochondria are involved in a wide variety of cellular activities, including energy production, chemical signaling, and regulation of cell growth, division, and death. Mitochondria contain their own DNA, known as mitochondrial DNA (mtDNA), which is essential for the normal function of these structures. It is likely that the MPV17 protein is involved in the maintenance of mtDNA. Having an adequate amount of mtDNA is essential for normal energy production within cells.  MPV17 gene mutations that cause MPV17-related hepatocerebral mitochondrial DNA depletion syndrome lead to production of a protein with impaired function. One mutation causes all cases of Navajo neurohepatopathy and results in the production of an unstable MPV17 protein that is quickly broken down. A dysfunctional or absent MPV17 protein leads to problems with the maintenance of mtDNA, which can cause a reduction in the amount of mtDNA (known as mitochondrial DNA depletion). Mitochondrial DNA depletion impairs mitochondrial function in many of the body's cells and tissues, particularly the brain, liver, and other tissues that have high energy requirements. Reduced mitochondrial function in the liver and brain lead to the liver failure and neurological dysfunction associated with MPV17-related hepatocerebral mitochondrial DNA depletion syndrome. Researchers suggest that the less mtDNA that is available in cells, the more severe the features of Navajo neurohepatopathy.",MPV17-related hepatocerebral mitochondrial DNA depletion syndrome,0000672,GHR,https://ghr.nlm.nih.gov/condition/mpv17-related-hepatocerebral-mitochondrial-dna-depletion-syndrome,C0342782,T047,Disorders
Is MPV17-related hepatocerebral mitochondrial DNA depletion syndrome inherited ?,0000672-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",MPV17-related hepatocerebral mitochondrial DNA depletion syndrome,0000672,GHR,https://ghr.nlm.nih.gov/condition/mpv17-related-hepatocerebral-mitochondrial-dna-depletion-syndrome,C0342782,T047,Disorders
What are the treatments for MPV17-related hepatocerebral mitochondrial DNA depletion syndrome ?,0000672-5,treatment,These resources address the diagnosis or management of MPV17-related hepatocerebral mitochondrial DNA depletion syndrome:  - Gene Review: Gene Review: MPV17-Related Hepatocerebral Mitochondrial DNA Depletion Syndrome  - Genetic Testing Registry: Navajo neurohepatopathy  - The United Mitochondrial Disease Foundation: Treatments and Therapies   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,MPV17-related hepatocerebral mitochondrial DNA depletion syndrome,0000672,GHR,https://ghr.nlm.nih.gov/condition/mpv17-related-hepatocerebral-mitochondrial-dna-depletion-syndrome,C0342782,T047,Disorders
What is (are) Muckle-Wells syndrome ?,0000673-1,information,"Muckle-Wells syndrome is a disorder characterized by periodic episodes of skin rash, fever, and joint pain. Progressive hearing loss and kidney damage also occur in this disorder.  People with Muckle-Wells syndrome have recurrent ""flare-ups"" that begin during infancy or early childhood. These episodes may appear to arise spontaneously or be triggered by cold, heat, fatigue, or other stresses. Affected individuals typically develop a non-itchy rash, mild to moderate fever, painful and swollen joints, and in some cases redness in the whites of the eyes (conjunctivitis).  Hearing loss caused by progressive nerve damage (sensorineural deafness) typically becomes apparent during the teenage years. Abnormal deposits of a protein called amyloid (amyloidosis) cause progressive kidney damage in about one-third of people with Muckle-Wells syndrome; these deposits may also damage other organs. In addition, pigmented skin lesions may occur in affected individuals.",Muckle-Wells syndrome,0000673,GHR,https://ghr.nlm.nih.gov/condition/muckle-wells-syndrome,C0268390,T047,Disorders
How many people are affected by Muckle-Wells syndrome ?,0000673-2,frequency,"Muckle-Wells syndrome is a rare disorder. It has been reported in many regions of the world, but its prevalence is unknown.",Muckle-Wells syndrome,0000673,GHR,https://ghr.nlm.nih.gov/condition/muckle-wells-syndrome,C0268390,T047,Disorders
What are the genetic changes related to Muckle-Wells syndrome ?,0000673-3,genetic changes,"Mutations in the NLRP3 gene (also known as CIAS1) cause Muckle-Wells syndrome. The NLRP3 gene provides instructions for making a protein called cryopyrin.  Cryopyrin belongs to a family of proteins called nucleotide-binding domain and leucine-rich repeat containing (NLR) proteins. These proteins are involved in the immune system, helping to regulate the process of inflammation. Inflammation occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight microbial invaders and facilitate tissue repair. When this has been accomplished, the body stops (inhibits) the inflammatory response to prevent damage to its own cells and tissues.  Cryopyrin is involved in the assembly of a molecular complex called an inflammasome, which helps trigger the inflammatory process. Researchers believe that NLRP3 gene mutations that cause Muckle-Wells syndrome result in a hyperactive cryopyrin protein and an inappropriate inflammatory response. Impairment of the body's mechanisms for controlling inflammation results in the episodes of fever and damage to the body's cells and tissues seen in Muckle-Wells syndrome.",Muckle-Wells syndrome,0000673,GHR,https://ghr.nlm.nih.gov/condition/muckle-wells-syndrome,C0268390,T047,Disorders
Is Muckle-Wells syndrome inherited ?,0000673-4,inheritance,"This condition is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, the inheritance pattern is unknown.",Muckle-Wells syndrome,0000673,GHR,https://ghr.nlm.nih.gov/condition/muckle-wells-syndrome,C0268390,T047,Disorders
What are the treatments for Muckle-Wells syndrome ?,0000673-5,treatment,These resources address the diagnosis or management of Muckle-Wells syndrome:  - Genetic Testing Registry: Familial amyloid nephropathy with urticaria AND deafness   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Muckle-Wells syndrome,0000673,GHR,https://ghr.nlm.nih.gov/condition/muckle-wells-syndrome,C0268390,T047,Disorders
What is (are) mucolipidosis II alpha/beta ?,0000674-1,information,"Mucolipidosis II alpha/beta (also known as I-cell disease) is a progressively debilitating disorder that affects many parts of the body. Most affected individuals do not survive past early childhood.  At birth, children with mucolipidosis II alpha/beta are small and have weak muscle tone (hypotonia) and a weak cry. Affected individuals grow slowly after birth and usually stop growing during the second year of life. Development is delayed, particularly the development of speech and motor skills such as sitting and standing.  Children with mucolipidosis II alpha/beta typically have several bone abnormalities, many of which are present at birth. Affected individuals may have an abnormally rounded upper back (kyphosis), feet that are abnormally rotated (clubfeet), dislocated hips, unusually shaped long bones, and short hands and fingers. People with this condition also have joint deformities (contractures) that significantly affect mobility. Most children with mucolipidosis II alpha/beta do not develop the ability to walk independently. Affected individuals have dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray.  Other features of mucolipidosis II alpha/beta include a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia), heart valve abnormalities, distinctive-looking facial features that are described as ""coarse,"" and overgrowth of the gums (gingival hypertrophy). Vocal cords can stiffen, resulting in a hoarse voice. The airway is narrow, which can contribute to prolonged or recurrent respiratory infections. Affected individuals may also have recurrent ear infections, which can lead to hearing loss.",mucolipidosis II alpha/beta,0000674,GHR,https://ghr.nlm.nih.gov/condition/mucolipidosis-ii-alpha-beta,C0020725,T047,Disorders
How many people are affected by mucolipidosis II alpha/beta ?,0000674-2,frequency,"Mucolipidosis II alpha/beta is a rare disorder, although its exact prevalence is unknown. It is estimated to occur in about 1 in 100,000 to 400,000 individuals worldwide.",mucolipidosis II alpha/beta,0000674,GHR,https://ghr.nlm.nih.gov/condition/mucolipidosis-ii-alpha-beta,C0020725,T047,Disorders
What are the genetic changes related to mucolipidosis II alpha/beta ?,0000674-3,genetic changes,"Mutations in the GNPTAB gene cause mucolipidosis II alpha/beta. This gene provides instructions for making part of an enzyme called GlcNAc-1-phosphotransferase. This enzyme helps prepare certain newly made enzymes for transport to lysosomes. Lysosomes are compartments within the cell that use digestive enzymes to break down large molecules into smaller ones that can be reused by cells. GlcNAc-1-phosphotransferase is involved in the process of attaching a molecule called mannose-6-phosphate (M6P) to specific digestive enzymes. Just as luggage is tagged at the airport to direct it to the correct destination, enzymes are often ""tagged"" after they are made so they get to where they are needed in the cell. M6P acts as a tag that indicates a digestive enzyme should be transported to the lysosome.  Mutations in the GNPTAB gene that cause mucolipidosis II alpha/beta prevent the production of any functional GlcNAc-1-phosphotransferase. Without this enzyme, digestive enzymes cannot be tagged with M6P and transported to lysosomes. Instead, they end up outside the cell and have increased digestive activity. The lack of digestive enzymes within lysosomes causes large molecules to accumulate there. Conditions that cause molecules to build up inside lysosomes, including mucolipidosis II alpha/beta, are called lysosomal storage disorders. The signs and symptoms of mucolipidosis II alpha/beta are most likely caused by the lack of digestive enzymes within lysosomes and the effects these enzymes have outside the cell.  Mutations in the GNPTAB gene can also cause a similar but milder disorder called mucolipidosis III alpha/beta. Instead of preventing the production of any enzyme, these mutations reduce the activity of GlcNAc-1-phosphotransferase. Mucolipidosis III alpha/beta and mucolipidosis II alpha/beta represent two ends of a spectrum of disease severity.",mucolipidosis II alpha/beta,0000674,GHR,https://ghr.nlm.nih.gov/condition/mucolipidosis-ii-alpha-beta,C0020725,T047,Disorders
Is mucolipidosis II alpha/beta inherited ?,0000674-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",mucolipidosis II alpha/beta,0000674,GHR,https://ghr.nlm.nih.gov/condition/mucolipidosis-ii-alpha-beta,C0020725,T047,Disorders
What are the treatments for mucolipidosis II alpha/beta ?,0000674-5,treatment,These resources address the diagnosis or management of mucolipidosis II alpha/beta:  - Gene Review: Gene Review: Mucolipidosis II  - Genetic Testing Registry: I cell disease  - MedlinePlus Encyclopedia: Clubfoot  - MedlinePlus Encyclopedia: Contracture deformity  - MedlinePlus Encyclopedia: Kyphosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,mucolipidosis II alpha/beta,0000674,GHR,https://ghr.nlm.nih.gov/condition/mucolipidosis-ii-alpha-beta,C0020725,T047,Disorders
What is (are) mucolipidosis III alpha/beta ?,0000675-1,information,"Mucolipidosis III alpha/beta is a slowly progressive disorder that affects many parts of the body. Signs and symptoms of this condition typically appear around age 3.  Individuals with mucolipidosis III alpha/beta grow slowly and have short stature. They also have stiff joints and dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Many affected individuals develop low bone mineral density (osteoporosis), which weakens the bones and makes them prone to fracture. Osteoporosis and progressive joint problems also cause bone pain that becomes more severe over time in people with mucolipidosis III alpha/beta.  People with mucolipidosis III alpha/beta often have heart valve abnormalities and mild clouding of the clear covering of the eye (cornea). Their facial features become slightly thickened or ""coarse"" over time. Affected individuals may also develop frequent ear and respiratory infections. About half of people with this condition have mild intellectual disability or learning problems. Individuals with mucolipidosis III alpha/beta generally survive into adulthood, but they may have a shortened lifespan.",mucolipidosis III alpha/beta,0000675,GHR,https://ghr.nlm.nih.gov/condition/mucolipidosis-iii-alpha-beta,C0033788,T047,Disorders
How many people are affected by mucolipidosis III alpha/beta ?,0000675-2,frequency,"Mucolipidosis III alpha/beta is a rare disorder, although its exact prevalence is unknown. It is estimated to occur in about 1 in 100,000 to 400,000 individuals worldwide.",mucolipidosis III alpha/beta,0000675,GHR,https://ghr.nlm.nih.gov/condition/mucolipidosis-iii-alpha-beta,C0033788,T047,Disorders
What are the genetic changes related to mucolipidosis III alpha/beta ?,0000675-3,genetic changes,"Mutations in the GNPTAB gene cause mucolipidosis III alpha/beta. This gene provides instructions for making a part (subunit) of an enzyme called GlcNAc-1-phosphotransferase. This enzyme helps prepare certain newly made enzymes for transport to lysosomes. Lysosomes are compartments within the cell that use digestive enzymes to break down large molecules into smaller ones that can be reused by cells. GlcNAc-1-phosphotransferase is involved in the process of attaching a molecule called mannose-6-phosphate (M6P) to specific digestive enzymes. Just as luggage is tagged at the airport to direct it to the correct destination, enzymes are often ""tagged"" after they are made so they get to where they are needed in the cell. M6P acts as a tag that indicates a digestive enzyme should be transported to the lysosome.  Mutations in the GNPTAB gene that cause mucolipidosis III alpha/beta result in reduced activity of GlcNAc-1-phosphotransferase. These mutations disrupt the tagging of digestive enzymes with M6P, which prevents many enzymes from reaching the lysosomes. Digestive enzymes that do not receive the M6P tag end up outside the cell, where they have increased activity. The shortage of digestive enzymes within lysosomes causes large molecules to accumulate there. Conditions that cause molecules to build up inside lysosomes, including mucolipidosis III alpha/beta, are called lysosomal storage disorders. The signs and symptoms of mucolipidosis III alpha/beta are most likely due to the shortage of digestive enzymes inside lysosomes and the effects these enzymes have outside the cell.  Mutations in the GNPTAB gene can also cause a similar but more severe disorder called mucolipidosis II alpha/beta. These mutations completely eliminate the function of GlcNAc-1-phosphotransferase. Mucolipidosis III alpha/beta and mucolipidosis II alpha/beta represent two ends of a spectrum of disease severity.",mucolipidosis III alpha/beta,0000675,GHR,https://ghr.nlm.nih.gov/condition/mucolipidosis-iii-alpha-beta,C0033788,T047,Disorders
Is mucolipidosis III alpha/beta inherited ?,0000675-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",mucolipidosis III alpha/beta,0000675,GHR,https://ghr.nlm.nih.gov/condition/mucolipidosis-iii-alpha-beta,C0033788,T047,Disorders
What are the treatments for mucolipidosis III alpha/beta ?,0000675-5,treatment,These resources address the diagnosis or management of mucolipidosis III alpha/beta:  - Gene Review: Gene Review: Mucolipidosis III Alpha/Beta  - Genetic Testing Registry: Pseudo-Hurler polydystrophy  - MedlinePlus Encyclopedia: Cloudy Cornea  - MedlinePlus Encyclopedia: Heart Valves   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,mucolipidosis III alpha/beta,0000675,GHR,https://ghr.nlm.nih.gov/condition/mucolipidosis-iii-alpha-beta,C0033788,T047,Disorders
What is (are) mucolipidosis III gamma ?,0000676-1,information,"Mucolipidosis III gamma is a slowly progressive disorder that affects many parts of the body. Signs and symptoms of this condition typically appear around age 3.  Individuals with mucolipidosis III gamma grow slowly and have short stature. They also have stiff joints and dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Many affected individuals develop low bone mineral density (osteoporosis), which weakens the bones and makes them prone to fracture. Osteoporosis and progressive joint problems in people with mucolipidosis III gamma also cause pain, which becomes more severe over time.  People with mucolipidosis III gamma often have heart valve abnormalities and mild clouding of the clear covering of the eye (cornea). Their facial features become slightly thickened or ""coarse"" as they get older. A small percentage of people with this condition have mild intellectual disability or learning problems. Individuals with mucolipidosis III gamma generally survive into adulthood, but they may have a shortened lifespan.",mucolipidosis III gamma,0000676,GHR,https://ghr.nlm.nih.gov/condition/mucolipidosis-iii-gamma,C1854896,T047,Disorders
How many people are affected by mucolipidosis III gamma ?,0000676-2,frequency,"Mucolipidosis III gamma is a rare disorder, although its exact prevalence is unknown. It is estimated to occur in about 1 in 100,000 to 400,000 individuals worldwide.",mucolipidosis III gamma,0000676,GHR,https://ghr.nlm.nih.gov/condition/mucolipidosis-iii-gamma,C1854896,T047,Disorders
What are the genetic changes related to mucolipidosis III gamma ?,0000676-3,genetic changes,"Mutations in the GNPTG gene cause mucolipidosis III gamma. This gene provides instructions for making one part (subunit) of an enzyme called GlcNAc-1-phosphotransferase. This enzyme helps prepare certain newly made enzymes for transport to lysosomes. Lysosomes are compartments within the cell that use digestive enzymes to break down large molecules into smaller ones that can be reused by cells. GlcNAc-1-phosphotransferase is involved in the process of attaching a molecule called mannose-6-phosphate (M6P) to specific digestive enzymes. Just as luggage is tagged at the airport to direct it to the correct destination, enzymes are often ""tagged"" after they are made so they get to where they are needed in the cell. M6P acts as a tag that indicates a digestive enzyme should be transported to the lysosome.  Mutations in the GNPTG gene that cause mucolipidosis III gamma result in reduced activity of GlcNAc-1-phosphotransferase. These mutations disrupt the tagging of digestive enzymes with M6P, which prevents many enzymes from reaching the lysosomes. Digestive enzymes that do not receive the M6P tag end up outside the cell, where they have increased activity. The shortage of digestive enzymes within lysosomes causes large molecules to accumulate there. Conditions that cause molecules to build up inside lysosomes, including mucolipidosis III gamma, are called lysosomal storage disorders. The signs and symptoms of mucolipidosis III gamma are most likely due to the shortage of digestive enzymes inside lysosomes and the effects these enzymes have outside the cell.",mucolipidosis III gamma,0000676,GHR,https://ghr.nlm.nih.gov/condition/mucolipidosis-iii-gamma,C1854896,T047,Disorders
Is mucolipidosis III gamma inherited ?,0000676-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",mucolipidosis III gamma,0000676,GHR,https://ghr.nlm.nih.gov/condition/mucolipidosis-iii-gamma,C1854896,T047,Disorders
What are the treatments for mucolipidosis III gamma ?,0000676-5,treatment,These resources address the diagnosis or management of mucolipidosis III gamma:  - Gene Review: Gene Review: Mucolipidosis III Gamma  - Genetic Testing Registry: Mucolipidosis III Gamma  - MedlinePlus Encyclopedia: Cloudy Cornea  - MedlinePlus Encyclopedia: Heart Valves   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,mucolipidosis III gamma,0000676,GHR,https://ghr.nlm.nih.gov/condition/mucolipidosis-iii-gamma,C1854896,T047,Disorders
What is (are) mucolipidosis type IV ?,0000677-1,information,"Mucolipidosis type IV is an inherited disorder characterized by delayed development and vision impairment that worsens over time. The severe form of the disorder is called typical mucolipidosis type IV, and the mild form is called atypical mucolipidosis type IV.  Approximately 95 percent of individuals with this condition have the severe form. People with typical mucolipidosis type IV have delayed development of mental and motor skills (psychomotor delay). Motor skills include sitting, standing, walking, grasping objects, and writing. Psychomotor delay is moderate to severe and usually becomes apparent during the first year of life. Affected individuals have intellectual disability, limited or absent speech, difficulty chewing and swallowing, weak muscle tone (hypotonia) that gradually turns into abnormal muscle stiffness (spasticity), and problems controlling hand movements. Most people with typical mucolipidosis type IV are unable to walk independently. In about 15 percent of affected individuals, the psychomotor problems worsen over time.  Vision may be normal at birth in people with typical mucolipidosis type IV, but it becomes increasingly impaired during the first decade of life. Individuals with this condition develop clouding of the clear covering of the eye (cornea) and progressive breakdown of the light-sensitive layer at the back of the eye (retina). By their early teens, affected individuals have severe vision loss or blindness.  People with typical mucolipidosis type IV also have impaired production of stomach acid (achlorhydria). Achlorhydria does not cause any symptoms in these individuals, but it does result in unusually high levels of gastrin in the blood. Gastrin is a hormone that regulates the production of stomach acid. Individuals with mucolipidosis type IV may not have enough iron in their blood, which can lead to a shortage of red blood cells (anemia). People with the severe form of this disorder usually survive to adulthood; however, they may have a shortened lifespan.  About 5 percent of affected individuals have atypical mucolipidosis type IV. These individuals usually have mild psychomotor delay and may develop the ability to walk. People with atypical mucolipidosis type IV tend to have milder eye abnormalities than those with the severe form of the disorder. Achlorhydria also may be present in mildly affected individuals.",mucolipidosis type IV,0000677,GHR,https://ghr.nlm.nih.gov/condition/mucolipidosis-type-iv,C0238286,T047,Disorders
How many people are affected by mucolipidosis type IV ?,0000677-2,frequency,"Mucolipidosis type IV is estimated to occur in 1 in 40,000 people. About 70 percent of affected individuals have Ashkenazi Jewish ancestry.",mucolipidosis type IV,0000677,GHR,https://ghr.nlm.nih.gov/condition/mucolipidosis-type-iv,C0238286,T047,Disorders
What are the genetic changes related to mucolipidosis type IV ?,0000677-3,genetic changes,"Mutations in the MCOLN1 gene cause mucolipidosis type IV. This gene provides instructions for making a protein called mucolipin-1. This protein is located in the membranes of lysosomes and endosomes, compartments within the cell that digest and recycle materials. While its function is not completely understood, mucolipin-1 plays a role in the transport (trafficking) of fats (lipids) and proteins between lysosomes and endosomes. Mucolipin-1 appears to be important for the development and maintenance of the brain and retina. In addition, this protein is likely critical for normal functioning of the cells in the stomach that produce digestive acids.  Most mutations in the MCOLN1 gene result in the production of a nonfunctional protein or prevent any protein from being produced. A lack of functional mucolipin-1 impairs transport of lipids and proteins, causing these substances to build up inside lysosomes. Conditions that cause molecules to accumulate inside the lysosomes, including mucolipidosis type IV, are called lysosomal storage disorders. Two mutations in the MCOLN1 gene account for almost all cases of mucolipidosis type IV in people with Ashkenazi Jewish ancestry. It remains unclear how mutations in this gene lead to the signs and symptoms of mucolipidosis type IV.",mucolipidosis type IV,0000677,GHR,https://ghr.nlm.nih.gov/condition/mucolipidosis-type-iv,C0238286,T047,Disorders
Is mucolipidosis type IV inherited ?,0000677-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",mucolipidosis type IV,0000677,GHR,https://ghr.nlm.nih.gov/condition/mucolipidosis-type-iv,C0238286,T047,Disorders
What are the treatments for mucolipidosis type IV ?,0000677-5,treatment,These resources address the diagnosis or management of mucolipidosis type IV:  - Gene Review: Gene Review: Mucolipidosis IV  - Genetic Testing Registry: Ganglioside sialidase deficiency  - MedlinePlus Encyclopedia: Gastrin   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,mucolipidosis type IV,0000677,GHR,https://ghr.nlm.nih.gov/condition/mucolipidosis-type-iv,C0238286,T047,Disorders
What is (are) mucopolysaccharidosis type I ?,0000678-1,information,"Mucopolysaccharidosis type I (MPS I) is a condition that affects many parts of the body. This disorder was once divided into three separate syndromes: Hurler syndrome (MPS I-H), Hurler-Scheie syndrome (MPS I-H/S), and Scheie syndrome (MPS I-S), listed from most to least severe. Because there is so much overlap between each of these three syndromes, MPS I is currently divided into the severe and attenuated types.  Children with MPS I often have no signs or symptoms of the condition at birth, although some have a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). People with severe MPS I generally begin to show other signs and symptoms of the disorder within the first year of life, while those with the attenuated form have milder features that develop later in childhood.  Individuals with MPS I may have a large head (macrocephaly), a buildup of fluid in the brain (hydrocephalus), heart valve abnormalities, distinctive-looking facial features that are described as ""coarse,"" an enlarged liver and spleen (hepatosplenomegaly), and a large tongue (macroglossia). Vocal cords can also enlarge, resulting in a deep, hoarse voice. The airway may become narrow in some people with MPS I, causing frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea).  People with MPS I often develop clouding of the clear covering of the eye (cornea), which can cause significant vision loss. Affected individuals may also have hearing loss and recurrent ear infections.  Some individuals with MPS I have short stature and joint deformities (contractures) that affect mobility. Most people with the severe form of the disorder also have dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Carpal tunnel syndrome develops in many children with this disorder and is characterized by numbness, tingling, and weakness in the hand and fingers. Narrowing of the spinal canal (spinal stenosis) in the neck can compress and damage the spinal cord.  While both forms of MPS I can affect many different organs and tissues, people with severe MPS I experience a decline in intellectual function and a more rapid disease progression. Developmental delay is usually present by age 1, and severely affected individuals eventually lose basic functional skills (developmentally regress). Children with this form of the disorder usually have a shortened lifespan, sometimes living only into late childhood. Individuals with attenuated MPS I typically live into adulthood and may or may not have a shortened lifespan. Some people with the attenuated type have learning disabilities, while others have no intellectual impairments. Heart disease and airway obstruction are major causes of death in people with both types of MPS I.",mucopolysaccharidosis type I,0000678,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-i,C0023786,T047,Disorders
How many people are affected by mucopolysaccharidosis type I ?,0000678-2,frequency,"Severe MPS I occurs in approximately 1 in 100,000 newborns. Attenuated MPS I is less common and occurs in about 1 in 500,000 newborns.",mucopolysaccharidosis type I,0000678,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-i,C0023786,T047,Disorders
What are the genetic changes related to mucopolysaccharidosis type I ?,0000678-3,genetic changes,"Mutations in the IDUA gene cause MPS I. The IDUA gene provides instructions for producing an enzyme that is involved in the breakdown of large sugar molecules called glycosaminoglycans (GAGs). GAGs were originally called mucopolysaccharides, which is where this condition gets its name. Mutations in the IDUA gene reduce or completely eliminate the function of the IDUA enzyme. The lack of IDUA enzyme activity leads to the accumulation of GAGs within cells, specifically inside the lysosomes. Lysosomes are compartments in the cell that digest and recycle different types of molecules. Conditions that cause molecules to build up inside the lysosomes, including MPS I, are called lysosomal storage disorders. The accumulation of GAGs increases the size of the lysosomes, which is why many tissues and organs are enlarged in this disorder. Researchers believe that the GAGs may also interfere with the functions of other proteins inside the lysosomes and disrupt the movement of molecules inside the cell.",mucopolysaccharidosis type I,0000678,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-i,C0023786,T047,Disorders
Is mucopolysaccharidosis type I inherited ?,0000678-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",mucopolysaccharidosis type I,0000678,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-i,C0023786,T047,Disorders
What are the treatments for mucopolysaccharidosis type I ?,0000678-5,treatment,These resources address the diagnosis or management of mucopolysaccharidosis type I:  - Baby's First Test  - Gene Review: Gene Review: Mucopolysaccharidosis Type I  - Genetic Testing Registry: Mucopolysaccharidosis type I  - MedlinePlus Encyclopedia: Hurler Syndrome  - MedlinePlus Encyclopedia: Mucopolysaccharides  - MedlinePlus Encyclopedia: Scheie Syndrome  - National MPS Society: Treatments   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,mucopolysaccharidosis type I,0000678,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-i,C0023786,T047,Disorders
What is (are) mucopolysaccharidosis type II ?,0000679-1,information,"Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is a condition that affects many different parts of the body and occurs almost exclusively in males. It is a progressively debilitating disorder; however, the rate of progression varies among affected individuals.  At birth, individuals with MPS II do not display any features of the condition. Between ages 2 and 4, they develop full lips, large rounded cheeks, a broad nose, and an enlarged tongue (macroglossia). The vocal cords also enlarge, which results in a deep, hoarse voice. Narrowing of the airway causes frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea). As the disorder progresses, individuals need medical assistance to keep their airway open.  Many other organs and tissues are affected in MPS II. Individuals with this disorder often have a large head (macrocephaly), a buildup of fluid in the brain (hydrocephalus), an enlarged liver and spleen (hepatosplenomegaly), and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). People with MPS II usually have thick skin that is not very stretchy. Some affected individuals also have distinctive white skin growths that look like pebbles. Most people with this disorder develop hearing loss and have recurrent ear infections. Some individuals with MPS II develop problems with the light-sensitive tissue in the back of the eye (retina) and have reduced vision. Carpal tunnel syndrome commonly occurs in children with this disorder and is characterized by numbness, tingling, and weakness in the hand and fingers. Narrowing of the spinal canal (spinal stenosis) in the neck can compress and damage the spinal cord. The heart is also significantly affected by MPS II, and many individuals develop heart valve problems. Heart valve abnormalities can cause the heart to become enlarged (ventricular hypertrophy) and can eventually lead to heart failure.  Children with MPS II grow steadily until about age 5, and then their growth slows and they develop short stature. Individuals with this condition have joint deformities (contractures) that significantly affect mobility. Most people with MPS II also have dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Dysostosis multiplex includes a generalized thickening of most long bones, particularly the ribs.  There are two types of MPS II, called the severe and mild types. While both types affect many different organs and tissues as described above, people with severe MPS II also experience a decline in intellectual function and a more rapid disease progression. Individuals with the severe form begin to lose basic functional skills (developmentally regress) between the ages of 6 and 8. The life expectancy of these individuals is 10 to 20 years. Individuals with mild MPS II also have a shortened lifespan, but they typically live into adulthood and their intelligence is not affected. Heart disease and airway obstruction are major causes of death in people with both types of MPS II.",mucopolysaccharidosis type II,0000679,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-ii,C0026705,T047,Disorders
How many people are affected by mucopolysaccharidosis type II ?,0000679-2,frequency,"MPS II occurs in approximately 1 in 100,000 to 1 in 170,000 males.",mucopolysaccharidosis type II,0000679,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-ii,C0026705,T047,Disorders
What are the genetic changes related to mucopolysaccharidosis type II ?,0000679-3,genetic changes,"Mutations in the IDS gene cause MPS II. The IDS gene provides instructions for producing the I2S enzyme, which is involved in the breakdown of large sugar molecules called glycosaminoglycans (GAGs). GAGs were originally called mucopolysaccharides, which is where this condition gets its name. Mutations in the IDS gene reduce or completely eliminate the function of the I2S enzyme. Lack of I2S enzyme activity leads to the accumulation of GAGs within cells, specifically inside the lysosomes. Lysosomes are compartments in the cell that digest and recycle different types of molecules. Conditions that cause molecules to build up inside the lysosomes, including MPS II, are called lysosomal storage disorders. The accumulation of GAGs increases the size of the lysosomes, which is why many tissues and organs are enlarged in this disorder. Researchers believe that the GAGs may also interfere with the functions of other proteins inside the lysosomes and disrupt the movement of molecules inside the cell.",mucopolysaccharidosis type II,0000679,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-ii,C0026705,T047,Disorders
Is mucopolysaccharidosis type II inherited ?,0000679-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",mucopolysaccharidosis type II,0000679,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-ii,C0026705,T047,Disorders
What are the treatments for mucopolysaccharidosis type II ?,0000679-5,treatment,"These resources address the diagnosis or management of mucopolysaccharidosis type II:  - Baby's First Test  - Gene Review: Gene Review: Mucopolysaccharidosis Type II  - Genetic Testing Registry: Mucopolysaccharidosis, MPS-II  - MedlinePlus Encyclopedia: Hunter syndrome  - MedlinePlus Encyclopedia: Mucopolysaccharides   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",mucopolysaccharidosis type II,0000679,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-ii,C0026705,T047,Disorders
What is (are) mucopolysaccharidosis type III ?,0000680-1,information,"Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a progressive disorder that mainly affects the brain and spinal cord (central nervous system).  People with MPS III generally do not display any features of the condition at birth, but they begin to show signs and symptoms of the disorder during early childhood. Affected children often initially have delayed speech and behavior problems. They may become restless, destructive, anxious, or aggressive. Sleep disturbances are also very common in children with MPS III. This condition causes progressive intellectual disability and the loss of previously acquired skills (developmental regression). In later stages of the disorder, people with MPS III may develop seizures and movement disorders.  The physical features of MPS III are less pronounced than those of other types of mucopolysaccharidosis. Individuals with MPS III typically have mildly ""coarse"" facial features, a large head (macrocephaly), a slightly enlarged liver (mild hepatomegaly), and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). Some people with MPS III have short stature, joint stiffness, or mild dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Affected individuals often develop chronic diarrhea and recurrent upper respiratory and ear infections. People with MPS III may also experience hearing loss and vision problems.  MPS III is divided into types IIIA, IIIB, IIIC, and IIID, which are distinguished by their genetic cause. The different types of MPS III have similar signs and symptoms, although the features of MPS IIIA typically appear earlier in life and progress more rapidly. People with MPS III usually live into adolescence or early adulthood.",mucopolysaccharidosis type III,0000680,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-iii,C0026706,T019,Disorders
How many people are affected by mucopolysaccharidosis type III ?,0000680-2,frequency,"MPS III is the most common type of mucopolysaccharidosis; the estimated incidence of all four types combined is 1 in 70,000 newborns. MPS IIIA and MPS IIIB are much more common than MPS IIIC and MPS IIID.",mucopolysaccharidosis type III,0000680,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-iii,C0026706,T019,Disorders
What are the genetic changes related to mucopolysaccharidosis type III ?,0000680-3,genetic changes,"Mutations in the GNS, HGSNAT, NAGLU, and SGSH genes cause MPS III. These genes provide instructions for making enzymes involved in the breakdown of large sugar molecules called glycosaminoglycans (GAGs). GAGs were originally called mucopolysaccharides, which is where this condition gets its name. The GNS, HGSNAT, NAGLU, and SGSH enzymes are involved in the step-wise breakdown of a subset of GAGs called heparan sulfate.  MPS IIIA is caused by mutations in the SGSH gene, and MPS IIIB is caused by NAGLU gene mutations. Mutations in the HGSNAT gene result in MPS IIIC, and GNS gene mutations cause MPS IIID. Mutations in these genes reduce or eliminate enzyme function. A lack of any one of these enzymes disrupts the breakdown of heparan sulfate. As a result, partially broken down heparan sulfate accumulates within cells, specifically inside the lysosomes. Lysosomes are compartments in the cell that digest and recycle different types of molecules. Conditions such as MPS III that cause molecules to build up inside the lysosomes are called lysosomal storage disorders. Researchers believe that the accumulation of GAGs interferes with the functions of other proteins inside the lysosomes and disrupts the normal functions of cells. It is unknown why the buildup of heparan sulfate mostly affects the central nervous system in MPS III.",mucopolysaccharidosis type III,0000680,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-iii,C0026706,T019,Disorders
Is mucopolysaccharidosis type III inherited ?,0000680-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",mucopolysaccharidosis type III,0000680,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-iii,C0026706,T019,Disorders
What are the treatments for mucopolysaccharidosis type III ?,0000680-5,treatment,"These resources address the diagnosis or management of mucopolysaccharidosis type III:  - Genetic Testing Registry: Mucopolysaccharidosis, MPS-III-A  - Genetic Testing Registry: Mucopolysaccharidosis, MPS-III-B  - Genetic Testing Registry: Mucopolysaccharidosis, MPS-III-C  - Genetic Testing Registry: Mucopolysaccharidosis, MPS-III-D  - MedlinePlus Encyclopedia: Sanfilippo Syndrome  - National MPS Society: A Guide to Understanding MPS III   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",mucopolysaccharidosis type III,0000680,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-iii,C0026706,T019,Disorders
What is (are) mucopolysaccharidosis type IV ?,0000681-1,information,"Mucopolysaccharidosis type IV (MPS IV), also known as Morquio syndrome, is a progressive condition that mainly affects the skeleton. The rate at which symptoms worsen varies among affected individuals.  The first signs and symptoms of MPS IV usually become apparent during early childhood. Affected individuals develop various skeletal abnormalities, including short stature, knock knees, and abnormalities of the ribs, chest, spine, hips, and wrists. People with MPS IV often have joints that are loose and very flexible (hypermobile), but they may also have restricted movement in certain joints. A characteristic feature of this condition is underdevelopment (hypoplasia) of a peg-like bone in the neck called the odontoid process. The odontoid process helps stabilize the spinal bones in the neck (cervical vertebrae). Odontoid hypoplasia can lead to misalignment of the cervical vertebrae, which may compress and damage the spinal cord, resulting in paralysis or death.  In people with MPS IV, the clear covering of the eye (cornea) typically becomes cloudy, which can cause vision loss. Some affected individuals have recurrent ear infections and hearing loss. The airway may become narrow in some people with MPS IV, leading to frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea). Other common features of this condition include mildly ""coarse"" facial features, thin tooth enamel, multiple cavities, heart valve abnormalities, a mildly enlarged liver (hepatomegaly), and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). Unlike some other types of mucopolysaccharidosis, MPS IV does not affect intelligence.  The life expectancy of individuals with MPS IV depends on the severity of symptoms. Severely affected individuals may survive only until late childhood or adolescence. Those with milder forms of the disorder usually live into adulthood, although their life expectancy may be reduced. Spinal cord compression and airway obstruction are major causes of death in people with MPS IV.",mucopolysaccharidosis type IV,0000681,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-iv,C0026707,T019,Disorders
How many people are affected by mucopolysaccharidosis type IV ?,0000681-2,frequency,"The exact prevalence of MPS IV is unknown, although it is estimated to occur in 1 in 200,000 to 300,000 individuals.",mucopolysaccharidosis type IV,0000681,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-iv,C0026707,T019,Disorders
What are the genetic changes related to mucopolysaccharidosis type IV ?,0000681-3,genetic changes,"Mutations in the GALNS and GLB1 genes cause MPS IV. These genes provide instructions for producing enzymes involved in the breakdown of large sugar molecules called glycosaminoglycans (GAGs). GAGs were originally called mucopolysaccharides, which is where this condition gets its name. When MPS IV is caused by mutations in the GALNS gene it is called MPS IV type A (MPS IVA), and when it is caused by mutations in the GLB1 gene it is called MPS IV type B (MPS IVB). In general, the two types of MPS IV cannot be distinguished by their signs and symptoms.  Mutations in the GALNS and GLB1 genes reduce or completely eliminate the activity of the enzymes produced from these genes. Without these enzymes, GAGs accumulate within cells, specifically inside the lysosomes. Lysosomes are compartments in the cell that break down and recycle different types of molecules. Conditions such as MPS IV that cause molecules to build up inside the lysosomes are called lysosomal storage disorders. In MPS IV, GAGs accumulate to toxic levels in many tissues and organs, particularly in the bones. The accumulation of GAGs causes the bone deformities in this disorder. Researchers believe that the buildup of GAGs may also cause the features of MPS IV by interfering with the functions of other proteins inside lysosomes and disrupting the movement of molecules inside the cell.",mucopolysaccharidosis type IV,0000681,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-iv,C0026707,T019,Disorders
Is mucopolysaccharidosis type IV inherited ?,0000681-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",mucopolysaccharidosis type IV,0000681,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-iv,C0026707,T019,Disorders
What are the treatments for mucopolysaccharidosis type IV ?,0000681-5,treatment,"These resources address the diagnosis or management of mucopolysaccharidosis type IV:  - Genetic Testing Registry: Morquio syndrome  - Genetic Testing Registry: Mucopolysaccharidosis, MPS-IV-A  - Genetic Testing Registry: Mucopolysaccharidosis, MPS-IV-B  - MedlinePlus Encyclopedia: Morquio syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",mucopolysaccharidosis type IV,0000681,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-iv,C0026707,T019,Disorders
What is (are) mucopolysaccharidosis type VI ?,0000682-1,information,"Mucopolysaccharidosis type VI (MPS VI), also known as Maroteaux-Lamy syndrome, is a progressive condition that causes many tissues and organs to enlarge and become inflamed or scarred. Skeletal abnormalities are also common in this condition. The rate at which symptoms worsen varies among affected individuals.  People with MPS VI generally do not display any features of the condition at birth. They often begin to show signs and symptoms of MPS VI during early childhood. The features of MPS VI include a large head (macrocephaly), a buildup of fluid in the brain (hydrocephalus), distinctive-looking facial features that are described as ""coarse,"" and a large tongue (macroglossia). Affected individuals also frequently develop heart valve abnormalities, an enlarged liver and spleen (hepatosplenomegaly), and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). The airway may become narrow in some people with MPS VI, leading to frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea). The clear covering of the eye (cornea) typically becomes cloudy, which can cause significant vision loss. People with MPS VI may also have recurrent ear infections and hearing loss. Unlike other types of mucopolysaccharidosis, MPS VI does not affect intelligence.  MPS VI causes various skeletal abnormalities, including short stature and joint deformities (contractures) that affect mobility. Individuals with this condition may also have dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Carpal tunnel syndrome develops in many children with MPS VI and is characterized by numbness, tingling, and weakness in the hands and fingers. People with MPS VI may develop a narrowing of the spinal canal (spinal stenosis) in the neck, which can compress and damage the spinal cord.  The life expectancy of individuals with MPS VI depends on the severity of symptoms. Without treatment, severely affected individuals may survive only until late childhood or adolescence. Those with milder forms of the disorder usually live into adulthood, although their life expectancy may be reduced. Heart disease and airway obstruction are major causes of death in people with MPS VI.",mucopolysaccharidosis type VI,0000682,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-vi,C0026709,T047,Disorders
How many people are affected by mucopolysaccharidosis type VI ?,0000682-2,frequency,"The exact incidence of MPS VI is unknown, although it is estimated to occur in 1 in 250,000 to 600,000 newborns.",mucopolysaccharidosis type VI,0000682,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-vi,C0026709,T047,Disorders
What are the genetic changes related to mucopolysaccharidosis type VI ?,0000682-3,genetic changes,"Mutations in the ARSB gene cause MPS VI. The ARSB gene provides instructions for producing an enzyme called arylsulfatase B, which is involved in the breakdown of large sugar molecules called glycosaminoglycans (GAGs). GAGs were originally called mucopolysaccharides, which is where this condition gets its name. Mutations in the ARSB gene reduce or completely eliminate the function of arylsulfatase B. The lack of arylsulfatase B activity leads to the accumulation of GAGs within cells, specifically inside the lysosomes. Lysosomes are compartments in the cell that digest and recycle different types of molecules. Conditions such as MPS VI that cause molecules to build up inside the lysosomes are called lysosomal storage disorders. The accumulation of GAGs within lysosomes increases the size of the cells, which is why many tissues and organs are enlarged in this disorder. Researchers believe that the buildup of GAGs may also interfere with the functions of other proteins inside lysosomes, triggering inflammation and cell death.",mucopolysaccharidosis type VI,0000682,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-vi,C0026709,T047,Disorders
Is mucopolysaccharidosis type VI inherited ?,0000682-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",mucopolysaccharidosis type VI,0000682,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-vi,C0026709,T047,Disorders
What are the treatments for mucopolysaccharidosis type VI ?,0000682-5,treatment,These resources address the diagnosis or management of mucopolysaccharidosis type VI:  - Emory University Lysosomal Storage Disease Center  - Genetic Testing Registry: Mucopolysaccharidosis type VI  - MedlinePlus Encyclopedia: Mucopolysaccharides  - National Institute of Neurological Disorders and Stroke: Mucopolysaccharidoses Fact Sheet  - National MPS Society: Treatments   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,mucopolysaccharidosis type VI,0000682,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-vi,C0026709,T047,Disorders
What is (are) mucopolysaccharidosis type VII ?,0000683-1,information,"Mucopolysaccharidosis type VII (MPS VII), also known as Sly syndrome, is a progressive condition that affects most tissues and organs. The severity of MPS VII varies widely among affected individuals.  The most severe cases of MPS VII are characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. Most babies with hydrops fetalis are stillborn or die soon after birth. Other people with MPS VII typically begin to show signs and symptoms of the condition during early childhood. The features of MPS VII include a large head (macrocephaly), a buildup of fluid in the brain (hydrocephalus), distinctive-looking facial features that are described as ""coarse,"" and a large tongue (macroglossia). Affected individuals also frequently develop an enlarged liver and spleen (hepatosplenomegaly), heart valve abnormalities, and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). The airway may become narrow in some people with MPS VII, leading to frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea). The clear covering of the eye (cornea) becomes cloudy, which can cause significant vision loss. People with MPS VII may also have recurrent ear infections and hearing loss. Affected individuals may have developmental delay and progressive intellectual disability, although intelligence is unaffected in some people with this condition.  MPS VII causes various skeletal abnormalities that become more pronounced with age, including short stature and joint deformities (contractures) that affect mobility. Individuals with this condition may also have dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Carpal tunnel syndrome develops in many children with MPS VII and is characterized by numbness, tingling, and weakness in the hands and fingers. People with MPS VII may develop a narrowing of the spinal canal (spinal stenosis) in the neck, which can compress and damage the spinal cord.  The life expectancy of individuals with MPS VII depends on the severity of symptoms. Some affected individuals do not survive infancy, while others may live into adolescence or adulthood. Heart disease and airway obstruction are major causes of death in people with MPS VII.",mucopolysaccharidosis type VII,0000683,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-vii,C0085132,T047,Disorders
How many people are affected by mucopolysaccharidosis type VII ?,0000683-2,frequency,"The exact incidence of MPS VII is unknown, although it is estimated to occur in 1 in 250,000 newborns. It is one of the rarest types of mucopolysaccharidosis.",mucopolysaccharidosis type VII,0000683,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-vii,C0085132,T047,Disorders
What are the genetic changes related to mucopolysaccharidosis type VII ?,0000683-3,genetic changes,"Mutations in the GUSB gene cause MPS VII. This gene provides instructions for producing the beta-glucuronidase (-glucuronidase) enzyme, which is involved in the breakdown of large sugar molecules called glycosaminoglycans (GAGs). GAGs were originally called mucopolysaccharides, which is where this condition gets its name. Mutations in the GUSB gene reduce or completely eliminate the function of -glucuronidase. The shortage (deficiency) of -glucuronidase leads to the accumulation of GAGs within cells, specifically inside the lysosomes. Lysosomes are compartments in the cell that digest and recycle different types of molecules. Conditions such as MPS VII that cause molecules to build up inside the lysosomes are called lysosomal storage disorders. The accumulation of GAGs increases the size of the lysosomes, which is why many tissues and organs are enlarged in this disorder. Researchers believe that the GAGs may also interfere with the functions of other proteins inside the lysosomes and disrupt many normal functions of cells.",mucopolysaccharidosis type VII,0000683,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-vii,C0085132,T047,Disorders
Is mucopolysaccharidosis type VII inherited ?,0000683-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",mucopolysaccharidosis type VII,0000683,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-vii,C0085132,T047,Disorders
What are the treatments for mucopolysaccharidosis type VII ?,0000683-5,treatment,These resources address the diagnosis or management of mucopolysaccharidosis type VII:  - Genetic Testing Registry: Mucopolysaccharidosis type VII  - National MPS Society: A Guide to Understanding MPS VII   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,mucopolysaccharidosis type VII,0000683,GHR,https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-vii,C0085132,T047,Disorders
What is (are) Muenke syndrome ?,0000684-1,information,"Muenke syndrome is a condition characterized by the premature closure of certain bones of the skull (craniosynostosis) during development, which affects the shape of the head and face.  Many people with this disorder have a premature fusion of skull bones along the coronal suture, the growth line which goes over the head from ear to ear. Other parts of the skull may be malformed as well. These changes can result in an abnormally shaped head, wide-set eyes, and flattened cheekbones. About 5 percent of affected individuals have an enlarged head (macrocephaly). People with Muenke syndrome may also have mild abnormalities of the hands or feet, and hearing loss has been observed in some cases. Most people with this condition have normal intellect, but developmental delay and learning disabilities are possible.  The signs and symptoms of Muenke syndrome vary among affected people, and some findings overlap with those seen in other craniosynostosis syndromes. Between 6 percent and 7 percent of people with the gene mutation associated with Muenke syndrome do not have any of the characteristic features of the disorder.",Muenke syndrome,0000684,GHR,https://ghr.nlm.nih.gov/condition/muenke-syndrome,C1864436,T019,Disorders
How many people are affected by Muenke syndrome ?,0000684-2,frequency,"Muenke syndrome occurs in about 1 in 30,000 newborns. This condition accounts for an estimated 8 percent of all cases of craniosynostosis.",Muenke syndrome,0000684,GHR,https://ghr.nlm.nih.gov/condition/muenke-syndrome,C1864436,T019,Disorders
What are the genetic changes related to Muenke syndrome ?,0000684-3,genetic changes,"Mutations in the FGFR3 gene cause Muenke syndrome.  The FGFR3 gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. A single mutation in the FGFR3 gene is responsible for Muenke syndrome. This mutation causes the FGFR3 protein to be overly active, which interferes with normal bone growth and allows the bones of the skull to fuse before they should.",Muenke syndrome,0000684,GHR,https://ghr.nlm.nih.gov/condition/muenke-syndrome,C1864436,T019,Disorders
Is Muenke syndrome inherited ?,0000684-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Muenke syndrome,0000684,GHR,https://ghr.nlm.nih.gov/condition/muenke-syndrome,C1864436,T019,Disorders
What are the treatments for Muenke syndrome ?,0000684-5,treatment,These resources address the diagnosis or management of Muenke syndrome:  - Gene Review: Gene Review: FGFR-Related Craniosynostosis Syndromes  - Gene Review: Gene Review: Muenke Syndrome  - Genetic Testing Registry: Muenke syndrome  - MedlinePlus Encyclopedia: Craniosynostosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Muenke syndrome,0000684,GHR,https://ghr.nlm.nih.gov/condition/muenke-syndrome,C1864436,T019,Disorders
"What is (are) multicentric osteolysis, nodulosis, and arthropathy ?",0000685-1,information,"Multicentric osteolysis, nodulosis, and arthropathy (MONA) describes a rare inherited disease characterized by a loss of bone tissue (osteolysis), particularly in the hands and feet. MONA includes a condition formerly called nodulosis-arthropathy-osteolysis (NAO) syndrome. It may also include a similar disorder called Torg syndrome, although it is unknown whether Torg syndrome is actually part of MONA or a separate disorder caused by a mutation in a different gene.  In most cases of MONA, bone loss begins in the hands and feet, causing pain and limiting movement. Bone abnormalities can later spread to other areas of the body, with joint problems (arthropathy) occurring in the elbows, shoulders, knees, hips, and spine. Most people with MONA develop low bone mineral density (osteopenia) and thinning of the bones (osteoporosis) throughout the skeleton. These abnormalities make bones brittle and more prone to fracture. The bone abnormalities also lead to short stature.  Many affected individuals develop subcutaneous nodules, which are firm lumps of noncancerous tissue underneath the skin, especially on the soles of the feet. Some affected individuals also have skin abnormalities including patches of dark, thick, and leathery skin. Other features of MONA can include clouding of the clear front covering of the eye (corneal opacity), excess hair growth (hypertrichosis), overgrowth of the gums, heart abnormalities, and distinctive facial features that are described as ""coarse.""","multicentric osteolysis, nodulosis, and arthropathy",0000685,GHR,https://ghr.nlm.nih.gov/condition/multicentric-osteolysis-nodulosis-and-arthropathy,C0221204,T046,Disorders
"How many people are affected by multicentric osteolysis, nodulosis, and arthropathy ?",0000685-2,frequency,MONA is rare; its prevalence is unknown. This condition has been reported in multiple populations worldwide.,"multicentric osteolysis, nodulosis, and arthropathy",0000685,GHR,https://ghr.nlm.nih.gov/condition/multicentric-osteolysis-nodulosis-and-arthropathy,C0221204,T046,Disorders
"What are the genetic changes related to multicentric osteolysis, nodulosis, and arthropathy ?",0000685-3,genetic changes,"MONA results from mutations in the MMP2 gene. This gene provides instructions for making an enzyme called matrix metallopeptidase 2, whose primary function is to cut (cleave) a protein called type IV collagen. Type IV collagen is a major structural component of basement membranes, which are thin, sheet-like structures that separate and support cells in many tissues. The activity of matrix metallopeptidase 2 appears to be important for a variety of body functions, including bone remodeling, which is a normal process in which old bone is broken down and new bone is created to replace it.  The MMP2 gene mutations that cause MONA completely eliminate the activity of the matrix metallopeptidase 2 enzyme, preventing the normal cleavage of type IV collagen. It is unclear how a loss of enzyme activity leads to the specific features of MONA. Researchers suspect that it somehow disrupts the balance of new bone creation and the breakdown of existing bone during bone remodeling, resulting in a progressive loss of bone tissue. How a shortage of matrix metallopeptidase 2 leads to the other features of MONA, such as subcutaneous nodules and skin abnormalities, is unknown.","multicentric osteolysis, nodulosis, and arthropathy",0000685,GHR,https://ghr.nlm.nih.gov/condition/multicentric-osteolysis-nodulosis-and-arthropathy,C0221204,T046,Disorders
"Is multicentric osteolysis, nodulosis, and arthropathy inherited ?",0000685-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.","multicentric osteolysis, nodulosis, and arthropathy",0000685,GHR,https://ghr.nlm.nih.gov/condition/multicentric-osteolysis-nodulosis-and-arthropathy,C0221204,T046,Disorders
"What are the treatments for multicentric osteolysis, nodulosis, and arthropathy ?",0000685-5,treatment,"These resources address the diagnosis or management of MONA:  - Genetic Testing Registry: Multicentric osteolysis, nodulosis and arthropathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","multicentric osteolysis, nodulosis, and arthropathy",0000685,GHR,https://ghr.nlm.nih.gov/condition/multicentric-osteolysis-nodulosis-and-arthropathy,C0221204,T046,Disorders
What is (are) multiminicore disease ?,0000686-1,information,"Multiminicore disease is a disorder that primarily affects muscles used for movement (skeletal muscles). This condition causes muscle weakness and related health problems that range from mild to life-threatening.  Researchers have identified at least four forms of multiminicore disease, which can be distinguished by their characteristic signs and symptoms. The most common form, called the classic form, causes muscle weakness beginning in infancy or early childhood. This weakness is most noticeable in muscles of the trunk and neck (axial muscles) and is less severe in the arm and leg muscles. Muscle weakness causes affected infants to appear ""floppy"" (hypotonic) and can delay the development of motor skills such as sitting, standing, and walking. The disease causes muscles of the ribcage and spine to stiffen. When combined with weakness of the muscles needed for breathing, this stiffness leads to severe or life-threatening respiratory problems. Almost all children with multiminicore disease develop an abnormal curvature of the spine (scoliosis), which appears during childhood and steadily worsens over time.  Other forms of multiminicore disease have different patterns of signs and symptoms. They are less common than the classic form, together accounting for about 25 percent of all cases. The atypical forms of the condition tend to be milder and cause few or no problems with breathing. The moderate form with hand involvement causes muscle weakness and looseness of the joints, particularly in the arms and hands. Another form of multiminicore disease, known as the antenatal form with arthrogryposis, is characterized by stiff, rigid joints throughout the body (arthrogryposis), distinctive facial features, and other birth defects. Paralysis of the eye muscles (external ophthalmoplegia) is a primary feature of another atypical form of multiminicore disease. This form of the condition also causes general muscle weakness and feeding difficulties that appear in the first year of life.  Many people with multiminicore disease also have an increased risk of a developing a severe reaction to certain drugs used during surgery and other invasive procedures. This reaction is called malignant hyperthermia. Malignant hyperthermia occurs in response to some anesthetic gases, which are used to block the sensation of pain, and with a particular type of muscle relaxant. If given these drugs, people at risk for malignant hyperthermia may experience muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), a high fever, increased acid levels in the blood and other tissues (acidosis), and a rapid heart rate. The complications of malignant hyperthermia can be life-threatening unless they are treated promptly.  Multiminicore disease gets its name from small, disorganized areas called minicores, which are found in muscle fibers of many affected individuals. These abnormal regions can only be seen under a microscope. Although the presence of minicores can help doctors diagnose multiminicore disease, it is unclear how they are related to muscle weakness and the other features of this condition.",multiminicore disease,0000686,GHR,https://ghr.nlm.nih.gov/condition/multiminicore-disease,C0270962,T019,Disorders
How many people are affected by multiminicore disease ?,0000686-2,frequency,"Multiminicore disease is thought to be a rare disorder, although its incidence is unknown.",multiminicore disease,0000686,GHR,https://ghr.nlm.nih.gov/condition/multiminicore-disease,C0270962,T019,Disorders
What are the genetic changes related to multiminicore disease ?,0000686-3,genetic changes,"Mutations in the RYR1 and SEPN1 genes cause multiminicore disease.  The severe, classic form of multiminicore disease is usually caused by mutations in the SEPN1 gene. This gene provides instructions for making a protein called selenoprotein N. Although its function is unknown, researchers suspect that this protein may play a role in the formation of muscle tissue before birth. It may also be important for normal muscle function after birth. It is unclear, however, how mutations in the SEPN1 gene lead to muscle weakness and the other features of multiminicore disease.  Atypical forms of multiminicore disease often result from mutations in the RYR1 gene. RYR1 mutations are also associated with an increased risk of malignant hyperthermia. This gene provides instructions for making a protein called ryanodine receptor 1, which plays an essential role in skeletal muscles. For the body to move normally, these muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of charged atoms (ions) into muscle cells. In response to certain signals, the ryanodine receptor 1 protein forms a channel that releases stored calcium ions within muscle cells. The resulting increase in calcium ion concentration inside muscle cells stimulates muscle fibers to contract.  Mutations in the RYR1 gene change the structure and function of the ryanodine receptor 1 protein. Some mutations may lead to problems with regulation of the RYR1 channel, while other mutations appear to change the shape of the channel in such a way that calcium ions cannot flow through properly. A disruption in calcium ion transport prevents muscles from contracting normally, leading to the muscle weakness characteristic of multiminicore disease.  In some affected families, the genetic cause of the disorder has not been found. Mutations in genes other than SEPN1 and RYR1 may underlie the condition in these families.",multiminicore disease,0000686,GHR,https://ghr.nlm.nih.gov/condition/multiminicore-disease,C0270962,T019,Disorders
Is multiminicore disease inherited ?,0000686-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",multiminicore disease,0000686,GHR,https://ghr.nlm.nih.gov/condition/multiminicore-disease,C0270962,T019,Disorders
What are the treatments for multiminicore disease ?,0000686-5,treatment,"These resources address the diagnosis or management of multiminicore disease:  - Gene Review: Gene Review: Multiminicore Disease  - Genetic Testing Registry: Minicore myopathy with external ophthalmoplegia  - Genetic Testing Registry: Minicore myopathy, antenatal onset, with arthrogryposis  - Genetic Testing Registry: Multiminicore Disease  - MedlinePlus Encyclopedia: Malignant Hyperthermia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",multiminicore disease,0000686,GHR,https://ghr.nlm.nih.gov/condition/multiminicore-disease,C0270962,T019,Disorders
What is (are) multiple cutaneous and mucosal venous malformations ?,0000687-1,information,"Multiple cutaneous and mucosal venous malformations (also known as VMCM) are bluish patches (lesions) on the skin (cutaneous) and the mucous membranes, such as the lining of the mouth and nose. These lesions represent areas where the underlying veins and other blood vessels did not develop properly (venous malformations). The lesions can be painful, especially when they extend from the skin into the muscles and joints, or when a calcium deposit forms within the lesion causing inflammation and swelling.  Most people with VMCM are born with at least one venous malformation. As affected individuals age, the lesions present from birth usually become larger and new lesions often appear. The size, number, and location of venous malformations vary among affected individuals, even among members of the same family.",multiple cutaneous and mucosal venous malformations,0000687,GHR,https://ghr.nlm.nih.gov/condition/multiple-cutaneous-and-mucosal-venous-malformations,C0241665,T033,Disorders
How many people are affected by multiple cutaneous and mucosal venous malformations ?,0000687-2,frequency,"VMCM appears to be a rare disorder, although its prevalence is unknown.",multiple cutaneous and mucosal venous malformations,0000687,GHR,https://ghr.nlm.nih.gov/condition/multiple-cutaneous-and-mucosal-venous-malformations,C0241665,T033,Disorders
What are the genetic changes related to multiple cutaneous and mucosal venous malformations ?,0000687-3,genetic changes,"Mutations in the TEK gene (also called the TIE2 gene) cause VMCM. The TEK gene provides instructions for making a protein called TEK receptor tyrosine kinase. This receptor protein triggers chemical signals needed for forming blood vessels (angiogenesis) and maintaining their structure. This signaling process facilitates communication between two types of cells within the walls of blood vessels, endothelial cells and smooth muscle cells. Communication between these two cell types is necessary to direct angiogenesis and ensure the structure and integrity of blood vessels.  TEK gene mutations that cause VMCM result in a TEK receptor that is always turned on (overactive). An overactive TEK receptor is thought to disrupt the communication between endothelial cells and smooth muscle cells. It is unclear how a lack of communication between these cells causes venous malformations. These abnormal blood vessels show a deficiency of smooth muscle cells while endothelial cells are maintained. Venous malformations cause lesions below the surface of the skin or mucous membranes, which are characteristic of VMCM.",multiple cutaneous and mucosal venous malformations,0000687,GHR,https://ghr.nlm.nih.gov/condition/multiple-cutaneous-and-mucosal-venous-malformations,C0241665,T033,Disorders
Is multiple cutaneous and mucosal venous malformations inherited ?,0000687-4,inheritance,"VMCM is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing venous malformations.  Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are not inherited, are called somatic mutations. Researchers have discovered that some VMCM lesions have one inherited and one somatic TEK gene mutation. It is not known if the somatic mutation occurs before or after the venous malformation forms. As lesions are localized and not all veins are malformed, it is thought that the inherited mutation alone is not enough to cause venous malformations.  In most cases, an affected person has one parent with the condition.",multiple cutaneous and mucosal venous malformations,0000687,GHR,https://ghr.nlm.nih.gov/condition/multiple-cutaneous-and-mucosal-venous-malformations,C0241665,T033,Disorders
What are the treatments for multiple cutaneous and mucosal venous malformations ?,0000687-5,treatment,These resources address the diagnosis or management of VMCM:  - Gene Review: Gene Review: Multiple Cutaneous and Mucosal Venous Malformations  - Genetic Testing Registry: Multiple Cutaneous and Mucosal Venous Malformations   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,multiple cutaneous and mucosal venous malformations,0000687,GHR,https://ghr.nlm.nih.gov/condition/multiple-cutaneous-and-mucosal-venous-malformations,C0241665,T033,Disorders
What is (are) multiple endocrine neoplasia ?,0000688-1,information,"Multiple endocrine neoplasia is a group of disorders that affect the body's network of hormone-producing glands (the endocrine system). Hormones are chemical messengers that travel through the bloodstream and regulate the function of cells and tissues throughout the body. Multiple endocrine neoplasia typically involves tumors (neoplasia) in at least two endocrine glands; tumors can also develop in other organs and tissues. These growths can be noncancerous (benign) or cancerous (malignant). If the tumors become cancerous, the condition can be life-threatening.  The major forms of multiple endocrine neoplasia are called type 1, type 2, and type 4. These types are distinguished by the genes involved, the types of hormones made, and the characteristic signs and symptoms.  Many different types of tumors are associated with multiple endocrine neoplasia. Type 1 frequently involves tumors of the parathyroid glands, the pituitary gland, and the pancreas. Tumors in these glands can lead to the overproduction of hormones. The most common sign of multiple endocrine neoplasia type 1 is overactivity of the parathyroid glands (hyperparathyroidism). Hyperparathyroidism disrupts the normal balance of calcium in the blood, which can lead to kidney stones, thinning of bones, nausea and vomiting, high blood pressure (hypertension), weakness, and fatigue.  The most common sign of multiple endocrine neoplasia type 2 is a form of thyroid cancer called medullary thyroid carcinoma. Some people with this disorder also develop a pheochromocytoma, which is an adrenal gland tumor that can cause dangerously high blood pressure. Multiple endocrine neoplasia type 2 is divided into three subtypes: type 2A, type 2B (formerly called type 3), and familial medullary thyroid carcinoma (FMTC). These subtypes differ in their characteristic signs and symptoms and risk of specific tumors; for example, hyperparathyroidism occurs only in type 2A, and medullary thyroid carcinoma is the only feature of FMTC. The signs and symptoms of multiple endocrine neoplasia type 2 are relatively consistent within any one family.  Multiple endocrine neoplasia type 4 appears to have signs and symptoms similar to those of type 1, although it is caused by mutations in a different gene. Hyperparathyroidism is the most common feature, followed by tumors of the pituitary gland, additional endocrine glands, and other organs.",multiple endocrine neoplasia,0000688,GHR,https://ghr.nlm.nih.gov/condition/multiple-endocrine-neoplasia,C0027662,T191,Disorders
How many people are affected by multiple endocrine neoplasia ?,0000688-2,frequency,"Multiple endocrine neoplasia type 1 affects about 1 in 30,000 people; multiple endocrine neoplasia type 2 affects an estimated 1 in 35,000 people. Among the subtypes of type 2, type 2A is the most common form, followed by FMTC. Type 2B is relatively uncommon, accounting for about 5 percent of all cases of type 2. The prevalence of multiple endocrine neoplasia type 4 is unknown, although the condition appears to be rare.",multiple endocrine neoplasia,0000688,GHR,https://ghr.nlm.nih.gov/condition/multiple-endocrine-neoplasia,C0027662,T191,Disorders
What are the genetic changes related to multiple endocrine neoplasia ?,0000688-3,genetic changes,"Mutations in the MEN1, RET, and CDKN1B genes can cause multiple endocrine neoplasia.  Mutations in the MEN1 gene cause multiple endocrine neoplasia type 1. This gene provides instructions for producing a protein called menin. Menin acts as a tumor suppressor, which means it normally keeps cells from growing and dividing too rapidly or in an uncontrolled way. Although the exact function of menin is unknown, it is likely involved in cell functions such as copying and repairing DNA and regulating the activity of other genes. When mutations inactivate both copies of the MEN1 gene, menin is no longer available to control cell growth and division. The loss of functional menin allows cells to divide too frequently, leading to the formation of tumors characteristic of multiple endocrine neoplasia type 1. It is unclear why these tumors preferentially affect endocrine tissues.  Mutations in the RET gene cause multiple endocrine neoplasia type 2. This gene provides instructions for producing a protein that is involved in signaling within cells. The RET protein triggers chemical reactions that instruct cells to respond to their environment, for example by dividing or maturing. Mutations in the RET gene overactivate the protein's signaling function, which can trigger cell growth and division in the absence of signals from outside the cell. This unchecked cell division can lead to the formation of tumors in endocrine glands and other tissues.  Mutations in the CDKN1B gene cause multiple endocrine neoplasia type 4. This gene provides instructions for making a protein called p27. Like the menin protein, p27 is a tumor suppressor that helps control the growth and division of cells. Mutations in the CDKN1B gene reduce the amount of functional p27, which allows cells to grow and divide unchecked. This unregulated cell division can lead to the development of tumors in endocrine glands and other tissues.",multiple endocrine neoplasia,0000688,GHR,https://ghr.nlm.nih.gov/condition/multiple-endocrine-neoplasia,C0027662,T191,Disorders
Is multiple endocrine neoplasia inherited ?,0000688-4,inheritance,"Most cases of multiple endocrine neoplasia type 1 are considered to have an autosomal dominant pattern of inheritance. People with this condition are born with one mutated copy of the MEN1 gene in each cell. In most cases, the altered gene is inherited from an affected parent. The remaining cases are a result of new mutations in the MEN1 gene, and occur in people with no history of the disorder in their family.  Unlike most other autosomal dominant conditions, in which one altered copy of a gene in each cell is sufficient to cause the disorder, two copies of the MEN1 gene must be altered to trigger tumor formation in multiple endocrine neoplasia type 1. A mutation in the second copy of the MEN1 gene occurs in a small number of cells during a person's lifetime. Almost everyone who is born with one MEN1 mutation acquires a second mutation in certain cells, which can then divide in an unregulated way to form tumors.  Multiple endocrine neoplasia type 2 and type 4 are also inherited in an autosomal dominant pattern. In these cases, one copy of the mutated gene is sufficient to cause the disorder. Affected individuals often inherit an altered RET or CDKN1B gene from one parent with the condition. Some cases, however, result from new mutations in the gene and occur in people without other affected family members.",multiple endocrine neoplasia,0000688,GHR,https://ghr.nlm.nih.gov/condition/multiple-endocrine-neoplasia,C0027662,T191,Disorders
What are the treatments for multiple endocrine neoplasia ?,0000688-5,treatment,"These resources address the diagnosis or management of multiple endocrine neoplasia:  - Gene Review: Gene Review: Multiple Endocrine Neoplasia Type 1  - Gene Review: Gene Review: Multiple Endocrine Neoplasia Type 2  - Genetic Testing Registry: Familial medullary thyroid carcinoma  - Genetic Testing Registry: Multiple endocrine neoplasia, type 1  - Genetic Testing Registry: Multiple endocrine neoplasia, type 2a  - Genetic Testing Registry: Multiple endocrine neoplasia, type 2b  - Genetic Testing Registry: Multiple endocrine neoplasia, type 4  - Genomics Education Programme (UK): Multiple Endocrine Neoplasia type 1  - Genomics Education Programme (UK): Multiple Endocrine Neoplasia type 2A  - MedlinePlus Encyclopedia: Hyperparathyroidism  - MedlinePlus Encyclopedia: Medullary Carcinoma of Thyroid  - MedlinePlus Encyclopedia: Multiple Endocrine Neoplasia (MEN) I  - MedlinePlus Encyclopedia: Multiple Endocrine Neoplasia (MEN) II  - MedlinePlus Encyclopedia: Pancreatic Islet Cell Tumor  - MedlinePlus Encyclopedia: Pheochromocytoma  - MedlinePlus Encyclopedia: Pituitary Tumor  - National Cancer Institute: Genetic Testing for Hereditary Cancer Syndromes  - New York Thyroid Center: Medullary Thyroid Cancer   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",multiple endocrine neoplasia,0000688,GHR,https://ghr.nlm.nih.gov/condition/multiple-endocrine-neoplasia,C0027662,T191,Disorders
What is (are) multiple epiphyseal dysplasia ?,0000689-1,information,"Multiple epiphyseal dysplasia is a disorder of cartilage and bone development primarily affecting the ends of the long bones in the arms and legs (epiphyses). There are two types of multiple epiphyseal dysplasia, which can be distinguished by their pattern of inheritance. Both the dominant and recessive types have relatively mild signs and symptoms, including joint pain that most commonly affects the hips and knees, early-onset arthritis, and a waddling walk. Although some people with multiple epiphyseal dysplasia have mild short stature as adults, most are of normal height. The majority of individuals are diagnosed during childhood; however, some mild cases may not be diagnosed until adulthood.  Recessive multiple epiphyseal dysplasia is distinguished from the dominant type by malformations of the hands, feet, and knees and abnormal curvature of the spine (scoliosis). About 50 percent of individuals with recessive multiple epiphyseal dysplasia are born with at least one abnormal feature, including an inward- and upward-turning foot (clubfoot), an opening in the roof of the mouth (cleft palate), an unusual curving of the fingers or toes (clinodactyly), or ear swelling. An abnormality of the kneecap called a double-layered patella is also relatively common.",multiple epiphyseal dysplasia,0000689,GHR,https://ghr.nlm.nih.gov/condition/multiple-epiphyseal-dysplasia,C0026760,T019,Disorders
How many people are affected by multiple epiphyseal dysplasia ?,0000689-2,frequency,"The incidence of dominant multiple epiphyseal dysplasia is estimated to be at least 1 in 10,000 newborns. The incidence of recessive multiple epiphyseal dysplasia is unknown. Both forms of this disorder may actually be more common because some people with mild symptoms are never diagnosed.",multiple epiphyseal dysplasia,0000689,GHR,https://ghr.nlm.nih.gov/condition/multiple-epiphyseal-dysplasia,C0026760,T019,Disorders
What are the genetic changes related to multiple epiphyseal dysplasia ?,0000689-3,genetic changes,"Mutations in the COMP, COL9A1, COL9A2, COL9A3, or MATN3 gene can cause dominant multiple epiphyseal dysplasia. These genes provide instructions for making proteins that are found in the spaces between cartilage-forming cells (chondrocytes). These proteins interact with each other and play an important role in cartilage and bone formation. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears.  The majority of individuals with dominant multiple epiphyseal dysplasia have mutations in the COMP gene. About 10 percent of affected individuals have mutations in the MATN3 gene. Mutations in the COMP or MATN3 gene prevent the release of the proteins produced from these genes into the spaces between the chondrocytes. The absence of these proteins leads to the formation of abnormal cartilage, which can cause the skeletal problems characteristic of dominant multiple epiphyseal dysplasia.  The COL9A1, COL9A2, and COL9A3 genes provide instructions for making a protein called type IX collagen. Collagens are a family of proteins that strengthen and support connective tissues, such as skin, bone, cartilage, tendons, and ligaments. Mutations in the COL9A1, COL9A2, or COL9A3 gene are found in less than five percent of individuals with dominant multiple epiphyseal dysplasia. It is not known how mutations in these genes cause the signs and symptoms of this disorder. Research suggests that mutations in these genes may cause type IX collagen to accumulate inside the cell or interact abnormally with other cartilage components.  Some people with dominant multiple epiphyseal dysplasia do not have a mutation in the COMP, COL9A1, COL9A2, COL9A3, or MATN3 gene. In these cases, the cause of the condition is unknown.  Mutations in the SLC26A2 gene cause recessive multiple epiphyseal dysplasia. This gene provides instructions for making a protein that is essential for the normal development of cartilage and for its conversion to bone. Mutations in the SLC26A2 gene alter the structure of developing cartilage, preventing bones from forming properly and resulting in the skeletal problems characteristic of recessive multiple epiphyseal dysplasia.",multiple epiphyseal dysplasia,0000689,GHR,https://ghr.nlm.nih.gov/condition/multiple-epiphyseal-dysplasia,C0026760,T019,Disorders
Is multiple epiphyseal dysplasia inherited ?,0000689-4,inheritance,"Multiple epiphyseal dysplasia can have different inheritance patterns.  This condition can be inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.  Multiple epiphyseal dysplasia can also be inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.",multiple epiphyseal dysplasia,0000689,GHR,https://ghr.nlm.nih.gov/condition/multiple-epiphyseal-dysplasia,C0026760,T019,Disorders
What are the treatments for multiple epiphyseal dysplasia ?,0000689-5,treatment,"These resources address the diagnosis or management of multiple epiphyseal dysplasia:  - Cedars-Sinai Medical Center  - Gene Review: Gene Review: Multiple Epiphyseal Dysplasia, Dominant  - Gene Review: Gene Review: Multiple Epiphyseal Dysplasia, Recessive  - Genetic Testing Registry: Multiple epiphyseal dysplasia 1  - Genetic Testing Registry: Multiple epiphyseal dysplasia 2  - Genetic Testing Registry: Multiple epiphyseal dysplasia 3  - Genetic Testing Registry: Multiple epiphyseal dysplasia 4  - Genetic Testing Registry: Multiple epiphyseal dysplasia 5  - Genetic Testing Registry: Multiple epiphyseal dysplasia 6   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",multiple epiphyseal dysplasia,0000689,GHR,https://ghr.nlm.nih.gov/condition/multiple-epiphyseal-dysplasia,C0026760,T019,Disorders
What is (are) multiple familial trichoepithelioma ?,0000690-1,information,"Multiple familial trichoepithelioma is a condition involving multiple skin tumors that develop from structures associated with the skin (skin appendages), such as hair follicles and sweat glands. People with multiple familial trichoepithelioma typically develop large numbers of smooth, round tumors called trichoepitheliomas, which arise from hair follicles. Trichoepitheliomas are generally noncancerous (benign) but occasionally develop into a type of skin cancer called basal cell carcinoma.  Individuals with multiple familial trichoepithelioma occasionally also develop other types of tumors, including growths called spiradenomas and cylindromas. Spiradenomas develop in sweat glands. The origin of cylindromas has been unclear; while previously thought to derive from sweat glands, they are now generally believed to begin in hair follicles. Affected individuals are also at increased risk of developing tumors in tissues other than skin appendages, particularly benign or malignant tumors of the salivary glands.  People with multiple familial trichoepithelioma typically begin developing tumors during childhood or adolescence. The tumors mostly appear on the face, especially in the folds in the skin between the nose and lips (nasolabial folds, sometimes called smile lines), but may also occur on the neck, scalp, or trunk. They may grow larger and increase in number over time.  In severe cases, the tumors may get in the way of the eyes, ears, nose, or mouth and affect vision, hearing, or other functions. The growths can be disfiguring and may contribute to depression or other psychological problems. For reasons that are unclear, females with multiple familial trichoepithelioma are often more severely affected than males.",multiple familial trichoepithelioma,0000690,GHR,https://ghr.nlm.nih.gov/condition/multiple-familial-trichoepithelioma,C1275122,T191,Disorders
How many people are affected by multiple familial trichoepithelioma ?,0000690-2,frequency,Multiple familial trichoepithelioma is a rare disorder; its prevalence is unknown.,multiple familial trichoepithelioma,0000690,GHR,https://ghr.nlm.nih.gov/condition/multiple-familial-trichoepithelioma,C1275122,T191,Disorders
What are the genetic changes related to multiple familial trichoepithelioma ?,0000690-3,genetic changes,"Multiple familial trichoepithelioma can be caused by mutations in the CYLD gene. This gene provides instructions for making a protein that helps regulate nuclear factor-kappa-B. Nuclear factor-kappa-B is a group of related proteins that help protect cells from self-destruction (apoptosis) in response to certain signals. In regulating the action of nuclear factor-kappa-B, the CYLD protein allows cells to respond properly to signals to self-destruct when appropriate, such as when the cells become abnormal. By this mechanism, the CYLD protein acts as a tumor suppressor, which means that it helps prevent cells from growing and dividing too fast or in an uncontrolled way.  People with CYLD-related multiple familial trichoepithelioma are born with a mutation in one of the two copies of the CYLD gene in each cell. This mutation prevents the cell from making functional CYLD protein from the altered copy of the gene. However, enough protein is usually produced from the other, normal copy of the gene to regulate cell growth effectively. For tumors to develop, a second mutation or deletion of genetic material involving the other copy of the CYLD gene must occur in certain cells during a person's lifetime.  When both copies of the CYLD gene are mutated in a particular cell, that cell cannot produce any functional CYLD protein. The loss of this protein allows the cell to grow and divide in an uncontrolled way to form a tumor. In people with multiple familial trichoepithelioma, a second CYLD mutation typically occurs in multiple cells over an affected person's lifetime. The loss of CYLD protein in these cells leads to the growth of skin appendage tumors.  Some researchers consider multiple familial trichoepithelioma and two related conditions called familial cylindromatosis and Brooke-Spiegler syndrome, which are also caused by CYLD gene mutations, to be different forms of the same disorder. It is unclear why mutations in the CYLD gene cause different patterns of skin appendage tumors in each of these conditions, or why the tumors are generally confined to the skin in these disorders.  Some people with multiple familial trichoepithelioma do not have mutations in the CYLD gene. Scientists are working to identify the genetic cause of the disorder in these individuals.",multiple familial trichoepithelioma,0000690,GHR,https://ghr.nlm.nih.gov/condition/multiple-familial-trichoepithelioma,C1275122,T191,Disorders
Is multiple familial trichoepithelioma inherited ?,0000690-4,inheritance,"Susceptibility to multiple familial trichoepithelioma has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell increases the risk of developing this condition. However, a second, non-inherited mutation is required for development of skin appendage tumors in this disorder.",multiple familial trichoepithelioma,0000690,GHR,https://ghr.nlm.nih.gov/condition/multiple-familial-trichoepithelioma,C1275122,T191,Disorders
What are the treatments for multiple familial trichoepithelioma ?,0000690-5,treatment,These resources address the diagnosis or management of multiple familial trichoepithelioma:  - Genetic Testing Registry: Familial multiple trichoepitheliomata  - Genetic Testing Registry: Trichoepithelioma multiple familial 2   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,multiple familial trichoepithelioma,0000690,GHR,https://ghr.nlm.nih.gov/condition/multiple-familial-trichoepithelioma,C1275122,T191,Disorders
What is (are) multiple lentigines syndrome ?,0000691-1,information,"Multiple lentigines syndrome (formerly called LEOPARD syndrome) is a condition that affects many areas of the body. The characteristic features associated with the condition include brown skin spots called lentigines that are similar to freckles, abnormalities in the electrical signals that control the heartbeat, widely spaced eyes (ocular hypertelorism), a narrowing of the artery from the heart to the lungs (pulmonary stenosis), abnormalities of the genitalia, short stature, and hearing loss. These features vary, however, even among affected individuals in the same family. Not all individuals affected with multiple lentigines syndrome have all the characteristic features of this condition.  The lentigines seen in multiple lentigines syndrome typically first appear in mid-childhood, mostly on the face, neck, and upper body. Affected individuals may have thousands of brown skin spots by the time they reach puberty. Unlike freckles, the appearance of lentigines has nothing to do with sun exposure. In addition to lentigines, people with this condition may have lighter brown skin spots called caf-au-lait spots. Caf-au-lait spots tend to develop before the lentigines, appearing within the first year of life in most affected people.  Abnormal electrical signaling in the heart can be a sign of other heart problems. Of the people with multiple lentigines syndrome who have heart problems, about 80 percent have hypertrophic cardiomyopathy, which is a thickening of the heart muscle that forces the heart to work harder to pump blood. The hypertrophic cardiomyopathy in affected individuals most often affects the lower left chamber of the heart (the left ventricle). Up to 20 percent of people with multiple lentigines syndrome who have heart problems have pulmonary stenosis.  People with multiple lentigines syndrome can have a distinctive facial appearance. In addition to ocular hypertelorism, affected individuals may have droopy eyelids (ptosis), thick lips, and low-set ears.  Abnormalities of the genitalia occur most often in males with multiple lentigines syndrome. The most common abnormality in affected males is undescended testes (cryptorchidism). Other males may have a urethra that opens on the underside of the penis (hypospadias). Males with multiple lentigines syndrome may have a reduced ability to have biological children (decreased fertility). Females with multiple lentigines syndrome may have poorly developed ovaries and delayed puberty.  At birth, people with multiple lentigines syndrome are typically of normal weight and height, but in some, growth slows over time. This slow growth results in short stature in 50 to 75 percent of people with multiple lentigines syndrome.  Approximately 20 percent of individuals with multiple lentigines syndrome develop hearing loss. This hearing loss is caused by abnormalities in the inner ear (sensorineural deafness) and can be present from birth or develop later in life.  Other signs and symptoms of multiple lentigines syndrome include learning disorders, mild developmental delay, a sunken or protruding chest, and extra folds of skin on the back of the neck.  Many of the signs and symptoms of multiple lentigines syndrome also occur in a similar disorder called Noonan syndrome. It can be difficult to tell the two disorders apart in early childhood. However, the features of the two disorders differ later in life.",multiple lentigines syndrome,0000691,GHR,https://ghr.nlm.nih.gov/condition/multiple-lentigines-syndrome,C0023321,T019,Disorders
How many people are affected by multiple lentigines syndrome ?,0000691-2,frequency,Multiple lentigines syndrome is thought to be a rare condition; approximately 200 cases have been reported worldwide.,multiple lentigines syndrome,0000691,GHR,https://ghr.nlm.nih.gov/condition/multiple-lentigines-syndrome,C0023321,T019,Disorders
What are the genetic changes related to multiple lentigines syndrome ?,0000691-3,genetic changes,"Mutations in the PTPN11, RAF1, or BRAF genes cause multiple lentigines syndrome. Approximately 90 percent of individuals with multiple lentigines syndrome have mutations in the PTPN11 gene. RAF1 and BRAF gene mutations are responsible for a total of about 10 percent of cases. A small proportion of people with multiple lentigines syndrome do not have an identified mutation in any of these three genes. In these individuals, the cause of the condition is unknown.  The PTPN11, RAF1, and BRAF genes all provide instructions for making proteins that are involved in important signaling pathways needed for the proper formation of several types of tissue during development. These proteins also play roles in the regulation of cell division, cell movement (migration), and cell differentiation (the process by which cells mature to carry out specific functions).  Mutations in the PTPN11, RAF1, or BRAF genes lead to the production of a protein that functions abnormally. This abnormal functioning impairs the protein's ability to respond to cell signals. A disruption in the regulation of systems that control cell growth and division leads to the characteristic features of multiple lentigines syndrome.",multiple lentigines syndrome,0000691,GHR,https://ghr.nlm.nih.gov/condition/multiple-lentigines-syndrome,C0023321,T019,Disorders
Is multiple lentigines syndrome inherited ?,0000691-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",multiple lentigines syndrome,0000691,GHR,https://ghr.nlm.nih.gov/condition/multiple-lentigines-syndrome,C0023321,T019,Disorders
What are the treatments for multiple lentigines syndrome ?,0000691-5,treatment,These resources address the diagnosis or management of multiple lentigines syndrome:  - Cincinnati Children's Hospital: Cardiomyopathies  - Gene Review: Gene Review: Noonan Syndrome with Multiple Lentigines  - Genetic Testing Registry: LEOPARD syndrome 1  - Genetic Testing Registry: LEOPARD syndrome 2  - Genetic Testing Registry: LEOPARD syndrome 3  - Genetic Testing Registry: Noonan syndrome with multiple lentigines  - MedlinePlus Encyclopedia: Hypertrophic Cardiomyopathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,multiple lentigines syndrome,0000691,GHR,https://ghr.nlm.nih.gov/condition/multiple-lentigines-syndrome,C0023321,T019,Disorders
What is (are) multiple mitochondrial dysfunctions syndrome ?,0000692-1,information,"Multiple mitochondrial dysfunctions syndrome is characterized by impairment of cellular structures called mitochondria, which are the energy-producing centers of cells. While certain mitochondrial disorders are caused by impairment of a single stage of energy production, individuals with multiple mitochondrial dysfunctions syndrome have reduced function of more than one stage. The signs and symptoms of this severe condition begin early in life, and affected individuals usually do not live past infancy.  Affected infants typically have severe brain dysfunction (encephalopathy), which can contribute to weak muscle tone (hypotonia), seizures, and delayed development of mental and movement abilities (psychomotor delay). These infants often have difficulty growing and gaining weight at the expected rate (failure to thrive). Most affected babies have a buildup of a chemical called lactic acid in the body (lactic acidosis), which can be life-threatening. They may also have high levels of a molecule called glycine (hyperglycinemia) or elevated levels of sugar (hyperglycemia) in the blood. Some babies with multiple mitochondrial dysfunctions syndrome have high blood pressure in the blood vessels that connect to the lungs (pulmonary hypertension) or weakening of the heart muscle (cardiomyopathy).",multiple mitochondrial dysfunctions syndrome,0000692,GHR,https://ghr.nlm.nih.gov/condition/multiple-mitochondrial-dysfunctions-syndrome,C3502075,T047,Disorders
How many people are affected by multiple mitochondrial dysfunctions syndrome ?,0000692-2,frequency,"Multiple mitochondrial dysfunctions syndrome is a rare condition; its prevalence is unknown. It is one of several conditions classified as mitochondrial disorders, which affect an estimated 1 in 5,000 people worldwide.",multiple mitochondrial dysfunctions syndrome,0000692,GHR,https://ghr.nlm.nih.gov/condition/multiple-mitochondrial-dysfunctions-syndrome,C3502075,T047,Disorders
What are the genetic changes related to multiple mitochondrial dysfunctions syndrome ?,0000692-3,genetic changes,"Multiple mitochondrial dysfunctions syndrome can be caused by mutations in the NFU1 or BOLA3 gene. The proteins produced from each of these genes appear to be involved in the formation of molecules called iron-sulfur (Fe-S) clusters or in the attachment of these clusters to other proteins. Certain proteins require attachment of Fe-S clusters to function properly.  The NFU-1 and BOLA3 proteins play an important role in mitochondria. In these structures, several proteins carry out a series of chemical steps to convert the energy in food into a form that cells can use. Many of the proteins involved in these steps require Fe-S clusters to function, including protein complexes called complex I, complex II, and complex III.  Fe-S clusters are also required for another mitochondrial protein to function; this protein is involved in the modification of additional proteins that aid in energy production in mitochondria, including the pyruvate dehydrogenase complex and the alpha-ketoglutarate dehydrogenase complex (also known as the oxoglutarate dehydrogenase complex). This modification is also critical to the function of the glycine cleavage system, a set of proteins that breaks down a protein building block (amino acid) called glycine when levels become too high.  Mutations in the NFU1 or BOLA3 gene reduce or eliminate production of the respective protein, which impairs Fe-S cluster formation. Consequently, proteins affected by the presence of Fe-S clusters, including those involved in energy production and glycine breakdown, cannot function normally. Reduced activity of complex I, II, or III, pyruvate dehydrogenase, or alpha-ketoglutarate dehydrogenase leads to potentially fatal lactic acidosis, encephalopathy, and other signs and symptoms of multiple mitochondrial dysfunctions syndrome. In some affected individuals, impairment of the glycine cleavage system leads to a buildup of glycine.",multiple mitochondrial dysfunctions syndrome,0000692,GHR,https://ghr.nlm.nih.gov/condition/multiple-mitochondrial-dysfunctions-syndrome,C3502075,T047,Disorders
Is multiple mitochondrial dysfunctions syndrome inherited ?,0000692-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",multiple mitochondrial dysfunctions syndrome,0000692,GHR,https://ghr.nlm.nih.gov/condition/multiple-mitochondrial-dysfunctions-syndrome,C3502075,T047,Disorders
What are the treatments for multiple mitochondrial dysfunctions syndrome ?,0000692-5,treatment,These resources address the diagnosis or management of multiple mitochondrial dysfunctions syndrome:  - Gene Review: Gene Review: Mitochondrial Disorders Overview  - Genetic Testing Registry: Multiple mitochondrial dysfunctions syndrome 1  - Genetic Testing Registry: Multiple mitochondrial dysfunctions syndrome 2  - Genetic Testing Registry: Multiple mitochondrial dysfunctions syndrome 3   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,multiple mitochondrial dysfunctions syndrome,0000692,GHR,https://ghr.nlm.nih.gov/condition/multiple-mitochondrial-dysfunctions-syndrome,C3502075,T047,Disorders
What is (are) multiple pterygium syndrome ?,0000693-1,information,"Multiple pterygium syndrome is a condition that is evident before birth with webbing of the skin (pterygium) at the joints and a lack of muscle movement (akinesia) before birth. Akinesia frequently results in muscle weakness and joint deformities called contractures that restrict the movement of joints (arthrogryposis). As a result, multiple pterygium syndrome can lead to further problems with movement such as arms and legs that cannot fully extend.  The two forms of multiple pterygium syndrome are differentiated by the severity of their symptoms. Multiple pterygium syndrome, Escobar type (sometimes referred to as Escobar syndrome) is the milder of the two types. Lethal multiple pterygium syndrome is fatal before birth or very soon after birth.  In people with multiple pterygium syndrome, Escobar type, the webbing typically affects the skin of the neck, fingers, forearms, inner thighs, and backs of the knee. People with this type may also have arthrogryposis. A side-to-side curvature of the spine (scoliosis) is sometimes seen. Affected individuals may also have respiratory distress at birth due to underdeveloped lungs (lung hypoplasia). People with multiple pterygium syndrome, Escobar type usually have distinctive facial features including droopy eyelids (ptosis), outside corners of the eyes that point downward (downslanting palpebral fissures), skin folds covering the inner corner of the eyes (epicanthal folds), a small jaw, and low-set ears. Males with this condition can have undescended testes (cryptorchidism). This condition does not worsen after birth, and affected individuals typically do not have muscle weakness later in life.  Lethal multiple pterygium syndrome has many of the same signs and symptoms as the Escobar type. In addition, affected fetuses may develop a buildup of excess fluid in the body (hydrops fetalis) or a fluid-filled sac typically found on the back of the neck (cystic hygroma). Individuals with this type have severe arthrogryposis. Lethal multiple pterygium syndrome is associated with abnormalities such as underdevelopment (hypoplasia) of the heart, lung, or brain; twisting of the intestines (intestinal malrotation); kidney abnormalities; an opening in the roof of the mouth (a cleft palate); and an unusually small head size (microcephaly). Affected individuals may also develop a hole in the muscle that separates the abdomen from the chest cavity (the diaphragm), a condition called a congenital diaphragmatic hernia. Lethal multiple pterygium syndrome is typically fatal in the second or third trimester of pregnancy.",multiple pterygium syndrome,0000693,GHR,https://ghr.nlm.nih.gov/condition/multiple-pterygium-syndrome,C0265261,T019,Disorders
How many people are affected by multiple pterygium syndrome ?,0000693-2,frequency,The prevalence of multiple pterygium syndrome is unknown.,multiple pterygium syndrome,0000693,GHR,https://ghr.nlm.nih.gov/condition/multiple-pterygium-syndrome,C0265261,T019,Disorders
What are the genetic changes related to multiple pterygium syndrome ?,0000693-3,genetic changes,"Mutations in the CHRNG gene cause most cases of multiple pterygium syndrome, Escobar type and a smaller percentage of cases of lethal multiple pterygium syndrome. The CHRNG gene provides instructions for making the gamma () protein component (subunit) of the acetylcholine receptor (AChR) protein. The AChR protein is found in the membrane of skeletal muscle cells and is critical for signaling between nerve and muscle cells. Signaling between these cells is necessary for movement. The AChR protein consists of five subunits. The  subunit is found only in the fetal AChR protein. At about the thirty-third week of pregnancy, the  subunit is replaced by another subunit to form adult AChR protein. The replacement of fetal AChR by adult AChR is the reason most people with multiple pterygium syndrome, Escobar type do not have problems with muscle movement after birth.  CHRNG gene mutations result in an impaired or missing  subunit. The severity of the CHRNG gene mutation influences the severity of the condition. Typically, mutations that prevent the production of any  subunit will result in the lethal type, while mutations that allow the production of some  subunit will lead to the Escobar type. Without a functional  subunit, the fetal AChR protein cannot be assembled or properly placed in the muscle cell membrane. As a result, the fetal AChR protein cannot function and the communication between nerve cells and muscle cells in the developing fetus is impaired. A lack of signaling between nerve and muscle cells leads to akinesia and pterygium before birth, and may result in many of the other signs and symptoms of multiple pterygium syndrome.  Mutations in other genes, most providing instructions for other AChR protein subunits, have been found to cause multiple pterygium syndrome. Changes in these genes can cause both the lethal and Escobar types of this condition, although they account for only a small number of cases. Some people with multiple pterygium syndrome do not have an identified mutation in any of the known genes associated with this condition. The cause of the disease in these individuals is unknown.",multiple pterygium syndrome,0000693,GHR,https://ghr.nlm.nih.gov/condition/multiple-pterygium-syndrome,C0265261,T019,Disorders
Is multiple pterygium syndrome inherited ?,0000693-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",multiple pterygium syndrome,0000693,GHR,https://ghr.nlm.nih.gov/condition/multiple-pterygium-syndrome,C0265261,T019,Disorders
What are the treatments for multiple pterygium syndrome ?,0000693-5,treatment,These resources address the diagnosis or management of multiple pterygium syndrome:  - Genetic Testing Registry: Lethal multiple pterygium syndrome  - Genetic Testing Registry: Multiple pterygium syndrome Escobar type   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,multiple pterygium syndrome,0000693,GHR,https://ghr.nlm.nih.gov/condition/multiple-pterygium-syndrome,C0265261,T019,Disorders
What is (are) multiple sclerosis ?,0000694-1,information,"Multiple sclerosis is a condition characterized by areas of damage (lesions) on the brain and spinal cord. These lesions are associated with destruction of the covering that protects nerves and promotes the efficient transmission of nerve impulses (the myelin sheath) and damage to nerve cells. Multiple sclerosis is considered an autoimmune disorder; autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs, in this case tissues of the nervous system.  Multiple sclerosis usually begins in early adulthood, between ages 20 and 40. The symptoms vary widely, and affected individuals can experience one or more effects of nervous system damage. Multiple sclerosis often causes sensory disturbances in the limbs, including a prickling or tingling sensation (paresthesia), numbness, pain, and itching. Some people experience Lhermitte sign, which is an electrical shock-like sensation that runs down the back and into the limbs. This sensation usually occurs when the head is bent forward. Problems with muscle control are common in people with multiple sclerosis. Affected individuals may have tremors, muscle stiffness (spasticity), exaggerated reflexes (hyperreflexia), weakness or partial paralysis of the muscles of the limbs, difficulty walking, or poor bladder control. Multiple sclerosis is also associated with vision problems, such as blurred or double vision or partial or complete vision loss. Infections that cause fever can make the symptoms worse.  There are several forms of multiple sclerosis: relapsing-remitting MS, secondary progressive MS, primary progressive MS, and progressive relapsing MS. The most common is the relapsing-remitting form, which affects approximately 80 percent of people with multiple sclerosis. Individuals with this form of the condition have periods during which they experience symptoms, called clinical attacks, followed by periods without any symptoms (remission). The triggers of clinical attacks and remissions are unknown. After about 10 years, relapsing-remitting MS usually develops into another form of the disorder called secondary progressive MS. In this form, there are no remissions, and symptoms of the condition continually worsen.  Primary progressive MS is the next most common form, affecting approximately 10 to 20 percent of people with multiple sclerosis. This form is characterized by constant symptoms that worsen over time, with no clinical attacks or remissions. Primary progressive MS typically begins later than the other forms, around age 40.  Progressive relapsing MS is a rare form of multiple sclerosis that initially appears like primary progressive MS, with constant symptoms. However, people with progressive relapsing MS also experience clinical attacks of more severe symptoms.",multiple sclerosis,0000694,GHR,https://ghr.nlm.nih.gov/condition/multiple-sclerosis,C0026769,T047,Disorders
How many people are affected by multiple sclerosis ?,0000694-2,frequency,"An estimated 1.1 to 2.5 million people worldwide have multiple sclerosis. Although the reason is unclear, this condition is more common in regions that are farther away from the equator. In Canada, parts of the northern United States, western and northern Europe, Russia, and southeastern Australia, the condition affects approximately 1 in 2,000 to 2,400 people. It is less common closer to the equator, such as in Asia, sub-Saharan Africa, and parts of South America, where about 1 in 20,000 people are affected. For unknown reasons, most forms of multiple sclerosis affect women twice as often as men; however, women and men are equally affected by primary progressive MS.",multiple sclerosis,0000694,GHR,https://ghr.nlm.nih.gov/condition/multiple-sclerosis,C0026769,T047,Disorders
What are the genetic changes related to multiple sclerosis ?,0000694-3,genetic changes,"Although the cause of multiple sclerosis is unknown, variations in dozens of genes are thought to be involved in multiple sclerosis risk. Changes in the HLA-DRB1 gene are the strongest genetic risk factors for developing multiple sclerosis. Other factors associated with an increased risk of developing multiple sclerosis include changes in the IL7R gene and environmental factors, such as exposure to the Epstein-Barr virus, low levels of vitamin D, and smoking.  The HLA-DRB1 gene belongs to a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Each HLA gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. Variations in several HLA genes have been associated with increased multiple sclerosis risk, but one particular variant of the HLA-DRB1 gene, called HLA-DRB1*15:01, is the most strongly linked genetic factor.  The IL7R gene provides instructions for making one piece of two different receptor proteins: the interleukin 7 (IL-7) receptor and the thymic stromal lymphopoietin (TSLP) receptor. Both receptors are embedded in the cell membrane of immune cells. These receptors stimulate signaling pathways that induce the growth and division (proliferation) and survival of immune cells. The genetic variation involved in multiple sclerosis leads to production of an IL-7 receptor that is not embedded in the cell membrane but is instead found inside the cell. It is unknown if this variation affects the TSLP receptor.  Because the HLA-DRB1 and IL-7R genes are involved in the immune system, changes in either might be related to the autoimmune response that damages the myelin sheath and nerve cells and leads to the signs and symptoms of multiple sclerosis. However, it is unclear exactly what role variations in either gene plays in development of the condition.",multiple sclerosis,0000694,GHR,https://ghr.nlm.nih.gov/condition/multiple-sclerosis,C0026769,T047,Disorders
Is multiple sclerosis inherited ?,0000694-4,inheritance,"The inheritance pattern of multiple sclerosis is unknown, although the condition does appear to be passed down through generations in families. The risk of developing multiple sclerosis is higher for siblings or children of a person with the condition than for the general population.",multiple sclerosis,0000694,GHR,https://ghr.nlm.nih.gov/condition/multiple-sclerosis,C0026769,T047,Disorders
What are the treatments for multiple sclerosis ?,0000694-5,treatment,These resources address the diagnosis or management of multiple sclerosis:  - Gene Review: Gene Review: Multiple Sclerosis Overview  - Multiple Sclerosis Association of America: Treatments for MS  - Multiple Sclerosis International Federation: About MS--Diagnosis  - National Multiple Sclerosis Society: Diagnosing Tools   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,multiple sclerosis,0000694,GHR,https://ghr.nlm.nih.gov/condition/multiple-sclerosis,C0026769,T047,Disorders
What is (are) multiple sulfatase deficiency ?,0000695-1,information,"Multiple sulfatase deficiency is a condition that mainly affects the brain, skin, and skeleton. Because the signs and symptoms of multiple sulfatase deficiency vary widely, researchers have split the condition into three types: neonatal, late-infantile, and juvenile.  The neonatal type is the most severe form, with signs and symptoms appearing soon after birth. Affected individuals have deterioration of tissue in the nervous system (leukodystrophy), which can contribute to movement problems, seizures, developmental delay, and slow growth. They also have dry, scaly skin (ichthyosis) and excess hair growth (hypertrichosis). Skeletal abnormalities can include abnormal side-to-side curvature of the spine (scoliosis), joint stiffness, and dysostosis multiplex, which refers to a specific pattern of skeletal abnormalities seen on x-ray. Individuals with the neonatal type typically have facial features that can be described as ""coarse."" Affected individuals may also have hearing loss, heart malformations, and an enlarged liver and spleen (hepatosplenomegaly). Many of the signs and symptoms of neonatal multiple sulfatase deficiency worsen over time.  The late-infantile type is the most common form of multiple sulfatase deficiency. It is characterized by normal cognitive development in early childhood followed by a progressive loss of mental abilities and movement (psychomotor regression) due to leukodystrophy or other brain abnormalities. Individuals with this form of the condition do not have as many features as those with the neonatal type, but they often have ichthyosis, skeletal abnormalities, and coarse facial features.  The juvenile type is the rarest form of multiple sulfatase deficiency. Signs and symptoms of the juvenile type appear in mid- to late childhood. Affected individuals have normal early cognitive development but then experience psychomotor regression; however, the regression in the juvenile type usually occurs at a slower rate than in the late-infantile type. Ichthyosis is also common in the juvenile type of multiple sulfatase deficiency.  Life expectancy is shortened in individuals with all types of multiple sulfatase deficiency. Typically, affected individuals survive only a few years after the signs and symptoms of the condition appear, but life expectancy varies depending on the severity of the condition and how quickly the neurological problems worsen.",multiple sulfatase deficiency,0000695,GHR,https://ghr.nlm.nih.gov/condition/multiple-sulfatase-deficiency,C0268263,T047,Disorders
How many people are affected by multiple sulfatase deficiency ?,0000695-2,frequency,Multiple sulfatase deficiency is estimated to occur in 1 per million individuals worldwide. Approximately 50 cases have been reported in the scientific literature.,multiple sulfatase deficiency,0000695,GHR,https://ghr.nlm.nih.gov/condition/multiple-sulfatase-deficiency,C0268263,T047,Disorders
What are the genetic changes related to multiple sulfatase deficiency ?,0000695-3,genetic changes,"Multiple sulfatase deficiency is caused by mutations in the SUMF1 gene. This gene provides instructions for making an enzyme called formylglycine-generating enzyme (FGE). This enzyme is found in a cell structure called the endoplasmic reticulum, which is involved in protein processing and transport. The FGE enzyme modifies other enzymes called sulfatases, which aid in breaking down substances that contain chemical groups known as sulfates. These substances include a variety of sugars, fats, and hormones.  Most SUMF1 gene mutations severely reduce the function of the FGE enzyme or lead to the production of an unstable enzyme that is quickly broken down. The activity of multiple sulfatases is impaired because the FGE enzyme modifies all known sulfatase enzymes. Sulfate-containing molecules that are not broken down build up in cells, often resulting in cell death. The death of cells in particular tissues, specifically the brain, skeleton, and skin, cause many of the signs and symptoms of multiple sulfatase deficiency.  Research indicates that mutations that lead to reduced FGE enzyme function are associated with the less severe cases of the condition, whereas mutations that lead to the production of an unstable FGE enzyme tend to be associated with the more severe cases of multiple sulfatase deficiency.",multiple sulfatase deficiency,0000695,GHR,https://ghr.nlm.nih.gov/condition/multiple-sulfatase-deficiency,C0268263,T047,Disorders
Is multiple sulfatase deficiency inherited ?,0000695-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",multiple sulfatase deficiency,0000695,GHR,https://ghr.nlm.nih.gov/condition/multiple-sulfatase-deficiency,C0268263,T047,Disorders
What are the treatments for multiple sulfatase deficiency ?,0000695-5,treatment,These resources address the diagnosis or management of multiple sulfatase deficiency:  - Genetic Testing Registry: Multiple sulfatase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,multiple sulfatase deficiency,0000695,GHR,https://ghr.nlm.nih.gov/condition/multiple-sulfatase-deficiency,C0268263,T047,Disorders
What is (are) multiple system atrophy ?,0000696-1,information,"Multiple system atrophy is a progressive brain disorder that affects movement and balance and disrupts the function of the autonomic nervous system. The autonomic nervous system controls body functions that are mostly involuntary, such as regulation of blood pressure.  Researchers have described two major types of multiple system atrophy, which are distinguished by their major signs and symptoms at the time of diagnosis. In one type, known as MSA-P, a group of movement abnormalities called parkinsonism are predominant. These abnormalities include unusually slow movement (bradykinesia), muscle rigidity, tremors, and an inability to hold the body upright and balanced (postural instability). The other type of multiple system atrophy, known as MSA-C, is characterized by cerebellar ataxia, which causes problems with coordination and balance. This form of the condition can also include speech difficulties (dysarthria) and problems controlling eye movement.  Both forms of multiple system atrophy are associated with abnormalities of the autonomic nervous system. The most frequent autonomic symptoms associated with multiple system atrophy are a sudden drop in blood pressure upon standing (orthostatic hypotension), urinary difficulties, and erectile dysfunction in men.  Multiple system atrophy usually occurs in older adults; on average, signs and symptoms appear around age 55. The signs and symptoms of the condition worsen with time, and affected individuals survive an average of 9 years after their diagnosis.",multiple system atrophy,0000696,GHR,https://ghr.nlm.nih.gov/condition/multiple-system-atrophy,C0393571,T047,Disorders
How many people are affected by multiple system atrophy ?,0000696-2,frequency,"Multiple system atrophy has a prevalence of about 2 to 5 per 100,000 people.",multiple system atrophy,0000696,GHR,https://ghr.nlm.nih.gov/condition/multiple-system-atrophy,C0393571,T047,Disorders
What are the genetic changes related to multiple system atrophy ?,0000696-3,genetic changes,"Multiple system atrophy is a complex condition that is likely caused by the interaction of multiple genetic and environmental factors. Some of these factors have been identified, but many remain unknown.  Changes in several genes have been studied as possible risk factors for multiple system atrophy. The only confirmed genetic risk factors are variants in the SNCA gene. This gene provides instructions for making a protein called alpha-synuclein, which is abundant in normal brain cells but whose function is unknown. Studies suggest that several common variations in the SNCA gene are associated with an increased risk of multiple system atrophy in people of European descent. However, it is unclear how having one of these SNCA gene variants increases the risk of developing this condition.  Researchers have also examined environmental factors that could contribute to the risk of multiple system atrophy. Initial studies suggested that exposure to solvents, certain types of plastic or metal, and other potential toxins might be associated with the condition. However, these associations have not been confirmed.  Multiple system atrophy is characterized by clumps of abnormal alpha-synuclein protein that build up in cells in many parts of the brain and spinal cord. Over time, these clumps (which are known as inclusions) damage cells in parts of the nervous system that control movement, balance and coordination, and autonomic functioning. The progressive loss of cells in these regions underlies the major features of multiple system atrophy.",multiple system atrophy,0000696,GHR,https://ghr.nlm.nih.gov/condition/multiple-system-atrophy,C0393571,T047,Disorders
Is multiple system atrophy inherited ?,0000696-4,inheritance,"Most cases of multiple system atrophy are sporadic, which means they occur in people with no history of the disorder in their family. Rarely, the condition has been reported to run in families; however, it does not have a clear pattern of inheritance.",multiple system atrophy,0000696,GHR,https://ghr.nlm.nih.gov/condition/multiple-system-atrophy,C0393571,T047,Disorders
What are the treatments for multiple system atrophy ?,0000696-5,treatment,These resources address the diagnosis or management of multiple system atrophy:  - Genetic Testing Registry: Shy-Drager syndrome  - Vanderbilt Autonomic Dysfunction Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,multiple system atrophy,0000696,GHR,https://ghr.nlm.nih.gov/condition/multiple-system-atrophy,C0393571,T047,Disorders
What is (are) myasthenia gravis ?,0000697-1,information,"Myasthenia gravis is a disorder that causes weakness of the skeletal muscles, which are muscles that the body uses for movement. The weakness most often starts in the muscles around the eyes, causing drooping of the eyelids (ptosis) and difficulty coordinating eye movements, which results in blurred or double vision. In a form of the disorder called ocular myasthenia, the weakness remains confined to the eye muscles. In most people with myasthenia gravis, however, additional muscles in the face and neck are affected. Affected individuals may have unusual facial expressions, difficulty holding up the head, speech impairment (dysarthria), and chewing and swallowing problems (dysphagia) that may lead to choking, gagging, or drooling.  Other muscles in the body are also affected in some people with myasthenia gravis. The muscles of the arms and legs may be involved, causing affected individuals to have changes in their gait or trouble with lifting objects, rising from a seated position, or climbing stairs. The muscle weakness tends to fluctuate over time; it typically worsens with activity and improves with rest.  Weakness of the muscles in the chest wall and the muscle that separates the abdomen from the chest cavity (the diaphragm) can cause breathing problems in some people with myasthenia gravis. About 10 percent of people with this disorder experience a potentially life-threatening complication in which these respiratory muscles weaken to the point that breathing is dangerously impaired, and the affected individual requires ventilation assistance. This respiratory failure, called a myasthenic crisis, may be triggered by stresses such as infections or reactions to medications.  People can develop myasthenia gravis at any age. For reasons that are unknown, it is most commonly diagnosed in women younger than age 40 and men older than age 60. It is uncommon in children, but some infants born to women with myasthenia gravis show signs and symptoms of the disorder for the first few days or weeks of life. This temporary occurrence of symptoms is called transient neonatal myasthenia gravis.",myasthenia gravis,0000697,GHR,https://ghr.nlm.nih.gov/condition/myasthenia-gravis,C0026896,T047,Disorders
How many people are affected by myasthenia gravis ?,0000697-2,frequency,"Myasthenia gravis affects about 20 per 100,000 people worldwide. The prevalence has been increasing in recent decades, which likely results from earlier diagnosis and better treatments leading to longer lifespans for affected individuals.",myasthenia gravis,0000697,GHR,https://ghr.nlm.nih.gov/condition/myasthenia-gravis,C0026896,T047,Disorders
What are the genetic changes related to myasthenia gravis ?,0000697-3,genetic changes,"Researchers believe that variations in particular genes may increase the risk of myasthenia gravis, but the identity of these genes is unknown. Many factors likely contribute to the risk of developing this complex disorder.  Myasthenia gravis is an autoimmune disorder, which occurs when the immune system malfunctions and attacks the body's own tissues and organs. In myasthenia gravis, the immune system disrupts the transmission of nerve impulses to muscles by producing a protein called an antibody that attaches (binds) to proteins important for nerve signal transmission. Antibodies normally bind to specific foreign particles and germs, marking them for destruction, but the antibody in myasthenia gravis attacks a normal human protein. In most affected individuals, the antibody targets a protein called acetylcholine receptor (AChR); in others, the antibodies attack a related protein called muscle-specific kinase (MuSK). In both cases, the abnormal antibodies lead to a reduction of available AChR.  The AChR protein is critical for signaling between nerve and muscle cells, which is necessary for movement. In myasthenia gravis, because of the abnormal immune response, less AChR is present, which reduces signaling between nerve and muscle cells. These signaling abnormalities lead to decreased muscle movement and the muscle weakness characteristic of this condition.  It is unclear why the immune system malfunctions in people with myasthenia gravis. About 75 percent of affected individuals have an abnormally large and overactive thymus, which is a gland located behind the breastbone that plays an important role in the immune system. The thymus sometimes develops tumors (thymomas) that are usually noncancerous (benign). However, the relationship between the thymus problems and the specific immune system malfunction that occurs in myasthenia gravis is not well understood.  People with myasthenia gravis are at increased risk of developing other autoimmune disorders, including autoimmune thyroid disease and systemic lupus erythematosus. Gene variations that affect immune system function likely affect the risk of developing myasthenia gravis and other autoimmune disorders.  Some families are affected by an inherited disorder with symptoms similar to those of myasthenia gravis, but in which antibodies to the AChR or MuSK proteins are not present. This condition, which is not an autoimmune disorder, is called congenital myasthenic syndrome.",myasthenia gravis,0000697,GHR,https://ghr.nlm.nih.gov/condition/myasthenia-gravis,C0026896,T047,Disorders
Is myasthenia gravis inherited ?,0000697-4,inheritance,"In most cases, myasthenia gravis is not inherited and occurs in people with no history of the disorder in their family. About 3 to 5 percent of affected individuals have other family members with myasthenia gravis or other autoimmune disorders, but the inheritance pattern is unknown.",myasthenia gravis,0000697,GHR,https://ghr.nlm.nih.gov/condition/myasthenia-gravis,C0026896,T047,Disorders
What are the treatments for myasthenia gravis ?,0000697-5,treatment,These resources address the diagnosis or management of myasthenia gravis:  - Cleveland Clinic  - Genetic Testing Registry: Myasthenia gravis  - Genetic Testing Registry: Myasthenia gravis with thymus hyperplasia  - MedlinePlus Encyclopedia: Acetylcholine Receptor Antibody  - MedlinePlus Encyclopedia: Tensilon Test   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,myasthenia gravis,0000697,GHR,https://ghr.nlm.nih.gov/condition/myasthenia-gravis,C0026896,T047,Disorders
What is (are) mycosis fungoides ?,0000698-1,information,"Mycosis fungoides is the most common form of a type of blood cancer called cutaneous T-cell lymphoma. Cutaneous T-cell lymphomas occur when certain white blood cells, called T cells, become cancerous; these cancers characteristically affect the skin, causing different types of skin lesions. Although the skin is involved, the skin cells themselves are not cancerous. Mycosis fungoides usually occurs in adults over age 50, although affected children have been identified.  Mycosis fungoides progresses slowly through several stages, although not all people with the condition progress through all stages. Most affected individuals initially develop skin lesions called patches, which are flat, scaly, pink or red areas on the skin that can be itchy. Cancerous T cells, which cause the formation of patches, are found in these lesions. The skin cells themselves are not cancerous; the skin problems result when cancerous T cells move from the blood into the skin. Patches are most commonly found on the lower abdomen, upper thighs, buttocks, and breasts. They can disappear and reappear or remain stable over time. In most affected individuals, patches progress to plaques, the next stage of mycosis fungoides.  Plaques are raised lesions that are usually reddish, purplish, or brownish in color and itchy. Plaques commonly occur in the same body regions as patches. While some plaques arise from patches, others develop on their own, and an affected person can have both patches and plaques simultaneously. As with patches, cancerous T cells are found in plaques. Plaques can remain stable or can develop into tumors. Not everyone with patches or plaques develops tumors.  The tumors in mycosis fungoides, which are composed of cancerous T cells, are raised nodules that are thicker and deeper than plaques. They can arise from patches or plaques or occur on their own. Mycosis fungoides was so named because the tumors can resemble mushrooms, a type of fungus. Common locations for tumor development include the upper thighs and groin, breasts, armpits, and the crook of the elbow. Open sores may develop on the tumors, often leading to infection.  In any stage of mycosis fungoides, the cancerous T cells can spread to other organs, including the lymph nodes, spleen, liver, and lungs, although this most commonly occurs in the tumor stage. In addition, affected individuals have an increased risk of developing another lymphoma or other type of cancer.",mycosis fungoides,0000698,GHR,https://ghr.nlm.nih.gov/condition/mycosis-fungoides,C0026948,T191,Disorders
How many people are affected by mycosis fungoides ?,0000698-2,frequency,"Mycosis fungoides occurs in about 1 in 100,000 to 350,000 individuals. It accounts for approximately 70 percent of cutaneous T-cell lymphomas. For unknown reasons, mycosis fungoides affects males nearly twice as often as females. In the United States, there are an estimated 3.6 cases per million people each year. The condition has been found in regions around the world.",mycosis fungoides,0000698,GHR,https://ghr.nlm.nih.gov/condition/mycosis-fungoides,C0026948,T191,Disorders
What are the genetic changes related to mycosis fungoides ?,0000698-3,genetic changes,"The cause of mycosis fungoides is unknown. Most affected individuals have one or more chromosomal abnormalities, such as the loss or gain of genetic material. These abnormalities occur during a person's lifetime and are found only in the DNA of cancerous cells. Abnormalities have been found on most chromosomes, but some regions are more commonly affected than others. People with this condition tend to have additions of DNA in regions of chromosomes 7 and 17 or loss of DNA from regions of chromosomes 9 and 10. It is unclear whether these genetic changes play a role in mycosis fungoides, although the tendency to acquire chromosome abnormalities (chromosomal instability) is a feature of many cancers. It can lead to genetic changes that allow cells to grow and divide uncontrollably.  Other research suggests that certain variants of HLA class II genes are associated with mycosis fungoides. HLA genes help the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Each HLA gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. The specific variants are inherited through families. Certain variations of HLA genes may affect the risk of developing mycosis fungoides or may impact progression of the disorder.  It is possible that other factors, such as environmental exposure or certain bacterial or viral infections, are involved in the development of mycosis fungoides. However, the influence of genetic and environmental factors on the development of this complex disorder remains unclear.",mycosis fungoides,0000698,GHR,https://ghr.nlm.nih.gov/condition/mycosis-fungoides,C0026948,T191,Disorders
Is mycosis fungoides inherited ?,0000698-4,inheritance,"The inheritance pattern of mycosis fungoides has not been determined. Although the condition has been found in multiple members of more than a dozen families, it most often occurs in people with no history of the disorder in their family and is typically not inherited.",mycosis fungoides,0000698,GHR,https://ghr.nlm.nih.gov/condition/mycosis-fungoides,C0026948,T191,Disorders
What are the treatments for mycosis fungoides ?,0000698-5,treatment,These resources address the diagnosis or management of mycosis fungoides:  - Cancer Research UK: Treatments for Cutaneous T-Cell Lymphoma  - Genetic Testing Registry: Mycosis fungoides  - Lymphoma Research Foundation: Cutaneous T-Cell Lymphoma Treatment Options  - National Cancer Institute: Mycosis Fungoides and the Szary Syndrome Treatment   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,mycosis fungoides,0000698,GHR,https://ghr.nlm.nih.gov/condition/mycosis-fungoides,C0026948,T191,Disorders
What is (are) MyD88 deficiency ?,0000699-1,information,"MyD88 deficiency is an inherited disorder of the immune system (primary immunodeficiency). This primary immunodeficiency affects the innate immune response, which is the body's early, nonspecific response to foreign invaders (pathogens). MyD88 deficiency leads to abnormally frequent and severe infections by a subset of bacteria known as pyogenic bacteria. (Infection with pyogenic bacteria causes the production of pus.) However, affected individuals have normal resistance to other common bacteria, viruses, fungi, and parasites. The most common infections in MyD88 deficiency are caused by the Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa bacteria. Most people with this condition have their first bacterial infection before age 2, and the infections can be life-threatening in infancy and childhood. Infections become less frequent by about age 10.  Children with MyD88 deficiency develop invasive bacterial infections, which can involve the blood (septicemia), the membrane covering the brain and spinal cord (meningitis), or the joints (leading to inflammation and arthritis). Invasive infections can also cause areas of tissue breakdown and pus production (abscesses) on internal organs. In addition, affected individuals can have localized infections of the ears, nose, or throat. Although fever is a common reaction to bacterial infections, many people with MyD88 deficiency do not at first develop a high fever in response to these infections, even if the infection is severe.",MyD88 deficiency,0000699,GHR,https://ghr.nlm.nih.gov/condition/myd88-deficiency,C2677092,T047,Disorders
How many people are affected by MyD88 deficiency ?,0000699-2,frequency,The prevalence of MyD88 deficiency is unknown. At least 24 affected individuals have been described in the medical literature.,MyD88 deficiency,0000699,GHR,https://ghr.nlm.nih.gov/condition/myd88-deficiency,C2677092,T047,Disorders
What are the genetic changes related to MyD88 deficiency ?,0000699-3,genetic changes,"MyD88 deficiency is caused by mutations in the MYD88 gene, which provides instructions for making a protein that plays an important role in stimulating the immune system to respond to bacterial infection. The MyD88 protein is part of a signaling pathway that is involved in early recognition of pathogens and the initiation of inflammation to fight infection. This signaling pathway is part of the innate immune response.  Mutations in the MYD88 gene lead to the production of a nonfunctional protein or no protein at all. The loss of functional MyD88 protein prevents the immune system from triggering inflammation in response to pathogens that would normally help fight the infections. Because the early immune response is insufficient, bacterial infections occur often and become severe and invasive.  Researchers suggest that as the immune system matures, other systems compensate for the loss of MyD88 protein, accounting for the improvement in the condition that occurs by adolescence.",MyD88 deficiency,0000699,GHR,https://ghr.nlm.nih.gov/condition/myd88-deficiency,C2677092,T047,Disorders
Is MyD88 deficiency inherited ?,0000699-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",MyD88 deficiency,0000699,GHR,https://ghr.nlm.nih.gov/condition/myd88-deficiency,C2677092,T047,Disorders
What are the treatments for MyD88 deficiency ?,0000699-5,treatment,These resources address the diagnosis or management of MyD88 deficiency:  - Genetic Testing Registry: Myd88 deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,MyD88 deficiency,0000699,GHR,https://ghr.nlm.nih.gov/condition/myd88-deficiency,C2677092,T047,Disorders
What is (are) MYH9-related disorder ?,0000700-1,information,"MYH9-related disorder is a condition that can have many signs and symptoms, including bleeding problems, hearing loss, kidney (renal) disease, and clouding of the lens of the eyes (cataracts).  The bleeding problems in people with MYH9-related disorder are due to thrombocytopenia. Thrombocytopenia is a reduced level of circulating platelets, which are cell fragments that normally assist with blood clotting. People with MYH9-related disorder typically experience easy bruising, and affected women have excessive bleeding during menstruation (menorrhagia). The platelets in people with MYH9-related disorder are larger than normal. These enlarged platelets have difficulty moving into tiny blood vessels like capillaries. As a result, the platelet level is even lower in these small vessels, further impairing clotting.  Some people with MYH9-related disorder develop hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss). Hearing loss may be present from birth or can develop anytime into late adulthood.  An estimated 30 to 70 percent of people with MYH9-related disorder develop renal disease, usually beginning in early adulthood. The first sign of renal disease in MYH9-related disorder is typically protein or blood in the urine. Renal disease in these individuals particularly affects structures called glomeruli, which are clusters of tiny blood vessels that help filter waste products from the blood. The resulting damage to the kidneys can lead to kidney failure and end-stage renal disease (ESRD).  Some affected individuals develop cataracts in early adulthood that worsen over time.  Not everyone with MYH9-related disorder has all of the major features. All individuals with MYH9-related disorder have thrombocytopenia and enlarged platelets. Most commonly, affected individuals will also have hearing loss and renal disease. Cataracts are the least common sign of this disorder.  MYH9-related disorder was previously thought to be four separate disorders: May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome, and Sebastian syndrome. All of these disorders involved thrombocytopenia and enlarged platelets and were distinguished by some combination of hearing loss, renal disease, and cataracts. When it was discovered that these four conditions all had the same genetic cause, they were combined and renamed MYH9-related disorder.",MYH9-related disorder,0000700,GHR,https://ghr.nlm.nih.gov/condition/myh9-related-disorder,C0012634,T047,Disorders
How many people are affected by MYH9-related disorder ?,0000700-2,frequency,The incidence of MYH9-related disorder is unknown. More than 200 affected families have been reported in the scientific literature.,MYH9-related disorder,0000700,GHR,https://ghr.nlm.nih.gov/condition/myh9-related-disorder,C0012634,T047,Disorders
What are the genetic changes related to MYH9-related disorder ?,0000700-3,genetic changes,"MYH9-related disorder is caused by mutations in the MYH9 gene. The MYH9 gene provides instructions for making a protein called myosin-9. This protein is one part (subunit) of the myosin IIA protein.  There are three forms of myosin II, called myosin IIA, myosin IIB and myosin IIC. The three forms are found throughout the body and perform similar functions. They play roles in cell movement (cell motility); maintenance of cell shape; and cytokinesis, which is the step in cell division when the fluid surrounding the nucleus (the cytoplasm) divides to form two separate cells. While some cells use more than one type of myosin II, certain blood cells such as platelets and white blood cells (leukocytes) use only myosin IIA.  MYH9 gene mutations that cause MYH9-related disorder typically result in a nonfunctional version of the myosin-9 protein. The nonfunctional protein cannot properly interact with other subunits to form myosin IIA. Platelets and leukocytes, which only use myosin IIA, are most affected by a lack of functional myosin-9. It is thought that a lack of functional myosin IIA leads to the release of large, immature platelets in the bloodstream, resulting in a reduced amount of normal platelets. In leukocytes, the nonfunctional myosin-9 clumps together. These clumps of protein, called inclusion bodies, are a hallmark of MYH9-related disorder and are present in the leukocytes of everyone with this condition.",MYH9-related disorder,0000700,GHR,https://ghr.nlm.nih.gov/condition/myh9-related-disorder,C0012634,T047,Disorders
Is MYH9-related disorder inherited ?,0000700-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In most cases, an affected person inherits the mutation from one affected parent. Approximately 30 percent of cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",MYH9-related disorder,0000700,GHR,https://ghr.nlm.nih.gov/condition/myh9-related-disorder,C0012634,T047,Disorders
What are the treatments for MYH9-related disorder ?,0000700-5,treatment,These resources address the diagnosis or management of MYH9-related disorder:  - Gene Review: Gene Review: MYH9-Related Disorders  - Genetic Testing Registry: Epstein syndrome  - Genetic Testing Registry: Fechtner syndrome  - Genetic Testing Registry: Macrothrombocytopenia and progressive sensorineural deafness  - Genetic Testing Registry: May-Hegglin anomaly  - Genetic Testing Registry: Sebastian syndrome  - MedlinePlus Encyclopedia: Glomerulonephritis  - MedlinePlus Encyclopedia: Thrombocytopenia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,MYH9-related disorder,0000700,GHR,https://ghr.nlm.nih.gov/condition/myh9-related-disorder,C0012634,T047,Disorders
What is (are) Myhre syndrome ?,0000701-1,information,"Myhre syndrome is a condition with features affecting many systems and functions of the body.  People with Myhre syndrome usually have delayed development of language and motor skills such as crawling and walking. Most have intellectual disability that ranges from mild to moderate. Some have behavioral issues such as features of autism or related developmental disorders affecting communication and social interaction.  People with Myhre syndrome often have hearing loss, which can be caused by changes in the inner ear (sensorineural deafness), changes in the middle ear (conductive hearing loss), or both (mixed hearing loss).  Growth is reduced in people with this disorder, beginning before birth and continuing through adolescence. Affected individuals have a low birth weight and are generally shorter than about 97 percent of their peers throughout life.  People with Myhre syndrome typically have stiffness of the skin and are usually described as having a muscular appearance. Skeletal abnormalities associated with this disorder include thickening of the skull bones, flattened bones of the spine (platyspondyly), broad ribs, underdevelopment of the winglike structures of the pelvis (hypoplastic iliac wings), and unusually short fingers and toes (brachydactyly). Affected individuals often have joint problems (arthropathy), including stiffness and limited mobility.  Typical facial features in people with Myhre syndrome include narrow openings of the eyelids (short palpebral fissures), a shortened distance between the nose and upper lip (a short philtrum), a sunken appearance of the middle of the face (midface hypoplasia), a small mouth with a thin upper lip, and a protruding jaw (prognathism). Some affected individuals also have an opening in the roof of the mouth (a cleft palate), a split in the lip (a cleft lip), or both.  Other features that occur in some people with this disorder include constriction of the throat (laryngotracheal stenosis), high blood pressure (hypertension), heart or eye abnormalities, and in males, undescended testes (cryptorchidism).  A disorder sometimes called laryngotracheal stenosis, arthropathy, prognathism, and short stature (LAPS) syndrome is now generally considered to be the same condition as Myhre syndrome because it has similar symptoms and the same genetic cause.",Myhre syndrome,0000701,GHR,https://ghr.nlm.nih.gov/condition/myhre-syndrome,C0796081,T047,Disorders
How many people are affected by Myhre syndrome ?,0000701-2,frequency,"Myhre syndrome is a rare disorder. Only about 30 cases have been documented in the medical literature. For reasons that are unknown, most affected individuals have been males.",Myhre syndrome,0000701,GHR,https://ghr.nlm.nih.gov/condition/myhre-syndrome,C0796081,T047,Disorders
What are the genetic changes related to Myhre syndrome ?,0000701-3,genetic changes,"Mutations in the SMAD4 gene cause Myhre syndrome. The SMAD4 gene provides instructions for making a protein involved in transmitting chemical signals from the cell surface to the nucleus. This signaling pathway, called the transforming growth factor beta (TGF-) pathway, allows the environment outside the cell to affect how the cell produces other proteins. As part of this pathway, the SMAD4 protein interacts with other proteins to control the activity of particular genes. These genes influence many areas of development.  Some researchers believe that the SMAD4 gene mutations that cause Myhre syndrome impair the ability of the SMAD4 protein to attach (bind) properly with the other proteins involved in the signaling pathway. Other studies have suggested that these mutations result in an abnormally stable SMAD4 protein that remains active in the cell longer. Changes in SMAD4 binding or availability may result in abnormal signaling in many cell types, which affects development of several body systems and leads to the signs and symptoms of Myhre syndrome.",Myhre syndrome,0000701,GHR,https://ghr.nlm.nih.gov/condition/myhre-syndrome,C0796081,T047,Disorders
Is Myhre syndrome inherited ?,0000701-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Myhre syndrome,0000701,GHR,https://ghr.nlm.nih.gov/condition/myhre-syndrome,C0796081,T047,Disorders
What are the treatments for Myhre syndrome ?,0000701-5,treatment,These resources address the diagnosis or management of Myhre syndrome:  - Centers for Disease Control and Prevention: Types of Hearing Loss  - Genetic Testing Registry: Myhre syndrome  - National Institute on Deafness and Other Communication Disorders: Communication Considerations for Parents of Deaf and Hard-of-Hearing Children   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Myhre syndrome,0000701,GHR,https://ghr.nlm.nih.gov/condition/myhre-syndrome,C0796081,T047,Disorders
What is (are) myoclonic epilepsy myopathy sensory ataxia ?,0000702-1,information,"Myoclonic epilepsy myopathy sensory ataxia, commonly called MEMSA, is part of a group of conditions called the POLG-related disorders. The conditions in this group feature a range of similar signs and symptoms involving muscle-, nerve-, and brain-related functions. The signs and symptoms of MEMSA typically appear during young adulthood. This condition had previously been known as spinocerebellar ataxia with epilepsy (SCAE).  The first symptom of MEMSA is usually cerebellar ataxia, which refers to problems with coordination and balance due to defects in the part of the brain that is involved in coordinating movement (cerebellum). Recurrent seizures (epilepsy) usually develop later, often in combination with uncontrollable muscle jerks (myoclonus). The seizures usually begin in the right arm and spread to become generalized throughout the body. Additionally, affected individuals may have severe brain dysfunction (encephalopathy) or muscle weakness (myopathy). The myopathy can affect muscles close to the center of the body (proximal), such as the muscles of the hips, thighs, upper arms, or neck, or muscles farther away from the center of the body (distal), such as the muscles of the hands or feet. The myopathy may be especially noticeable during exercise (exercise intolerance).",myoclonic epilepsy myopathy sensory ataxia,0000702,GHR,https://ghr.nlm.nih.gov/condition/myoclonic-epilepsy-myopathy-sensory-ataxia,C0014544,T047,Disorders
How many people are affected by myoclonic epilepsy myopathy sensory ataxia ?,0000702-2,frequency,The prevalence of myoclonic epilepsy myopathy sensory ataxia is unknown.,myoclonic epilepsy myopathy sensory ataxia,0000702,GHR,https://ghr.nlm.nih.gov/condition/myoclonic-epilepsy-myopathy-sensory-ataxia,C0014544,T047,Disorders
What are the genetic changes related to myoclonic epilepsy myopathy sensory ataxia ?,0000702-3,genetic changes,"MEMSA is caused by mutations in the POLG gene. This gene provides instructions for making one part, the alpha subunit, of a protein called polymerase gamma (pol ). Pol  functions in mitochondria, which are structures within cells that use oxygen to convert the energy from food into a form cells can use. Mitochondria each contain a small amount of DNA, known as mitochondrial DNA (mtDNA), which is essential for the normal function of these structures. Pol  ""reads"" sequences of mtDNA and uses them as templates to produce new copies of mtDNA in a process called DNA replication.  Most POLG gene mutations change single protein building blocks (amino acids) in the alpha subunit of pol . These changes result in a mutated pol  that has a reduced ability to replicate DNA. Although the mechanism is unknown, mutations in the POLG gene often result in fewer copies of mtDNA (mtDNA depletion), particularly in muscle, brain, or liver cells. MtDNA depletion causes a decrease in cellular energy, which could account for the signs and symptoms of MEMSA.",myoclonic epilepsy myopathy sensory ataxia,0000702,GHR,https://ghr.nlm.nih.gov/condition/myoclonic-epilepsy-myopathy-sensory-ataxia,C0014544,T047,Disorders
Is myoclonic epilepsy myopathy sensory ataxia inherited ?,0000702-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",myoclonic epilepsy myopathy sensory ataxia,0000702,GHR,https://ghr.nlm.nih.gov/condition/myoclonic-epilepsy-myopathy-sensory-ataxia,C0014544,T047,Disorders
What are the treatments for myoclonic epilepsy myopathy sensory ataxia ?,0000702-5,treatment,These resources address the diagnosis or management of MEMSA:  - Gene Review: Gene Review: POLG-Related Disorders  - Genetic Testing Registry: Myoclonic epilepsy myopathy sensory ataxia  - United Mitochondrial Disease Foundation: Diagnosis of Mitochondrial Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,myoclonic epilepsy myopathy sensory ataxia,0000702,GHR,https://ghr.nlm.nih.gov/condition/myoclonic-epilepsy-myopathy-sensory-ataxia,C0014544,T047,Disorders
What is (are) myoclonic epilepsy with ragged-red fibers ?,0000703-1,information,"Myoclonic epilepsy with ragged-red fibers (MERRF) is a disorder that affects many parts of the body, particularly the muscles and nervous system. In most cases, the signs and symptoms of this disorder appear during childhood or adolescence. The features of MERRF vary widely among affected individuals, even among members of the same family.  MERRF is characterized by muscle twitches (myoclonus), weakness (myopathy), and progressive stiffness (spasticity). When the muscle cells of affected individuals are stained and viewed under a microscope, these cells usually appear abnormal. These abnormal muscle cells are called ragged-red fibers. Other features of MERRF include recurrent seizures (epilepsy), difficulty coordinating movements (ataxia), a loss of sensation in the extremities (peripheral neuropathy), and slow deterioration of intellectual function (dementia). People with this condition may also develop hearing loss or optic atrophy, which is the degeneration (atrophy) of nerve cells that carry visual information from the eyes to the brain. Affected individuals sometimes have short stature and a form of heart disease known as cardiomyopathy. Less commonly, people with MERRF develop fatty tumors, called lipomas, just under the surface of the skin.",myoclonic epilepsy with ragged-red fibers,0000703,GHR,https://ghr.nlm.nih.gov/condition/myoclonic-epilepsy-with-ragged-red-fibers,C3275417,T047,Disorders
How many people are affected by myoclonic epilepsy with ragged-red fibers ?,0000703-2,frequency,"MERRF is a rare condition; its prevalence is unknown. MERRF is part of a group of conditions known as mitochondrial disorders, which affect an estimated 1 in 5,000 people worldwide.",myoclonic epilepsy with ragged-red fibers,0000703,GHR,https://ghr.nlm.nih.gov/condition/myoclonic-epilepsy-with-ragged-red-fibers,C3275417,T047,Disorders
What are the genetic changes related to myoclonic epilepsy with ragged-red fibers ?,0000703-3,genetic changes,"Mutations in the MT-TK gene are the most common cause of MERRF, occurring in more than 80 percent of all cases. Less frequently, mutations in the MT-TL1, MT-TH, and MT-TS1 genes have been reported to cause the signs and symptoms of MERRF. People with mutations in the MT-TL1, MT-TH, or MT-TS1 gene typically have signs and symptoms of other mitochondrial disorders as well as those of MERRF.  The MT-TK, MT-TL1, MT-TH, and MT-TS1 genes are contained in mitochondrial DNA (mtDNA). Mitochondria are structures within cells that use oxygen to convert the energy from food into a form cells can use through a process called oxidative phosphorylation. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA. The genes associated with MERRF provide instructions for making molecules called transfer RNAs, which are chemical cousins of DNA. These molecules help assemble protein building blocks called amino acids into full-length, functioning proteins within mitochondria. These proteins perform the steps of oxidative phosphorylation.  Mutations that cause MERRF impair the ability of mitochondria to make proteins, use oxygen, and produce energy. These mutations particularly affect organs and tissues with high energy requirements, such as the brain and muscles. Researchers have not determined how changes in mtDNA lead to the specific signs and symptoms of MERRF.  A small percentage of MERRF cases are caused by mutations in other mitochondrial genes, and in some cases the cause of the condition is unknown.",myoclonic epilepsy with ragged-red fibers,0000703,GHR,https://ghr.nlm.nih.gov/condition/myoclonic-epilepsy-with-ragged-red-fibers,C3275417,T047,Disorders
Is myoclonic epilepsy with ragged-red fibers inherited ?,0000703-4,inheritance,"MERRF is inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mtDNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children.  In most cases, people with MERRF inherit an altered mitochondrial gene from their mother, who may or may not show symptoms of the disorder. Less commonly, the disorder results from a new mutation in a mitochondrial gene and occurs in people with no family history of MERRF.",myoclonic epilepsy with ragged-red fibers,0000703,GHR,https://ghr.nlm.nih.gov/condition/myoclonic-epilepsy-with-ragged-red-fibers,C3275417,T047,Disorders
What are the treatments for myoclonic epilepsy with ragged-red fibers ?,0000703-5,treatment,These resources address the diagnosis or management of MERRF:  - Gene Review: Gene Review: MERRF  - Genetic Testing Registry: Myoclonus with epilepsy with ragged red fibers  - Kennedy Krieger Institute: Mitochondrial Disorders  - MedlinePlus Encyclopedia: Lipoma  - MedlinePlus Encyclopedia: Optic nerve atrophy  - MedlinePlus Encyclopedia: Peripheral Neuropathy  - MitoAction: Tips and Tools for Living with Mito  - United Mitochondrial Disease Foundation: Treatments and Therapies   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,myoclonic epilepsy with ragged-red fibers,0000703,GHR,https://ghr.nlm.nih.gov/condition/myoclonic-epilepsy-with-ragged-red-fibers,C3275417,T047,Disorders
What is (are) myoclonus-dystonia ?,0000704-1,information,"Myoclonus-dystonia is a movement disorder that typically affects the upper half of the body. Individuals with this condition experience quick, involuntary muscle jerking or twitching (myoclonus) that usually affects their arms, neck, and trunk. Less frequently, the legs are involved as well. More than half of affected individuals also develop dystonia, which is a pattern of involuntary muscle contractions that causes twisting and pulling movements of specific body parts. The dystonia associated with myoclonus-dystonia may affect a single part of the body, causing isolated problems such as a writer's cramp in the hand, or it may involve multiple areas of the body. Rarely, people with this condition have dystonia as their only symptom.  The movement problems usually appear in childhood or early adolescence, and myoclonus is typically the initial symptom. Myoclonus may be triggered by movement or stimulation of the affected body area, stress, sudden noise, or caffeine. In some cases, the myoclonus gets worse over time; in other cases, people experience a spontaneous improvement (remission) of their symptoms. It is unclear why the movement abnormalities improve in some people but not in others.  People with myoclonus-dystonia may have an increased risk for developing psychological conditions such as depression, anxiety, panic attacks, and obsessive-compulsive disorder (OCD).",myoclonus-dystonia,0000704,GHR,https://ghr.nlm.nih.gov/condition/myoclonus-dystonia,C1834570,T047,Disorders
How many people are affected by myoclonus-dystonia ?,0000704-2,frequency,The prevalence of myoclonus-dystonia is unknown. This condition has been described in people worldwide.,myoclonus-dystonia,0000704,GHR,https://ghr.nlm.nih.gov/condition/myoclonus-dystonia,C1834570,T047,Disorders
What are the genetic changes related to myoclonus-dystonia ?,0000704-3,genetic changes,"Mutations in the SGCE gene cause myoclonus-dystonia. The SGCE gene provides instructions for making a protein called epsilon ()-sarcoglycan, whose function is unknown. The -sarcoglycan protein is located within the cell membranes of many tissues, but it is most abundant in nerve cells (neurons) in the brain and in muscle cells.  SGCE gene mutations that cause myoclonus-dystonia result in a shortage of -sarcoglycan protein. The protein shortage seems to affect the regions of the brain involved in coordinating movements (the cerebellum) and controlling movements (the basal ganglia). Thus, the movement problems experienced by people with myoclonus-dystonia are caused by dysfunction in the brain, not the muscles. People with this condition show no signs of muscle disease. It is unknown why SGCE gene mutations seem only to affect the brain.",myoclonus-dystonia,0000704,GHR,https://ghr.nlm.nih.gov/condition/myoclonus-dystonia,C1834570,T047,Disorders
Is myoclonus-dystonia inherited ?,0000704-4,inheritance,"Myoclonus-dystonia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  People normally inherit one copy of each gene from their mother and one copy from their father. For most genes, both copies are active, or ""turned on,"" in all cells. For a small subset of genes, however, only one of the two copies is active. For some of these genes, only the copy inherited from a person's father (the paternal copy) is active, while for other genes, only the copy inherited from a person's mother (the maternal copy) is active. These differences in gene activation based on the gene's parent of origin are caused by a phenomenon called genomic imprinting.  Only the paternal copy of the SGCE gene is active. Myoclonus-dystonia occurs when mutations affect the paternal copy of the SGCE gene. Mutations in the maternal copy of the gene typically do not cause any health problems.",myoclonus-dystonia,0000704,GHR,https://ghr.nlm.nih.gov/condition/myoclonus-dystonia,C1834570,T047,Disorders
What are the treatments for myoclonus-dystonia ?,0000704-5,treatment,These resources address the diagnosis or management of myoclonus-dystonia:  - Gene Review: Gene Review: Myoclonus-Dystonia  - Genetic Testing Registry: Myoclonic dystonia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,myoclonus-dystonia,0000704,GHR,https://ghr.nlm.nih.gov/condition/myoclonus-dystonia,C1834570,T047,Disorders
What is (are) myofibrillar myopathy ?,0000705-1,information,"Myofibrillar myopathy is part of a group of disorders called muscular dystrophies that affect muscle function and cause weakness. Myofibrillar myopathy primarily affects skeletal muscles, which are muscles that the body uses for movement. In some cases, the heart (cardiac) muscle is also affected.  The signs and symptoms of myofibrillar myopathy vary widely among affected individuals, typically depending on the condition's genetic cause. Most people with this disorder begin to develop muscle weakness (myopathy) in mid-adulthood. However, features of this condition can appear anytime between infancy and late adulthood. Muscle weakness most often begins in the hands and feet (distal muscles), but some people first experience weakness in the muscles near the center of the body (proximal muscles). Other affected individuals develop muscle weakness throughout their body. Facial muscle weakness can cause swallowing and speech difficulties. Muscle weakness worsens over time.  Other signs and symptoms of myofibrillar myopathy can include a weakened heart muscle (cardiomyopathy), muscle pain (myalgia), loss of sensation and weakness in the limbs (peripheral neuropathy), and respiratory failure. Individuals with this condition may have skeletal problems including joint stiffness (contractures) and abnormal side-to-side curvature of the spine (scoliosis). Rarely, people with this condition develop clouding of the lens of the eyes (cataracts).",myofibrillar myopathy,0000705,GHR,https://ghr.nlm.nih.gov/condition/myofibrillar-myopathy,C2678065,T047,Disorders
How many people are affected by myofibrillar myopathy ?,0000705-2,frequency,The prevalence of myofibrillar myopathy is unknown.,myofibrillar myopathy,0000705,GHR,https://ghr.nlm.nih.gov/condition/myofibrillar-myopathy,C2678065,T047,Disorders
What are the genetic changes related to myofibrillar myopathy ?,0000705-3,genetic changes,"Mutations in several genes can cause myofibrillar myopathy. These genes provide instructions for making proteins that play important roles in muscle fibers. Within muscle fibers, these proteins are involved in the assembly of structures called sarcomeres. Sarcomeres are necessary for muscles to tense (contract). The proteins associated with myofibrillar myopathy are normally active on rod-like structures within the sarcomere called Z-discs. Z-discs link neighboring sarcomeres together to form myofibrils, the basic unit of muscle fibers. The linking of sarcomeres and formation of myofibrils provide strength for muscle fibers during repeated muscle contraction and relaxation.  Gene mutations that cause myofibrillar myopathy disrupt the function of skeletal and cardiac muscle. Various muscle proteins form clumps (aggregates) in the muscle fibers of affected individuals. The aggregates prevent these proteins from functioning normally, which reduces linking between neighboring sarcomeres. As a result, muscle fiber strength is diminished.  At least six genes have been associated with myofibrillar myopathy. Mutations in these six genes account for approximately half of all cases of this condition. Mutations in the DES, MYOT, and LDB3 genes are responsible for the majority of cases of myofibrillar myopathy when the genetic cause is known.",myofibrillar myopathy,0000705,GHR,https://ghr.nlm.nih.gov/condition/myofibrillar-myopathy,C2678065,T047,Disorders
Is myofibrillar myopathy inherited ?,0000705-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",myofibrillar myopathy,0000705,GHR,https://ghr.nlm.nih.gov/condition/myofibrillar-myopathy,C2678065,T047,Disorders
What are the treatments for myofibrillar myopathy ?,0000705-5,treatment,"These resources address the diagnosis or management of myofibrillar myopathy:  - Gene Review: Gene Review: Myofibrillar Myopathy  - Genetic Testing Registry: Alpha-B crystallinopathy  - Genetic Testing Registry: Myofibrillar myopathy  - Genetic Testing Registry: Myofibrillar myopathy 1  - Genetic Testing Registry: Myofibrillar myopathy, BAG3-related  - Genetic Testing Registry: Myofibrillar myopathy, ZASP-related  - Genetic Testing Registry: Myofibrillar myopathy, filamin C-related  - Genetic Testing Registry: Myotilinopathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",myofibrillar myopathy,0000705,GHR,https://ghr.nlm.nih.gov/condition/myofibrillar-myopathy,C2678065,T047,Disorders
What is (are) myopathy with deficiency of iron-sulfur cluster assembly enzyme ?,0000706-1,information,"Myopathy with deficiency of iron-sulfur cluster assembly enzyme is an inherited disorder that primarily affects muscles used for movement (skeletal muscles). This condition does not usually affect other types of muscle, such as the heart (cardiac) muscle.  From early childhood, affected individuals experience extreme fatigue in response to physical activity (exercise intolerance). Mild exertion results in a rapid heartbeat (tachycardia), shortness of breath, and muscle weakness and pain. However, people with this condition typically have normal muscle strength when they are at rest.  Prolonged or recurrent physical activity causes more severe signs and symptoms, including a breakdown of muscle tissue (rhabdomyolysis). The destruction of muscle tissue releases a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria). Myoglobin causes the urine to be red or brown. This protein can also damage the kidneys, in some cases leading to life-threatening kidney failure.  In most affected individuals, the muscle problems associated with this condition do not worsen with time. However, at least two people with a severe variant of this disorder have experienced progressive muscle weakness and wasting starting in childhood.",myopathy with deficiency of iron-sulfur cluster assembly enzyme,0000706,GHR,https://ghr.nlm.nih.gov/condition/myopathy-with-deficiency-of-iron-sulfur-cluster-assembly-enzyme,C0240066,T047,Disorders
How many people are affected by myopathy with deficiency of iron-sulfur cluster assembly enzyme ?,0000706-2,frequency,This condition has been reported in several families of northern Swedish ancestry.,myopathy with deficiency of iron-sulfur cluster assembly enzyme,0000706,GHR,https://ghr.nlm.nih.gov/condition/myopathy-with-deficiency-of-iron-sulfur-cluster-assembly-enzyme,C0240066,T047,Disorders
What are the genetic changes related to myopathy with deficiency of iron-sulfur cluster assembly enzyme ?,0000706-3,genetic changes,"Myopathy with deficiency of iron-sulfur cluster assembly enzyme is caused by mutations in the ISCU gene. This gene provides instructions for making a protein called the iron-sulfur cluster assembly enzyme. As its name suggests, this enzyme is involved in the formation of clusters of iron and sulfur atoms (Fe-S clusters). These clusters are critical for the function of many different proteins, including those needed for DNA repair and the regulation of iron levels. Proteins containing Fe-S clusters are also necessary for energy production within mitochondria, which are the cell structures that convert the energy from food into a form that cells can use.  Mutations in the ISCU gene severely limit the amount of iron-sulfur cluster assembly enzyme that is made in cells. A shortage of this enzyme prevents the normal production of proteins that contain Fe-S clusters, which disrupts a variety of cellular activities. A reduction in the amount of iron-sulfur cluster assembly enzyme is particularly damaging to skeletal muscle cells. Within the mitochondria of these cells, a lack of this enzyme causes problems with energy production and an overload of iron. These defects lead to exercise intolerance and the other features of myopathy with deficiency of iron-sulfur cluster assembly enzyme.",myopathy with deficiency of iron-sulfur cluster assembly enzyme,0000706,GHR,https://ghr.nlm.nih.gov/condition/myopathy-with-deficiency-of-iron-sulfur-cluster-assembly-enzyme,C0240066,T047,Disorders
Is myopathy with deficiency of iron-sulfur cluster assembly enzyme inherited ?,0000706-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",myopathy with deficiency of iron-sulfur cluster assembly enzyme,0000706,GHR,https://ghr.nlm.nih.gov/condition/myopathy-with-deficiency-of-iron-sulfur-cluster-assembly-enzyme,C0240066,T047,Disorders
What are the treatments for myopathy with deficiency of iron-sulfur cluster assembly enzyme ?,0000706-5,treatment,"These resources address the diagnosis or management of myopathy with deficiency of iron-sulfur cluster assembly enzyme:  - Gene Review: Gene Review: Myopathy with Deficiency of ISCU  - Genetic Testing Registry: Myopathy with lactic acidosis, hereditary  - MedlinePlus Encyclopedia: Rhabdomyolysis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",myopathy with deficiency of iron-sulfur cluster assembly enzyme,0000706,GHR,https://ghr.nlm.nih.gov/condition/myopathy-with-deficiency-of-iron-sulfur-cluster-assembly-enzyme,C0240066,T047,Disorders
What is (are) myosin storage myopathy ?,0000707-1,information,"Myosin storage myopathy is a condition that causes muscle weakness (myopathy) that does not worsen or worsens very slowly over time. This condition is characterized by the formation of protein clumps, which contain a protein called myosin, within certain muscle fibers. The signs and symptoms of myosin storage myopathy usually become noticeable in childhood, although they can occur later. Because of muscle weakness, affected individuals may start walking later than usual and have a waddling gait, trouble climbing stairs, and difficulty lifting the arms above shoulder level. Muscle weakness also causes some affected individuals to have trouble breathing.",myosin storage myopathy,0000707,GHR,https://ghr.nlm.nih.gov/condition/myosin-storage-myopathy,C1842160,T047,Disorders
How many people are affected by myosin storage myopathy ?,0000707-2,frequency,Myosin storage myopathy is a rare condition. Its prevalence is unknown.,myosin storage myopathy,0000707,GHR,https://ghr.nlm.nih.gov/condition/myosin-storage-myopathy,C1842160,T047,Disorders
What are the genetic changes related to myosin storage myopathy ?,0000707-3,genetic changes,"Mutations in the MYH7 gene cause myosin storage myopathy. The MYH7 gene provides instructions for making a protein known as the cardiac beta ()-myosin heavy chain. This protein is found in heart (cardiac) muscle and in type I skeletal muscle fibers, one of two types of fibers that make up the muscles that the body uses for movement. Cardiac -myosin heavy chain is the major component of the thick filament in muscle cell structures called sarcomeres. Sarcomeres, which are made up of thick and thin filaments, are the basic units of muscle contraction. The overlapping thick and thin filaments attach to each other and release, which allows the filaments to move relative to one another so that muscles can contract.  Mutations in the MYH7 gene lead to the production of an altered cardiac -myosin heavy chain protein, which is thought to be less able to form thick filaments. The altered proteins accumulate in type I skeletal muscle fibers, forming the protein clumps characteristic of the disorder. It is unclear how these changes lead to muscle weakness in people with myosin storage myopathy.",myosin storage myopathy,0000707,GHR,https://ghr.nlm.nih.gov/condition/myosin-storage-myopathy,C1842160,T047,Disorders
Is myosin storage myopathy inherited ?,0000707-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",myosin storage myopathy,0000707,GHR,https://ghr.nlm.nih.gov/condition/myosin-storage-myopathy,C1842160,T047,Disorders
What are the treatments for myosin storage myopathy ?,0000707-5,treatment,These resources address the diagnosis or management of myosin storage myopathy:  - Genetic Testing Registry: Myosin storage myopathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,myosin storage myopathy,0000707,GHR,https://ghr.nlm.nih.gov/condition/myosin-storage-myopathy,C1842160,T047,Disorders
What is (are) myostatin-related muscle hypertrophy ?,0000708-1,information,"Myostatin-related muscle hypertrophy is a rare condition characterized by reduced body fat and increased muscle size. Affected individuals have up to twice the usual amount of muscle mass in their bodies. They also tend to have increased muscle strength. Myostatin-related muscle hypertrophy is not known to cause any medical problems, and affected individuals are intellectually normal.",myostatin-related muscle hypertrophy,0000708,GHR,https://ghr.nlm.nih.gov/condition/myostatin-related-muscle-hypertrophy,C2931112,T019,Disorders
How many people are affected by myostatin-related muscle hypertrophy ?,0000708-2,frequency,The prevalence of this condition is unknown.,myostatin-related muscle hypertrophy,0000708,GHR,https://ghr.nlm.nih.gov/condition/myostatin-related-muscle-hypertrophy,C2931112,T019,Disorders
What are the genetic changes related to myostatin-related muscle hypertrophy ?,0000708-3,genetic changes,"Mutations in the MSTN gene cause myostatin-related muscle hypertrophy. The MSTN gene provides instructions for making a protein called myostatin, which is active in muscles used for movement (skeletal muscles) both before and after birth. This protein normally restrains muscle growth, ensuring that muscles do not grow too large. Mutations that reduce the production of functional myostatin lead to an overgrowth of muscle tissue.",myostatin-related muscle hypertrophy,0000708,GHR,https://ghr.nlm.nih.gov/condition/myostatin-related-muscle-hypertrophy,C2931112,T019,Disorders
Is myostatin-related muscle hypertrophy inherited ?,0000708-4,inheritance,"Myostatin-related muscle hypertrophy has a pattern of inheritance known as incomplete autosomal dominance. People with a mutation in both copies of the MSTN gene in each cell (homozygotes) have significantly increased muscle mass and strength. People with a mutation in one copy of the MSTN gene in each cell (heterozygotes) also have increased muscle bulk, but to a lesser degree.",myostatin-related muscle hypertrophy,0000708,GHR,https://ghr.nlm.nih.gov/condition/myostatin-related-muscle-hypertrophy,C2931112,T019,Disorders
What are the treatments for myostatin-related muscle hypertrophy ?,0000708-5,treatment,These resources address the diagnosis or management of myostatin-related muscle hypertrophy:  - Gene Review: Gene Review: Myostatin-Related Muscle Hypertrophy  - Genetic Testing Registry: Myostatin-related muscle hypertrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,myostatin-related muscle hypertrophy,0000708,GHR,https://ghr.nlm.nih.gov/condition/myostatin-related-muscle-hypertrophy,C2931112,T019,Disorders
What is (are) myotonia congenita ?,0000709-1,information,"Myotonia congenita is a disorder that affects muscles used for movement (skeletal muscles). Beginning in childhood, people with this condition experience bouts of sustained muscle tensing (myotonia) that prevent muscles from relaxing normally. Although myotonia can affect any skeletal muscles, including muscles of the face and tongue, it occurs most often in the legs. Myotonia causes muscle stiffness that can interfere with movement. In some people the stiffness is very mild, while in other cases it may be severe enough to interfere with walking, running, and other activities of daily life. These muscle problems are particularly noticeable during movement following a period of rest. Many affected individuals find that repeated movements can temporarily alleviate their muscle stiffness, a phenomenon known as the warm-up effect.  The two major types of myotonia congenita are known as Thomsen disease and Becker disease. These conditions are distinguished by the severity of their symptoms and their patterns of inheritance. Becker disease usually appears later in childhood than Thomsen disease and causes more severe muscle stiffness, particularly in males. People with Becker disease often experience temporary attacks of muscle weakness, particularly in the arms and hands, brought on by movement after periods of rest. They may also develop mild, permanent muscle weakness over time. This muscle weakness is not seen in people with Thomsen disease.",myotonia congenita,0000709,GHR,https://ghr.nlm.nih.gov/condition/myotonia-congenita,C2936781,T047,Disorders
How many people are affected by myotonia congenita ?,0000709-2,frequency,"Myotonia congenita is estimated to affect 1 in 100,000 people worldwide. This condition is more common in northern Scandinavia, where it occurs in approximately 1 in 10,000 people.",myotonia congenita,0000709,GHR,https://ghr.nlm.nih.gov/condition/myotonia-congenita,C2936781,T047,Disorders
What are the genetic changes related to myotonia congenita ?,0000709-3,genetic changes,"Mutations in the CLCN1 gene cause myotonia congenita.  The CLCN1 gene provides instructions for making a protein that is critical for the normal function of skeletal muscle cells. For the body to move normally, skeletal muscles must tense (contract) and relax in a coordinated way. Muscle contraction and relaxation are controlled by the flow of charged atoms (ions) into and out of muscle cells. Specifically, the protein produced from the CLCN1 gene forms a channel that controls the flow of negatively charged chlorine atoms (chloride ions) into these cells. The main function of this channel is to stabilize the cells' electrical charge, which prevents muscles from contracting abnormally.  Mutations in the CLCN1 gene alter the usual structure or function of chloride channels. The altered channels cannot properly regulate ion flow, reducing the movement of chloride ions into skeletal muscle cells. This disruption in chloride ion flow triggers prolonged muscle contractions, which are the hallmark of myotonia.",myotonia congenita,0000709,GHR,https://ghr.nlm.nih.gov/condition/myotonia-congenita,C2936781,T047,Disorders
Is myotonia congenita inherited ?,0000709-4,inheritance,"The two forms of myotonia congenita have different patterns of inheritance. Thomsen disease is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.  Becker disease is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.  Because several CLCN1 mutations can cause either Becker disease or Thomsen disease, doctors usually rely on characteristic signs and symptoms to distinguish the two forms of myotonia congenita.",myotonia congenita,0000709,GHR,https://ghr.nlm.nih.gov/condition/myotonia-congenita,C2936781,T047,Disorders
What are the treatments for myotonia congenita ?,0000709-5,treatment,"These resources address the diagnosis or management of myotonia congenita:  - Gene Review: Gene Review: Myotonia Congenita  - Genetic Testing Registry: Congenital myotonia, autosomal dominant form  - Genetic Testing Registry: Congenital myotonia, autosomal recessive form  - Genetic Testing Registry: Myotonia congenita  - MedlinePlus Encyclopedia: Myotonia congenita   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",myotonia congenita,0000709,GHR,https://ghr.nlm.nih.gov/condition/myotonia-congenita,C2936781,T047,Disorders
What is (are) myotonic dystrophy ?,0000710-1,information,"Myotonic dystrophy is part of a group of inherited disorders called muscular dystrophies. It is the most common form of muscular dystrophy that begins in adulthood.  Myotonic dystrophy is characterized by progressive muscle wasting and weakness. People with this disorder often have prolonged muscle contractions (myotonia) and are not able to relax certain muscles after use. For example, a person may have difficulty releasing their grip on a doorknob or handle. Also, affected people may have slurred speech or temporary locking of their jaw.  Other signs and symptoms of myotonic dystrophy include clouding of the lens of the eye (cataracts) and abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects). In affected men, hormonal changes may lead to early balding and an inability to father a child (infertility). The features of this disorder often develop during a person's twenties or thirties, although they can occur at any age. The severity of the condition varies widely among affected people, even among members of the same family.  There are two major types of myotonic dystrophy: type 1 and type 2. Their signs and symptoms overlap, although type 2 tends to be milder than type 1. The muscle weakness associated with type 1 particularly affects the lower legs, hands, neck, and face. Muscle weakness in type 2 primarily involves the muscles of the neck, shoulders, elbows, and hips. The two types of myotonic dystrophy are caused by mutations in different genes.  A variation of type 1 myotonic dystrophy, called congenital myotonic dystrophy, is apparent at birth. Characteristic features include weak muscle tone (hypotonia), an inward- and upward-turning foot (clubfoot), breathing problems, delayed development, and intellectual disability. Some of these health problems can be life-threatening.",myotonic dystrophy,0000710,GHR,https://ghr.nlm.nih.gov/condition/myotonic-dystrophy,C0027126,T047,Disorders
How many people are affected by myotonic dystrophy ?,0000710-2,frequency,"Myotonic dystrophy affects at least 1 in 8,000 people worldwide. The prevalence of the two types of myotonic dystrophy varies among different geographic and ethnic populations. In most populations, type 1 appears to be more common than type 2. However, recent studies suggest that type 2 may be as common as type 1 among people in Germany and Finland.",myotonic dystrophy,0000710,GHR,https://ghr.nlm.nih.gov/condition/myotonic-dystrophy,C0027126,T047,Disorders
What are the genetic changes related to myotonic dystrophy ?,0000710-3,genetic changes,"Myotonic dystrophy type 1 is caused by mutations in the DMPK gene, while type 2 results from mutations in the CNBP gene. The specific functions of these genes are unclear. The protein produced from the DMPK gene may play a role in communication within cells. It appears to be important for the correct functioning of cells in the heart, brain, and skeletal muscles (which are used for movement). The protein produced from the CNBP gene is found primarily in the heart and in skeletal muscles, where it probably helps regulate the function of other genes.  Similar changes in the structure of the DMPK and CNBP genes cause the two forms of myotonic dystrophy. In each case, a segment of DNA is abnormally repeated many times, forming an unstable region in the gene. The mutated gene produces an expanded version of messenger RNA, which is a molecular blueprint of the gene that is normally used to guide the production of proteins. The abnormally long messenger RNA forms clumps inside the cell that interfere with the production of many other proteins. These changes prevent muscle cells and cells in other tissues from functioning normally, which leads to the signs and symptoms of myotonic dystrophy.",myotonic dystrophy,0000710,GHR,https://ghr.nlm.nih.gov/condition/myotonic-dystrophy,C0027126,T047,Disorders
Is myotonic dystrophy inherited ?,0000710-4,inheritance,"Both types of myotonic dystrophy are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.  As myotonic dystrophy is passed from one generation to the next, the disorder generally begins earlier in life and signs and symptoms become more severe. This phenomenon, called anticipation, has been reported with both types of myotonic dystrophy. However, the evidence for anticipation appears to be strongest in myotonic dystrophy type 1. In this form of the disorder, anticipation is caused by an increase in the length of the unstable region in the DMPK gene. It is less clear whether anticipation occurs in myotonic dystrophy type 2, and the mechanism is unknown. A longer unstable region in the CNBP gene does not appear to influence the age of onset of the disorder.",myotonic dystrophy,0000710,GHR,https://ghr.nlm.nih.gov/condition/myotonic-dystrophy,C0027126,T047,Disorders
What are the treatments for myotonic dystrophy ?,0000710-5,treatment,These resources address the diagnosis or management of myotonic dystrophy:  - Gene Review: Gene Review: Myotonic Dystrophy Type 1  - Gene Review: Gene Review: Myotonic Dystrophy Type 2  - Genetic Testing Registry: Myotonic dystrophy type 2  - Genetic Testing Registry: Steinert myotonic dystrophy syndrome  - MedlinePlus Encyclopedia: Muscular Dystrophy  - University of Washington: Myotonic Dystrophy: Making an Informed Choice About Genetic Testing   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,myotonic dystrophy,0000710,GHR,https://ghr.nlm.nih.gov/condition/myotonic-dystrophy,C0027126,T047,Disorders
What is (are) N-acetylglutamate synthase deficiency ?,0000711-1,information,"N-acetylglutamate synthase deficiency is an inherited disorder that causes ammonia to accumulate in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.  N-acetylglutamate synthase deficiency may become evident in the first few days of life. An infant with this condition may be lacking in energy (lethargic) or unwilling to eat, and have a poorly controlled breathing rate or body temperature. Some babies with this disorder may experience seizures or unusual body movements, or go into a coma. Complications of N-acetylglutamate synthase deficiency may include developmental delay and intellectual disability.  In some affected individuals, signs and symptoms of N-acetylglutamate synthase deficiency are less severe, and do not appear until later in life. Some people with this form of the disorder cannot tolerate high-protein foods such as meat. They may experience sudden episodes of ammonia toxicity, resulting in vomiting, lack of coordination, confusion or coma, in response to illness or other stress.",N-acetylglutamate synthase deficiency,0000711,GHR,https://ghr.nlm.nih.gov/condition/n-acetylglutamate-synthase-deficiency,C0268543,T047,Disorders
How many people are affected by N-acetylglutamate synthase deficiency ?,0000711-2,frequency,"N-acetylglutamate synthase deficiency is a very rare disorder. Only a few cases have been reported worldwide, and the overall incidence is unknown.",N-acetylglutamate synthase deficiency,0000711,GHR,https://ghr.nlm.nih.gov/condition/n-acetylglutamate-synthase-deficiency,C0268543,T047,Disorders
What are the genetic changes related to N-acetylglutamate synthase deficiency ?,0000711-3,genetic changes,"Mutations in the NAGS gene cause N-acetylglutamate synthase deficiency.  N-acetylglutamate synthase deficiency belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions that occurs in liver cells. This cycle processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys.  The NAGS gene provides instructions for making the enzyme N-acetylglutamate synthase, which helps produce a compound called N-acetylglutamate. This compound is needed to activate another enzyme, carbamoyl phosphate synthetase I, which controls the first step of the urea cycle.  In people with N-acetylglutamate synthase deficiency, N-acetylglutamate is not available in sufficient quantities, or is not present at all. As a result, urea cannot be produced normally, and excess nitrogen accumulates in the blood in the form of ammonia. This accumulation of ammonia causes the neurological problems and other signs and symptoms of N-acetylglutamate synthase deficiency.",N-acetylglutamate synthase deficiency,0000711,GHR,https://ghr.nlm.nih.gov/condition/n-acetylglutamate-synthase-deficiency,C0268543,T047,Disorders
Is N-acetylglutamate synthase deficiency inherited ?,0000711-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",N-acetylglutamate synthase deficiency,0000711,GHR,https://ghr.nlm.nih.gov/condition/n-acetylglutamate-synthase-deficiency,C0268543,T047,Disorders
What are the treatments for N-acetylglutamate synthase deficiency ?,0000711-5,treatment,"These resources address the diagnosis or management of N-acetylglutamate synthase deficiency:  - Gene Review: Gene Review: Urea Cycle Disorders Overview  - Genetic Testing Registry: Hyperammonemia, type III  - MedlinePlus Encyclopedia: Hereditary Urea Cycle Abnormality   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",N-acetylglutamate synthase deficiency,0000711,GHR,https://ghr.nlm.nih.gov/condition/n-acetylglutamate-synthase-deficiency,C0268543,T047,Disorders
What is (are) Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis ?,0000712-1,information,"Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis (NFJS/DPR) represents a rare type of ectodermal dysplasia, a group of about 150 conditions characterized by abnormal development of ectodermal tissues including the skin, hair, nails, teeth, and sweat glands. NFJS and DPR were originally described as separate conditions; however, because they have similar features and are caused by mutations in the same gene, they are now often considered forms of the same disorder.  Among the most common signs of NFJS/DPR is a net-like pattern of dark brown or gray skin coloring, known as reticulate hyperpigmentation. This darker pigmentation is seen most often on the neck, chest, and abdomen, although it can also occur in and around the eyes and mouth. Reticulate hyperpigmentation appears in infancy or early childhood. It may fade with age or persist throughout life.  NFJS/DPR also affects the skin on the hands and feet. The skin on the palms of the hands and soles of the feet often becomes thick, hard, and callused, a condition known as palmoplantar keratoderma. Some affected individuals also have blistering on their palms and soles. Their fingernails and toenails may be malformed, brittle, and either thicker or thinner than usual. Most affected individuals are missing the patterned ridges on the skin of the hands and feet, called dermatoglyphs, that are the basis for each person's unique fingerprints.  Additional features of NFJS/DPR can include a reduced ability to sweat (hypohidrosis) or excess sweating (hyperhidrosis) and dental abnormalities. Some affected individuals also have hair loss (alopecia) on the scalp, eyebrows, and underarms. The alopecia is described as noncicatricial because it does not leave scars (cicatrices).",Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis,0000712,GHR,https://ghr.nlm.nih.gov/condition/naegeli-franceschetti-jadassohn-syndrome-dermatopathia-pigmentosa-reticularis,C0406778,T019,Disorders
How many people are affected by Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis ?,0000712-2,frequency,NFJS/DPR is a rare condition; its prevalence is unknown. Only a few affected families have been reported in the medical literature.,Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis,0000712,GHR,https://ghr.nlm.nih.gov/condition/naegeli-franceschetti-jadassohn-syndrome-dermatopathia-pigmentosa-reticularis,C0406778,T019,Disorders
What are the genetic changes related to Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis ?,0000712-3,genetic changes,"NFJS/DPR results from mutations in the KRT14 gene. This gene provides instructions for making a protein called keratin 14. Keratins are tough, fibrous proteins that provide strength and resiliency to the outer layer of the skin (the epidermis). Researchers believe that keratin 14 may also play a role in the formation of sweat glands and the development of dermatoglyphs.  The KRT14 gene mutations that cause NFJS/DPR most likely reduce the amount of functional keratin 14 that is produced in cells. A shortage of this protein makes cells in the epidermis more likely to self-destruct (undergo apoptosis). The resulting loss of these cells alters the normal development and structure of ectodermal tissues, which likely underlies most of the skin and nail problems characteristic of NFJS/DPR. However, it is unclear how a shortage of keratin 14 is related to changes in skin pigmentation.",Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis,0000712,GHR,https://ghr.nlm.nih.gov/condition/naegeli-franceschetti-jadassohn-syndrome-dermatopathia-pigmentosa-reticularis,C0406778,T019,Disorders
Is Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis inherited ?,0000712-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis,0000712,GHR,https://ghr.nlm.nih.gov/condition/naegeli-franceschetti-jadassohn-syndrome-dermatopathia-pigmentosa-reticularis,C0406778,T019,Disorders
What are the treatments for Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis ?,0000712-5,treatment,These resources address the diagnosis or management of NFJS/DPR:  - Foundation for Ichthyosis and Related Skin Types (FIRST): Palmoplantar Keratodermas  - Genetic Testing Registry: Dermatopathia pigmentosa reticularis  - Genetic Testing Registry: Naegeli-Franceschetti-Jadassohn syndrome  - MedlinePlus Encyclopedia: Ectodermal Dysplasia  - MedlinePlus Encyclopedia: Nail Abnormalities   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis,0000712,GHR,https://ghr.nlm.nih.gov/condition/naegeli-franceschetti-jadassohn-syndrome-dermatopathia-pigmentosa-reticularis,C0406778,T019,Disorders
What is (are) Nager syndrome ?,0000713-1,information,"Nager syndrome is a rare condition that mainly affects the development of the face, hands, and arms. The severity of this disorder varies among affected individuals.  Children with Nager syndrome are born with underdeveloped cheek bones (malar hypoplasia) and a very small lower jaw (micrognathia). They often have an opening in the roof of the mouth called a cleft palate. These abnormalities frequently cause feeding problems in infants with Nager syndrome. The airway is usually restricted due to the micrognathia, which can lead to life-threatening breathing problems.  People with Nager syndrome often have eyes that slant downward, absent eyelashes, and a notch in the lower eyelids called an eyelid coloboma. Many affected individuals have small or unusually formed ears, and about 60 percent have hearing loss caused by defects in the middle ear (conductive hearing loss). Nager syndrome does not affect a person's intelligence, although speech development may be delayed due to hearing impairment.  Individuals with Nager syndrome have bone abnormalities in their hands and arms. The most common abnormality is malformed or absent thumbs. Affected individuals may also have fingers that are unusually curved (clinodactyly) or fused together (syndactyly). Their forearms may be shortened due to the partial or complete absence of a bone called the radius. People with Nager syndrome sometimes have difficulty fully extending their elbows. This condition can also cause bone abnormalities in the legs and feet.  Less commonly, affected individuals have abnormalities of the heart, kidneys, genitalia, and urinary tract.",Nager syndrome,0000713,GHR,https://ghr.nlm.nih.gov/condition/nager-syndrome,C0265245,T019,Disorders
How many people are affected by Nager syndrome ?,0000713-2,frequency,"Nager syndrome is a rare condition, although its prevalence is unknown. More than 75 cases have been reported in the medical literature.",Nager syndrome,0000713,GHR,https://ghr.nlm.nih.gov/condition/nager-syndrome,C0265245,T019,Disorders
What are the genetic changes related to Nager syndrome ?,0000713-3,genetic changes,"The cause of Nager syndrome is unknown. Although the specific genes involved have not been identified, researchers believe that this condition is caused by changes in a particular region of chromosome 9 in some families.  Nager syndrome disrupts the development of structures called the first and second pharyngeal arches. The pharyngeal arches are five paired structures that form on each side of the head and neck during embryonic development. These structures develop into the bones, skin, nerves, and muscles of the head and neck. In particular, the first and second pharyngeal arches develop into the jaw, the nerves and muscles for chewing and facial expressions, the bones in the middle ear, and the outer ear. The cause of the abnormal development of the pharyngeal arches in Nager syndrome is unknown. It is also unclear why affected individuals have bone abnormalities in their arms and legs.",Nager syndrome,0000713,GHR,https://ghr.nlm.nih.gov/condition/nager-syndrome,C0265245,T019,Disorders
Is Nager syndrome inherited ?,0000713-4,inheritance,"Most cases of Nager syndrome are sporadic, which means that they occur in people with no history of the disorder in their family. Less commonly, this condition has been found to run in families. When the disorder is familial, it can have an autosomal dominant or an autosomal recessive pattern of inheritance.  Autosomal dominant inheritance means one copy of an altered gene in each cell is sufficient to cause the disorder, although no genes have been associated with Nager syndrome. In autosomal dominant Nager syndrome, an affected person usually inherits the condition from one affected parent.  Autosomal recessive inheritance means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of a mutated gene, but they typically do not show signs and symptoms of the condition. Nager syndrome is thought to have an autosomal recessive inheritance pattern when unaffected parents have more than one affected child.  The underlying genetic cause may differ among unrelated individuals with Nager syndrome, even among those with the same pattern of inheritance.",Nager syndrome,0000713,GHR,https://ghr.nlm.nih.gov/condition/nager-syndrome,C0265245,T019,Disorders
What are the treatments for Nager syndrome ?,0000713-5,treatment,These resources address the diagnosis or management of Nager syndrome:  - Genetic Testing Registry: Nager syndrome  - University of California San Francisco Medical Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Nager syndrome,0000713,GHR,https://ghr.nlm.nih.gov/condition/nager-syndrome,C0265245,T019,Disorders
What is (are) nail-patella syndrome ?,0000714-1,information,"Nail-patella syndrome is characterized by abnormalities of the nails, knees, elbows, and pelvis. The features of nail-patella syndrome vary in severity between affected individuals, even among members of the same family.  Nail abnormalities are seen in almost all individuals with nail-patella syndrome. The nails may be absent or underdeveloped and discolored, split, ridged, or pitted. The fingernails are more likely to be affected than the toenails, and the thumbnails are usually the most severely affected. In many people with this condition, the areas at the base of the nails (lunulae) are triangular instead of the usual crescent shape.  Individuals with nail-patella syndrome also commonly have skeletal abnormalities involving the knees, elbows, and hips. The kneecaps (patellae) are small, irregularly shaped, or absent, and dislocation of the patella is common. Some people with this condition may not be able to fully extend their arms or turn their palms up while keeping their elbows straight. The elbows may also be angled outward (cubitus valgus) or have abnormal webbing. Many individuals with nail-patella syndrome have horn-like outgrowths of the iliac bones of the pelvis (iliac horns). These abnormal projections may be felt through the skin, but they do not cause any symptoms and are usually detected on a pelvic x-ray. Iliac horns are very common in people with nail-patella syndrome and are rarely, if ever, seen in people without this condition.  Other areas of the body may also be affected in nail-patella syndrome, particularly the eyes and kidneys. Individuals with this condition are at risk of developing increased pressure within the eyes (glaucoma) at an early age. Some people develop kidney disease, which can progress to kidney failure.",nail-patella syndrome,0000714,GHR,https://ghr.nlm.nih.gov/condition/nail-patella-syndrome,C0027341,T019,Disorders
How many people are affected by nail-patella syndrome ?,0000714-2,frequency,"The prevalence of nail-patella syndrome is estimated to be 1 in 50,000 individuals.",nail-patella syndrome,0000714,GHR,https://ghr.nlm.nih.gov/condition/nail-patella-syndrome,C0027341,T019,Disorders
What are the genetic changes related to nail-patella syndrome ?,0000714-3,genetic changes,"Mutations in the LMX1B gene cause nail-patella syndrome. The LMX1B gene provides instructions for producing a protein that attaches (binds) to specific regions of DNA and regulates the activity of other genes. On the basis of this role, the LMX1B protein is called a transcription factor. The LMX1B protein appears to be particularly important during early embryonic development of the limbs, kidneys, and eyes. Mutations in the LMX1B gene lead to the production of an abnormally short, nonfunctional protein or affect the protein's ability to bind to DNA. It is unclear how mutations in the LMX1B gene lead to the signs and symptoms of nail-patella syndrome.",nail-patella syndrome,0000714,GHR,https://ghr.nlm.nih.gov/condition/nail-patella-syndrome,C0027341,T019,Disorders
Is nail-patella syndrome inherited ?,0000714-4,inheritance,"Nail-patella syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the LMX1B gene. These cases occur in people with no history of the disorder in their family.",nail-patella syndrome,0000714,GHR,https://ghr.nlm.nih.gov/condition/nail-patella-syndrome,C0027341,T019,Disorders
What are the treatments for nail-patella syndrome ?,0000714-5,treatment,These resources address the diagnosis or management of nail-patella syndrome:  - Gene Review: Gene Review: Nail-Patella Syndrome  - Genetic Testing Registry: Nail-patella syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,nail-patella syndrome,0000714,GHR,https://ghr.nlm.nih.gov/condition/nail-patella-syndrome,C0027341,T019,Disorders
What is (are) Nakajo-Nishimura syndrome ?,0000715-1,information,"Nakajo-Nishimura syndrome is an inherited condition that affects many parts of the body and has been described only in the Japanese population. Beginning in infancy or early childhood, affected individuals develop red, swollen lumps (nodular erythema) on the skin that occur most often in cold weather; recurrent fevers; and elongated fingers and toes with widened and rounded tips (clubbing).  Later in childhood, affected individuals develop joint pain and joint deformities called contractures that limit movement, particularly in the hands, wrists, and elbows. They also experience weakness and wasting of muscles, along with a loss of fatty tissue (lipodystrophy), mainly in the upper body. The combination of muscle and fat loss worsens over time, leading to an extremely thin (emaciated) appearance in the face, chest, and arms.  Other signs and symptoms of Nakajo-Nishimura syndrome can include an enlarged liver and spleen (hepatosplenomegaly), a shortage of red blood cells (anemia), a reduced amount of blood clotting cells called platelets (thrombocytopenia), and abnormal deposits of calcium (calcification) in an area of the brain called the basal ganglia. Intellectual disability has been reported in some affected individuals.  The signs and symptoms of Nakajo-Nishimura syndrome overlap with those of two other conditions: one called joint contractures, muscular atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP) syndrome; and the other called chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome. All three conditions are characterized by skin abnormalities and lipodystrophy. Although they are often considered separate disorders, they are caused by mutations in the same gene, and some researchers believe they may represent different forms of a single condition.",Nakajo-Nishimura syndrome,0000715,GHR,https://ghr.nlm.nih.gov/condition/nakajo-nishimura-syndrome,C1850568,T047,Disorders
How many people are affected by Nakajo-Nishimura syndrome ?,0000715-2,frequency,Nakajo-Nishimura syndrome appears to be rare and has been described only in the Japanese population. About 30 cases have been reported in the medical literature.,Nakajo-Nishimura syndrome,0000715,GHR,https://ghr.nlm.nih.gov/condition/nakajo-nishimura-syndrome,C1850568,T047,Disorders
What are the genetic changes related to Nakajo-Nishimura syndrome ?,0000715-3,genetic changes,"Nakajo-Nishimura syndrome is caused by mutations in the PSMB8 gene. This gene provides instructions for making one part (subunit) of specialized cell structures called immunoproteasomes, which are found primarily in immune system cells. Immunoproteasomes play an important role in regulating the immune system's response to foreign invaders, such as viruses and bacteria. One of the primary functions of immunoproteasomes is to help the immune system distinguish the body's own proteins from proteins made by foreign invaders, so the immune system can respond appropriately to infection.  Mutations in the PSMB8 gene greatly reduce the amount of protein produced from the PSMB8 gene, which impairs the normal assembly of immunoproteasomes and causes the immune system to malfunction. For unknown reasons, the malfunctioning immune system triggers abnormal inflammation that can damage the body's own tissues and organs; as a result, Nakajo-Nishimura syndrome is classified as an autoinflammatory disorder.  Abnormal inflammation likely underlies many of the signs and symptoms of Nakajo-Nishimura syndrome, including the nodular erythema, recurrent fevers, joint problems, and hepatosplenomegaly. It is less clear how mutations in the PSMB8 gene lead to muscle wasting and lipodystrophy. Studies suggest that the protein produced from the PSMB8 gene may play a separate role in the maturation of fat cells (adipocytes), and a shortage of this protein may interfere with the normal development and function of these cells.",Nakajo-Nishimura syndrome,0000715,GHR,https://ghr.nlm.nih.gov/condition/nakajo-nishimura-syndrome,C1850568,T047,Disorders
Is Nakajo-Nishimura syndrome inherited ?,0000715-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Nakajo-Nishimura syndrome,0000715,GHR,https://ghr.nlm.nih.gov/condition/nakajo-nishimura-syndrome,C1850568,T047,Disorders
What are the treatments for Nakajo-Nishimura syndrome ?,0000715-5,treatment,These resources address the diagnosis or management of Nakajo-Nishimura syndrome:  - Genetic Testing Registry: Nakajo syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Nakajo-Nishimura syndrome,0000715,GHR,https://ghr.nlm.nih.gov/condition/nakajo-nishimura-syndrome,C1850568,T047,Disorders
What is (are) narcolepsy ?,0000716-1,information,"Narcolepsy is a chronic sleep disorder that disrupts the normal sleep-wake cycle. Although this condition can appear at any age, it most often begins in adolescence.  Narcolepsy is characterized by excessive daytime sleepiness. Affected individuals feel tired during the day, and several times a day they may experience an overwhelming urge to sleep. ""Sleep attacks"" can occur at unusual times, such as during a meal or in the middle of a conversation. They last from a few seconds to a few minutes and often lead to a longer nap, after which affected individuals wake up feeling refreshed.  Another common feature of narcolepsy is cataplexy, which is a sudden loss of muscle tone in response to strong emotion (such as laughing, surprise, or anger). These episodes of muscle weakness can cause an affected person to slump over or fall, which occasionally leads to injury. Episodes of cataplexy usually last just a few seconds, and they may occur from several times a day to a few times a year. Most people diagnosed with narcolepsy also have cataplexy. However, some do not, which has led researchers to distinguish two major forms of the condition: narcolepsy with cataplexy and narcolepsy without cataplexy.  Narcolepsy also affects nighttime sleep. Most affected individuals have trouble sleeping for more than a few hours at night. They often experience vivid hallucinations while falling asleep (hypnogogic hallucinations) or while waking up (hypnopompic hallucinations). Affected individuals often have realistic and distressing dreams, and they may act out their dreams by moving excessively or talking in their sleep. Many people with narcolepsy also experience sleep paralysis, which is an inability to move or speak for a short period while falling asleep or awakening. The combination of hallucinations, vivid dreams, and sleep paralysis is often frightening and unpleasant for affected individuals.  Some people with narcolepsy have all of the major features of the disorder, while others have only one or two. Most of the signs and symptoms persist throughout life, although episodes of cataplexy may become less frequent with age and treatment.",narcolepsy,0000716,GHR,https://ghr.nlm.nih.gov/condition/narcolepsy,C0027404,T047,Disorders
How many people are affected by narcolepsy ?,0000716-2,frequency,"Narcolepsy affects about 1 in 2,000 people in the United States and Western Europe. However, the disorder is likely underdiagnosed, particularly in people with mild symptoms. Worldwide, narcolepsy appears to be most common in Japan, where it affects an estimated 1 in 600 people.",narcolepsy,0000716,GHR,https://ghr.nlm.nih.gov/condition/narcolepsy,C0027404,T047,Disorders
What are the genetic changes related to narcolepsy ?,0000716-3,genetic changes,"Narcolepsy probably results from a combination of genetic and environmental factors, some of which have been identified, but many of which remain unknown.  In most cases of narcolepsy with cataplexy, and in some cases without cataplexy, sleep abnormalities result from a loss of particular brain cells (neurons) in a part of the brain called the hypothalamus. These cells normally produce chemicals called hypocretins (also known as orexins), which have many important functions in the body. In particular, hypocretins regulate the daily sleep-wake cycle. It is unclear what triggers the death of hypocretin-producing neurons in people with narcolepsy, although evidence increasingly points to an abnormality of the immune system.  Researchers have identified changes in several genes that influence the risk of developing narcolepsy. The most well-studied of these genes is HLA-DQB1, which provides instructions for making part of a protein that plays an important role in the immune system. The HLA-DQB1 gene is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). The HLA-DQB1 gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. A variation of the HLA-DQB1 gene called HLA-DQB1*06:02 has been strongly associated with narcolepsy, particularly in people who also have cataplexy and a loss of hypocretins. Most people with narcolepsy have the HLA-DQB1*06:02 variation, and many also have specific versions of other, closely related HLA genes. It is unclear how these genetic changes influence the risk of developing the condition.  Variations in several additional genes have also been associated with narcolepsy. Many of these genes are thought to play roles in immune system function. However, variations in these genes probably make only a small contribution to the overall risk of developing narcolepsy. Other genetic and environmental factors are also likely to influence a person's chances of developing this disorder. For example, studies suggest that bacterial or viral infections such as strep throat (streptococcus), colds, and influenza may be involved in triggering narcolepsy in people who are at risk.",narcolepsy,0000716,GHR,https://ghr.nlm.nih.gov/condition/narcolepsy,C0027404,T047,Disorders
Is narcolepsy inherited ?,0000716-4,inheritance,"Most cases of narcolepsy are sporadic, which means they occur in people with no history of the disorder in their family. A small percentage of all cases have been reported to run in families; however, the condition does not have a clear pattern of inheritance. First-degree relatives (parents, siblings, and children) of people with narcolepsy with cataplexy have a 40 times greater risk of developing the condition compared with people in the general population.",narcolepsy,0000716,GHR,https://ghr.nlm.nih.gov/condition/narcolepsy,C0027404,T047,Disorders
What are the treatments for narcolepsy ?,0000716-5,treatment,"These resources address the diagnosis or management of narcolepsy:  - Genetic Testing Registry: Narcolepsy 1  - Genetic Testing Registry: Narcolepsy 2, susceptibility to  - Genetic Testing Registry: Narcolepsy 3  - Genetic Testing Registry: Narcolepsy 4, susceptibility to  - Genetic Testing Registry: Narcolepsy 5, susceptibility to  - Narcolepsy Network: Treatment   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",narcolepsy,0000716,GHR,https://ghr.nlm.nih.gov/condition/narcolepsy,C0027404,T047,Disorders
What is (are) nemaline myopathy ?,0000717-1,information,"Nemaline myopathy is a disorder that primarily affects skeletal muscles, which are muscles that the body uses for movement. People with nemaline myopathy have muscle weakness (myopathy) throughout the body, but it is typically most severe in the muscles of the face, neck, and limbs. This weakness can worsen over time. Affected individuals may have feeding and swallowing difficulties, foot deformities, abnormal curvature of the spine (scoliosis), and joint deformities (contractures). Most people with nemaline myopathy are able to walk, although some affected children may begin walking later than usual. As the condition progresses, some people may require wheelchair assistance. In severe cases, the muscles used for breathing are affected and life-threatening breathing difficulties can occur.  Nemaline myopathy is divided into six types. In order of decreasing severity, the types are: severe congenital, Amish, intermediate congenital, typical congenital, childhood-onset, and adult-onset. The types are distinguished by the age when symptoms first appear and the severity of symptoms; however, there is overlap among the various types. The severe congenital type is the most life-threatening. Most individuals with this type do not survive past early childhood due to respiratory failure. The Amish type solely affects the Old Order Amish population of Pennsylvania and is typically fatal in early childhood. The most common type of nemaline myopathy is the typical congenital type, which is characterized by muscle weakness and feeding problems beginning in infancy. Most of these individuals do not have severe breathing problems and can walk unassisted. People with the childhood-onset type usually develop muscle weakness in adolescence. The adult-onset type is the mildest of all the various types. People with this type usually develop muscle weakness between ages 20 and 50.",nemaline myopathy,0000717,GHR,https://ghr.nlm.nih.gov/condition/nemaline-myopathy,C0206157,T047,Disorders
How many people are affected by nemaline myopathy ?,0000717-2,frequency,"Nemaline myopathy has an estimated incidence of 1 in 50,000 individuals.",nemaline myopathy,0000717,GHR,https://ghr.nlm.nih.gov/condition/nemaline-myopathy,C0206157,T047,Disorders
What are the genetic changes related to nemaline myopathy ?,0000717-3,genetic changes,"Mutations in one of many genes can cause nemaline myopathy. These genes provide instructions for producing proteins that play important roles in skeletal muscles. Within skeletal muscle cells, these proteins are found in structures called sarcomeres. Sarcomeres are necessary for muscles to tense (contract). Many of the proteins associated with nemaline myopathy interact within the sarcomere to facilitate muscle contraction. When the skeletal muscle cells of people with nemaline myopathy are stained and viewed under a microscope, these cells usually appear abnormal. These abnormal muscle cells contain rod-like structures called nemaline bodies.  Most cases of nemaline myopathy with a known genetic cause result from mutations in one of two genes, NEB or ACTA1. NEB gene mutations account for about 50 percent of all cases of nemaline myopathy and ACTA1 gene mutations account for 15 to 25 percent of all cases. When nemaline myopathy is caused by NEB gene mutations, signs and symptoms are typically present at birth or beginning in early childhood. When nemaline myopathy is caused by ACTA1 gene mutations, the condition's severity and age of onset vary widely. Mutations in the other genes associated with nemaline myopathy each account for only a small percentage of cases.  Mutations in any of the genes associated with nemaline myopathy lead to disorganization of the proteins found in the sarcomeres of skeletal muscles. The disorganized proteins cannot interact normally, which disrupts muscle contraction. Inefficient muscle contraction leads to muscle weakness and the other features of nemaline myopathy.  Some individuals with nemaline myopathy do not have an identified mutation. The genetic cause of the disorder is unknown in these individuals.",nemaline myopathy,0000717,GHR,https://ghr.nlm.nih.gov/condition/nemaline-myopathy,C0206157,T047,Disorders
Is nemaline myopathy inherited ?,0000717-4,inheritance,"Nemaline myopathy is usually inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Less often, this condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",nemaline myopathy,0000717,GHR,https://ghr.nlm.nih.gov/condition/nemaline-myopathy,C0206157,T047,Disorders
What are the treatments for nemaline myopathy ?,0000717-5,treatment,These resources address the diagnosis or management of nemaline myopathy:  - Gene Review: Gene Review: Nemaline Myopathy  - Genetic Testing Registry: Nemaline myopathy  - Genetic Testing Registry: Nemaline myopathy 1  - Genetic Testing Registry: Nemaline myopathy 10  - Genetic Testing Registry: Nemaline myopathy 2  - Genetic Testing Registry: Nemaline myopathy 3  - Genetic Testing Registry: Nemaline myopathy 4  - Genetic Testing Registry: Nemaline myopathy 5  - Genetic Testing Registry: Nemaline myopathy 6  - Genetic Testing Registry: Nemaline myopathy 7  - Genetic Testing Registry: Nemaline myopathy 8  - Genetic Testing Registry: Nemaline myopathy 9   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,nemaline myopathy,0000717,GHR,https://ghr.nlm.nih.gov/condition/nemaline-myopathy,C0206157,T047,Disorders
What is (are) neonatal onset multisystem inflammatory disease ?,0000718-1,information,"Neonatal onset multisystem inflammatory disease (NOMID) is a disorder that causes persistent inflammation and tissue damage primarily affecting the nervous system, skin, and joints. Recurrent episodes of mild fever may also occur in this disorder.  People with NOMID have a skin rash that is usually present from birth. The rash persists throughout life, although it changes in size and location.  Affected individuals often have headaches, seizures, and vomiting resulting from chronic meningitis, which is inflammation of the tissue that covers and protects the brain and spinal cord (meninges). Intellectual disability may occur in some people with this disorder. Hearing and vision problems may result from nerve damage and inflammation in various tissues of the eyes.  People with NOMID experience joint inflammation, swelling, and cartilage overgrowth, causing characteristic prominent knees and other skeletal abnormalities that worsen over time. Joint deformities called contractures may restrict the movement of certain joints.  Other features of this disorder include short stature with shortening of the lower legs and forearms, and characteristic facial features such as a prominent forehead and protruding eyes. Abnormal deposits of a protein called amyloid (amyloidosis) may cause progressive kidney damage.",neonatal onset multisystem inflammatory disease,0000718,GHR,https://ghr.nlm.nih.gov/condition/neonatal-onset-multisystem-inflammatory-disease,C0409818,T047,Disorders
How many people are affected by neonatal onset multisystem inflammatory disease ?,0000718-2,frequency,NOMID is a very rare disorder; approximately 100 affected individuals have been reported worldwide.,neonatal onset multisystem inflammatory disease,0000718,GHR,https://ghr.nlm.nih.gov/condition/neonatal-onset-multisystem-inflammatory-disease,C0409818,T047,Disorders
What are the genetic changes related to neonatal onset multisystem inflammatory disease ?,0000718-3,genetic changes,"Mutations in the NLRP3 gene (also known as CIAS1) cause NOMID. The NLRP3 gene provides instructions for making a protein called cryopyrin.  Cryopyrin belongs to a family of proteins called nucleotide-binding domain and leucine-rich repeat containing (NLR) proteins. These proteins are involved in the immune system, helping to regulate the process of inflammation. Inflammation occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight microbial invaders and facilitate tissue repair. When this has been accomplished, the body stops (inhibits) the inflammatory response to prevent damage to its own cells and tissues.  Cryopyrin is involved in the assembly of a molecular complex called an inflammasome, which helps trigger the inflammatory process. Researchers believe that NLRP3 mutations that cause NOMID result in a hyperactive cryopyrin protein and an inappropriate inflammatory response. Impairment of the body's mechanisms for controlling inflammation results in the episodes of fever and widespread inflammatory damage to the body's cells and tissues seen in NOMID.  In about 50 percent of individuals diagnosed with NOMID, no mutations in the NLRP3 gene have been identified. The cause of NOMID in these individuals is unknown.",neonatal onset multisystem inflammatory disease,0000718,GHR,https://ghr.nlm.nih.gov/condition/neonatal-onset-multisystem-inflammatory-disease,C0409818,T047,Disorders
Is neonatal onset multisystem inflammatory disease inherited ?,0000718-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In almost all cases, NOMID results from new mutations. These cases occur in people with no history of the disorder in their family. A few cases have been reported in which an affected person has inherited the mutation from one affected parent.",neonatal onset multisystem inflammatory disease,0000718,GHR,https://ghr.nlm.nih.gov/condition/neonatal-onset-multisystem-inflammatory-disease,C0409818,T047,Disorders
What are the treatments for neonatal onset multisystem inflammatory disease ?,0000718-5,treatment,"These resources address the diagnosis or management of NOMID:  - Genetic Testing Registry: Chronic infantile neurological, cutaneous and articular syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",neonatal onset multisystem inflammatory disease,0000718,GHR,https://ghr.nlm.nih.gov/condition/neonatal-onset-multisystem-inflammatory-disease,C0409818,T047,Disorders
What is (are) nephrogenic diabetes insipidus ?,0000719-1,information,"Nephrogenic diabetes insipidus is a disorder of water balance. The body normally balances fluid intake with the excretion of fluid in urine. However, people with nephrogenic diabetes insipidus produce too much urine (polyuria), which causes them to be excessively thirsty (polydipsia). Affected individuals can quickly become dehydrated if they do not drink enough water, especially in hot weather or when they are sick.  Nephrogenic diabetes insipidus can be either acquired or hereditary. The acquired form is brought on by certain drugs and chronic diseases and can occur at any time during life. The hereditary form is caused by genetic mutations, and its signs and symptoms usually become apparent within the first few months of life.  Infants with hereditary nephrogenic diabetes insipidus may eat poorly and fail to gain weight and grow at the expected rate (failure to thrive). They may also be irritable and experience fevers, diarrhea, and vomiting. Recurrent episodes of dehydration can lead to slow growth and delayed development. If the condition is not well-managed, over time it can damage the bladder and kidneys leading to pain, infections, and kidney failure. With appropriate treatment, affected individuals usually have few complications and a normal lifespan.  Nephrogenic diabetes insipidus should not be confused with diabetes mellitus, which is much more common. Diabetes mellitus is characterized by high blood sugar levels resulting from a shortage of the hormone insulin or an insensitivity to this hormone. Although nephrogenic diabetes insipidus and diabetes mellitus have some features in common, they are separate disorders with different causes.",nephrogenic diabetes insipidus,0000719,GHR,https://ghr.nlm.nih.gov/condition/nephrogenic-diabetes-insipidus,C0162283,T047,Disorders
How many people are affected by nephrogenic diabetes insipidus ?,0000719-2,frequency,"The prevalence of nephrogenic diabetes insipidus is unknown, although the condition is thought to be rare. The acquired form occurs more frequently than the hereditary form.",nephrogenic diabetes insipidus,0000719,GHR,https://ghr.nlm.nih.gov/condition/nephrogenic-diabetes-insipidus,C0162283,T047,Disorders
What are the genetic changes related to nephrogenic diabetes insipidus ?,0000719-3,genetic changes,"The hereditary form of nephrogenic diabetes insipidus can be caused by mutations in at least two genes. About 90 percent of all cases of hereditary nephrogenic diabetes insipidus result from mutations in the AVPR2 gene. Most of the remaining 10 percent of cases are caused by mutations in the AQP2 gene. Both of these genes provide instructions for making proteins that help determine how much water is excreted in urine.  The acquired form of nephrogenic diabetes insipidus can result from chronic kidney disease, certain medications (such as lithium), low levels of potassium in the blood (hypokalemia), high levels of calcium in the blood (hypercalcemia), or an obstruction of the urinary tract.  The kidneys filter the blood to remove waste and excess fluid, which are stored in the bladder as urine. The balance between fluid intake and urine excretion is controlled by a hormone called vasopressin or antidiuretic hormone (ADH). ADH directs the kidneys to concentrate urine by reabsorbing some of the water into the bloodstream. Normally, when a person's fluid intake is low or when a lot of fluid is lost (for example, through sweating), increased levels of ADH in the blood tell the kidneys to make less urine. When fluid intake is adequate, lower levels of ADH tell the kidneys to make more urine.  Mutations in the AVPR2 or AQP2 genes prevent the kidneys from responding to signals from ADH. Chronic kidney disease, certain drugs, and other factors can also impair the kidneys' ability to respond to this hormone. As a result, the kidneys do not reabsorb water as they should, and the body makes excessive amounts of urine. These problems with water balance are characteristic of nephrogenic diabetes insipidus.",nephrogenic diabetes insipidus,0000719,GHR,https://ghr.nlm.nih.gov/condition/nephrogenic-diabetes-insipidus,C0162283,T047,Disorders
Is nephrogenic diabetes insipidus inherited ?,0000719-4,inheritance,"When nephrogenic diabetes insipidus results from mutations in the AVPR2 gene, the condition has an X-linked recessive pattern of inheritance. The AVPR2 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation usually has to occur in both copies of the gene to cause the disorder. However, some females who carry a single mutated copy of the AVPR2 gene have features of nephrogenic diabetes insipidus, including polyuria and polydipsia. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  When nephrogenic diabetes insipidus is caused by mutations in the AQP2 gene, it can have either an autosomal recessive or, less commonly, an autosomal dominant pattern of inheritance. In autosomal recessive inheritance, both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. In autosomal dominant inheritance, one mutated copy of the AQP2 gene in each cell is sufficient to cause the disorder.",nephrogenic diabetes insipidus,0000719,GHR,https://ghr.nlm.nih.gov/condition/nephrogenic-diabetes-insipidus,C0162283,T047,Disorders
What are the treatments for nephrogenic diabetes insipidus ?,0000719-5,treatment,"These resources address the diagnosis or management of nephrogenic diabetes insipidus:  - Gene Review: Gene Review: Nephrogenic Diabetes Insipidus  - Genetic Testing Registry: Nephrogenic diabetes insipidus  - Genetic Testing Registry: Nephrogenic diabetes insipidus, X-linked  - Genetic Testing Registry: Nephrogenic diabetes insipidus, autosomal  - MedlinePlus Encyclopedia: ADH  - MedlinePlus Encyclopedia: Diabetes Insipidus - Nephrogenic   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",nephrogenic diabetes insipidus,0000719,GHR,https://ghr.nlm.nih.gov/condition/nephrogenic-diabetes-insipidus,C0162283,T047,Disorders
What is (are) nephronophthisis ?,0000720-1,information,"Nephronophthisis is a disorder that affects the kidneys. It is characterized by inflammation and scarring (fibrosis) that impairs kidney function. These abnormalities lead to increased urine production (polyuria), excessive thirst (polydipsia), general weakness, and extreme tiredness (fatigue). In addition, affected individuals develop fluid-filled cysts in the kidneys, usually in an area known as the corticomedullary region. Another feature of nephronophthisis is a shortage of red blood cells, a condition known as anemia.  Nephronophthisis eventually leads to end-stage renal disease (ESRD), a life-threatening failure of kidney function that occurs when the kidneys are no longer able to filter fluids and waste products from the body effectively. Nephronophthisis can be classified by the approximate age at which ESRD begins: around age 1 (infantile), around age 13 (juvenile), and around age 19 (adolescent).  About 85 percent of all cases of nephronophthisis are isolated, which means they occur without other signs and symptoms. Some people with nephronophthisis have additional features, which can include liver fibrosis, heart abnormalities, or mirror image reversal of the position of one or more organs inside the body (situs inversus).  Nephronophthisis can occur as part of separate syndromes that affect other areas of the body; these are often referred to as nephronophthisis-associated ciliopathies. For example, Senior-Lken syndrome is characterized by the combination of nephronophthisis and a breakdown of the light-sensitive tissue at the back of the eye (retinal degeneration); Joubert syndrome affects many parts of the body, causing neurological problems and other features, which can include nephronophthisis.",nephronophthisis,0000720,GHR,https://ghr.nlm.nih.gov/condition/nephronophthisis,C0687120,T047,Disorders
How many people are affected by nephronophthisis ?,0000720-2,frequency,"Nephronophthisis is found in populations worldwide. It occurs in an estimated 1 in 50,000 newborns in Canada, 1 in 100,000 in Finland, and 1 in 922,000 in the United States. Its incidence in other populations is unknown. Nephronophthisis is the most common genetic cause of ESRD in children and young adults.",nephronophthisis,0000720,GHR,https://ghr.nlm.nih.gov/condition/nephronophthisis,C0687120,T047,Disorders
What are the genetic changes related to nephronophthisis ?,0000720-3,genetic changes,"Nephronophthisis has several genetic causes, which are used to split the condition into distinct types. Nephronophthisis type 1, which is the most common type of the disorder and one cause of juvenile nephronophthisis, results from changes affecting the NPHP1 gene. The proteins produced from NPHP1 and the other genes involved in nephronophthisis are known or suspected to play roles in cell structures called cilia. Cilia are microscopic, finger-like projections that stick out from the surface of cells and are involved in chemical signaling. Cilia are important for the structure and function of many types of cells and tissues, including cells in the kidneys, liver, and brain and the light-sensitive tissue at the back of the eye (the retina).  The genetic mutations involved in nephronophthisis are thought to impair the structure or function of cilia in some way, which likely disrupts important chemical signaling pathways during development. Although researchers believe that defective cilia lead to the features of nephronophthisis, the mechanism remains unclear. It is unknown why some people with mutations in nephronophthisis-associated genes have only kidney problems, while others develop additional signs and symptoms.",nephronophthisis,0000720,GHR,https://ghr.nlm.nih.gov/condition/nephronophthisis,C0687120,T047,Disorders
Is nephronophthisis inherited ?,0000720-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",nephronophthisis,0000720,GHR,https://ghr.nlm.nih.gov/condition/nephronophthisis,C0687120,T047,Disorders
What are the treatments for nephronophthisis ?,0000720-5,treatment,These resources address the diagnosis or management of nephronophthisis:  - Genetic Testing Registry: Adolescent nephronophthisis  - Genetic Testing Registry: Infantile nephronophthisis  - Genetic Testing Registry: Nephronophthisis  - Genetic Testing Registry: Nephronophthisis 1  - Genetic Testing Registry: Nephronophthisis 11  - Genetic Testing Registry: Nephronophthisis 12  - Genetic Testing Registry: Nephronophthisis 14  - Genetic Testing Registry: Nephronophthisis 15  - Genetic Testing Registry: Nephronophthisis 16  - Genetic Testing Registry: Nephronophthisis 18  - Genetic Testing Registry: Nephronophthisis 4  - Genetic Testing Registry: Nephronophthisis 7  - Genetic Testing Registry: Nephronophthisis 9  - Merck Manual Professional Edition   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,nephronophthisis,0000720,GHR,https://ghr.nlm.nih.gov/condition/nephronophthisis,C0687120,T047,Disorders
What is (are) Netherton syndrome ?,0000721-1,information,"Netherton syndrome is a disorder that affects the skin, hair, and immune system. Newborns with Netherton syndrome have skin that is red and scaly (ichthyosiform erythroderma), and the skin may leak fluid. Some affected infants are born with a tight, clear sheath covering their skin called a collodion membrane. This membrane is usually shed during the first few weeks of life. Because newborns with this disorder are missing the protection provided by normal skin, they are at risk of becoming dehydrated and developing infections in the skin or throughout the body (sepsis), which can be life-threatening. Affected babies may also fail to grow and gain weight at the expected rate (failure to thrive). The health of older children and adults with Netherton syndrome usually improves, although they often remain underweight and of short stature.  After infancy, the severity of the skin abnormalities varies among people with Netherton syndrome and can fluctuate over time. The skin may continue to be red and scaly, especially during the first few years of life. Some affected individuals have intermittent redness or experience outbreaks of a distinctive skin abnormality called ichthyosis linearis circumflexa, involving patches of multiple ring-like lesions. The triggers for the outbreaks are not known, but researchers suggest that stress or infections may be involved.  Itchiness is a common problem for affected individuals, and scratching can lead to frequent infections. Dead skin cells are shed at an abnormal rate and often accumulate in the ear canals, which can affect hearing if not removed regularly. The skin is abnormally absorbent of substances such as lotions and ointments, which can result in excessive blood levels of some topical medications. Because the ability of the skin to protect against heat and cold is impaired, affected individuals may have difficulty regulating their body temperature.  People with Netherton syndrome have hair that is fragile and breaks easily. Some strands of hair vary in diameter, with thicker and thinner spots. This feature is known as bamboo hair, trichorrhexis nodosa, or trichorrhexis invaginata. In addition to the hair on the scalp, the eyelashes and eyebrows may be affected. The hair abnormality in Netherton syndrome may not be noticed in infancy because babies often have sparse hair.  Most people with Netherton syndrome have immune system-related problems such as food allergies, hay fever, asthma, or an inflammatory skin disorder called eczema.",Netherton syndrome,0000721,GHR,https://ghr.nlm.nih.gov/condition/netherton-syndrome,C0265962,T019,Disorders
How many people are affected by Netherton syndrome ?,0000721-2,frequency,"Netherton syndrome is estimated to affect 1 in 200,000 newborns.",Netherton syndrome,0000721,GHR,https://ghr.nlm.nih.gov/condition/netherton-syndrome,C0265962,T019,Disorders
What are the genetic changes related to Netherton syndrome ?,0000721-3,genetic changes,"Netherton syndrome is caused by mutations in the SPINK5 gene. This gene provides instructions for making a protein called LEKT1. LEKT1 is a type of serine peptidase inhibitor. Serine peptidase inhibitors control the activity of enzymes called serine peptidases, which break down other proteins. LEKT1 is found in the skin and in the thymus, which is a gland located behind the breastbone that plays an important role in the immune system by producing white blood cells called lymphocytes. LEKT1 controls the activity of certain serine peptidases in the outer layer of skin (the epidermis), especially the tough outer surface known as the stratum corneum, which provides a sturdy barrier between the body and its environment. Serine peptidase enzymes are involved in normal skin shedding by helping to break the connections between cells of the stratum corneum. LEKT1 is also involved in normal hair growth, the development of lymphocytes in the thymus, and the control of peptidases that trigger immune system function.  Mutations in the SPINK5 gene result in a LEKT1 protein that is unable to control serine peptidase activity. The lack of LEKT1 function allows the serine peptidases to be abnormally active and break down too many proteins in the stratum corneum. As a result, too much skin shedding takes place, and the stratum corneum is too thin and breaks down easily, resulting in the skin abnormalities that occur in Netherton syndrome. Loss of LEKT1 function also results in abnormal hair growth and immune dysfunction that leads to allergies, asthma, and eczema.",Netherton syndrome,0000721,GHR,https://ghr.nlm.nih.gov/condition/netherton-syndrome,C0265962,T019,Disorders
Is Netherton syndrome inherited ?,0000721-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Netherton syndrome,0000721,GHR,https://ghr.nlm.nih.gov/condition/netherton-syndrome,C0265962,T019,Disorders
What are the treatments for Netherton syndrome ?,0000721-5,treatment,These resources address the diagnosis or management of Netherton syndrome:  - Genetic Testing Registry: Netherton syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Netherton syndrome,0000721,GHR,https://ghr.nlm.nih.gov/condition/netherton-syndrome,C0265962,T019,Disorders
What is (are) neuroblastoma ?,0000722-1,information,"Neuroblastoma is a type of cancer that most often affects children. Neuroblastoma occurs when immature nerve cells called neuroblasts become abnormal and multiply uncontrollably to form a tumor. Most commonly, the tumor originates in the nerve tissue of the adrenal gland located above each kidney. Other common sites for tumors to form include the nerve tissue in the abdomen, chest, neck, or pelvis. Neuroblastoma can spread (metastasize) to other parts of the body such as the bones, liver, or skin.  Individuals with neuroblastoma may develop general signs and symptoms such as irritability, fever, tiredness (fatigue), pain, loss of appetite, weight loss, or diarrhea. More specific signs and symptoms depend on the location of the tumor and where it has spread. A tumor in the abdomen can cause abdominal swelling. A tumor in the chest may lead to difficulty breathing. A tumor in the neck can cause nerve damage known as Horner syndrome, which leads to drooping eyelids, small pupils, decreased sweating, and red skin. Tumor metastasis to the bone can cause bone pain, bruises, pale skin, or dark circles around the eyes. Tumors in the backbone can press on the spinal cord and cause weakness, numbness, or paralysis in the arms or legs. A rash of bluish or purplish bumps that look like blueberries indicates that the neuroblastoma has spread to the skin.  In addition, neuroblastoma tumors can release hormones that may cause other signs and symptoms such as high blood pressure, rapid heartbeat, flushing of the skin, and sweating. In rare instances, individuals with neuroblastoma may develop opsoclonus myoclonus syndrome, which causes rapid eye movements and jerky muscle motions. This condition occurs when the immune system malfunctions and attacks nerve tissue.  Neuroblastoma occurs most often in children before age 5 and rarely occurs in adults.",neuroblastoma,0000722,GHR,https://ghr.nlm.nih.gov/condition/neuroblastoma,C0027819,T191,Disorders
How many people are affected by neuroblastoma ?,0000722-2,frequency,"Neuroblastoma is the most common cancer in infants younger than 1 year. It occurs in 1 in 100,000 children and is diagnosed in about 650 children each year in the United States.",neuroblastoma,0000722,GHR,https://ghr.nlm.nih.gov/condition/neuroblastoma,C0027819,T191,Disorders
What are the genetic changes related to neuroblastoma ?,0000722-3,genetic changes,"Neuroblastoma and other cancers occur when a buildup of genetic mutations in critical genesthose that control cell growth and division (proliferation) or maturation (differentiation)allow cells to grow and divide uncontrollably to form a tumor. In most cases, these genetic changes are acquired during a person's lifetime and are called somatic mutations. Somatic mutations are present only in certain cells and are not inherited. When neuroblastoma is associated with somatic mutations, it is called sporadic neuroblastoma. It is thought that somatic mutations in at least two genes are required to cause sporadic neuroblastoma. Less commonly, gene mutations that increase the risk of developing cancer can be inherited from a parent. When the mutation associated with neuroblastoma is inherited, the condition is called familial neuroblastoma. Mutations in the ALK and PHOX2B genes have been shown to increase the risk of developing sporadic and familial neuroblastoma. It is likely that there are other genes involved in the formation of neuroblastoma.  Several mutations in the ALK gene are involved in the development of sporadic and familial neuroblastoma. The ALK gene provides instructions for making a protein called anaplastic lymphoma kinase. Although the specific function of this protein is unknown, it appears to play an important role in cell proliferation. Mutations in the ALK gene result in an abnormal version of anaplastic lymphoma kinase that is constantly turned on (constitutively activated). Constitutively active anaplastic lymphoma kinase may induce abnormal proliferation of immature nerve cells and lead to neuroblastoma.  Several mutations in the PHOX2B gene have been identified in sporadic and familial neuroblastoma. The PHOX2B gene is important for the formation and differentiation of nerve cells. Mutations in this gene are believed to interfere with the PHOX2B protein's role in promoting nerve cell differentiation. This disruption of differentiation results in an excess of immature nerve cells and leads to neuroblastoma.  Deletion of certain regions of chromosome 1 and chromosome 11 are associated with neuroblastoma. Researchers believe the deleted regions in these chromosomes could contain a gene that keeps cells from growing and dividing too quickly or in an uncontrolled way, called a tumor suppressor gene. When a tumor suppressor gene is deleted, cancer can occur. The KIF1B gene is a tumor suppressor gene located in the deleted region of chromosome 1, and mutations in this gene have been identified in some people with familial neuroblastoma, indicating it is involved in neuroblastoma development or progression. There are several other possible tumor suppressor genes in the deleted region of chromosome 1. No tumor suppressor genes have been identified in the deleted region of chromosome 11.  Another genetic change found in neuroblastoma is associated with the severity of the disease but not thought to cause it. About 25 percent of people with neuroblastoma have extra copies of the MYCN gene, a phenomenon called gene amplification. It is unknown how amplification of this gene contributes to the aggressive nature of neuroblastoma.",neuroblastoma,0000722,GHR,https://ghr.nlm.nih.gov/condition/neuroblastoma,C0027819,T191,Disorders
Is neuroblastoma inherited ?,0000722-4,inheritance,"Most people with neuroblastoma have sporadic neuroblastoma, meaning the condition arose from somatic mutations in the body's cells and was not inherited.  About 1 to 2 percent of affected individuals have familial neuroblastoma. This form of the condition has an autosomal dominant inheritance pattern, which means one copy of the altered gene in each cell increases the risk of developing the disorder. However, the inheritance is considered to have incomplete penetrance because not everyone who inherits the altered gene from a parent develops neuroblastoma. Having the altered gene predisposes an individual to develop neuroblastoma, but an additional somatic mutation is probably needed to cause the condition.",neuroblastoma,0000722,GHR,https://ghr.nlm.nih.gov/condition/neuroblastoma,C0027819,T191,Disorders
What are the treatments for neuroblastoma ?,0000722-5,treatment,These resources address the diagnosis or management of neuroblastoma:  - American Cancer Society: Diagnosis of Neuroblastoma  - Gene Review: Gene Review: ALK-Related Neuroblastic Tumor Susceptibility  - Genetic Testing Registry: Neuroblastoma  - Genetic Testing Registry: Neuroblastoma 2  - Genetic Testing Registry: Neuroblastoma 3  - National Cancer Institute  - The Children's Hospital of Pennsylvania   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,neuroblastoma,0000722,GHR,https://ghr.nlm.nih.gov/condition/neuroblastoma,C0027819,T191,Disorders
What is (are) neuroferritinopathy ?,0000723-1,information,"Neuroferritinopathy is a disorder in which iron gradually accumulates in the brain. Certain brain regions that help control movement (basal ganglia) are particularly affected. People with neuroferritinopathy have progressive problems with movement that begin at about age 40. These movement problems can include involuntary jerking motions (chorea), rhythmic shaking (tremor), difficulty coordinating movements (ataxia), or uncontrolled tensing of muscles (dystonia). Symptoms of the disorder may be more apparent on one side of the body than on the other. Affected individuals may also have difficulty swallowing (dysphagia) and speaking (dysarthria).  Intelligence is unaffected in most people with neuroferritinopathy, but some individuals develop a gradual decline in thinking and reasoning abilities (dementia). Personality changes such as reduced inhibitions and difficulty controlling emotions may also occur as the disorder progresses.",neuroferritinopathy,0000723,GHR,https://ghr.nlm.nih.gov/condition/neuroferritinopathy,C1853578,T047,Disorders
How many people are affected by neuroferritinopathy ?,0000723-2,frequency,The prevalence of neuroferritinopathy is unknown. Fewer than 100 individuals with this disorder have been reported.,neuroferritinopathy,0000723,GHR,https://ghr.nlm.nih.gov/condition/neuroferritinopathy,C1853578,T047,Disorders
What are the genetic changes related to neuroferritinopathy ?,0000723-3,genetic changes,"Mutations in the FTL gene cause neuroferritinopathy. The FTL gene provides instructions for making the ferritin light chain, which is one part (subunit) of a protein called ferritin. Ferritin stores and releases iron in cells. Each ferritin molecule can hold as many as 4,500 iron atoms. This storage capacity allows ferritin to regulate the amount of iron in the cells and tissues.  Mutations in the FTL gene that cause neuroferritinopathy are believed to reduce ferritin's ability to store iron, resulting in the release of excess iron in nerve cells (neurons) of the brain. The cells may respond by producing more ferritin in an attempt to handle the free iron. Excess iron and ferritin accumulate in the brain, particularly in the basal ganglia, resulting in the movement problems and other neurological changes seen in neuroferritinopathy.",neuroferritinopathy,0000723,GHR,https://ghr.nlm.nih.gov/condition/neuroferritinopathy,C1853578,T047,Disorders
Is neuroferritinopathy inherited ?,0000723-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In most cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.",neuroferritinopathy,0000723,GHR,https://ghr.nlm.nih.gov/condition/neuroferritinopathy,C1853578,T047,Disorders
What are the treatments for neuroferritinopathy ?,0000723-5,treatment,These resources address the diagnosis or management of neuroferritinopathy:  - Gene Review: Gene Review: Neuroferritinopathy  - Genetic Testing Registry: Neuroferritinopathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,neuroferritinopathy,0000723,GHR,https://ghr.nlm.nih.gov/condition/neuroferritinopathy,C1853578,T047,Disorders
What is (are) neurofibromatosis type 1 ?,0000724-1,information,"Neurofibromatosis type 1 is a condition characterized by changes in skin coloring (pigmentation) and the growth of tumors along nerves in the skin, brain, and other parts of the body. The signs and symptoms of this condition vary widely among affected people.  Beginning in early childhood, almost all people with neurofibromatosis type 1 have multiple caf-au-lait spots, which are flat patches on the skin that are darker than the surrounding area. These spots increase in size and number as the individual grows older. Freckles in the underarms and groin typically develop later in childhood.  Most adults with neurofibromatosis type 1 develop neurofibromas, which are noncancerous (benign) tumors that are usually located on or just under the skin. These tumors may also occur in nerves near the spinal cord or along nerves elsewhere in the body. Some people with neurofibromatosis type 1 develop cancerous tumors that grow along nerves. These tumors, which usually develop in adolescence or adulthood, are called malignant peripheral nerve sheath tumors. People with neurofibromatosis type 1 also have an increased risk of developing other cancers, including brain tumors and cancer of blood-forming tissue (leukemia).  During childhood, benign growths called Lisch nodules often appear in the colored part of the eye (the iris). Lisch nodules do not interfere with vision. Some affected individuals also develop tumors that grow along the nerve leading from the eye to the brain (the optic nerve). These tumors, which are called optic gliomas, may lead to reduced vision or total vision loss. In some cases, optic gliomas have no effect on vision.  Additional signs and symptoms of neurofibromatosis type 1 include high blood pressure (hypertension), short stature, an unusually large head (macrocephaly), and skeletal abnormalities such as an abnormal curvature of the spine (scoliosis). Although most people with neurofibromatosis type 1 have normal intelligence, learning disabilities and attention deficit hyperactivity disorder (ADHD) occur frequently in affected individuals.",neurofibromatosis type 1,0000724,GHR,https://ghr.nlm.nih.gov/condition/neurofibromatosis-type-1,C0027831,T191,Disorders
How many people are affected by neurofibromatosis type 1 ?,0000724-2,frequency,"Neurofibromatosis type 1 occurs in 1 in 3,000 to 4,000 people worldwide.",neurofibromatosis type 1,0000724,GHR,https://ghr.nlm.nih.gov/condition/neurofibromatosis-type-1,C0027831,T191,Disorders
What are the genetic changes related to neurofibromatosis type 1 ?,0000724-3,genetic changes,"Mutations in the NF1 gene cause neurofibromatosis type 1.  The NF1 gene provides instructions for making a protein called neurofibromin. This protein is produced in many cells, including nerve cells and specialized cells surrounding nerves (oligodendrocytes and Schwann cells). Neurofibromin acts as a tumor suppressor, which means that it keeps cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in the NF1 gene lead to the production of a nonfunctional version of neurofibromin that cannot regulate cell growth and division. As a result, tumors such as neurofibromas can form along nerves throughout the body. It is unclear how mutations in the NF1 gene lead to the other features of neurofibromatosis type 1, such as caf-au-lait spots and learning disabilities.",neurofibromatosis type 1,0000724,GHR,https://ghr.nlm.nih.gov/condition/neurofibromatosis-type-1,C0027831,T191,Disorders
Is neurofibromatosis type 1 inherited ?,0000724-4,inheritance,"Neurofibromatosis type 1 is considered to have an autosomal dominant pattern of inheritance. People with this condition are born with one mutated copy of the NF1 gene in each cell. In about half of cases, the altered gene is inherited from an affected parent. The remaining cases result from new mutations in the NF1 gene and occur in people with no history of the disorder in their family.  Unlike most other autosomal dominant conditions, in which one altered copy of a gene in each cell is sufficient to cause the disorder, two copies of the NF1 gene must be altered to trigger tumor formation in neurofibromatosis type 1. A mutation in the second copy of the NF1 gene occurs during a person's lifetime in specialized cells surrounding nerves. Almost everyone who is born with one NF1 mutation acquires a second mutation in many cells and develops the tumors characteristic of neurofibromatosis type 1.",neurofibromatosis type 1,0000724,GHR,https://ghr.nlm.nih.gov/condition/neurofibromatosis-type-1,C0027831,T191,Disorders
What are the treatments for neurofibromatosis type 1 ?,0000724-5,treatment,"These resources address the diagnosis or management of neurofibromatosis type 1:  - Gene Review: Gene Review: Neurofibromatosis 1  - Genetic Testing Registry: Neurofibromatosis, type 1  - MedlinePlus Encyclopedia: Neurofibromatosis-1   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",neurofibromatosis type 1,0000724,GHR,https://ghr.nlm.nih.gov/condition/neurofibromatosis-type-1,C0027831,T191,Disorders
What is (are) neurofibromatosis type 2 ?,0000725-1,information,"Neurofibromatosis type 2 is a disorder characterized by the growth of noncancerous tumors in the nervous system. The most common tumors associated with neurofibromatosis type 2 are called vestibular schwannomas or acoustic neuromas. These growths develop along the nerve that carries information from the inner ear to the brain (the auditory nerve). Tumors that occur on other nerves are also commonly found with this condition.  The signs and symptoms of neurofibromatosis type 2 usually appear during adolescence or in a person's early twenties, although they can begin at any age. The most frequent early symptoms of vestibular schwannomas are hearing loss, ringing in the ears (tinnitus), and problems with balance. In most cases, these tumors occur in both ears by age 30. If tumors develop elsewhere in the nervous system, signs and symptoms vary according to their location. Complications of tumor growth can include changes in vision, numbness or weakness in the arms or legs, and fluid buildup in the brain. Some people with neurofibromatosis type 2 also develop clouding of the lens (cataracts) in one or both eyes, often beginning in childhood.",neurofibromatosis type 2,0000725,GHR,https://ghr.nlm.nih.gov/condition/neurofibromatosis-type-2,C0027832,T191,Disorders
How many people are affected by neurofibromatosis type 2 ?,0000725-2,frequency,"Neurofibromatosis type 2 has an estimated incidence of 1 in 33,000 people worldwide.",neurofibromatosis type 2,0000725,GHR,https://ghr.nlm.nih.gov/condition/neurofibromatosis-type-2,C0027832,T191,Disorders
What are the genetic changes related to neurofibromatosis type 2 ?,0000725-3,genetic changes,"Mutations in the NF2 gene cause neurofibromatosis type 2. The NF2 gene provides instructions for making a protein called merlin (also known as schwannomin). This protein is produced in the nervous system, particularly in Schwann cells, which surround and insulate nerve cells (neurons) in the brain and spinal cord. Merlin acts as a tumor suppressor, which means that it keeps cells from growing and dividing too rapidly or in an uncontrolled way. Although its exact function is unknown, this protein is likely also involved in controlling cell movement, cell shape, and communication between cells. Mutations in the NF2 gene lead to the production of a nonfunctional version of the merlin protein that cannot regulate the growth and division of cells. Research suggests that the loss of merlin allows cells, especially Schwann cells, to multiply too frequently and form the tumors characteristic of neurofibromatosis type 2.",neurofibromatosis type 2,0000725,GHR,https://ghr.nlm.nih.gov/condition/neurofibromatosis-type-2,C0027832,T191,Disorders
Is neurofibromatosis type 2 inherited ?,0000725-4,inheritance,"Neurofibromatosis type 2 is considered to have an autosomal dominant pattern of inheritance. People with this condition are born with one mutated copy of the NF2 gene in each cell. In about half of cases, the altered gene is inherited from an affected parent. The remaining cases result from new mutations in the NF2 gene and occur in people with no history of the disorder in their family.  Unlike most other autosomal dominant conditions, in which one altered copy of a gene in each cell is sufficient to cause the disorder, two copies of the NF2 gene must be altered to trigger tumor formation in neurofibromatosis type 2. A mutation in the second copy of the NF2 gene occurs in Schwann cells or other cells in the nervous system during a person's lifetime. Almost everyone who is born with one NF2 mutation acquires a second mutation (known as a somatic mutation) in these cells and develops the tumors characteristic of neurofibromatosis type 2.",neurofibromatosis type 2,0000725,GHR,https://ghr.nlm.nih.gov/condition/neurofibromatosis-type-2,C0027832,T191,Disorders
What are the treatments for neurofibromatosis type 2 ?,0000725-5,treatment,"These resources address the diagnosis or management of neurofibromatosis type 2:  - Boston Children's Hospital  - Gene Review: Gene Review: Neurofibromatosis 2  - Genetic Testing Registry: Neurofibromatosis, type 2  - MedlinePlus Encyclopedia: Acoustic Neuroma  - MedlinePlus Encyclopedia: Neurofibromatosis 2  - Neurofibromatosis Clinic, Massachusetts General Hospital   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",neurofibromatosis type 2,0000725,GHR,https://ghr.nlm.nih.gov/condition/neurofibromatosis-type-2,C0027832,T191,Disorders
What is (are) neurohypophyseal diabetes insipidus ?,0000726-1,information,"Neurohypophyseal diabetes insipidus is a disorder of water balance. The body normally balances fluid intake with the excretion of fluid in urine. However, people with neurohypophyseal diabetes insipidus produce too much urine (polyuria), which causes them to be excessively thirsty (polydipsia). Affected people need to urinate frequently, which can disrupt daily activities and sleep.  People with neurohypophyseal diabetes insipidus can quickly become dehydrated if they do not drink enough water. Dehydration can lead to constipation and dry skin. If the disorder is not treated, more serious complications of dehydration can occur. These include confusion, low blood pressure, seizures, and coma.  Neurohypophyseal diabetes insipidus can be either acquired or familial. The acquired form is brought on by injuries, tumors, and other factors, and can occur at any time during life. The familial form is caused by genetic mutations; its signs and symptoms usually become apparent in childhood and worsen over time.  Neurohypophyseal diabetes insipidus should not be confused with diabetes mellitus, which is much more common. Diabetes mellitus is characterized by high blood sugar levels resulting from a shortage of the hormone insulin or an insensitivity to this hormone. Although neurohypophyseal diabetes insipidus and diabetes mellitus have some features in common, they are separate disorders with different causes.",neurohypophyseal diabetes insipidus,0000726,GHR,https://ghr.nlm.nih.gov/condition/neurohypophyseal-diabetes-insipidus,C0687720,T047,Disorders
How many people are affected by neurohypophyseal diabetes insipidus ?,0000726-2,frequency,"Neurohypophyseal diabetes insipidus is thought to be rare, although its exact incidence is unknown. The acquired form occurs much more frequently than the familial form.",neurohypophyseal diabetes insipidus,0000726,GHR,https://ghr.nlm.nih.gov/condition/neurohypophyseal-diabetes-insipidus,C0687720,T047,Disorders
What are the genetic changes related to neurohypophyseal diabetes insipidus ?,0000726-3,genetic changes,"The familial form of neurohypophyseal diabetes insipidus is caused by mutations in the AVP gene. This gene provides instructions for making a hormone called vasopressin or antidiuretic hormone (ADH). This hormone, which is produced and stored in the brain, helps control the body's water balance.  The kidneys filter the blood to remove waste and excess fluid, which are stored in the bladder as urine. ADH controls the balance between fluid intake and urine excretion. Normally, when a person's fluid intake is low or when a lot of fluid is lost (for example, through sweating), the brain releases more ADH into the bloodstream. High levels of this hormone direct the kidneys to reabsorb more water and to make less urine. When fluid intake is adequate, the brain releases less ADH. Lower levels of this hormone cause the kidneys to reabsorb less water and to make more urine.  Mutations in the AVP gene result in progressive damage to the brain cells where ADH is produced. These cells ultimately die, causing a shortage of ADH. Without this hormone, the kidneys do not reabsorb water as they should, and the body makes excessive amounts of urine. These problems with water balance are characteristic of neurohypophyseal diabetes insipidus.  The acquired form of neurohypophyseal diabetes insipidus results when the areas of the brain that produce or store ADH are damaged by head injuries, brain tumors, brain surgery, certain diseases and infections, or bleeding in the brain. A loss of ADH disrupts the body's water balance, leading to excessive urine production and the other features of the disorder.  In 30 to 50 percent of all cases of neurohypophyseal diabetes insipidus, the cause of the disorder is unknown. Studies suggest that some of these cases may have an autoimmune basis. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. For unknown reasons, in some people with neurohypophyseal diabetes insipidus the immune system appears to damage the brain cells that normally produce ADH.",neurohypophyseal diabetes insipidus,0000726,GHR,https://ghr.nlm.nih.gov/condition/neurohypophyseal-diabetes-insipidus,C0687720,T047,Disorders
Is neurohypophyseal diabetes insipidus inherited ?,0000726-4,inheritance,"Familial neurohypophyseal diabetes insipidus is almost always inherited in an autosomal dominant pattern, which means one copy of the altered AVP gene in each cell is sufficient to cause the disorder.  In a few affected families, the condition has had an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means that both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",neurohypophyseal diabetes insipidus,0000726,GHR,https://ghr.nlm.nih.gov/condition/neurohypophyseal-diabetes-insipidus,C0687720,T047,Disorders
What are the treatments for neurohypophyseal diabetes insipidus ?,0000726-5,treatment,These resources address the diagnosis or management of neurohypophyseal diabetes insipidus:  - Genetic Testing Registry: Neurohypophyseal diabetes insipidus  - MedlinePlus Encyclopedia: ADH  - MedlinePlus Encyclopedia: Diabetes Insipidus - Central   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,neurohypophyseal diabetes insipidus,0000726,GHR,https://ghr.nlm.nih.gov/condition/neurohypophyseal-diabetes-insipidus,C0687720,T047,Disorders
What is (are) neuromyelitis optica ?,0000727-1,information,"Neuromyelitis optica is an autoimmune disorder that affects the nerves of the eyes and the central nervous system, which includes the brain and spinal cord. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. In neuromyelitis optica, the autoimmune attack causes inflammation of the nerves, and the resulting damage leads to the signs and symptoms of the condition.  Neuromyelitis optica is characterized by optic neuritis, which is inflammation of the nerve that carries information from the eye to the brain (optic nerve). Optic neuritis causes eye pain and vision loss, which can occur in one or both eyes.  Neuromyelitis optica is also characterized by transverse myelitis, which is inflammation of the spinal cord. The inflammation associated with transverse myelitis damages the spinal cord, causing a lesion that often extends the length of three or more bones of the spine (vertebrae). In addition, myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses, can be damaged. Transverse myelitis causes weakness, numbness, and paralysis of the arms and legs. Other effects of spinal cord damage can include disturbances in sensations, loss of bladder and bowel control, uncontrollable hiccupping, and nausea. In addition, muscle weakness may make breathing difficult and can cause life-threatening respiratory failure in people with neuromyelitis optica.  There are two forms of neuromyelitis optica, the relapsing form and the monophasic form. The relapsing form is most common. This form is characterized by recurrent episodes of optic neuritis and transverse myelitis. These episodes can be months or years apart, and there is usually partial recovery between episodes. However, most affected individuals eventually develop permanent muscle weakness and vision impairment that persist even between episodes. For unknown reasons, approximately nine times more women than men have the relapsing form. The monophasic form, which is less common, causes a single episode of neuromyelitis optica that can last several months. People with this form of the condition can also have lasting muscle weakness or paralysis and vision loss. This form affects men and women equally. The onset of either form of neuromyelitis optica can occur anytime from childhood to adulthood, although the condition most frequently begins in a person's forties.  Approximately one-quarter of individuals with neuromyelitis optica have signs or symptoms of another autoimmune disorder such as myasthenia gravis, systemic lupus erythematosus, or Sjgren syndrome. Some scientists believe that a condition described in Japanese patients as optic-spinal multiple sclerosis (or opticospinal multiple sclerosis) that affects the nerves of the eyes and central nervous system is the same as neuromyelitis optica.",neuromyelitis optica,0000727,GHR,https://ghr.nlm.nih.gov/condition/neuromyelitis-optica,C0027873,T047,Disorders
How many people are affected by neuromyelitis optica ?,0000727-2,frequency,"Neuromyelitis optica affects approximately 1 to 2 per 100,000 people worldwide. Women are affected by this condition more frequently than men.",neuromyelitis optica,0000727,GHR,https://ghr.nlm.nih.gov/condition/neuromyelitis-optica,C0027873,T047,Disorders
What are the genetic changes related to neuromyelitis optica ?,0000727-3,genetic changes,"No genes associated with neuromyelitis optica have been identified. However, a small percentage of people with this condition have a family member who is also affected, which indicates that there may be one or more genetic changes that increase susceptibility. It is thought that the inheritance of this condition is complex and that many environmental and genetic factors are involved in the development of the condition.  The aquaporin-4 protein (AQP4), a normal protein in the body, plays a role in neuromyelitis optica. The aquaporin-4 protein is found in several body systems but is most abundant in tissues of the central nervous system. Approximately 70 percent of people with this disorder produce an immune protein called an antibody that attaches (binds) to the aquaporin-4 protein. Antibodies normally bind to specific foreign particles and germs, marking them for destruction, but the antibody in people with neuromyelitis optica attacks a normal human protein; this type of antibody is called an autoantibody. The autoantibody in this condition is called NMO-IgG or anti-AQP4.  The binding of the NMO-IgG autoantibody to the aquaporin-4 protein turns on (activates) the complement system, which is a group of immune system proteins that work together to destroy pathogens, trigger inflammation, and remove debris from cells and tissues. Complement activation leads to the inflammation of the optic nerve and spinal cord that is characteristic of neuromyelitis optica, resulting in the signs and symptoms of the condition.  The levels of the NMO-IgG autoantibody are high during episodes of neuromyelitis optica, and the levels decrease between episodes with treatment of the disorder. However, it is unclear what triggers episodes to begin or end.",neuromyelitis optica,0000727,GHR,https://ghr.nlm.nih.gov/condition/neuromyelitis-optica,C0027873,T047,Disorders
Is neuromyelitis optica inherited ?,0000727-4,inheritance,"Neuromyelitis optica is usually not inherited. Rarely, this condition is passed through generations in families, but the inheritance pattern is unknown.",neuromyelitis optica,0000727,GHR,https://ghr.nlm.nih.gov/condition/neuromyelitis-optica,C0027873,T047,Disorders
What are the treatments for neuromyelitis optica ?,0000727-5,treatment,These resources address the diagnosis or management of neuromyelitis optica:  - Genetic Testing Registry: Neuromyelitis optica  - National Institute of Neurological Disorders and Stroke: Neuromyelitis Optica Information Page  - The Transverse Myelitis Association: Acute Treatments   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,neuromyelitis optica,0000727,GHR,https://ghr.nlm.nih.gov/condition/neuromyelitis-optica,C0027873,T047,Disorders
"What is (are) neuropathy, ataxia, and retinitis pigmentosa ?",0000728-1,information,"Neuropathy, ataxia, and retinitis pigmentosa (NARP) is a condition that causes a variety of signs and symptoms chiefly affecting the nervous system. Beginning in childhood or early adulthood, most people with NARP experience numbness, tingling, or pain in the arms and legs (sensory neuropathy); muscle weakness; and problems with balance and coordination (ataxia). Many affected individuals also have vision loss caused by changes in the light-sensitive tissue that lines the back of the eye (the retina). In some cases, the vision loss results from a condition called retinitis pigmentosa. This eye disease causes the light-sensing cells of the retina gradually to deteriorate.  Learning disabilities and developmental delays are often seen in children with NARP, and older individuals with this condition may experience a loss of intellectual function (dementia). Other features of NARP include seizures, hearing loss, and abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects). These signs and symptoms vary among affected individuals.","neuropathy, ataxia, and retinitis pigmentosa",0000728,GHR,https://ghr.nlm.nih.gov/condition/neuropathy-ataxia-and-retinitis-pigmentosa,C0004134,T047,Disorders
"How many people are affected by neuropathy, ataxia, and retinitis pigmentosa ?",0000728-2,frequency,"The prevalence of NARP is unknown. This disorder is probably less common than a similar but more severe condition, Leigh syndrome, which affects about 1 in 40,000 people.","neuropathy, ataxia, and retinitis pigmentosa",0000728,GHR,https://ghr.nlm.nih.gov/condition/neuropathy-ataxia-and-retinitis-pigmentosa,C0004134,T047,Disorders
"What are the genetic changes related to neuropathy, ataxia, and retinitis pigmentosa ?",0000728-3,genetic changes,"NARP results from mutations in the MT-ATP6 gene. This gene is contained in mitochondrial DNA, also known as mtDNA. Mitochondria are structures within cells that convert the energy from food into a form that cells can use. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA.  The MT-ATP6 gene provides instructions for making a protein that is essential for normal mitochondrial function. Through a series of chemical reactions, mitochondria use oxygen and simple sugars to create adenosine triphosphate (ATP), the cell's main energy source. The MT-ATP6 protein forms one part (subunit) of an enzyme called ATP synthase, which is responsible for the last step in ATP production. Mutations in the MT-ATP6 gene alter the structure or function of ATP synthase, reducing the ability of mitochondria to make ATP. It remains unclear how this disruption in mitochondrial energy production leads to muscle weakness, vision loss, and the other specific features of NARP.","neuropathy, ataxia, and retinitis pigmentosa",0000728,GHR,https://ghr.nlm.nih.gov/condition/neuropathy-ataxia-and-retinitis-pigmentosa,C0004134,T047,Disorders
"Is neuropathy, ataxia, and retinitis pigmentosa inherited ?",0000728-4,inheritance,"This condition is inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mtDNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children.  Most of the body's cells contain thousands of mitochondria, each with one or more copies of mtDNA. The severity of some mitochondrial disorders is associated with the percentage of mitochondria in each cell that has a particular genetic change. Most individuals with NARP have a specific MT-ATP6 mutation in 70 percent to 90 percent of their mitochondria. When this mutation is present in a higher percentage of a person's mitochondriagreater than 90 percent to 95 percentit causes a more severe condition known as maternally inherited Leigh syndrome. Because these two conditions result from the same genetic changes and can occur in different members of a single family, researchers believe that they may represent a spectrum of overlapping features instead of two distinct syndromes.","neuropathy, ataxia, and retinitis pigmentosa",0000728,GHR,https://ghr.nlm.nih.gov/condition/neuropathy-ataxia-and-retinitis-pigmentosa,C0004134,T047,Disorders
"What are the treatments for neuropathy, ataxia, and retinitis pigmentosa ?",0000728-5,treatment,These resources address the diagnosis or management of NARP:  - Gene Review: Gene Review: Mitochondrial DNA-Associated Leigh Syndrome and NARP  - Gene Review: Gene Review: Mitochondrial Disorders Overview  - Genetic Testing Registry: Neuropathy ataxia retinitis pigmentosa syndrome  - MedlinePlus Encyclopedia: Retinitis pigmentosa   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,"neuropathy, ataxia, and retinitis pigmentosa",0000728,GHR,https://ghr.nlm.nih.gov/condition/neuropathy-ataxia-and-retinitis-pigmentosa,C0004134,T047,Disorders
What is (are) neutral lipid storage disease with myopathy ?,0000729-1,information,"Neutral lipid storage disease with myopathy is a condition in which fats (lipids) are stored abnormally in organs and tissues throughout the body. People with this condition have muscle weakness (myopathy) due to the accumulation of fats in muscle tissue. Other features of this condition may include a fatty liver, a weakened and enlarged heart (cardiomyopathy), inflammation of the pancreas (pancreatitis), reduced thyroid activity (hypothyroidism), and type 2 diabetes mellitus (the most common form of diabetes). Signs and symptoms of neutral lipid storage disease with myopathy vary greatly among affected individuals.",neutral lipid storage disease with myopathy,0000729,GHR,https://ghr.nlm.nih.gov/condition/neutral-lipid-storage-disease-with-myopathy,C0154251,T047,Disorders
How many people are affected by neutral lipid storage disease with myopathy ?,0000729-2,frequency,Neutral lipid storage disease with myopathy is a rare condition; its incidence is unknown.,neutral lipid storage disease with myopathy,0000729,GHR,https://ghr.nlm.nih.gov/condition/neutral-lipid-storage-disease-with-myopathy,C0154251,T047,Disorders
What are the genetic changes related to neutral lipid storage disease with myopathy ?,0000729-3,genetic changes,"Mutations in the PNPLA2 gene cause neutral lipid storage disease with myopathy. The PNPLA2 gene provides instructions for making an enzyme called adipose triglyceride lipase (ATGL). The ATGL enzyme plays a role in breaking down fats called triglycerides. Triglycerides are an important source of stored energy in cells. These fats must be broken down into simpler molecules called fatty acids before they can be used for energy.  PNPLA2 gene mutations impair the ATGL enzyme's ability to break down triglycerides. These triglycerides then accumulate in muscle and tissues throughout the body, resulting in the signs and symptoms of neutral lipid storage disease with myopathy.",neutral lipid storage disease with myopathy,0000729,GHR,https://ghr.nlm.nih.gov/condition/neutral-lipid-storage-disease-with-myopathy,C0154251,T047,Disorders
Is neutral lipid storage disease with myopathy inherited ?,0000729-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",neutral lipid storage disease with myopathy,0000729,GHR,https://ghr.nlm.nih.gov/condition/neutral-lipid-storage-disease-with-myopathy,C0154251,T047,Disorders
What are the treatments for neutral lipid storage disease with myopathy ?,0000729-5,treatment,These resources address the diagnosis or management of neutral lipid storage disease with myopathy:  - Genetic Testing Registry: Neutral lipid storage disease with myopathy  - MedlinePlus Encyclopedia: Hypothyroidism  - MedlinePlus Encyclopedia: Type 2 Diabetes   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,neutral lipid storage disease with myopathy,0000729,GHR,https://ghr.nlm.nih.gov/condition/neutral-lipid-storage-disease-with-myopathy,C0154251,T047,Disorders
What is (are) Nicolaides-Baraitser syndrome ?,0000730-1,information,"Nicolaides-Baraitser syndrome is a condition that affects many body systems. Affected individuals can have a wide variety of signs and symptoms, but the most common are sparse scalp hair, small head size (microcephaly), distinct facial features, short stature, prominent finger joints, unusually short fingers and toes (brachydactyly), recurrent seizures (epilepsy), and moderate to severe intellectual disability with impaired language development.  In people with Nicolaides-Baraitser syndrome, the sparse scalp hair is often noticeable in infancy. The amount of hair decreases over time, but the growth rate and texture of the hair that is present is normal. Affected adults generally have very little hair. In rare cases, the amount of scalp hair increases over time. As affected individuals age, their eyebrows may become less full, but their eyelashes almost always remain normal. At birth, the hair on the face may be abnormally thick (hypertrichosis) but thins out over time.  Most affected individuals grow slowly, resulting in short stature and microcephaly. Sometimes, growth before birth is unusually slow.  The characteristic facial features of people with Nicolaides-Baraitser syndrome include a triangular face, deep-set eyes, a thin nasal bridge, wide nostrils, a pointed nasal tip, and a thick lower lip. Many affected individuals have a lack of fat under the skin (subcutaneous fat) of the face, which may cause premature wrinkling. Throughout their bodies, people with Nicolaides-Baraitser syndrome may have pale skin with veins that are visible on the skin surface due to the lack of subcutaneous fat.  In people with Nicolaides-Baraitser syndrome, a lack of subcutaneous fat in the hands makes the finger joints appear larger than normal. Over time, the fingertips become broad and oval shaped. Additionally, there is a wide gap between the first and second toes (known as a sandal gap).  Most people with Nicolaides-Baraitser syndrome have epilepsy, which often begins in infancy. Affected individuals can experience multiple seizure types, and the seizures can be difficult to control with medication.  Almost everyone with Nicolaides-Baraitser syndrome has moderate to severe intellectual disability. Early developmental milestones, such as crawling and walking, are often normally achieved, but further development is limited, and language development is severely impaired. At least one-third of affected individuals never develop speech, while others lose their verbal communication over time. People with this condition are often described as having a happy demeanor and being very friendly, although they can exhibit moments of aggression and temper tantrums.  Other signs and symptoms of Nicolaides-Baraitser syndrome include an inflammatory skin disorder called eczema. About half of individuals with Nicolaides-Baraitser syndrome have a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). Some affected individuals have dental abnormalities such as widely spaced teeth, delayed eruption of teeth, and absent teeth (hypodontia). Most affected males have undescended testes (cryptorchidism) and females may have underdeveloped breasts. Nearly half of individuals with Nicolaides-Baraitser syndrome have feeding problems.",Nicolaides-Baraitser syndrome,0000730,GHR,https://ghr.nlm.nih.gov/condition/nicolaides-baraitser-syndrome,C1303073,T047,Disorders
How many people are affected by Nicolaides-Baraitser syndrome ?,0000730-2,frequency,Nicolaides-Baraitser syndrome is likely a rare condition; approximately 75 cases have been reported in the scientific literature.,Nicolaides-Baraitser syndrome,0000730,GHR,https://ghr.nlm.nih.gov/condition/nicolaides-baraitser-syndrome,C1303073,T047,Disorders
What are the genetic changes related to Nicolaides-Baraitser syndrome ?,0000730-3,genetic changes,"Nicolaides-Baraitser syndrome is caused by mutations in the SMARCA2 gene. This gene provides instructions for making one piece (subunit) of a group of similar protein complexes known as SWI/SNF complexes. These complexes regulate gene activity (expression) by a process known as chromatin remodeling. Chromatin is the network of DNA and proteins that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. Chromatin remodeling is one way gene expression is regulated during development; when DNA is tightly packed, gene expression is lower than when DNA is loosely packed. To provide energy for chromatin remodeling, the SMARCA2 protein uses a molecule called ATP.  The SMARCA2 gene mutations that cause Nicolaides-Baraitser syndrome result in the production of an altered protein that interferes with the normal function of the SWI/SNF complexes. These altered proteins are able to form SWI/SNF complexes, but the complexes are nonfunctional. As a result, they cannot participate in chromatin remodeling. Disturbance of this regulatory process alters the activity of many genes, which likely explains the diverse signs and symptoms of Nicolaides-Baraitser syndrome.",Nicolaides-Baraitser syndrome,0000730,GHR,https://ghr.nlm.nih.gov/condition/nicolaides-baraitser-syndrome,C1303073,T047,Disorders
Is Nicolaides-Baraitser syndrome inherited ?,0000730-4,inheritance,"Nicolaides-Baraitser syndrome follows an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  All cases of this condition result from new (de novo) mutations in the gene that occur during the formation of reproductive cells (eggs or sperm) or in early embryonic development. These cases occur in people with no history of the disorder in their family.",Nicolaides-Baraitser syndrome,0000730,GHR,https://ghr.nlm.nih.gov/condition/nicolaides-baraitser-syndrome,C1303073,T047,Disorders
What are the treatments for Nicolaides-Baraitser syndrome ?,0000730-5,treatment,These resources address the diagnosis or management of Nicolaides-Baraitser syndrome:  - Gene Review: Gene Review: Nicolaides-Baraitser Syndrome  - Genetic Testing Registry: Nicolaides-Baraitser syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Nicolaides-Baraitser syndrome,0000730,GHR,https://ghr.nlm.nih.gov/condition/nicolaides-baraitser-syndrome,C1303073,T047,Disorders
What is (are) Niemann-Pick disease ?,0000731-1,information,"Niemann-Pick disease is a condition that affects many body systems. It has a wide range of symptoms that vary in severity. Niemann-Pick disease is divided into four main types: type A, type B, type C1, and type C2. These types are classified on the basis of genetic cause and the signs and symptoms of the condition.  Infants with Niemann-Pick disease type A usually develop an enlarged liver and spleen (hepatosplenomegaly) by age 3 months and fail to gain weight and grow at the expected rate (failure to thrive). The affected children develop normally until around age 1 year when they experience a progressive loss of mental abilities and movement (psychomotor regression). Children with Niemann-Pick disease type A also develop widespread lung damage (interstitial lung disease) that can cause recurrent lung infections and eventually lead to respiratory failure. All affected children have an eye abnormality called a cherry-red spot, which can be identified with an eye examination. Children with Niemann-Pick disease type A generally do not survive past early childhood.  Niemann-Pick disease type B usually presents in mid-childhood. The signs and symptoms of this type are similar to type A, but not as severe. People with Niemann-Pick disease type B often have hepatosplenomegaly, recurrent lung infections, and a low number of platelets in the blood (thrombocytopenia). They also have short stature and slowed mineralization of bone (delayed bone age). About one-third of affected individuals have the cherry-red spot eye abnormality or neurological impairment. People with Niemann-Pick disease type B usually survive into adulthood.  The signs and symptoms of Niemann-Pick disease types C1 and C2 are very similar; these types differ only in their genetic cause. Niemann-Pick disease types C1 and C2 usually become apparent in childhood, although signs and symptoms can develop at any time. People with these types usually develop difficulty coordinating movements (ataxia), an inability to move the eyes vertically (vertical supranuclear gaze palsy), poor muscle tone (dystonia), severe liver disease, and interstitial lung disease. Individuals with Niemann-Pick disease types C1 and C2 have problems with speech and swallowing that worsen over time, eventually interfering with feeding. Affected individuals often experience progressive decline in intellectual function and about one-third have seizures. People with these types may survive into adulthood.",Niemann-Pick disease,0000731,GHR,https://ghr.nlm.nih.gov/condition/niemann-pick-disease,C0028064,T047,Disorders
How many people are affected by Niemann-Pick disease ?,0000731-2,frequency,"Niemann-Pick disease types A and B is estimated to affect 1 in 250,000 individuals. Niemann-Pick disease type A occurs more frequently among individuals of Ashkenazi (eastern and central European) Jewish descent than in the general population. The incidence within the Ashkenazi population is approximately 1 in 40,000 individuals.  Combined, Niemann-Pick disease types C1 and C2 are estimated to affect 1 in 150,000 individuals; however, type C1 is by far the more common type, accounting for 95 percent of cases. The disease occurs more frequently in people of French-Acadian descent in Nova Scotia. In Nova Scotia, a population of affected French-Acadians were previously designated as having Niemann-Pick disease type D, however, it was shown that these individuals have mutations in the gene associated with Niemann-Pick disease type C1.",Niemann-Pick disease,0000731,GHR,https://ghr.nlm.nih.gov/condition/niemann-pick-disease,C0028064,T047,Disorders
What are the genetic changes related to Niemann-Pick disease ?,0000731-3,genetic changes,"Niemann-Pick disease types A and B is caused by mutations in the SMPD1 gene. This gene provides instructions for producing an enzyme called acid sphingomyelinase. This enzyme is found in lysosomes, which are compartments within cells that break down and recycle different types of molecules. Acid sphingomyelinase is responsible for the conversion of a fat (lipid) called sphingomyelin into another type of lipid called ceramide. Mutations in SMPD1 lead to a shortage of acid sphingomyelinase, which results in reduced break down of sphingomyelin, causing this fat to accumulate in cells. This fat buildup causes cells to malfunction and eventually die. Over time, cell loss impairs function of tissues and organs including the brain, lungs, spleen, and liver in people with Niemann-Pick disease types A and B.  Mutations in either the NPC1 or NPC2 gene cause Niemann-Pick disease type C. The proteins produced from these genes are involved in the movement of lipids within cells. Mutations in these genes lead to a shortage of functional protein, which prevents movement of cholesterol and other lipids, leading to their accumulation in cells. Because these lipids are not in their proper location in cells, many normal cell functions that require lipids (such as cell membrane formation) are impaired. The accumulation of lipids as well as the cell dysfunction eventually leads to cell death, causing the tissue and organ damage seen in Niemann-Pick disease types C1 and C2.",Niemann-Pick disease,0000731,GHR,https://ghr.nlm.nih.gov/condition/niemann-pick-disease,C0028064,T047,Disorders
Is Niemann-Pick disease inherited ?,0000731-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Niemann-Pick disease,0000731,GHR,https://ghr.nlm.nih.gov/condition/niemann-pick-disease,C0028064,T047,Disorders
What are the treatments for Niemann-Pick disease ?,0000731-5,treatment,"These resources address the diagnosis or management of Niemann-Pick disease:  - Baby's First Test  - Gene Review: Gene Review: Acid Sphingomyelinase Deficiency  - Gene Review: Gene Review: Niemann-Pick Disease Type C  - Genetic Testing Registry: Niemann-Pick disease type C1  - Genetic Testing Registry: Niemann-Pick disease type C2  - Genetic Testing Registry: Niemann-Pick disease, type A  - Genetic Testing Registry: Niemann-Pick disease, type B  - Genetic Testing Registry: Niemann-Pick disease, type C  - Genetic Testing Registry: Niemann-Pick disease, type D  - Genetic Testing Registry: Niemann-pick disease, intermediate, protracted neurovisceral  - Genetic Testing Registry: Sphingomyelin/cholesterol lipidosis  - MedlinePlus Encyclopedia: Niemann-Pick Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Niemann-Pick disease,0000731,GHR,https://ghr.nlm.nih.gov/condition/niemann-pick-disease,C0028064,T047,Disorders
What is (are) Nijmegen breakage syndrome ?,0000732-1,information,"Nijmegen breakage syndrome is a condition characterized by short stature, an unusually small head size (microcephaly), distinctive facial features, recurrent respiratory tract infections, an increased risk of cancer, intellectual disability, and other health problems.  People with this condition typically grow slowly during infancy and early childhood. After this period of slow growth, affected individuals grow at a normal rate but remain shorter than their peers. Microcephaly is apparent from birth in the majority of affected individuals. The head does not grow at the same rate as the rest of the body, so it appears that the head is getting smaller as the body grows (progressive microcephaly). Individuals with Nijmegen breakage syndrome have distinctive facial features that include a sloping forehead, a prominent nose, large ears, a small jaw, and outside corners of the eyes that point upward (upslanting palpebral fissures). These facial features typically become apparent by age 3.  People with Nijmegen breakage syndrome have a malfunctioning immune system (immunodeficiency) with abnormally low levels of immune system proteins called immunoglobulin G (IgG) and immunoglobulin A (IgA). Affected individuals also have a shortage of immune system cells called T cells. The immune system abnormalities increase susceptibility to recurrent infections, such as bronchitis, pneumonia, sinusitis, and other infections affecting the upper respiratory tract and lungs.  Individuals with Nijmegen breakage syndrome have an increased risk of developing cancer, most commonly a cancer of immune system cells called non-Hodgkin lymphoma. About half of individuals with Nijmegen breakage syndrome develop non-Hodgkin lymphoma, usually before age 15. Other cancers seen in people with Nijmegen breakage syndrome include brain tumors such as medulloblastoma and glioma, and a cancer of muscle tissue called rhabdomyosarcoma. People with Nijmegen breakage syndrome are 50 times more likely to develop cancer than people without this condition.  Intellectual development is normal in most people with this condition for the first year or two of life, but then development becomes delayed. Skills decline over time, and most affected children and adults have mild to moderate intellectual disability.  Most affected woman have premature ovarian failure and do not begin menstruation by age 16 (primary amenorrhea) or have infrequent menstrual periods. Most women with Nijmegen breakage syndrome are unable to have biological children (infertile).",Nijmegen breakage syndrome,0000732,GHR,https://ghr.nlm.nih.gov/condition/nijmegen-breakage-syndrome,C0398791,T019,Disorders
How many people are affected by Nijmegen breakage syndrome ?,0000732-2,frequency,"The exact prevalence of Nijmegen breakage syndrome is unknown. This condition is estimated to affect one in 100,000 newborns worldwide, but is thought to be most common in the Slavic populations of Eastern Europe.",Nijmegen breakage syndrome,0000732,GHR,https://ghr.nlm.nih.gov/condition/nijmegen-breakage-syndrome,C0398791,T019,Disorders
What are the genetic changes related to Nijmegen breakage syndrome ?,0000732-3,genetic changes,"Mutations in the NBN gene cause Nijmegen breakage syndrome. The NBN gene provides instructions for making a protein called nibrin. This protein is involved in several critical cellular functions, including the repair of damaged DNA. Nibrin interacts with two other proteins as part of a larger protein complex. This protein complex works to mend broken strands of DNA. DNA can be damaged by agents such as toxic chemicals or radiation. Breaks in DNA strands also occur naturally when chromosomes exchange genetic material in preparation for cell division. Repairing DNA prevents cells from accumulating genetic damage that can cause them to die or to divide uncontrollably. The nibrin protein and the proteins with which it interacts help maintain the stability of a cell's genetic information through its roles in repairing damaged DNA and regulating cell division.  The NBN gene mutations that cause this condition typically lead to the production of an abnormally short version of the nibrin protein. The defective protein is missing important regions, preventing it from responding to DNA damage effectively. As a result, affected individuals are sensitive to the effects of radiation exposure and other agents that can cause breaks in DNA. Nijmegen breakage syndrome gets its name from numerous breaks in DNA that occur in affected people's cells. A buildup of mistakes in DNA can trigger cells to grow and divide abnormally, increasing the risk of cancer in people with Nijmegen breakage syndrome. Nibrin's role in regulating cell division and cell growth (proliferation) is thought to lead to the immunodeficiency seen in affected individuals. A lack of functional nibrin results in less immune cell proliferation. A decrease in the amount of immune cells that are produced leads to reduced amounts of immunoglobulins and other features of immunodeficiency. It is unclear how mutations in the NBN gene cause the other features of Nijmegen breakage syndrome.",Nijmegen breakage syndrome,0000732,GHR,https://ghr.nlm.nih.gov/condition/nijmegen-breakage-syndrome,C0398791,T019,Disorders
Is Nijmegen breakage syndrome inherited ?,0000732-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Nijmegen breakage syndrome,0000732,GHR,https://ghr.nlm.nih.gov/condition/nijmegen-breakage-syndrome,C0398791,T019,Disorders
What are the treatments for Nijmegen breakage syndrome ?,0000732-5,treatment,"These resources address the diagnosis or management of Nijmegen breakage syndrome:  - Boston Children's Hospital: Pneumonia in Children  - Boston Children's Hospital: Sinusitis in Children  - Cleveland Clinic: Bronchitis  - Gene Review: Gene Review: Nijmegen Breakage Syndrome  - Genetic Testing Registry: Microcephaly, normal intelligence and immunodeficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Nijmegen breakage syndrome,0000732,GHR,https://ghr.nlm.nih.gov/condition/nijmegen-breakage-syndrome,C0398791,T019,Disorders
What is (are) nonbullous congenital ichthyosiform erythroderma ?,0000733-1,information,"Nonbullous congenital ichthyosiform erythroderma (NBCIE) is a condition that mainly affects the skin. Some affected infants are born with a tight, clear sheath covering their skin called a collodion membrane. This membrane is usually shed during the first few weeks of life. Individuals with NBCIE have skin that is red (erythema) and covered with fine white scales. Some people with NBCIE have outward turning eyelids and lips, a thickening of the skin on the palms and soles of the feet (keratoderma), and nails that do not grow normally (nail dystrophy). Infants with NBCIE may develop infections, an excessive loss of fluids (dehydration), and respiratory problems early in life.",nonbullous congenital ichthyosiform erythroderma,0000733,GHR,https://ghr.nlm.nih.gov/condition/nonbullous-congenital-ichthyosiform-erythroderma,C0079154,T019,Disorders
How many people are affected by nonbullous congenital ichthyosiform erythroderma ?,0000733-2,frequency,"NBCIE is estimated to affect 1 in 200,000 to 300,000 individuals in the United States. This condition is more common in Norway, where an estimated 1 in 90,000 people are affected.",nonbullous congenital ichthyosiform erythroderma,0000733,GHR,https://ghr.nlm.nih.gov/condition/nonbullous-congenital-ichthyosiform-erythroderma,C0079154,T019,Disorders
What are the genetic changes related to nonbullous congenital ichthyosiform erythroderma ?,0000733-3,genetic changes,"Mutations in at least three genes can cause NBCIE. These genes provide instructions for making proteins that are found in the outermost layer of the skin (the epidermis). The epidermis forms a protective barrier between the body and its surrounding environment. The skin abnormalities associated with NBCIE disrupt this protective barrier, making it more difficult for affected infants to control water loss, regulate body temperature, and fight infections.  Mutations in the ALOX12B and ALOXE3 genes are responsible for the majority of cases of NBCIE. Mutations in one other gene associated with this condition are found in only a small percentage of cases. In some people with NBCIE, the cause of the disorder is unknown. Researchers are looking for additional genes that are associated with NBCIE.",nonbullous congenital ichthyosiform erythroderma,0000733,GHR,https://ghr.nlm.nih.gov/condition/nonbullous-congenital-ichthyosiform-erythroderma,C0079154,T019,Disorders
Is nonbullous congenital ichthyosiform erythroderma inherited ?,0000733-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",nonbullous congenital ichthyosiform erythroderma,0000733,GHR,https://ghr.nlm.nih.gov/condition/nonbullous-congenital-ichthyosiform-erythroderma,C0079154,T019,Disorders
What are the treatments for nonbullous congenital ichthyosiform erythroderma ?,0000733-5,treatment,These resources address the diagnosis or management of nonbullous congenital ichthyosiform erythroderma:  - Foundation for Ichthyosis and Related Skin Types (FIRST): Treatments  - Gene Review: Gene Review: Autosomal Recessive Congenital Ichthyosis  - Genetic Testing Registry: Autosomal recessive congenital ichthyosis 2   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,nonbullous congenital ichthyosiform erythroderma,0000733,GHR,https://ghr.nlm.nih.gov/condition/nonbullous-congenital-ichthyosiform-erythroderma,C0079154,T019,Disorders
What is (are) nonsyndromic aplasia cutis congenita ?,0000734-1,information,"Nonsyndromic aplasia cutis congenita is a condition in which babies are born with localized areas of missing skin (lesions). These areas resemble ulcers or open wounds, although they are sometimes already healed at birth. Lesions most commonly occur on the top of the head (skull vertex), although they can be found on the torso or limbs. In some cases, the bone and other tissues under the skin defect are also underdeveloped.  Most affected babies have a single lesion. The lesions vary in size and can be differently shaped: some are round or oval, others rectangular, and still others star-shaped. They usually leave a scar after they heal. When the scalp is involved, there may be an absence of hair growth (alopecia) in the affected area.  When the underlying bone and other tissues are involved, affected individuals are at higher risk of infections. If these severe defects occur on the head, the membrane that covers the brain (the dura mater) may be exposed, and life-threatening bleeding may occur from nearby vessels.  Skin lesions are typically the only feature of nonsyndromic aplasia cutis congenita, although other skin problems and abnormalities of the bones and other tissues occur rarely. However, the characteristic skin lesions can occur as one of many symptoms in other conditions, including Johanson-Blizzard syndrome and Adams-Oliver syndrome. These instances are described as syndromic aplasia cutis congenita.",nonsyndromic aplasia cutis congenita,0000734,GHR,https://ghr.nlm.nih.gov/condition/nonsyndromic-aplasia-cutis-congenita,C0282160,T019,Disorders
How many people are affected by nonsyndromic aplasia cutis congenita ?,0000734-2,frequency,"Aplasia cutis congenita affects approximately 1 in 10,000 newborns. The incidence of the nonsyndromic form is unknown.",nonsyndromic aplasia cutis congenita,0000734,GHR,https://ghr.nlm.nih.gov/condition/nonsyndromic-aplasia-cutis-congenita,C0282160,T019,Disorders
What are the genetic changes related to nonsyndromic aplasia cutis congenita ?,0000734-3,genetic changes,"Nonsyndromic aplasia cutis congenita can have different causes, and often the cause is unknown. Because the condition is sometimes found in multiple members of a family, it is thought to have a genetic component; however, the genetic factors are not fully understood. Researchers suggest that genes important for skin growth may be involved. It is thought that impairments of skin growth more commonly affect the skin at the top of the head because that region needs to be able to grow quickly to cover the fast-growing skull of a developing baby.  In some cases, nonsyndromic aplasia cutis congenita is caused by exposure to a drug called methimazole before birth. This medication is given to treat an overactive thyroid gland. Babies whose mothers take this medication during pregnancy are at increased risk of having the condition. In addition, certain viral infections in a pregnant mother can cause the baby to be born with the skin lesions characteristic of nonsyndromic aplasia cutis congenita. Other cases are thought to be caused by injury to the baby during development.",nonsyndromic aplasia cutis congenita,0000734,GHR,https://ghr.nlm.nih.gov/condition/nonsyndromic-aplasia-cutis-congenita,C0282160,T019,Disorders
Is nonsyndromic aplasia cutis congenita inherited ?,0000734-4,inheritance,"Most cases of nonsyndromic aplasia cutis congenita are sporadic, which means they occur in people with no history of the disorder in their family. When the condition runs in families, inheritance usually follows an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. Rarely, the condition appears to follow an autosomal recessive pattern of inheritance, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",nonsyndromic aplasia cutis congenita,0000734,GHR,https://ghr.nlm.nih.gov/condition/nonsyndromic-aplasia-cutis-congenita,C0282160,T019,Disorders
What are the treatments for nonsyndromic aplasia cutis congenita ?,0000734-5,treatment,These resources address the diagnosis or management of nonsyndromic aplasia cutis congenita:  - Genetic Testing Registry: Aplasia cutis congenita   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,nonsyndromic aplasia cutis congenita,0000734,GHR,https://ghr.nlm.nih.gov/condition/nonsyndromic-aplasia-cutis-congenita,C0282160,T019,Disorders
What is (are) nonsyndromic hearing loss ?,0000735-1,information,"Nonsyndromic hearing loss is a partial or total loss of hearing that is not associated with other signs and symptoms. In contrast, syndromic hearing loss occurs with signs and symptoms affecting other parts of the body.  Nonsyndromic hearing loss can be classified in several different ways. One common way is by the condition's pattern of inheritance: autosomal dominant (DFNA), autosomal recessive (DFNB), X-linked (DFNX), or mitochondrial (which does not have a special designation). Each of these types of hearing loss includes multiple subtypes. DFNA, DFNB, and DFNX subtypes are numbered in the order in which they were first described. For example, DFNA1 was the first type of autosomal dominant nonsyndromic hearing loss to be identified. The various inheritance patterns of nonsyndromic hearing loss are described in more detail below.  The characteristics of nonsyndromic hearing loss vary among the different types. Hearing loss can affect one ear (unilateral) or both ears (bilateral). Degrees of hearing loss range from mild (difficulty understanding soft speech) to profound (inability to hear even very loud noises). The term ""deafness"" is often used to describe severe-to-profound hearing loss. Hearing loss can be stable, or it may be progressive, becoming more severe as a person gets older. Particular types of nonsyndromic hearing loss show distinctive patterns of hearing loss. For example, the loss may be more pronounced at high, middle, or low tones.  Most forms of nonsyndromic hearing loss are described as sensorineural, which means they are associated with a permanent loss of hearing caused by damage to structures in the inner ear. The inner ear processes sound and sends the information to the brain in the form of electrical nerve impulses. Less commonly, nonsyndromic hearing loss is described as conductive, meaning it results from changes in the middle ear. The middle ear contains three tiny bones that help transfer sound from the eardrum to the inner ear. Some forms of nonsyndromic hearing loss, particularly a type called DFNX2, involve changes in both the inner ear and the middle ear. This combination is called mixed hearing loss.  Depending on the type, nonsyndromic hearing loss can become apparent at any time from infancy to old age. Hearing loss that is present before a child learns to speak is classified as prelingual or congenital. Hearing loss that occurs after the development of speech is classified as postlingual.",nonsyndromic hearing loss,0000735,GHR,https://ghr.nlm.nih.gov/condition/nonsyndromic-hearing-loss,C3711374,T047,Disorders
How many people are affected by nonsyndromic hearing loss ?,0000735-2,frequency,"Between 2 and 3 per 1,000 children in the United States are born with detectable hearing loss in one or both ears. The prevalence of hearing loss increases with age; the condition affects 1 in 8 people in the United States age 12 and older, or about 30 million people. By age 85, more than half of all people experience hearing loss.",nonsyndromic hearing loss,0000735,GHR,https://ghr.nlm.nih.gov/condition/nonsyndromic-hearing-loss,C3711374,T047,Disorders
What are the genetic changes related to nonsyndromic hearing loss ?,0000735-3,genetic changes,"The causes of nonsyndromic hearing loss are complex. Researchers have identified more than 90 genes that, when altered, are associated with nonsyndromic hearing loss. Many of these genes are involved in the development and function of the inner ear. Mutations in these genes contribute to hearing loss by interfering with critical steps in processing sound. Different mutations in the same gene can be associated with different types of hearing loss, and some genes are associated with both syndromic and nonsyndromic forms. In many affected families, the factors contributing to hearing loss have not been identified.  Most cases of nonsyndromic hearing loss are inherited in an autosomal recessive pattern. About half of all severe-to-profound autosomal recessive nonsyndromic hearing loss results from mutations in the GJB2 gene; these cases are designated DFNB1. The GJB2 gene provides instructions for making a protein called connexin 26, which is a member of the connexin protein family. Mutations in another connexin gene, GJB6, can also cause DFNB1. The GJB6 gene provides instructions for making a protein called connexin 30. Connexin proteins form channels called gap junctions, which allow communication between neighboring cells, including cells in the inner ear. Mutations in the GJB2 or GJB6 gene alter their respective connexin proteins, which changes the structure of gap junctions and may affect the function or survival of cells that are needed for hearing.  The most common cause of moderate autosomal recessive nonsyndromic hearing loss is mutations in the STRC gene. These mutations cause a form of the condition known as DFNB16. Mutations in more than 60 other genes can also cause autosomal recessive nonsyndromic hearing loss. Many of these gene mutations have been found in one or a few families.  Nonsyndromic hearing loss can also be inherited in an autosomal dominant pattern. Mutations in at least 30 genes have been identified in people with autosomal dominant nonsyndromic hearing loss; mutations in some of these genes (including GJB2 and GJB6) can also cause autosomal recessive forms of the condition. Although no single gene is associated with a majority of autosomal dominant nonsyndromic hearing loss cases, mutations in a few genes, such as KCNQ4 and TECTA, are relatively common. Mutations in many of the other genes associated with autosomal dominant nonsyndromic hearing loss have been found in only one or a few families.  X-linked and mitochondrial forms of nonsyndromic hearing loss are rare. About half of all X-linked cases are caused by mutations in the POU3F4 gene. This form of the condition is designated DFNX2. Mutations in at least three other genes have also been identified in people with X-linked nonsyndromic hearing loss.  Mitochondrial forms of hearing loss result from changes in mitochondrial DNA (mtDNA). Mitochondria are structures within cells that convert the energy from food into a form that cells can use. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA. Only a few mutations in mtDNA have been associated with hearing loss, and their role in the condition is still being studied.  Mutations in some of the genes associated with nonsyndromic hearing loss can also cause syndromic forms of hearing loss, such as Usher syndrome (CDH23 and MYO7A, among others), Pendred syndrome (SLC26A4), Wolfram syndrome (WFS1), and Stickler syndrome (COL11A2). It is often unclear how mutations in the same gene can cause isolated hearing loss in some individuals and hearing loss with additional signs and symptoms in others.  In addition to genetic changes, hearing loss can result from environmental factors or a combination of genetic risk and a person's environmental exposures. Environmental causes of hearing loss include certain medications, specific infections before or after birth, and exposure to loud noise over an extended period. Age is also a major risk factor for hearing loss. Age-related hearing loss (presbyacusis) is thought to have both genetic and environmental influences.",nonsyndromic hearing loss,0000735,GHR,https://ghr.nlm.nih.gov/condition/nonsyndromic-hearing-loss,C3711374,T047,Disorders
Is nonsyndromic hearing loss inherited ?,0000735-4,inheritance,"As discussed above, nonsyndromic hearing loss has different patterns of inheritance. Between 75 and 80 percent of cases are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Usually, each parent of an individual with autosomal recessive hearing loss carries one copy of the mutated gene but does not have hearing loss.  Another 20 to 25 percent of nonsyndromic hearing loss has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the condition. Most people with autosomal dominant hearing loss inherit an altered copy of the gene from a parent who also has hearing loss.  Between 1 and 2 percent of cases have an X-linked pattern of inheritance. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. Males with X-linked nonsyndromic hearing loss tend to develop more severe hearing loss earlier in life than females who inherit a copy of the same gene mutation. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  Mitochondrial forms of the condition, which result from changes to mtDNA, account for less than 1 percent of all nonsyndromic hearing loss in the United States. These cases are inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mtDNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children.  In some cases, hearing loss occurs in people with no history of the condition in their family. These cases are described as sporadic, and the cause of the hearing loss is often unknown. When hearing loss results from environmental factors, it is not inherited.",nonsyndromic hearing loss,0000735,GHR,https://ghr.nlm.nih.gov/condition/nonsyndromic-hearing-loss,C3711374,T047,Disorders
What are the treatments for nonsyndromic hearing loss ?,0000735-5,treatment,"These resources address the diagnosis or management of nonsyndromic hearing loss:  - Baby's First Test: Hearing Loss  - Gene Review: Gene Review: Deafness and Hereditary Hearing Loss Overview  - Genetic Testing Registry: Deafness, X-linked  - Genetic Testing Registry: Hereditary hearing loss and deafness  - Genetic Testing Registry: Non-syndromic genetic deafness  - MedlinePlus Encyclopedia: Age-related hearing loss  - MedlinePlus Encyclopedia: Audiology  - MedlinePlus Encyclopedia: Hearing loss  - MedlinePlus Encyclopedia: Hearing or speech impairment - resources   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",nonsyndromic hearing loss,0000735,GHR,https://ghr.nlm.nih.gov/condition/nonsyndromic-hearing-loss,C3711374,T047,Disorders
What is (are) nonsyndromic holoprosencephaly ?,0000736-1,information,"Nonsyndromic holoprosencephaly is an abnormality of brain development that also affects the head and face. Normally, the brain divides into two halves (hemispheres) during early development. Holoprosencephaly occurs when the brain fails to divide properly into the right and left hemispheres. This condition is called nonsyndromic to distinguish it from other types of holoprosencephaly caused by genetic syndromes, chromosome abnormalities, or substances that cause birth defects (teratogens). The severity of nonsyndromic holoprosencephaly varies widely among affected individuals, even within the same family.  Nonsyndromic holoprosencephaly can be grouped into four types according to the degree of brain division. From most to least severe, the types are known as alobar, semi-lobar, lobar, and middle interhemispheric variant (MIHV). In the most severe forms of nonsyndromic holoprosencephaly, the brain does not divide at all. These affected individuals have one central eye (cyclopia) and a tubular nasal structure (proboscis) located above the eye. Most babies with severe nonsyndromic holoprosencephaly die before birth or soon after. In the less severe forms, the brain is partially divided and the eyes are usually set close together (hypotelorism). The life expectancy of these affected individuals varies depending on the severity of symptoms.  People with nonsyndromic holoprosencephaly often have a small head (microcephaly), although they can develop a buildup of fluid in the brain (hydrocephalus) that causes increased head size (macrocephaly). Other features may include an opening in the roof of the mouth (cleft palate) with or without a split in the upper lip (cleft lip), one central front tooth instead of two (a single maxillary central incisor), and a flat nasal bridge. The eyeballs may be abnormally small (microphthalmia) or absent (anophthalmia).  Some individuals with nonsyndromic holoprosencephaly have a distinctive pattern of facial features, including a narrowing of the head at the temples, outside corners of the eyes that point upward (upslanting palpebral fissures), large ears, a short nose with upturned nostrils, and a broad and deep space between the nose and mouth (philtrum). In general, the severity of facial features is directly related to the severity of the brain abnormalities. However, individuals with mildly affected facial features can have severe brain abnormalities. Some people do not have apparent structural brain abnormalities but have some of the facial features associated with this condition. These individuals are considered to have a form of the disorder known as microform holoprosencephaly and are typically identified after the birth of a severely affected family member.  Most people with nonsyndromic holoprosencephaly have developmental delay and intellectual disability. Affected individuals also frequently have a malfunctioning pituitary gland, which is a gland located at the base of the brain that produces several hormones. Because pituitary dysfunction leads to the partial or complete absence of these hormones, it can cause a variety of disorders. Most commonly, people with nonsyndromic holoprosencephaly and pituitary dysfunction develop diabetes insipidus, a condition that disrupts the balance between fluid intake and urine excretion. Dysfunction in other parts of the brain can cause seizures, feeding difficulties, and problems regulating body temperature, heart rate, and breathing. The sense of smell may be diminished (hyposmia) or completely absent (anosmia) if the part of the brain that processes smells is underdeveloped or missing.",nonsyndromic holoprosencephaly,0000736,GHR,https://ghr.nlm.nih.gov/condition/nonsyndromic-holoprosencephaly,C3711749,T047,Disorders
How many people are affected by nonsyndromic holoprosencephaly ?,0000736-2,frequency,"Nonsyndromic holoprosencephaly accounts for approximately 25 to 50 percent of all cases of holoprosencephaly, which affects an estimated 1 in 10,000 newborns.",nonsyndromic holoprosencephaly,0000736,GHR,https://ghr.nlm.nih.gov/condition/nonsyndromic-holoprosencephaly,C3711749,T047,Disorders
What are the genetic changes related to nonsyndromic holoprosencephaly ?,0000736-3,genetic changes,"Mutations in 11 genes have been found to cause nonsyndromic holoprosencephaly. These genes provide instructions for making proteins that are important for normal embryonic development, particularly for determining the shape of the brain and face. About 25 percent of people with nonsyndromic holoprosencephaly have a mutation in one of these four genes: SHH, ZIC2, SIX3, or TGIF1. Mutations in the other genes related to nonsyndromic holoprosencephaly are found in only a small percentage of cases. Many individuals with this condition do not have an identified gene mutation. The cause of the disorder is unknown in these individuals.  The brain normally divides into right and left hemispheres during the third to fourth week of pregnancy. To establish the line that separates the two hemispheres (the midline), the activity of many genes must be tightly regulated and coordinated. These genes provide instructions for making signaling proteins, which instruct the cells within the brain to form the right and left hemispheres.  Signaling proteins are also important for the formation of the eyes. During early development, the cells that develop into the eyes form a single structure called the eye field. This structure is located in the center of the developing face. The signaling protein produced from the SHH gene causes the eye field to separate into two distinct eyes. The SIX3 gene is involved in the formation of the lens of the eye and the specialized tissue at the back of the eye that detects light and color (the retina).  Mutations in the genes that cause nonsyndromic holoprosencephaly lead to the production of abnormal or nonfunctional signaling proteins. Without the correct signals, the eyes will not form normally and the brain does not separate into two hemispheres. The development of other parts of the face is affected if the eyes do not move to their proper position. The signs and symptoms of nonsyndromic holoprosencephaly are caused by abnormal development of the brain and face.  Researchers believe that other genetic or environmental factors, many of which have not been identified, play a role in determining the severity of nonsyndromic holoprosencephaly.",nonsyndromic holoprosencephaly,0000736,GHR,https://ghr.nlm.nih.gov/condition/nonsyndromic-holoprosencephaly,C3711749,T047,Disorders
Is nonsyndromic holoprosencephaly inherited ?,0000736-4,inheritance,"Nonsyndromic holoprosencephaly is inherited in an autosomal dominant pattern, which means an alteration in one copy of a gene in each cell is usually sufficient to cause the disorder. However, not all people with a gene mutation will develop signs and symptoms of the condition.  In some cases, an affected person inherits the mutation from one parent who may or may not have mild features of the condition. Other cases result from a new gene mutation and occur in people with no history of the disorder in their family.",nonsyndromic holoprosencephaly,0000736,GHR,https://ghr.nlm.nih.gov/condition/nonsyndromic-holoprosencephaly,C3711749,T047,Disorders
What are the treatments for nonsyndromic holoprosencephaly ?,0000736-5,treatment,These resources address the diagnosis or management of nonsyndromic holoprosencephaly:  - Gene Review: Gene Review: Holoprosencephaly Overview  - Genetic Testing Registry: Holoprosencephaly 1  - Genetic Testing Registry: Holoprosencephaly 10  - Genetic Testing Registry: Holoprosencephaly 2  - Genetic Testing Registry: Holoprosencephaly 3  - Genetic Testing Registry: Holoprosencephaly 4  - Genetic Testing Registry: Holoprosencephaly 5  - Genetic Testing Registry: Holoprosencephaly 6  - Genetic Testing Registry: Holoprosencephaly 7  - Genetic Testing Registry: Holoprosencephaly 8  - Genetic Testing Registry: Holoprosencephaly 9  - Genetic Testing Registry: Holoprosencephaly sequence  - Genetic Testing Registry: NODAL-Related Holoprosencephaly   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,nonsyndromic holoprosencephaly,0000736,GHR,https://ghr.nlm.nih.gov/condition/nonsyndromic-holoprosencephaly,C3711749,T047,Disorders
What is (are) nonsyndromic paraganglioma ?,0000737-1,information,"Paraganglioma is a type of noncancerous (benign) tumor that occurs in structures called paraganglia. Paraganglia are groups of cells that are found near nerve cell bunches called ganglia. Paragangliomas are usually found in the head, neck, or torso. However, a type of paraganglioma known as pheochromocytoma develops in the adrenal glands. Adrenal glands are located on top of each kidney and produce hormones in response to stress. Most people with paraganglioma develop only one tumor in their lifetime.  Some people develop a paraganglioma or pheochromocytoma as part of a hereditary syndrome that may affect other organs and tissues in the body. However, the tumors often are not associated with any syndromes, in which case the condition is called nonsyndromic paraganglioma or pheochromocytoma.  Pheochromocytomas and some other paragangliomas are associated with ganglia of the sympathetic nervous system. The sympathetic nervous system controls the ""fight-or-flight"" response, a series of changes in the body due to hormones released in response to stress. Although most sympathetic paragangliomas are pheochromocytomas, some are found outside the adrenal glands, usually in the abdomen, and are called extra-adrenal paragangliomas. Most sympathetic paragangliomas, including pheochromocytomas, produce hormones called catecholamines, such as epinephrine (adrenaline) or norepinephrine. These excess catecholamines can cause signs and symptoms such as high blood pressure (hypertension), episodes of rapid heartbeat (palpitations), headaches, or sweating.  Most paragangliomas are associated with ganglia of the parasympathetic nervous system, which controls involuntary body functions such as digestion and saliva formation. Parasympathetic paragangliomas, typically found in the head and neck, usually do not produce hormones. However, large tumors may cause signs and symptoms such as coughing, hearing loss in one ear, or difficulty swallowing.  Although most paragangliomas and pheochromocytomas are noncancerous, some can become cancerous (malignant) and spread to other parts of the body (metastasize). Extra-adrenal paragangliomas become malignant more often than other types of paraganglioma or pheochromocytoma.",nonsyndromic paraganglioma,0000737,GHR,https://ghr.nlm.nih.gov/condition/nonsyndromic-paraganglioma,C0030421,T191,Disorders
How many people are affected by nonsyndromic paraganglioma ?,0000737-2,frequency,"It is estimated that the prevalence of pheochromocytoma is 1 in 500,000 people, and the prevalence of other paragangliomas is 1 in 1 million people. These statistics include syndromic and nonsyndromic paraganglioma and pheochromocytoma.",nonsyndromic paraganglioma,0000737,GHR,https://ghr.nlm.nih.gov/condition/nonsyndromic-paraganglioma,C0030421,T191,Disorders
What are the genetic changes related to nonsyndromic paraganglioma ?,0000737-3,genetic changes,"The VHL, RET, SDHB, and SDHD genes can be mutated in both syndromic and nonsyndromic forms of paraganglioma and pheochromocytoma. Mutations in at least three additional genes, TMEM127, SDHA, and KIF1B, have been identified in people with the nonsyndromic form of these conditions. Gene mutations increase the risk of developing paraganglioma or pheochromocytoma by affecting control of cell growth and division.  Mutations in the VHL, SDHA, SDHB, and SDHD genes increase the risk of developing nonsyndromic paraganglioma or pheochromocytoma. The protein produced from the VHL gene helps break down other, unneeded proteins, including a protein called HIF that stimulates cell division and blood vessel formation under certain cellular conditions. The proteins produced from the SDHA, SHDB, and SDHD genes are each pieces (subunits) of an enzyme that is important for energy production in the cell. This enzyme also plays a role in the breakdown of the HIF protein. Mutations in the VHL, SDHA, SDHB, and SDHD genes stabilize the HIF protein, causing it to build up in cells. Excess HIF protein stimulates cells to divide and triggers the production of blood vessels when they are not needed. Rapid and uncontrolled cell division, along with the formation of new blood vessels, can lead to the development of tumors.  Mutations in the RET gene have been found in nonsyndromic pheochromocytoma in addition to a pheochromocytoma-predisposing syndrome. The protein produced from the RET gene is involved in signaling within cells that can stimulate cell division or maturation. Mutations in the RET gene overactivate the protein's signaling function, which can trigger cell growth and division in the absence of signals from outside the cell. This unchecked cell division can lead to the formation of tumors in the adrenal glands.  Mutations in the TMEM127 gene have been identified most commonly in people with nonsyndromic pheochromocytoma and are rarely seen in people with other paraganglioma. The TMEM127 protein normally controls a signaling pathway that induces cell growth and survival. Studies suggest that mutations in the TMEM127 gene lead to abnormal activation of cell growth, which may cause tumor formation.  Mutations in the KIF1B gene have been reported in nonsyndromic pheochromocytoma. Studies suggest that these mutations impair the function of the KIF1B protein, which normally triggers cells to self-destruct in a process called apoptosis. When apoptosis is impaired, cells grow and divide too quickly or in an uncontrolled way, potentially leading to tumor formation.  Many people with nonsyndromic paraganglioma or pheochromocytoma do not have a mutation in any of the genes associated with the conditions. It is likely that other, unidentified genes also predispose to development of paraganglioma or pheochromocytoma.",nonsyndromic paraganglioma,0000737,GHR,https://ghr.nlm.nih.gov/condition/nonsyndromic-paraganglioma,C0030421,T191,Disorders
Is nonsyndromic paraganglioma inherited ?,0000737-4,inheritance,"Nonsyndromic paraganglioma can be inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing a paraganglioma or pheochromocytoma. People with mutations in the gene inherit an increased risk of this condition, not the condition itself. Not all people with this condition have a mutation in the gene, and not all people with a gene mutation will develop the disorder.  Most cases of nonsyndromic paraganglioma and pheochromocytoma are considered sporadic, which means the tumors occur in people with no history of the disorder in their family.",nonsyndromic paraganglioma,0000737,GHR,https://ghr.nlm.nih.gov/condition/nonsyndromic-paraganglioma,C0030421,T191,Disorders
What are the treatments for nonsyndromic paraganglioma ?,0000737-5,treatment,These resources address the diagnosis or management of nonsyndromic paraganglioma:  - Genetic Testing Registry: Pheochromocytoma   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,nonsyndromic paraganglioma,0000737,GHR,https://ghr.nlm.nih.gov/condition/nonsyndromic-paraganglioma,C0030421,T191,Disorders
What is (are) Noonan syndrome ?,0000738-1,information,"Noonan syndrome is a condition that affects many areas of the body. It is characterized by mildly unusual facial characteristics, short stature, heart defects, bleeding problems, skeletal malformations, and many other signs and symptoms.  People with Noonan syndrome have distinctive facial features such as a deep groove in the area between the nose and mouth (philtrum), widely spaced eyes that are usually pale blue or blue-green in color, and low-set ears that are rotated backward. Affected individuals may have a high arch in the roof of the mouth (high-arched palate), poor alignment of the teeth, and a small lower jaw (micrognathia). Many children with Noonan syndrome have a short neck and both children and adults may have excess neck skin (also called webbing) and a low hairline at the back of the neck.  Approximately 50 to 70 percent of individuals with Noonan syndrome have short stature. At birth, they are usually of normal length and weight, but growth slows over time. Abnormal levels of growth hormone may contribute to the slow growth.  Individuals with Noonan syndrome often have either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum). Some affected people may also have an abnormal side-to-side curvature of the spine (scoliosis).  Most people with Noonan syndrome have a heart defect. The most common heart defect is a narrowing of the valve that controls blood flow from the heart to the lungs (pulmonary valve stenosis). Some affected individuals have hypertrophic cardiomyopathy, which is a thickening of the heart muscle that forces the heart to work harder to pump blood.  A variety of bleeding disorders have been associated with Noonan syndrome. Some people may have excessive bruising, nosebleeds, or prolonged bleeding following injury or surgery. Women with a bleeding disorder typically have excessive bleeding during menstruation (menorrhagia) or childbirth.  Adolescent males with Noonan syndrome typically experience delayed puberty. Affected individuals go through puberty starting at age 13 or 14 and have a reduced pubertal growth spurt. Most males with Noonan syndrome have undescended testicles (cryptorchidism), which may be related to delayed puberty or to infertility (inability to father a child) later in life. Females with Noonan syndrome typically have normal puberty and fertility.  Noonan syndrome can cause a variety of other signs and symptoms. Most children diagnosed with Noonan syndrome have normal intelligence, but a small percentage has special educational needs, and some have intellectual disability. Some affected individuals have vision or hearing problems. Infants with Noonan syndrome may be born with puffy hands and feet caused by a buildup of fluid (lymphedema), which can go away on its own. Affected infants may also have feeding problems, which typically get better by age 1 or 2. Older individuals can also develop lymphedema, usually in the ankles and lower legs.",Noonan syndrome,0000738,GHR,https://ghr.nlm.nih.gov/condition/noonan-syndrome,C0028326,T019,Disorders
How many people are affected by Noonan syndrome ?,0000738-2,frequency,"Noonan syndrome occurs in approximately 1 in 1,000 to 2,500 people.",Noonan syndrome,0000738,GHR,https://ghr.nlm.nih.gov/condition/noonan-syndrome,C0028326,T019,Disorders
What are the genetic changes related to Noonan syndrome ?,0000738-3,genetic changes,"Mutations in the PTPN11, SOS1, RAF1, KRAS, NRAS and BRAF genes cause Noonan syndrome.  Most cases of Noonan syndrome result from mutations in one of three genes, PTPN11, SOS1, or RAF1. PTPN11 gene mutations account for approximately 50 percent of all cases of Noonan syndrome. SOS1 gene mutations account for 10 to 15 percent and RAF1 gene mutations account for 5 to 10 percent of Noonan syndrome cases. About 2 percent of people with Noonan syndrome have mutations in the KRAS gene and usually have a more severe or atypical form of the disorder. It is not known how many cases are caused by mutations in the BRAF or NRAS genes, but it is likely a very small proportion. The cause of Noonan syndrome in the remaining 20 percent of people with this disorder is unknown.  The PTPN11, SOS1, RAF1, KRAS, NRAS and BRAF genes all provide instructions for making proteins that are important in signaling pathways needed for the proper formation of several types of tissue during development. These proteins also play roles in cell division, cell movement, and cell differentiation (the process by which cells mature to carry out specific functions). Mutations in any of the genes listed above cause the resulting protein to be continuously active, rather than switching on and off in response to cell signals. This constant activation disrupts the regulation of systems that control cell growth and division, leading to the characteristic features of Noonan syndrome.",Noonan syndrome,0000738,GHR,https://ghr.nlm.nih.gov/condition/noonan-syndrome,C0028326,T019,Disorders
Is Noonan syndrome inherited ?,0000738-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Noonan syndrome,0000738,GHR,https://ghr.nlm.nih.gov/condition/noonan-syndrome,C0028326,T019,Disorders
What are the treatments for Noonan syndrome ?,0000738-5,treatment,These resources address the diagnosis or management of Noonan syndrome:  - Gene Review: Gene Review: Noonan Syndrome  - Genetic Testing Registry: Noonan syndrome  - Genetic Testing Registry: Noonan syndrome 1  - Genetic Testing Registry: Noonan syndrome 2  - Genetic Testing Registry: Noonan syndrome 3  - Genetic Testing Registry: Noonan syndrome 4  - Genetic Testing Registry: Noonan syndrome 5  - Genetic Testing Registry: Noonan syndrome 6  - Genetic Testing Registry: Noonan syndrome 7  - MedlinePlus Encyclopedia: Noonan Syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Noonan syndrome,0000738,GHR,https://ghr.nlm.nih.gov/condition/noonan-syndrome,C0028326,T019,Disorders
What is (are) Norrie disease ?,0000739-1,information,"Norrie disease is an inherited eye disorder that leads to blindness in male infants at birth or soon after birth. It causes abnormal development of the retina, the layer of sensory cells that detect light and color, with masses of immature retinal cells accumulating at the back of the eye. As a result, the pupils appear white when light is shone on them, a sign called leukocoria. The irises (colored portions of the eyes) or the entire eyeballs may shrink and deteriorate during the first months of life, and cataracts (cloudiness in the lens of the eye) may eventually develop.  About one third of individuals with Norrie disease develop progressive hearing loss, and more than half experience developmental delays in motor skills such as sitting up and walking. Other problems may include mild to moderate intellectual disability, often with psychosis, and abnormalities that can affect circulation, breathing, digestion, excretion, or reproduction.",Norrie disease,0000739,GHR,https://ghr.nlm.nih.gov/condition/norrie-disease,C0266526,T019,Disorders
How many people are affected by Norrie disease ?,0000739-2,frequency,Norrie disease is a rare disorder; its exact incidence is unknown. It is not associated with any specific racial or ethnic group.,Norrie disease,0000739,GHR,https://ghr.nlm.nih.gov/condition/norrie-disease,C0266526,T019,Disorders
What are the genetic changes related to Norrie disease ?,0000739-3,genetic changes,"Mutations in the NDP gene cause Norrie disease.  The NDP gene provides instructions for making a protein called norrin. Norrin participates in the Wnt cascade, a sequence of steps that affect the way cells and tissues develop. In particular, norrin seems to play a critical role in the specialization of retinal cells for their unique sensory capabilities. It is also involved in the establishment of a blood supply to tissues of the retina and the inner ear, and the development of other body systems.  In order to initiate the Wnt cascade, norrin must bind (attach) to another protein called frizzled-4. Mutations in the norrin protein interfere with its ability to bind to frizzled-4, resulting in the signs and symptoms of Norrie disease.",Norrie disease,0000739,GHR,https://ghr.nlm.nih.gov/condition/norrie-disease,C0266526,T019,Disorders
Is Norrie disease inherited ?,0000739-4,inheritance,"This condition is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In X-linked recessive inheritance, a female with one altered copy of the gene in each cell is called a carrier. She can pass on the gene, but generally does not experience signs and symptoms of the disorder. In rare cases, however, carrier females have shown some retinal abnormalities or mild hearing loss associated with Norrie disease.",Norrie disease,0000739,GHR,https://ghr.nlm.nih.gov/condition/norrie-disease,C0266526,T019,Disorders
What are the treatments for Norrie disease ?,0000739-5,treatment,These resources address the diagnosis or management of Norrie disease:  - Gene Review: Gene Review: NDP-Related Retinopathies  - Genetic Testing Registry: Atrophia bulborum hereditaria   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Norrie disease,0000739,GHR,https://ghr.nlm.nih.gov/condition/norrie-disease,C0266526,T019,Disorders
What is (are) North American Indian childhood cirrhosis ?,0000740-1,information,"North American Indian childhood cirrhosis is a rare liver disorder that occurs in children. The liver malfunction causes yellowing of the skin and whites of the eyes (jaundice) in affected infants. The disorder worsens with age, progressively damaging the liver and leading to chronic, irreversible liver disease (cirrhosis) in childhood or adolescence. Unless it is treated with liver transplantation, North American Indian childhood cirrhosis typically causes life-threatening complications including liver failure.",North American Indian childhood cirrhosis,0000740,GHR,https://ghr.nlm.nih.gov/condition/north-american-indian-childhood-cirrhosis,C1858051,T047,Disorders
How many people are affected by North American Indian childhood cirrhosis ?,0000740-2,frequency,"North American Indian childhood cirrhosis has been found only in children of Ojibway-Cree descent in the Abitibi region of northwestern Quebec, Canada. At least 30 affected individuals from this population have been reported.",North American Indian childhood cirrhosis,0000740,GHR,https://ghr.nlm.nih.gov/condition/north-american-indian-childhood-cirrhosis,C1858051,T047,Disorders
What are the genetic changes related to North American Indian childhood cirrhosis ?,0000740-3,genetic changes,"North American Indian childhood cirrhosis results from at least one known mutation in the UTP4 gene. This gene provides instructions for making a protein called cirhin, whose precise function is unknown. Within cells, cirhin is located in a structure called the nucleolus, which is a small region inside the nucleus where ribosomal RNA (rRNA) is produced. A chemical cousin of DNA, rRNA is a molecule that helps assemble protein building blocks (amino acids) into functioning proteins. Researchers believe that cirhin may play a role in processing rRNA. Studies also suggest that cirhin may function by interacting with other proteins.  Cirhin is found in many different types of cells, so it is unclear why the effects of North American Indian childhood cirrhosis appear to be limited to the liver. Researchers are working to determine how a UTP4 gene mutation causes the progressive liver damage characteristic of this disorder.",North American Indian childhood cirrhosis,0000740,GHR,https://ghr.nlm.nih.gov/condition/north-american-indian-childhood-cirrhosis,C1858051,T047,Disorders
Is North American Indian childhood cirrhosis inherited ?,0000740-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",North American Indian childhood cirrhosis,0000740,GHR,https://ghr.nlm.nih.gov/condition/north-american-indian-childhood-cirrhosis,C1858051,T047,Disorders
What are the treatments for North American Indian childhood cirrhosis ?,0000740-5,treatment,These resources address the diagnosis or management of North American Indian childhood cirrhosis:  - Children's Organ Transplant Association  - Genetic Testing Registry: North american indian childhood cirrhosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,North American Indian childhood cirrhosis,0000740,GHR,https://ghr.nlm.nih.gov/condition/north-american-indian-childhood-cirrhosis,C1858051,T047,Disorders
What is (are) Northern epilepsy ?,0000741-1,information,"Northern epilepsy is a genetic condition that causes recurrent seizures (epilepsy) beginning in childhood, usually between ages 5 and 10. Seizures are often the generalized tonic-clonic type, which involve muscle rigidity, convulsions, and loss of consciousness. These seizures typically last less than 5 minutes but can last up to 15 minutes. Some people with Northern epilepsy also experience partial seizures, which do not cause a loss of consciousness. The seizures occur approximately one to two times per month until adolescence; then the frequency decreases to about four to six times per year by early adulthood. By middle age, seizures become even less frequent.  Two to 5 years after the start of seizures, people with Northern epilepsy begin to experience a decline in intellectual function, which can result in mild intellectual disability. Problems with coordination usually begin in young adulthood and lead to clumsiness and difficulty with fine motor activities such as writing, using eating utensils, and fastening buttons. During this time, affected individuals often begin to develop balance problems and they walk slowly with short, wide steps. These intellectual and movement problems worsen over time. A loss of sharp vision (reduced visual acuity) may also occur in early to mid-adulthood.  Individuals with Northern epilepsy often live into late adulthood, but depending on the severity of the intellectual disability and movement impairments, they may require assistance with tasks of everyday living.  Northern epilepsy is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which are also known as Batten disease. These disorders affect the nervous system and typically cause progressive problems with vision, movement, and thinking ability. The different types of NCLs are distinguished by the age at which signs and symptoms first appear. Northern epilepsy is the mildest form of NCL.",Northern epilepsy,0000741,GHR,https://ghr.nlm.nih.gov/condition/northern-epilepsy,C1864923,T047,Disorders
How many people are affected by Northern epilepsy ?,0000741-2,frequency,"Northern epilepsy appears to affect only individuals of Finnish ancestry, particularly those from the Kainuu region of northern Finland. Approximately 1 in 10,000 individuals in this region have the condition.",Northern epilepsy,0000741,GHR,https://ghr.nlm.nih.gov/condition/northern-epilepsy,C1864923,T047,Disorders
What are the genetic changes related to Northern epilepsy ?,0000741-3,genetic changes,"Mutations in the CLN8 gene cause Northern epilepsy. The CLN8 gene provides instructions for making a protein whose function is not well understood. The CLN8 protein is thought to play a role in transporting materials in and out of a cell structure called the endoplasmic reticulum. The endoplasmic reticulum is involved in protein production, processing, and transport. Based on the structure of the CLN8 protein, it may also help regulate the levels of fats (lipids) in cells.  A single CLN8 gene mutation has been identified to cause Northern epilepsy. Nearly all affected individuals have this mutation in both copies of the CLN8 gene in each cell. The effects of this mutation on protein function are unclear. Unlike other forms of NCL that result in the accumulation of large amounts of fatty substances called lipopigments in cells, contributing to cell death, Northern epilepsy is associated with very little lipopigment buildup. People with Northern epilepsy do have mild brain abnormalities resulting from cell death, but the cause of this brain cell death is unknown. It is also unclear how changes in the CLN8 protein and a loss of brain cells cause the neurological problems associated with Northern epilepsy.",Northern epilepsy,0000741,GHR,https://ghr.nlm.nih.gov/condition/northern-epilepsy,C1864923,T047,Disorders
Is Northern epilepsy inherited ?,0000741-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Northern epilepsy,0000741,GHR,https://ghr.nlm.nih.gov/condition/northern-epilepsy,C1864923,T047,Disorders
What are the treatments for Northern epilepsy ?,0000741-5,treatment,"These resources address the diagnosis or management of Northern epilepsy:  - Gene Review: Gene Review: Neuronal Ceroid-Lipofuscinoses  - Genetic Testing Registry: Ceroid lipofuscinosis, neuronal, 8, northern epilepsy variant   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Northern epilepsy,0000741,GHR,https://ghr.nlm.nih.gov/condition/northern-epilepsy,C1864923,T047,Disorders
What is (are) Ochoa syndrome ?,0000742-1,information,"Ochoa syndrome is a disorder characterized by urinary problems and unusual facial expressions.  The urinary problems associated with Ochoa syndrome typically become apparent in early childhood or adolescence. People with this disorder may have difficulty controlling the flow of urine (incontinence), which can lead to bedwetting. Individuals with Ochoa syndrome may be unable to completely empty the bladder, often resulting in vesicoureteral reflux, a condition in which urine backs up into the ducts that normally carry it from each kidney to the bladder (the ureters). Urine may also accumulate in the kidneys (hydronephrosis). Vesicoureteral reflux and hydronephrosis can lead to frequent infections of the urinary tract and kidney inflammation (pyelonephritis), causing damage that may eventually result in kidney failure.  Individuals with Ochoa syndrome also exhibit a characteristic frown-like facial grimace when they try to smile or laugh, often described as inversion of facial expression. While this feature may appear earlier than the urinary tract symptoms, perhaps as early as an infant begins to smile, it is often not brought to medical attention.  Approximately two-thirds of individuals with Ochoa syndrome also experience problems with bowel function, such as constipation, loss of bowel control, or muscle spasms of the anus.",Ochoa syndrome,0000742,GHR,https://ghr.nlm.nih.gov/condition/ochoa-syndrome,C0403555,T019,Disorders
How many people are affected by Ochoa syndrome ?,0000742-2,frequency,Ochoa syndrome is a rare disorder. About 150 cases have been reported in the medical literature.,Ochoa syndrome,0000742,GHR,https://ghr.nlm.nih.gov/condition/ochoa-syndrome,C0403555,T019,Disorders
What are the genetic changes related to Ochoa syndrome ?,0000742-3,genetic changes,"Ochoa syndrome can be caused by mutations in the HPSE2 gene. This gene provides instructions for making a protein called heparanase 2. The function of this protein is not well understood.  Mutations in the HPSE2 gene that cause Ochoa syndrome result in changes in the heparanase 2 protein that likely prevent it from functioning. The connection between HPSE2 gene mutations and the features of Ochoa syndrome are unclear. Because the areas of the brain that control facial expression and urination are in close proximity, some researchers have suggested that the genetic changes may lead to an abnormality in this brain region that may account for the symptoms of Ochoa syndrome. Other researchers believe that a defective heparanase 2 protein may lead to problems with the development of the urinary tract or with muscle function in the face and bladder.  Some people with Ochoa syndrome do not have mutations in the HPSE2 gene. In these individuals, the cause of the disorder is unknown.",Ochoa syndrome,0000742,GHR,https://ghr.nlm.nih.gov/condition/ochoa-syndrome,C0403555,T019,Disorders
Is Ochoa syndrome inherited ?,0000742-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Ochoa syndrome,0000742,GHR,https://ghr.nlm.nih.gov/condition/ochoa-syndrome,C0403555,T019,Disorders
What are the treatments for Ochoa syndrome ?,0000742-5,treatment,These resources address the diagnosis or management of Ochoa syndrome:  - Gene Review: Gene Review: Urofacial Syndrome  - Genetic Testing Registry: Ochoa syndrome  - National Institute of Diabetes and Digestive and Kidney Diseases: Urodynamic Testing  - Scripps Health: Self-Catheterization -- Female  - Scripps Health: Self-Catheterization -- Male   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Ochoa syndrome,0000742,GHR,https://ghr.nlm.nih.gov/condition/ochoa-syndrome,C0403555,T019,Disorders
What is (are) ocular albinism ?,0000743-1,information,"Ocular albinism is a genetic condition that primarily affects the eyes. This condition reduces the coloring (pigmentation) of the iris, which is the colored part of the eye, and the retina, which is the light-sensitive tissue at the back of the eye. Pigmentation in the eye is essential for normal vision.  Ocular albinism is characterized by severely impaired sharpness of vision (visual acuity) and problems with combining vision from both eyes to perceive depth (stereoscopic vision). Although the vision loss is permanent, it does not worsen over time. Other eye abnormalities associated with this condition include rapid, involuntary eye movements (nystagmus); eyes that do not look in the same direction (strabismus); and increased sensitivity to light (photophobia). Many affected individuals also have abnormalities involving the optic nerves, which carry visual information from the eye to the brain.  Unlike some other forms of albinism, ocular albinism does not significantly affect the color of the skin and hair. People with this condition may have a somewhat lighter complexion than other members of their family, but these differences are usually minor.  The most common form of ocular albinism is known as the Nettleship-Falls type or type 1. Other forms of ocular albinism are much rarer and may be associated with additional signs and symptoms, such as hearing loss.",ocular albinism,0000743,GHR,https://ghr.nlm.nih.gov/condition/ocular-albinism,C0078917,T019,Disorders
How many people are affected by ocular albinism ?,0000743-2,frequency,"The most common form of this disorder, ocular albinism type 1, affects at least 1 in 60,000 males. The classic signs and symptoms of this condition are much less common in females.",ocular albinism,0000743,GHR,https://ghr.nlm.nih.gov/condition/ocular-albinism,C0078917,T019,Disorders
What are the genetic changes related to ocular albinism ?,0000743-3,genetic changes,"Ocular albinism type 1 results from mutations in the GPR143 gene. This gene provides instructions for making a protein that plays a role in pigmentation of the eyes and skin. It helps control the growth of melanosomes, which are cellular structures that produce and store a pigment called melanin. Melanin is the substance that gives skin, hair, and eyes their color. In the retina, this pigment also plays a role in normal vision.  Most mutations in the GPR143 gene alter the size or shape of the GPR143 protein. Many of these genetic changes prevent the protein from reaching melanosomes to control their growth. In other cases, the protein reaches melanosomes normally but mutations disrupt the protein's function. As a result of these changes, melanosomes in skin cells and the retina can grow abnormally large. Researchers are uncertain how these giant melanosomes are related to vision loss and other eye abnormalities in people with ocular albinism.  Rare cases of ocular albinism are not caused by mutations in the GPR143 gene. In these cases, the genetic cause of the condition is often unknown.",ocular albinism,0000743,GHR,https://ghr.nlm.nih.gov/condition/ocular-albinism,C0078917,T019,Disorders
Is ocular albinism inherited ?,0000743-4,inheritance,"Ocular albinism type 1 is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the GPR143 gene in each cell is sufficient to cause the characteristic features of ocular albinism. Because females have two copies of the X chromosome, women with only one copy of a GPR143 mutation in each cell usually do not experience vision loss or other significant eye abnormalities. They may have mild changes in retinal pigmentation that can be detected during an eye examination.",ocular albinism,0000743,GHR,https://ghr.nlm.nih.gov/condition/ocular-albinism,C0078917,T019,Disorders
What are the treatments for ocular albinism ?,0000743-5,treatment,"These resources address the diagnosis or management of ocular albinism:  - Gene Review: Gene Review: Ocular Albinism, X-Linked  - Genetic Testing Registry: Albinism ocular late onset sensorineural deafness  - Genetic Testing Registry: Albinism, ocular, with sensorineural deafness  - Genetic Testing Registry: Ocular albinism, type I  - MedlinePlus Encyclopedia: Albinism   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",ocular albinism,0000743,GHR,https://ghr.nlm.nih.gov/condition/ocular-albinism,C0078917,T019,Disorders
What is (are) oculocutaneous albinism ?,0000744-1,information,"Oculocutaneous albinism is a group of conditions that affect coloring (pigmentation) of the skin, hair, and eyes. Affected individuals typically have very fair skin and white or light-colored hair. Long-term sun exposure greatly increases the risk of skin damage and skin cancers, including an aggressive form of skin cancer called melanoma, in people with this condition. Oculocutaneous albinism also reduces pigmentation of the colored part of the eye (the iris) and the light-sensitive tissue at the back of the eye (the retina). People with this condition usually have vision problems such as reduced sharpness; rapid, involuntary eye movements (nystagmus); and increased sensitivity to light (photophobia).  Researchers have identified multiple types of oculocutaneous albinism, which are distinguished by their specific skin, hair, and eye color changes and by their genetic cause. Oculocutaneous albinism type 1 is characterized by white hair, very pale skin, and light-colored irises. Type 2 is typically less severe than type 1; the skin is usually a creamy white color and hair may be light yellow, blond, or light brown. Type 3 includes a form of albinism called rufous oculocutaneous albinism, which usually affects dark-skinned people. Affected individuals have reddish-brown skin, ginger or red hair, and hazel or brown irises. Type 3 is often associated with milder vision abnormalities than the other forms of oculocutaneous albinism. Type 4 has signs and symptoms similar to those seen with type 2.  Several additional types of this disorder have been proposed, each affecting one or a few families.",oculocutaneous albinism,0000744,GHR,https://ghr.nlm.nih.gov/condition/oculocutaneous-albinism,C0078918,T019,Disorders
How many people are affected by oculocutaneous albinism ?,0000744-2,frequency,"Overall, an estimated 1 in 20,000 people worldwide are born with oculocutaneous albinism. The condition affects people in many ethnic groups and geographical regions. Types 1 and 2 are the most common forms of this condition; types 3 and 4 are less common. Type 2 occurs more frequently in African Americans, some Native American groups, and people from sub-Saharan Africa. Type 3, specifically rufous oculocutaneous albinism, has been described primarily in people from southern Africa. Studies suggest that type 4 occurs more frequently in the Japanese and Korean populations than in people from other parts of the world.",oculocutaneous albinism,0000744,GHR,https://ghr.nlm.nih.gov/condition/oculocutaneous-albinism,C0078918,T019,Disorders
What are the genetic changes related to oculocutaneous albinism ?,0000744-3,genetic changes,"Oculocutaneous albinism can result from mutations in several genes, including TYR, OCA2, TYRP1, and SLC45A2. Changes in the TYR gene cause type 1; mutations in the OCA2 gene are responsible for type 2; TYRP1 mutations cause type 3; and changes in the SLC45A2 gene result in type 4. Mutations in additional genes likely underlie the other forms of this disorder. The genes associated with oculocutaneous albinism are involved in producing a pigment called melanin, which is the substance that gives skin, hair, and eyes their color. In the retina, melanin also plays a role in normal vision. Mutations in any of these genes disrupt the ability of cells to make melanin, which reduces pigmentation in the skin, hair, and eyes. A lack of melanin in the retina leads to the vision problems characteristic of oculocutaneous albinism.  Alterations in the MC1R gene can change the appearance of people with oculocutaneous albinism type 2. This gene helps regulate melanin production and is responsible for some normal variation in pigmentation. People with genetic changes in both the OCA2 and MC1R genes have many of the usual features of oculocutaneous albinism type 2, including light-colored eyes and vision problems; however, they typically have red hair instead of the usual yellow, blond, or light brown hair seen with this condition.  Some individuals with oculocutaneous albinism do not have mutations in any of the known genes. In these people, the genetic cause of the condition is unknown.",oculocutaneous albinism,0000744,GHR,https://ghr.nlm.nih.gov/condition/oculocutaneous-albinism,C0078918,T019,Disorders
Is oculocutaneous albinism inherited ?,0000744-4,inheritance,"Oculocutaneous albinism is inherited in an autosomal recessive pattern, which means both copies of a gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they do not show signs and symptoms of the condition.",oculocutaneous albinism,0000744,GHR,https://ghr.nlm.nih.gov/condition/oculocutaneous-albinism,C0078918,T019,Disorders
What are the treatments for oculocutaneous albinism ?,0000744-5,treatment,These resources address the diagnosis or management of oculocutaneous albinism:  - Gene Review: Gene Review: Oculocutaneous Albinism Type 1  - Gene Review: Gene Review: Oculocutaneous Albinism Type 2  - Gene Review: Gene Review: Oculocutaneous Albinism Type 4  - Genetic Testing Registry: Oculocutaneous albinism  - MedlinePlus Encyclopedia: Albinism   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,oculocutaneous albinism,0000744,GHR,https://ghr.nlm.nih.gov/condition/oculocutaneous-albinism,C0078918,T019,Disorders
What is (are) oculodentodigital dysplasia ?,0000745-1,information,"Oculodentodigital dysplasia is a condition that affects many parts of the body, particularly the eyes (oculo-), teeth (dento-), and fingers (digital). Common features in people with this condition are small eyes (microphthalmia) and other eye abnormalities that can lead to vision loss. Affected individuals also frequently have tooth abnormalities, such as small or missing teeth, weak enamel, multiple cavities, and early tooth loss. Other common features of this condition include a thin nose and webbing of the skin (syndactyly) between the fourth and fifth fingers.  Less common features of oculodentodigital dysplasia include sparse hair growth (hypotrichosis), brittle nails, an unusual curvature of the fingers (camptodactyly), syndactyly of the toes, small head size (microcephaly), and an opening in the roof of the mouth (cleft palate). Some affected individuals experience neurological problems such as a lack of bladder or bowel control, difficulty coordinating movements (ataxia), abnormal muscle stiffness (spasticity), hearing loss, and impaired speech (dysarthria). A few people with oculodentodigital dysplasia also have a skin condition called palmoplantar keratoderma. Palmoplantar keratoderma causes the skin on the palms and the soles of the feet to become thick, scaly, and calloused.  Some features of oculodentodigital dysplasia are evident at birth, while others become apparent with age.",oculodentodigital dysplasia,0000745,GHR,https://ghr.nlm.nih.gov/condition/oculodentodigital-dysplasia,C0812437,T019,Disorders
How many people are affected by oculodentodigital dysplasia ?,0000745-2,frequency,"The exact incidence of oculodentodigital dysplasia is unknown. It has been diagnosed in fewer than 1,000 people worldwide. More cases are likely undiagnosed.",oculodentodigital dysplasia,0000745,GHR,https://ghr.nlm.nih.gov/condition/oculodentodigital-dysplasia,C0812437,T019,Disorders
What are the genetic changes related to oculodentodigital dysplasia ?,0000745-3,genetic changes,"Mutations in the GJA1 gene cause oculodentodigital dysplasia. The GJA1 gene provides instructions for making a protein called connexin43. This protein forms one part (a subunit) of channels called gap junctions, which allow direct communication between cells. Gap junctions formed by connexin43 proteins are found in many tissues throughout the body.  GJA1 gene mutations result in abnormal connexin43 proteins. Channels formed with abnormal proteins are often permanently closed. Some mutations prevent connexin43 proteins from traveling to the cell surface where they are needed to form channels between cells. Impaired functioning of these channels disrupts cell-to-cell communication, which likely interferes with normal cell growth and cell specialization, processes that determine the shape and function of many different parts of the body. These developmental problems cause the signs and symptoms of oculodentodigital dysplasia.",oculodentodigital dysplasia,0000745,GHR,https://ghr.nlm.nih.gov/condition/oculodentodigital-dysplasia,C0812437,T019,Disorders
Is oculodentodigital dysplasia inherited ?,0000745-4,inheritance,"Most cases of oculodentodigital dysplasia are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  Less commonly, oculodentodigital dysplasia can be inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Fewer than ten cases of autosomal recessive oculodentodigital dysplasia have been reported.",oculodentodigital dysplasia,0000745,GHR,https://ghr.nlm.nih.gov/condition/oculodentodigital-dysplasia,C0812437,T019,Disorders
What are the treatments for oculodentodigital dysplasia ?,0000745-5,treatment,These resources address the diagnosis or management of oculodentodigital dysplasia:  - Genetic Testing Registry: Oculodentodigital dysplasia  - MedlinePlus Encyclopedia: Webbing of the fingers or toes  - UC Davis Children's Hospital: Cleft and Craniofacial Reconstruction   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,oculodentodigital dysplasia,0000745,GHR,https://ghr.nlm.nih.gov/condition/oculodentodigital-dysplasia,C0812437,T019,Disorders
What is (are) oculofaciocardiodental syndrome ?,0000746-1,information,"Oculofaciocardiodental (OFCD) syndrome is a condition that affects the development of the eyes (oculo-), facial features (facio-), heart (cardio-) and teeth (dental). This condition occurs only in females.  The eye abnormalities associated with OFCD syndrome can affect one or both eyes. Many people with this condition are born with eyeballs that are abnormally small (microphthalmia). Other eye problems can include clouding of the lens (cataract) and a higher risk of glaucoma, an eye disease that increases the pressure in the eye. These abnormalities can lead to vision loss or blindness.  People with OFCD syndrome often have a long, narrow face with distinctive facial features, including deep-set eyes and a broad nasal tip that is divided by a cleft. Some affected people have an opening in the roof of the mouth called a cleft palate.  Heart defects are another common feature of OFCD syndrome. Babies with this condition may be born with a hole between two chambers of the heart (an atrial or ventricular septal defect) or a leak in one of the valves that controls blood flow through the heart (mitral valve prolapse).  Teeth with very large roots (radiculomegaly) are characteristic of OFCD syndrome. Additional dental abnormalities can include delayed loss of primary (baby) teeth, missing or abnormally small teeth, misaligned teeth, and defective tooth enamel.",oculofaciocardiodental syndrome,0000746,GHR,https://ghr.nlm.nih.gov/condition/oculofaciocardiodental-syndrome,C1846265,T047,Disorders
How many people are affected by oculofaciocardiodental syndrome ?,0000746-2,frequency,OFCD syndrome is very rare; the incidence is estimated to be less than 1 in 1 million people.,oculofaciocardiodental syndrome,0000746,GHR,https://ghr.nlm.nih.gov/condition/oculofaciocardiodental-syndrome,C1846265,T047,Disorders
What are the genetic changes related to oculofaciocardiodental syndrome ?,0000746-3,genetic changes,"Mutations in the BCOR gene cause OFCD syndrome. The BCOR gene provides instructions for making a protein called the BCL6 corepressor. This protein helps regulate the activity of other genes. Little is known about the protein's function, although it appears to play an important role in early embryonic development. Several mutations in the BCOR gene have been found in people with OFCD syndrome. These mutations prevent the production of any functional protein from the altered gene, which disrupts the normal development of the eyes and several other organs and tissues before birth.",oculofaciocardiodental syndrome,0000746,GHR,https://ghr.nlm.nih.gov/condition/oculofaciocardiodental-syndrome,C1846265,T047,Disorders
Is oculofaciocardiodental syndrome inherited ?,0000746-4,inheritance,"This condition is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. Some cells produce a normal amount of BCL6 corepressor protein and other cells produce none. The resulting overall reduction in the amount of this protein leads to the signs and symptoms of OFCD syndrome.  In males (who have only one X chromosome), mutations result in a total loss of the BCL6 corepressor protein. A lack of this protein appears to be lethal very early in development, so no males are born with OFCD syndrome.",oculofaciocardiodental syndrome,0000746,GHR,https://ghr.nlm.nih.gov/condition/oculofaciocardiodental-syndrome,C1846265,T047,Disorders
What are the treatments for oculofaciocardiodental syndrome ?,0000746-5,treatment,These resources address the diagnosis or management of oculofaciocardiodental syndrome:  - Genetic Testing Registry: Oculofaciocardiodental syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,oculofaciocardiodental syndrome,0000746,GHR,https://ghr.nlm.nih.gov/condition/oculofaciocardiodental-syndrome,C1846265,T047,Disorders
What is (are) oculopharyngeal muscular dystrophy ?,0000747-1,information,"Oculopharyngeal muscular dystrophy is a genetic condition characterized by muscle weakness that begins in adulthood, typically after age 40. The first symptom in people with this disorder is usually droopy eyelids (ptosis), followed by difficulty swallowing (dysphagia). The swallowing difficulties begin with food, but as the condition progresses, liquids can be difficult to swallow as well. Many people with this condition have weakness and wasting (atrophy) of the tongue. These problems with food intake may cause malnutrition. Some affected individuals also have weakness in other facial muscles.  Individuals with oculopharyngeal muscular dystrophy frequently have weakness in the muscles near the center of the body (proximal muscles), particularly muscles in the upper legs and hips. The weakness progresses slowly over time, and people may need the aid of a cane or a walker. Rarely, affected individuals need wheelchair assistance.  There are two types of oculopharyngeal muscular dystrophy, which are distinguished by their pattern of inheritance. They are known as the autosomal dominant and autosomal recessive types.",oculopharyngeal muscular dystrophy,0000747,GHR,https://ghr.nlm.nih.gov/condition/oculopharyngeal-muscular-dystrophy,C0270952,T047,Disorders
How many people are affected by oculopharyngeal muscular dystrophy ?,0000747-2,frequency,"In Europe, the prevalence of oculopharyngeal muscular dystrophy is estimated to be 1 in 100,000 people. The autosomal dominant form of this condition is much more common in the French-Canadian population of the Canadian province of Quebec, where it is estimated to affect 1 in 1,000 individuals. Autosomal dominant oculopharyngeal muscular dystrophy is also seen more frequently in the Bukharan (Central Asian) Jewish population of Israel, affecting 1 in 600 people.  The autosomal recessive form of this condition is very rare; only a few cases of autosomal recessive oculopharyngeal muscular dystrophy have been identified.",oculopharyngeal muscular dystrophy,0000747,GHR,https://ghr.nlm.nih.gov/condition/oculopharyngeal-muscular-dystrophy,C0270952,T047,Disorders
What are the genetic changes related to oculopharyngeal muscular dystrophy ?,0000747-3,genetic changes,"Mutations in the PABPN1 gene cause oculopharyngeal muscular dystrophy. The PABPN1 gene provides instructions for making a protein that is active (expressed) throughout the body. In cells, the PABPN1 protein plays an important role in processing molecules called messenger RNAs (mRNAs), which serve as genetic blueprints for making proteins. The protein alters a region at the end of the mRNA molecule that protects the mRNA from being broken down and allows it to move within the cell.  The PABPN1 protein contains an area where the protein building block (amino acid) alanine is repeated 10 times. This stretch of alanines is known as a polyalanine tract. The role of the polyalanine tract in normal PABPN1 protein function is unknown.  Mutations in the PABPN1 gene that cause oculopharyngeal muscular dystrophy result in a PABPN1 protein that has an extended polyalanine tract. The extra alanines cause the PABPN1 protein to form clumps within muscle cells that accumulate because they cannot be broken down. These clumps (called intranuclear inclusions) are thought to impair the normal functioning of muscle cells and eventually cause cell death. The progressive loss of muscle cells most likely causes the muscle weakness seen in people with oculopharyngeal muscular dystrophy. It is not known why dysfunctional PABPN1 proteins seem to affect only certain muscle cells.",oculopharyngeal muscular dystrophy,0000747,GHR,https://ghr.nlm.nih.gov/condition/oculopharyngeal-muscular-dystrophy,C0270952,T047,Disorders
Is oculopharyngeal muscular dystrophy inherited ?,0000747-4,inheritance,"Most cases of oculopharyngeal muscular dystrophy are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. People with autosomal dominant oculopharyngeal muscular dystrophy have a mutation resulting in a PABPN1 protein with an expanded polyalanine tract of between 12 and 17 alanines.  Less commonly, oculopharyngeal muscular dystrophy can be inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. In autosomal recessive oculopharyngeal muscular dystrophy, PABPN1 mutations lead to a polyalanine tract that is 11 alanines long. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",oculopharyngeal muscular dystrophy,0000747,GHR,https://ghr.nlm.nih.gov/condition/oculopharyngeal-muscular-dystrophy,C0270952,T047,Disorders
What are the treatments for oculopharyngeal muscular dystrophy ?,0000747-5,treatment,These resources address the diagnosis or management of oculopharyngeal muscular dystrophy:  - Gene Review: Gene Review: Oculopharyngeal Muscular Dystrophy  - Genetic Testing Registry: Oculopharyngeal muscular dystrophy  - MedlinePlus Encyclopedia: Ptosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,oculopharyngeal muscular dystrophy,0000747,GHR,https://ghr.nlm.nih.gov/condition/oculopharyngeal-muscular-dystrophy,C0270952,T047,Disorders
"What is (are) Ohdo syndrome, Maat-Kievit-Brunner type ?",0000748-1,information,"The Maat-Kievit-Brunner type of Ohdo syndrome is a rare condition characterized by intellectual disability and distinctive facial features. It has only been reported in males.  The intellectual disability associated with this condition varies from mild to severe, and the development of motor skills (such as sitting, standing, and walking) is delayed. Some affected individuals also have behavioral problems.  Distinctive facial features often seen in this condition include a narrowing of the eye opening (blepharophimosis), droopy eyelids (ptosis), prominent cheeks, a broad nasal bridge, a nose with a rounded tip, a large space between the nose and upper lip (a long philtrum), and a narrow mouth. Some affected individuals also have widely set eyes (hypertelorism), an unusually small chin (micrognathia), and small and low-set ears. As people with the condition get older, these facial characteristics become more pronounced and the face becomes more triangular.  Other possible signs of this condition include dental problems, weak muscle tone (hypotonia), and hearing loss.","Ohdo syndrome, Maat-Kievit-Brunner type",0000748,GHR,https://ghr.nlm.nih.gov/condition/ohdo-syndrome-maat-kievit-brunner-type,C3698541,T047,Disorders
"How many people are affected by Ohdo syndrome, Maat-Kievit-Brunner type ?",0000748-2,frequency,"The Maat-Kievit-Brunner type of Ohdo syndrome is a very rare condition, with only a few affected individuals reported in the medical literature.","Ohdo syndrome, Maat-Kievit-Brunner type",0000748,GHR,https://ghr.nlm.nih.gov/condition/ohdo-syndrome-maat-kievit-brunner-type,C3698541,T047,Disorders
"What are the genetic changes related to Ohdo syndrome, Maat-Kievit-Brunner type ?",0000748-3,genetic changes,"The Maat-Kievit-Brunner type of Ohdo syndrome results from mutations in the MED12 gene. This gene provides instructions for making a protein that helps regulate gene activity; it is thought to play an essential role in development both before and after birth. The MED12 gene mutations that cause this condition alter the structure of the MED12 protein, impairing its ability to control gene activity. It is unclear how these changes lead to the particular cognitive and physical features of the Maat-Kievit-Brunner type of Ohdo syndrome.","Ohdo syndrome, Maat-Kievit-Brunner type",0000748,GHR,https://ghr.nlm.nih.gov/condition/ohdo-syndrome-maat-kievit-brunner-type,C3698541,T047,Disorders
"Is Ohdo syndrome, Maat-Kievit-Brunner type inherited ?",0000748-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The MED12 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder.  Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. Females with only one altered copy of the gene in each cell are called carriers. They do not usually experience health problems related to the condition, but they can pass the mutation to their children. Sons who inherit the altered gene will have the condition, while daughters who inherit the altered gene will be carriers.  A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.","Ohdo syndrome, Maat-Kievit-Brunner type",0000748,GHR,https://ghr.nlm.nih.gov/condition/ohdo-syndrome-maat-kievit-brunner-type,C3698541,T047,Disorders
"What are the treatments for Ohdo syndrome, Maat-Kievit-Brunner type ?",0000748-5,treatment,"These resources address the diagnosis or management of Ohdo syndrome, Maat-Kievit-Brunner type:  - Genetic Testing Registry: Ohdo syndrome, X-linked   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","Ohdo syndrome, Maat-Kievit-Brunner type",0000748,GHR,https://ghr.nlm.nih.gov/condition/ohdo-syndrome-maat-kievit-brunner-type,C3698541,T047,Disorders
"What is (are) Ohdo syndrome, Say-Barber-Biesecker-Young-Simpson variant ?",0000749-1,information,"The Say-Barber-Biesecker-Young-Simpson (SBBYS) variant of Ohdo syndrome is a rare condition characterized by genital abnormalities in males, missing or underdeveloped kneecaps (patellae), intellectual disability, distinctive facial features, and abnormalities affecting other parts of the body.  Males with the SBBYS variant of Ohdo syndrome typically have undescended testes (cryptorchidism). Females with this condition have normal genitalia.  Missing or underdeveloped patellae is the most common skeletal abnormality associated with the SBBYS variant of Ohdo syndrome. Affected individuals also have joint stiffness involving the hips, knees, and ankles that can impair movement. Although joints in the lower body are stiff, joints in the arms and upper body may be unusually loose (lax). Many people with this condition have long thumbs and first (big) toes.  The SBBYS variant of Ohdo syndrome is also associated with delayed development and intellectual disability, which are often severe. Many affected infants have weak muscle tone (hypotonia) that leads to breathing and feeding difficulties.  The SBBYS variant of Ohdo syndrome is characterized by a mask-like, non-expressive face. Additionally, affected individuals may have distinctive facial features such as prominent cheeks, a broad nasal bridge or a nose with a rounded tip, a narrowing of the eye opening (blepharophimosis), droopy eyelids (ptosis), and abnormalities of the tear (lacrimal) glands. About one-third of affected individuals are born with an opening in the roof of the mouth called a cleft palate. The SBBYS variant of Ohdo syndrome can also be associated with heart defects and dental problems.","Ohdo syndrome, Say-Barber-Biesecker-Young-Simpson variant",0000749,GHR,https://ghr.nlm.nih.gov/condition/ohdo-syndrome-say-barber-biesecker-young-simpson-variant,C1863557,T047,Disorders
"How many people are affected by Ohdo syndrome, Say-Barber-Biesecker-Young-Simpson variant ?",0000749-2,frequency,The SBBYS variant of Ohdo syndrome is estimated to occur in fewer than 1 per million people. At least 19 cases have been reported in the medical literature.,"Ohdo syndrome, Say-Barber-Biesecker-Young-Simpson variant",0000749,GHR,https://ghr.nlm.nih.gov/condition/ohdo-syndrome-say-barber-biesecker-young-simpson-variant,C1863557,T047,Disorders
"What are the genetic changes related to Ohdo syndrome, Say-Barber-Biesecker-Young-Simpson variant ?",0000749-3,genetic changes,"The SBBYS variant of Ohdo syndrome is caused by mutations in the KAT6B gene. This gene provides instructions for making a type of enzyme called a histone acetyltransferase. These enzymes modify histones, which are structural proteins that attach (bind) to DNA and give chromosomes their shape. By adding a small molecule called an acetyl group to histones, histone acetyltransferases control the activity of certain genes. Little is known about the function of the histone acetyltransferase produced from the KAT6B gene. It appears to regulate genes that are important for early development, including development of the skeleton and nervous system.  The mutations that cause the SBBYS variant of Ohdo syndrome likely prevent the production of functional histone acetyltransferase from one copy of the KAT6B gene in each cell. Studies suggest that the resulting shortage of this enzyme impairs the regulation of various genes during early development. However, it is unclear how these changes lead to the specific features of the condition.","Ohdo syndrome, Say-Barber-Biesecker-Young-Simpson variant",0000749,GHR,https://ghr.nlm.nih.gov/condition/ohdo-syndrome-say-barber-biesecker-young-simpson-variant,C1863557,T047,Disorders
"Is Ohdo syndrome, Say-Barber-Biesecker-Young-Simpson variant inherited ?",0000749-4,inheritance,"This condition has an autosomal dominant inheritance pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Almost all reported cases have resulted from new mutations in the gene and have occurred in people with no history of the disorder in their family.","Ohdo syndrome, Say-Barber-Biesecker-Young-Simpson variant",0000749,GHR,https://ghr.nlm.nih.gov/condition/ohdo-syndrome-say-barber-biesecker-young-simpson-variant,C1863557,T047,Disorders
"What are the treatments for Ohdo syndrome, Say-Barber-Biesecker-Young-Simpson variant ?",0000749-5,treatment,"These resources address the diagnosis or management of Ohdo syndrome, SBBYS variant:  - Gene Review: Gene Review: KAT6B-Related Disorders  - Genetic Testing Registry: Young Simpson syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","Ohdo syndrome, Say-Barber-Biesecker-Young-Simpson variant",0000749,GHR,https://ghr.nlm.nih.gov/condition/ohdo-syndrome-say-barber-biesecker-young-simpson-variant,C1863557,T047,Disorders
What is (are) Ollier disease ?,0000750-1,information,"Ollier disease is a disorder characterized by multiple enchondromas, which are noncancerous (benign) growths of cartilage that develop within the bones. These growths most commonly occur in the limb bones, especially in the bones of the hands and feet; however, they may also occur in the skull, ribs, and bones of the spine (vertebrae). Enchondromas may result in severe bone deformities, shortening of the limbs, and fractures.  The signs and symptoms of Ollier disease may be detectable at birth, although they generally do not become apparent until around the age of 5. Enchondromas develop near the ends of bones, where normal growth occurs, and they frequently stop forming after affected individuals stop growing in early adulthood. As a result of the bone deformities associated with Ollier disease, people with this disorder generally have short stature and underdeveloped muscles.  Although the enchondromas associated with Ollier disease start out as benign, they may become cancerous (malignant). In particular, affected individuals may develop bone cancers called chondrosarcomas, especially in the skull. People with Ollier disease also have an increased risk of other cancers, such as ovarian or liver cancer.  People with Ollier disease usually have a normal lifespan, and intelligence is unaffected. The extent of their physical impairment depends on their individual skeletal deformities, but in most cases they have no major limitations in their activities.  A related disorder called Maffucci syndrome also involves multiple enchondromas but is distinguished by the presence of red or purplish growths in the skin consisting of tangles of abnormal blood vessels (hemangiomas).",Ollier disease,0000750,GHR,https://ghr.nlm.nih.gov/condition/ollier-disease,C0014084,T019,Disorders
How many people are affected by Ollier disease ?,0000750-2,frequency,"Ollier disease is estimated to occur in 1 in 100,000 people.",Ollier disease,0000750,GHR,https://ghr.nlm.nih.gov/condition/ollier-disease,C0014084,T019,Disorders
What are the genetic changes related to Ollier disease ?,0000750-3,genetic changes,"In most people with Ollier disease, the disorder is caused by mutations in the IDH1 or IDH2 gene. These genes provide instructions for making enzymes called isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2, respectively. These enzymes convert a compound called isocitrate to another compound called 2-ketoglutarate. This reaction also produces a molecule called NADPH, which is necessary for many cellular processes. IDH1 or IDH2 gene mutations cause the enzyme produced from the respective gene to take on a new, abnormal function. Although these mutations have been found in some cells of enchondromas in people with Ollier disease, the relationship between the mutations and the signs and symptoms of the disorder is not well understood.  Mutations in other genes may also account for some cases of Ollier disease.",Ollier disease,0000750,GHR,https://ghr.nlm.nih.gov/condition/ollier-disease,C0014084,T019,Disorders
Is Ollier disease inherited ?,0000750-4,inheritance,"Ollier disease is not inherited. The mutations that cause this disorder are somatic, which means they occur during a person's lifetime. A somatic mutation occurs in a single cell. As that cell continues to grow and divide, the cells derived from it also have the same mutation. In Ollier disease, the mutation is thought to occur in a cell during early development before birth; cells that arise from that abnormal cell have the mutation, while the body's other cells do not. This situation is called mosaicism.",Ollier disease,0000750,GHR,https://ghr.nlm.nih.gov/condition/ollier-disease,C0014084,T019,Disorders
What are the treatments for Ollier disease ?,0000750-5,treatment,These resources address the diagnosis or management of Ollier disease:  - Genetic Testing Registry: Enchondromatosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Ollier disease,0000750,GHR,https://ghr.nlm.nih.gov/condition/ollier-disease,C0014084,T019,Disorders
What is (are) ophthalmo-acromelic syndrome ?,0000751-1,information,"Ophthalmo-acromelic syndrome is a condition that results in malformations of the eyes, hands, and feet. The features of this condition are present from birth. The eyes are often absent or severely underdeveloped (anophthalmia), or they may be abnormally small (microphthalmia). Usually both eyes are similarly affected in this condition, but if only one eye is small or missing, the other eye may have a defect such as a gap or split in its structures (coloboma).  The most common hand and foot malformation seen in ophthalmo-acromelic syndrome is missing fingers or toes (oligodactyly). Other frequent malformations include fingers or toes that are fused together (syndactyly) or extra fingers or toes (polydactyly). These skeletal malformations are often described as acromelic, meaning that they occur in the bones that are away from the center of the body. Additional skeletal abnormalities involving the long bones of the arms and legs or the spinal bones (vertebrae) can also occur. Affected individuals may have distinctive facial features, an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate), or intellectual disability.",ophthalmo-acromelic syndrome,0000751,GHR,https://ghr.nlm.nih.gov/condition/ophthalmo-acromelic-syndrome,C0599973,T019,Disorders
How many people are affected by ophthalmo-acromelic syndrome ?,0000751-2,frequency,The prevalence of ophthalmo-acromelic syndrome is not known; approximately 35 cases have been reported in the medical literature.,ophthalmo-acromelic syndrome,0000751,GHR,https://ghr.nlm.nih.gov/condition/ophthalmo-acromelic-syndrome,C0599973,T019,Disorders
What are the genetic changes related to ophthalmo-acromelic syndrome ?,0000751-3,genetic changes,"Mutations in the SMOC1 gene cause ophthalmo-acromelic syndrome. The SMOC1 gene provides instructions for making a protein called secreted modular calcium-binding protein 1 (SMOC-1). This protein is found in basement membranes, which are thin, sheet-like structures that support cells in many tissues and help anchor cells to one another during embryonic development. The SMOC-1 protein attaches (binds) to many different proteins and is thought to regulate molecules called growth factors that stimulate the growth and development of tissues throughout the body. These growth factors play important roles in skeletal formation, normal shaping (patterning) of the limbs, as well as eye formation and development. The SMOC-1 protein also likely promotes the maturation (differentiation) of cells that build bones, called osteoblasts.  SMOC1 gene mutations often result in a nonfunctional SMOC-1 protein. The loss of SMOC-1 could disrupt growth factor signaling, which would impair the normal development of the skeleton, limbs, and eyes. These changes likely underlie the anophthalmia and skeletal malformations of ophthalmo-acromelic syndrome. It is unclear how SMOC1 gene mutations lead to the other features of this condition.  Some people with ophthalmo-acromelic syndrome do not have an identified mutation in the SMOC1 gene. The cause of the condition in these individuals is unknown.",ophthalmo-acromelic syndrome,0000751,GHR,https://ghr.nlm.nih.gov/condition/ophthalmo-acromelic-syndrome,C0599973,T019,Disorders
Is ophthalmo-acromelic syndrome inherited ?,0000751-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",ophthalmo-acromelic syndrome,0000751,GHR,https://ghr.nlm.nih.gov/condition/ophthalmo-acromelic-syndrome,C0599973,T019,Disorders
What are the treatments for ophthalmo-acromelic syndrome ?,0000751-5,treatment,These resources address the diagnosis or management of ophthalmo-acromelic syndrome:  - Genetic Testing Registry: Anophthalmos with limb anomalies   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,ophthalmo-acromelic syndrome,0000751,GHR,https://ghr.nlm.nih.gov/condition/ophthalmo-acromelic-syndrome,C0599973,T019,Disorders
What is (are) Opitz G/BBB syndrome ?,0000752-1,information,"Opitz G/BBB syndrome is a genetic condition that causes several abnormalities along the midline of the body. ""G/BBB"" represents the first letters of the last names of the families first diagnosed with this disorder and ""Opitz"" is the last name of the doctor who first described the signs and symptoms. There are two forms of Opitz G/BBB syndrome, X-linked Opitz G/BBB syndrome and autosomal dominant Opitz G/BBB syndrome. The two forms are distinguished by their genetic causes and patterns of inheritance. The signs and symptoms of the two forms are generally the same.  Nearly everyone with Opitz G/BBB syndrome has wide-spaced eyes (ocular hypertelorism). Affected individuals commonly have defects of the voice box (larynx), windpipe (trachea), or esophagus. These throat abnormalities can cause difficulty swallowing or breathing, in some cases resulting in recurrent pneumonia or life-threatening breathing problems. A common defect is a gap between the trachea and esophagus (laryngeal cleft) that allows food or fluids to enter the airway. The cleft can vary in size, and infants may struggle to breathe when feeding. Most males with Opitz G/BBB syndrome have genital abnormalities such as the urethra opening on the underside of the penis (hypospadias), undescended testes (cryptorchidism), an underdeveloped scrotum, or a scrotum divided into two lobes (bifid scrotum). These genital abnormalities can lead to problems in the urinary tract.  Mild intellectual disability and developmental delay occur in about 50 percent of people with Opitz G/BBB syndrome. Affected individuals have delayed motor skills, such as walking, speech delay, and learning difficulties. Some people with Opitz G/BBB syndrome have features of autistic spectrum disorders, which are characterized by impaired communication and socialization skills. About half of affected individuals also have an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate). Some have cleft palate without cleft lip. Less common features of Opitz G/BBB syndrome, affecting less than half of people with this disorder, include minor heart defects, an obstruction of the anal opening (imperforate anus), and brain defects such as a small or absent connection between the left and right halves of the brain (corpus callosum). Distinct facial features that may be seen in this disorder include a prominent forehead, widow's peak hairline, flat nasal bridge, thin upper lip, and low-set ears. These features vary among affected individuals, even within the same family.",Opitz G/BBB syndrome,0000752,GHR,https://ghr.nlm.nih.gov/condition/opitz-g-bbb-syndrome,C1408833,T047,Disorders
How many people are affected by Opitz G/BBB syndrome ?,0000752-2,frequency,"X-linked Opitz G/BBB syndrome is thought to affect 1 in 10,000 to 50,000 males, although it is likely that this condition is underdiagnosed.  The incidence of autosomal dominant Opitz G/BBB syndrome is unknown. It is part of a larger condition known as 22q11.2 deletion syndrome, which is estimated to affect 1 in 4,000 people.",Opitz G/BBB syndrome,0000752,GHR,https://ghr.nlm.nih.gov/condition/opitz-g-bbb-syndrome,C1408833,T047,Disorders
What are the genetic changes related to Opitz G/BBB syndrome ?,0000752-3,genetic changes,"X-linked Opitz G/BBB syndrome is caused by mutations in the MID1 gene. The MID1 gene provides instructions for making a protein called midline-1. This protein attaches (binds) to microtubules, which are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). Microtubules help cells maintain their shape, assist in the process of cell division, and are essential for the movement of cells (cell migration). Midline-1 assists in recycling certain proteins that need to be reused instead of broken down. MID1 gene mutations lead to a decrease in midline-1 function, which prevents protein recycling. The resulting accumulation of proteins impairs microtubule function, leading to problems with cell division and migration. It is unclear how these changes disrupt normal development and cause the signs and symptoms of Opitz G/BBB syndrome.  Autosomal dominant Opitz G/BBB syndrome is caused by changes in chromosome 22. Some affected individuals have a deletion of a small piece of chromosome 22, specifically at an area of the chromosome designated 22q11.2. Because this same region is deleted in another condition called 22q11.2 deletion syndrome, researchers often consider Opitz/GBBB syndrome caused by this genetic change to be a form of 22q11.2 deletion syndrome. It is not known which of the deleted genes contribute to the signs and symptoms of Opitz G/BBB syndrome.  In other people, autosomal dominant Opitz/GBBB syndrome is caused by a mutation in the SPECC1L gene, which is near the 22q11.2 region but is not in the area that is typically deleted in other individuals with autosomal dominant Opitz G/BBB syndrome or 22q11.2 deletion syndrome. The SPECC1L gene provides instructions for making a protein called cytospin-A. This protein interacts with components of the cytoskeleton and stabilizes microtubules, which is necessary for these fibers to regulate various cell processes including the movement of cells to their proper location (cell migration). Cytospin-A is particularly involved in the migration of cells that will form the facial features. Mutations in the SPECC1L gene result in the production of a protein with a decreased ability to interact with components of the cytoskeleton. As a result, microtubules are disorganized and cells have trouble migrating to their proper location. Because the SPECC1L gene plays a role in facial development, mutations in this gene likely account for the cleft lip and palate seen in some individuals with Opitz G/BBB syndrome, but it is unclear how SPECC1L gene mutations cause the other features of this disorder.  Some people with Opitz G/BBB syndrome do not have any of the genetic changes described above. The cause of the condition in these individuals is unknown.",Opitz G/BBB syndrome,0000752,GHR,https://ghr.nlm.nih.gov/condition/opitz-g-bbb-syndrome,C1408833,T047,Disorders
Is Opitz G/BBB syndrome inherited ?,0000752-4,inheritance,"When caused by mutations in the MID1 gene, Opitz G/BBB syndrome has an X-linked pattern of inheritance. It is considered X-linked because the MID1 gene is located on the X chromosome, one of the two sex chromosomes in each cell. In males, who have only one X chromosome, a mutation in the only copy of the gene in each cell is sufficient to cause the condition. In females, who have two copies of the X chromosome, one altered copy of the gene in each cell can lead to less severe features of the condition or may cause no symptoms at all. Because it is unlikely that females will have two altered copies of the MID1 gene, females with X-linked Opitz G/BBB syndrome typically have hypertelorism as the only sign of the disorder. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  Rarely, Opitz G/BBB syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. These cases are caused by a mutation in the SPECC1L gene or by a deletion of genetic material from one copy of chromosome 22 in each cell. Males and females with autosomal dominant Opitz G/BBB syndrome usually have the same severity of symptoms.  In both types of Opitz G/BBB syndrome, some affected people inherit the genetic change from an affected parent. Other cases may result from new mutations. These cases occur in people with no history of the disorder in their family.",Opitz G/BBB syndrome,0000752,GHR,https://ghr.nlm.nih.gov/condition/opitz-g-bbb-syndrome,C1408833,T047,Disorders
What are the treatments for Opitz G/BBB syndrome ?,0000752-5,treatment,These resources address the diagnosis or management of Opitz G/BBB syndrome:  - Gene Review: Gene Review: 22q11.2 Deletion Syndrome  - Gene Review: Gene Review: X-Linked Opitz G/BBB Syndrome  - Genetic Testing Registry: Opitz G/BBB syndrome  - Genetic Testing Registry: Opitz-Frias syndrome  - MedlinePlus Encyclopedia: Hypospadias  - MedlinePlus Encyclopedia: Imperforate Anus   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Opitz G/BBB syndrome,0000752,GHR,https://ghr.nlm.nih.gov/condition/opitz-g-bbb-syndrome,C1408833,T047,Disorders
What is (are) optic atrophy type 1 ?,0000753-1,information,"Optic atrophy type 1 is a condition that affects vision. Individuals with this condition have progressive vision loss that typically begins within the first decade of life. The severity of the vision loss varies widely among affected people, even among members of the same family. People with this condition can range from having nearly normal vision to complete blindness. The vision loss usually progresses slowly.  People with optic atrophy type 1 frequently have problems with color vision that make it difficult or impossible to distinguish between shades of blue and green. Other vision problems associated with this condition include a progressive narrowing of the field of vision (tunnel vision) and an abnormally pale appearance (pallor) of the nerve that relays visual information from the eye to the brain (optic nerve). Optic nerve pallor can be detected during an eye examination.",optic atrophy type 1,0000753,GHR,https://ghr.nlm.nih.gov/condition/optic-atrophy-type-1,C0338508,T047,Disorders
How many people are affected by optic atrophy type 1 ?,0000753-2,frequency,"Optic atrophy type 1 is estimated to affect 1 in 50,000 people worldwide. This condition is more common in Denmark, where it affects approximately 1 in 10,000 people.",optic atrophy type 1,0000753,GHR,https://ghr.nlm.nih.gov/condition/optic-atrophy-type-1,C0338508,T047,Disorders
What are the genetic changes related to optic atrophy type 1 ?,0000753-3,genetic changes,"Optic atrophy type 1 is caused by mutations in the OPA1 gene. The protein produced from this gene is made in many types of cells and tissues throughout the body. The OPA1 protein is found inside mitochondria, which are the energy-producing centers of cells. The OPA1 protein plays a key role in the organization of the shape and structure of the mitochondria and in the self-destruction of cells (apoptosis). The OPA1 protein is also involved in a process called oxidative phosphorylation, from which cells derive much of their energy. Additionally, the protein plays a role in the maintenance of the small amount of DNA within mitochondria, called mitochondrial DNA (mtDNA).  Mutations in the OPA1 gene lead to overall dysfunction of mitochondria. The structure of the mitochondria become disorganized and cells are more susceptible to self-destruction. OPA1 gene mutations lead to mitochondria with reduced energy-producing capabilities. The maintenance of mtDNA is also sometimes impaired, resulting in mtDNA mutations.  The vision problems experienced by people with optic atrophy type 1 are due to mitochondrial dysfunction, leading to the breakdown of structures that transmit visual information from the eyes to the brain. Affected individuals first experience a progressive loss of nerve cells within the retina, called retinal ganglion cells. The loss of these cells is followed by the degeneration (atrophy) of the optic nerve. The optic nerve is partly made up of specialized extensions of retinal ganglion cells called axons; when the retinal ganglion cells die, the optic nerve cannot transmit visual information to the brain normally.  It is unclear why the OPA1 gene mutations that cause optic atrophy type 1 only affect the eyes. Retinal ganglion cells have many mitochondria and especially high energy requirements, which researchers believe may make them particularly vulnerable to mitochondrial dysfunction and decreases in energy production.  Some individuals with optic atrophy type 1 do not have identified mutations in the OPA1 gene. In these cases, the cause of the condition is unknown.",optic atrophy type 1,0000753,GHR,https://ghr.nlm.nih.gov/condition/optic-atrophy-type-1,C0338508,T047,Disorders
Is optic atrophy type 1 inherited ?,0000753-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",optic atrophy type 1,0000753,GHR,https://ghr.nlm.nih.gov/condition/optic-atrophy-type-1,C0338508,T047,Disorders
What are the treatments for optic atrophy type 1 ?,0000753-5,treatment,These resources address the diagnosis or management of optic atrophy type 1:  - Gene Review: Gene Review: Optic Atrophy Type 1  - Genetic Testing Registry: Dominant hereditary optic atrophy  - MedlinePlus Encyclopedia: Optic Nerve Atrophy  - MedlinePlus Encyclopedia: Visual Acuity Test   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,optic atrophy type 1,0000753,GHR,https://ghr.nlm.nih.gov/condition/optic-atrophy-type-1,C0338508,T047,Disorders
What is (are) oral-facial-digital syndrome ?,0000754-1,information,"Oral-facial-digital syndrome is actually a group of related conditions that affect the development of the oral cavity (the mouth and teeth), facial features, and digits (fingers and toes).  Researchers have identified at least 13 potential forms of oral-facial-digital syndrome. The different types are classified by their patterns of signs and symptoms. However, the features of the various types overlap significantly, and some types are not well defined. The classification system for oral-facial-digital syndrome continues to evolve as researchers find more affected individuals and learn more about this disorder.  The signs and symptoms of oral-facial-digital syndrome vary widely. However, most forms of this disorder involve problems with development of the oral cavity, facial features, and digits. Most forms are also associated with brain abnormalities and some degree of intellectual disability.  Abnormalities of the oral cavity that occur in many types of oral-facial-digital syndrome include a split (cleft) in the tongue, a tongue with an unusual lobed shape, and the growth of noncancerous tumors or nodules on the tongue. Affected individuals may also have extra, missing, or defective teeth. Another common feature is an opening in the roof of the mouth (a cleft palate). Some people with oral-facial-digital syndrome have bands of extra tissue (called hyperplastic frenula) that abnormally attach the lip to the gums.  Distinctive facial features often associated with oral-facial-digital syndrome include a split in the lip (a cleft lip); a wide nose with a broad, flat nasal bridge; and widely spaced eyes (hypertelorism).  Abnormalities of the digits can affect both the fingers and the toes in people with oral-facial-digital syndrome. These abnormalities include fusion of certain fingers or toes (syndactyly), digits that are shorter than usual (brachydactyly), or digits that are unusually curved (clinodactyly). The presence of extra digits (polydactyly) is also seen in most forms of oral-facial-digital syndrome.  Other features occur in only one or a few types of oral-facial digital syndrome. These features help distinguish the different forms of the disorder. For example, the most common form of oral-facial-digital syndrome, type I, is associated with polycystic kidney disease. This kidney disease is characterized by the growth of fluid-filled sacs (cysts) that interfere with the kidneys' ability to filter waste products from the blood. Other forms of oral-facial-digital syndrome are characterized by neurological problems, particular changes in the structure of the brain, bone abnormalities, vision loss, and heart defects.",oral-facial-digital syndrome,0000754,GHR,https://ghr.nlm.nih.gov/condition/oral-facial-digital-syndrome,C1510460,T019,Disorders
How many people are affected by oral-facial-digital syndrome ?,0000754-2,frequency,"Oral-facial-digital syndrome has an estimated incidence of 1 in 50,000 to 250,000 newborns. Type I accounts for the majority of cases of this disorder. The other forms of oral-facial-digital syndrome are very rare; most have been identified in only one or a few families.",oral-facial-digital syndrome,0000754,GHR,https://ghr.nlm.nih.gov/condition/oral-facial-digital-syndrome,C1510460,T019,Disorders
What are the genetic changes related to oral-facial-digital syndrome ?,0000754-3,genetic changes,"Only one gene, OFD1, has been associated with oral-facial-digital syndrome. Mutations in this gene cause oral-facial-digital syndrome type I. OFD1 gene mutations were also found in an affected family whose disorder was classified as type VII; however, researchers now believe that type VII is the same as type I.  The OFD1 gene provides instructions for making a protein whose function is not fully understood. It appears to play an important role in the early development of many parts of the body, including the brain, face, limbs, and kidneys. Mutations in the OFD1 gene prevent cells from making enough functional OFD1 protein, which disrupts the normal development of these structures. It is unclear how a shortage of this protein causes the specific features of oral-facial-digital syndrome type I.  Researchers are actively searching for the genetic changes responsible for the other forms of oral-facial-digital syndrome.",oral-facial-digital syndrome,0000754,GHR,https://ghr.nlm.nih.gov/condition/oral-facial-digital-syndrome,C1510460,T019,Disorders
Is oral-facial-digital syndrome inherited ?,0000754-4,inheritance,"Oral-facial-digital syndrome type I is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. Some cells produce a normal amount of OFD1 protein and other cells produce none. The resulting overall reduction in the amount of this protein leads to the signs and symptoms of oral-facial-digital syndrome type I.  In males (who have only one X chromosome), mutations result in a total loss of the OFD1 protein. A lack of this protein is usually lethal very early in development, so very few males are born with oral-facial-digital syndrome type I. Affected males usually die before birth, although a few have lived into early infancy.  Most of the other forms of oral-facial-digital syndrome are inherited in an autosomal recessive pattern, which suggests that both copies of a causative gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",oral-facial-digital syndrome,0000754,GHR,https://ghr.nlm.nih.gov/condition/oral-facial-digital-syndrome,C1510460,T019,Disorders
What are the treatments for oral-facial-digital syndrome ?,0000754-5,treatment,These resources address the diagnosis or management of oral-facial-digital syndrome:  - Gene Review: Gene Review: Oral-Facial-Digital Syndrome Type I  - Genetic Testing Registry: Mohr syndrome  - Genetic Testing Registry: Oral-facial-digital syndrome  - Genetic Testing Registry: Orofacial-digital syndrome III  - Genetic Testing Registry: Orofacial-digital syndrome IV  - Genetic Testing Registry: Orofaciodigital syndrome 10  - Genetic Testing Registry: Orofaciodigital syndrome 11  - Genetic Testing Registry: Orofaciodigital syndrome 5  - Genetic Testing Registry: Orofaciodigital syndrome 6  - Genetic Testing Registry: Orofaciodigital syndrome 7  - Genetic Testing Registry: Orofaciodigital syndrome 8  - Genetic Testing Registry: Orofaciodigital syndrome 9  - Genetic Testing Registry: Orofaciodigital syndromes  - MedlinePlus Encyclopedia: Cleft Lip and Palate  - MedlinePlus Encyclopedia: Polycystic Kidney Disease  - MedlinePlus Encyclopedia: Polydactyly   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,oral-facial-digital syndrome,0000754,GHR,https://ghr.nlm.nih.gov/condition/oral-facial-digital-syndrome,C1510460,T019,Disorders
What is (are) ornithine transcarbamylase deficiency ?,0000755-1,information,"Ornithine transcarbamylase deficiency is an inherited disorder that causes ammonia to accumulate in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.  Ornithine transcarbamylase deficiency often becomes evident in the first few days of life. An infant with ornithine transcarbamylase deficiency may be lacking in energy (lethargic) or unwilling to eat, and have poorly-controlled breathing rate or body temperature. Some babies with this disorder may experience seizures or unusual body movements, or go into a coma. Complications from ornithine transcarbamylase deficiency may include developmental delay and intellectual disability. Progressive liver damage, skin lesions, and brittle hair may also be seen.  In some affected individuals, signs and symptoms of ornithine transcarbamylase may be less severe, and may not appear until later in life.",ornithine transcarbamylase deficiency,0000755,GHR,https://ghr.nlm.nih.gov/condition/ornithine-transcarbamylase-deficiency,C0268542,T047,Disorders
How many people are affected by ornithine transcarbamylase deficiency ?,0000755-2,frequency,"Ornithine transcarbamylase deficiency is believed to occur in approximately 1 in every 80,000 people.",ornithine transcarbamylase deficiency,0000755,GHR,https://ghr.nlm.nih.gov/condition/ornithine-transcarbamylase-deficiency,C0268542,T047,Disorders
What are the genetic changes related to ornithine transcarbamylase deficiency ?,0000755-3,genetic changes,"Mutations in the OTC gene cause ornithine transcarbamylase deficiency.  Ornithine transcarbamylase deficiency belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions that occurs in liver cells. It processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys.  In ornithine transcarbamylase deficiency, the enzyme that starts a specific reaction within the urea cycle is damaged or missing. The urea cycle cannot proceed normally, and nitrogen accumulates in the bloodstream in the form of ammonia.  Ammonia is especially damaging to the nervous system, so ornithine transcarbamylase deficiency causes neurological problems as well as eventual damage to the liver.",ornithine transcarbamylase deficiency,0000755,GHR,https://ghr.nlm.nih.gov/condition/ornithine-transcarbamylase-deficiency,C0268542,T047,Disorders
Is ornithine transcarbamylase deficiency inherited ?,0000755-4,inheritance,"Ornithine transcarbamylase deficiency is an X-linked disorder. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), mutations in both copies of the gene will cause the disorder. Some females with only one altered copy of the OTC gene also show signs and symptoms of ornithine transcarbamylase deficiency.",ornithine transcarbamylase deficiency,0000755,GHR,https://ghr.nlm.nih.gov/condition/ornithine-transcarbamylase-deficiency,C0268542,T047,Disorders
What are the treatments for ornithine transcarbamylase deficiency ?,0000755-5,treatment,These resources address the diagnosis or management of ornithine transcarbamylase deficiency:  - Baby's First Test  - Gene Review: Gene Review: Ornithine Transcarbamylase Deficiency  - Gene Review: Gene Review: Urea Cycle Disorders Overview  - Genetic Testing Registry: Ornithine carbamoyltransferase deficiency  - MedlinePlus Encyclopedia: Hereditary urea cycle abnormality   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,ornithine transcarbamylase deficiency,0000755,GHR,https://ghr.nlm.nih.gov/condition/ornithine-transcarbamylase-deficiency,C0268542,T047,Disorders
What is (are) ornithine translocase deficiency ?,0000756-1,information,"Ornithine translocase deficiency is an inherited disorder that causes ammonia to accumulate in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.  Ornithine translocase deficiency varies widely in its severity and age of onset. An infant with ornithine translocase deficiency may be lacking in energy (lethargic) or refuse to eat, or have poorly controlled breathing or body temperature. Some babies with this disorder may experience seizures or unusual body movements, or go into a coma. Episodes of illness may coincide with the introduction of high-protein formulas or solid foods into the diet.  In most affected individuals, signs and symptoms of ornithine translocase deficiency do not appear until later in life. Later-onset forms of ornithine translocase deficiency are usually less severe than the infantile form. Some people with later-onset ornithine translocase deficiency cannot tolerate high-protein foods, such as meat. Occasionally, high-protein meals or stress caused by illness or periods without food (fasting) may cause ammonia to accumulate more quickly in the blood. This rapid increase of ammonia may lead to episodes of vomiting, lack of energy (lethargy), problems with coordination (ataxia), confusion, or blurred vision. Complications of ornithine translocase deficiency may include developmental delay, learning disabilities, and stiffness caused by abnormal tensing of the muscles (spasticity).",ornithine translocase deficiency,0000756,GHR,https://ghr.nlm.nih.gov/condition/ornithine-translocase-deficiency,C0268540,T047,Disorders
How many people are affected by ornithine translocase deficiency ?,0000756-2,frequency,Ornithine translocase deficiency is a very rare disorder. Fewer than 100 affected individuals have been reported worldwide.,ornithine translocase deficiency,0000756,GHR,https://ghr.nlm.nih.gov/condition/ornithine-translocase-deficiency,C0268540,T047,Disorders
What are the genetic changes related to ornithine translocase deficiency ?,0000756-3,genetic changes,"Mutations in the SLC25A15 gene cause ornithine translocase deficiency.  Ornithine translocase deficiency belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions that occurs in liver cells. This cycle processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys.  The SLC25A15 gene provides instructions for making a protein called a mitochondrial ornithine transporter. This protein is needed to move a molecule called ornithine within the mitochondria (the energy-producing centers in cells). Specifically, this protein transports ornithine across the inner membrane of mitochondria to the region called the mitochondrial matrix, where it participates in the urea cycle.  Mutations in the SLC25A15 gene result in a mitochondrial ornithine transporter that is unstable or the wrong shape, and which cannot bring ornithine to the mitochondrial matrix. This failure of ornithine transport causes an interruption of the urea cycle and the accumulation of ammonia, resulting in the signs and symptoms of ornithine translocase deficiency.",ornithine translocase deficiency,0000756,GHR,https://ghr.nlm.nih.gov/condition/ornithine-translocase-deficiency,C0268540,T047,Disorders
Is ornithine translocase deficiency inherited ?,0000756-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",ornithine translocase deficiency,0000756,GHR,https://ghr.nlm.nih.gov/condition/ornithine-translocase-deficiency,C0268540,T047,Disorders
What are the treatments for ornithine translocase deficiency ?,0000756-5,treatment,These resources address the diagnosis or management of ornithine translocase deficiency:  - Baby's First Test  - Gene Review: Gene Review: Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome  - Gene Review: Gene Review: Urea Cycle Disorders Overview  - Genetic Testing Registry: Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome  - MedlinePlus Encyclopedia: Hereditary urea cycle abnormality   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,ornithine translocase deficiency,0000756,GHR,https://ghr.nlm.nih.gov/condition/ornithine-translocase-deficiency,C0268540,T047,Disorders
What is (are) osteogenesis imperfecta ?,0000757-1,information,"Osteogenesis imperfecta (OI) is a group of genetic disorders that mainly affect the bones. The term ""osteogenesis imperfecta"" means imperfect bone formation. People with this condition have bones that break easily, often from mild trauma or with no apparent cause. Multiple fractures are common, and in severe cases, can occur even before birth. Milder cases may involve only a few fractures over a person's lifetime.  There are at least eight recognized forms of osteogenesis imperfecta, designated type I through type VIII. The types can be distinguished by their signs and symptoms, although their characteristic features overlap. Type I is the mildest form of osteogenesis imperfecta and type II is the most severe; other types of this condition have signs and symptoms that fall somewhere between these two extremes. Increasingly, genetic factors are used to define the different forms of osteogenesis imperfecta.  The milder forms of osteogenesis imperfecta, including type I, are characterized by bone fractures during childhood and adolescence that often result from minor trauma. Fractures occur less frequently in adulthood. People with mild forms of the condition typically have a blue or grey tint to the part of the eye that is usually white (the sclera), and may develop hearing loss in adulthood. Affected individuals are usually of normal or near normal height.  Other types of osteogenesis imperfecta are more severe, causing frequent bone fractures that may begin before birth and result from little or no trauma. Additional features of these conditions can include blue sclerae, short stature, hearing loss, respiratory problems, and a disorder of tooth development called dentinogenesis imperfecta. The most severe forms of osteogenesis imperfecta, particularly type II, can include an abnormally small, fragile rib cage and underdeveloped lungs. Infants with these abnormalities have life-threatening problems with breathing and often die shortly after birth.",osteogenesis imperfecta,0000757,GHR,https://ghr.nlm.nih.gov/condition/osteogenesis-imperfecta,C0029434,T019,Disorders
How many people are affected by osteogenesis imperfecta ?,0000757-2,frequency,"This condition affects an estimated 6 to 7 per 100,000 people worldwide. Types I and IV are the most common forms of osteogenesis imperfecta, affecting 4 to 5 per 100,000 people.",osteogenesis imperfecta,0000757,GHR,https://ghr.nlm.nih.gov/condition/osteogenesis-imperfecta,C0029434,T019,Disorders
What are the genetic changes related to osteogenesis imperfecta ?,0000757-3,genetic changes,"Mutations in the COL1A1, COL1A2, CRTAP, and P3H1 genes cause osteogenesis imperfecta.  Mutations in the COL1A1 and COL1A2 genes are responsible for more than 90 percent of all cases of osteogenesis imperfecta. These genes provide instructions for making proteins that are used to assemble type I collagen. This type of collagen is the most abundant protein in bone, skin, and other connective tissues that provide structure and strength to the body.  Most of the mutations that cause osteogenesis imperfecta type I occur in the COL1A1 gene. These genetic changes reduce the amount of type I collagen produced in the body, which causes bones to be brittle and to fracture easily. The mutations responsible for most cases of osteogenesis imperfecta types II, III, and IV occur in either the COL1A1 or COL1A2 gene. These mutations typically alter the structure of type I collagen molecules. A defect in the structure of type I collagen weakens connective tissues, particularly bone, resulting in the characteristic features of osteogenesis imperfecta.  Mutations in the CRTAP and P3H1 genes are responsible for rare, often severe cases of osteogenesis imperfecta. Cases caused by CRTAP mutations are usually classified as type VII; when P3H1 mutations underlie the condition, it is classified as type VIII. The proteins produced from these genes work together to process collagen into its mature form. Mutations in either gene disrupt the normal folding, assembly, and secretion of collagen molecules. These defects weaken connective tissues, leading to severe bone abnormalities and problems with growth.  In cases of osteogenesis imperfecta without identified mutations in one of the genes described above, the cause of the disorder is unknown. These cases include osteogenesis imperfecta types V and VI. Researchers are working to identify additional genes that may be responsible for these conditions.",osteogenesis imperfecta,0000757,GHR,https://ghr.nlm.nih.gov/condition/osteogenesis-imperfecta,C0029434,T019,Disorders
Is osteogenesis imperfecta inherited ?,0000757-4,inheritance,"Most cases of osteogenesis imperfecta have an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the condition. Many people with type I or type IV osteogenesis imperfecta inherit a mutation from a parent who has the disorder. Most infants with more severe forms of osteogenesis imperfecta (such as type II and type III) have no history of the condition in their family. In these infants, the condition is caused by new (sporadic) mutations in the COL1A1 or COL1A2 gene.  Less commonly, osteogenesis imperfecta has an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means two copies of the gene in each cell are altered. The parents of a child with an autosomal recessive disorder typically are not affected, but each carry one copy of the altered gene. Some cases of osteogenesis imperfecta type III are autosomal recessive; these cases usually result from mutations in genes other than COL1A1 and COL1A2. When osteogenesis imperfecta is caused by mutations in the CRTAP or P3H1 gene, the condition also has an autosomal recessive pattern of inheritance.",osteogenesis imperfecta,0000757,GHR,https://ghr.nlm.nih.gov/condition/osteogenesis-imperfecta,C0029434,T019,Disorders
What are the treatments for osteogenesis imperfecta ?,0000757-5,treatment,"These resources address the diagnosis or management of osteogenesis imperfecta:  - Gene Review: Gene Review: COL1A1/2-Related Osteogenesis Imperfecta  - Genetic Testing Registry: Osteogenesis imperfecta  - Genetic Testing Registry: Osteogenesis imperfecta type 5  - Genetic Testing Registry: Osteogenesis imperfecta type 6  - Genetic Testing Registry: Osteogenesis imperfecta type 7  - Genetic Testing Registry: Osteogenesis imperfecta type 8  - Genetic Testing Registry: Osteogenesis imperfecta type I  - Genetic Testing Registry: Osteogenesis imperfecta type III  - Genetic Testing Registry: Osteogenesis imperfecta with normal sclerae, dominant form  - Genetic Testing Registry: Osteogenesis imperfecta, recessive perinatal lethal  - MedlinePlus Encyclopedia: Osteogenesis Imperfecta   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",osteogenesis imperfecta,0000757,GHR,https://ghr.nlm.nih.gov/condition/osteogenesis-imperfecta,C0029434,T019,Disorders
What is (are) osteoglophonic dysplasia ?,0000758-1,information,"Osteoglophonic dysplasia is a condition characterized by abnormal bone growth that leads to severe head and face (craniofacial) abnormalities, dwarfism, and other features. The term osteoglophonic refers to the bones (osteo-) having distinctive hollowed out (-glophonic) areas that appear as holes on x-ray images.  Premature fusion of certain bones in the skull (craniosynostosis) typically occurs in osteoglophonic dysplasia. The craniosynostosis associated with this disorder may give the head a tall appearance, often referred to in the medical literature as a tower-shaped skull, or a relatively mild version of a deformity called a cloverleaf skull. Characteristic facial features in people with osteoglophonic dysplasia include a prominent forehead (frontal bossing), widely spaced eyes (hypertelorism), flattening of the bridge of the nose and of the middle of the face (midface hypoplasia), a large tongue (macroglossia), a protruding jaw (prognathism), and a short neck. People with this condition usually have no visible teeth because the teeth never emerge from the jaw (clinical anodontia). In addition, the gums are often overgrown (hypertrophic gingiva).  Infants with osteoglophonic dysplasia often experience failure to thrive, which means they do not gain weight and grow at the expected rate. Affected individuals have short, bowed legs and arms and are short in stature. They also have flat feet and short, broad hands and fingers.  The life expectancy of people with osteoglophonic dysplasia depends on the extent of their craniofacial abnormalities; those that obstruct the air passages and affect the mouth and teeth can lead to respiratory problems and cause difficulty with eating and drinking. Despite the skull abnormalities, intelligence is generally not affected in this disorder.",osteoglophonic dysplasia,0000758,GHR,https://ghr.nlm.nih.gov/condition/osteoglophonic-dysplasia,C0432283,T019,Disorders
How many people are affected by osteoglophonic dysplasia ?,0000758-2,frequency,Osteoglophonic dysplasia is a rare disorder; its prevalence is unknown. Only about 15 cases have been reported in the medical literature.,osteoglophonic dysplasia,0000758,GHR,https://ghr.nlm.nih.gov/condition/osteoglophonic-dysplasia,C0432283,T019,Disorders
What are the genetic changes related to osteoglophonic dysplasia ?,0000758-3,genetic changes,"Osteoglophonic dysplasia is caused by mutations in the FGFR1 gene, which provides instructions for making a protein called fibroblast growth factor receptor 1. This protein is one of four fibroblast growth factor receptors, which are related proteins that bind (attach) to other proteins called fibroblast growth factors. The growth factors and their receptors are involved in important processes such as cell division, regulation of cell growth and maturation, formation of blood vessels, wound healing, and embryonic development. In particular, they play a major role in skeletal development.  The FGFR1 protein spans the cell membrane, so that one end of the protein remains inside the cell and the other end projects from the outer surface of the cell. When a fibroblast growth factor binds to the part of the FGFR1 protein outside the cell, the receptor triggers a cascade of chemical reactions inside the cell that instruct the cell to undergo certain changes, such as maturing to take on specialized functions. The FGFR1 protein is thought to play an important role in the development of the nervous system. This protein may also help regulate the growth of long bones, such as the large bones in the arms and legs.  FGFR1 gene mutations that cause osteoglophonic dysplasia change single building blocks (amino acids) in the FGFR1 protein. The altered FGFR1 protein appears to cause prolonged signaling, which promotes premature fusion of bones in the skull and disrupts the regulation of bone growth in the arms and legs.",osteoglophonic dysplasia,0000758,GHR,https://ghr.nlm.nih.gov/condition/osteoglophonic-dysplasia,C0432283,T019,Disorders
Is osteoglophonic dysplasia inherited ?,0000758-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family. However, some affected individuals inherit the mutation from an affected parent.",osteoglophonic dysplasia,0000758,GHR,https://ghr.nlm.nih.gov/condition/osteoglophonic-dysplasia,C0432283,T019,Disorders
What are the treatments for osteoglophonic dysplasia ?,0000758-5,treatment,These resources address the diagnosis or management of osteoglophonic dysplasia:  - Genetic Testing Registry: Osteoglophonic dysplasia  - Seattle Children's Hospital: Dwarfism and Bone Dysplasias   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,osteoglophonic dysplasia,0000758,GHR,https://ghr.nlm.nih.gov/condition/osteoglophonic-dysplasia,C0432283,T019,Disorders
What is (are) osteopetrosis ?,0000759-1,information,"Osteopetrosis is a bone disease that makes bones abnormally dense and prone to breakage (fracture). Researchers have described several major types of osteopetrosis, which are usually distinguished by their pattern of inheritance: autosomal dominant, autosomal recessive, or X-linked. The different types of the disorder can also be distinguished by the severity of their signs and symptoms.  Autosomal dominant osteopetrosis (ADO), which is also called Albers-Schnberg disease, is typically the mildest type of the disorder. Some affected individuals have no symptoms. In these people, the unusually dense bones may be discovered by accident when an x-ray is done for another reason. In affected individuals who develop signs and symptoms, the major features of the condition include multiple bone fractures, abnormal side-to-side curvature of the spine (scoliosis) or other spinal abnormalities, arthritis in the hips, and a bone infection called osteomyelitis. These problems usually become apparent in late childhood or adolescence.  Autosomal recessive osteopetrosis (ARO) is a more severe form of the disorder that becomes apparent in early infancy. Affected individuals have a high risk of bone fracture resulting from seemingly minor bumps and falls. Their abnormally dense skull bones pinch nerves in the head and face (cranial nerves), often resulting in vision loss, hearing loss, and paralysis of facial muscles. Dense bones can also impair the function of bone marrow, preventing it from producing new blood cells and immune system cells. As a result, people with severe osteopetrosis are at risk of abnormal bleeding, a shortage of red blood cells (anemia), and recurrent infections. In the most severe cases, these bone marrow abnormalities can be life-threatening in infancy or early childhood.  Other features of autosomal recessive osteopetrosis can include slow growth and short stature, dental abnormalities, and an enlarged liver and spleen (hepatosplenomegaly). Depending on the genetic changes involved, people with severe osteopetrosis can also have brain abnormalities, intellectual disability, or recurrent seizures (epilepsy).  A few individuals have been diagnosed with intermediate autosomal osteopetrosis (IAO), a form of the disorder that can have either an autosomal dominant or an autosomal recessive pattern of inheritance. The signs and symptoms of this condition become noticeable in childhood and include an increased risk of bone fracture and anemia. People with this form of the disorder typically do not have life-threatening bone marrow abnormalities. However, some affected individuals have had abnormal calcium deposits (calcifications) in the brain, intellectual disability, and a form of kidney disease called renal tubular acidosis.  Rarely, osteopetrosis can have an X-linked pattern of inheritance. In addition to abnormally dense bones, the X-linked form of the disorder is characterized by abnormal swelling caused by a buildup of fluid (lymphedema) and a condition called anhydrotic ectodermal dysplasia that affects the skin, hair, teeth, and sweat glands. Affected individuals also have a malfunctioning immune system (immunodeficiency), which allows severe, recurrent infections to develop. Researchers often refer to this condition as OL-EDA-ID, an acronym derived from each of the major features of the disorder.",osteopetrosis,0000759,GHR,https://ghr.nlm.nih.gov/condition/osteopetrosis,C0029454,T047,Disorders
How many people are affected by osteopetrosis ?,0000759-2,frequency,"Autosomal dominant osteopetrosis is the most common form of the disorder, affecting about 1 in 20,000 people. Autosomal recessive osteopetrosis is rarer, occurring in an estimated 1 in 250,000 people.  Other forms of osteopetrosis are very rare. Only a few cases of intermediate autosomal osteopetrosis and OL-EDA-ID have been reported in the medical literature.",osteopetrosis,0000759,GHR,https://ghr.nlm.nih.gov/condition/osteopetrosis,C0029454,T047,Disorders
What are the genetic changes related to osteopetrosis ?,0000759-3,genetic changes,"Mutations in at least nine genes cause the various types of osteopetrosis. Mutations in the CLCN7 gene are responsible for about 75 percent of cases of autosomal dominant osteopetrosis, 10 to 15 percent of cases of autosomal recessive osteopetrosis, and all known cases of intermediate autosomal osteopetrosis. TCIRG1 gene mutations cause about 50 percent of cases of autosomal recessive osteopetrosis. Mutations in other genes are less common causes of autosomal dominant and autosomal recessive forms of the disorder. The X-linked type of osteopetrosis, OL-EDA-ID, results from mutations in the IKBKG gene. In about 30 percent of all cases of osteopetrosis, the cause of the condition is unknown.  The genes associated with osteopetrosis are involved in the formation, development, and function of specialized cells called osteoclasts. These cells break down bone tissue during bone remodeling, a normal process in which old bone is removed and new bone is created to replace it. Bones are constantly being remodeled, and the process is carefully controlled to ensure that bones stay strong and healthy.  Mutations in any of the genes associated with osteopetrosis lead to abnormal or missing osteoclasts. Without functional osteoclasts, old bone is not broken down as new bone is formed. As a result, bones throughout the skeleton become unusually dense. The bones are also structurally abnormal, making them prone to fracture. These problems with bone remodeling underlie all of the major features of osteopetrosis.",osteopetrosis,0000759,GHR,https://ghr.nlm.nih.gov/condition/osteopetrosis,C0029454,T047,Disorders
Is osteopetrosis inherited ?,0000759-4,inheritance,"Osteopetrosis can have several different patterns of inheritance. Most commonly, the disorder has an autosomal dominant inheritance pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. Most people with autosomal dominant osteopetrosis inherit the condition from an affected parent.  Osteopetrosis can also be inherited in an autosomal recessive pattern, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  OL-EDA-ID is inherited in an X-linked recessive pattern. The IKBKG gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",osteopetrosis,0000759,GHR,https://ghr.nlm.nih.gov/condition/osteopetrosis,C0029454,T047,Disorders
What are the treatments for osteopetrosis ?,0000759-5,treatment,"These resources address the diagnosis or management of osteopetrosis:  - Gene Review: Gene Review: CLCN7-Related Osteopetrosis  - Genetic Testing Registry: Ectodermal dysplasia, anhidrotic, with immunodeficiency, osteopetrosis, and lymphedema  - Genetic Testing Registry: OSTEOPETROSIS, AUTOSOMAL RECESSIVE 5  - Genetic Testing Registry: Osteopetrosis and infantile neuroaxonal dystrophy  - Genetic Testing Registry: Osteopetrosis autosomal dominant type 2  - Genetic Testing Registry: Osteopetrosis autosomal recessive 1  - Genetic Testing Registry: Osteopetrosis autosomal recessive 2  - Genetic Testing Registry: Osteopetrosis autosomal recessive 4  - Genetic Testing Registry: Osteopetrosis autosomal recessive 6  - Genetic Testing Registry: Osteopetrosis autosomal recessive 7  - Genetic Testing Registry: Osteopetrosis with renal tubular acidosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",osteopetrosis,0000759,GHR,https://ghr.nlm.nih.gov/condition/osteopetrosis,C0029454,T047,Disorders
What is (are) osteoporosis-pseudoglioma syndrome ?,0000760-1,information,"Osteoporosis-pseudoglioma syndrome is a rare condition characterized by severe thinning of the bones (osteoporosis) and eye abnormalities that lead to vision loss. In people with this condition, osteoporosis is usually recognized in early childhood. It is caused by a shortage of minerals, such as calcium, in bones (decreased bone mineral density), which makes the bones brittle and prone to fracture. Affected individuals often have multiple bone fractures, including in the bones that form the spine (vertebrae). Multiple fractures can cause collapse of the affected vertebrae (compressed vertebrae), abnormal side-to-side curvature of the spine (scoliosis), short stature, and limb deformities. Decreased bone mineral density can also cause softening or thinning of the skull (craniotabes).  Most affected individuals have impaired vision at birth or by early infancy and are blind by young adulthood. Vision problems are usually caused by one of several eye conditions, grouped together as pseudoglioma, that affect the light-sensitive tissue at the back of the eye (the retina), although other eye conditions have been identified in affected individuals. Pseudogliomas are so named because, on examination, the conditions resemble an eye tumor known as a retinal glioma.  Rarely, people with osteoporosis-pseudoglioma syndrome have additional signs or symptoms such as mild intellectual disability, weak muscle tone (hypotonia), abnormally flexible joints, or seizures.",osteoporosis-pseudoglioma syndrome,0000760,GHR,https://ghr.nlm.nih.gov/condition/osteoporosis-pseudoglioma-syndrome,C0432252,T047,Disorders
How many people are affected by osteoporosis-pseudoglioma syndrome ?,0000760-2,frequency,Osteoporosis-pseudoglioma syndrome is a rare disorder that occurs in approximately 1 in 2 million people.,osteoporosis-pseudoglioma syndrome,0000760,GHR,https://ghr.nlm.nih.gov/condition/osteoporosis-pseudoglioma-syndrome,C0432252,T047,Disorders
What are the genetic changes related to osteoporosis-pseudoglioma syndrome ?,0000760-3,genetic changes,"Osteoporosis-pseudoglioma syndrome is caused by mutations in the LRP5 gene. This gene provides instructions for making a protein that participates in a chemical signaling pathway that affects the way cells and tissues develop. In particular, the LRP5 protein helps regulate bone mineral density and plays a critical role in development of the retina.  LRP5 gene mutations that cause osteoporosis-pseudoglioma syndrome prevent cells from making any LRP5 protein or lead to a protein that cannot function. Loss of this protein's function disrupts the chemical signaling pathways that are needed for the formation of bone and for normal retinal development, leading to the bone and eye abnormalities characteristic of osteoporosis-pseudoglioma syndrome.",osteoporosis-pseudoglioma syndrome,0000760,GHR,https://ghr.nlm.nih.gov/condition/osteoporosis-pseudoglioma-syndrome,C0432252,T047,Disorders
Is osteoporosis-pseudoglioma syndrome inherited ?,0000760-4,inheritance,"Osteoporosis-pseudoglioma syndrome is inherited in an autosomal recessive pattern, which means both copies of the LRP5 gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. However, some carriers may have decreased bone mineral density.",osteoporosis-pseudoglioma syndrome,0000760,GHR,https://ghr.nlm.nih.gov/condition/osteoporosis-pseudoglioma-syndrome,C0432252,T047,Disorders
What are the treatments for osteoporosis-pseudoglioma syndrome ?,0000760-5,treatment,These resources address the diagnosis or management of osteoporosis-pseudoglioma syndrome:  - Genetic Testing Registry: Osteoporosis with pseudoglioma  - Lucile Packard Children's Hospital at Stanford: Juvenile Osteoporosis  - MedlinePlus Encyclopedia: Bone Mineral Density Test  - Merck Manual Home Health Edition: Osteoporosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,osteoporosis-pseudoglioma syndrome,0000760,GHR,https://ghr.nlm.nih.gov/condition/osteoporosis-pseudoglioma-syndrome,C0432252,T047,Disorders
What is (are) otopalatodigital syndrome type 1 ?,0000761-1,information,"Otopalatodigital syndrome type 1 is a disorder primarily involving abnormalities in skeletal development. It is a member of a group of related conditions called otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 2, frontometaphyseal dysplasia, and Melnick-Needles syndrome. In general, these disorders involve hearing loss caused by malformations in the tiny bones in the ears (ossicles), problems in the development of the roof of the mouth (palate), and skeletal abnormalities involving the fingers and/or toes (digits).  Otopalatodigital syndrome type 1 is usually the mildest of the otopalatodigital spectrum disorders. People with this condition usually have characteristic facial features including wide-set and downward-slanting eyes; prominent brow ridges; and a small, flat nose. Affected individuals also have hearing loss and chest deformities. They have abnormalities of the fingers and toes, such as blunt, square-shaped (spatulate) fingertips; shortened thumbs and big toes; and unusually long second toes.  Affected individuals may be born with an opening in the roof of the mouth (a cleft palate). They may have mildly bowed limbs, and limited range of motion in some joints. People with otopalatodigital syndrome type 1 may be somewhat shorter than other members of their family. Males with this disorder often have more severe signs and symptoms than do females, who may show only the characteristic facial features.",otopalatodigital syndrome type 1,0000761,GHR,https://ghr.nlm.nih.gov/condition/otopalatodigital-syndrome-type-1,C0265251,T019,Disorders
How many people are affected by otopalatodigital syndrome type 1 ?,0000761-2,frequency,"Otopalatodigital syndrome type 1 is a rare disorder, affecting fewer than 1 in every 100,000 individuals. Its specific incidence is unknown.",otopalatodigital syndrome type 1,0000761,GHR,https://ghr.nlm.nih.gov/condition/otopalatodigital-syndrome-type-1,C0265251,T019,Disorders
What are the genetic changes related to otopalatodigital syndrome type 1 ?,0000761-3,genetic changes,"Mutations in the FLNA gene cause otopalatodigital syndrome type 1.  The FLNA gene provides instructions for producing the protein filamin A, which helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. Filamin A binds to another protein called actin, and helps the actin to form the branching network of filaments that make up the cytoskeleton. Filamin A also links actin to many other proteins to perform various functions within the cell.  A small number of mutations in the FLNA gene have been identified in people with otopalatodigital syndrome type 1. The mutations all result in changes to the filamin A protein in the region that binds to actin. The mutations responsible for otopalatodigital syndrome type 1 are described as ""gain-of-function"" because they appear to enhance the activity of the filamin A protein or give the protein a new, atypical function. Researchers believe that the mutations may change the way the filamin A protein helps regulate processes involved in skeletal development, but it is not known how changes in the protein relate to the specific signs and symptoms of otopalatodigital syndrome type 1.",otopalatodigital syndrome type 1,0000761,GHR,https://ghr.nlm.nih.gov/condition/otopalatodigital-syndrome-type-1,C0265251,T019,Disorders
Is otopalatodigital syndrome type 1 inherited ?,0000761-4,inheritance,"This condition is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In most cases, males experience more severe symptoms of the disorder than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",otopalatodigital syndrome type 1,0000761,GHR,https://ghr.nlm.nih.gov/condition/otopalatodigital-syndrome-type-1,C0265251,T019,Disorders
What are the treatments for otopalatodigital syndrome type 1 ?,0000761-5,treatment,"These resources address the diagnosis or management of otopalatodigital syndrome type 1:  - Gene Review: Gene Review: Otopalatodigital Spectrum Disorders  - Genetic Testing Registry: Oto-palato-digital syndrome, type I   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",otopalatodigital syndrome type 1,0000761,GHR,https://ghr.nlm.nih.gov/condition/otopalatodigital-syndrome-type-1,C0265251,T019,Disorders
What is (are) otopalatodigital syndrome type 2 ?,0000762-1,information,"Otopalatodigital syndrome type 2 is a disorder involving abnormalities in skeletal development and other health problems. It is a member of a group of related conditions called otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 1, frontometaphyseal dysplasia, and Melnick-Needles syndrome. In general, these disorders involve hearing loss caused by malformations in the tiny bones in the ears (ossicles), problems in the development of the roof of the mouth (palate), and skeletal abnormalities involving the fingers and/or toes (digits). Otopalatodigital syndrome type 2 also tends to cause problems in other areas of the body, such as the brain and heart.  People with otopalatodigital syndrome type 2 have characteristic facial features including wide-set and downward-slanting eyes; prominent brow ridges; a broad, flat nose; and a very small lower jaw and chin (micrognathia). The base of the skull may be thickened. Some people with this disorder have hearing loss. Affected individuals are usually of short stature and may have abnormalities of the fingers and toes, such as unusual curvature of the fingers (camptodactyly) and shortened or absent thumbs and big toes. They may have bowed limbs; underdeveloped, irregular ribs that may cause problems with breathing; and other abnormal or absent bones. Some may be born with an opening in the roof of the mouth (a cleft palate).  In addition to skeletal abnormalities, individuals with otopalatodigital syndrome type 2 may have developmental delay, increased fluid in the center of the brain (hydrocephalus), protrusion of the abdominal organs through the navel (omphalocele), heart defects, chest abnormalities, obstruction of the ducts between the kidneys and bladder (ureters), and, in males, opening of the urethra on the underside of the penis (hypospadias).  Males with otopalatodigital syndrome type 2 generally have much more severe signs and symptoms than do females. Males with the disorder usually do not live beyond their first year, because their underdeveloped rib cage does not allow sufficient lung expansion for breathing.",otopalatodigital syndrome type 2,0000762,GHR,https://ghr.nlm.nih.gov/condition/otopalatodigital-syndrome-type-2,C0039082,T019,Disorders
How many people are affected by otopalatodigital syndrome type 2 ?,0000762-2,frequency,"Otopalatodigital syndrome type 2 is a rare disorder, affecting fewer than 1 in every 100,000 individuals. Its specific incidence is unknown.",otopalatodigital syndrome type 2,0000762,GHR,https://ghr.nlm.nih.gov/condition/otopalatodigital-syndrome-type-2,C0039082,T019,Disorders
What are the genetic changes related to otopalatodigital syndrome type 2 ?,0000762-3,genetic changes,"Mutations in the FLNA gene cause otopalatodigital syndrome type 2.  The FLNA gene provides instructions for producing the protein filamin A, which helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. Filamin A binds to another protein called actin, and helps the actin to form the branching network of filaments that make up the cytoskeleton. Filamin A also links actin to many other proteins to perform various functions within the cell.  A small number of mutations in the FLNA gene have been identified in people with otopalatodigital syndrome type 2. The mutations all result in changes to the filamin A protein in the region that binds to actin. The mutations responsible for otopalatodigital syndrome type 2 are described as ""gain-of-function"" because they appear to enhance the activity of the filamin A protein or give the protein a new, atypical function. Researchers believe that the mutations may change the way the filamin A protein helps regulate processes involved in skeletal development, but it is not known how changes in the protein relate to the specific signs and symptoms of otopalatodigital syndrome type 2.",otopalatodigital syndrome type 2,0000762,GHR,https://ghr.nlm.nih.gov/condition/otopalatodigital-syndrome-type-2,C0039082,T019,Disorders
Is otopalatodigital syndrome type 2 inherited ?,0000762-4,inheritance,"This condition is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In most cases, males experience more severe symptoms of the disorder than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",otopalatodigital syndrome type 2,0000762,GHR,https://ghr.nlm.nih.gov/condition/otopalatodigital-syndrome-type-2,C0039082,T019,Disorders
What are the treatments for otopalatodigital syndrome type 2 ?,0000762-5,treatment,"These resources address the diagnosis or management of otopalatodigital syndrome type 2:  - Gene Review: Gene Review: Otopalatodigital Spectrum Disorders  - Genetic Testing Registry: Oto-palato-digital syndrome, type II   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",otopalatodigital syndrome type 2,0000762,GHR,https://ghr.nlm.nih.gov/condition/otopalatodigital-syndrome-type-2,C0039082,T019,Disorders
What is (are) otospondylomegaepiphyseal dysplasia ?,0000763-1,information,"Otospondylomegaepiphyseal dysplasia (OSMED) is a skeletal disorder characterized by skeletal abnormalities, distinctive facial features, and severe hearing loss. The condition involves the ears (oto-), affects the bones of the spine (spondylo-), and enlarges the ends (epiphyses) of long bones in the arms and legs. The features of OSMED are similar to those of another skeletal disorder, Weissenbacher-Zweymller syndrome.  People with OSMED are often shorter than average because the bones in their legs are unusually short. Other skeletal features include enlarged joints; short arms, hands, and fingers; and flattened bones of the spine (platyspondyly). People with the disorder often experience back and joint pain, limited joint movement, and arthritis that begins early in life.  Severe high-tone hearing loss is common in people with OSMED. Typical facial features include protruding eyes; a flattened bridge of the nose; an upturned nose with a large, rounded tip; and a small lower jaw. Virtually all affected infants are born with an opening in the roof of the mouth (a cleft palate). The skeletal features of OSMED tend to diminish during childhood, but other signs and symptoms, such as hearing loss and joint pain, persist into adulthood.",otospondylomegaepiphyseal dysplasia,0000763,GHR,https://ghr.nlm.nih.gov/condition/otospondylomegaepiphyseal-dysplasia,C1855310,T019,Disorders
How many people are affected by otospondylomegaepiphyseal dysplasia ?,0000763-2,frequency,This condition is rare; the prevalence is unknown. Only a few families with OSMED have been reported worldwide.,otospondylomegaepiphyseal dysplasia,0000763,GHR,https://ghr.nlm.nih.gov/condition/otospondylomegaepiphyseal-dysplasia,C1855310,T019,Disorders
What are the genetic changes related to otospondylomegaepiphyseal dysplasia ?,0000763-3,genetic changes,Mutations in the COL11A2 gene cause OSMED. The COL11A2 gene is one of several genes that provide instructions for the production of type XI collagen. This type of collagen is important for the normal development of bones and other connective tissues that form the body's supportive framework. Mutations in the COL11A2 gene that cause OSMED disrupt the production or assembly of type XI collagen molecules. The loss of type XI collagen prevents bones and other connective tissues from developing properly.,otospondylomegaepiphyseal dysplasia,0000763,GHR,https://ghr.nlm.nih.gov/condition/otospondylomegaepiphyseal-dysplasia,C1855310,T019,Disorders
Is otospondylomegaepiphyseal dysplasia inherited ?,0000763-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",otospondylomegaepiphyseal dysplasia,0000763,GHR,https://ghr.nlm.nih.gov/condition/otospondylomegaepiphyseal-dysplasia,C1855310,T019,Disorders
What are the treatments for otospondylomegaepiphyseal dysplasia ?,0000763-5,treatment,These resources address the diagnosis or management of OSMED:  - Genetic Testing Registry: Otospondylomegaepiphyseal dysplasia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,otospondylomegaepiphyseal dysplasia,0000763,GHR,https://ghr.nlm.nih.gov/condition/otospondylomegaepiphyseal-dysplasia,C1855310,T019,Disorders
What is (are) ovarian cancer ?,0000764-1,information,"Ovarian cancer is a disease that affects women. In this form of cancer, certain cells in the ovary become abnormal and multiply uncontrollably to form a tumor. The ovaries are the female reproductive organs in which egg cells are produced. In about 90 percent of cases, ovarian cancer occurs after age 40, and most cases occur after age 60.  The most common form of ovarian cancer begins in epithelial cells, which are the cells that line the surfaces and cavities of the body. These cancers can arise in the epithelial cells on the surface of the ovary. However, researchers suggest that many or even most ovarian cancers begin in epithelial cells on the fringes (fimbriae) at the end of one of the fallopian tubes, and the cancerous cells migrate to the ovary.  Cancer can also begin in epithelial cells that form the lining of the abdomen (the peritoneum). This form of cancer, called primary peritoneal cancer, resembles epithelial ovarian cancer in its origin, symptoms, progression, and treatment. Primary peritoneal cancer often spreads to the ovaries. It can also occur even if the ovaries have been removed. Because cancers that begin in the ovaries, fallopian tubes, and peritoneum are so similar and spread easily from one of these structures to the others, they are often difficult to distinguish. These cancers are so closely related that they are generally considered collectively by experts.  In about 10 percent of cases, ovarian cancer develops not in epithelial cells but in germ cells, which are precursors to egg cells, or in hormone-producing ovarian cells called granulosa cells.  In its early stages, ovarian cancer usually does not cause noticeable symptoms. As the cancer progresses, signs and symptoms can include pain or a feeling of heaviness in the pelvis or lower abdomen, bloating, feeling full quickly when eating, back pain, vaginal bleeding between menstrual periods or after menopause, or changes in urinary or bowel habits. However, these changes can occur as part of many different conditions. Having one or more of these symptoms does not mean that a woman has ovarian cancer.  In some cases, cancerous tumors can invade surrounding tissue and spread to other parts of the body. If ovarian cancer spreads, cancerous tumors most often appear in the abdominal cavity or on the surfaces of nearby organs such as the bladder or colon. Tumors that begin at one site and then spread to other areas of the body are called metastatic cancers.  Some ovarian cancers cluster in families. These cancers are described as hereditary and are associated with inherited gene mutations. Hereditary ovarian cancers tend to develop earlier in life than non-inherited (sporadic) cases.  Because it is often diagnosed at a late stage, ovarian cancer can be difficult to treat; it leads to the deaths of about 140,000 women annually, more than any other gynecological cancer. However, when it is diagnosed and treated early, the 5-year survival rate is high.",ovarian cancer,0000764,GHR,https://ghr.nlm.nih.gov/condition/ovarian-cancer,C0029925,T191,Disorders
How many people are affected by ovarian cancer ?,0000764-2,frequency,"Ovarian cancer affects about 12 in 100,000 women per year.",ovarian cancer,0000764,GHR,https://ghr.nlm.nih.gov/condition/ovarian-cancer,C0029925,T191,Disorders
What are the genetic changes related to ovarian cancer ?,0000764-3,genetic changes,"Cancers occur when a buildup of mutations in critical genesthose that control cell growth and division or repair damaged DNAallow cells to grow and divide uncontrollably to form a tumor. Most cases of ovarian cancer are sporadic; in these cases the associated genetic changes are acquired during a person's lifetime and are present only in certain cells in the ovary. These changes, which are called somatic mutations, are not inherited. Somatic mutations in the TP53 gene occur in almost half of all ovarian cancers. The protein produced from this gene is described as a tumor suppressor because it helps keep cells from growing and dividing too fast or in an uncontrolled way. Most of these mutations change single protein building blocks (amino acids) in the p53 protein, which reduces or eliminates the protein's tumor suppressor function. Because the altered protein is less able to regulate cell growth and division, a cancerous tumor may develop. Somatic mutations in many other genes have also been found in ovarian cancer cells.  In hereditary ovarian cancer, the associated genetic changes are passed down within a family. These changes, classified as germline mutations, are present in all the body's cells. In people with germline mutations, other inherited and somatic gene changes, together with environmental and lifestyle factors, also influence whether a woman will develop ovarian cancer.  Germline mutations are involved in more than one-fifth of ovarian cancer cases. Between 65 and 85 percent of these mutations are in the BRCA1 or BRCA2 gene. These gene mutations are described as ""high penetrance"" because they are associated with a high risk of developing ovarian cancer, breast cancer, and several other types of cancer in women. Compared to a 1.6 percent lifetime risk of developing ovarian cancer for women in the total population, the lifetime risk in women with a BRCA1 gene mutation is 40 to 60 percent, and the lifetime risk in women with a BRCA2 gene mutation is 20 to 35 percent. Men with mutations in these genes also have an increased risk of developing several forms of cancer. The proteins produced from the BRCA1 and BRCA2 genes are tumor suppressors that are involved in fixing damaged DNA, which helps to maintain the stability of a cell's genetic information. Mutations in these genes impair DNA repair, allowing potentially damaging mutations to persist in DNA. As these defects accumulate, they can trigger cells to grow and divide without control or order to form a tumor.  A significantly increased risk of ovarian cancer is also a feature of certain rare genetic syndromes, including a disorder called Lynch syndrome. Lynch syndrome is most often associated with mutations in the MLH1 or MSH2 gene and accounts for between 10 and 15 percent of hereditary ovarian cancers. Other rare genetic syndromes may also be associated with an increased risk of ovarian cancer. The proteins produced from the genes associated with these syndromes act as tumor suppressors. Mutations in any of these genes can allow cells to grow and divide unchecked, leading to the development of a cancerous tumor. Like BRCA1 and BRCA2, these genes are considered ""high penetrance"" because mutations greatly increase a person's chance of developing cancer. In addition to ovarian cancer, mutations in these genes increase the risk of several other types of cancer in both men and women.  Germline mutations in dozens of other genes have been studied as possible risk factors for ovarian cancer. These genes are described as ""low penetrance"" or ""moderate penetrance"" because changes in each of these genes appear to make only a small or moderate contribution to overall ovarian cancer risk. Some of these genes provide instructions for making proteins that interact with the proteins produced from the BRCA1 or BRCA2 genes. Others act through different pathways. Researchers suspect that the combined influence of variations in these genes may significantly impact a person's risk of developing ovarian cancer.  In many families, the genetic changes associated with hereditary ovarian cancer are unknown. Identifying additional genetic risk factors for ovarian cancer is an active area of medical research.  In addition to genetic changes, researchers have identified many personal and environmental factors that contribute to a woman's risk of developing ovarian cancer. These factors include age, ethnic background, and hormonal and reproductive factors. A history of ovarian cancer in closely related family members is also an important risk factor, particularly if the cancer occurred in early adulthood.",ovarian cancer,0000764,GHR,https://ghr.nlm.nih.gov/condition/ovarian-cancer,C0029925,T191,Disorders
Is ovarian cancer inherited ?,0000764-4,inheritance,"Most cases of ovarian cancer are not caused by inherited genetic factors. These cancers are associated with somatic mutations that are acquired during a person's lifetime, and they do not cluster in families.  A predisposition to cancer caused by a germline mutation is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase a person's chance of developing cancer. Although ovarian cancer occurs only in women, the mutated gene can be inherited from either the mother or the father. It is important to note that people inherit an increased likelihood of developing cancer, not the disease itself. Not all people who inherit mutations in these genes will ultimately develop cancer.  In many cases of ovarian cancer that clusters in families, the genetic basis for the disease and the mechanism of inheritance are unclear.",ovarian cancer,0000764,GHR,https://ghr.nlm.nih.gov/condition/ovarian-cancer,C0029925,T191,Disorders
What are the treatments for ovarian cancer ?,0000764-5,treatment,These resources address the diagnosis or management of ovarian cancer:  - Dana-Farber Cancer Institute  - Familial Ovarian Cancer Registry  - Fred Hutchinson Cancer Research Center  - Gene Review: Gene Review: BRCA1 and BRCA2 Hereditary Breast/Ovarian Cancer  - Genetic Testing Registry: Hereditary breast and ovarian cancer syndrome  - Genetic Testing Registry: Ovarian cancer  - Genomics Education Programme (UK): Hereditary Breast and Ovarian Cancer  - M.D. Anderson Cancer Center  - MedlinePlus Encyclopedia: BRCA1 and BRCA2 Gene Testing  - MedlinePlus Encyclopedia: CA-125 Blood Test  - Memorial Sloan-Kettering Cancer Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,ovarian cancer,0000764,GHR,https://ghr.nlm.nih.gov/condition/ovarian-cancer,C0029925,T191,Disorders
What is (are) pachyonychia congenita ?,0000765-1,information,"Pachyonychia congenita is a condition that primarily affects the nails and skin. The signs and symptoms of this condition usually become apparent within the first few months of life.  Almost everyone with pachyonychia congenita has hypertrophic nail dystrophy, which causes the fingernails and toenails to become thick and abnormally shaped. Many affected children also develop very painful blisters and calluses on the soles of the feet and, less commonly, on the palms of the hands. This condition is known as palmoplantar keratoderma. Severe blisters and calluses on the feet can make it painful or impossible to walk.  Pachyonychia congenita can have several additional features, which vary among affected individuals. These features include thick, white patches on the tongue and inside of the cheeks (oral leukokeratosis); bumps called follicular keratoses that develop around hair follicles on the elbows, knees, and waistline; cysts in the armpits, groin, back, or scalp; and excessive sweating on the palms and soles (palmoplantar hyperhidrosis). Some affected individuals also develop widespread cysts called steatocystomas, which are filled with an oily substance called sebum that normally lubricates the skin and hair. Some babies with pachyonychia congenita have prenatal or natal teeth, which are teeth that are present at birth or in early infancy. Rarely, pachyonychia congenita can affect the voice box (larynx), potentially leading to hoarseness or breathing problems.  Researchers used to split pachyonychia congenita into two types, PC-1 and PC-2, based on the genetic cause and pattern of signs and symptoms. However, as more affected individuals were identified, it became clear that the features of the two types overlapped considerably. Now researchers prefer to describe pachyonychia congenita based on the gene that is altered.",pachyonychia congenita,0000765,GHR,https://ghr.nlm.nih.gov/condition/pachyonychia-congenita,C0265334,T019,Disorders
How many people are affected by pachyonychia congenita ?,0000765-2,frequency,"Although the prevalence of pachyonychia congenita is unknown, it appears to be rare. There are probably several thousand people worldwide with this disorder.",pachyonychia congenita,0000765,GHR,https://ghr.nlm.nih.gov/condition/pachyonychia-congenita,C0265334,T019,Disorders
What are the genetic changes related to pachyonychia congenita ?,0000765-3,genetic changes,"Mutations in several genes, including KRT6A, KRT6B, KRT6C, KRT16, and KRT17, can cause pachyonychia congenita. All of these genes provide instructions for making tough, fibrous proteins called keratins. These proteins form networks that provide strength and resilience to the tissues that make up the skin, hair, and nails.  When pachyonychia congenita is caused by mutations in the KRT6A gene, it is classified as PC-K6a. Similarly, KRT6B gene mutations cause PC-K6b, KRT6C gene mutations cause PC-K6c, KRT16 gene mutations cause PC-K16, and KRT17 gene mutations cause PC-K17.  Mutations in keratin genes alter the structure of keratin proteins, which prevents these proteins from forming strong, stable networks within cells. Without this network, skin cells become fragile and are easily damaged, making the skin less resistant to friction and minor trauma. Even normal activities such as walking can cause skin cells to break down, resulting in the formation of severe, painful blisters and calluses. Defective keratins also disrupt the growth and function of cells in the hair follicles and nails, resulting in the other features of pachyonychia congenita.",pachyonychia congenita,0000765,GHR,https://ghr.nlm.nih.gov/condition/pachyonychia-congenita,C0265334,T019,Disorders
Is pachyonychia congenita inherited ?,0000765-4,inheritance,"Pachyonychia congenita is considered an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In about half of all cases, an affected person inherits the mutation from one affected parent. The other half of cases result from a new (de novo) mutation in the gene that occurs during the formation of reproductive cells (eggs or sperm) or in early embryonic development. These cases occur in people with no history of the disorder in their family.",pachyonychia congenita,0000765,GHR,https://ghr.nlm.nih.gov/condition/pachyonychia-congenita,C0265334,T019,Disorders
What are the treatments for pachyonychia congenita ?,0000765-5,treatment,"These resources address the diagnosis or management of pachyonychia congenita:  - Gene Review: Gene Review: Pachyonychia Congenita  - Genetic Testing Registry: Pachyonychia congenita 4  - Genetic Testing Registry: Pachyonychia congenita syndrome  - Genetic Testing Registry: Pachyonychia congenita type 2  - Genetic Testing Registry: Pachyonychia congenita, type 1  - MedlinePlus Encyclopedia: Nail Abnormalities  - MedlinePlus Encyclopedia: Natal Teeth   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",pachyonychia congenita,0000765,GHR,https://ghr.nlm.nih.gov/condition/pachyonychia-congenita,C0265334,T019,Disorders
What is (are) Paget disease of bone ?,0000766-1,information,"Paget disease of bone is a disorder that causes bones to grow larger and weaker than normal. Affected bones may be misshapen and easily broken (fractured).  The classic form of Paget disease of bone typically appears in middle age or later. It usually occurs in one or a few bones and does not spread from one bone to another. Any bones can be affected, although the disease most commonly affects bones in the spine, pelvis, skull, or legs.  Many people with classic Paget disease of bone do not experience any symptoms associated with their bone abnormalities. The disease is often diagnosed unexpectedly by x-rays or laboratory tests done for other reasons. People who develop symptoms are most likely to experience pain. The affected bones may themselves be painful, or pain may be caused by arthritis in nearby joints. Arthritis results when the distortion of bones, particularly weight-bearing bones in the legs, causes extra wear and tear on the joints. Arthritis most frequently affects the knees and hips in people with this disease.  Other complications of Paget disease of bone depend on which bones are affected. If the disease occurs in bones of the skull, it can cause an enlarged head, hearing loss, headaches, and dizziness. If the disease affects bones in the spine, it can lead to numbness and tingling (due to pinched nerves) and abnormal spinal curvature. In the leg bones, the disease can cause bowed legs and difficulty walking.  A rare type of bone cancer called osteosarcoma has been associated with Paget disease of bone. This type of cancer probably occurs in less than 1 in 1,000 people with this disease.  Early-onset Paget disease of bone is a less common form of the disease that appears in a person's teens or twenties. Its features are similar to those of the classic form of the disease, although it is more likely to affect the skull, spine, and ribs (the axial skeleton) and the small bones of the hands. The early-onset form of the disorder is also associated with hearing loss early in life.",Paget disease of bone,0000766,GHR,https://ghr.nlm.nih.gov/condition/paget-disease-of-bone,C0029401,T047,Disorders
How many people are affected by Paget disease of bone ?,0000766-2,frequency,Classic Paget disease of bone occurs in approximately 1 percent of people older than 40 in the United States. Scientists estimate that about 1 million people in this country have the disease. It is most common in people of western European heritage.  Early-onset Paget disease of bone is much rarer. This form of the disorder has been reported in only a few families.,Paget disease of bone,0000766,GHR,https://ghr.nlm.nih.gov/condition/paget-disease-of-bone,C0029401,T047,Disorders
What are the genetic changes related to Paget disease of bone ?,0000766-3,genetic changes,"A combination of genetic and environmental factors likely play a role in causing Paget disease of bone. Researchers have identified changes in several genes that increase the risk of the disorder. Other factors, including infections with certain viruses, may be involved in triggering the disease in people who are at risk. However, the influence of genetic and environmental factors on the development of Paget disease of bone remains unclear.  Researchers have identified variations in three genes that are associated with Paget disease of bone: SQSTM1, TNFRSF11A, and TNFRSF11B. Mutations in the SQSTM1 gene are the most common genetic cause of classic Paget disease of bone, accounting for 10 to 50 percent of cases that run in families and 5 to 30 percent of cases in which there is no family history of the disease. Variations in the TNFRSF11B gene also appear to increase the risk of the classic form of the disorder, particularly in women. TNFRSF11A mutations cause the early-onset form of Paget disease of bone.  The SQSTM1, TNFRSF11A, and TNFRSF11B genes are involved in bone remodeling, a normal process in which old bone is broken down and new bone is created to replace it. Bones are constantly being remodeled, and the process is carefully controlled to ensure that bones stay strong and healthy. Paget disease of bone disrupts the bone remodeling process. Affected bone is broken down abnormally and then replaced much faster than usual. When the new bone tissue grows, it is larger, weaker, and less organized than normal bone. It is unclear why these problems with bone remodeling affect some bones but not others in people with this disease.  Researchers are looking for additional genes that may influence a person's chances of developing Paget disease of bone. Studies suggest that genetic variations in certain regions of chromosome 2, chromosome 5, and chromosome 10 appear to contribute to disease risk. However, the associated genes on these chromosomes have not been identified.",Paget disease of bone,0000766,GHR,https://ghr.nlm.nih.gov/condition/paget-disease-of-bone,C0029401,T047,Disorders
Is Paget disease of bone inherited ?,0000766-4,inheritance,"In 15 to 40 percent of all cases of classic Paget disease of bone, the disorder has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that having one copy of an altered gene in each cell is sufficient to cause the disorder.  In the remaining cases, the inheritance pattern of classic Paget disease of bone is unclear. Many affected people have no family history of the disease, although it sometimes clusters in families. Studies suggest that close relatives of people with classic Paget disease of bone are 7 to 10 times more likely to develop the disease than people without an affected relative.  Early-onset Paget disease of bone is inherited in an autosomal dominant pattern. In people with this form of the disorder, having one altered copy of the TNFRSF11A gene in each cell is sufficient to cause the disease.",Paget disease of bone,0000766,GHR,https://ghr.nlm.nih.gov/condition/paget-disease-of-bone,C0029401,T047,Disorders
What are the treatments for Paget disease of bone ?,0000766-5,treatment,"These resources address the diagnosis or management of Paget disease of bone:  - Genetic Testing Registry: Osteitis deformans  - Genetic Testing Registry: Paget disease of bone 4  - Genetic Testing Registry: Paget disease of bone, familial  - MedlinePlus Encyclopedia: Paget's Disease of the Bone   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Paget disease of bone,0000766,GHR,https://ghr.nlm.nih.gov/condition/paget-disease-of-bone,C0029401,T047,Disorders
What is (are) Pallister-Hall syndrome ?,0000767-1,information,"Pallister-Hall syndrome is a disorder that affects the development of many parts of the body. Most people with this condition have extra fingers and/or toes (polydactyly), and the skin between some fingers or toes may be fused (cutaneous syndactyly). An abnormal growth in the brain called a hypothalamic hamartoma is characteristic of this disorder. In many cases, these growths do not cause any medical problems; however, some hypothalamic hamartomas lead to seizures or hormone abnormalities that can be life-threatening in infancy. Other features of Pallister-Hall syndrome include a malformation of the airway called a bifid epiglottis, an obstruction of the anal opening (imperforate anus), and kidney abnormalities. Although the signs and symptoms of this disorder vary from mild to severe, only a small percentage of affected people have serious complications.",Pallister-Hall syndrome,0000767,GHR,https://ghr.nlm.nih.gov/condition/pallister-hall-syndrome,C0265220,T047,Disorders
How many people are affected by Pallister-Hall syndrome ?,0000767-2,frequency,This condition is very rare; its prevalence is unknown.,Pallister-Hall syndrome,0000767,GHR,https://ghr.nlm.nih.gov/condition/pallister-hall-syndrome,C0265220,T047,Disorders
What are the genetic changes related to Pallister-Hall syndrome ?,0000767-3,genetic changes,"Mutations in the GLI3 gene cause Pallister-Hall syndrome.  The GLI3 gene provides instructions for making a protein that controls gene expression, which is a process that regulates whether genes are turned on or off in particular cells. By interacting with certain genes at specific times during development, the GLI3 protein plays a role in the normal shaping (patterning) of many organs and tissues before birth.  Mutations that cause Pallister-Hall syndrome typically lead to the production of an abnormally short version of the GLI3 protein. Unlike the normal GLI3 protein, which can turn target genes on or off, the short protein can only turn off (repress) target genes. Researchers are working to determine how this change in the protein's function affects early development. It remains uncertain how GLI3 mutations can cause polydactyly, hypothalamic hamartoma, and the other features of Pallister-Hall syndrome.",Pallister-Hall syndrome,0000767,GHR,https://ghr.nlm.nih.gov/condition/pallister-hall-syndrome,C0265220,T047,Disorders
Is Pallister-Hall syndrome inherited ?,0000767-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits a mutation in the GLI3 gene from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",Pallister-Hall syndrome,0000767,GHR,https://ghr.nlm.nih.gov/condition/pallister-hall-syndrome,C0265220,T047,Disorders
What are the treatments for Pallister-Hall syndrome ?,0000767-5,treatment,These resources address the diagnosis or management of Pallister-Hall syndrome:  - Gene Review: Gene Review: Pallister-Hall Syndrome  - Genetic Testing Registry: Pallister-Hall syndrome  - MedlinePlus Encyclopedia: Epiglottis (Image)  - MedlinePlus Encyclopedia: Imperforate Anus  - MedlinePlus Encyclopedia: Polydactyly   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Pallister-Hall syndrome,0000767,GHR,https://ghr.nlm.nih.gov/condition/pallister-hall-syndrome,C0265220,T047,Disorders
What is (are) Pallister-Killian mosaic syndrome ?,0000768-1,information,"Pallister-Killian mosaic syndrome is a developmental disorder that affects many parts of the body. This condition is characterized by extremely weak muscle tone (hypotonia) in infancy and early childhood, intellectual disability, distinctive facial features, sparse hair, areas of unusual skin coloring (pigmentation), and other birth defects.  Most babies with Pallister-Killian mosaic syndrome are born with significant hypotonia, which can cause difficulty breathing and problems with feeding. Hypotonia also interferes with the normal development of motor skills such as sitting, standing, and walking. About 30 percent of affected individuals are ultimately able to walk without assistance. Additional developmental delays result from intellectual disability, which is usually severe to profound. Speech is often limited or absent in people with this condition.  Pallister-Killian mosaic syndrome is associated with a distinctive facial appearance that is often described as ""coarse."" Characteristic facial features include a high, rounded forehead; a broad nasal bridge; a short nose; widely spaced eyes; low-set ears; rounded cheeks; and a wide mouth with a thin upper lip and a large tongue. Some affected children are born with an opening in the roof of the mouth (cleft palate) or a high arched palate.  Most children with Pallister-Killian mosaic syndrome have sparse hair on their heads, particularly around the temples. These areas may fill in as affected children get older. Many affected individuals also have streaks or patches of skin that are darker or lighter than the surrounding skin. These skin changes can occur anywhere on the body, and they may be apparent at birth or occur later in life.  Additional features of Pallister-Killian mosaic syndrome can include hearing loss, vision impairment, seizures, extra nipples, genital abnormalities, and heart defects. Affected individuals may also have skeletal abnormalities such as extra fingers and/or toes, large big toes (halluces), and unusually short arms and legs. About 40 percent of affected infants are born with a congenital diaphragmatic hernia, which is a hole in the muscle that separates the abdomen from the chest cavity (the diaphragm). This potentially serious birth defect allows the stomach and intestines to move into the chest, where they can crowd the developing heart and lungs.  The signs and symptoms of Pallister-Killian mosaic syndrome vary, although most people with this disorder have severe to profound intellectual disability and other serious health problems. The most severe cases involve birth defects that are life-threatening in early infancy. However, several affected people have had milder features, including mild intellectual disability and less noticeable physical abnormalities.",Pallister-Killian mosaic syndrome,0000768,GHR,https://ghr.nlm.nih.gov/condition/pallister-killian-mosaic-syndrome,C0265449,T019,Disorders
How many people are affected by Pallister-Killian mosaic syndrome ?,0000768-2,frequency,"Pallister-Killian mosaic syndrome appears to be a rare condition, although its exact prevalence is unknown. This disorder may be underdiagnosed because it can be difficult to detect in people with mild signs and symptoms. As a result, most diagnoses are made in children with more severe features of the disorder. More than 150 people with Pallister-Killian mosaic syndrome have been reported in the medical literature.",Pallister-Killian mosaic syndrome,0000768,GHR,https://ghr.nlm.nih.gov/condition/pallister-killian-mosaic-syndrome,C0265449,T019,Disorders
What are the genetic changes related to Pallister-Killian mosaic syndrome ?,0000768-3,genetic changes,"Pallister-Killian mosaic syndrome is usually caused by the presence of an abnormal extra chromosome called an isochromosome 12p or i(12p). An isochromosome is a chromosome with two identical arms. Normal chromosomes have one long (q) arm and one short (p) arm, but isochromosomes have either two q arms or two p arms. Isochromosome 12p is a version of chromosome 12 made up of two p arms.  Cells normally have two copies of each chromosome, one inherited from each parent. In people with Pallister-Killian mosaic syndrome, cells have the two usual copies of chromosome 12, but some cells also have the isochromosome 12p. These cells have a total of four copies of all the genes on the p arm of chromosome 12. The extra genetic material from the isochromosome disrupts the normal course of development, causing the characteristic features of this disorder.  Although Pallister-Killian mosaic syndrome is usually caused by the presence of an isochromosome 12p, other, more complex chromosomal changes involving chromosome 12 are responsible for the disorder in rare cases.",Pallister-Killian mosaic syndrome,0000768,GHR,https://ghr.nlm.nih.gov/condition/pallister-killian-mosaic-syndrome,C0265449,T019,Disorders
Is Pallister-Killian mosaic syndrome inherited ?,0000768-4,inheritance,"Pallister-Killian mosaic syndrome is not inherited. The chromosomal change responsible for the disorder typically occurs as a random event during the formation of reproductive cells (eggs or sperm) in a parent of the affected individual, usually the mother. Affected individuals have no history of the disorder in their families.  An error in cell division called nondisjunction likely results in a reproductive cell containing an isochromosome 12p. If this atypical reproductive cell contributes to the genetic makeup of a child, the child will have two normal copies of chromosome 12 along with an isochromosome 12p.  As cells divide during early development, some cells lose the isochromosome 12p, while other cells retain the abnormal chromosome. This situation is called mosaicism. Almost all cases of Pallister-Killian mosaic syndrome are caused by mosaicism for an isochromosome 12p. If all of the body's cells contained the isochromosome, the resulting syndrome would probably not be compatible with life.",Pallister-Killian mosaic syndrome,0000768,GHR,https://ghr.nlm.nih.gov/condition/pallister-killian-mosaic-syndrome,C0265449,T019,Disorders
What are the treatments for Pallister-Killian mosaic syndrome ?,0000768-5,treatment,These resources address the diagnosis or management of Pallister-Killian mosaic syndrome:  - Genetic Testing Registry: Pallister-Killian syndrome  - MedlinePlus Encyclopedia: Chromosome  - MedlinePlus Encyclopedia: Mosaicism   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Pallister-Killian mosaic syndrome,0000768,GHR,https://ghr.nlm.nih.gov/condition/pallister-killian-mosaic-syndrome,C0265449,T019,Disorders
What is (are) palmoplantar keratoderma with deafness ?,0000769-1,information,"Palmoplantar keratoderma with deafness is a disorder characterized by skin abnormalities and hearing loss. Affected individuals develop unusually thick skin on the palms of the hands and soles of the feet (palmoplantar keratoderma) beginning in childhood. Hearing loss ranges from mild to profound. It begins in early childhood and gets worse over time. Affected individuals have particular trouble hearing high-pitched sounds.  The signs and symptoms of this disorder may vary even within the same family, with some individuals developing only skin abnormalities and others developing only hearing loss.",palmoplantar keratoderma with deafness,0000769,GHR,https://ghr.nlm.nih.gov/condition/palmoplantar-keratoderma-with-deafness,C1835672,T047,Disorders
How many people are affected by palmoplantar keratoderma with deafness ?,0000769-2,frequency,Palmoplantar keratoderma with deafness is a rare disorder; its prevalence is unknown. At least 10 affected families have been identified.,palmoplantar keratoderma with deafness,0000769,GHR,https://ghr.nlm.nih.gov/condition/palmoplantar-keratoderma-with-deafness,C1835672,T047,Disorders
What are the genetic changes related to palmoplantar keratoderma with deafness ?,0000769-3,genetic changes,"Palmoplantar keratoderma with deafness can be caused by mutations in the GJB2 or MT-TS1 genes.  The GJB2 gene provides instructions for making a protein called gap junction beta 2, more commonly known as connexin 26. Connexin 26 is a member of the connexin protein family. Connexin proteins form channels called gap junctions that permit the transport of nutrients, charged atoms (ions), and signaling molecules between neighboring cells that are in contact with each other. Gap junctions made with connexin 26 transport potassium ions and certain small molecules.  Connexin 26 is found in cells throughout the body, including the inner ear and the skin. In the inner ear, channels made from connexin 26 are found in a snail-shaped structure called the cochlea. These channels may help to maintain the proper level of potassium ions required for the conversion of sound waves to electrical nerve impulses. This conversion is essential for normal hearing. In addition, connexin 26 may be involved in the maturation of certain cells in the cochlea. Connexin 26 also plays a role in the growth, maturation, and stability of the outermost layer of skin (the epidermis).  The GJB2 gene mutations that cause palmoplantar keratoderma with deafness change single protein building blocks (amino acids) in connexin 26. The altered protein probably disrupts the function of normal connexin 26 in cells, and may interfere with the function of other connexin proteins. This disruption could affect skin growth and also impair hearing by disturbing the conversion of sound waves to nerve impulses.  Palmoplantar keratoderma with deafness can also be caused by a mutation in the MT-TS1 gene. This gene provides instructions for making a particular type of RNA, a molecule that is a chemical cousin of DNA. This type of RNA, called transfer RNA (tRNA), helps assemble amino acids into full-length, functioning proteins. The MT-TS1 gene provides instructions for a specific form of tRNA that is designated as tRNASer(UCN). This molecule attaches to a particular amino acid, serine (Ser), and inserts it into the appropriate locations in many different proteins.  The tRNASer(UCN) molecule is present only in cellular structures called mitochondria. These structures convert energy from food into a form that cells can use. Through a process called oxidative phosphorylation, mitochondria use oxygen, simple sugars, and fatty acids to create adenosine triphosphate (ATP), the cell's main energy source. The tRNASer(UCN) molecule is involved in the assembly of proteins that carry out oxidative phosphorylation.  The MT-TS1 gene mutation that causes palmoplantar keratoderma with deafness leads to reduced levels of tRNASer(UCN) to assemble proteins within mitochondria. Reduced production of proteins needed for oxidative phosphorylation may impair the ability of mitochondria to make ATP. Researchers have not determined why the effects of the mutation are limited to cells in the inner ear and the skin in this condition.",palmoplantar keratoderma with deafness,0000769,GHR,https://ghr.nlm.nih.gov/condition/palmoplantar-keratoderma-with-deafness,C1835672,T047,Disorders
Is palmoplantar keratoderma with deafness inherited ?,0000769-4,inheritance,"Palmoplantar keratoderma with deafness can have different inheritance patterns. When this disorder is caused by GJB2 gene mutations, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  When palmoplantar keratoderma with deafness is caused by mutations in the MT-TS1 gene, it is inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mitochondrial DNA (mtDNA). Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children.",palmoplantar keratoderma with deafness,0000769,GHR,https://ghr.nlm.nih.gov/condition/palmoplantar-keratoderma-with-deafness,C1835672,T047,Disorders
What are the treatments for palmoplantar keratoderma with deafness ?,0000769-5,treatment,These resources address the diagnosis or management of palmoplantar keratoderma with deafness:  - Foundation for Ichthyosis and Related Skin Types: Palmoplantar Keratodermas  - Genetic Testing Registry: Keratoderma palmoplantar deafness   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,palmoplantar keratoderma with deafness,0000769,GHR,https://ghr.nlm.nih.gov/condition/palmoplantar-keratoderma-with-deafness,C1835672,T047,Disorders
What is (are) pantothenate kinase-associated neurodegeneration ?,0000770-1,information,"Pantothenate kinase-associated neurodegeneration (formerly called Hallervorden-Spatz syndrome) is a disorder of the nervous system. This condition is characterized by progressive difficulty with movement, typically beginning in childhood. Movement abnormalities include involuntary muscle spasms, rigidity, and trouble with walking that worsens over time. Many people with this condition also develop problems with speech (dysarthria), and some develop vision loss. Additionally, affected individuals may experience a loss of intellectual function (dementia) and psychiatric symptoms such as behavioral problems, personality changes, and depression.  Pantothenate kinase-associated neurodegeneration is characterized by an abnormal buildup of iron in certain areas of the brain. A particular change called the eye-of-the-tiger sign, which indicates an accumulation of iron, is typically seen on magnetic resonance imaging (MRI) scans of the brain in people with this disorder.  Researchers have described classic and atypical forms of pantothenate kinase-associated neurodegeneration. The classic form usually appears in early childhood, causing severe problems with movement that worsen rapidly. Features of the atypical form appear later in childhood or adolescence and progress more slowly. Signs and symptoms vary, but the atypical form is more likely than the classic form to involve speech defects and psychiatric problems.  A condition called HARP (hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration), which was historically described as a separate syndrome, is now considered part of pantothenate kinase-associated neurodegeneration. Although HARP is much rarer than classic pantothenate kinase-associated neurodegeneration, both conditions involve problems with movement, dementia, and vision abnormalities.",pantothenate kinase-associated neurodegeneration,0000770,GHR,https://ghr.nlm.nih.gov/condition/pantothenate-kinase-associated-neurodegeneration,C0027746,T049,Disorders
How many people are affected by pantothenate kinase-associated neurodegeneration ?,0000770-2,frequency,The precise incidence of this condition is unknown. It is estimated to affect 1 to 3 per million people worldwide.,pantothenate kinase-associated neurodegeneration,0000770,GHR,https://ghr.nlm.nih.gov/condition/pantothenate-kinase-associated-neurodegeneration,C0027746,T049,Disorders
What are the genetic changes related to pantothenate kinase-associated neurodegeneration ?,0000770-3,genetic changes,"Mutations in the PANK2 gene cause pantothenate kinase-associated neurodegeneration.  The PANK2 gene provides instructions for making an enzyme called pantothenate kinase 2. This enzyme is active in mitochondria, the energy-producing centers within cells, where it plays a critical role in the formation of a molecule called coenzyme A. Found in all living cells, coenzyme A is essential for the body's production of energy from carbohydrates, fats, and some protein building blocks (amino acids).  Mutations in the PANK2 gene likely result in the production of an abnormal version of pantothenate kinase 2 or prevent cells from making any of this enzyme. A lack of functional pantothenate kinase 2 disrupts the production of coenzyme A and allows potentially harmful compounds to build up in the brain. This buildup leads to swelling and tissue damage, and allows iron to accumulate abnormally in certain parts of the brain. Researchers have not determined how these changes result in the specific features of pantothenate kinase-associated neurodegeneration. Because pantothenate kinase 2 functions in mitochondria, the signs and symptoms of this condition may be related to impaired energy production.",pantothenate kinase-associated neurodegeneration,0000770,GHR,https://ghr.nlm.nih.gov/condition/pantothenate-kinase-associated-neurodegeneration,C0027746,T049,Disorders
Is pantothenate kinase-associated neurodegeneration inherited ?,0000770-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",pantothenate kinase-associated neurodegeneration,0000770,GHR,https://ghr.nlm.nih.gov/condition/pantothenate-kinase-associated-neurodegeneration,C0027746,T049,Disorders
What are the treatments for pantothenate kinase-associated neurodegeneration ?,0000770-5,treatment,"These resources address the diagnosis or management of pantothenate kinase-associated neurodegeneration:  - Gene Review: Gene Review: Pantothenate Kinase-Associated Neurodegeneration  - Genetic Testing Registry: Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration  - MedlinePlus Encyclopedia: Hallervorden-Spatz Disease  - MedlinePlus Encyclopedia: MRI   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",pantothenate kinase-associated neurodegeneration,0000770,GHR,https://ghr.nlm.nih.gov/condition/pantothenate-kinase-associated-neurodegeneration,C0027746,T049,Disorders
What is (are) paramyotonia congenita ?,0000771-1,information,"Paramyotonia congenita is a disorder that affects muscles used for movement (skeletal muscles). Beginning in infancy or early childhood, people with this condition experience bouts of sustained muscle tensing (myotonia) that prevent muscles from relaxing normally. Myotonia causes muscle stiffness that typically appears after exercise and can be induced by muscle cooling. This stiffness chiefly affects muscles in the face, neck, arms, and hands, although it can also affect muscles used for breathing and muscles in the lower body. Unlike many other forms of myotonia, the muscle stiffness associated with paramyotonia congenita tends to worsen with repeated movements.  Most peopleeven those without muscle diseasefeel that their muscles do not work as well when they are cold. This effect is dramatic in people with paramyotonia congenita. Exposure to cold initially causes muscle stiffness in these individuals, and prolonged cold exposure leads to temporary episodes of mild to severe muscle weakness that may last for several hours at a time. Some older people with paramyotonia congenita develop permanent muscle weakness that can be disabling.",paramyotonia congenita,0000771,GHR,https://ghr.nlm.nih.gov/condition/paramyotonia-congenita,C0221055,T047,Disorders
How many people are affected by paramyotonia congenita ?,0000771-2,frequency,"Paramyotonia congenita is an uncommon disorder; it is estimated to affect fewer than 1 in 100,000 people.",paramyotonia congenita,0000771,GHR,https://ghr.nlm.nih.gov/condition/paramyotonia-congenita,C0221055,T047,Disorders
What are the genetic changes related to paramyotonia congenita ?,0000771-3,genetic changes,"Mutations in the SCN4A gene cause paramyotonia congenita. This gene provides instructions for making a protein that is critical for the normal function of skeletal muscle cells. For the body to move normally, skeletal muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of positively charged atoms (ions), including sodium, into skeletal muscle cells. The SCN4A protein forms channels that control the flow of sodium ions into these cells.  Mutations in the SCN4A gene alter the usual structure and function of sodium channels. The altered channels cannot effectively regulate the flow of sodium ions into skeletal muscle cells. The resulting increase in ion flow interferes with normal muscle contraction and relaxation, leading to episodes of muscle stiffness and weakness.",paramyotonia congenita,0000771,GHR,https://ghr.nlm.nih.gov/condition/paramyotonia-congenita,C0221055,T047,Disorders
Is paramyotonia congenita inherited ?,0000771-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In many cases, an affected person has one parent with the condition.",paramyotonia congenita,0000771,GHR,https://ghr.nlm.nih.gov/condition/paramyotonia-congenita,C0221055,T047,Disorders
What are the treatments for paramyotonia congenita ?,0000771-5,treatment,These resources address the diagnosis or management of paramyotonia congenita:  - Genetic Testing Registry: Paramyotonia congenita of von Eulenburg  - Periodic Paralysis International: How is Periodic Paralysis Diagnosed?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,paramyotonia congenita,0000771,GHR,https://ghr.nlm.nih.gov/condition/paramyotonia-congenita,C0221055,T047,Disorders
What is (are) Parkes Weber syndrome ?,0000772-1,information,"Parkes Weber syndrome is a disorder of the vascular system, which is the body's complex network of blood vessels. The vascular system consists of arteries, which carry oxygen-rich blood from the heart to the body's various organs and tissues; veins, which carry blood back to the heart; and capillaries, which are tiny blood vessels that connect arteries and veins.  Parkes Weber syndrome is characterized by vascular abnormalities known as capillary malformations and arteriovenous fistulas (AVFs), which are present from birth. The capillary malformations increase blood flow near the surface of the skin. They usually look like large, flat, pink stains on the skin, and because of their color are sometimes called ""port-wine stains."" In people with Parkes Weber syndrome, capillary malformations occur together with multiple micro-AVFs, which are tiny abnormal connections between arteries and veins that affect blood circulation. These AVFs can be associated with life-threatening complications including abnormal bleeding and heart failure.  Another characteristic feature of Parkes Weber syndrome is overgrowth of one limb, most commonly a leg. Abnormal growth occurs in bones and soft tissues, making one of the limbs longer and larger around than the corresponding one.  Some vascular abnormalities seen in Parkes Weber syndrome are similar to those that occur in a condition called capillary malformation-arteriovenous malformation syndrome (CM-AVM). CM-AVM and some cases of Parkes Weber syndrome have the same genetic cause.",Parkes Weber syndrome,0000772,GHR,https://ghr.nlm.nih.gov/condition/parkes-weber-syndrome,C0022739,T019,Disorders
How many people are affected by Parkes Weber syndrome ?,0000772-2,frequency,Parkes Weber syndrome is a rare condition; its exact prevalence is unknown.,Parkes Weber syndrome,0000772,GHR,https://ghr.nlm.nih.gov/condition/parkes-weber-syndrome,C0022739,T019,Disorders
What are the genetic changes related to Parkes Weber syndrome ?,0000772-3,genetic changes,"Some cases of Parkes Weber syndrome result from mutations in the RASA1 gene. When the condition is caused by RASA1 gene mutations, affected individuals usually have multiple capillary malformations. People with Parkes Weber syndrome who do not have multiple capillary malformations are unlikely to have mutations in the RASA1 gene; in these cases, the cause of the condition is often unknown.  The RASA1 gene provides instructions for making a protein known as p120-RasGAP, which is involved in transmitting chemical signals from outside the cell to the nucleus. These signals help control several important cell functions, including the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), and cell movement. The role of the p120-RasGAP protein is not fully understood, although it appears to be essential for the normal development of the vascular system.  Mutations in the RASA1 gene lead to the production of a nonfunctional version of the p120-RasGAP protein. A loss of this protein's activity disrupts tightly regulated chemical signaling during development. However, it is unclear how these changes lead to the specific vascular abnormalities and limb overgrowth seen in people with Parkes Weber syndrome.",Parkes Weber syndrome,0000772,GHR,https://ghr.nlm.nih.gov/condition/parkes-weber-syndrome,C0022739,T019,Disorders
Is Parkes Weber syndrome inherited ?,0000772-4,inheritance,"Most cases of Parkes Weber syndrome occur in people with no history of the condition in their family. These cases are described as sporadic.  When Parkes Weber syndrome is caused by mutations in the RASA1 gene, it is sometimes inherited from an affected parent. In these cases, the condition has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder.",Parkes Weber syndrome,0000772,GHR,https://ghr.nlm.nih.gov/condition/parkes-weber-syndrome,C0022739,T019,Disorders
What are the treatments for Parkes Weber syndrome ?,0000772-5,treatment,These resources address the diagnosis or management of Parkes Weber syndrome:  - Gene Review: Gene Review: RASA1-Related Disorders  - Genetic Testing Registry: Parkes Weber syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Parkes Weber syndrome,0000772,GHR,https://ghr.nlm.nih.gov/condition/parkes-weber-syndrome,C0022739,T019,Disorders
What is (are) Parkinson disease ?,0000773-1,information,"Parkinson disease is a progressive disorder of the nervous system. The disorder affects several regions of the brain, especially an area called the substantia nigra that controls balance and movement.  Often the first symptom of Parkinson disease is trembling or shaking (tremor) of a limb, especially when the body is at rest. Typically, the tremor begins on one side of the body, usually in one hand. Tremors can also affect the arms, legs, feet, and face. Other characteristic symptoms of Parkinson disease include rigidity or stiffness of the limbs and torso, slow movement (bradykinesia) or an inability to move (akinesia), and impaired balance and coordination (postural instability). These symptoms worsen slowly over time.  Parkinson disease can also affect emotions and thinking ability (cognition). Some affected individuals develop psychiatric conditions such as depression and visual hallucinations. People with Parkinson disease also have an increased risk of developing dementia, which is a decline in intellectual functions including judgment and memory.  Generally, Parkinson disease that begins after age 50 is called late-onset disease. The condition is described as early-onset disease if signs and symptoms begin before age 50. Early-onset cases that begin before age 20 are sometimes referred to as juvenile-onset Parkinson disease.",Parkinson disease,0000773,GHR,https://ghr.nlm.nih.gov/condition/parkinson-disease,C0030567,T047,Disorders
How many people are affected by Parkinson disease ?,0000773-2,frequency,"Parkinson disease affects more than 1 million people in North America and more than 4 million people worldwide. In the United States, Parkinson disease occurs in approximately 13 per 100,000 people, and about 60,000 new cases are identified each year.  The late-onset form is the most common type of Parkinson disease, and the risk of developing this condition increases with age. Because more people are living longer, the number of people with this disease is expected to increase in coming decades.",Parkinson disease,0000773,GHR,https://ghr.nlm.nih.gov/condition/parkinson-disease,C0030567,T047,Disorders
What are the genetic changes related to Parkinson disease ?,0000773-3,genetic changes,"Most cases of Parkinson disease probably result from a complex interaction of environmental and genetic factors. These cases are classified as sporadic and occur in people with no apparent history of the disorder in their family. The cause of these sporadic cases remains unclear.  Approximately 15 percent of people with Parkinson disease have a family history of this disorder. Familial cases of Parkinson disease can be caused by mutations in the LRRK2, PARK2, PARK7, PINK1, or SNCA gene, or by alterations in genes that have not been identified. Mutations in some of these genes may also play a role in cases that appear to be sporadic (not inherited).  Alterations in certain genes, including GBA and UCHL1, do not cause Parkinson disease but appear to modify the risk of developing the condition in some families. Variations in other genes that have not been identified probably also contribute to Parkinson disease risk.  It is not fully understood how genetic changes cause Parkinson disease or influence the risk of developing the disorder. Many Parkinson disease symptoms occur when nerve cells (neurons) in the substantia nigra die or become impaired. Normally, these cells produce a chemical messenger called dopamine, which transmits signals within the brain to produce smooth physical movements. When these dopamine-producing neurons are damaged or die, communication between the brain and muscles weakens. Eventually, the brain becomes unable to control muscle movement.  Some gene mutations appear to disturb the cell machinery that breaks down (degrades) unwanted proteins in dopamine-producing neurons. As a result, undegraded proteins accumulate, leading to the impairment or death of these cells. Other mutations may affect the function of mitochondria, the energy-producing structures within cells. As a byproduct of energy production, mitochondria make unstable molecules called free radicals that can damage cells. Cells normally counteract the effects of free radicals before they cause damage, but mutations can disrupt this process. As a result, free radicals may accumulate and impair or kill dopamine-producing neurons.  In most cases of Parkinson disease, protein deposits called Lewy bodies appear in dead or dying dopamine-producing neurons. (When Lewy bodies are not present, the condition is sometimes referred to as parkinsonism.) It is unclear whether Lewy bodies play a role in killing nerve cells or if they are part of the cells' response to the disease.",Parkinson disease,0000773,GHR,https://ghr.nlm.nih.gov/condition/parkinson-disease,C0030567,T047,Disorders
Is Parkinson disease inherited ?,0000773-4,inheritance,"Most cases of Parkinson disease occur in people with no apparent family history of the disorder. These sporadic cases may not be inherited, or they may have an inheritance pattern that is unknown.  Among familial cases of Parkinson disease, the inheritance pattern differs depending on the gene that is altered. If the LRRK2 or SNCA gene is involved, the disorder is inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.  If the PARK2, PARK7, or PINK1 gene is involved, Parkinson disease is inherited in an autosomal recessive pattern. This type of inheritance means that two copies of the gene in each cell are altered. Most often, the parents of an individual with autosomal recessive Parkinson disease each carry one copy of the altered gene but do not show signs and symptoms of the disorder.  When genetic alterations modify the risk of developing Parkinson disease, the inheritance pattern is usually unknown.",Parkinson disease,0000773,GHR,https://ghr.nlm.nih.gov/condition/parkinson-disease,C0030567,T047,Disorders
What are the treatments for Parkinson disease ?,0000773-5,treatment,"These resources address the diagnosis or management of Parkinson disease:  - Gene Review: Gene Review: Parkinson Disease Overview  - Genetic Testing Registry: Parkinson disease 1  - Genetic Testing Registry: Parkinson disease 10  - Genetic Testing Registry: Parkinson disease 11  - Genetic Testing Registry: Parkinson disease 12  - Genetic Testing Registry: Parkinson disease 13  - Genetic Testing Registry: Parkinson disease 14  - Genetic Testing Registry: Parkinson disease 15  - Genetic Testing Registry: Parkinson disease 16  - Genetic Testing Registry: Parkinson disease 17  - Genetic Testing Registry: Parkinson disease 18  - Genetic Testing Registry: Parkinson disease 2  - Genetic Testing Registry: Parkinson disease 3  - Genetic Testing Registry: Parkinson disease 4  - Genetic Testing Registry: Parkinson disease 5  - Genetic Testing Registry: Parkinson disease 6, autosomal recessive early-onset  - Genetic Testing Registry: Parkinson disease 7  - Genetic Testing Registry: Parkinson disease 8, autosomal dominant  - Genetic Testing Registry: Parkinson disease, late-onset  - Genetic Testing Registry: Parkinson disease, mitochondrial  - MedlinePlus Encyclopedia: Parkinson's Disease  - Michael J. Fox Foundation for Parkinson's Research: What Drugs Are Used to Treat Parkinson's Disease and How Do They Work?  - National Institute of Neurological Disorders and Stroke: Deep Brain Stimulation for Parkinson's Disease  - Parkinson's Disease Foundation: Diagnosis  - Parkinson's Disease Foundation: Medications & Treatments   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Parkinson disease,0000773,GHR,https://ghr.nlm.nih.gov/condition/parkinson-disease,C0030567,T047,Disorders
What is (are) paroxysmal extreme pain disorder ?,0000774-1,information,"Paroxysmal extreme pain disorder is a condition characterized by skin redness and warmth (flushing) and attacks of severe pain in various parts of the body. The area of flushing typically corresponds to the site of the pain. The pain attacks experienced by people with paroxysmal extreme pain disorder usually last seconds to minutes, but in some cases can last hours. These attacks can start as early as infancy. Early in life, the pain is typically concentrated in the lower part of the body, especially around the rectum, and is usually triggered by a bowel movement. Some children may develop constipation, which is thought to be due to fear of triggering a pain attack. Pain attacks in these young children may also be accompanied by seizures, slow heartbeat, or short pauses in breathing (apnea).  As a person with paroxysmal extreme pain disorder ages, the location of pain changes. Pain attacks switch from affecting the lower body to affecting the head and face, especially the eyes and jaw. Triggers of these pain attacks include changes in temperature (such as a cold wind) and emotional distress as well as eating spicy foods and drinking cold drinks.  Paroxysmal extreme pain disorder is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and pain.",paroxysmal extreme pain disorder,0000774,GHR,https://ghr.nlm.nih.gov/condition/paroxysmal-extreme-pain-disorder,C1833661,T047,Disorders
How many people are affected by paroxysmal extreme pain disorder ?,0000774-2,frequency,Paroxysmal extreme pain disorder is a rare condition; approximately 80 affected individuals have been described in the scientific literature.,paroxysmal extreme pain disorder,0000774,GHR,https://ghr.nlm.nih.gov/condition/paroxysmal-extreme-pain-disorder,C1833661,T047,Disorders
What are the genetic changes related to paroxysmal extreme pain disorder ?,0000774-3,genetic changes,"Mutations in the SCN9A gene cause paroxysmal extreme pain disorder. The SCN9A gene provides instructions for making one part (the alpha subunit) of a sodium channel called NaV1.7. Sodium channels transport positively charged sodium atoms (sodium ions) into cells and play a key role in a cell's ability to generate and transmit electrical signals. NaV1.7 sodium channels are found in nerve cells called nociceptors that transmit pain signals to the spinal cord and brain.  The SCN9A gene mutations that cause paroxysmal extreme pain disorder result in NaV1.7 sodium channels that do not close completely when it is turned off, allowing sodium ions to flow abnormally into nociceptors. This increase in sodium ions enhances transmission of pain signals, leading to the pain attacks experienced by people with paroxysmal extreme pain disorder. It is unknown why the pain attacks associated with this condition change location over time or what causes the other features of this condition such as seizures and changes in breathing.",paroxysmal extreme pain disorder,0000774,GHR,https://ghr.nlm.nih.gov/condition/paroxysmal-extreme-pain-disorder,C1833661,T047,Disorders
Is paroxysmal extreme pain disorder inherited ?,0000774-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",paroxysmal extreme pain disorder,0000774,GHR,https://ghr.nlm.nih.gov/condition/paroxysmal-extreme-pain-disorder,C1833661,T047,Disorders
What are the treatments for paroxysmal extreme pain disorder ?,0000774-5,treatment,These resources address the diagnosis or management of paroxysmal extreme pain disorder:  - Genetic Testing Registry: Paroxysmal extreme pain disorder   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,paroxysmal extreme pain disorder,0000774,GHR,https://ghr.nlm.nih.gov/condition/paroxysmal-extreme-pain-disorder,C1833661,T047,Disorders
What is (are) paroxysmal nocturnal hemoglobinuria ?,0000775-1,information,"Paroxysmal nocturnal hemoglobinuria is an acquired disorder that leads to the premature death and impaired production of blood cells. The disorder affects red blood cells (erythrocytes), which carry oxygen; white blood cells (leukocytes), which protect the body from infection; and platelets (thrombocytes), which are involved in blood clotting. Paroxysmal nocturnal hemoglobinuria affects both sexes equally, and can occur at any age, although it is most often diagnosed in young adulthood.  People with paroxysmal nocturnal hemoglobinuria have sudden, recurring episodes of symptoms (paroxysmal symptoms), which may be triggered by stresses on the body, such as infections or physical exertion. During these episodes, red blood cells are prematurely destroyed (hemolysis). Affected individuals may pass dark-colored urine due to the presence of hemoglobin, the oxygen-carrying protein in blood. The abnormal presence of hemoglobin in the urine is called hemoglobinuria. In many, but not all cases, hemoglobinuria is most noticeable in the morning, upon passing urine that has accumulated in the bladder during the night (nocturnal).  The premature destruction of red blood cells results in a deficiency of these cells in the blood (hemolytic anemia), which can cause signs and symptoms such as fatigue, weakness, abnormally pale skin (pallor), shortness of breath, and an increased heart rate. People with paroxysmal nocturnal hemoglobinuria may also be prone to infections due to a deficiency of white blood cells.  Abnormal platelets associated with paroxysmal nocturnal hemoglobinuria can cause problems in the blood clotting process. As a result, people with this disorder may experience abnormal blood clotting (thrombosis), especially in large abdominal veins; or, less often, episodes of severe bleeding (hemorrhage).  Individuals with paroxysmal nocturnal hemoglobinuria are at increased risk of developing cancer in blood-forming cells (leukemia).  In some cases, people who have been treated for another blood disease called aplastic anemia may develop paroxysmal nocturnal hemoglobinuria.",paroxysmal nocturnal hemoglobinuria,0000775,GHR,https://ghr.nlm.nih.gov/condition/paroxysmal-nocturnal-hemoglobinuria,C0024790,T047,Disorders
How many people are affected by paroxysmal nocturnal hemoglobinuria ?,0000775-2,frequency,"Paroxysmal nocturnal hemoglobinuria is a rare disorder, estimated to affect between 1 and 5 per million people.",paroxysmal nocturnal hemoglobinuria,0000775,GHR,https://ghr.nlm.nih.gov/condition/paroxysmal-nocturnal-hemoglobinuria,C0024790,T047,Disorders
What are the genetic changes related to paroxysmal nocturnal hemoglobinuria ?,0000775-3,genetic changes,"Mutations in the PIGA gene cause paroxysmal nocturnal hemoglobinuria.  The PIGA gene provides instructions for making a protein called phosphatidylinositol glycan class A. This protein takes part in a series of steps that produce a molecule called GPI anchor. GPI anchor attaches many different proteins to the cell membrane, thereby ensuring that these proteins are available when needed at the surface of the cell.  Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are called somatic mutations, are not inherited. In people with paroxysmal nocturnal hemoglobinuria, somatic mutations of the PIGA gene occur in blood-forming cells called hematopoietic stem cells, which are found mainly in the bone marrow. These mutations result in the production of abnormal blood cells. As the abnormal hematopoietic stem cells multiply, increasing numbers of abnormal blood cells are formed, alongside normal blood cells produced by normal hematopoietic stem cells.  The premature destruction of red blood cells seen in paroxysmal nocturnal hemoglobinuria is caused by a component of the immune system called complement. Complement consists of a group of proteins that work together to destroy foreign invaders such as bacteria and viruses. To protect the individual's own cells from being destroyed, this process is tightly controlled by complement-regulating proteins. Complement-regulating proteins normally protect red blood cells from destruction by complement. In people with paroxysmal nocturnal hemoglobinuria, however, abnormal red blood cells are missing two important complement-regulating proteins that need the GPI anchor protein to attach them to the cell membrane. These red blood cells are prematurely destroyed, leading to hemolytic anemia.  Research suggests that certain abnormal white blood cells that are also part of the immune system may mistakenly attack normal blood-forming cells, in a malfunction called an autoimmune process. In addition, abnormal hematopoietic stem cells in people with paroxysmal nocturnal hemoglobinuria may be less susceptible than normal cells to a process called apoptosis, which causes cells to self-destruct when they are damaged or unneeded. These features of the disorder may increase the proportion of abnormal blood cells in the body. The proportion of abnormal blood cells affects the severity of the signs and symptoms of paroxysmal nocturnal hemoglobinuria, including the risk of hemoglobinuria and thrombosis.",paroxysmal nocturnal hemoglobinuria,0000775,GHR,https://ghr.nlm.nih.gov/condition/paroxysmal-nocturnal-hemoglobinuria,C0024790,T047,Disorders
Is paroxysmal nocturnal hemoglobinuria inherited ?,0000775-4,inheritance,"This condition is acquired, rather than inherited. It results from new mutations in the PIGA gene, and generally occurs in people with no previous history of the disorder in their family. The condition is not passed down to children of affected individuals.",paroxysmal nocturnal hemoglobinuria,0000775,GHR,https://ghr.nlm.nih.gov/condition/paroxysmal-nocturnal-hemoglobinuria,C0024790,T047,Disorders
What are the treatments for paroxysmal nocturnal hemoglobinuria ?,0000775-5,treatment,These resources address the diagnosis or management of paroxysmal nocturnal hemoglobinuria:  - Duke University School of Medicine: Hemostasis & Thrombosis Center  - Genetic Testing Registry: Paroxysmal nocturnal hemoglobinuria  - MedlinePlus Encyclopedia: Paroxysmal nocturnal hemoglobinuria (PNH)  - Memorial Sloan-Kettering Cancer Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,paroxysmal nocturnal hemoglobinuria,0000775,GHR,https://ghr.nlm.nih.gov/condition/paroxysmal-nocturnal-hemoglobinuria,C0024790,T047,Disorders
What is (are) Partington syndrome ?,0000776-1,information,"Partington syndrome is a neurological disorder that causes intellectual disability along with a condition called focal dystonia that particularly affects movement of the hands. Partington syndrome usually occurs in males; when it occurs in females, the signs and symptoms are often less severe.  The intellectual disability associated with Partington syndrome usually ranges from mild to moderate. Some affected individuals have characteristics of autism spectrum disorders that affect communication and social interaction. Recurrent seizures (epilepsy) may also occur in Partington syndrome.  Focal dystonia of the hands is a feature that distinguishes Partington syndrome from other intellectual disability syndromes. Dystonias are a group of movement problems characterized by involuntary, sustained muscle contractions; tremors; and other uncontrolled movements. The term ""focal"" refers to a type of dystonia that affects a single part of the body, in this case the hands. In Partington syndrome, focal dystonia of the hands, which is called the Partington sign, begins in early childhood and gradually gets worse. This condition typically causes difficulty with grasping movements or using a pen or pencil.  People with Partington syndrome may also have dystonia affecting other parts of the body; dystonia affecting the muscles in the face and those involved in speech may cause impaired speech (dysarthria). People with this disorder may also have an awkward way of walking (gait). Signs and symptoms can vary widely, even within the same family.",Partington syndrome,0000776,GHR,https://ghr.nlm.nih.gov/condition/partington-syndrome,C0220775,T047,Disorders
How many people are affected by Partington syndrome ?,0000776-2,frequency,The prevalence of Partington syndrome is unknown. About 20 cases have been described in the medical literature.,Partington syndrome,0000776,GHR,https://ghr.nlm.nih.gov/condition/partington-syndrome,C0220775,T047,Disorders
What are the genetic changes related to Partington syndrome ?,0000776-3,genetic changes,"Partington syndrome is caused by mutations in the ARX gene. This gene provides instructions for producing a protein that regulates the activity of other genes. Within the developing brain, the ARX protein is involved with movement (migration) and communication of nerve cells (neurons). In particular, this protein regulates genes that play a role in the migration of specialized neurons (interneurons) to their proper location. Interneurons relay signals between other neurons.  The normal ARX protein contains four regions where a protein building block (amino acid) called alanine is repeated multiple times. These stretches of alanines are known as polyalanine tracts. The most common mutation that causes Partington syndrome, a duplication of genetic material written as c.428_451dup, adds extra alanines to the second polyalanine tract in the ARX protein. This type of mutation is called a polyalanine repeat expansion. The expansion likely impairs ARX protein function and may disrupt normal interneuron migration in the developing brain, leading to the intellectual disability and dystonia characteristic of Partington syndrome.",Partington syndrome,0000776,GHR,https://ghr.nlm.nih.gov/condition/partington-syndrome,C0220775,T047,Disorders
Is Partington syndrome inherited ?,0000776-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. Females with one altered copy of the gene may have some signs and symptoms related to the condition. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",Partington syndrome,0000776,GHR,https://ghr.nlm.nih.gov/condition/partington-syndrome,C0220775,T047,Disorders
What are the treatments for Partington syndrome ?,0000776-5,treatment,These resources address the diagnosis or management of Partington syndrome:  - American Academy of Child and Adolescent Psychiatry: Services in School for Children with Special Needs  - American Academy of Pediatrics: What is a Developmental/Behavioral Pediatrician?  - Centers for Disease Control and Prevention: Developmental Screening Fact Sheet  - Genetic Testing Registry: Partington X-linked mental retardation syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Partington syndrome,0000776,GHR,https://ghr.nlm.nih.gov/condition/partington-syndrome,C0220775,T047,Disorders
What is (are) PDGFRA-associated chronic eosinophilic leukemia ?,0000777-1,information,"PDGFRA-associated chronic eosinophilic leukemia is a form of blood cell cancer characterized by an elevated number of cells called eosinophils in the blood. These cells help fight infections by certain parasites and are involved in the inflammation associated with allergic reactions. However, these circumstances do not account for the increased number of eosinophils in PDGFRA-associated chronic eosinophilic leukemia.  Another characteristic feature of PDGFRA-associated chronic eosinophilic leukemia is organ damage caused by the excess eosinophils. Eosinophils release substances to aid in the immune response, but the release of excessive amounts of these substances causes damage to one or more organs, most commonly the heart, skin, lungs, or nervous system. Eosinophil-associated organ damage can lead to a heart condition known as eosinophilic endomyocardial disease, skin rashes, coughing, difficulty breathing, swelling (edema) in the lower limbs, confusion, changes in behavior, or impaired movement or sensations. People with PDGFRA-associated chronic eosinophilic leukemia can also have an enlarged spleen (splenomegaly) and elevated levels of certain chemicals called vitamin B12 and tryptase in the blood.  Some people with PDGFRA-associated chronic eosinophilic leukemia have an increased number of other types of white blood cells, such as neutrophils or mast cells. Occasionally, people with PDGFRA-associated chronic eosinophilic leukemia develop other blood cell cancers, such as acute myeloid leukemia or B-cell or T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma.  PDGFRA-associated chronic eosinophilic leukemia is often grouped with a related condition called hypereosinophilic syndrome. These two conditions have very similar signs and symptoms; however, the cause of hypereosinophilic syndrome is unknown.",PDGFRA-associated chronic eosinophilic leukemia,0000777,GHR,https://ghr.nlm.nih.gov/condition/pdgfra-associated-chronic-eosinophilic-leukemia,C0346421,T191,Disorders
How many people are affected by PDGFRA-associated chronic eosinophilic leukemia ?,0000777-2,frequency,"PDGFRA-associated chronic eosinophilic leukemia is a rare condition; however, the exact prevalence is unknown.",PDGFRA-associated chronic eosinophilic leukemia,0000777,GHR,https://ghr.nlm.nih.gov/condition/pdgfra-associated-chronic-eosinophilic-leukemia,C0346421,T191,Disorders
What are the genetic changes related to PDGFRA-associated chronic eosinophilic leukemia ?,0000777-3,genetic changes,"PDGFRA-associated chronic eosinophilic leukemia is caused by mutations in the PDGFRA gene. This condition usually occurs as a result of genetic rearrangements that fuse part of the PDGFRA gene with part of another gene. Rarely, changes in single DNA building blocks (point mutations) in the PDGFRA gene are found in people with this condition. Genetic rearrangements and point mutations affecting the PDGFRA gene are somatic mutations, which are mutations acquired during a person's lifetime that are present only in certain cells. The somatic mutation occurs initially in a single cell, which continues to grow and divide, producing a group of cells with the same mutation (a clonal population).  The most common genetic abnormality in PDGFRA-associated chronic eosinophilic leukemia results from a deletion of genetic material from chromosome 4, which brings together part of the PDGFRA gene and part of the FIP1L1 gene, creating the FIP1L1-PDGFRA fusion gene.  The FIP1L1 gene provides instructions for a protein that plays a role in forming the genetic blueprints for making proteins (messenger RNA or mRNA).  The PDGFRA gene provides instructions for making a receptor protein that is found in the cell membrane of certain cell types. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. When the ligand attaches (binds), the PDGFRA receptor protein is turned on (activated), which leads to activation of a series of proteins in multiple signaling pathways. These signaling pathways control many important cellular processes, such as cell growth and division (proliferation) and cell survival.  The FIP1L1-PDGFRA fusion gene (as well as other PDGFRA fusion genes) provides instructions for making a fusion protein that has the function of the normal PDGFRA protein. However, the fusion protein does not require ligand binding to be activated. Similarly, point mutations in the PDGFRA gene can result in a PDGFRA protein that is activated without ligand binding. As a result, the signaling pathways are constantly turned on (constitutively activated), which increases the proliferation and survival of cells. When the FIP1L1-PDGFRA fusion gene mutation or point mutations in the PDGFRA gene occur in blood cell precursors, the growth of eosinophils (and occasionally other blood cells, such as neutrophils and mast cells) is poorly controlled, leading to PDGFRA-associated chronic eosinophilic leukemia. It is unclear why eosinophils are preferentially affected by this genetic change.",PDGFRA-associated chronic eosinophilic leukemia,0000777,GHR,https://ghr.nlm.nih.gov/condition/pdgfra-associated-chronic-eosinophilic-leukemia,C0346421,T191,Disorders
Is PDGFRA-associated chronic eosinophilic leukemia inherited ?,0000777-4,inheritance,"PDGFRA-associated chronic eosinophilic leukemia is not inherited and occurs in people with no history of the condition in their families. Mutations that lead to a PDGFRA fusion gene and PDGFRA point mutations are somatic mutations, which means they occur during a person's lifetime and are found only in certain cells. Somatic mutations are not inherited. Males are more likely to develop PDGFRA-associated chronic eosinophilic leukemia than females because, for unknown reasons, PDGFRA fusion genes are found more often in males.",PDGFRA-associated chronic eosinophilic leukemia,0000777,GHR,https://ghr.nlm.nih.gov/condition/pdgfra-associated-chronic-eosinophilic-leukemia,C0346421,T191,Disorders
What are the treatments for PDGFRA-associated chronic eosinophilic leukemia ?,0000777-5,treatment,These resources address the diagnosis or management of PDGFRA-associated chronic eosinophilic leukemia:  - Cancer.Net: Leukemia - Eosinophilic: Treatment  - Genetic Testing Registry: Idiopathic hypereosinophilic syndrome  - MedlinePlus Encyclopedia: Eosinophil Count - Absolute  - Seattle Cancer Care Alliance: Hypereosinophilia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,PDGFRA-associated chronic eosinophilic leukemia,0000777,GHR,https://ghr.nlm.nih.gov/condition/pdgfra-associated-chronic-eosinophilic-leukemia,C0346421,T191,Disorders
What is (are) PDGFRB-associated chronic eosinophilic leukemia ?,0000778-1,information,"PDGFRB-associated chronic eosinophilic leukemia is a type of cancer of blood-forming cells. It is characterized by an elevated number of white blood cells called eosinophils in the blood. These cells help fight infections by certain parasites and are involved in the inflammation associated with allergic reactions. However, these circumstances do not account for the increased number of eosinophils in PDGFRB-associated chronic eosinophilic leukemia. Some people with this condition have an increased number of other types of white blood cells, such as neutrophils or mast cells, in addition to eosinophils. People with this condition can have an enlarged spleen (splenomegaly) or enlarged liver (hepatomegaly). Some affected individuals develop skin rashes, likely as a result of an abnormal immune response due to the increased number of eosinophils.",PDGFRB-associated chronic eosinophilic leukemia,0000778,GHR,https://ghr.nlm.nih.gov/condition/pdgfrb-associated-chronic-eosinophilic-leukemia,C3711560,T191,Disorders
How many people are affected by PDGFRB-associated chronic eosinophilic leukemia ?,0000778-2,frequency,"The exact prevalence of PDGFRB-associated chronic eosinophilic leukemia is unknown. For unknown reasons, males are up to nine times more likely than females to develop PDGFRB-associated chronic eosinophilic leukemia.",PDGFRB-associated chronic eosinophilic leukemia,0000778,GHR,https://ghr.nlm.nih.gov/condition/pdgfrb-associated-chronic-eosinophilic-leukemia,C3711560,T191,Disorders
What are the genetic changes related to PDGFRB-associated chronic eosinophilic leukemia ?,0000778-3,genetic changes,"PDGFRB-associated chronic eosinophilic leukemia is caused by genetic rearrangements that join part of the PDGFRB gene with part of another gene. At least 20 genes have been found that fuse with the PDGFRB gene to cause PDGFRB-associated chronic eosinophilic leukemia. The most common genetic abnormality in this condition results from a rearrangement (translocation) of genetic material that brings part of the PDGFRB gene on chromosome 5 together with part of the ETV6 gene on chromosome 12, creating the ETV6-PDGFRB fusion gene.  The PDGFRB gene provides instructions for making a protein that plays a role in turning on (activating) signaling pathways that control many cell processes, including cell growth and division (proliferation). The ETV6 gene provides instructions for making a protein that turns off (represses) gene activity. This protein is important in development before birth and in regulating blood cell formation. The protein produced from the ETV6-PDGFRB fusion gene, called ETV6/PDGFR, functions differently than the proteins normally produced from the individual genes. Like the normal PDGFR protein, the ETV6/PDGFR fusion protein turns on signaling pathways. However, the fusion protein does not need to be turned on to be active, so the signaling pathways are constantly turned on (constitutively activated). The fusion protein is unable to repress gene activity regulated by the normal ETV6 protein, so gene activity is increased. The constitutively active signaling pathways and abnormal gene activity increase the proliferation and survival of cells.  When the ETV6-PDGFRB fusion gene mutation occurs in cells that develop into blood cells, the growth of eosinophils (and occasionally other blood cells, such as neutrophils and mast cells) is poorly controlled, leading to PDGFRB-associated chronic eosinophilic leukemia. It is unclear why eosinophils are preferentially affected by this genetic change.",PDGFRB-associated chronic eosinophilic leukemia,0000778,GHR,https://ghr.nlm.nih.gov/condition/pdgfrb-associated-chronic-eosinophilic-leukemia,C3711560,T191,Disorders
Is PDGFRB-associated chronic eosinophilic leukemia inherited ?,0000778-4,inheritance,"PDGFRB-associated chronic eosinophilic leukemia is not inherited and occurs in people with no history of the condition in their families. Chromosomal rearrangements that lead to a PDGFRB fusion gene are somatic mutations, which are mutations acquired during a person's lifetime and present only in certain cells. The somatic mutation occurs initially in a single cell, which continues to grow and divide, producing a group of cells with the same mutation (a clonal population).",PDGFRB-associated chronic eosinophilic leukemia,0000778,GHR,https://ghr.nlm.nih.gov/condition/pdgfrb-associated-chronic-eosinophilic-leukemia,C3711560,T191,Disorders
What are the treatments for PDGFRB-associated chronic eosinophilic leukemia ?,0000778-5,treatment,"These resources address the diagnosis or management of PDGFRB-associated chronic eosinophilic leukemia:  - Cancer.Net: Leukemia--Eosinophilic: Treatment  - Genetic Testing Registry: Myeloproliferative disorder, chronic, with eosinophilia  - MedlinePlus Encyclopedia: Eosinophil Count--Absolute  - Seattle Cancer Care Alliance: Hypereosinophilia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",PDGFRB-associated chronic eosinophilic leukemia,0000778,GHR,https://ghr.nlm.nih.gov/condition/pdgfrb-associated-chronic-eosinophilic-leukemia,C3711560,T191,Disorders
What is (are) Pearson marrow-pancreas syndrome ?,0000779-1,information,"Pearson marrow-pancreas syndrome is a severe disorder that usually begins in infancy. It causes problems with the development of blood-forming (hematopoietic) cells in the bone marrow that have the potential to develop into different types of blood cells. For this reason, Pearson marrow-pancreas syndrome is considered a bone marrow failure disorder. Function of the pancreas and other organs can also be affected.  Most affected individuals have a shortage of red blood cells (anemia), which can cause pale skin (pallor), weakness, and fatigue. Some of these individuals also have low numbers of white blood cells (neutropenia) and platelets (thrombocytopenia). Neutropenia can lead to frequent infections; thrombocytopenia sometimes causes easy bruising and bleeding. When visualized under the microscope, bone marrow cells from affected individuals may appear abnormal. Often, early blood cells (hematopoietic precursors) have multiple fluid-filled pockets called vacuoles. In addition, red blood cells in the bone marrow can have an abnormal buildup of iron that appears as a ring of blue staining in the cell after treatment with certain dyes. These abnormal cells are called ring sideroblasts.  In people with Pearson marrow-pancreas syndrome, the pancreas does not work as well as usual. The pancreas produces and releases enzymes that aid in the digestion of fats and proteins. Reduced function of this organ can lead to high levels of fats in the liver (liver steatosis). The pancreas also releases insulin, which helps maintain correct blood sugar levels. A small number of individuals with Pearson marrow-pancreas syndrome develop diabetes, a condition characterized by abnormally high blood sugar levels that can be caused by a shortage of insulin. In addition, affected individuals may have scarring (fibrosis) in the pancreas.  People with Pearson marrow-pancreas syndrome have a reduced ability to absorb nutrients from the diet (malabsorption), and most affected infants have an inability to grow and gain weight at the expected rate (failure to thrive). Another common occurrence in people with this condition is buildup in the body of a chemical called lactic acid (lactic acidosis), which can be life-threatening. In addition, liver and kidney problems can develop in people with this condition.  About half of children with this severe disorder die in infancy or early childhood due to severe lactic acidosis or liver failure. Many of those who survive develop signs and symptoms later in life of a related disorder called Kearns-Sayre syndrome. This condition causes weakness of muscles around the eyes and other problems.",Pearson marrow-pancreas syndrome,0000779,GHR,https://ghr.nlm.nih.gov/condition/pearson-marrow-pancreas-syndrome,C0342784,T047,Disorders
How many people are affected by Pearson marrow-pancreas syndrome ?,0000779-2,frequency,Pearson marrow-pancreas syndrome is a rare condition; its prevalence is unknown.,Pearson marrow-pancreas syndrome,0000779,GHR,https://ghr.nlm.nih.gov/condition/pearson-marrow-pancreas-syndrome,C0342784,T047,Disorders
What are the genetic changes related to Pearson marrow-pancreas syndrome ?,0000779-3,genetic changes,"Pearson marrow-pancreas syndrome is caused by defects in mitochondria, which are structures within cells that use oxygen to convert the energy from food into a form cells can use. This process is called oxidative phosphorylation. Although most DNA is packaged in chromosomes within the nucleus (nuclear DNA), mitochondria also have a small amount of their own DNA, called mitochondrial DNA (mtDNA). This type of DNA contains many genes essential for normal mitochondrial function. Pearson marrow-pancreas syndrome is caused by single, large deletions of mtDNA, which can range from 1,000 to 10,000 DNA building blocks (nucleotides). The most common deletion, which occurs in about 20 percent of affected individuals, removes 4,997 nucleotides.  The mtDNA deletions involved in Pearson marrow-pancreas syndrome result in the loss of genes that provide instructions for proteins involved in oxidative phosphorylation. These deletions impair oxidative phosphorylation and decrease the energy available to cells. It is not clear how loss of mtDNA leads to the specific signs and symptoms of Pearson marrow-pancreas syndrome, although the features of the condition are likely related to a lack of cellular energy.",Pearson marrow-pancreas syndrome,0000779,GHR,https://ghr.nlm.nih.gov/condition/pearson-marrow-pancreas-syndrome,C0342784,T047,Disorders
Is Pearson marrow-pancreas syndrome inherited ?,0000779-4,inheritance,Pearson marrow-pancreas syndrome is generally not inherited but arises from new (de novo) mutations that likely occur in early embryonic development.,Pearson marrow-pancreas syndrome,0000779,GHR,https://ghr.nlm.nih.gov/condition/pearson-marrow-pancreas-syndrome,C0342784,T047,Disorders
What are the treatments for Pearson marrow-pancreas syndrome ?,0000779-5,treatment,These resources address the diagnosis or management of Pearson marrow-pancreas syndrome:  - Gene Review: Gene Review: Mitochondrial DNA Deletion Syndromes  - Genetic Testing Registry: Pearson syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Pearson marrow-pancreas syndrome,0000779,GHR,https://ghr.nlm.nih.gov/condition/pearson-marrow-pancreas-syndrome,C0342784,T047,Disorders
What is (are) Pelizaeus-Merzbacher disease ?,0000780-1,information,"Pelizaeus-Merzbacher disease is an inherited condition involving the brain and spinal cord (central nervous system). This disease is one of a group of genetic disorders called leukodystrophies. Leukodystrophies are characterized by degeneration of myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. Pelizaeus-Merzbacher disease is caused by an inability to form myelin (dysmyelination). As a result, individuals with this condition have impaired intellectual functions, such as language and memory, and delayed motor skills, such as coordination and walking. Typically, motor skills are more severely affected than intellectual function; motor skills development tends to occur more slowly and usually stops in a person's teens, followed by gradual deterioration.  Pelizaeus-Merzbacher disease is divided into classic and connatal types. Although these two types differ in severity, their features can overlap.  Classic Pelizaeus-Merzbacher disease is the more common type. Within the first year of life, those affected with classic Pelizaeus-Merzbacher disease typically experience weak muscle tone (hypotonia), involuntary movements of the eyes (nystagmus), and delayed development of motor skills such as crawling or walking. As the child gets older, nystagmus usually stops but other movement disorders develop, including muscle stiffness (spasticity), problems with movement and balance (ataxia), and involuntary jerking (choreiform movements).  Connatal Pelizaeus-Merzbacher disease is the more severe of the two types. Symptoms can begin in infancy and include problems feeding, a whistling sound when breathing, progressive spasticity leading to joint deformities (contractures) that restrict movement, speech difficulties (dysarthria), ataxia, and seizures. Those affected with connatal Pelizaeus-Merzbacher disease show little development of motor skills and intellectual function.",Pelizaeus-Merzbacher disease,0000780,GHR,https://ghr.nlm.nih.gov/condition/pelizaeus-merzbacher-disease,C0205711,T047,Disorders
How many people are affected by Pelizaeus-Merzbacher disease ?,0000780-2,frequency,"The prevalence of Pelizaeus-Merzbacher disease is estimated to be 1 in 200,000 to 500,000 males in the United States. This condition rarely affects females.",Pelizaeus-Merzbacher disease,0000780,GHR,https://ghr.nlm.nih.gov/condition/pelizaeus-merzbacher-disease,C0205711,T047,Disorders
What are the genetic changes related to Pelizaeus-Merzbacher disease ?,0000780-3,genetic changes,"Mutations in the PLP1 gene cause Pelizaeus-Merzbacher disease. The PLP1 gene provides instructions for producing proteolipid protein 1 and a modified version (isoform) of proteolipid protein 1, called DM20. Proteolipid protein 1 and DM20 are primarily located in the central nervous system and are the main proteins found in myelin, the fatty covering that insulates nerve fibers. A lack of proteolipid protein 1 and DM20 can cause dysmyelination, which can impair nervous system function, resulting in the signs and symptoms of Pelizaeus-Merzbacher disease.  It is estimated that 5 percent to 20 percent of people with Pelizaeus-Merzbacher disease do not have identified mutations in the PLP1 gene. In these cases, the cause of the condition is unknown.",Pelizaeus-Merzbacher disease,0000780,GHR,https://ghr.nlm.nih.gov/condition/pelizaeus-merzbacher-disease,C0205711,T047,Disorders
Is Pelizaeus-Merzbacher disease inherited ?,0000780-4,inheritance,"This condition is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. Because females have two copies of the X chromosome, one altered copy of the gene in each cell usually leads to less severe symptoms in females than in males, or may cause no symptoms at all. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In X-linked recessive inheritance, a female with one altered copy of the gene in each cell is called a carrier. She can pass on the gene, but generally does not experience signs and symptoms of the disorder. Some females who carry a PLP1 mutation, however, may experience muscle stiffness and a decrease in intellectual function. Females with one PLP1 mutation have an increased risk of experiencing progressive deterioration of cognitive functions (dementia) later in life.",Pelizaeus-Merzbacher disease,0000780,GHR,https://ghr.nlm.nih.gov/condition/pelizaeus-merzbacher-disease,C0205711,T047,Disorders
What are the treatments for Pelizaeus-Merzbacher disease ?,0000780-5,treatment,These resources address the diagnosis or management of Pelizaeus-Merzbacher disease:  - Gene Review: Gene Review: PLP1-Related Disorders  - Genetic Testing Registry: Pelizaeus-Merzbacher disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Pelizaeus-Merzbacher disease,0000780,GHR,https://ghr.nlm.nih.gov/condition/pelizaeus-merzbacher-disease,C0205711,T047,Disorders
What is (are) Pendred syndrome ?,0000781-1,information,"Pendred syndrome is a disorder typically associated with hearing loss and a thyroid condition called a goiter. A goiter is an enlargement of the thyroid gland, which is a butterfly-shaped organ at the base of the neck that produces hormones. If a goiter develops in a person with Pendred syndrome, it usually forms between late childhood and early adulthood. In most cases, this enlargement does not cause the thyroid to malfunction.  In most people with Pendred syndrome, severe to profound hearing loss caused by changes in the inner ear (sensorineural hearing loss) is evident at birth. Less commonly, hearing loss does not develop until later in infancy or early childhood. Some affected individuals also have problems with balance caused by dysfunction of the vestibular system, which is the part of the inner ear that helps maintain the body's balance and orientation.  An inner ear abnormality called an enlarged vestibular aqueduct (EVA) is a characteristic feature of Pendred syndrome. The vestibular aqueduct is a bony canal that connects the inner ear with the inside of the skull. Some affected individuals also have an abnormally shaped cochlea, which is a snail-shaped structure in the inner ear that helps process sound. The combination of an enlarged vestibular aqueduct and an abnormally shaped cochlea is known as Mondini malformation.  Pendred syndrome shares features with other hearing loss and thyroid conditions, and it is unclear whether they are best considered as separate disorders or as a spectrum of related signs and symptoms. These conditions include a form of nonsyndromic hearing loss (hearing loss that does not affect other parts of the body) called DFNB4, and, in a small number of people, a form of congenital hypothyroidism resulting from an abnormally small thyroid gland (thyroid hypoplasia). All of these conditions are caused by mutations in the same gene.",Pendred syndrome,0000781,GHR,https://ghr.nlm.nih.gov/condition/pendred-syndrome,C0039082,T047,Disorders
How many people are affected by Pendred syndrome ?,0000781-2,frequency,"The prevalence of Pendred syndrome is unknown. However, researchers estimate that it accounts for 7 to 8 percent of all hearing loss that is present from birth (congenital hearing loss).",Pendred syndrome,0000781,GHR,https://ghr.nlm.nih.gov/condition/pendred-syndrome,C0039082,T047,Disorders
What are the genetic changes related to Pendred syndrome ?,0000781-3,genetic changes,"Mutations in the SLC26A4 gene cause about half of all cases of Pendred syndrome. The SLC26A4 gene provides instructions for making a protein called pendrin. This protein transports negatively charged particles (ions), including chloride, iodide, and bicarbonate, into and out of cells. Although the function of pendrin is not fully understood, this protein is important for maintaining the proper levels of ions in the thyroid and the inner ear. Mutations in the SLC26A4 gene alter the structure or function of pendrin, which disrupts ion transport. An imbalance of particular ions disrupts the development and function of the thyroid gland and structures in the inner ear, which leads to the characteristic features of Pendred syndrome.  In people with Pendred syndrome who do not have mutations in the SLC26A4 gene, the cause of the condition is unknown. Researchers suspect that other genetic and environmental factors may influence the condition.",Pendred syndrome,0000781,GHR,https://ghr.nlm.nih.gov/condition/pendred-syndrome,C0039082,T047,Disorders
Is Pendred syndrome inherited ?,0000781-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Pendred syndrome,0000781,GHR,https://ghr.nlm.nih.gov/condition/pendred-syndrome,C0039082,T047,Disorders
What are the treatments for Pendred syndrome ?,0000781-5,treatment,"These resources address the diagnosis or management of Pendred syndrome:  - Children's Hospital of Philadelphia, Center for Childhood Communication  - Gene Review: Gene Review: Pendred Syndrome/DFNB4  - Genetic Testing Registry: Pendred's syndrome  - MedlinePlus Encyclopedia: Goiter  - MedlinePlus Encyclopedia: Hearing Loss   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Pendred syndrome,0000781,GHR,https://ghr.nlm.nih.gov/condition/pendred-syndrome,C0039082,T047,Disorders
What is (are) periventricular heterotopia ?,0000782-1,information,"Periventricular heterotopia is a condition in which nerve cells (neurons) do not migrate properly during the early development of the fetal brain, from about the 6th week to the 24th week of pregnancy. Heterotopia means ""out of place."" In normal brain development, neurons form in the periventricular region, located around fluid-filled cavities (ventricles) near the center of the brain. The neurons then migrate outward to form the exterior of the brain (cerebral cortex) in six onion-like layers. In periventricular heterotopia, some neurons fail to migrate to their proper position and form clumps around the ventricles.  Periventricular heterotopia usually becomes evident when seizures first appear, often during the teenage years. The nodules around the ventricles are then typically discovered when magnetic resonance imaging (MRI) studies are done. Affected individuals usually have normal intelligence, although some have mild intellectual disability. Difficulty with reading and spelling (dyslexia) has been reported in some people with periventricular heterotopia.  Less commonly, individuals with periventricular heterotopia may have more severe brain malformations, small head size (microcephaly), developmental delays, recurrent infections, blood vessel abnormalities, or other problems. Periventricular heterotopia may also occur in association with other conditions such as Ehlers-Danlos syndrome, which results in extremely flexible joints, skin that stretches easily, and fragile blood vessels.",periventricular heterotopia,0000782,GHR,https://ghr.nlm.nih.gov/condition/periventricular-heterotopia,C3714789,,Disorders
How many people are affected by periventricular heterotopia ?,0000782-2,frequency,Periventricular heterotopia is a rare condition. Its incidence is unknown.,periventricular heterotopia,0000782,GHR,https://ghr.nlm.nih.gov/condition/periventricular-heterotopia,C3714789,,Disorders
What are the genetic changes related to periventricular heterotopia ?,0000782-3,genetic changes,"Periventricular heterotopia is related to chromosome 5.  Mutations in the ARFGEF2 and FLNA genes cause periventricular heterotopia.  In most cases, periventricular heterotopia is caused by mutations in the FLNA gene. This gene provides instructions for producing the protein filamin A, which helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. Certain mutations in the FLNA gene result in an impaired FLNA protein that cannot perform this function, disrupting the normal migration patterns of neurons during brain development.  Periventricular heterotopia can also be caused by mutations in the ARFGEF2 gene. This gene provides instructions for making a protein that is involved in the movement (trafficking) of small sac-like structures (vesicles) within the cell. Vesicle trafficking is important in controlling the migration of neurons during the development of the brain. Mutations in the ARFGEF2 gene may disrupt this function, which could result in the abnormal neuronal migration seen in periventricular heterotopia.  Researchers believe that mutations in the FLNA or ARFGEF2 genes may also result in weakening of the attachments (adhesion) between cells that form the lining of the ventricles. A weakened ventricular lining could allow some neurons to form clumps around the ventricles while others migrate normally to the exterior of the brain, as seen in periventricular heterotopia.  In a few cases, periventricular heterotopia has been associated with abnormalities in chromosome 5. In each case, the affected individual had extra genetic material caused by an abnormal duplication of part of this chromosome. It is not known how this duplicated genetic material results in the signs and symptoms of periventricular heterotopia.",periventricular heterotopia,0000782,GHR,https://ghr.nlm.nih.gov/condition/periventricular-heterotopia,C3714789,,Disorders
Is periventricular heterotopia inherited ?,0000782-4,inheritance,"Periventricular heterotopia can have different inheritance patterns. When this condition is caused by mutations in the FLNA gene, it is inherited in an X-linked dominant pattern.  A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. The inheritance is dominant if one copy of the altered gene in each cell is sufficient to cause the condition. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In X-linked periventricular heterotopia, males experience much more severe symptoms of the disorder than females, and in most cases die before birth.  In about 50 percent of cases of X-linked periventricular heterotopia, an affected person inherits the mutation from a mother who is also affected. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.  Periventricular heterotopia caused by mutations in the ARFGEF2 gene is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Individuals with periventricular heterotopia in whom ARFGEF2 gene mutations have been identified have a severe form of the disorder, including microcephaly, severe developmental delay, and seizures beginning in infancy. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.",periventricular heterotopia,0000782,GHR,https://ghr.nlm.nih.gov/condition/periventricular-heterotopia,C3714789,,Disorders
What are the treatments for periventricular heterotopia ?,0000782-5,treatment,"These resources address the diagnosis or management of periventricular heterotopia:  - Gene Review: Gene Review: FLNA-Related Periventricular Nodular Heterotopia  - Genetic Testing Registry: Heterotopia, periventricular, associated with chromosome 5p anomalies  - Genetic Testing Registry: Heterotopia, periventricular, autosomal recessive  - Genetic Testing Registry: X-linked periventricular heterotopia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",periventricular heterotopia,0000782,GHR,https://ghr.nlm.nih.gov/condition/periventricular-heterotopia,C3714789,,Disorders
What is (are) permanent neonatal diabetes mellitus ?,0000783-1,information,"Permanent neonatal diabetes mellitus is a type of diabetes that first appears within the first 6 months of life and persists throughout the lifespan. This form of diabetes is characterized by high blood sugar levels (hyperglycemia) resulting from a shortage of the hormone insulin. Insulin controls how much glucose (a type of sugar) is passed from the blood into cells for conversion to energy.  Individuals with permanent neonatal diabetes mellitus experience slow growth before birth (intrauterine growth retardation). Affected infants have hyperglycemia and an excessive loss of fluids (dehydration) and are unable to gain weight and grow at the expected rate (failure to thrive).  In some cases, people with permanent neonatal diabetes mellitus also have certain neurological problems, including developmental delay and recurrent seizures (epilepsy). This combination of developmental delay, epilepsy, and neonatal diabetes is called DEND syndrome. Intermediate DEND syndrome is a similar combination but with milder developmental delay and without epilepsy.  A small number of individuals with permanent neonatal diabetes mellitus have an underdeveloped pancreas. Because the pancreas produces digestive enzymes as well as secreting insulin and other hormones, affected individuals experience digestive problems such as fatty stools and an inability to absorb fat-soluble vitamins.",permanent neonatal diabetes mellitus,0000783,GHR,https://ghr.nlm.nih.gov/condition/permanent-neonatal-diabetes-mellitus,C1833104,T047,Disorders
How many people are affected by permanent neonatal diabetes mellitus ?,0000783-2,frequency,"About 1 in 400,000 infants are diagnosed with diabetes mellitus in the first few months of life. However, in about half of these babies the condition is transient and goes away on its own by age 18 months. The remainder are considered to have permanent neonatal diabetes mellitus.",permanent neonatal diabetes mellitus,0000783,GHR,https://ghr.nlm.nih.gov/condition/permanent-neonatal-diabetes-mellitus,C1833104,T047,Disorders
What are the genetic changes related to permanent neonatal diabetes mellitus ?,0000783-3,genetic changes,"Permanent neonatal diabetes mellitus may be caused by mutations in several genes.  About 30 percent of individuals with permanent neonatal diabetes mellitus have mutations in the KCNJ11 gene. An additional 20 percent of people with permanent neonatal diabetes mellitus have mutations in the ABCC8 gene. These genes provide instructions for making parts (subunits) of the ATP-sensitive potassium (K-ATP) channel. Each K-ATP channel consists of eight subunits, four produced from the KCNJ11 gene and four from the ABCC8 gene.  K-ATP channels are found across cell membranes in the insulin-secreting beta cells of the pancreas. These channels open and close in response to the amount of glucose in the bloodstream. Closure of the channels in response to increased glucose triggers the release of insulin out of beta cells and into the bloodstream, which helps control blood sugar levels.  Mutations in the KCNJ11 or ABCC8 gene that cause permanent neonatal diabetes mellitus result in K-ATP channels that do not close, leading to reduced insulin secretion from beta cells and impaired blood sugar control.  Mutations in the INS gene, which provides instructions for making insulin, have been identified in about 20 percent of individuals with permanent neonatal diabetes mellitus. Insulin is produced in a precursor form called proinsulin, which consists of a single chain of protein building blocks (amino acids). The proinsulin chain is cut (cleaved) to form individual pieces called the A and B chains, which are joined together by connections called disulfide bonds to form insulin. Mutations in the INS gene are believed to disrupt the cleavage of the proinsulin chain or the binding of the A and B chains to form insulin, leading to impaired blood sugar control.  Permanent neonatal diabetes mellitus can also be caused by mutations in other genes, some of which have not been identified.",permanent neonatal diabetes mellitus,0000783,GHR,https://ghr.nlm.nih.gov/condition/permanent-neonatal-diabetes-mellitus,C1833104,T047,Disorders
Is permanent neonatal diabetes mellitus inherited ?,0000783-4,inheritance,"Permanent neonatal diabetes mellitus can have different inheritance patterns.  When this condition is caused by mutations in the KCNJ11 or INS gene it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In about 90 percent of these cases, the condition results from new mutations in the gene and occurs in people with no history of the disorder in their family. In the remaining cases, an affected person inherits the mutation from one affected parent.  When permanent neonatal diabetes mellitus is caused by mutations in the ABCC8 gene, it may be inherited in either an autosomal dominant or autosomal recessive pattern. In autosomal recessive inheritance, both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Less commonly the condition is caused by mutations in other genes, and in these cases it is also inherited in an autosomal recessive pattern.",permanent neonatal diabetes mellitus,0000783,GHR,https://ghr.nlm.nih.gov/condition/permanent-neonatal-diabetes-mellitus,C1833104,T047,Disorders
What are the treatments for permanent neonatal diabetes mellitus ?,0000783-5,treatment,"These resources address the diagnosis or management of permanent neonatal diabetes mellitus:  - Gene Review: Gene Review: Permanent Neonatal Diabetes Mellitus  - Genetic Testing Registry: Pancreatic agenesis, congenital  - Genetic Testing Registry: Permanent neonatal diabetes mellitus  - University of Chicago Kovler Diabetes Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",permanent neonatal diabetes mellitus,0000783,GHR,https://ghr.nlm.nih.gov/condition/permanent-neonatal-diabetes-mellitus,C1833104,T047,Disorders
What is (are) peroxisomal acyl-CoA oxidase deficiency ?,0000784-1,information,"Peroxisomal acyl-CoA oxidase deficiency is a disorder that causes deterioration of nervous system functions (neurodegeneration) beginning in infancy. Newborns with peroxisomal acyl-CoA oxidase deficiency have weak muscle tone (hypotonia) and seizures. They may have unusual facial features, including widely spaced eyes (hypertelorism), a low nasal bridge, and low-set ears. Extra fingers or toes (polydactyly) or an enlarged liver (hepatomegaly) also occur in some affected individuals.  Most babies with peroxisomal acyl-CoA oxidase deficiency learn to walk and begin speaking, but they experience a gradual loss of these skills (developmental regression), usually beginning between the ages of 1 and 3. As the condition gets worse, affected children develop exaggerated reflexes (hyperreflexia), increased muscle tone (hypertonia), more severe and recurrent seizures (epilepsy), and loss of vision and hearing. Most children with peroxisomal acyl-CoA oxidase deficiency do not survive past early childhood.",peroxisomal acyl-CoA oxidase deficiency,0000784,GHR,https://ghr.nlm.nih.gov/condition/peroxisomal-acyl-coa-oxidase-deficiency,C1849678,T047,Disorders
How many people are affected by peroxisomal acyl-CoA oxidase deficiency ?,0000784-2,frequency,Peroxisomal acyl-CoA oxidase deficiency is a rare disorder. Its prevalence is unknown. Only a few dozen cases have been described in the medical literature.,peroxisomal acyl-CoA oxidase deficiency,0000784,GHR,https://ghr.nlm.nih.gov/condition/peroxisomal-acyl-coa-oxidase-deficiency,C1849678,T047,Disorders
What are the genetic changes related to peroxisomal acyl-CoA oxidase deficiency ?,0000784-3,genetic changes,"Peroxisomal acyl-CoA oxidase deficiency is caused by mutations in the ACOX1 gene, which provides instructions for making an enzyme called peroxisomal straight-chain acyl-CoA oxidase. This enzyme is found in sac-like cell structures (organelles) called peroxisomes, which contain a variety of enzymes that break down many different substances. The peroxisomal straight-chain acyl-CoA oxidase enzyme plays a role in the breakdown of certain fat molecules called very long-chain fatty acids (VLCFAs). Specifically, it is involved in the first step of a process called the peroxisomal fatty acid beta-oxidation pathway. This process shortens the VLCFA molecules by two carbon atoms at a time until the VLCFAs are converted to a molecule called acetyl-CoA, which is transported out of the peroxisomes for reuse by the cell.  ACOX1 gene mutations prevent the peroxisomal straight-chain acyl-CoA oxidase enzyme from breaking down VLCFAs efficiently. As a result, these fatty acids accumulate in the body. It is unclear exactly how VLCFA accumulation leads to the specific features of peroxisomal acyl-CoA oxidase deficiency. However, researchers suggest that the abnormal fatty acid accumulation triggers inflammation in the nervous system that leads to the breakdown of myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. Destruction of myelin leads to a loss of myelin-containing tissue (white matter) in the brain and spinal cord; loss of white matter is described as leukodystrophy. Leukodystrophy is likely involved in the development of the neurological abnormalities that occur in peroxisomal acyl-CoA oxidase deficiency.",peroxisomal acyl-CoA oxidase deficiency,0000784,GHR,https://ghr.nlm.nih.gov/condition/peroxisomal-acyl-coa-oxidase-deficiency,C1849678,T047,Disorders
Is peroxisomal acyl-CoA oxidase deficiency inherited ?,0000784-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",peroxisomal acyl-CoA oxidase deficiency,0000784,GHR,https://ghr.nlm.nih.gov/condition/peroxisomal-acyl-coa-oxidase-deficiency,C1849678,T047,Disorders
What are the treatments for peroxisomal acyl-CoA oxidase deficiency ?,0000784-5,treatment,These resources address the diagnosis or management of peroxisomal acyl-CoA oxidase deficiency:  - Gene Review: Gene Review: Leukodystrophy Overview  - Genetic Testing Registry: Pseudoneonatal adrenoleukodystrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,peroxisomal acyl-CoA oxidase deficiency,0000784,GHR,https://ghr.nlm.nih.gov/condition/peroxisomal-acyl-coa-oxidase-deficiency,C1849678,T047,Disorders
What is (are) Perrault syndrome ?,0000785-1,information,"Perrault syndrome is a rare condition that causes different patterns of signs and symptoms in affected males and females. A key feature of this condition is hearing loss, which occurs in both males and females. Affected females also have abnormalities of the ovaries. Neurological problems occur in some affected males and females.  In Perrault syndrome, the problems with hearing are caused by changes in the inner ear, which is known as sensorineural hearing loss. The impairment usually affects both ears and can be present at birth or begin in early childhood. Unless hearing is completely impaired at birth, the hearing problems worsen over time.  Females with Perrault syndrome have abnormal or missing ovaries (ovarian dysgenesis), although their external genitalia are normal. Severely affected girls do not begin menstruation by age 16 (primary amenorrhea), and most never have a menstrual period. Less severely affected women have an early loss of ovarian function (primary ovarian insufficiency); their menstrual periods begin in adolescence, but they become less frequent and eventually stop before age 40. Women with Perrault syndrome may have difficulty conceiving or be unable to have biological children (infertile).  Neurological problems in individuals with Perrault syndrome can include intellectual disability, difficulty with balance and coordinating movements (ataxia), and loss of sensation and weakness in the limbs (peripheral neuropathy). However, not everyone with this condition has neurological problems.",Perrault syndrome,0000785,GHR,https://ghr.nlm.nih.gov/condition/perrault-syndrome,C0685838,T019,Disorders
How many people are affected by Perrault syndrome ?,0000785-2,frequency,"Perrault syndrome is a rare disorder; fewer than 100 affected individuals have been described in the medical literature. It is likely that the condition is underdiagnosed, because males without an affected sister will likely be misdiagnosed as having isolated (nonsyndromic) hearing loss rather than Perrault syndrome.",Perrault syndrome,0000785,GHR,https://ghr.nlm.nih.gov/condition/perrault-syndrome,C0685838,T019,Disorders
What are the genetic changes related to Perrault syndrome ?,0000785-3,genetic changes,"Perrault syndrome has several genetic causes. C10orf2, CLPP, HARS2, LARS2, or HSD17B4 gene mutations have been found in a small number of affected individuals. The proteins produced from several of these genes, including C10orf2, CLPP, HARS2, and LARS2, function in cell structures called mitochondria, which convert the energy from food into a form that cells can use. Although the effect of these gene mutations on mitochondrial function is unknown, researchers speculate that disruption of mitochondrial energy production could underlie the signs and symptoms of Perrault syndrome.  The protein produced from the HSD17B4 gene is active in cell structures called peroxisomes, which contain a variety of enzymes that break down many different substances in cells. It is not known how mutations in this gene affect peroxisome function or lead to hearing loss in affected males and females and ovarian abnormalities in females with Perrault syndrome.  It is likely that other genes that have not been identified are also involved in this condition.",Perrault syndrome,0000785,GHR,https://ghr.nlm.nih.gov/condition/perrault-syndrome,C0685838,T019,Disorders
Is Perrault syndrome inherited ?,0000785-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they do not show signs and symptoms of the condition.",Perrault syndrome,0000785,GHR,https://ghr.nlm.nih.gov/condition/perrault-syndrome,C0685838,T019,Disorders
What are the treatments for Perrault syndrome ?,0000785-5,treatment,"These resources address the diagnosis or management of Perrault syndrome:  - Gene Review: Gene Review: Perrault Syndrome  - Genetic Testing Registry: Gonadal dysgenesis with auditory dysfunction, autosomal recessive inheritance  - Genetic Testing Registry: Perrault syndrome 2  - Genetic Testing Registry: Perrault syndrome 4  - Genetic Testing Registry: Perrault syndrome 5   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Perrault syndrome,0000785,GHR,https://ghr.nlm.nih.gov/condition/perrault-syndrome,C0685838,T019,Disorders
What is (are) Perry syndrome ?,0000786-1,information,"Perry syndrome is a progressive brain disease that is characterized by four major features: a pattern of movement abnormalities known as parkinsonism, psychiatric changes, weight loss, and abnormally slow breathing (hypoventilation). These signs and symptoms typically appear in a person's forties or fifties.  Parkinsonism and psychiatric changes are usually the earliest features of Perry syndrome. Signs of parkinsonism include unusually slow movements (bradykinesia), stiffness, and tremors. These movement abnormalities are often accompanied by changes in personality and behavior. The most frequent psychiatric changes that occur in people with Perry syndrome include depression, a general loss of interest and enthusiasm (apathy), withdrawal from friends and family, and suicidal thoughts. Many affected individuals also experience significant, unexplained weight loss early in the disease.  Hypoventilation is a later feature of Perry syndrome. Abnormally slow breathing most often occurs at night, causing affected individuals to wake up frequently. As the disease worsens, hypoventilation can result in a life-threatening lack of oxygen and respiratory failure.  People with Perry syndrome typically survive for about 5 years after signs and symptoms first appear. Most affected individuals ultimately die of respiratory failure or pneumonia. Suicide is another cause of death in this condition.",Perry syndrome,0000786,GHR,https://ghr.nlm.nih.gov/condition/perry-syndrome,C1868594,T047,Disorders
How many people are affected by Perry syndrome ?,0000786-2,frequency,Perry syndrome is very rare; about 50 affected individuals have been reported worldwide.,Perry syndrome,0000786,GHR,https://ghr.nlm.nih.gov/condition/perry-syndrome,C1868594,T047,Disorders
What are the genetic changes related to Perry syndrome ?,0000786-3,genetic changes,"Perry syndrome results from mutations in the DCTN1 gene. This gene provides instructions for making a protein called dynactin-1, which is involved in the transport of materials within cells. To move materials, dynactin-1 interacts with other proteins and with a track-like system of small tubes called microtubules. These components work together like a conveyer belt to move materials within cells. This transport system appears to be particularly important for the normal function and survival of nerve cells (neurons) in the brain.  Mutations in the DCTN1 gene alter the structure of dynactin-1, making it less able to attach (bind) to microtubules and transport materials within cells. This abnormality causes neurons to malfunction and ultimately die. A gradual loss of neurons in areas of the brain that regulate movement, emotion, and breathing underlies the signs and symptoms of Perry syndrome.",Perry syndrome,0000786,GHR,https://ghr.nlm.nih.gov/condition/perry-syndrome,C1868594,T047,Disorders
Is Perry syndrome inherited ?,0000786-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In most cases, an affected person inherits the mutation from one affected parent. However, some cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",Perry syndrome,0000786,GHR,https://ghr.nlm.nih.gov/condition/perry-syndrome,C1868594,T047,Disorders
What are the treatments for Perry syndrome ?,0000786-5,treatment,These resources address the diagnosis or management of Perry syndrome:  - Gene Review: Gene Review: Perry Syndrome  - Genetic Testing Registry: Perry syndrome  - MedlinePlus Encyclopedia: Major Depression  - MedlinePlus Encyclopedia: Primary Alveolar Hypoventilation  - National Parkinson Foundation: Treatment   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Perry syndrome,0000786,GHR,https://ghr.nlm.nih.gov/condition/perry-syndrome,C1868594,T047,Disorders
What is (are) persistent Mllerian duct syndrome ?,0000787-1,information,"Persistent Mllerian duct syndrome is a disorder of sexual development that affects males. Males with this disorder have normal male reproductive organs, though they also have a uterus and fallopian tubes, which are female reproductive organs. The uterus and fallopian tubes are derived from a structure called the Mllerian duct during development of the fetus. The Mllerian duct usually breaks down during early development in males, but it is retained in those with persistent Mllerian duct syndrome. Affected individuals have the normal chromosomes of a male (46,XY) and normal external male genitalia.  The first noted signs and symptoms in males with persistent Mllerian duct syndrome are usually undescended testes (cryptorchidism) or soft out-pouchings in the lower abdomen (inguinal hernias). The uterus and fallopian tubes are typically discovered when surgery is performed to treat these conditions.  The testes and female reproductive organs can be located in unusual positions in persistent Mllerian duct syndrome. Occasionally, both testes are undescended (bilateral cryptorchidism) and the uterus is in the pelvis. More often, one testis has descended into the scrotum normally, and one has not. Sometimes, the descended testis pulls the fallopian tube and uterus into the track through which it has descended. This creates a condition called hernia uteri inguinalis, a form of inguinal hernia. In other cases, the undescended testis from the other side of the body is also pulled into the same track, forming an inguinal hernia. This condition, called transverse testicular ectopia, is common in people with persistent Mllerian duct syndrome.  Other effects of persistent Mllerian duct syndrome may include the inability to father children (infertility) or blood in the semen (hematospermia). Also, the undescended testes may break down (degenerate) or develop cancer if left untreated.",persistent Mllerian duct syndrome,0000787,GHR,https://ghr.nlm.nih.gov/condition/persistent-mullerian-duct-syndrome,C0039082,T047,Disorders
How many people are affected by persistent Mllerian duct syndrome ?,0000787-2,frequency,"Persistent Mllerian duct syndrome is a rare disorder; however, the prevalence of the condition is unknown.",persistent Mllerian duct syndrome,0000787,GHR,https://ghr.nlm.nih.gov/condition/persistent-mullerian-duct-syndrome,C0039082,T047,Disorders
What are the genetic changes related to persistent Mllerian duct syndrome ?,0000787-3,genetic changes,"Most people with persistent Mllerian duct syndrome have mutations in the AMH gene or the AMHR2 gene. The AMH gene provides instructions for making a protein called anti-Mllerian hormone (AMH). The AMHR2 gene provides instructions for making a protein called AMH receptor type 2.  The AMH protein and AMH receptor type 2 protein are involved in male sex differentiation. All fetuses develop the Mllerian duct, the precursor to female reproductive organs. During development of a male fetus, these two proteins work together to induce breakdown (regression) of the Mllerian duct. Mutations in the AMH and AMHR2 genes lead to nonfunctional proteins that cannot signal for regression of the Mllerian duct. As a result of these mutations, the Mllerian duct persists and goes on to form a uterus and fallopian tubes.  Approximately 45 percent of cases of persistent Mllerian duct syndrome are caused by mutations in the AMH gene and are called persistent Mllerian duct syndrome type 1. Approximately 40 percent of cases are caused by mutations in the AMHR2 gene and are called persistent Mllerian duct syndrome type 2. In the remaining 15 percent of cases, no mutations in the AMH and AMHR2 genes have been identified, and the genes involved in causing the condition are unknown.",persistent Mllerian duct syndrome,0000787,GHR,https://ghr.nlm.nih.gov/condition/persistent-mullerian-duct-syndrome,C0039082,T047,Disorders
Is persistent Mllerian duct syndrome inherited ?,0000787-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. However, persistent Mllerian duct syndrome affects only males. Females with two mutated copies of the gene do not show signs and symptoms of the condition.",persistent Mllerian duct syndrome,0000787,GHR,https://ghr.nlm.nih.gov/condition/persistent-mullerian-duct-syndrome,C0039082,T047,Disorders
What are the treatments for persistent Mllerian duct syndrome ?,0000787-5,treatment,These resources address the diagnosis or management of persistent Mllerian duct syndrome:  - Genetic Testing Registry: Persistent Mullerian duct syndrome  - MedlinePlus Encyclopedia: Undescended testicle repair   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,persistent Mllerian duct syndrome,0000787,GHR,https://ghr.nlm.nih.gov/condition/persistent-mullerian-duct-syndrome,C0039082,T047,Disorders
What is (are) Peters plus syndrome ?,0000789-1,information,"Peters plus syndrome is an inherited condition that is characterized by eye abnormalities, short stature, an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate), distinctive facial features, and intellectual disability.  The eye problems in Peters plus syndrome occur in an area at the front part of the eye known as the anterior segment. The anterior segment consists of structures including the lens, the colored part of the eye (iris), and the clear covering of the eye (cornea). An eye problem called Peters anomaly is the most common anterior segment abnormality seen in Peters plus syndrome. Peters anomaly involves abnormal development of the anterior segment, which results in a cornea that is cloudy (opaque) and causes blurred vision. Peters anomaly may also be associated with clouding of the lenses of the eyes (cataracts) or other lens abnormalities. Peters anomaly is usually bilateral, which means that it affects both eyes. The severity of corneal clouding and other eye problems can vary between individuals with Peters plus syndrome, even among members of the same family. Many people with Peters plus syndrome experience vision loss that worsens over time.  All people with Peters plus syndrome have short stature, which is evident before birth. The height of adult males with this condition ranges from 141 centimeters to 155 centimeters (4 feet, 7 inches to 5 feet, 1 inch), and the height of adult females ranges from 128 centimeters to 151 centimeters (4 feet, 2 inches to 4 feet, 11 inches). Individuals with Peters plus syndrome also have shortened upper limbs (rhizomelia) and shortened fingers and toes (brachydactyly).  The characteristic facial features of Peters plus syndrome include a prominent forehead; small, malformed ears; narrow eyes; a long area between the nose and mouth (philtrum); and a pronounced double curve of the upper lip (Cupid's bow). The neck may also be broad and webbed. A cleft lip with or without a cleft palate is present in about half of the people with this condition.  Developmental milestones, such as walking and speech, are delayed in most children with Peters plus syndrome. Most affected individuals also have intellectual disability that can range from mild to severe, although some have normal intelligence. The severity of physical features does not predict the level of intellectual disability.  Less common signs and symptoms of Peters plus syndrome include heart defects, structural brain abnormalities, hearing loss, and kidney or genital abnormalities.",Peters plus syndrome,0000789,GHR,https://ghr.nlm.nih.gov/condition/peters-plus-syndrome,C0796012,T019,Disorders
How many people are affected by Peters plus syndrome ?,0000789-2,frequency,Peters plus syndrome is a rare disorder; its incidence is unknown. Fewer than 80 people with this condition have been reported worldwide.,Peters plus syndrome,0000789,GHR,https://ghr.nlm.nih.gov/condition/peters-plus-syndrome,C0796012,T019,Disorders
What are the genetic changes related to Peters plus syndrome ?,0000789-3,genetic changes,"Mutations in the B3GLCT gene cause Peters plus syndrome. The B3GLCT gene provides instructions for making an enzyme called beta 3-glucosyltransferase (B3Glc-T), which is involved in the complex process of adding sugar molecules to proteins (glycosylation). Glycosylation modifies proteins so they can perform a wider variety of functions. Most mutations in the B3GLCT gene lead to the production of an abnormally short, nonfunctional version of the B3Glc-T enzyme, which disrupts glycosylation. It is unclear how the loss of functional B3Glc-T enzyme leads to the signs and symptoms of Peters plus syndrome, but impaired glycosylation likely disrupts the function of many proteins, which may contribute to the variety of features.",Peters plus syndrome,0000789,GHR,https://ghr.nlm.nih.gov/condition/peters-plus-syndrome,C0796012,T019,Disorders
Is Peters plus syndrome inherited ?,0000789-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Peters plus syndrome,0000789,GHR,https://ghr.nlm.nih.gov/condition/peters-plus-syndrome,C0796012,T019,Disorders
What are the treatments for Peters plus syndrome ?,0000789-5,treatment,These resources address the diagnosis or management of Peters plus syndrome:  - Gene Review: Gene Review: Peters Plus Syndrome  - Genetic Testing Registry: Peters plus syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Peters plus syndrome,0000789,GHR,https://ghr.nlm.nih.gov/condition/peters-plus-syndrome,C0796012,T019,Disorders
What is (are) Peutz-Jeghers syndrome ?,0000790-1,information,"Peutz-Jeghers syndrome is characterized by the development of noncancerous growths called hamartomatous polyps in the gastrointestinal tract (particularly the stomach and intestines) and a greatly increased risk of developing certain types of cancer.  Children with Peutz-Jeghers syndrome often develop small, dark-colored spots on the lips, around and inside the mouth, near the eyes and nostrils, and around the anus. These spots may also occur on the hands and feet. They appear during childhood and often fade as the person gets older. In addition, most people with Peutz-Jeghers syndrome develop multiple polyps in the stomach and intestines during childhood or adolescence. Polyps can cause health problems such as recurrent bowel obstructions, chronic bleeding, and abdominal pain.  People with Peutz-Jeghers syndrome have a high risk of developing cancer during their lifetimes. Cancers of the gastrointestinal tract, pancreas, cervix, ovary, and breast are among the most commonly reported tumors.",Peutz-Jeghers syndrome,0000790,GHR,https://ghr.nlm.nih.gov/condition/peutz-jeghers-syndrome,C0031269,T047,Disorders
How many people are affected by Peutz-Jeghers syndrome ?,0000790-2,frequency,"The prevalence of this condition is uncertain; estimates range from 1 in 25,000 to 300,000 individuals.",Peutz-Jeghers syndrome,0000790,GHR,https://ghr.nlm.nih.gov/condition/peutz-jeghers-syndrome,C0031269,T047,Disorders
What are the genetic changes related to Peutz-Jeghers syndrome ?,0000790-3,genetic changes,"Mutations in the STK11 gene (also known as LKB1) cause most cases of Peutz-Jeghers syndrome. The STK11 gene is a tumor suppressor gene, which means that it normally prevents cells from growing and dividing too rapidly or in an uncontrolled way. A mutation in this gene alters the structure or function of the STK11 protein, disrupting its ability to restrain cell division. The resulting uncontrolled cell growth leads to the formation of noncancerous polyps and cancerous tumors in people with Peutz-Jeghers syndrome.  A small percentage of people with Peutz-Jeghers syndrome do not have mutations in the STK11 gene. In these cases, the cause of the disorder is unknown.",Peutz-Jeghers syndrome,0000790,GHR,https://ghr.nlm.nih.gov/condition/peutz-jeghers-syndrome,C0031269,T047,Disorders
Is Peutz-Jeghers syndrome inherited ?,0000790-4,inheritance,"Peutz-Jeghers syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing noncancerous polyps and cancerous tumors. In about half of all cases, an affected person inherits a mutation in the STK11 gene from one affected parent. The remaining cases occur in people with no history of Peutz-Jeghers syndrome in their family. These cases appear to result from new (de novo) mutations in the STK11 gene.",Peutz-Jeghers syndrome,0000790,GHR,https://ghr.nlm.nih.gov/condition/peutz-jeghers-syndrome,C0031269,T047,Disorders
What are the treatments for Peutz-Jeghers syndrome ?,0000790-5,treatment,These resources address the diagnosis or management of Peutz-Jeghers syndrome:  - Gene Review: Gene Review: Peutz-Jeghers Syndrome  - Genetic Testing Registry: Peutz-Jeghers syndrome  - MedlinePlus Encyclopedia: Peutz-Jeghers Syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Peutz-Jeghers syndrome,0000790,GHR,https://ghr.nlm.nih.gov/condition/peutz-jeghers-syndrome,C0031269,T047,Disorders
What is (are) Pfeiffer syndrome ?,0000791-1,information,"Pfeiffer syndrome is a genetic disorder characterized by the premature fusion of certain skull bones (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face. Pfeiffer syndrome also affects bones in the hands and feet.  Many of the characteristic facial features of Pfeiffer syndrome result from premature fusion of the skull bones. Abnormal growth of these bones leads to bulging and wide-set eyes, a high forehead, an underdeveloped upper jaw, and a beaked nose. More than half of all children with Pfeiffer syndrome have hearing loss; dental problems are also common.  In people with Pfeiffer syndrome, the thumbs and first (big) toes are wide and bend away from the other digits. Unusually short fingers and toes (brachydactyly) are also common, and there may be some webbing or fusion between the digits (syndactyly).  Pfeiffer syndrome is divided into three subtypes. Type 1, also known as classic Pfeiffer syndrome, has symptoms as described above. Most individuals with type 1 Pfeiffer syndrome have normal intelligence and a normal life span. Types 2 and 3 are more severe forms of Pfeiffer syndrome that often involve problems with the nervous system. The premature fusion of skull bones can limit brain growth, leading to delayed development and other neurological problems. Type 2 is distinguished from type 3 by the presence of a cloverleaf-shaped head, which is caused by more extensive fusion of bones in the skull.",Pfeiffer syndrome,0000791,GHR,https://ghr.nlm.nih.gov/condition/pfeiffer-syndrome,C0220658,T019,Disorders
How many people are affected by Pfeiffer syndrome ?,0000791-2,frequency,"Pfeiffer syndrome affects about 1 in 100,000 individuals.",Pfeiffer syndrome,0000791,GHR,https://ghr.nlm.nih.gov/condition/pfeiffer-syndrome,C0220658,T019,Disorders
What are the genetic changes related to Pfeiffer syndrome ?,0000791-3,genetic changes,"Pfeiffer syndrome results from mutations in the FGFR1 or FGFR2 gene. These genes provide instructions for making proteins known as fibroblast growth receptors 1 and 2. Among their multiple functions, these proteins signal immature cells to become bone cells during embryonic development. A mutation in either the FGFR1 or FGFR2 gene alters protein function and causes prolonged signaling, which can promote the premature fusion of skull bones and affect the development of bones in the hands and feet.  Type 1 Pfeiffer syndrome is caused by mutations in either the FGFR1 or FGFR2 gene. Types 2 and 3 are caused by mutations in the FGFR2 gene, and have not been associated with changes in the FGFR1 gene.",Pfeiffer syndrome,0000791,GHR,https://ghr.nlm.nih.gov/condition/pfeiffer-syndrome,C0220658,T019,Disorders
Is Pfeiffer syndrome inherited ?,0000791-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Pfeiffer syndrome,0000791,GHR,https://ghr.nlm.nih.gov/condition/pfeiffer-syndrome,C0220658,T019,Disorders
What are the treatments for Pfeiffer syndrome ?,0000791-5,treatment,These resources address the diagnosis or management of Pfeiffer syndrome:  - Gene Review: Gene Review: FGFR-Related Craniosynostosis Syndromes  - Genetic Testing Registry: Pfeiffer syndrome  - MedlinePlus Encyclopedia: Craniosynostosis  - MedlinePlus Encyclopedia: Webbing of fingers or toes   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Pfeiffer syndrome,0000791,GHR,https://ghr.nlm.nih.gov/condition/pfeiffer-syndrome,C0220658,T019,Disorders
What is (are) phenylketonuria ?,0000792-1,information,"Phenylketonuria (commonly known as PKU) is an inherited disorder that increases the levels of a substance called phenylalanine in the blood. Phenylalanine is a building block of proteins (an amino acid) that is obtained through the diet. It is found in all proteins and in some artificial sweeteners. If PKU is not treated, phenylalanine can build up to harmful levels in the body, causing intellectual disability and other serious health problems.  The signs and symptoms of PKU vary from mild to severe. The most severe form of this disorder is known as classic PKU. Infants with classic PKU appear normal until they are a few months old. Without treatment, these children develop permanent intellectual disability. Seizures, delayed development, behavioral problems, and psychiatric disorders are also common. Untreated individuals may have a musty or mouse-like odor as a side effect of excess phenylalanine in the body. Children with classic PKU tend to have lighter skin and hair than unaffected family members and are also likely to have skin disorders such as eczema.  Less severe forms of this condition, sometimes called variant PKU and non-PKU hyperphenylalaninemia, have a smaller risk of brain damage. People with very mild cases may not require treatment with a low-phenylalanine diet.  Babies born to mothers with PKU and uncontrolled phenylalanine levels (women who no longer follow a low-phenylalanine diet) have a significant risk of intellectual disability because they are exposed to very high levels of phenylalanine before birth. These infants may also have a low birth weight and grow more slowly than other children. Other characteristic medical problems include heart defects or other heart problems, an abnormally small head size (microcephaly), and behavioral problems. Women with PKU and uncontrolled phenylalanine levels also have an increased risk of pregnancy loss.",phenylketonuria,0000792,GHR,https://ghr.nlm.nih.gov/condition/phenylketonuria,C0031485,T047,Disorders
How many people are affected by phenylketonuria ?,0000792-2,frequency,"The occurrence of PKU varies among ethnic groups and geographic regions worldwide. In the United States, PKU occurs in 1 in 10,000 to 15,000 newborns. Most cases of PKU are detected shortly after birth by newborn screening, and treatment is started promptly. As a result, the severe signs and symptoms of classic PKU are rarely seen.",phenylketonuria,0000792,GHR,https://ghr.nlm.nih.gov/condition/phenylketonuria,C0031485,T047,Disorders
What are the genetic changes related to phenylketonuria ?,0000792-3,genetic changes,"Mutations in the PAH gene cause phenylketonuria.  The PAH gene provides instructions for making an enzyme called phenylalanine hydroxylase. This enzyme converts the amino acid phenylalanine to other important compounds in the body. If gene mutations reduce the activity of phenylalanine hydroxylase, phenylalanine from the diet is not processed effectively. As a result, this amino acid can build up to toxic levels in the blood and other tissues. Because nerve cells in the brain are particularly sensitive to phenylalanine levels, excessive amounts of this substance can cause brain damage.  Classic PKU, the most severe form of the disorder, occurs when phenylalanine hydroxylase activity is severely reduced or absent. People with untreated classic PKU have levels of phenylalanine high enough to cause severe brain damage and other serious medical problems. Mutations in the PAH gene that allow the enzyme to retain some activity result in milder versions of this condition, such as variant PKU or non-PKU hyperphenylalaninemia.  Changes in other genes may influence the severity of PKU, but little is known about these additional genetic factors.",phenylketonuria,0000792,GHR,https://ghr.nlm.nih.gov/condition/phenylketonuria,C0031485,T047,Disorders
Is phenylketonuria inherited ?,0000792-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",phenylketonuria,0000792,GHR,https://ghr.nlm.nih.gov/condition/phenylketonuria,C0031485,T047,Disorders
What are the treatments for phenylketonuria ?,0000792-5,treatment,These resources address the diagnosis or management of phenylketonuria:  - Baby's First Test  - Gene Review: Gene Review: Phenylalanine Hydroxylase Deficiency  - Genetic Testing Registry: Phenylketonuria  - MedlinePlus Encyclopedia: Phenylketonuria  - MedlinePlus Encyclopedia: Serum Phenylalanine Screening   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,phenylketonuria,0000792,GHR,https://ghr.nlm.nih.gov/condition/phenylketonuria,C0031485,T047,Disorders
What is (are) phosphoglycerate dehydrogenase deficiency ?,0000793-1,information,"Phosphoglycerate dehydrogenase deficiency is a condition characterized by an unusually small head size (microcephaly); impaired development of physical reactions, movements, and speech (psychomotor retardation); and recurrent seizures (epilepsy). Different types of phosphoglycerate dehydrogenase deficiency have been described; they are distinguished by their severity and the age at which symptoms first begin. Most affected individuals have the infantile form, which is the most severe form, and are affected from infancy. Symptoms of the juvenile and adult types appear later in life; these types are very rare.  In phosphoglycerate dehydrogenase deficiency there is a progressive loss of brain cells leading to a loss of brain tissue (brain atrophy), specifically affecting the fatty tissue known as myelin that surrounds nerve cells (hypomyelination). Frequently, the tissue that connects the two halves of the brain (corpus callosum) is small and thin, and the fluid-filled cavities (ventricles) near the center of the brain are enlarged. Because development of the brain is disrupted, the head does not grow at the same rate as the body, so it appears that the head is getting smaller as the body grows (progressive microcephaly). Poor brain growth leads to an inability to achieve many developmental milestones such as sitting unsupported and speaking. Many affected infants also have difficulty feeding.  The seizures in phosphoglycerate dehydrogenase deficiency can vary in type. Recurrent muscle contractions called infantile spasms are typical early in the disorder. Without early treatment, seizures may progress to tonic-clonic seizures, which involve a loss of consciousness, muscle rigidity, and convulsions; myoclonic seizures, which involve rapid, uncontrolled muscle jerks; or drop attacks, which are sudden episodes of weak muscle tone.  Individuals with the infantile form of phosphoglycerate dehydrogenase deficiency develop many of the features described above. Individuals with the juvenile form typically have epilepsy as well as mild developmental delay and intellectual disability. Only one case of the adult form has been reported; signs and symptoms began in mid-adulthood and included mild intellectual disability; difficulty coordinating movements (ataxia); and numbness, tingling, and pain in the arms and legs (sensory neuropathy).",phosphoglycerate dehydrogenase deficiency,0000793,GHR,https://ghr.nlm.nih.gov/condition/phosphoglycerate-dehydrogenase-deficiency,C1866174,T047,Disorders
How many people are affected by phosphoglycerate dehydrogenase deficiency ?,0000793-2,frequency,"This condition is likely a rare disorder, but its prevalence is unknown. At least 15 cases have been described in the scientific literature.",phosphoglycerate dehydrogenase deficiency,0000793,GHR,https://ghr.nlm.nih.gov/condition/phosphoglycerate-dehydrogenase-deficiency,C1866174,T047,Disorders
What are the genetic changes related to phosphoglycerate dehydrogenase deficiency ?,0000793-3,genetic changes,"Mutations in the PHGDH gene cause phosphoglycerate dehydrogenase deficiency. The PHGDH gene provides instructions for making the parts (subunits) that make up the phosphoglycerate dehydrogenase enzyme. Four PHGDH subunits combine to form the enzyme. This enzyme is involved in the production of the protein building block (amino acid) serine. Specifically, the enzyme converts a substance called 3-phosphoglycerate to 3-phosphohydroxypyruvate in the first step in serine production. Serine is necessary for the development and function of the brain and spinal cord (central nervous system). Serine is a part of chemical messengers called neurotransmitters that transmit signals in the nervous system. Proteins that form cell membranes and myelin also contain serine. Serine can be obtained from the diet, but brain cells must produce their own serine because dietary serine cannot cross the protective barrier that allows only certain substances to pass between blood vessels and the brain (the blood-brain barrier).  PHGDH gene mutations result in the production of an enzyme with decreased function. As a result, less 3-phosphoglycerate is converted into 3-phosphohydroxypyruvate than normal and serine production is stalled at the first step. The lack of serine likely prevents the production of proteins and neurotransmitters in the brain and impairs the formation of normal cells and myelin. These disruptions in normal brain development lead to the signs and symptoms of phosphoglycerate dehydrogenase deficiency.",phosphoglycerate dehydrogenase deficiency,0000793,GHR,https://ghr.nlm.nih.gov/condition/phosphoglycerate-dehydrogenase-deficiency,C1866174,T047,Disorders
Is phosphoglycerate dehydrogenase deficiency inherited ?,0000793-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",phosphoglycerate dehydrogenase deficiency,0000793,GHR,https://ghr.nlm.nih.gov/condition/phosphoglycerate-dehydrogenase-deficiency,C1866174,T047,Disorders
What are the treatments for phosphoglycerate dehydrogenase deficiency ?,0000793-5,treatment,These resources address the diagnosis or management of phosphoglycerate dehydrogenase deficiency:  - Genetic Testing Registry: Phosphoglycerate dehydrogenase deficiency  - Seattle Children's Hospital: Epilepsy Symptoms and Diagnosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,phosphoglycerate dehydrogenase deficiency,0000793,GHR,https://ghr.nlm.nih.gov/condition/phosphoglycerate-dehydrogenase-deficiency,C1866174,T047,Disorders
What is (are) phosphoglycerate kinase deficiency ?,0000794-1,information,"Phosphoglycerate kinase deficiency is a genetic disorder that affects the body's ability to break down the simple sugar glucose, which is the primary energy source for most cells. Researchers have described two major forms of the condition. The most common form is sometimes called the hemolytic form. It is characterized by a condition known as chronic hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely. Chronic hemolytic anemia can lead to unusually pale skin (pallor), yellowing of the eyes and skin (jaundice), fatigue, shortness of breath, and a rapid heart rate. Some people with the hemolytic form also have symptoms related to abnormal brain function, including intellectual disability, seizures, and stroke.  The other form of phosphoglycerate kinase deficiency is often called the myopathic form. It primarily affects muscles, causing progressive weakness, pain, and cramping, particularly with exercise. During exercise, muscle tissue can be broken down, releasing a protein called myoglobin. This protein is processed by the kidneys and released in the urine (myoglobinuria). If untreated, myoglobinuria can lead to kidney failure.  Most people with phosphoglycerate kinase deficiency have either the hemolytic form or the myopathic form. However, other combinations of signs and symptoms (such as muscle weakness with neurologic symptoms) have also been reported.",phosphoglycerate kinase deficiency,0000794,GHR,https://ghr.nlm.nih.gov/condition/phosphoglycerate-kinase-deficiency,C3469599,T046,Disorders
How many people are affected by phosphoglycerate kinase deficiency ?,0000794-2,frequency,Phosphoglycerate kinase deficiency appears to be a rare disorder. About 30 families with affected members have been reported in the scientific literature.,phosphoglycerate kinase deficiency,0000794,GHR,https://ghr.nlm.nih.gov/condition/phosphoglycerate-kinase-deficiency,C3469599,T046,Disorders
What are the genetic changes related to phosphoglycerate kinase deficiency ?,0000794-3,genetic changes,"Phosphoglycerate kinase deficiency is caused by mutations in the PGK1 gene. This gene provides instructions for making an enzyme called phosphoglycerate kinase, which is involved in a critical energy-producing process in cells known as glycolysis. During glycolysis, the simple sugar glucose is broken down to produce energy.  Mutations in the PGK1 gene reduce the activity of phosphoglycerate kinase, which disrupts energy production and leads to cell damage or cell death. It is unclear why this abnormality preferentially affects red blood cells and brain cells in some people and muscle cells in others. Researchers speculate that different PGK1 gene mutations may have varying effects on the activity of phosphoglycerate kinase in different types of cells.",phosphoglycerate kinase deficiency,0000794,GHR,https://ghr.nlm.nih.gov/condition/phosphoglycerate-kinase-deficiency,C3469599,T046,Disorders
Is phosphoglycerate kinase deficiency inherited ?,0000794-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The PGK1 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Females with one altered PGK1 gene, however, may have some features of phosphoglycerate kinase deficiency, such as anemia. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",phosphoglycerate kinase deficiency,0000794,GHR,https://ghr.nlm.nih.gov/condition/phosphoglycerate-kinase-deficiency,C3469599,T046,Disorders
What are the treatments for phosphoglycerate kinase deficiency ?,0000794-5,treatment,These resources address the diagnosis or management of phosphoglycerate kinase deficiency:  - Children Living with Inherited Metabolic Diseases (CLIMB) (UK): Phosphoglycerate Kinase Deficiency  - Genetic Testing Registry: Deficiency of phosphoglycerate kinase  - Genetic Testing Registry: Phosphoglycerate kinase 1 deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,phosphoglycerate kinase deficiency,0000794,GHR,https://ghr.nlm.nih.gov/condition/phosphoglycerate-kinase-deficiency,C3469599,T046,Disorders
What is (are) phosphoglycerate mutase deficiency ?,0000795-1,information,"Phosphoglycerate mutase deficiency is a disorder that primarily affects muscles used for movement (skeletal muscles). Beginning in childhood or adolescence, affected individuals experience muscle aches or cramping following strenuous physical activity. Some people with this condition also have recurrent episodes of myoglobinuria. Myoglobinuria occurs when muscle tissue breaks down abnormally and releases a protein called myoglobin, which is processed by the kidneys and released in the urine. If untreated, myoglobinuria can lead to kidney failure.  In some cases of phosphoglycerate mutase deficiency, microscopic tube-shaped structures called tubular aggregates are seen in muscle fibers. It is unclear how tubular aggregates are associated with the signs and symptoms of the disorder.",phosphoglycerate mutase deficiency,0000795,GHR,https://ghr.nlm.nih.gov/condition/phosphoglycerate-mutase-deficiency,C0268149,T047,Disorders
How many people are affected by phosphoglycerate mutase deficiency ?,0000795-2,frequency,Phosphoglycerate mutase deficiency is a rare condition; about 15 affected people have been reported in the medical literature. Most affected individuals have been African American.,phosphoglycerate mutase deficiency,0000795,GHR,https://ghr.nlm.nih.gov/condition/phosphoglycerate-mutase-deficiency,C0268149,T047,Disorders
What are the genetic changes related to phosphoglycerate mutase deficiency ?,0000795-3,genetic changes,"Phosphoglycerate mutase deficiency is caused by mutations in the PGAM2 gene. This gene provides instructions for making an enzyme called phosphoglycerate mutase, which is involved in a critical energy-producing process in cells known as glycolysis. During glycolysis, the simple sugar glucose is broken down to produce energy.  The version of phosphoglycerate mutase produced from the PGAM2 gene is found primarily in skeletal muscle cells. Mutations in the PGAM2 gene greatly reduce the activity of phosphoglycerate mutase, which disrupts energy production in these cells. This defect underlies the muscle cramping and myoglobinuria that occur after strenuous exercise in affected individuals.",phosphoglycerate mutase deficiency,0000795,GHR,https://ghr.nlm.nih.gov/condition/phosphoglycerate-mutase-deficiency,C0268149,T047,Disorders
Is phosphoglycerate mutase deficiency inherited ?,0000795-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the PGAM2 gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. However, people who carry one altered copy of the PGAM2 gene may have some features of phosphoglycerate mutase deficiency, including episodes of exercise-induced muscle cramping and myoglobinuria.",phosphoglycerate mutase deficiency,0000795,GHR,https://ghr.nlm.nih.gov/condition/phosphoglycerate-mutase-deficiency,C0268149,T047,Disorders
What are the treatments for phosphoglycerate mutase deficiency ?,0000795-5,treatment,These resources address the diagnosis or management of phosphoglycerate mutase deficiency:  - Genetic Testing Registry: Glycogen storage disease type X   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,phosphoglycerate mutase deficiency,0000795,GHR,https://ghr.nlm.nih.gov/condition/phosphoglycerate-mutase-deficiency,C0268149,T047,Disorders
What is (are) phosphoribosylpyrophosphate synthetase superactivity ?,0000796-1,information,"Phosphoribosylpyrophosphate synthetase superactivity (PRS superactivity) is characterized by the overproduction and accumulation of uric acid (a waste product of normal chemical processes) in the blood and urine. The overproduction of uric acid can lead to gout, which is arthritis caused by an accumulation of uric acid crystals in the joints. Individuals with PRS superactivity also develop kidney or bladder stones that may result in episodes of acute kidney failure.  There are two forms of PRS superactivity, a severe form that begins in infancy or early childhood, and a milder form that typically appears in late adolescence or early adulthood. In both forms, a kidney or bladder stone is often the first symptom. Gout and impairment of kidney function may develop if the condition is not adequately controlled with medication and dietary restrictions. People with the severe form may also have neurological problems, including hearing loss caused by changes in the inner ear (sensorineural hearing loss), weak muscle tone (hypotonia), impaired muscle coordination (ataxia), and developmental delay.",phosphoribosylpyrophosphate synthetase superactivity,0000796,GHR,https://ghr.nlm.nih.gov/condition/phosphoribosylpyrophosphate-synthetase-superactivity,C1970827,T047,Disorders
How many people are affected by phosphoribosylpyrophosphate synthetase superactivity ?,0000796-2,frequency,PRS superactivity is believed to be a rare disorder. Approximately 30 families with the condition have been reported. More than two thirds of these families are affected by the milder form of the disease.,phosphoribosylpyrophosphate synthetase superactivity,0000796,GHR,https://ghr.nlm.nih.gov/condition/phosphoribosylpyrophosphate-synthetase-superactivity,C1970827,T047,Disorders
What are the genetic changes related to phosphoribosylpyrophosphate synthetase superactivity ?,0000796-3,genetic changes,"Certain mutations in the PRPS1 gene cause PRS superactivity. The PRPS1 gene provides instructions for making an enzyme called phosphoribosyl pyrophosphate synthetase 1, or PRPP synthetase 1. This enzyme helps produce a molecule called phosphoribosyl pyrophosphate (PRPP). PRPP is involved in producing purine and pyrimidine nucleotides. These nucleotides are building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in the cell. PRPP synthetase 1 and PRPP also play a key role in recycling purines from the breakdown of DNA and RNA, a faster and more efficient way of making purines available.  In people with the more severe form of PRS superactivity, PRPS1 gene mutations change single protein building blocks (amino acids) in the PRPP synthetase 1 enzyme, resulting in a poorly regulated, overactive enzyme. In the milder form of PRS superactivity, the PRPS1 gene is overactive for reasons that are not well understood. PRPS1 gene overactivity increases the production of normal PRPP synthetase 1 enzyme, which increases the availability of PRPP. In both forms of the disorder, excessive amounts of purines are generated.  Under these conditions, uric acid, a waste product of purine breakdown, accumulates in the body. A buildup of uric acid crystals can cause gout, kidney stones, and bladder stones. It is unclear how PRPS1 gene mutations are related to the neurological problems associated with the severe form of PRS superactivity.",phosphoribosylpyrophosphate synthetase superactivity,0000796,GHR,https://ghr.nlm.nih.gov/condition/phosphoribosylpyrophosphate-synthetase-superactivity,C1970827,T047,Disorders
Is phosphoribosylpyrophosphate synthetase superactivity inherited ?,0000796-4,inheritance,"This condition is inherited in an X-linked pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell sometimes causes the disorder.  In most reported cases, affected individuals have inherited the mutation from a parent who carries an altered copy of the PRPS1 gene. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. PRS superactivity may also result from new mutations in the PRPS1 gene and can occur in people with no history of the disorder in their family.",phosphoribosylpyrophosphate synthetase superactivity,0000796,GHR,https://ghr.nlm.nih.gov/condition/phosphoribosylpyrophosphate-synthetase-superactivity,C1970827,T047,Disorders
What are the treatments for phosphoribosylpyrophosphate synthetase superactivity ?,0000796-5,treatment,"These resources address the diagnosis or management of PRS superactivity:  - Gene Review: Gene Review: Phosphoribosylpyrophosphate Synthetase Superactivity  - Genetic Testing Registry: Phosphoribosylpyrophosphate synthetase superactivity  - MedlinePlus Encyclopedia: Hearing Loss  - MedlinePlus Encyclopedia: Movement, Uncoordinated   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",phosphoribosylpyrophosphate synthetase superactivity,0000796,GHR,https://ghr.nlm.nih.gov/condition/phosphoribosylpyrophosphate-synthetase-superactivity,C1970827,T047,Disorders
What is (are) piebaldism ?,0000797-1,information,"Piebaldism is a condition characterized by the absence of cells called melanocytes in certain areas of the skin and hair. Melanocytes produce the pigment melanin, which contributes to hair, eye, and skin color. The absence of melanocytes leads to patches of skin and hair that are lighter than normal. Approximately 90 percent of affected individuals have a white section of hair near their front hairline (a white forelock). The eyelashes, the eyebrows, and the skin under the forelock may also be unpigmented.  People with piebaldism usually have other unpigmented patches of skin, typically appearing symmetrically on both sides of the body. There may be spots or patches of pigmented skin within or around the borders of the unpigmented areas.  In most cases, the unpigmented areas are present at birth and do not increase in size or number. The unpigmented patches are at increased risk of sunburn and skin cancer related to excessive sun exposure. Some people with piebaldism are self-conscious about the appearance of the unpigmented patches, which may be more noticeable in darker-skinned people. Aside from these potential issues, this condition has no effect on the health of the affected individual.",piebaldism,0000797,GHR,https://ghr.nlm.nih.gov/condition/piebaldism,C0080024,T047,Disorders
How many people are affected by piebaldism ?,0000797-2,frequency,The prevalence of piebaldism is unknown.,piebaldism,0000797,GHR,https://ghr.nlm.nih.gov/condition/piebaldism,C0080024,T047,Disorders
What are the genetic changes related to piebaldism ?,0000797-3,genetic changes,"Piebaldism can be caused by mutations in the KIT and SNAI2 genes. Piebaldism may also be a feature of other conditions, such as Waardenburg syndrome; these conditions have other genetic causes and additional signs and symptoms.  The KIT gene provides instructions for making a protein that is involved in signaling within cells. KIT protein signaling is important for the development of certain cell types, including melanocytes. The KIT gene mutations responsible for piebaldism lead to a nonfunctional KIT protein. The loss of KIT signaling is thought to disrupt the growth and division (proliferation) and movement (migration) of melanocytes during development, resulting in patches of skin that lack pigmentation.  The SNAI2 gene (often called SLUG) provides instructions for making a protein called snail 2. Research indicates that the snail 2 protein is required during embryonic growth for the development of cells called neural crest cells. Neural crest cells migrate from the developing spinal cord to specific regions in the embryo and give rise to many tissues and cell types, including melanocytes. The snail 2 protein probably plays a role in the formation and survival of melanocytes. SNAI2 gene mutations that cause piebaldism probably reduce the production of the snail 2 protein. Shortage of the snail 2 protein may disrupt the development of melanocytes in certain areas of the skin and hair, causing the patchy loss of pigment.  Piebaldism is sometimes mistaken for another condition called vitiligo, which also causes unpigmented patches of skin. People are not born with vitiligo, but acquire it later in life, and it is not caused by specific genetic mutations. For unknown reasons, in people with vitiligo the immune system appears to damage the melanocytes in the skin.",piebaldism,0000797,GHR,https://ghr.nlm.nih.gov/condition/piebaldism,C0080024,T047,Disorders
Is piebaldism inherited ?,0000797-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",piebaldism,0000797,GHR,https://ghr.nlm.nih.gov/condition/piebaldism,C0080024,T047,Disorders
What are the treatments for piebaldism ?,0000797-5,treatment,These resources address the diagnosis or management of piebaldism:  - Genetic Testing Registry: Partial albinism   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,piebaldism,0000797,GHR,https://ghr.nlm.nih.gov/condition/piebaldism,C0080024,T047,Disorders
What is (are) pilomatricoma ?,0000798-1,information,"Pilomatricoma, also known as pilomatrixoma, is a type of noncancerous (benign) skin tumor associated with hair follicles. Hair follicles are specialized structures in the skin where hair growth occurs. Pilomatricomas occur most often on the head or neck, although they can also be found on the arms, torso, or legs. A pilomatricoma feels like a small, hard lump under the skin. This type of tumor grows relatively slowly and usually does not cause pain or other symptoms. Most affected individuals have a single tumor, although rarely multiple pilomatricomas can occur. If a pilomatricoma is removed surgically, it tends not to grow back (recur).  Most pilomatricomas occur in people under the age of 20. However, these tumors can also appear later in life. Almost all pilomatricomas are benign, but a very small percentage are cancerous (malignant). Unlike the benign form, the malignant version of this tumor (known as a pilomatrix carcinoma) occurs most often in middle age or late in life.  Pilomatricoma usually occurs without other signs or symptoms (isolated), but this type of tumor has also rarely been reported with inherited conditions. Disorders that can be associated with pilomatricoma include Gardner syndrome, which is characterized by multiple growths (polyps) and cancers of the colon and rectum; myotonic dystrophy, which is a form of muscular dystrophy; and Rubinstein-Taybi syndrome, which is a condition that affects many parts of the body and is associated with an increased risk of both benign and malignant tumors.",pilomatricoma,0000798,GHR,https://ghr.nlm.nih.gov/condition/pilomatricoma,C0206711,T191,Disorders
How many people are affected by pilomatricoma ?,0000798-2,frequency,"Pilomatricoma is an uncommon tumor. The exact prevalence is unknown, but pilomatricoma probably accounts for less than 1 percent of all benign skin tumors.",pilomatricoma,0000798,GHR,https://ghr.nlm.nih.gov/condition/pilomatricoma,C0206711,T191,Disorders
What are the genetic changes related to pilomatricoma ?,0000798-3,genetic changes,"Mutations in the CTNNB1 gene are found in almost all cases of isolated pilomatricoma. These mutations are somatic, which means they are acquired during a person's lifetime and are present only in tumor cells. Somatic mutations are not inherited.  The CTNNB1 gene provides instructions for making a protein called beta-catenin. This protein plays an important role in sticking cells together (cell adhesion) and in communication between cells. It is also involved in cell signaling as part of the WNT signaling pathway. This pathway promotes the growth and division (proliferation) of cells and helps determine the specialized functions a cell will have (differentiation). WNT signaling is involved in many aspects of development before birth, as well as the maintenance and repair of adult tissues.  Among its many activities, beta-catenin appears to be necessary for the normal function of hair follicles. This protein is active in cells that make up a part of the hair follicle known as the matrix. These cells divide and mature to form the different components of the hair follicle and the hair shaft. As matrix cells divide, the hair shaft is pushed upward and extends beyond the skin.  Mutations in the CTNNB1 gene lead to a version of beta-catenin that is always turned on (constitutively active). The overactive protein triggers matrix cells to divide too quickly and in an uncontrolled way, leading to the formation of a pilomatricoma.  Most pilomatrix carcinomas, the malignant version of pilomatricoma, also have somatic mutations in the CTNNB1 gene. It is unclear why some pilomatricomas are cancerous but most others are not.",pilomatricoma,0000798,GHR,https://ghr.nlm.nih.gov/condition/pilomatricoma,C0206711,T191,Disorders
Is pilomatricoma inherited ?,0000798-4,inheritance,"Most people with isolated pilomatricoma do not have any other affected family members. However, rare families with multiple affected members have been reported. In these cases, the inheritance pattern of the condition (if any) is unknown.",pilomatricoma,0000798,GHR,https://ghr.nlm.nih.gov/condition/pilomatricoma,C0206711,T191,Disorders
What are the treatments for pilomatricoma ?,0000798-5,treatment,These resources address the diagnosis or management of pilomatricoma:  - Genetic Testing Registry: Pilomatrixoma   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,pilomatricoma,0000798,GHR,https://ghr.nlm.nih.gov/condition/pilomatricoma,C0206711,T191,Disorders
What is (are) Pitt-Hopkins syndrome ?,0000799-1,information,"Pitt-Hopkins syndrome is a condition characterized by intellectual disability and developmental delay, breathing problems, recurrent seizures (epilepsy), and distinctive facial features.  People with Pitt-Hopkins syndrome have moderate to severe intellectual disability. Most affected individuals have delayed development of mental and motor skills (psychomotor delay). They are delayed in learning to walk and developing fine motor skills such as picking up small items with their fingers. People with Pitt-Hopkins syndrome typically do not develop speech; some may learn to say a few words. Many affected individuals exhibit features of autistic spectrum disorders, which are characterized by impaired communication and socialization skills.  Breathing problems in individuals with Pitt-Hopkins syndrome are characterized by episodes of rapid breathing (hyperventilation) followed by periods in which breathing slows or stops (apnea). These episodes can cause a lack of oxygen in the blood, leading to a bluish appearance of the skin or lips (cyanosis). In some cases, the lack of oxygen can cause loss of consciousness. Some older individuals with Pitt-Hopkins syndrome develop widened and rounded tips of the fingers and toes (clubbing) because of recurrent episodes of decreased oxygen in the blood. The breathing problems occur only when the person is awake and typically first appear in mid-childhood, but they can begin as early as infancy. Episodes of hyperventilation and apnea can be triggered by emotions such as excitement or anxiety or by extreme tiredness (fatigue).  Epilepsy occurs in most people with Pitt-Hopkins syndrome and usually begins during childhood, although it can be present from birth.  Individuals with Pitt-Hopkins syndrome have distinctive facial features that include thin eyebrows, sunken eyes, a prominent nose with a high nasal bridge, a pronounced double curve of the upper lip (Cupid's bow), a wide mouth with full lips, and widely spaced teeth. The ears are usually thick and cup-shaped.  Children with Pitt-Hopkins syndrome typically have a happy, excitable demeanor with frequent smiling, laughter, and hand-flapping movements. However, they can also experience anxiety and behavioral problems.  Other features of Pitt-Hopkins syndrome may include constipation and other gastrointestinal problems, an unusually small head (microcephaly), nearsightedness (myopia), eyes that do not look in the same direction (strabismus), short stature, and minor brain abnormalities. Affected individuals may also have small hands and feet, a single crease across the palms of the hands, flat feet (pes planus), or unusually fleshy pads at the tips of the fingers and toes. Males with Pitt-Hopkins syndrome may have undescended testes (cryptorchidism).",Pitt-Hopkins syndrome,0000799,GHR,https://ghr.nlm.nih.gov/condition/pitt-hopkins-syndrome,C1970431,T047,Disorders
How many people are affected by Pitt-Hopkins syndrome ?,0000799-2,frequency,Pitt-Hopkins syndrome is thought to be a very rare condition. Approximately 500 affected individuals have been reported worldwide.,Pitt-Hopkins syndrome,0000799,GHR,https://ghr.nlm.nih.gov/condition/pitt-hopkins-syndrome,C1970431,T047,Disorders
What are the genetic changes related to Pitt-Hopkins syndrome ?,0000799-3,genetic changes,"Mutations in the TCF4 gene cause Pitt-Hopkins syndrome. This gene provides instructions for making a protein that attaches (binds) to other proteins and then binds to specific regions of DNA to help control the activity of many other genes. On the basis of its DNA binding and gene controlling activities, the TCF4 protein is known as a transcription factor. The TCF4 protein plays a role in the maturation of cells to carry out specific functions (cell differentiation) and the self-destruction of cells (apoptosis).  TCF4 gene mutations disrupt the protein's ability to bind to DNA and control the activity of certain genes. These disruptions, particularly the inability of the TCF4 protein to control the activity of genes involved in nervous system development and function, contribute to the signs and symptoms of Pitt-Hopkins syndrome. Furthermore, additional proteins interact with the TCF4 protein to carry out specific functions. When the TCF4 protein is nonfunctional, these other proteins are also unable to function normally. It is also likely that the loss of the normal proteins that are attached to the nonfunctional TCF4 proteins contribute to the features of this condition. The loss of one protein in particular, the ASCL1 protein, is thought to be associated with breathing problems in people with Pitt-Hopkins syndrome.",Pitt-Hopkins syndrome,0000799,GHR,https://ghr.nlm.nih.gov/condition/pitt-hopkins-syndrome,C1970431,T047,Disorders
Is Pitt-Hopkins syndrome inherited ?,0000799-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Pitt-Hopkins syndrome,0000799,GHR,https://ghr.nlm.nih.gov/condition/pitt-hopkins-syndrome,C1970431,T047,Disorders
What are the treatments for Pitt-Hopkins syndrome ?,0000799-5,treatment,These resources address the diagnosis or management of Pitt-Hopkins syndrome:  - Gene Review: Gene Review: Pitt-Hopkins Syndrome  - Genetic Testing Registry: Pitt-Hopkins syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Pitt-Hopkins syndrome,0000799,GHR,https://ghr.nlm.nih.gov/condition/pitt-hopkins-syndrome,C1970431,T047,Disorders
"What is (are) platyspondylic lethal skeletal dysplasia, Torrance type ?",0000800-1,information,"Platyspondylic lethal skeletal dysplasia, Torrance type is a severe disorder of bone growth. People with this condition have very short arms and legs, underdeveloped pelvic bones, and unusually short fingers and toes (brachydactyly). This disorder is also characterized by flattened spinal bones (platyspondyly) and an exaggerated curvature of the lower back (lordosis). Infants with this condition are born with a small chest with short ribs that can restrict the growth and expansion of the lungs.  As a result of these serious health problems, some affected fetuses do not survive to term. Infants born with platyspondylic lethal skeletal dysplasia, Torrance type usually die at birth or shortly thereafter from respiratory failure. A few affected people with milder signs and symptoms have lived into adulthood.","platyspondylic lethal skeletal dysplasia, Torrance type",0000800,GHR,https://ghr.nlm.nih.gov/condition/platyspondylic-lethal-skeletal-dysplasia-torrance-type,C3151529,T019,Disorders
"How many people are affected by platyspondylic lethal skeletal dysplasia, Torrance type ?",0000800-2,frequency,This condition is very rare; only a few affected individuals have been reported worldwide.,"platyspondylic lethal skeletal dysplasia, Torrance type",0000800,GHR,https://ghr.nlm.nih.gov/condition/platyspondylic-lethal-skeletal-dysplasia-torrance-type,C3151529,T019,Disorders
"What are the genetic changes related to platyspondylic lethal skeletal dysplasia, Torrance type ?",0000800-3,genetic changes,"Platyspondylic lethal skeletal dysplasia, Torrance type is one of a spectrum of skeletal disorders caused by mutations in the COL2A1 gene. This gene provides instructions for making a protein that forms type II collagen. This type of collagen is found mostly in the clear gel that fills the eyeball (the vitreous) and in cartilage. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Type II collagen is essential for the normal development of bones and other connective tissues that form the body's supportive framework.  All of the COL2A1 mutations that have been found to cause platyspondylic lethal skeletal dysplasia, Torrance type occur in a region of the protein called the C-propeptide domain. These mutations interfere with the assembly of type II collagen molecules, reducing the amount of this type of collagen in the body. Instead of forming collagen molecules, the abnormal COL2A1 protein builds up in cartilage cells (chondrocytes). These changes disrupt the normal development of bones and other connective tissues, leading to the skeletal abnormalities characteristic of platyspondylic lethal skeletal dysplasia, Torrance type.","platyspondylic lethal skeletal dysplasia, Torrance type",0000800,GHR,https://ghr.nlm.nih.gov/condition/platyspondylic-lethal-skeletal-dysplasia-torrance-type,C3151529,T019,Disorders
"Is platyspondylic lethal skeletal dysplasia, Torrance type inherited ?",0000800-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.","platyspondylic lethal skeletal dysplasia, Torrance type",0000800,GHR,https://ghr.nlm.nih.gov/condition/platyspondylic-lethal-skeletal-dysplasia-torrance-type,C3151529,T019,Disorders
"What are the treatments for platyspondylic lethal skeletal dysplasia, Torrance type ?",0000800-5,treatment,"These resources address the diagnosis or management of platyspondylic lethal skeletal dysplasia, Torrance type:  - Genetic Testing Registry: Platyspondylic lethal skeletal dysplasia Torrance type  - MedlinePlus Encyclopedia: Lordosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","platyspondylic lethal skeletal dysplasia, Torrance type",0000800,GHR,https://ghr.nlm.nih.gov/condition/platyspondylic-lethal-skeletal-dysplasia-torrance-type,C3151529,T019,Disorders
What is (are) PMM2-congenital disorder of glycosylation ?,0000801-1,information,"PMM2-congenital disorder of glycosylation (PMM2-CDG, also known as congenital disorder of glycosylation type Ia) is an inherited condition that affects many parts of the body. The type and severity of problems associated with PMM2-CDG vary widely among affected individuals, sometimes even among members of the same family.  Individuals with PMM2-CDG typically develop signs and symptoms of the condition during infancy. Affected infants may have weak muscle tone (hypotonia), retracted (inverted) nipples, an abnormal distribution of fat, eyes that do not look in the same direction (strabismus), developmental delay, and a failure to gain weight and grow at the expected rate (failure to thrive). Infants with PMM2-CDG also frequently have an underdeveloped cerebellum, which is the part of the brain that coordinates movement. Distinctive facial features are sometimes present in affected individuals, including a high forehead, a triangular face, large ears, and a thin upper lip. Children with PMM2-CDG may also have elevated liver function test results, seizures, fluid around the heart (pericardial effusion), and blood clotting disorders. About 20 percent of affected infants do not survive the first year of life due to multiple organ failure.  The most severe cases of PMM2-CDG are characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. Most babies with hydrops fetalis are stillborn or die soon after birth.  People with PMM2-CDG who survive infancy may have moderate intellectual disability, and some are unable to walk independently. Affected individuals may also experience stroke-like episodes that involve an extreme lack of energy (lethargy) and temporary paralysis. Recovery from these episodes usually occurs over a period of a few weeks to several months.  During adolescence or adulthood, individuals with PMM2-CDG have reduced sensation and weakness in their arms and legs (peripheral neuropathy), an abnormal curvature of the spine (kyphoscoliosis), impaired muscle coordination (ataxia), and joint deformities (contractures). Some affected individuals have an eye disorder called retinitis pigmentosa that causes vision loss. Females with PMM2-CDG have hypergonadotropic hypogonadism, which affects the production of hormones that direct sexual development. As a result, females with PMM2-CDG do not go through puberty. Affected males experience normal puberty but often have small testes.",PMM2-congenital disorder of glycosylation,0000801,GHR,https://ghr.nlm.nih.gov/condition/pmm2-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
How many people are affected by PMM2-congenital disorder of glycosylation ?,0000801-2,frequency,More than 800 individuals with PMM2-CDG have been identified worldwide.,PMM2-congenital disorder of glycosylation,0000801,GHR,https://ghr.nlm.nih.gov/condition/pmm2-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
What are the genetic changes related to PMM2-congenital disorder of glycosylation ?,0000801-3,genetic changes,"PMM2-CDG is caused by mutations in the PMM2 gene. This gene provides instructions for making an enzyme called phosphomannomutase 2 (PMM2). The PMM2 enzyme is involved in a process called glycosylation, which attaches groups of sugar molecules (oligosaccharides) to proteins. Glycosylation modifies proteins so they can perform a wider variety of functions. Mutations in the PMM2 gene lead to the production of an abnormal PMM2 enzyme with reduced activity. Without a properly functioning PMM2 enzyme, glycosylation cannot proceed normally. As a result, incorrect oligosaccharides are produced and attached to proteins. The wide variety of signs and symptoms in PMM2-CDG are likely due to the production of abnormally glycosylated proteins in many organs and tissues.",PMM2-congenital disorder of glycosylation,0000801,GHR,https://ghr.nlm.nih.gov/condition/pmm2-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
Is PMM2-congenital disorder of glycosylation inherited ?,0000801-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",PMM2-congenital disorder of glycosylation,0000801,GHR,https://ghr.nlm.nih.gov/condition/pmm2-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
What are the treatments for PMM2-congenital disorder of glycosylation ?,0000801-5,treatment,These resources address the diagnosis or management of PMM2-CDG:  - Gene Review: Gene Review: PMM2-CDG (CDG-Ia)  - Genetic Testing Registry: Carbohydrate-deficient glycoprotein syndrome type I   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,PMM2-congenital disorder of glycosylation,0000801,GHR,https://ghr.nlm.nih.gov/condition/pmm2-congenital-disorder-of-glycosylation,C0242354,T019,Disorders
What is (are) Pol III-related leukodystrophy ?,0000802-1,information,"Pol III-related leukodystrophy is a disorder that affects the nervous system and other parts of the body. Leukodystrophies are conditions that involve abnormalities of the nervous system's white matter, which consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses.  Pol III-related leukodystrophy is a hypomyelinating disease, which means that the nervous system of affected individuals has a reduced ability to form myelin. Hypomyelination underlies most of the neurological problems associated with Pol III-related leukodystrophy. A small number of people with this disorder also have a loss of nerve cells in a part of the brain involved in coordinating movements (cerebellar atrophy) and underdevelopment (hypoplasia) of tissue that connects the left and right halves of the brain (the corpus callosum). These brain abnormalities likely contribute to the neurological problems in affected individuals.  People with Pol III-related leukodystrophy usually have intellectual disability ranging from mild to severe, which gradually worsens over time. Some affected individuals have normal intelligence in early childhood but develop mild intellectual disability during the course of the disease.  Difficulty coordinating movements (ataxia), which begins in childhood and slowly worsens over time, is a characteristic feature of Pol III-related leukodystrophy. Affected children typically have delayed development of motor skills such as walking. Their gait is unstable, and they usually walk with their feet wide apart for balance. Affected individuals may eventually need to use a walker or wheelchair. Involuntary rhythmic shaking (tremor) of the arms and hands may occur in this disorder. In some cases the tremor occurs mainly during movement (intentional tremor); other affected individuals experience the tremor both during movement and at rest.  Development of the teeth (dentition) is often abnormal in Pol III-related leukodystrophy, resulting in the absence of some teeth (known as hypodontia or oligodontia). Some affected infants are born with a few teeth (natal teeth), which fall out during the first weeks of life. The primary (deciduous) teeth appear later than usual, beginning at about age 2. In Pol III-related leukodystrophy, the teeth may not appear in the usual sequence, in which front teeth (incisors) appear before back teeth (molars). Instead, molars often appear first, with incisors appearing later or not at all. Permanent teeth are also delayed, and may not appear until adolescence. The teeth may also be unusually shaped.  Some individuals with Pol III-related leukodystrophy have excessive salivation and difficulty chewing or swallowing (dysphagia), which can lead to choking. They may also have speech impairment (dysarthria). People with Pol III-related leukodystrophy often have abnormalities in eye movement, such as progressive vertical gaze palsy, which is restricted up-and-down eye movement that worsens over time. Nearsightedness is common in affected individuals, and clouding of the lens of the eyes (cataracts) has also been reported. Deterioration (atrophy) of the nerves that carry information from the eyes to the brain (the optic nerves) and seizures may also occur in this disorder.  Hypogonadotropic hypogonadism, which is a condition caused by reduced production of hormones that direct sexual development, may occur in Pol III-related leukodystrophy. Affected individuals have delayed development of the typical signs of puberty, such as the growth of body hair.  People with Pol III-related leukodystrophy may have different combinations of its signs and symptoms. These varied combinations of clinical features were originally described as separate disorders. Affected individuals may be diagnosed with ataxia, delayed dentition, and hypomyelination (ADDH); hypomyelination, hypodontia, hypogonadotropic hypogonadism (4H syndrome); tremor-ataxia with central hypomyelination (TACH); leukodystrophy with oligodontia (LO); or hypomyelination with cerebellar atrophy and hypoplasia of the corpus callosum (HCAHC). Because these disorders were later found to have the same genetic cause, researchers now group them as variations of the single condition Pol III-related leukodystrophy.",Pol III-related leukodystrophy,0000802,GHR,https://ghr.nlm.nih.gov/condition/pol-iii-related-leukodystrophy,C0445223,T047,Disorders
How many people are affected by Pol III-related leukodystrophy ?,0000802-2,frequency,"Pol III-related leukodystrophy is a rare disorder; its prevalence is unknown. Only about 40 cases have been described in the medical literature. However, researchers believe that a significant percentage of people with an unspecified hypomyelinating leukodystrophy could have Pol III-related leukodystrophy.",Pol III-related leukodystrophy,0000802,GHR,https://ghr.nlm.nih.gov/condition/pol-iii-related-leukodystrophy,C0445223,T047,Disorders
What are the genetic changes related to Pol III-related leukodystrophy ?,0000802-3,genetic changes,"Pol III-related leukodystrophy is caused by mutations in the POLR3A or POLR3B gene. These genes provide instructions for making the two largest parts (subunits) of an enzyme called RNA polymerase III. This enzyme is involved in the production (synthesis) of ribonucleic acid (RNA), a chemical cousin of DNA. The RNA polymerase III enzyme attaches (binds) to DNA and synthesizes RNA in accordance with the instructions carried by the DNA, a process called transcription. RNA polymerase III helps synthesize several forms of RNA, including ribosomal RNA (rRNA) and transfer RNA (tRNA). Molecules of rRNA and tRNA assemble protein building blocks (amino acids) into working proteins; this process is essential for the normal functioning and survival of cells.  Researchers suggest that mutations in the POLR3A or POLR3B gene may impair the ability of subunits of the RNA polymerase III enzyme to assemble properly or result in an RNA polymerase III with impaired ability to bind to DNA. Reduced function of the RNA polymerase III molecule likely affects development and function of many parts of the body, including the nervous system and the teeth, but the relationship between POLR3A and POLR3B gene mutations and the specific signs and symptoms of Pol III-related leukodystrophy is unknown.",Pol III-related leukodystrophy,0000802,GHR,https://ghr.nlm.nih.gov/condition/pol-iii-related-leukodystrophy,C0445223,T047,Disorders
Is Pol III-related leukodystrophy inherited ?,0000802-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Pol III-related leukodystrophy,0000802,GHR,https://ghr.nlm.nih.gov/condition/pol-iii-related-leukodystrophy,C0445223,T047,Disorders
What are the treatments for Pol III-related leukodystrophy ?,0000802-5,treatment,These resources address the diagnosis or management of Pol III-related leukodystrophy:  - Eastman Dental Hospital: Hypodontia Clinic  - Gene Review: Gene Review: Pol III-Related Leukodystrophies  - Genetic Testing Registry: Pol III-related leukodystrophy  - Johns Hopkins Medicine: Treating Ataxia  - National Ataxia Foundation: Diagnosis of Ataxia  - UCSF Benioff Children's Hospital: Hypodontia  - University of Chicago Ataxia Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Pol III-related leukodystrophy,0000802,GHR,https://ghr.nlm.nih.gov/condition/pol-iii-related-leukodystrophy,C0445223,T047,Disorders
What is (are) Poland syndrome ?,0000803-1,information,"Poland syndrome is a disorder in which affected individuals are born with missing or underdeveloped muscles on one side of the body, resulting in abnormalities that can affect the chest, shoulder, arm, and hand. The extent and severity of the abnormalities vary among affected individuals.  People with Poland syndrome are typically missing part of one of the major chest muscles, called the pectoralis major. In most affected individuals, the missing part is the large section of the muscle that normally runs from the upper arm to the breastbone (sternum). The abnormal pectoralis major muscle may cause the chest to appear concave. In some cases, additional muscles on the affected side of the torso, including muscles in the chest wall, side, and shoulder, may be missing or underdeveloped. There may also be rib cage abnormalities, such as shortened ribs, and the ribs may be noticeable due to less fat under the skin (subcutaneous fat). Breast and nipple abnormalities may also occur, and underarm (axillary) hair is sometimes sparse or abnormally placed. In most cases, the abnormalities in the chest area do not cause health problems or affect movement.  Many people with Poland syndrome have hand abnormalities on the affected side, commonly including an underdeveloped hand with abnormally short fingers (brachydactyly); small, underdeveloped (vestigial) fingers; and some fingers that are fused together (syndactyly). This combination of hand abnormalities is called symbrachydactyly. Some affected individuals have only one or two of these features, or have a mild hand abnormality that is hardly noticeable; more severe abnormalities can cause problems with use of the hand. The bones of the forearm (radius and ulna) are shortened in some people with Poland syndrome, but this shortening may also be difficult to detect unless measured.  Mild cases of Poland syndrome without hand involvement may not be evident until puberty, when the differences (asymmetry) between the two sides of the chest become more apparent. By contrast, severely affected individuals have abnormalities of the chest, hand, or both that are apparent at birth. In rare cases, severely affected individuals have abnormalities of internal organs such as a lung or a kidney, or the heart is abnormally located in the right side of the chest (dextrocardia).  Rarely, chest and hand abnormalities resembling those of Poland syndrome occur on both sides of the body, but researchers disagree as to whether this condition is a variant of Poland syndrome or a different disorder.",Poland syndrome,0000803,GHR,https://ghr.nlm.nih.gov/condition/poland-syndrome,C0032357,T019,Disorders
How many people are affected by Poland syndrome ?,0000803-2,frequency,"Poland syndrome has been estimated to occur in 1 in 20,000 newborns. For unknown reasons, this disorder occurs more than twice as often in males than in females. Poland syndrome may be underdiagnosed because mild cases without hand involvement may never come to medical attention.",Poland syndrome,0000803,GHR,https://ghr.nlm.nih.gov/condition/poland-syndrome,C0032357,T019,Disorders
What are the genetic changes related to Poland syndrome ?,0000803-3,genetic changes,"The cause of Poland syndrome is unknown. Researchers have suggested that it may result from a disruption of blood flow during development before birth. This disruption is thought to occur at about the sixth week of embryonic development and affect blood vessels that will become the subclavian and vertebral arteries on each side of the body. The arteries normally supply blood to embryonic tissues that give rise to the chest wall and hand on their respective sides. Variations in the site and extent of the disruption may explain the range of signs and symptoms that occur in Poland syndrome. Abnormality of an embryonic structure called the apical ectodermal ridge, which helps direct early limb development, may also be involved in this disorder.  Rare cases of Poland syndrome are thought to be caused by a genetic change that can be passed down in families, but no related genes have been identified.",Poland syndrome,0000803,GHR,https://ghr.nlm.nih.gov/condition/poland-syndrome,C0032357,T019,Disorders
Is Poland syndrome inherited ?,0000803-4,inheritance,"Most cases of Poland syndrome are sporadic, which means they are not inherited and occur in people with no history of the disorder in their families. Rarely, this condition is passed through generations in families. In these families the condition appears to be inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder, although no associated genes have been found.",Poland syndrome,0000803,GHR,https://ghr.nlm.nih.gov/condition/poland-syndrome,C0032357,T019,Disorders
What are the treatments for Poland syndrome ?,0000803-5,treatment,These resources address the diagnosis or management of Poland syndrome:  - Children's Medical Center of Dallas  - Great Ormond Street Hospital (UK): Treatment Options for Symbrachydactyly  - St. Louis Children's Hospital: Chest Wall Deformities   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Poland syndrome,0000803,GHR,https://ghr.nlm.nih.gov/condition/poland-syndrome,C0032357,T019,Disorders
What is (are) polycystic kidney disease ?,0000804-1,information,"Polycystic kidney disease is a disorder that affects the kidneys and other organs. Clusters of fluid-filled sacs, called cysts, develop in the kidneys and interfere with their ability to filter waste products from the blood. The growth of cysts causes the kidneys to become enlarged and can lead to kidney failure. Cysts may also develop in other organs, particularly the liver.  Frequent complications of polycystic kidney disease include dangerously high blood pressure (hypertension), pain in the back or sides, blood in the urine (hematuria), recurrent urinary tract infections, kidney stones, and heart valve abnormalities. Additionally, people with polycystic kidney disease have an increased risk of an abnormal bulging (an aneurysm) in a large blood vessel called the aorta or in blood vessels at the base of the brain. Aneurysms can be life-threatening if they tear or rupture.  The two major forms of polycystic kidney disease are distinguished by the usual age of onset and the pattern in which it is passed through families. The autosomal dominant form (sometimes called ADPKD) has signs and symptoms that typically begin in adulthood, although cysts in the kidney are often present from birth or childhood. Autosomal dominant polycystic kidney disease can be further divided into type 1 and type 2, depending on the genetic cause. The autosomal recessive form of polycystic kidney disease (sometimes called ARPKD) is much rarer and is often lethal early in life. The signs and symptoms of this condition are usually apparent at birth or in early infancy.",polycystic kidney disease,0000804,GHR,https://ghr.nlm.nih.gov/condition/polycystic-kidney-disease,C0022680,T047,Disorders
How many people are affected by polycystic kidney disease ?,0000804-2,frequency,"Polycystic kidney disease is a fairly common genetic disorder. It affects about 500,000 people in the United States. The autosomal dominant form of the disease is much more common than the autosomal recessive form. Autosomal dominant polycystic kidney disease affects 1 in 500 to 1,000 people, while the autosomal recessive type occurs in an estimated 1 in 20,000 to 40,000 people.",polycystic kidney disease,0000804,GHR,https://ghr.nlm.nih.gov/condition/polycystic-kidney-disease,C0022680,T047,Disorders
What are the genetic changes related to polycystic kidney disease ?,0000804-3,genetic changes,"Mutations in the PKD1, PKD2, and PKHD1 genes cause polycystic kidney disease.  Mutations in either the PKD1 or PKD2 gene can cause autosomal dominant polycystic kidney disease; PKD1 gene mutations cause ADPKD type 1, and PKD2 gene mutations cause ADPKD type 2. These genes provide instructions for making proteins whose functions are not fully understood. Researchers believe that they are involved in transmitting chemical signals from outside the cell to the cell's nucleus. The two proteins work together to promote normal kidney development, organization, and function. Mutations in the PKD1 or PKD2 gene lead to the formation of thousands of cysts, which disrupt the normal functions of the kidneys and other organs. People with mutations in the PKD2 gene, particularly women, typically have a less severe form of the disease than people with PKD1 mutations. The signs and symptoms, including a decline in kidney function, tend to appear later in adulthood in people with a PKD2 mutation.  Mutations in the PKHD1 gene cause autosomal recessive polycystic kidney disease. This gene provides instructions for making a protein whose exact function is unknown; however, the protein likely transmits chemical signals from outside the cell to the cell nucleus. Researchers have not determined how mutations in the PKHD1 gene lead to the formation of numerous cysts characteristic of polycystic kidney disease.  Although polycystic kidney disease is usually a genetic disorder, a small percentage of cases are not caused by gene mutations. These cases are called acquired polycystic kidney disease. This form of the disorder occurs most often in people with other types of kidney disease who have been treated for several years with hemodialysis (a procedure that filters waste products from the blood).",polycystic kidney disease,0000804,GHR,https://ghr.nlm.nih.gov/condition/polycystic-kidney-disease,C0022680,T047,Disorders
Is polycystic kidney disease inherited ?,0000804-4,inheritance,"Most cases of polycystic kidney disease have an autosomal dominant pattern of inheritance. People with this condition are born with one mutated copy of the PKD1 or PKD2 gene in each cell. In about 90 percent of these cases, an affected person inherits the mutation from one affected parent. The other 10 percent of cases result from a new mutation in one of the genes and occur in people with no history of the disorder in their family.  Although one altered copy of a gene in each cell is sufficient to cause the disorder, an additional mutation in the second copy of the PKD1 or PKD2 gene may make cysts grow faster and increase the severity of the disease. The rate at which cysts enlarge and cause a loss of kidney function varies widely, and may be influenced by mutations in other genes that have not been identified.  Polycystic kidney disease also can be inherited in an autosomal recessive pattern. People with this form of the condition have two altered copies of the PKHD1 gene in each cell. The parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene.",polycystic kidney disease,0000804,GHR,https://ghr.nlm.nih.gov/condition/polycystic-kidney-disease,C0022680,T047,Disorders
What are the treatments for polycystic kidney disease ?,0000804-5,treatment,"These resources address the diagnosis or management of polycystic kidney disease:  - Gene Review: Gene Review: Polycystic Kidney Disease, Autosomal Dominant  - Gene Review: Gene Review: Polycystic Kidney Disease, Autosomal Recessive  - Genetic Testing Registry: Polycystic kidney disease 2  - Genetic Testing Registry: Polycystic kidney disease 3, autosomal dominant  - Genetic Testing Registry: Polycystic kidney disease, adult type  - Genetic Testing Registry: Polycystic kidney disease, infantile type  - MedlinePlus Encyclopedia: Polycystic kidney disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",polycystic kidney disease,0000804,GHR,https://ghr.nlm.nih.gov/condition/polycystic-kidney-disease,C0022680,T047,Disorders
What is (are) polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy ?,0000805-1,information,"Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, commonly known as PLOSL, is a progressive disorder that affects the bones and brain. ""Polycystic lipomembranous osteodysplasia"" refers to cyst-like bone changes that can be seen on x-rays. ""Sclerosing leukoencephalopathy"" describes specific changes in the brain that are found in people with this disorder.  The bone abnormalities associated with PLOSL usually become apparent in a person's twenties. In most affected individuals, pain and tenderness in the ankles and feet are the first symptoms of the disease. Several years later, broken bones (fractures) begin to occur frequently, particularly in bones of the ankles, feet, wrists, and hands. Bone pain and fractures are caused by thinning of the bones (osteoporosis) and cyst-like changes. These abnormalities weaken bones and make them more likely to break.  The brain abnormalities characteristic of PLOSL typically appear in a person's thirties. Personality changes are among the first noticeable problems, followed by a loss of judgment, feelings of intense happiness (euphoria), a loss of inhibition, and poor concentration. These neurologic changes cause significant problems in an affected person's social and family life. As the disease progresses, it causes a severe decline in thinking and reasoning abilities (dementia). Affected people ultimately become unable to walk, speak, or care for themselves. People with this disease usually live only into their thirties or forties.",polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy,0000805,GHR,https://ghr.nlm.nih.gov/condition/polycystic-lipomembranous-osteodysplasia-with-sclerosing-leukoencephalopathy,C0410533,T019,Disorders
How many people are affected by polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy ?,0000805-2,frequency,"PLOSL is a very rare condition. It was first reported in the Finnish population, where it has an estimated prevalence of 1 to 2 per million people. This condition has also been diagnosed in more than 100 people in the Japanese population. Although affected individuals have been reported worldwide, PLOSL appears to be less common in other countries.",polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy,0000805,GHR,https://ghr.nlm.nih.gov/condition/polycystic-lipomembranous-osteodysplasia-with-sclerosing-leukoencephalopathy,C0410533,T019,Disorders
What are the genetic changes related to polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy ?,0000805-3,genetic changes,"Mutations in the TREM2 gene or the TYROBP gene (also called DAP12) can cause PLOSL. The proteins produced from these two genes work together to activate certain kinds of cells. These proteins appear to be particularly important in osteoclasts, which are specialized cells that break down and remove (resorb) bone tissue that is no longer needed. These cells are involved in bone remodeling, which is a normal process that replaces old bone tissue with new bone. The TREM2 and TYROBP proteins are also critical for the normal function of microglia, which are a type of immune cell in the brain and spinal cord (central nervous system). Although these proteins play essential roles in osteoclasts and microglia, their exact function in these cells is unclear.  Mutations in the TREM2 or TYROBP gene disrupt normal bone growth and lead to progressive brain abnormalities in people with PLOSL. Researchers believe that the bone changes seen with this disorder are related to malfunctioning osteoclasts, which are less able to resorb bone tissue during bone remodeling. In the central nervous system, TREM2 or TYROBP mutations cause widespread abnormalities of microglia. Researchers are working to determine how these abnormalities lead to the progressive neurological problems associated with PLOSL.",polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy,0000805,GHR,https://ghr.nlm.nih.gov/condition/polycystic-lipomembranous-osteodysplasia-with-sclerosing-leukoencephalopathy,C0410533,T019,Disorders
Is polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy inherited ?,0000805-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy,0000805,GHR,https://ghr.nlm.nih.gov/condition/polycystic-lipomembranous-osteodysplasia-with-sclerosing-leukoencephalopathy,C0410533,T019,Disorders
What are the treatments for polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy ?,0000805-5,treatment,These resources address the diagnosis or management of PLOSL:  - Gene Review: Gene Review: Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL)  - Genetic Testing Registry: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy  - MedlinePlus Encyclopedia: Dementia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy,0000805,GHR,https://ghr.nlm.nih.gov/condition/polycystic-lipomembranous-osteodysplasia-with-sclerosing-leukoencephalopathy,C0410533,T019,Disorders
What is (are) polycythemia vera ?,0000806-1,information,"Polycythemia vera is a condition characterized by an increased number of red blood cells in the bloodstream. Affected individuals may also have excess white blood cells and blood clotting cells called platelets. These extra cells cause the blood to be thicker than normal. As a result, abnormal blood clots are more likely to form and block the flow of blood through arteries and veins. Individuals with polycythemia vera have an increased risk of deep vein thrombosis (DVT), a type of blood clot that occurs in the deep veins of the arms or legs. If a DVT travels through the bloodstream and lodges in the lungs, it can cause a life-threatening clot known as a pulmonary embolism (PE). Affected individuals also have an increased risk of heart attack and stroke caused by blood clots in the heart and brain.  Polycythemia vera typically develops in adulthood, around age 60, although in rare cases it occurs in children and young adults. This condition may not cause any symptoms in its early stages. Some people with polycythemia vera experience headaches, dizziness, ringing in the ears (tinnitus), impaired vision, or itchy skin. Affected individuals frequently have reddened skin because of the extra red blood cells. Other complications of polycythemia vera include an enlarged spleen (splenomegaly), stomach ulcers, gout (a form of arthritis caused by a buildup of uric acid in the joints), heart disease, and cancer of blood-forming cells (leukemia).",polycythemia vera,0000806,GHR,https://ghr.nlm.nih.gov/condition/polycythemia-vera,C0032463,T191,Disorders
How many people are affected by polycythemia vera ?,0000806-2,frequency,"The prevalence of polycythemia vera varies worldwide. The condition affects an estimated 44 to 57 per 100,000 individuals in the United States. For unknown reasons, men develop polycythemia vera more frequently than women.",polycythemia vera,0000806,GHR,https://ghr.nlm.nih.gov/condition/polycythemia-vera,C0032463,T191,Disorders
What are the genetic changes related to polycythemia vera ?,0000806-3,genetic changes,"Mutations in the JAK2 and TET2 genes are associated with polycythemia vera. Although it remains unclear exactly what initiates polycythemia vera, researchers believe that it begins when mutations occur in the DNA of a hematopoietic stem cell. These stem cells are located in the bone marrow and have the potential to develop into red blood cells, white blood cells, and platelets. JAK2 gene mutations seem to be particularly important for the development of polycythemia vera, as nearly all affected individuals have a mutation in this gene. The JAK2 gene provides instructions for making a protein that promotes the growth and division (proliferation) of cells. The JAK2 protein is especially important for controlling the production of blood cells from hematopoietic stem cells.  JAK2 gene mutations result in the production of a JAK2 protein that is constantly turned on (constitutively activated), which increases production of blood cells and prolongs their survival. With so many extra cells in the bloodstream, abnormal blood clots are more likely to form. Thicker blood also flows more slowly throughout the body, which prevents organs from receiving enough oxygen. Many of the signs and symptoms of polycythemia vera are related to a shortage of oxygen in body tissues.  The function of the TET2 gene is unknown. Although mutations in the TET2 gene have been found in approximately 16 percent of people with polycythemia vera, it is unclear what role these mutations play in the development of the condition.",polycythemia vera,0000806,GHR,https://ghr.nlm.nih.gov/condition/polycythemia-vera,C0032463,T191,Disorders
Is polycythemia vera inherited ?,0000806-4,inheritance,"Most cases of polycythemia vera are not inherited. This condition is associated with genetic changes that are somatic, which means they are acquired during a person's lifetime and are present only in certain cells.  In rare instances, polycythemia vera has been found to run in families. In some of these families, the risk of developing polycythemia vera appears to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of an altered gene in each cell is sufficient to increase the risk of developing polycythemia vera, although the cause of this condition in familial cases is unknown. In these families, people seem to inherit an increased risk of polycythemia vera, not the disease itself.",polycythemia vera,0000806,GHR,https://ghr.nlm.nih.gov/condition/polycythemia-vera,C0032463,T191,Disorders
What are the treatments for polycythemia vera ?,0000806-5,treatment,These resources address the diagnosis or management of polycythemia vera:  - Genetic Testing Registry: Polycythemia vera  - MPN Research Foundation: Diagnosis  - MedlinePlus Encyclopedia: Polycythemia Vera   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,polycythemia vera,0000806,GHR,https://ghr.nlm.nih.gov/condition/polycythemia-vera,C0032463,T191,Disorders
What is (are) polymicrogyria ?,0000807-1,information,"Polymicrogyria is a condition characterized by abnormal development of the brain before birth. The surface of the brain normally has many ridges or folds, called gyri. In people with polymicrogyria, the brain develops too many folds, and the folds are unusually small. The name of this condition literally means too many (poly-) small (micro-) folds (-gyria) in the surface of the brain.  Polymicrogyria can affect part of the brain or the whole brain. When the condition affects one side of the brain, researchers describe it as unilateral. When it affects both sides of the brain, it is described as bilateral. The signs and symptoms associated with polymicrogyria depend on how much of the brain, and which particular brain regions, are affected.  Researchers have identified multiple forms of polymicrogyria. The mildest form is known as unilateral focal polymicrogyria. This form of the condition affects a relatively small area on one side of the brain. It may cause minor neurological problems, such as mild seizures that can be easily controlled with medication. Some people with unilateral focal polymicrogyria do not have any problems associated with the condition.  Bilateral forms of polymicrogyria tend to cause more severe neurological problems. Signs and symptoms of these conditions can include recurrent seizures (epilepsy), delayed development, crossed eyes, problems with speech and swallowing, and muscle weakness or paralysis. The most severe form of the disorder, bilateral generalized polymicrogyria, affects the entire brain. This condition causes severe intellectual disability, problems with movement, and seizures that are difficult or impossible to control with medication.  Polymicrogyria most often occurs as an isolated feature, although it can occur with other brain abnormalities. It is also a feature of several genetic syndromes characterized by intellectual disability and multiple birth defects. These include 22q11.2 deletion syndrome, Adams-Oliver syndrome, Aicardi syndrome, Galloway-Mowat syndrome, Joubert syndrome, and Zellweger spectrum disorder.",polymicrogyria,0000807,GHR,https://ghr.nlm.nih.gov/condition/polymicrogyria,C0266464,T019,Disorders
How many people are affected by polymicrogyria ?,0000807-2,frequency,"The prevalence of isolated polymicrogyria is unknown. Researchers believe that it may be relatively common overall, although the individual forms of the disorder (such as bilateral generalized polymicrogyria) are probably rare.",polymicrogyria,0000807,GHR,https://ghr.nlm.nih.gov/condition/polymicrogyria,C0266464,T019,Disorders
What are the genetic changes related to polymicrogyria ?,0000807-3,genetic changes,"In most people with polymicrogyria, the cause of the condition is unknown. However, researchers have identified several environmental and genetic factors that can be responsible for the disorder. Environmental causes of polymicrogyria include certain infections during pregnancy and a lack of oxygen to the fetus (intrauterine ischemia).  Researchers are investigating the genetic causes of polymicrogyria. The condition can result from deletions or rearrangements of genetic material from several different chromosomes. Additionally, mutations in one gene, ADGRG1, have been found to cause a severe form of the condition called bilateral frontoparietal polymicrogyria (BFPP). The ADGRG1 gene appears to be critical for the normal development of the outer layer of the brain. Researchers believe that many other genes are probably involved in the different forms of polymicrogyria.",polymicrogyria,0000807,GHR,https://ghr.nlm.nih.gov/condition/polymicrogyria,C0266464,T019,Disorders
Is polymicrogyria inherited ?,0000807-4,inheritance,"Isolated polymicrogyria can have different inheritance patterns. Several forms of the condition, including bilateral frontoparietal polymicrogyria (which is associated with mutations in the ADGRG1 gene), have an autosomal recessive pattern of inheritance. In autosomal recessive inheritance, both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Polymicrogyria can also have an autosomal dominant inheritance pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Other forms of polymicrogyria appear to have an X-linked pattern of inheritance. Genes associated with X-linked conditions are located on the X chromosome, which is one of the two sex chromosomes. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  Some people with polymicrogyria have relatives with the disorder, while other affected individuals have no family history of the condition. When an individual is the only affected person in his or her family, it can be difficult to determine the cause and possible inheritance pattern of the disorder.",polymicrogyria,0000807,GHR,https://ghr.nlm.nih.gov/condition/polymicrogyria,C0266464,T019,Disorders
What are the treatments for polymicrogyria ?,0000807-5,treatment,"These resources address the diagnosis or management of polymicrogyria:  - Gene Review: Gene Review: Polymicrogyria Overview  - Genetic Testing Registry: Congenital bilateral perisylvian syndrome  - Genetic Testing Registry: Polymicrogyria, asymmetric  - Genetic Testing Registry: Polymicrogyria, bilateral frontoparietal  - Genetic Testing Registry: Polymicrogyria, bilateral occipital   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",polymicrogyria,0000807,GHR,https://ghr.nlm.nih.gov/condition/polymicrogyria,C0266464,T019,Disorders
What is (are) Pompe disease ?,0000808-1,information,"Pompe disease is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. The accumulation of glycogen in certain organs and tissues, especially muscles, impairs their ability to function normally.  Researchers have described three types of Pompe disease, which differ in severity and the age at which they appear. These types are known as classic infantile-onset, non-classic infantile-onset, and late-onset.  The classic form of infantile-onset Pompe disease begins within a few months of birth. Infants with this disorder typically experience muscle weakness (myopathy), poor muscle tone (hypotonia), an enlarged liver (hepatomegaly), and heart defects. Affected infants may also fail to gain weight and grow at the expected rate (failure to thrive) and have breathing problems. If untreated, this form of Pompe disease leads to death from heart failure in the first year of life.  The non-classic form of infantile-onset Pompe disease usually appears by age 1. It is characterized by delayed motor skills (such as rolling over and sitting) and progressive muscle weakness. The heart may be abnormally large (cardiomegaly), but affected individuals usually do not experience heart failure. The muscle weakness in this disorder leads to serious breathing problems, and most children with non-classic infantile-onset Pompe disease live only into early childhood.  The late-onset type of Pompe disease may not become apparent until later in childhood, adolescence, or adulthood. Late-onset Pompe disease is usually milder than the infantile-onset forms of this disorder and is less likely to involve the heart. Most individuals with late-onset Pompe disease experience progressive muscle weakness, especially in the legs and the trunk, including the muscles that control breathing. As the disorder progresses, breathing problems can lead to respiratory failure.",Pompe disease,0000808,GHR,https://ghr.nlm.nih.gov/condition/pompe-disease,C0017921,T019,Disorders
How many people are affected by Pompe disease ?,0000808-2,frequency,"Pompe disease affects about 1 in 40,000 people in the United States. The incidence of this disorder varies among different ethnic groups.",Pompe disease,0000808,GHR,https://ghr.nlm.nih.gov/condition/pompe-disease,C0017921,T019,Disorders
What are the genetic changes related to Pompe disease ?,0000808-3,genetic changes,"Mutations in the GAA gene cause Pompe disease. The GAA gene provides instructions for producing an enzyme called acid alpha-glucosidase (also known as acid maltase). This enzyme is active in lysosomes, which are structures that serve as recycling centers within cells. The enzyme normally breaks down glycogen into a simpler sugar called glucose, which is the main energy source for most cells.  Mutations in the GAA gene prevent acid alpha-glucosidase from breaking down glycogen effectively, which allows this sugar to build up to toxic levels in lysosomes. This buildup damages organs and tissues throughout the body, particularly the muscles, leading to the progressive signs and symptoms of Pompe disease.",Pompe disease,0000808,GHR,https://ghr.nlm.nih.gov/condition/pompe-disease,C0017921,T019,Disorders
Is Pompe disease inherited ?,0000808-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Pompe disease,0000808,GHR,https://ghr.nlm.nih.gov/condition/pompe-disease,C0017921,T019,Disorders
What are the treatments for Pompe disease ?,0000808-5,treatment,"These resources address the diagnosis or management of Pompe disease:  - Baby's First Test  - Gene Review: Gene Review: Glycogen Storage Disease Type II (Pompe Disease)  - Genetic Testing Registry: Glycogen storage disease type II, infantile  - Genetic Testing Registry: Glycogen storage disease, type II   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Pompe disease,0000808,GHR,https://ghr.nlm.nih.gov/condition/pompe-disease,C0017921,T019,Disorders
What is (are) pontocerebellar hypoplasia ?,0000809-1,information,"Pontocerebellar hypoplasia is a group of related conditions that affect the development of the brain. The term ""pontocerebellar"" refers to the pons and the cerebellum, which are the brain structures that are most severely affected in many forms of this disorder. The pons is located at the base of the brain in an area called the brainstem, where it transmits signals between the cerebellum and the rest of the brain. The cerebellum, which is located at the back of the brain, normally coordinates movement. The term ""hypoplasia"" refers to the underdevelopment of these brain regions.  Pontocerebellar hypoplasia also causes impaired growth of other parts of the brain, leading to an unusually small head size (microcephaly). This microcephaly is usually not apparent at birth but becomes noticeable as brain growth continues to be slow in infancy and early childhood.  Researchers have described at least ten types of pontocerebellar hypoplasia. All forms of this condition are characterized by impaired brain development, delayed development overall, problems with movement, and intellectual disability. The brain abnormalities are usually present at birth, and in some cases they can be detected before birth. Many children with pontocerebellar hypoplasia live only into infancy or childhood, although some affected individuals have lived into adulthood.  The two major forms of pontocerebellar hypoplasia are designated as type 1 (PCH1) and type 2 (PCH2). In addition to the brain abnormalities described above, PCH1 causes problems with muscle movement resulting from a loss of specialized nerve cells called motor neurons in the spinal cord, similar to another genetic disorder known as spinal muscular atrophy. Individuals with PCH1 also have very weak muscle tone (hypotonia), joint deformities called contractures, vision impairment, and breathing and feeding problems that are evident from early infancy.  Common features of PCH2 include a lack of voluntary motor skills (such as grasping objects, sitting, or walking), problems with swallowing (dysphagia), and an absence of communication, including speech. Affected children typically develop temporary jitteriness (generalized clonus) in early infancy, abnormal patterns of movement described as chorea or dystonia, and stiffness (spasticity). Many also have impaired vision and seizures.  The other forms of pontocerebellar hypoplasia, designated as type 3 (PCH3) through type 10 (PCH10), appear to be rare and have each been reported in only a small number of individuals. Because the different types have overlapping features, and some are caused by mutations in the same genes, researchers have proposed that the types be considered as a spectrum instead of distinct conditions.",pontocerebellar hypoplasia,0000809,GHR,https://ghr.nlm.nih.gov/condition/pontocerebellar-hypoplasia,C1261175,T019,Disorders
How many people are affected by pontocerebellar hypoplasia ?,0000809-2,frequency,"The prevalence of pontocerebellar hypoplasia is unknown, although most forms of the disorder appear to be very rare.",pontocerebellar hypoplasia,0000809,GHR,https://ghr.nlm.nih.gov/condition/pontocerebellar-hypoplasia,C1261175,T019,Disorders
What are the genetic changes related to pontocerebellar hypoplasia ?,0000809-3,genetic changes,"Pontocerebellar hypoplasia can result from mutations in several genes. About half of all cases of PCH1 are caused by mutations in the EXOSC3 gene. PCH1 can also result from mutations in several other genes, including TSEN54, RARS2, and VRK1. PCH2 is caused by mutations in the TSEN54, TSEN2, TSEN34, or SEPSECS gene. In addition to causing PCH1 and PCH2, mutations in the TSEN54 gene can cause PCH4 and PCH5. Mutations in the RARS2 gene, in addition to causing PCH1, can result in PCH6. The remaining types of pontocerebellar hypoplasia are caused by mutations in other genes. In some cases, the genetic cause of pontocerebellar hypoplasia is unknown.  The genes associated with pontocerebellar hypoplasia appear to play essential roles in the development and survival of nerve cells (neurons). Many of these genes are known or suspected to be involved in processing RNA molecules, which are chemical cousins of DNA. Fully processed, mature RNA molecules are essential for the normal functioning of all cells, including neurons. Studies suggest that abnormal RNA processing likely underlies the abnormal brain development characteristic of pontocerebellar hypoplasia, although the exact mechanism is unknown. Researchers hypothesize that developing neurons in certain areas of the brain may be particularly sensitive to problems with RNA processing.  Some of the genes associated with pontocerebellar hypoplasia have functions unrelated to RNA processing. In most cases, it is unclear how mutations in these genes impair brain development.",pontocerebellar hypoplasia,0000809,GHR,https://ghr.nlm.nih.gov/condition/pontocerebellar-hypoplasia,C1261175,T019,Disorders
Is pontocerebellar hypoplasia inherited ?,0000809-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",pontocerebellar hypoplasia,0000809,GHR,https://ghr.nlm.nih.gov/condition/pontocerebellar-hypoplasia,C1261175,T019,Disorders
What are the treatments for pontocerebellar hypoplasia ?,0000809-5,treatment,These resources address the diagnosis or management of pontocerebellar hypoplasia:  - Gene Review: Gene Review: EXOSC3-Related Pontocerebellar Hypoplasia  - Gene Review: Gene Review: TSEN54-Related Pontocerebellar Hypoplasia  - Genetic Testing Registry: Pontoneocerebellar hypoplasia  - MedlinePlus Encyclopedia: Microcephaly   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,pontocerebellar hypoplasia,0000809,GHR,https://ghr.nlm.nih.gov/condition/pontocerebellar-hypoplasia,C1261175,T019,Disorders
What is (are) popliteal pterygium syndrome ?,0000810-1,information,"Popliteal pterygium syndrome is a condition that affects the development of the face, skin, and genitals. Most people with this disorder are born with a cleft lip, a cleft palate (an opening in the roof of the mouth), or both. Affected individuals may have depressions (pits) near the center of the lower lip, which may appear moist due to the presence of salivary and mucous glands in the pits. Small mounds of tissue on the lower lip may also occur. In some cases, people with popliteal pterygium syndrome have missing teeth.  Individuals with popliteal pterygium syndrome may be born with webs of skin on the backs of the legs across the knee joint, which may impair mobility unless surgically removed. Affected individuals may also have webbing or fusion of the fingers or toes (syndactyly), characteristic triangular folds of skin over the nails of the large toes, or tissue connecting the upper and lower eyelids or the upper and lower jaws. They may have abnormal genitals, including unusually small external genital folds (hypoplasia of the labia majora) in females. Affected males may have undescended testes (cryptorchidism) or a scrotum divided into two lobes (bifid scrotum).  People with popliteal pterygium syndrome who have cleft lip and/or palate, like other individuals with these facial conditions, may have an increased risk of delayed language development, learning disabilities, or other mild cognitive problems. The average IQ of individuals with popliteal pterygium syndrome is not significantly different from that of the general population.",popliteal pterygium syndrome,0000810,GHR,https://ghr.nlm.nih.gov/condition/popliteal-pterygium-syndrome,C0265259,T019,Disorders
How many people are affected by popliteal pterygium syndrome ?,0000810-2,frequency,"Popliteal pterygium syndrome is a rare condition, occurring in approximately 1 in 300,000 individuals.",popliteal pterygium syndrome,0000810,GHR,https://ghr.nlm.nih.gov/condition/popliteal-pterygium-syndrome,C0265259,T019,Disorders
What are the genetic changes related to popliteal pterygium syndrome ?,0000810-3,genetic changes,"Mutations in the IRF6 gene cause popliteal pterygium syndrome. The IRF6 gene provides instructions for making a protein that plays an important role in early development. This protein is a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of particular genes.  The IRF6 protein is active in cells that give rise to tissues in the head and face. It is also involved in the development of other parts of the body, including the skin and genitals.  Mutations in the IRF6 gene that cause popliteal pterygium syndrome may change the transcription factor's effect on the activity of certain genes. This affects the development and maturation of tissues in the face, skin, and genitals, resulting in the signs and symptoms of popliteal pterygium syndrome.",popliteal pterygium syndrome,0000810,GHR,https://ghr.nlm.nih.gov/condition/popliteal-pterygium-syndrome,C0265259,T019,Disorders
Is popliteal pterygium syndrome inherited ?,0000810-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",popliteal pterygium syndrome,0000810,GHR,https://ghr.nlm.nih.gov/condition/popliteal-pterygium-syndrome,C0265259,T019,Disorders
What are the treatments for popliteal pterygium syndrome ?,0000810-5,treatment,These resources address the diagnosis or management of popliteal pterygium syndrome:  - Gene Review: Gene Review: IRF6-Related Disorders  - Genetic Testing Registry: Popliteal pterygium syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,popliteal pterygium syndrome,0000810,GHR,https://ghr.nlm.nih.gov/condition/popliteal-pterygium-syndrome,C0265259,T019,Disorders
What is (are) porphyria ?,0000811-1,information,"Porphyria is a group of disorders caused by abnormalities in the chemical steps that lead to heme production. Heme is a vital molecule for all of the body's organs, although it is most abundant in the blood, bone marrow, and liver. Heme is a component of several iron-containing proteins called hemoproteins, including hemoglobin (the protein that carries oxygen in the blood).  Researchers have identified several types of porphyria, which are distinguished by their genetic cause and their signs and symptoms. Some types of porphyria, called cutaneous porphyrias, primarily affect the skin. Areas of skin exposed to the sun become fragile and blistered, which can lead to infection, scarring, changes in skin coloring (pigmentation), and increased hair growth. Cutaneous porphyrias include congenital erythropoietic porphyria, erythropoietic protoporphyria, hepatoerythropoietic porphyria, and porphyria cutanea tarda.  Other types of porphyria, called acute porphyrias, primarily affect the nervous system. These disorders are described as ""acute"" because their signs and symptoms appear quickly and usually last a short time. Episodes of acute porphyria can cause abdominal pain, vomiting, constipation, and diarrhea. During an episode, a person may also experience muscle weakness, seizures, fever, and mental changes such as anxiety and hallucinations. These signs and symptoms can be life-threatening, especially if the muscles that control breathing become paralyzed. Acute porphyrias include acute intermittent porphyria and ALAD deficiency porphyria. Two other forms of porphyria, hereditary coproporphyria and variegate porphyria, can have both acute and cutaneous symptoms.  The porphyrias can also be split into erythropoietic and hepatic types, depending on where damaging compounds called porphyrins and porphyrin precursors first build up in the body. In erythropoietic porphyrias, these compounds originate in the bone marrow. Erythropoietic porphyrias include erythropoietic protoporphyria and congenital erythropoietic porphyria. Health problems associated with erythropoietic porphyrias include a low number of red blood cells (anemia) and enlargement of the spleen (splenomegaly). The other types of porphyrias are considered hepatic porphyrias. In these disorders, porphyrins and porphyrin precursors originate primarily in the liver, leading to abnormal liver function and an increased risk of developing liver cancer.  Environmental factors can strongly influence the occurrence and severity of signs and symptoms of porphyria. Alcohol, smoking, certain drugs, hormones, other illnesses, stress, and dieting or periods without food (fasting) can all trigger the signs and symptoms of some forms of the disorder. Additionally, exposure to sunlight worsens the skin damage in people with cutaneous porphyrias.",porphyria,0000811,GHR,https://ghr.nlm.nih.gov/condition/porphyria,C0032708,T047,Disorders
How many people are affected by porphyria ?,0000811-2,frequency,"The exact prevalence of porphyria is unknown, but it probably ranges from 1 in 500 to 1 in 50,000 people worldwide. Overall, porphyria cutanea tarda is the most common type of porphyria. For some forms of porphyria, the prevalence is unknown because many people with a genetic mutation associated with the disease never experience signs or symptoms.  Acute intermittent porphyria is the most common form of acute porphyria in most countries. It may occur more frequently in northern European countries, such as Sweden, and in the United Kingdom. Another form of the disorder, hereditary coproporphyria, has been reported mostly in Europe and North America. Variegate porphyria is most common in the Afrikaner population of South Africa; about 3 in 1,000 people in this population have the genetic change that causes this form of the disorder.",porphyria,0000811,GHR,https://ghr.nlm.nih.gov/condition/porphyria,C0032708,T047,Disorders
What are the genetic changes related to porphyria ?,0000811-3,genetic changes,"Each form of porphyria results from mutations in one of these genes: ALAD, ALAS2, CPOX, FECH, HMBS, PPOX, UROD, or UROS.  The genes related to porphyria provide instructions for making the enzymes needed to produce heme. Mutations in most of these genes reduce enzyme activity, which limits the amount of heme the body can produce. As a result, compounds called porphyrins and porphyrin precursors, which are formed during the process of heme production, can build up abnormally in the liver and other organs. When these substances accumulate in the skin and interact with sunlight, they cause the cutaneous forms of porphyria. The acute forms of the disease occur when porphyrins and porphyrin precursors build up in and damage the nervous system.  One type of porphyria, porphyria cutanea tarda, results from both genetic and nongenetic factors. About 20 percent of cases are related to mutations in the UROD gene. The remaining cases are not associated with UROD gene mutations and are classified as sporadic. Many factors contribute to the development of porphyria cutanea tarda. These include an increased amount of iron in the liver, alcohol consumption, smoking, hepatitis C or HIV infection, or certain hormones. Mutations in the HFE gene (which cause an iron overload disorder called hemochromatosis) are also associated with porphyria cutanea tarda. Other, as-yet-unidentified genetic factors may also play a role in this form of porphyria.",porphyria,0000811,GHR,https://ghr.nlm.nih.gov/condition/porphyria,C0032708,T047,Disorders
Is porphyria inherited ?,0000811-4,inheritance,"Some types of porphyria are inherited in an autosomal dominant pattern, which means one copy of the gene in each cell is mutated. This single mutation is sufficient to reduce the activity of an enzyme needed for heme production, which increases the risk of developing signs and symptoms of porphyria. Autosomal dominant porphyrias include acute intermittent porphyria, most cases of erythropoietic protoporphyria, hereditary coproporphyria, and variegate porphyria. Although the gene mutations associated with some cases of porphyria cutanea tarda also have an autosomal dominant inheritance pattern, most people with this form of porphyria do not have an inherited gene mutation.  Other porphyrias are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition. Porphyrias with an autosomal recessive pattern of inheritance include ALAD deficiency porphyria, congenital erythropoietic porphyria, and some cases of erythropoietic protoporphyria.  When erythropoietic protoporphyria is caused by mutations in the ALAS2 gene, it has an X-linked dominant pattern of inheritance. The ALAS2 gene is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell may be sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. Males may experience more severe symptoms of the disorder than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  Mutations in the UROD gene are related to both porphyria cutanea tarda and hepatoerythropoietic porphyria. Individuals who inherit one altered copy of the UROD gene are at increased risk for porphyria cutanea tarda. (Multiple genetic and nongenetic factors contribute to this condition.) People who inherit two altered copies of the UROD gene in each cell develop hepatoerythropoietic porphyria.",porphyria,0000811,GHR,https://ghr.nlm.nih.gov/condition/porphyria,C0032708,T047,Disorders
What are the treatments for porphyria ?,0000811-5,treatment,"These resources address the diagnosis or management of porphyria:  - Gene Review: Gene Review: Acute Intermittent Porphyria  - Gene Review: Gene Review: Congenital Erythropoietic Porphyria  - Gene Review: Gene Review: Erythropoietic Protoporphyria, Autosomal Recessive  - Gene Review: Gene Review: Hereditary Coproporphyria  - Gene Review: Gene Review: Porphyria Cutanea Tarda, Type II  - Gene Review: Gene Review: Variegate Porphyria  - Gene Review: Gene Review: X-Linked Protoporphyria  - Genetic Testing Registry: Acute intermittent porphyria  - Genetic Testing Registry: Congenital erythropoietic porphyria  - Genetic Testing Registry: Erythropoietic protoporphyria  - Genetic Testing Registry: Familial porphyria cutanea tarda  - Genetic Testing Registry: Hereditary coproporphyria  - Genetic Testing Registry: Porphyria  - Genetic Testing Registry: Protoporphyria, erythropoietic, X-linked  - Genetic Testing Registry: Variegate porphyria  - MedlinePlus Encyclopedia: Porphyria  - MedlinePlus Encyclopedia: Porphyria cutanea tarda on the hands  - MedlinePlus Encyclopedia: Porphyrins - Blood  - MedlinePlus Encyclopedia: Porphyrins - Urine   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",porphyria,0000811,GHR,https://ghr.nlm.nih.gov/condition/porphyria,C0032708,T047,Disorders
What is (are) potassium-aggravated myotonia ?,0000812-1,information,"Potassium-aggravated myotonia is a disorder that affects muscles used for movement (skeletal muscles). Beginning in childhood or adolescence, people with this condition experience bouts of sustained muscle tensing (myotonia) that prevent muscles from relaxing normally. Myotonia causes muscle stiffness that worsens after exercise and may be aggravated by eating potassium-rich foods such as bananas and potatoes. Stiffness occurs in skeletal muscles throughout the body. Potassium-aggravated myotonia ranges in severity from mild episodes of muscle stiffness to severe, disabling disease with frequent attacks. Unlike some other forms of myotonia, potassium-aggravated myotonia is not associated with episodes of muscle weakness.",potassium-aggravated myotonia,0000812,GHR,https://ghr.nlm.nih.gov/condition/potassium-aggravated-myotonia,C2931826,T047,Disorders
How many people are affected by potassium-aggravated myotonia ?,0000812-2,frequency,This condition appears to be rare; it has been reported in only a few individuals and families worldwide.,potassium-aggravated myotonia,0000812,GHR,https://ghr.nlm.nih.gov/condition/potassium-aggravated-myotonia,C2931826,T047,Disorders
What are the genetic changes related to potassium-aggravated myotonia ?,0000812-3,genetic changes,"Mutations in the SCN4A gene cause potassium-aggravated myotonia.  The SCN4A gene provides instructions for making a protein that is critical for the normal function of skeletal muscle cells. For the body to move normally, skeletal muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of positively charged atoms (ions), including sodium, into skeletal muscle cells. The SCN4A protein forms channels that control the flow of sodium ions into these cells.  Mutations in the SCN4A gene alter the usual structure and function of sodium channels. The altered channels cannot properly regulate ion flow, increasing the movement of sodium ions into skeletal muscle cells. The influx of extra sodium ions triggers prolonged muscle contractions, which are the hallmark of myotonia.",potassium-aggravated myotonia,0000812,GHR,https://ghr.nlm.nih.gov/condition/potassium-aggravated-myotonia,C2931826,T047,Disorders
Is potassium-aggravated myotonia inherited ?,0000812-4,inheritance,"Potassium-aggravated myotonia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits a mutation in the SCN4A gene from one affected parent. Other cases result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.",potassium-aggravated myotonia,0000812,GHR,https://ghr.nlm.nih.gov/condition/potassium-aggravated-myotonia,C2931826,T047,Disorders
What are the treatments for potassium-aggravated myotonia ?,0000812-5,treatment,These resources address the diagnosis or management of potassium-aggravated myotonia:  - Genetic Testing Registry: Potassium aggravated myotonia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,potassium-aggravated myotonia,0000812,GHR,https://ghr.nlm.nih.gov/condition/potassium-aggravated-myotonia,C2931826,T047,Disorders
What is (are) Potocki-Shaffer syndrome ?,0000813-1,information,"Potocki-Shaffer syndrome is a disorder that affects development of the bones, nerve cells in the brain, and other tissues. Most people with this condition have multiple noncancerous (benign) bone tumors called osteochondromas. In rare instances, these tumors become cancerous. People with Potocki-Shaffer syndrome also have enlarged openings in the two bones that make up much of the top and sides of the skull (enlarged parietal foramina). These abnormal openings form extra ""soft spots"" on the head, in addition to the two that newborns normally have. Unlike the usual newborn soft spots, the enlarged parietal foramina remain open throughout life.  The signs and symptoms of Potocki-Shaffer syndrome vary widely. In addition to multiple osteochondromas and enlarged parietal foramina, affected individuals often have intellectual disability and delayed development of speech, motor skills (such as sitting and walking), and social skills. Many people with this condition have distinctive facial features, which can include a wide, short skull (brachycephaly); a prominent forehead; a narrow bridge of the nose; a shortened distance between the nose and upper lip (a short philtrum); and a downturned mouth. Less commonly, Potocki-Shaffer syndrome causes vision problems, additional skeletal abnormalities, and defects in the heart, kidneys, and urinary tract.",Potocki-Shaffer syndrome,0000813,GHR,https://ghr.nlm.nih.gov/condition/potocki-shaffer-syndrome,C1832588,T047,Disorders
How many people are affected by Potocki-Shaffer syndrome ?,0000813-2,frequency,"Potocki-Shaffer syndrome is a rare condition, although its prevalence is unknown. Fewer than 100 cases have been reported in the scientific literature.",Potocki-Shaffer syndrome,0000813,GHR,https://ghr.nlm.nih.gov/condition/potocki-shaffer-syndrome,C1832588,T047,Disorders
What are the genetic changes related to Potocki-Shaffer syndrome ?,0000813-3,genetic changes,"Potocki-Shaffer syndrome (also known as proximal 11p deletion syndrome) is caused by a deletion of genetic material from the short (p) arm of chromosome 11 at a position designated 11p11.2. The size of the deletion varies among affected individuals. Studies suggest that the full spectrum of features is caused by a deletion of at least 2.1 million DNA building blocks (base pairs), also written as 2.1 megabases (Mb). The loss of multiple genes within the deleted region causes the varied signs and symptoms of Potocki-Shaffer syndrome.  In particular, deletion of the EXT2, ALX4, and PHF21A genes are associated with several of the characteristic features of Potocki-Shaffer syndrome. Research shows that loss of the EXT2 gene is associated with the development of multiple osteochondromas in affected individuals. Deletion of another gene, ALX4, causes the enlarged parietal foramina found in people with this condition. In addition, loss of the PHF21A gene is the cause of intellectual disability and distinctive facial features in many people with the condition. The loss of additional genes in the deleted region likely contributes to the other features of Potocki-Shaffer syndrome.",Potocki-Shaffer syndrome,0000813,GHR,https://ghr.nlm.nih.gov/condition/potocki-shaffer-syndrome,C1832588,T047,Disorders
Is Potocki-Shaffer syndrome inherited ?,0000813-4,inheritance,"Potocki-Shaffer syndrome follows an autosomal dominant inheritance pattern, which means a deletion of genetic material from one copy of chromosome 11 is sufficient to cause the disorder. In some cases, an affected person inherits the chromosome with a deleted segment from an affected parent. More commonly, the condition results from a deletion that occurs during the formation of reproductive cells (eggs and sperm) in a parent or in early fetal development. These cases occur in people with no history of the disorder in their family.",Potocki-Shaffer syndrome,0000813,GHR,https://ghr.nlm.nih.gov/condition/potocki-shaffer-syndrome,C1832588,T047,Disorders
What are the treatments for Potocki-Shaffer syndrome ?,0000813-5,treatment,These resources address the diagnosis or management of Potocki-Shaffer syndrome:  - Genetic Testing Registry: Potocki-Shaffer syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Potocki-Shaffer syndrome,0000813,GHR,https://ghr.nlm.nih.gov/condition/potocki-shaffer-syndrome,C1832588,T047,Disorders
What is (are) PPM-X syndrome ?,0000814-1,information,"PPM-X syndrome is a condition characterized by psychotic disorders (most commonly bipolar disorder), a pattern of movement abnormalities known as parkinsonism, and mild to severe intellectual disability. Other symptoms include increased muscle tone and exaggerated reflexes. Affected males may have enlarged testes (macro-orchidism). Not all affected individuals have all these symptoms, but most have intellectual disability. Males with this condition are typically more severely affected than females, who usually have only mild intellectual disability.",PPM-X syndrome,0000814,GHR,https://ghr.nlm.nih.gov/condition/ppm-x-syndrome,C3713418,T047,Disorders
How many people are affected by PPM-X syndrome ?,0000814-2,frequency,The prevalence of PPM-X syndrome is unknown.,PPM-X syndrome,0000814,GHR,https://ghr.nlm.nih.gov/condition/ppm-x-syndrome,C3713418,T047,Disorders
What are the genetic changes related to PPM-X syndrome ?,0000814-3,genetic changes,"Mutations in the MECP2 gene cause PPM-X syndrome. The MECP2 gene provides instructions for making a protein called MeCP2 that is critical for normal brain function. Researchers believe that this protein has several functions, including regulating other genes in the brain by switching them off when they are not needed. The MeCP2 protein likely plays a role in maintaining connections (synapses) between nerve cells. The MeCP2 protein may also control the production of different versions of certain proteins in nerve cells. Although mutations in the MECP2 gene disrupt the normal function of nerve cells, it is unclear how these mutations lead to the signs and symptoms of PPM-X syndrome.  Some MECP2 gene mutations that cause PPM-X syndrome disrupt attachment (binding) of the MeCP2 protein to DNA, and other mutations alter the 3-dimensional shape of the protein. These mutations lead to the production of a MeCP2 protein that cannot properly interact with DNA or other proteins and so cannot control the expression of genes. It is unclear how MECP2 gene mutations lead to the signs and symptoms of PPM-X syndrome, but misregulation of genes in the brain likely plays a role.",PPM-X syndrome,0000814,GHR,https://ghr.nlm.nih.gov/condition/ppm-x-syndrome,C3713418,T047,Disorders
Is PPM-X syndrome inherited ?,0000814-4,inheritance,"More than 99 percent of PPM-X syndrome cases occur in people with no history of the disorder in their family. Many of these cases result from new mutations in the MECP2 gene.  A few families with more than one affected family member have been described. These cases helped researchers determine that PPM-X syndrome has an X-linked pattern of inheritance. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. One copy of the altered gene in each cell is sufficient to cause the condition, although females with one altered copy of the gene are usually less severely affected than males.",PPM-X syndrome,0000814,GHR,https://ghr.nlm.nih.gov/condition/ppm-x-syndrome,C3713418,T047,Disorders
What are the treatments for PPM-X syndrome ?,0000814-5,treatment,These resources address the diagnosis or management of PPM-X syndrome:  - Cincinnati Children's Hospital: MECP2-Related Disorders  - Gene Review: Gene Review: MECP2-Related Disorders   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,PPM-X syndrome,0000814,GHR,https://ghr.nlm.nih.gov/condition/ppm-x-syndrome,C3713418,T047,Disorders
What is (are) Prader-Willi syndrome ?,0000815-1,information,"Prader-Willi syndrome is a complex genetic condition that affects many parts of the body. In infancy, this condition is characterized by weak muscle tone (hypotonia), feeding difficulties, poor growth, and delayed development. Beginning in childhood, affected individuals develop an insatiable appetite, which leads to chronic overeating (hyperphagia) and obesity. Some people with Prader-Willi syndrome, particularly those with obesity, also develop type 2 diabetes mellitus (the most common form of diabetes).  People with Prader-Willi syndrome typically have mild to moderate intellectual impairment and learning disabilities. Behavioral problems are common, including temper outbursts, stubbornness, and compulsive behavior such as picking at the skin. Sleep abnormalities can also occur. Additional features of this condition include distinctive facial features such as a narrow forehead, almond-shaped eyes, and a triangular mouth; short stature; and small hands and feet. Some people with Prader-Willi syndrome have unusually fair skin and light-colored hair. Both affected males and affected females have underdeveloped genitals. Puberty is delayed or incomplete, and most affected individuals are unable to have children (infertile).",Prader-Willi syndrome,0000815,GHR,https://ghr.nlm.nih.gov/condition/prader-willi-syndrome,C0032897,T019,Disorders
How many people are affected by Prader-Willi syndrome ?,0000815-2,frequency,"Prader-Willi syndrome affects an estimated 1 in 10,000 to 30,000 people worldwide.",Prader-Willi syndrome,0000815,GHR,https://ghr.nlm.nih.gov/condition/prader-willi-syndrome,C0032897,T019,Disorders
What are the genetic changes related to Prader-Willi syndrome ?,0000815-3,genetic changes,"Prader-Willi syndrome is caused by the loss of function of genes in a particular region of chromosome 15. People normally inherit one copy of this chromosome from each parent. Some genes are turned on (active) only on the copy that is inherited from a person's father (the paternal copy). This parent-specific gene activation is caused by a phenomenon called genomic imprinting.  Most cases of Prader-Willi syndrome (about 70 percent) occur when a segment of the paternal chromosome 15 is deleted in each cell. People with this chromosomal change are missing certain critical genes in this region because the genes on the paternal copy have been deleted, and the genes on the maternal copy are turned off (inactive). In another 25 percent of cases, a person with Prader-Willi syndrome has two copies of chromosome 15 inherited from his or her mother (maternal copies) instead of one copy from each parent. This phenomenon is called maternal uniparental disomy. Rarely, Prader-Willi syndrome can also be caused by a chromosomal rearrangement called a translocation, or by a mutation or other defect that abnormally turns off (inactivates) genes on the paternal chromosome 15.  It appears likely that the characteristic features of Prader-Willi syndrome result from the loss of function of several genes on chromosome 15. Among these are genes that provide instructions for making molecules called small nucleolar RNAs (snoRNAs). These molecules have a variety of functions, including helping to regulate other types of RNA molecules. (RNA molecules play essential roles in producing proteins and in other cell activities.) Studies suggest that the loss of a particular group of snoRNA genes, known as the SNORD116 cluster, may play a major role in causing the signs and symptoms of Prader-Willi syndrome. However, it is unknown how a missing SNORD116 cluster could contribute to intellectual disability, behavioral problems, and the physical features of the disorder.  In some people with Prader-Willi syndrome, the loss of a gene called OCA2 is associated with unusually fair skin and light-colored hair. The OCA2 gene is located on the segment of chromosome 15 that is often deleted in people with this disorder. However, loss of the OCA2 gene does not cause the other signs and symptoms of Prader-Willi syndrome. The protein produced from this gene helps determine the coloring (pigmentation) of the skin, hair, and eyes.  Researchers are studying other genes on chromosome 15 that may also be related to the major signs and symptoms of this condition.",Prader-Willi syndrome,0000815,GHR,https://ghr.nlm.nih.gov/condition/prader-willi-syndrome,C0032897,T019,Disorders
Is Prader-Willi syndrome inherited ?,0000815-4,inheritance,"Most cases of Prader-Willi syndrome are not inherited, particularly those caused by a deletion in the paternal chromosome 15 or by maternal uniparental disomy. These genetic changes occur as random events during the formation of reproductive cells (eggs and sperm) or in early embryonic development. Affected people typically have no history of the disorder in their family.  Rarely, a genetic change responsible for Prader-Willi syndrome can be inherited. For example, it is possible for a genetic change that abnormally inactivates genes on the paternal chromosome 15 to be passed from one generation to the next.",Prader-Willi syndrome,0000815,GHR,https://ghr.nlm.nih.gov/condition/prader-willi-syndrome,C0032897,T019,Disorders
What are the treatments for Prader-Willi syndrome ?,0000815-5,treatment,These resources address the diagnosis or management of Prader-Willi syndrome:  - Gene Review: Gene Review: Prader-Willi Syndrome  - Genetic Testing Registry: Prader-Willi syndrome  - MedlinePlus Encyclopedia: Hypotonia  - MedlinePlus Encyclopedia: Prader-Willi Syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Prader-Willi syndrome,0000815,GHR,https://ghr.nlm.nih.gov/condition/prader-willi-syndrome,C0032897,T019,Disorders
What is (are) preeclampsia ?,0000816-1,information,"Preeclampsia is a complication of pregnancy in which affected women develop high blood pressure (hypertension) and can also have abnormally high levels of protein in their urine. This condition usually occurs in the last few months of pregnancy and often requires the early delivery of the infant.  Many women with mild preeclampsia do not feel ill, and the problem is first detected through blood pressure and urine testing in their doctor's office. Other early features of the disorder are swelling (edema) of the face or hands and a weight gain of more than 2 pounds within a few days. More severely affected women may experience headaches, dizziness, irritability, shortness of breath, a decrease in urination, upper abdominal pain, nausea, or vomiting. Vision changes may develop, including flashing lights or spots, increased sensitivity to light (photophobia), blurry vision, or temporary blindness.  In most cases, preeclampsia is mild and goes away within a few weeks after the baby is born. In severe cases, however, preeclampsia can impact the mother's organs such as the heart, liver, and kidneys and can lead to life-threatening complications. Extreme hypertension in the mother can cause bleeding in the brain (hemorrhagic stroke). The effects of high blood pressure on the brain (hypertensive encephalopathy) may also result in seizures. If seizures occur, the condition is considered to have progressed to eclampsia, which can result in coma. Without treatment to help prevent seizures, about 1 in 200 women with preeclampsia develop eclampsia.  Between 10 and 20 percent of women with severe preeclampsia develop another potentially life-threatening complication called HELLP syndrome. HELLP stands for hemolysis (premature red blood cell breakdown), elevated liver enzyme levels, and low platelets (cell fragments involved in blood clotting), which are the key features of this condition.  Severe preeclampsia can also affect the fetus, with impairment of blood and oxygen flow leading to growth problems or stillbirth. Infants delivered early due to preeclampsia may have complications associated with prematurity, such as breathing problems caused by underdeveloped lungs.  Women who have had preeclampsia have approximately twice the lifetime risk of heart disease and stroke than do women in the general population. Researchers suggest this may be due to common factors that increase the risk of preeclampsia, heart disease, and stroke.",preeclampsia,0000816,GHR,https://ghr.nlm.nih.gov/condition/preeclampsia,C0032914,T046,Disorders
How many people are affected by preeclampsia ?,0000816-2,frequency,"Preeclampsia is a common condition in all populations, occurring in 2 to 8 percent of pregnancies. It occurs more frequently in women of African or Hispanic descent than it does in women of European descent.",preeclampsia,0000816,GHR,https://ghr.nlm.nih.gov/condition/preeclampsia,C0032914,T046,Disorders
What are the genetic changes related to preeclampsia ?,0000816-3,genetic changes,"The specific causes of preeclampsia are not well understood. In pregnancy, blood volume normally increases to support the fetus, and the mother's body must adjust to handle this extra fluid. In some women the body does not react normally to the fluid changes of pregnancy, leading to the problems with high blood pressure and urine production in the kidneys that occur in preeclampsia.  The reasons for these abnormal reactions to the changes of pregnancy vary in different women and may differ depending on the stage of the pregnancy at which the condition develops. Studies suggest that preeclampsia is related to a problem with the placenta, the link between the mother's blood supply and the fetus. If there is an insufficient connection between the placenta and the arteries of the uterus, the placenta does not get enough blood. It responds by releasing a variety of substances, including molecules that affect the lining of blood vessels (the vascular endothelium). By mechanisms that are unclear, the reaction of the vascular endothelium appears to increase factors that cause the blood vessels to narrow (constrict), and decrease factors that would cause them to widen (dilate). As a result, the blood vessels constrict abnormally, causing hypertension. These blood vessel abnormalities also affect the kidneys, causing some proteins that are normally absorbed into the blood to be released in the urine instead.  Researchers are studying whether variations in genes involved in fluid balance, the functioning of the vascular endothelium, or placental development affect the risk of developing preeclampsia. Many other factors likely also contribute to the risk of developing this complex disorder. These risk factors include a first pregnancy; a pregnancy with twins or higher multiples; obesity; being older than 35 or younger than 20; a history of diabetes, hypertension, or kidney disease; and preeclampsia in a previous pregnancy. Socioeconomic status and ethnicity have also been associated with preeclampsia risk. The incidence of preeclampsia in the United States has increased by 30 percent in recent years, which has been attributed in part to an increase in older mothers and multiple births resulting from the use of assisted reproductive technologies.",preeclampsia,0000816,GHR,https://ghr.nlm.nih.gov/condition/preeclampsia,C0032914,T046,Disorders
Is preeclampsia inherited ?,0000816-4,inheritance,"Most cases of preeclampsia do not seem to be inherited. The tendency to develop preeclampsia does seem to run in some families; however, the inheritance pattern is unknown.",preeclampsia,0000816,GHR,https://ghr.nlm.nih.gov/condition/preeclampsia,C0032914,T046,Disorders
What are the treatments for preeclampsia ?,0000816-5,treatment,"These resources address the diagnosis or management of preeclampsia:  - Eunice Kennedy Shriver National Institute of Child Health and Human Development: How Do Health Care Providers Diagnose Preeclampsia, Eclampsia, and HELLP syndrome?  - Eunice Kennedy Shriver National Institute of Child Health and Human Development: What Are the Treatments for Preeclampsia, Eclampsia, and HELLP Syndrome?  - Genetic Testing Registry: Preeclampsia/eclampsia 1  - Genetic Testing Registry: Preeclampsia/eclampsia 2  - Genetic Testing Registry: Preeclampsia/eclampsia 3  - Genetic Testing Registry: Preeclampsia/eclampsia 4  - Genetic Testing Registry: Preeclampsia/eclampsia 5  - MedlinePlus Encyclopedia: Preeclampsia Self-care   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",preeclampsia,0000816,GHR,https://ghr.nlm.nih.gov/condition/preeclampsia,C0032914,T046,Disorders
What is (are) prekallikrein deficiency ?,0000817-1,information,"Prekallikrein deficiency is a blood condition that usually causes no health problems. In people with this condition, blood tests show a prolonged activated partial thromboplastin time (PTT), a result that is typically associated with bleeding problems; however, bleeding problems generally do not occur in prekallikrein deficiency. The condition is usually discovered when blood tests are done for other reasons.  A few people with prekallikrein deficiency have experienced health problems related to blood clotting such as heart attack, stroke, a clot in the deep veins of the arms or legs (deep vein thrombosis), nosebleeds, or excessive bleeding after surgery. However, these are common problems in the general population, and most affected individuals have other risk factors for developing them, so it is unclear whether their occurrence is related to prekallikrein deficiency.",prekallikrein deficiency,0000817,GHR,https://ghr.nlm.nih.gov/condition/prekallikrein-deficiency,C0272339,T047,Disorders
How many people are affected by prekallikrein deficiency ?,0000817-2,frequency,"The prevalence of prekallikrein deficiency is unknown. Approximately 80 affected individuals in about 30 families have been described in the medical literature. Because prekallikrein deficiency usually does not cause any symptoms, researchers suspect that most people with the condition are never diagnosed.",prekallikrein deficiency,0000817,GHR,https://ghr.nlm.nih.gov/condition/prekallikrein-deficiency,C0272339,T047,Disorders
What are the genetic changes related to prekallikrein deficiency ?,0000817-3,genetic changes,"Prekallikrein deficiency is caused by mutations in the KLKB1 gene, which provides instructions for making a protein called prekallikrein. This protein, when converted to an active form called plasma kallikrein in the blood, is involved in the early stages of blood clotting. Plasma kallikrein plays a role in a process called the intrinsic coagulation pathway (also called the contact activation pathway). This pathway turns on (activates) proteins that are needed later in the clotting process. Blood clots protect the body after an injury by sealing off damaged blood vessels and preventing further blood loss.  The KLKB1 gene mutations that cause prekallikrein deficiency reduce or eliminate functional plasma kallikrein, which likely impairs the intrinsic coagulation pathway. Researchers suggest that this lack (deficiency) of functional plasma kallikrein protein does not generally cause any symptoms because another process called the extrinsic coagulation pathway (also known as the tissue factor pathway) can compensate for the impaired intrinsic coagulation pathway.",prekallikrein deficiency,0000817,GHR,https://ghr.nlm.nih.gov/condition/prekallikrein-deficiency,C0272339,T047,Disorders
Is prekallikrein deficiency inherited ?,0000817-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",prekallikrein deficiency,0000817,GHR,https://ghr.nlm.nih.gov/condition/prekallikrein-deficiency,C0272339,T047,Disorders
What are the treatments for prekallikrein deficiency ?,0000817-5,treatment,These resources address the diagnosis or management of prekallikrein deficiency:  - Genetic Testing Registry: Prekallikrein deficiency  - Massachusetts General Hospital Laboratory Handbook: Prekallikrein   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,prekallikrein deficiency,0000817,GHR,https://ghr.nlm.nih.gov/condition/prekallikrein-deficiency,C0272339,T047,Disorders
What is (are) PRICKLE1-related progressive myoclonus epilepsy with ataxia ?,0000818-1,information,"PRICKLE1-related progressive myoclonus epilepsy with ataxia is a rare inherited condition characterized by recurrent seizures (epilepsy) and problems with movement. The signs and symptoms of this disorder usually begin between the ages of 5 and 10.  Problems with balance and coordination (ataxia) are usually the first symptoms of PRICKLE1-related progressive myoclonus epilepsy with ataxia. Affected children often have trouble walking. Their gait is unbalanced and wide-based, and they may fall frequently. Later, children with this condition develop episodes of involuntary muscle jerking or twitching (myoclonus), which cause additional problems with movement. Myoclonus can also affect muscles in the face, leading to difficulty swallowing and slurred speech (dysarthria).  Beginning later in childhood, some affected individuals develop tonic-clonic or grand mal seizures. These seizures involve a loss of consciousness, muscle rigidity, and convulsions. They often occur at night (nocturnally) while the person is sleeping.  PRICKLE1-related progressive myoclonus epilepsy with ataxia does not seem to affect intellectual ability. Although a few affected individuals have died in childhood, many have lived into adulthood.",PRICKLE1-related progressive myoclonus epilepsy with ataxia,0000818,GHR,https://ghr.nlm.nih.gov/condition/prickle1-related-progressive-myoclonus-epilepsy-with-ataxia,C0445223,T047,Disorders
How many people are affected by PRICKLE1-related progressive myoclonus epilepsy with ataxia ?,0000818-2,frequency,The prevalence of PRICKLE1-related progressive myoclonus epilepsy with ataxia is unknown. The condition has been reported in three large families from Jordan and northern Israel and in at least two unrelated individuals.,PRICKLE1-related progressive myoclonus epilepsy with ataxia,0000818,GHR,https://ghr.nlm.nih.gov/condition/prickle1-related-progressive-myoclonus-epilepsy-with-ataxia,C0445223,T047,Disorders
What are the genetic changes related to PRICKLE1-related progressive myoclonus epilepsy with ataxia ?,0000818-3,genetic changes,"PRICKLE1-related progressive myoclonus epilepsy with ataxia is caused by mutations in the PRICKLE1 gene. This gene provides instructions for making a protein called prickle homolog 1, whose function is unknown. Studies suggest that it interacts with other proteins that are critical for brain development and function.  Mutations in the PRICKLE1 gene alter the structure of prickle homolog 1 and disrupt its ability to interact with other proteins. However, it is unclear how these changes lead to movement problems, seizures, and the other features of PRICKLE1-related progressive myoclonus epilepsy with ataxia.",PRICKLE1-related progressive myoclonus epilepsy with ataxia,0000818,GHR,https://ghr.nlm.nih.gov/condition/prickle1-related-progressive-myoclonus-epilepsy-with-ataxia,C0445223,T047,Disorders
Is PRICKLE1-related progressive myoclonus epilepsy with ataxia inherited ?,0000818-4,inheritance,"Some cases of PRICKLE1-related progressive myoclonus epilepsy with ataxia are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Other cases of PRICKLE1-related progressive myoclonus epilepsy with ataxia are considered autosomal dominant because one copy of the altered gene in each cell is sufficient to cause the disorder. These cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",PRICKLE1-related progressive myoclonus epilepsy with ataxia,0000818,GHR,https://ghr.nlm.nih.gov/condition/prickle1-related-progressive-myoclonus-epilepsy-with-ataxia,C0445223,T047,Disorders
What are the treatments for PRICKLE1-related progressive myoclonus epilepsy with ataxia ?,0000818-5,treatment,These resources address the diagnosis or management of PRICKLE1-related progressive myoclonus epilepsy with ataxia:  - Gene Review: Gene Review: PRICKLE1-Related Progressive Myoclonus Epilepsy with Ataxia  - Genetic Testing Registry: Progressive myoclonus epilepsy with ataxia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,PRICKLE1-related progressive myoclonus epilepsy with ataxia,0000818,GHR,https://ghr.nlm.nih.gov/condition/prickle1-related-progressive-myoclonus-epilepsy-with-ataxia,C0445223,T047,Disorders
What is (are) primary carnitine deficiency ?,0000819-1,information,"Primary carnitine deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). Carnitine, a natural substance acquired mostly through the diet, is used by cells to process fats and produce energy.  Signs and symptoms of primary carnitine deficiency typically appear during infancy or early childhood and can include severe brain dysfunction (encephalopathy), a weakened and enlarged heart (cardiomyopathy), confusion, vomiting, muscle weakness, and low blood sugar (hypoglycemia). The severity of this condition varies among affected individuals. Some people with primary carnitine deficiency are asymptomatic, which means they do not have any signs or symptoms of the condition. All individuals with this disorder are at risk for heart failure, liver problems, coma, and sudden death.  Problems related to primary carnitine deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.",primary carnitine deficiency,0000819,GHR,https://ghr.nlm.nih.gov/condition/primary-carnitine-deficiency,C0342788,T047,Disorders
How many people are affected by primary carnitine deficiency ?,0000819-2,frequency,"The incidence of primary carnitine deficiency in the general population is approximately 1 in 100,000 newborns. In Japan, this disorder affects 1 in every 40,000 newborns.",primary carnitine deficiency,0000819,GHR,https://ghr.nlm.nih.gov/condition/primary-carnitine-deficiency,C0342788,T047,Disorders
What are the genetic changes related to primary carnitine deficiency ?,0000819-3,genetic changes,"Mutations in the SLC22A5 gene cause primary carnitine deficiency. This gene provides instructions for making a protein called OCTN2 that transports carnitine into cells. Cells need carnitine to bring certain types of fats (fatty acids) into mitochondria, which are the energy-producing centers within cells. Fatty acids are a major source of energy for the heart and muscles. During periods of fasting, fatty acids are also an important energy source for the liver and other tissues.  Mutations in the SLC22A5 gene result in an absent or dysfunctional OCTN2 protein. As a result, there is a shortage (deficiency) of carnitine within cells. Without carnitine, fatty acids cannot enter mitochondria and be used to make energy. Reduced energy production can lead to some of the features of primary carnitine deficiency, such as muscle weakness and hypoglycemia. Fatty acids may also build up in cells and damage the liver, heart, and muscles. This abnormal buildup causes the other signs and symptoms of the disorder.",primary carnitine deficiency,0000819,GHR,https://ghr.nlm.nih.gov/condition/primary-carnitine-deficiency,C0342788,T047,Disorders
Is primary carnitine deficiency inherited ?,0000819-4,inheritance,"Primary carnitine deficiency is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive disorder are carriers, which means they each carry one copy of the mutated gene. Carriers of SLC22A5 gene mutations may have some signs and symptoms related to the condition.",primary carnitine deficiency,0000819,GHR,https://ghr.nlm.nih.gov/condition/primary-carnitine-deficiency,C0342788,T047,Disorders
What are the treatments for primary carnitine deficiency ?,0000819-5,treatment,These resources address the diagnosis or management of primary carnitine deficiency:  - Baby's First Test  - Gene Review: Gene Review: Systemic Primary Carnitine Deficiency  - Genetic Testing Registry: Renal carnitine transport defect  - The Linus Pauling Institute: L-Carnitine   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,primary carnitine deficiency,0000819,GHR,https://ghr.nlm.nih.gov/condition/primary-carnitine-deficiency,C0342788,T047,Disorders
What is (are) primary ciliary dyskinesia ?,0000820-1,information,"Primary ciliary dyskinesia is a disorder characterized by chronic respiratory tract infections, abnormally positioned internal organs, and the inability to have children (infertility). The signs and symptoms of this condition are caused by abnormal cilia and flagella. Cilia are microscopic, finger-like projections that stick out from the surface of cells. They are found in the linings of the airway, the reproductive system, and other organs and tissues. Flagella are tail-like structures, similar to cilia, that propel sperm cells forward.  In the respiratory tract, cilia move back and forth in a coordinated way to move mucus towards the throat. This movement of mucus helps to eliminate fluid, bacteria, and particles from the lungs. Most babies with primary ciliary dyskinesia experience breathing problems at birth, which suggests that cilia play an important role in clearing fetal fluid from the lungs. Beginning in early childhood, affected individuals develop frequent respiratory tract infections. Without properly functioning cilia in the airway, bacteria remain in the respiratory tract and cause infection. People with primary ciliary dyskinesia also have year-round nasal congestion and a chronic cough. Chronic respiratory tract infections can result in a condition called bronchiectasis, which damages the passages, called bronchi, leading from the windpipe to the lungs and can cause life-threatening breathing problems.  Some individuals with primary ciliary dyskinesia have abnormally placed organs within their chest and abdomen. These abnormalities arise early in embryonic development when the differences between the left and right sides of the body are established. About 50 percent of people with primary ciliary dyskinesia have a mirror-image reversal of their internal organs (situs inversus totalis). For example, in these individuals the heart is on the right side of the body instead of on the left. Situs inversus totalis does not cause any apparent health problems. When someone with primary ciliary dyskinesia has situs inversus totalis, they are often said to have Kartagener syndrome.  Approximately 12 percent of people with primary ciliary dyskinesia have a condition known as heterotaxy syndrome or situs ambiguus, which is characterized by abnormalities of the heart, liver, intestines, or spleen. These organs may be structurally abnormal or improperly positioned. In addition, affected individuals may lack a spleen (asplenia) or have multiple spleens (polysplenia). Heterotaxy syndrome results from problems establishing the left and right sides of the body during embryonic development. The severity of heterotaxy varies widely among affected individuals.  Primary ciliary dyskinesia can also lead to infertility. Vigorous movements of the flagella are necessary to propel the sperm cells forward to the female egg cell. Because their sperm do not move properly, males with primary ciliary dyskinesia are usually unable to father children. Infertility occurs in some affected females and is likely due to abnormal cilia in the fallopian tubes.  Another feature of primary ciliary dyskinesia is recurrent ear infections (otitis media), especially in young children. Otitis media can lead to permanent hearing loss if untreated. The ear infections are likely related to abnormal cilia within the inner ear.  Rarely, individuals with primary ciliary dyskinesia have an accumulation of fluid in the brain (hydrocephalus), likely due to abnormal cilia in the brain.",primary ciliary dyskinesia,0000820,GHR,https://ghr.nlm.nih.gov/condition/primary-ciliary-dyskinesia,C0008780,T019,Disorders
How many people are affected by primary ciliary dyskinesia ?,0000820-2,frequency,"Primary ciliary dyskinesia occurs in approximately 1 in 16,000 individuals.",primary ciliary dyskinesia,0000820,GHR,https://ghr.nlm.nih.gov/condition/primary-ciliary-dyskinesia,C0008780,T019,Disorders
What are the genetic changes related to primary ciliary dyskinesia ?,0000820-3,genetic changes,"Primary ciliary dyskinesia can result from mutations in many different genes. These genes provide instructions for making proteins that form the inner structure of cilia and produce the force needed for cilia to bend. Coordinated back and forth movement of cilia is necessary for the normal functioning of many organs and tissues. The movement of cilia also helps establish the left-right axis (the imaginary line that separates the left and right sides of the body) during embryonic development.  Mutations in the genes that cause primary ciliary dyskinesia result in defective cilia that move abnormally or are unable to move (immotile). Because cilia have many important functions within the body, defects in these cell structures cause a variety of signs and symptoms.  Mutations in the DNAI1 and DNAH5 genes account for up to 30 percent of all cases of primary ciliary dyskinesia. Mutations in the other genes associated with this condition are found in only a small percentage of cases. In many people with primary ciliary dyskinesia, the cause of the disorder is unknown.",primary ciliary dyskinesia,0000820,GHR,https://ghr.nlm.nih.gov/condition/primary-ciliary-dyskinesia,C0008780,T019,Disorders
Is primary ciliary dyskinesia inherited ?,0000820-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",primary ciliary dyskinesia,0000820,GHR,https://ghr.nlm.nih.gov/condition/primary-ciliary-dyskinesia,C0008780,T019,Disorders
What are the treatments for primary ciliary dyskinesia ?,0000820-5,treatment,"These resources address the diagnosis or management of primary ciliary dyskinesia:  - Gene Review: Gene Review: Primary Ciliary Dyskinesia  - Genetic Testing Registry: Ciliary dyskinesia, primary, 17  - Genetic Testing Registry: Kartagener syndrome  - Genetic Testing Registry: Primary ciliary dyskinesia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",primary ciliary dyskinesia,0000820,GHR,https://ghr.nlm.nih.gov/condition/primary-ciliary-dyskinesia,C0008780,T019,Disorders
What is (are) primary hyperoxaluria ?,0000821-1,information,"Primary hyperoxaluria is a rare condition characterized by recurrent kidney and bladder stones. The condition often results in end stage renal disease (ESRD), which is a life-threatening condition that prevents the kidneys from filtering fluids and waste products from the body effectively.  Primary hyperoxaluria results from the overproduction of a substance called oxalate. Oxalate is filtered through the kidneys and excreted as a waste product in urine, leading to abnormally high levels of this substance in urine (hyperoxaluria). During its excretion, oxalate can combine with calcium to form calcium oxalate, a hard compound that is the main component of kidney and bladder stones. Deposits of calcium oxalate can damage the kidneys and other organs and lead to blood in the urine (hematuria), urinary tract infections, kidney damage, ESRD, and injury to other organs. Over time, kidney function decreases such that the kidneys can no longer excrete as much oxalate as they receive. As a result oxalate levels in the blood rise, and the substance gets deposited in tissues throughout the body (systemic oxalosis), particularly in bones and the walls of blood vessels. Oxalosis in bones can cause fractures.  There are three types of primary hyperoxaluria that differ in their severity and genetic cause. In primary hyperoxaluria type 1, kidney stones typically begin to appear anytime from childhood to early adulthood, and ESRD can develop at any age. Primary hyperoxaluria type 2 is similar to type 1, but ESRD develops later in life. In primary hyperoxaluria type 3, affected individuals often develop kidney stones in early childhood, but few cases of this type have been described so additional signs and symptoms of this type are unclear.",primary hyperoxaluria,0000821,GHR,https://ghr.nlm.nih.gov/condition/primary-hyperoxaluria,C0020501,T047,Disorders
How many people are affected by primary hyperoxaluria ?,0000821-2,frequency,"Primary hyperoxaluria is estimated to affect 1 in 58,000 individuals worldwide. Type 1 is the most common form, accounting for approximately 80 percent of cases. Types 2 and 3 each account for about 10 percent of cases.",primary hyperoxaluria,0000821,GHR,https://ghr.nlm.nih.gov/condition/primary-hyperoxaluria,C0020501,T047,Disorders
What are the genetic changes related to primary hyperoxaluria ?,0000821-3,genetic changes,"Mutations in the AGXT, GRHPR, and HOGA1 genes cause primary hyperoxaluria types 1, 2, and 3, respectively. These genes provide instructions for making enzymes that are involved in the breakdown and processing of protein building blocks (amino acids) and other compounds. The enzyme produced from the HOGA1 gene is involved in the breakdown of an amino acid, which results in the formation of a compound called glyoxylate. This compound is further broken down by the enzymes produced from the AGXT and GRHPR genes.  Mutations in the AGXT, GRHPR, or HOGA1 gene lead to a decrease in production or activity of the respective proteins, which prevents the normal breakdown of glyoxylate. AGXT and GRHPR gene mutations result in an accumulation of glyoxylate, which is then converted to oxalate for removal from the body as a waste product. HOGA1 gene mutations also result in excess oxalate, although researchers are unsure as to how this occurs. Oxalate that is not excreted from the body combines with calcium to form calcium oxalate deposits, which can damage the kidneys and other organs.",primary hyperoxaluria,0000821,GHR,https://ghr.nlm.nih.gov/condition/primary-hyperoxaluria,C0020501,T047,Disorders
Is primary hyperoxaluria inherited ?,0000821-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",primary hyperoxaluria,0000821,GHR,https://ghr.nlm.nih.gov/condition/primary-hyperoxaluria,C0020501,T047,Disorders
What are the treatments for primary hyperoxaluria ?,0000821-5,treatment,These resources address the diagnosis or management of primary hyperoxaluria:  - Gene Review: Gene Review: Primary Hyperoxaluria Type 1  - Gene Review: Gene Review: Primary Hyperoxaluria Type 2  - Gene Review: Gene Review: Primary Hyperoxaluria Type 3  - Genetic Testing Registry: Hyperoxaluria  - Genetic Testing Registry: Primary hyperoxaluria   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,primary hyperoxaluria,0000821,GHR,https://ghr.nlm.nih.gov/condition/primary-hyperoxaluria,C0020501,T047,Disorders
What is (are) primary macronodular adrenal hyperplasia ?,0000822-1,information,"Primary macronodular adrenal hyperplasia (PMAH) is a disorder characterized by multiple lumps (nodules) in the adrenal glands, which are small hormone-producing glands located on top of each kidney. These nodules, which usually are found in both adrenal glands (bilateral) and vary in size, cause adrenal gland enlargement (hyperplasia) and result in the production of higher-than-normal levels of the hormone cortisol. Cortisol is an important hormone that suppresses inflammation and protects the body from physical stress such as infection or trauma through several mechanisms including raising blood sugar levels.  PMAH typically becomes evident in a person's forties or fifties. It is considered a form of Cushing syndrome, which is characterized by increased levels of cortisol resulting from one of many possible causes. These increased cortisol levels lead to weight gain in the face and upper body, fragile skin, bone loss, fatigue, and other health problems. However, some people with PMAH do not experience these signs and symptoms and are said to have subclinical Cushing syndrome.",primary macronodular adrenal hyperplasia,0000822,GHR,https://ghr.nlm.nih.gov/condition/primary-macronodular-adrenal-hyperplasia,C0342495,T190,Disorders
How many people are affected by primary macronodular adrenal hyperplasia ?,0000822-2,frequency,"PMAH is a rare disorder. It is present in less than 1 percent of cases of endogenous Cushing syndrome, which describes forms of Cushing syndrome caused by factors internal to the body rather than by external factors such as long-term use of certain medicines called corticosteroids. The prevalence of endogenous Cushing syndrome is about 1 in 26,000 people.",primary macronodular adrenal hyperplasia,0000822,GHR,https://ghr.nlm.nih.gov/condition/primary-macronodular-adrenal-hyperplasia,C0342495,T190,Disorders
What are the genetic changes related to primary macronodular adrenal hyperplasia ?,0000822-3,genetic changes,"In about half of individuals with PMAH, the condition is caused by mutations in the ARMC5 gene. This gene provides instructions for making a protein that is thought to act as a tumor suppressor, which means that it helps to prevent cells from growing and dividing too rapidly or in an uncontrolled way. ARMC5 gene mutations are believed to impair the protein's tumor-suppressor function, which allows the overgrowth of certain cells. It is unclear why this overgrowth is limited to the formation of adrenal gland nodules in people with PMAH.  PMAH can also be caused by mutations in the GNAS gene. This gene provides instructions for making one component, the stimulatory alpha subunit, of a protein complex called a guanine nucleotide-binding protein (G protein). The G protein produced from the GNAS gene helps stimulate the activity of an enzyme called adenylate cyclase. This enzyme is involved in controlling the production of several hormones that help regulate the activity of certain endocrine glands, including the adrenal glands. The GNAS gene mutations that cause PMAH are believed to result in an overactive G protein. Research suggests that the overactive G protein may increase levels of adenylate cyclase and result in the overproduction of another compound called cyclic AMP (cAMP). An excess of cAMP may trigger abnormal cell growth and lead to the adrenal nodules characteristic of PMAH.  Mutations in other genes, some of which are unknown, can also cause PMAH.",primary macronodular adrenal hyperplasia,0000822,GHR,https://ghr.nlm.nih.gov/condition/primary-macronodular-adrenal-hyperplasia,C0342495,T190,Disorders
Is primary macronodular adrenal hyperplasia inherited ?,0000822-4,inheritance,"People with PMAH caused by ARMC5 gene mutations inherit one copy of the mutated gene in each cell. The inheritance is considered autosomal dominant because one copy of the mutated gene is sufficient to make an individual susceptible to PMAH. However, the condition develops only when affected individuals acquire another mutation in the other copy of the ARMC5 gene in certain cells of the adrenal glands. This second mutation is described as somatic. Instead of being passed from parent to child, somatic mutations are acquired during a person's lifetime and are present only in certain cells. Because somatic mutations are also required for PMAH to occur, some people who have inherited the altered ARMC5 gene never develop the condition, a situation known as reduced penetrance.  When PMAH is caused by GNAS gene mutations, the condition is not inherited. The GNAS gene mutations that cause PMAH are somatic mutations. In PMAH, the gene mutation is believed to occur early in embryonic development. Cells with the mutated GNAS gene can be found in both adrenal glands.",primary macronodular adrenal hyperplasia,0000822,GHR,https://ghr.nlm.nih.gov/condition/primary-macronodular-adrenal-hyperplasia,C0342495,T190,Disorders
What are the treatments for primary macronodular adrenal hyperplasia ?,0000822-5,treatment,These resources address the diagnosis or management of PMAH:  - Eunice Kennedy Shriver National Institute of Child Health and Human Development: How Do Health Care Providers Diagnose Adrenal Gland Disorders?  - Eunice Kennedy Shriver National Institute of Child Health and Human Development: What are the Treatments for Adrenal Gland Disorders?  - Genetic Testing Registry: Acth-independent macronodular adrenal hyperplasia 2   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,primary macronodular adrenal hyperplasia,0000822,GHR,https://ghr.nlm.nih.gov/condition/primary-macronodular-adrenal-hyperplasia,C0342495,T190,Disorders
What is (are) primary myelofibrosis ?,0000823-1,information,"Primary myelofibrosis is a condition characterized by the buildup of scar tissue (fibrosis) in the bone marrow, the tissue that produces blood cells. Because of the fibrosis, the bone marrow is unable to make enough normal blood cells. The shortage of blood cells causes many of the signs and symptoms of primary myelofibrosis.  Initially, most people with primary myelofibrosis have no signs or symptoms. Eventually, fibrosis can lead to a reduction in the number of red blood cells, white blood cells, and platelets. A shortage of red blood cells (anemia) often causes extreme tiredness (fatigue) or shortness of breath. A loss of white blood cells can lead to an increased number of infections, and a reduction of platelets can cause easy bleeding or bruising.  Because blood cell formation (hematopoiesis) in the bone marrow is disrupted, other organs such as the spleen or liver may begin to produce blood cells. This process, called extramedullary hematopoiesis, often leads to an enlarged spleen (splenomegaly) or an enlarged liver (hepatomegaly). People with splenomegaly may feel pain or fullness in the abdomen, especially below the ribs on the left side. Other common signs and symptoms of primary myelofibrosis include fever, night sweats, and bone pain.  Primary myelofibrosis is most commonly diagnosed in people aged 50 to 80 but can occur at any age.",primary myelofibrosis,0000823,GHR,https://ghr.nlm.nih.gov/condition/primary-myelofibrosis,C0001815,T191,Disorders
How many people are affected by primary myelofibrosis ?,0000823-2,frequency,"Primary myelofibrosis is a rare condition that affects approximately 1 in 500,000 people worldwide.",primary myelofibrosis,0000823,GHR,https://ghr.nlm.nih.gov/condition/primary-myelofibrosis,C0001815,T191,Disorders
What are the genetic changes related to primary myelofibrosis ?,0000823-3,genetic changes,"Mutations in the JAK2, MPL, CALR, and TET2 genes are associated with most cases of primary myelofibrosis. The JAK2 and MPL genes provide instructions for making proteins that promote the growth and division (proliferation) of blood cells. The CALR gene provides instructions for making a protein with multiple functions, including ensuring the proper folding of newly formed proteins and maintaining the correct levels of stored calcium in cells. The TET2 gene provides instructions for making a protein whose function is unknown.  The proteins produced from the JAK2 and MPL genes are both part of a signaling pathway called the JAK/STAT pathway, which transmits chemical signals from outside the cell to the cell's nucleus. The protein produced from the MPL gene, called thrombopoietin receptor, turns on (activates) the pathway, and the JAK2 protein transmits signals after activation. Through the JAK/STAT pathway, these two proteins promote the proliferation of blood cells, particularly a type of blood cell known as a megakaryocyte.  Mutations in either the JAK2 gene or the MPL gene that are associated with primary myelofibrosis lead to overactivation of the JAK/STAT pathway. The abnormal activation of JAK/STAT signaling leads to overproduction of abnormal megakaryocytes, and these megakaryocytes stimulate another type of cell to release collagen. Collagen is a protein that normally provides structural support for the cells in the bone marrow. However, in primary myelofibrosis, the excess collagen forms scar tissue in the bone marrow.  Although mutations in the CALR gene and the TET2 gene are relatively common in primary myelofibrosis, it is unclear how these mutations are involved in the development of the condition.  Some people with primary myelofibrosis do not have a mutation in any of the known genes associated with this condition. Researchers are working to identify other genes that may be involved in the condition.",primary myelofibrosis,0000823,GHR,https://ghr.nlm.nih.gov/condition/primary-myelofibrosis,C0001815,T191,Disorders
Is primary myelofibrosis inherited ?,0000823-4,inheritance,This condition is generally not inherited but arises from gene mutations that occur in early blood-forming cells after conception. These alterations are called somatic mutations.,primary myelofibrosis,0000823,GHR,https://ghr.nlm.nih.gov/condition/primary-myelofibrosis,C0001815,T191,Disorders
What are the treatments for primary myelofibrosis ?,0000823-5,treatment,These resources address the diagnosis or management of primary myelofibrosis:  - Genetic Testing Registry: Myelofibrosis  - Merck Manual Professional Version: Primary Myelofibrosis  - Myeloproliferative Neoplasm (MPN) Research Foundation: Primary Myelofibrosis (PMF)   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,primary myelofibrosis,0000823,GHR,https://ghr.nlm.nih.gov/condition/primary-myelofibrosis,C0001815,T191,Disorders
What is (are) primary sclerosing cholangitis ?,0000824-1,information,"Primary sclerosing cholangitis is a condition that affects the bile ducts. These ducts carry bile (a fluid that helps to digest fats) from the liver, where bile is produced, to the gallbladder, where it is stored, and to the small intestine, where it aids in digestion. Primary sclerosing cholangitis occurs because of inflammation in the bile ducts (cholangitis) that leads to scarring (sclerosis) and narrowing of the ducts. As a result, bile cannot be released to the gallbladder and small intestine, and it builds up in the liver.  Primary sclerosing cholangitis is usually diagnosed around age 40, and for unknown reasons, it affects men twice as often as women. Many people have no signs or symptoms of the condition when they are diagnosed, but routine blood tests reveal liver problems. When apparent, the earliest signs and symptoms of primary sclerosing cholangitis include extreme tiredness (fatigue), discomfort in the abdomen, and severe itchiness (pruritus). As the condition worsens, affected individuals may develop yellowing of the skin and whites of the eyes (jaundice) and an enlarged spleen (splenomegaly). Eventually, the buildup of bile damages the liver cells, causing chronic liver disease (cirrhosis) and liver failure. Without bile available to digest them, fats pass through the body. As a result, weight loss and shortages of vitamins that are absorbed with and stored in fats (fat-soluble vitamins) can occur. A fat-soluble vitamin called vitamin D helps absorb calcium and helps bones harden, and lack of this vitamin can cause thinning of the bones (osteoporosis) in people with primary sclerosing cholangitis.  Primary sclerosing cholangitis is often associated with another condition called inflammatory bowel disease, which is characterized by inflammation of the intestines that causes open sores (ulcers) in the intestines and abdominal pain. However, the reason for this link is unclear. Approximately 70 percent of people with primary sclerosing cholangitis have inflammatory bowel disease, most commonly a form of the condition known as ulcerative colitis. In addition, people with primary sclerosing cholangitis are more likely to have an autoimmune disorder, such as type 1 diabetes, celiac disease, or thyroid disease, than people without the condition. Autoimmune disorders occur when the immune system malfunctions and attacks the body's tissues and organs. People with primary sclerosing cholangitis also have an increased risk of developing cancer, particularly cancer of the bile ducts (cholangiocarcinoma).",primary sclerosing cholangitis,0000824,GHR,https://ghr.nlm.nih.gov/condition/primary-sclerosing-cholangitis,C0566602,T047,Disorders
How many people are affected by primary sclerosing cholangitis ?,0000824-2,frequency,"An estimated 1 in 10,000 people have primary sclerosing cholangitis, and the condition is diagnosed in approximately 1 in 100,000 people per year worldwide.",primary sclerosing cholangitis,0000824,GHR,https://ghr.nlm.nih.gov/condition/primary-sclerosing-cholangitis,C0566602,T047,Disorders
What are the genetic changes related to primary sclerosing cholangitis ?,0000824-3,genetic changes,"Primary sclerosing cholangitis is thought to arise from a combination of genetic and environmental factors. Researchers believe that genetic changes play a role in this condition because it often occurs in several members of a family and because immediate family members of someone with primary sclerosing cholangitis have an increased risk of developing the condition. It is likely that specific genetic variations increase a person's risk of developing primary sclerosing cholangitis, and then exposure to certain environmental factors triggers the disorder. However, the genetic changes that increase susceptibility and the environmental triggers remain unclear.  There is evidence that variations in certain genes involved in immune function influence the risk of developing primary sclerosing cholangitis. The most commonly associated genes belong to a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Each HLA gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. Specific variations of several HLA genes seem to be present more often in people with primary sclerosing cholangitis than in people who do not have the disorder. These variations may dysregulate the body's immune response, leading to the inflammation of the bile ducts in people with primary sclerosing cholangitis. However, the mechanism is not well understood. Researchers are also studying variations in other genes related to the body's immune function to understand how they contribute to the risk of developing this condition.",primary sclerosing cholangitis,0000824,GHR,https://ghr.nlm.nih.gov/condition/primary-sclerosing-cholangitis,C0566602,T047,Disorders
Is primary sclerosing cholangitis inherited ?,0000824-4,inheritance,"The inheritance pattern of primary sclerosing cholangitis is unknown because many genetic and environmental factors are likely to be involved. This condition tends to cluster in families, however, and having an affected family member is a risk factor for developing the disease.",primary sclerosing cholangitis,0000824,GHR,https://ghr.nlm.nih.gov/condition/primary-sclerosing-cholangitis,C0566602,T047,Disorders
What are the treatments for primary sclerosing cholangitis ?,0000824-5,treatment,These resources address the diagnosis or management of primary sclerosing cholangitis:  - American Liver Foundation: Primary Sclerosing Cholangitis (PSC)  - Genetic Testing Registry: Primary sclerosing cholangitis  - MedlinePlus Encyclopedia: Sclerosing Cholangitis  - University of California San Francisco Medical Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,primary sclerosing cholangitis,0000824,GHR,https://ghr.nlm.nih.gov/condition/primary-sclerosing-cholangitis,C0566602,T047,Disorders
What is (are) primary spontaneous pneumothorax ?,0000825-1,information,"Primary spontaneous pneumothorax is an abnormal accumulation of air in the space between the lungs and the chest cavity (called the pleural space) that can result in the partial or complete collapse of a lung. This type of pneumothorax is described as primary because it occurs in the absence of lung disease such as emphysema. Spontaneous means the pneumothorax was not caused by an injury such as a rib fracture. Primary spontaneous pneumothorax is likely due to the formation of small sacs of air (blebs) in lung tissue that rupture, causing air to leak into the pleural space. Air in the pleural space creates pressure on the lung and can lead to its collapse. A person with this condition may feel chest pain on the side of the collapsed lung and shortness of breath.  Blebs may be present on an individual's lung (or lungs) for a long time before they rupture. Many things can cause a bleb to rupture, such as changes in air pressure or a very sudden deep breath. Often, people who experience a primary spontaneous pneumothorax have no prior sign of illness; the blebs themselves typically do not cause any symptoms and are visible only on medical imaging. Affected individuals may have one bleb to more than thirty blebs. Once a bleb ruptures and causes a pneumothorax, there is an estimated 13 to 60 percent chance that the condition will recur.",primary spontaneous pneumothorax,0000825,GHR,https://ghr.nlm.nih.gov/condition/primary-spontaneous-pneumothorax,C1868193,T047,Disorders
How many people are affected by primary spontaneous pneumothorax ?,0000825-2,frequency,"Primary spontaneous pneumothorax is more common in men than in women. This condition occurs in 7.4 to 18 per 100,000 men each year and 1.2 to 6 per 100,000 women each year.",primary spontaneous pneumothorax,0000825,GHR,https://ghr.nlm.nih.gov/condition/primary-spontaneous-pneumothorax,C1868193,T047,Disorders
What are the genetic changes related to primary spontaneous pneumothorax ?,0000825-3,genetic changes,"Mutations in the FLCN gene can cause primary spontaneous pneumothorax, although these mutations appear to be a very rare cause of this condition. The FLCN gene provides instructions for making a protein called folliculin. In the lungs, folliculin is found in the connective tissue cells that allow the lungs to contract and expand when breathing. Folliculin is also produced in cells that line the small air sacs (alveoli). Researchers have not determined the protein's function, but they believe it may help control the growth and division of cells. Folliculin may play a role in repairing and re-forming lung tissue following damage. Researchers have not determined how FLCN gene mutations lead to the formation of blebs and increase the risk of primary spontaneous pneumothorax. One theory is that the altered folliculin protein may trigger inflammation within the lung tissue that could alter and damage the tissue, causing blebs.  Primary spontaneous pneumothorax most often occurs in people without an identified gene mutation. The cause of the condition in these individuals is often unknown. Tall young men are at increased risk of developing primary spontaneous pneumothorax; researchers suggest that rapid growth of the chest during growth spurts may increase the likelihood of forming blebs. Smoking can also contribute to the development of primary spontaneous pneumothorax.",primary spontaneous pneumothorax,0000825,GHR,https://ghr.nlm.nih.gov/condition/primary-spontaneous-pneumothorax,C1868193,T047,Disorders
Is primary spontaneous pneumothorax inherited ?,0000825-4,inheritance,"When this condition is caused by mutations in the FLCN gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, a person inherits the FLCN gene mutation from an affected parent. People who have an FLCN gene mutation associated with primary spontaneous pneumothorax all appear to develop blebs, but it is estimated that only 40 percent of those individuals go on to have a primary spontaneous pneumothorax.",primary spontaneous pneumothorax,0000825,GHR,https://ghr.nlm.nih.gov/condition/primary-spontaneous-pneumothorax,C1868193,T047,Disorders
What are the treatments for primary spontaneous pneumothorax ?,0000825-5,treatment,"These resources address the diagnosis or management of primary spontaneous pneumothorax:  - Genetic Testing Registry: Pneumothorax, primary spontaneous  - MedlinePlus Encyclopedia: Chest Tube Insertion  - MedlinePlus Encyclopedia: Collapsed Lung  - Merck Manual for Patients and Caregivers   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",primary spontaneous pneumothorax,0000825,GHR,https://ghr.nlm.nih.gov/condition/primary-spontaneous-pneumothorax,C1868193,T047,Disorders
What is (are) prion disease ?,0000826-1,information,"Prion disease represents a group of conditions that affect the nervous system in humans and animals. In people, these conditions impair brain function, causing changes in memory, personality, and behavior; a decline in intellectual function (dementia); and abnormal movements, particularly difficulty with coordinating movements (ataxia). The signs and symptoms of prion disease typically begin in adulthood and worsen with time, leading to death within a few months to several years.",prion disease,0000826,GHR,https://ghr.nlm.nih.gov/condition/prion-disease,C0162534,T046,Disorders
How many people are affected by prion disease ?,0000826-2,frequency,"These disorders are very rare. Although the exact prevalence of prion disease is unknown, studies suggest that this group of conditions affects about one person per million worldwide each year. Approximately 350 new cases are reported annually in the United States.",prion disease,0000826,GHR,https://ghr.nlm.nih.gov/condition/prion-disease,C0162534,T046,Disorders
What are the genetic changes related to prion disease ?,0000826-3,genetic changes,"Between 10 and 15 percent of all cases of prion disease are caused by mutations in the PRNP gene. Because they can run in families, these forms of prion disease are classified as familial. Familial prion diseases, which have overlapping signs and symptoms, include familial Creutzfeldt-Jakob disease (CJD), Gerstmann-Strussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI).  The PRNP gene provides instructions for making a protein called prion protein (PrP). Although the precise function of this protein is unknown, researchers have proposed roles in several important processes. These include the transport of copper into cells, protection of brain cells (neurons) from injury (neuroprotection), and communication between neurons. In familial forms of prion disease, PRNP gene mutations result in the production of an abnormally shaped protein, known as PrPSc, from one copy of the gene. In a process that is not fully understood, PrPSc can attach (bind) to the normal protein (PrPC) and promote its transformation into PrPSc. The abnormal protein builds up in the brain, forming clumps that damage or destroy neurons. The loss of these cells creates microscopic sponge-like holes (vacuoles) in the brain, which leads to the signs and symptoms of prion disease.  The other 85 to 90 percent of cases of prion disease are classified as either sporadic or acquired. People with sporadic prion disease have no family history of the disease and no identified mutation in the PRNP gene. Sporadic disease occurs when PrPC spontaneously, and for unknown reasons, is transformed into PrPSc. Sporadic forms of prion disease include sporadic Creutzfeldt-Jakob disease (sCJD), sporadic fatal insomnia (sFI), and variably protease-sensitive prionopathy (VPSPr).  Acquired prion disease results from exposure to PrPSc from an outside source. For example, variant Creutzfeldt-Jakob disease (vCJD) is a type of acquired prion disease in humans that results from eating beef products containing PrPSc from cattle with prion disease. In cows, this form of the disease is known as bovine spongiform encephalopathy (BSE) or, more commonly, ""mad cow disease."" Another example of an acquired human prion disease is kuru, which was identified in the South Fore population in Papua New Guinea. The disorder was transmitted when individuals ate affected human tissue during cannibalistic funeral rituals.  Rarely, prion disease can be transmitted by accidental exposure to PrPSc-contaminated tissues during a medical procedure. This type of prion disease, which accounts for 1 to 2 percent of all cases, is classified as iatrogenic.",prion disease,0000826,GHR,https://ghr.nlm.nih.gov/condition/prion-disease,C0162534,T046,Disorders
Is prion disease inherited ?,0000826-4,inheritance,"Familial forms of prion disease are inherited in an autosomal dominant pattern, which means one copy of the altered PRNP gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the altered gene from one affected parent. In some people, familial forms of prion disease are caused by a new mutation in the gene that occurs during the formation of a parent's reproductive cells (eggs or sperm) or in early embryonic development. Although such people do not have an affected parent, they can pass the genetic change to their children.  The sporadic, acquired, and iatrogenic forms of prion disease, including kuru and variant Creutzfeldt-Jakob disease, are not inherited.",prion disease,0000826,GHR,https://ghr.nlm.nih.gov/condition/prion-disease,C0162534,T046,Disorders
What are the treatments for prion disease ?,0000826-5,treatment,"These resources address the diagnosis or management of prion disease:  - Creutzfeldt-Jakob Disease Foundation: Suggestions for Patient Care  - Gene Review: Gene Review: Genetic Prion Diseases  - Genetic Testing Registry: Genetic prion diseases  - MedlinePlus Encyclopedia: Creutzfeldt-Jakob disease  - MedlinePlus Encyclopedia: Kuru  - University of California, San Fransisco Memory and Aging Center: Living With Creutzfeldt-Jakob Disease  - University of California, San Fransisco Memory and Aging Center: Treatments for Creutzfeldt-Jakob Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",prion disease,0000826,GHR,https://ghr.nlm.nih.gov/condition/prion-disease,C0162534,T046,Disorders
What is (are) progressive external ophthalmoplegia ?,0000827-1,information,"Progressive external ophthalmoplegia is a condition characterized by weakness of the eye muscles. The condition typically appears in adults between ages 18 and 40. The most common signs and symptoms of progressive external ophthalmoplegia are drooping eyelids (ptosis), which can affect one or both eyelids, and weakness or paralysis of the muscles that move the eye (ophthalmoplegia). Affected individuals may also have general weakness of the skeletal muscles (myopathy), particularly in the neck, arms, or legs. The weakness may be especially noticeable during exercise (exercise intolerance). Muscle weakness may also cause difficulty swallowing (dysphagia).  When the muscle cells of affected individuals are stained and viewed under a microscope, these cells usually appear abnormal. These abnormal muscle cells contain an excess of structures called mitochondria and are known as ragged-red fibers. Additionally, a close study of muscle cells may reveal abnormalities in a type of DNA found in mitochondria called mitochondrial DNA (mtDNA). Affected individuals often have large deletions of genetic material from mtDNA in muscle tissue.  Although muscle weakness is the primary symptom of progressive external ophthalmoplegia, this condition can be accompanied by other signs and symptoms. In these instances, the condition is referred to as progressive external ophthalmoplegia plus (PEO+). Additional signs and symptoms can include hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss), weakness and loss of sensation in the limbs due to nerve damage (neuropathy), impaired muscle coordination (ataxia), a pattern of movement abnormalities known as parkinsonism, or depression.  Progressive external ophthalmoplegia is part of a spectrum of disorders with overlapping signs and symptoms. Similar disorders include other conditions caused by POLG gene mutations, such as ataxia neuropathy spectrum, as well as other mtDNA deletion disorders, such as Kearns-Sayre syndrome. Like progressive external ophthalmoplegia, the other conditions in this spectrum can involve weakness of the eye muscles. However, these conditions have many additional features not shared by most people with progressive external ophthalmoplegia.",progressive external ophthalmoplegia,0000827,GHR,https://ghr.nlm.nih.gov/condition/progressive-external-ophthalmoplegia,C0162674,T047,Disorders
How many people are affected by progressive external ophthalmoplegia ?,0000827-2,frequency,The prevalence of progressive external ophthalmoplegia is unknown.,progressive external ophthalmoplegia,0000827,GHR,https://ghr.nlm.nih.gov/condition/progressive-external-ophthalmoplegia,C0162674,T047,Disorders
What are the genetic changes related to progressive external ophthalmoplegia ?,0000827-3,genetic changes,"Progressive external ophthalmoplegia is a condition caused by defects in mitochondria, which are structures within cells that use oxygen to convert the energy from food into a form cells can use. This process is called oxidative phosphorylation. Although most DNA is packaged in chromosomes within the nucleus (nuclear DNA), mitochondria also have a small amount of their own DNA, called mitochondrial DNA or mtDNA.  Progressive external ophthalmoplegia can result from mutations in several different genes. In some cases, mutations in the MT-TL1 gene, which is located in mtDNA, cause progressive external ophthalmoplegia. In other cases, mutations in nuclear DNA are responsible for the condition, particularly mutations in the POLG, SLC25A4, and C10orf2 genes. These genes are critical for mtDNA maintenance. Although the mechanism is unclear, mutations in any of these three genes lead to large deletions of mtDNA, ranging from 2,000 to 10,000 DNA building blocks (nucleotides).  Researchers have not determined how deletions of mtDNA lead to the specific signs and symptoms of progressive external ophthalmoplegia, although the features of the condition are probably related to impaired oxidative phosphorylation. It has been suggested that eye muscles are commonly affected by mitochondrial defects because they are especially dependent on oxidative phosphorylation for energy.",progressive external ophthalmoplegia,0000827,GHR,https://ghr.nlm.nih.gov/condition/progressive-external-ophthalmoplegia,C0162674,T047,Disorders
Is progressive external ophthalmoplegia inherited ?,0000827-4,inheritance,"Progressive external ophthalmoplegia can have different inheritance patterns depending on the gene involved.  When this condition is caused by mutations in the MT-TL1 gene, it is inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mtDNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children.  When the nuclear genes POLG, SLC25A4, or C10orf2 are involved, progressive external ophthalmoplegia is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  Certain mutations in the POLG gene can also cause a form of the condition that is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Some mutations in the POLG gene that cause progressive external ophthalmoplegia occur during a person's lifetime and are not inherited. These genetic changes are called somatic mutations.",progressive external ophthalmoplegia,0000827,GHR,https://ghr.nlm.nih.gov/condition/progressive-external-ophthalmoplegia,C0162674,T047,Disorders
What are the treatments for progressive external ophthalmoplegia ?,0000827-5,treatment,These resources address the diagnosis or management of progressive external ophthalmoplegia:  - Gene Review: Gene Review: Mitochondrial DNA Deletion Syndromes  - Gene Review: Gene Review: POLG-Related Disorders  - Genetic Testing Registry: Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 1  - Genetic Testing Registry: Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 2  - Genetic Testing Registry: Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 3  - Genetic Testing Registry: Progressive external ophthalmoplegia  - United Mitochondrial Disease Foundation: Diagnosis of Mitochondrial Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,progressive external ophthalmoplegia,0000827,GHR,https://ghr.nlm.nih.gov/condition/progressive-external-ophthalmoplegia,C0162674,T047,Disorders
What is (are) progressive familial heart block ?,0000828-1,information,"Progressive familial heart block is a genetic condition that alters the normal beating of the heart. A normal heartbeat is controlled by electrical signals that move through the heart in a highly coordinated way. These signals begin in a specialized cluster of cells called the sinoatrial node (the heart's natural pacemaker) located in the heart's upper chambers (the atria). From there, a group of cells called the atrioventricular node carries the electrical signals to another cluster of cells called the bundle of His. This bundle separates into multiple thin spindles called bundle branches, which carry electrical signals into the heart's lower chambers (the ventricles). Electrical impulses move from the sinoatrial node down to the bundle branches, stimulating a normal heartbeat in which the ventricles contract slightly later than the atria.  Heart block occurs when the electrical signaling is obstructed anywhere from the atria to the ventricles. In people with progressive familial heart block, the condition worsens over time: early in the disorder, the electrical signals are partially blocked, but the block eventually becomes complete, preventing any signals from passing through the heart. Partial heart block causes a slow or irregular heartbeat (bradycardia or arrhythmia, respectively), and can lead to the buildup of scar tissue (fibrosis) in the cells that carry electrical impulses. Fibrosis contributes to the development of complete heart block, resulting in uncoordinated electrical signaling between the atria and the ventricles and inefficient pumping of blood in the heart. Complete heart block can cause a sensation of fluttering or pounding in the chest (palpitations), shortness of breath, fainting (syncope), or sudden cardiac arrest and death.  Progressive familial heart block can be divided into type I and type II, with type I being further divided into types IA and IB. These types differ in where in the heart signaling is interrupted and the genetic cause. In types IA and IB, the heart block originates in the bundle branch, and in type II, the heart block originates in the atrioventricular node. The different types of progressive familial heart block have similar signs and symptoms.  Most cases of heart block are not genetic and are not considered progressive familial heart block. The most common cause of heart block is fibrosis of the heart, which occurs as a normal process of aging. Other causes of heart block can include the use of certain medications or an infection of the heart tissue.",progressive familial heart block,0000828,GHR,https://ghr.nlm.nih.gov/condition/progressive-familial-heart-block,C1879286,T047,Disorders
How many people are affected by progressive familial heart block ?,0000828-2,frequency,"The prevalence of progressive familial heart block is unknown. In the United States, about 1 in 5,000 individuals have complete heart block from any cause; worldwide, about 1 in 2,500 individuals have complete heart block.",progressive familial heart block,0000828,GHR,https://ghr.nlm.nih.gov/condition/progressive-familial-heart-block,C1879286,T047,Disorders
What are the genetic changes related to progressive familial heart block ?,0000828-3,genetic changes,"Mutations in the SCN5A and TRPM4 genes cause most cases of progressive familial heart block types IA and IB, respectively. The proteins produced from these genes are channels that allow positively charged atoms (cations) into and out of cells. Both channels are abundant in heart (cardiac) cells and play key roles in these cells' ability to generate and transmit electrical signals. These channels play a major role in signaling the start of each heartbeat, coordinating the contractions of the atria and ventricles, and maintaining a normal heart rhythm.  The SCN5A and TRPM4 gene mutations that cause progressive familial heart block alter the normal function of the channels. As a result of these channel alterations, cardiac cells have difficulty producing and transmitting the electrical signals that are necessary to coordinate normal heartbeats, leading to heart block. Death of these impaired cardiac cells over time can lead to fibrosis, worsening the heart block.  Mutations in other genes, some of which are unknown, account for the remaining cases of progressive familial heart block.",progressive familial heart block,0000828,GHR,https://ghr.nlm.nih.gov/condition/progressive-familial-heart-block,C1879286,T047,Disorders
Is progressive familial heart block inherited ?,0000828-4,inheritance,"Progressive familial heart block types I and II are inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. Some people with TRPM4 gene mutations never develop the condition, a situation known as reduced penetrance.  In most cases, an affected person has one parent with progressive familial heart block.",progressive familial heart block,0000828,GHR,https://ghr.nlm.nih.gov/condition/progressive-familial-heart-block,C1879286,T047,Disorders
What are the treatments for progressive familial heart block ?,0000828-5,treatment,"These resources address the diagnosis or management of progressive familial heart block:  - American Heart Association: Common Tests for Arrhythmia  - Genetic Testing Registry: Progressive familial heart block type 1A  - Genetic Testing Registry: Progressive familial heart block type 1B  - Genetic Testing Registry: Progressive familial heart block type 2  - MedlinePlus Health Topic: Pacemakers and Implantable Defibrillators  - National Heart, Lung, and Blood Institute: How Does a Pacemaker Work?  - National Heart, Lung, and Blood Institute: How is Sudden Cardiac Arrest Diagnosed?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",progressive familial heart block,0000828,GHR,https://ghr.nlm.nih.gov/condition/progressive-familial-heart-block,C1879286,T047,Disorders
What is (are) progressive familial intrahepatic cholestasis ?,0000829-1,information,"Progressive familial intrahepatic cholestasis (PFIC) is a disorder that causes progressive liver disease, which typically leads to liver failure. In people with PFIC, liver cells are less able to secrete a digestive fluid called bile. The buildup of bile in liver cells causes liver disease in affected individuals.  Signs and symptoms of PFIC typically begin in infancy and are related to bile buildup and liver disease. Specifically, affected individuals experience severe itching, yellowing of the skin and whites of the eyes (jaundice), failure to gain weight and grow at the expected rate (failure to thrive), high blood pressure in the vein that supplies blood to the liver (portal hypertension), and an enlarged liver and spleen (hepatosplenomegaly).  There are three known types of PFIC: PFIC1, PFIC2, and PFIC3. The types are also sometimes described as shortages of particular proteins needed for normal liver function. Each type has a different genetic cause.  In addition to signs and symptoms related to liver disease, people with PFIC1 may have short stature, deafness, diarrhea, inflammation of the pancreas (pancreatitis), and low levels of fat-soluble vitamins (vitamins A, D, E, and K) in the blood. Affected individuals typically develop liver failure before adulthood.  The signs and symptoms of PFIC2 are typically related to liver disease only; however, these signs and symptoms tend to be more severe than those experienced by people with PFIC1. People with PFIC2 often develop liver failure within the first few years of life. Additionally, affected individuals are at increased risk of developing a type of liver cancer called hepatocellular carcinoma.  Most people with PFIC3 have signs and symptoms related to liver disease only. Signs and symptoms of PFIC3 usually do not appear until later in infancy or early childhood; rarely, people are diagnosed in early adulthood. Liver failure can occur in childhood or adulthood in people with PFIC3.",progressive familial intrahepatic cholestasis,0000829,GHR,https://ghr.nlm.nih.gov/condition/progressive-familial-intrahepatic-cholestasis,C0268312,T019,Disorders
How many people are affected by progressive familial intrahepatic cholestasis ?,0000829-2,frequency,"PFIC is estimated to affect 1 in 50,000 to 100,000 people worldwide. PFIC type 1 is much more common in the Inuit population of Greenland and the Old Order Amish population of the United States.",progressive familial intrahepatic cholestasis,0000829,GHR,https://ghr.nlm.nih.gov/condition/progressive-familial-intrahepatic-cholestasis,C0268312,T019,Disorders
What are the genetic changes related to progressive familial intrahepatic cholestasis ?,0000829-3,genetic changes,"Mutations in the ATP8B1, ABCB11, and ABCB4 genes can cause PFIC.  ATP8B1 gene mutations cause PFIC1. The ATP8B1 gene provides instructions for making a protein that helps to maintain an appropriate balance of bile acids, a component of bile. This process, known as bile acid homeostasis, is critical for the normal secretion of bile and the proper functioning of liver cells. In its role in maintaining bile acid homeostasis, some researchers believe that the ATP8B1 protein is involved in moving certain fats across cell membranes. Mutations in the ATP8B1 gene result in the buildup of bile acids in liver cells, damaging these cells and causing liver disease. The ATP8B1 protein is found throughout the body, but it is unclear how a lack of this protein causes short stature, deafness, and other signs and symptoms of PFIC1.  Mutations in the ABCB11 gene are responsible for PFIC2. The ABCB11 gene provides instructions for making a protein called the bile salt export pump (BSEP). This protein is found in the liver, and its main role is to move bile salts (a component of bile) out of liver cells. Mutations in the ABCB11 gene result in the buildup of bile salts in liver cells, damaging these cells and causing liver disease.  ABCB4 gene mutations cause PFIC3. The ABCB4 gene provides instructions for making a protein that moves certain fats called phospholipids across cell membranes. Outside liver cells, phospholipids attach (bind) to bile acids. Large amounts of bile acids can be toxic when they are not bound to phospholipids. Mutations in the ABCB4 gene lead to a lack of phospholipids available to bind to bile acids. A buildup of free bile acids damages liver cells and leads to liver disease.  Some people with PFIC do not have a mutation in the ATP8B1, ABCB11, or ABCB4 gene. In these cases, the cause of the condition is unknown.",progressive familial intrahepatic cholestasis,0000829,GHR,https://ghr.nlm.nih.gov/condition/progressive-familial-intrahepatic-cholestasis,C0268312,T019,Disorders
Is progressive familial intrahepatic cholestasis inherited ?,0000829-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",progressive familial intrahepatic cholestasis,0000829,GHR,https://ghr.nlm.nih.gov/condition/progressive-familial-intrahepatic-cholestasis,C0268312,T019,Disorders
What are the treatments for progressive familial intrahepatic cholestasis ?,0000829-5,treatment,These resources address the diagnosis or management of progressive familial intrahepatic cholestasis:  - Gene Review: Gene Review: ATP8B1 Deficiency  - Genetic Testing Registry: Progressive familial intrahepatic cholestasis 2  - Genetic Testing Registry: Progressive familial intrahepatic cholestasis 3  - Genetic Testing Registry: Progressive intrahepatic cholestasis  - MedlinePlus Encyclopedia: Cholestasis  - MedlinePlus Encyclopedia: Hepatocellular Carcinoma   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,progressive familial intrahepatic cholestasis,0000829,GHR,https://ghr.nlm.nih.gov/condition/progressive-familial-intrahepatic-cholestasis,C0268312,T019,Disorders
What is (are) progressive osseous heteroplasia ?,0000830-1,information,"Progressive osseous heteroplasia is a disorder in which bone forms within skin and muscle tissue. Bone that forms outside the skeleton is called heterotopic or ectopic bone. In progressive osseous heteroplasia, ectopic bone formation begins in the deep layers of the skin (dermis and subcutaneous fat) and gradually moves into other tissues such as skeletal muscle and tendons. The bony lesions within the skin may be painful and may develop into open sores (ulcers). Over time, joints can become involved, resulting in impaired mobility.  Signs and symptoms of progressive osseous heteroplasia usually become noticeable during infancy. In some affected individuals, however, this may not occur until later in childhood or in early adulthood.",progressive osseous heteroplasia,0000830,GHR,https://ghr.nlm.nih.gov/condition/progressive-osseous-heteroplasia,C0334041,T191,Disorders
How many people are affected by progressive osseous heteroplasia ?,0000830-2,frequency,Progressive osseous heteroplasia is a rare condition. Its exact incidence is unknown.,progressive osseous heteroplasia,0000830,GHR,https://ghr.nlm.nih.gov/condition/progressive-osseous-heteroplasia,C0334041,T191,Disorders
What are the genetic changes related to progressive osseous heteroplasia ?,0000830-3,genetic changes,"Progressive osseous heteroplasia is caused by a mutation in the GNAS gene. The GNAS gene provides instructions for making one part of a protein complex called a guanine nucleotide-binding protein, or a G protein.  In a process called signal transduction, G proteins trigger a complex network of signaling pathways that ultimately influence many cell functions. The protein produced from the GNAS gene is believed to play a key role in signaling pathways that help regulate the development of bone (osteogenesis), preventing bony tissue from being produced outside the skeleton.  The GNAS gene mutations that cause progressive osseous heteroplasia disrupt the function of the G protein and impair its ability to regulate osteogenesis. As a result, bony tissue grows outside the skeleton and causes the complications associated with this disorder.",progressive osseous heteroplasia,0000830,GHR,https://ghr.nlm.nih.gov/condition/progressive-osseous-heteroplasia,C0334041,T191,Disorders
Is progressive osseous heteroplasia inherited ?,0000830-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  People normally inherit one copy of each gene from their mother and one copy from their father. For most genes, both copies are active, or ""turned on,"" in all cells. For a small subset of genes, however, only one of the two copies is active. For some of these genes, only the copy inherited from a person's father (the paternal copy) is active, while for other genes, only the copy inherited from a person's mother (the maternal copy) is active. These differences in gene activation based on the gene's parent of origin are caused by a phenomenon called genomic imprinting.  The GNAS gene has a complex genomic imprinting pattern. In some cells of the body the maternal copy of the gene is active, while in others the paternal copy is active. Progressive osseous heteroplasia occurs when mutations affect the paternal copy of the gene.",progressive osseous heteroplasia,0000830,GHR,https://ghr.nlm.nih.gov/condition/progressive-osseous-heteroplasia,C0334041,T191,Disorders
What are the treatments for progressive osseous heteroplasia ?,0000830-5,treatment,These resources address the diagnosis or management of progressive osseous heteroplasia:  - Genetic Testing Registry: Progressive osseous heteroplasia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,progressive osseous heteroplasia,0000830,GHR,https://ghr.nlm.nih.gov/condition/progressive-osseous-heteroplasia,C0334041,T191,Disorders
What is (are) progressive pseudorheumatoid dysplasia ?,0000831-1,information,"Progressive pseudorheumatoid dysplasia (PPRD) is a joint disease that worsens over time. This condition is characterized by breakdown (degeneration) of the cartilage between bones (articular cartilage). This cartilage covers and protects the ends of bones, and its degeneration leads to pain and stiffness in the joints and other features of PPRD.  PPRD usually begins in childhood, between ages 3 and 8. The first indications are usually an abnormal walking pattern, weakness and fatigue when active, and stiffness in the joints in the fingers and in the knees. Other signs and symptoms that develop over time include permanently bent fingers (camptodactyly), enlarged finger and knee joints (often mistaken as swelling), and a reduced amount of space between the bones at the hip and knee joints. Hip pain is a common problem by adolescence. Affected individuals have flattened bones in the spine (platyspondyly) that are abnormally shaped (beaked), which leads to an abnormal front-to-back curvature of the spine (kyphosis) and a short torso. At birth, people with PPRD are of normal length, but by adulthood, they are usually shorter than their peers. Affected adults also have abnormal deposits of calcium around the elbow, knee, and hip joints and limited movement in all joints, including those of the spine.  PPRD is often mistaken for another joint disorder that affects young people called juvenile rheumatoid arthritis. However, the joint problems in juvenile rheumatoid arthritis are associated with inflammation, while those in PPRD are not.",progressive pseudorheumatoid dysplasia,0000831,GHR,https://ghr.nlm.nih.gov/condition/progressive-pseudorheumatoid-dysplasia,C0432215,T019,Disorders
How many people are affected by progressive pseudorheumatoid dysplasia ?,0000831-2,frequency,"PPRD has been estimated to occur in approximately 1 per million people in the United Kingdom. The condition is thought to be more common in Turkey and the Middle East, although its prevalence in these regions is unknown. The condition in all regions is likely underdiagnosed because it is often misdiagnosed as juvenile rheumatoid arthritis.",progressive pseudorheumatoid dysplasia,0000831,GHR,https://ghr.nlm.nih.gov/condition/progressive-pseudorheumatoid-dysplasia,C0432215,T019,Disorders
What are the genetic changes related to progressive pseudorheumatoid dysplasia ?,0000831-3,genetic changes,"PPRD is caused by mutations in the WISP3 gene. The function of the protein produced from this gene is not well understood, although it is thought to play a role in bone growth and cartilage maintenance. The WISP3 protein is made in cells called chondrocytes, which produce and maintain cartilage. This protein is associated with the production of certain proteins that make up cartilage, but its role in their production is unclear. WISP3 may also help control signaling pathways involved in the development of cartilage and bone and may help regulate the breakdown of cartilage components.  WISP3 gene mutations lead to an altered protein that may not function. Loss of WISP3 protein function likely disrupts normal cartilage maintenance and bone growth, leading to the cartilage degeneration and joint problems that occur in PPRD.",progressive pseudorheumatoid dysplasia,0000831,GHR,https://ghr.nlm.nih.gov/condition/progressive-pseudorheumatoid-dysplasia,C0432215,T019,Disorders
Is progressive pseudorheumatoid dysplasia inherited ?,0000831-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",progressive pseudorheumatoid dysplasia,0000831,GHR,https://ghr.nlm.nih.gov/condition/progressive-pseudorheumatoid-dysplasia,C0432215,T019,Disorders
What are the treatments for progressive pseudorheumatoid dysplasia ?,0000831-5,treatment,These resources address the diagnosis or management of progressive pseudorheumatoid dysplasia:  - Cedars-Sinai: Skeletal Dysplasias  - Gene Review: Gene Review: Progressive Pseudorheumatoid Dysplasia  - Genetic Testing Registry: Progressive pseudorheumatoid dysplasia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,progressive pseudorheumatoid dysplasia,0000831,GHR,https://ghr.nlm.nih.gov/condition/progressive-pseudorheumatoid-dysplasia,C0432215,T019,Disorders
What is (are) progressive supranuclear palsy ?,0000832-1,information,"Progressive supranuclear palsy is a brain disorder that affects movement, vision, speech, and thinking ability (cognition). The signs and symptoms of this disorder usually become apparent in mid- to late adulthood, most often in a person's 60s. Most people with progressive supranuclear palsy survive 5 to 9 years after the disease first appears, although a few affected individuals have lived for more than a decade.  Loss of balance and frequent falls are the most common early signs of progressive supranuclear palsy. Affected individuals have problems with walking, including poor coordination and an unsteady, lurching gait. Other movement abnormalities develop as the disease progresses, including unusually slow movements (bradykinesia), clumsiness, and stiffness of the trunk muscles. These problems worsen with time, and most affected people ultimately require wheelchair assistance.  Progressive supranuclear palsy is also characterized by abnormal eye movements, which typically develop several years after the other movement problems first appear. Restricted up-and-down eye movement (vertical gaze palsy) is a hallmark of this disease. Other eye movement problems include difficulty opening and closing the eyelids, infrequent blinking, and pulling back (retraction) of the eyelids. These abnormalities can lead to blurred vision, an increased sensitivity to light (photophobia), and a staring gaze.  Additional features of progressive supranuclear palsy include slow and slurred speech (dysarthria) and trouble swallowing (dysphagia). Most affected individuals also experience changes in personality and behavior, such as a general loss of interest and enthusiasm (apathy). They develop problems with cognition, including difficulties with attention, planning, and problem solving. As the cognitive and behavioral problems worsen, affected individuals increasingly require help with personal care and other activities of daily living.",progressive supranuclear palsy,0000832,GHR,https://ghr.nlm.nih.gov/condition/progressive-supranuclear-palsy,C0038868,T047,Disorders
How many people are affected by progressive supranuclear palsy ?,0000832-2,frequency,"The exact prevalence of progressive supranuclear palsy is unknown. It may affect about 6 in 100,000 people worldwide.",progressive supranuclear palsy,0000832,GHR,https://ghr.nlm.nih.gov/condition/progressive-supranuclear-palsy,C0038868,T047,Disorders
What are the genetic changes related to progressive supranuclear palsy ?,0000832-3,genetic changes,"In most cases, the genetic cause of progressive supranuclear palsy is unknown. Rarely, the disease results from mutations in the MAPT gene. Certain normal variations (polymorphisms) in the MAPT gene have also been associated with an increased risk of developing progressive supranuclear palsy.  The MAPT gene provides instructions for making a protein called tau. This protein is found throughout the nervous system, including in nerve cells (neurons) in the brain. It is involved in assembling and stabilizing microtubules, which are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). Microtubules help cells maintain their shape, assist in the process of cell division, and are essential for the transport of materials within cells.  The signs and symptoms of progressive supranuclear palsy appear to be related to abnormalities in the tau protein. In people with MAPT gene mutations, genetic changes disrupt the protein's normal structure and function. However, abnormal tau is also found in affected individuals without MAPT gene mutations. The defective tau protein assembles into abnormal clumps within neurons and other brain cells, although it is unclear what effect these clumps have on cell function and survival. Progressive supranuclear palsy is characterized by the gradual death of brain cells, particularly in structures deep within the brain that are essential for coordinating movement. This loss of brain cells underlies the movement abnormalities and other features of progressive supranuclear palsy.  This condition is one of several related diseases known as tauopathies, which are characterized by an abnormal buildup of tau in the brain.  Researchers suspect that other genetic and environmental factors also contribute to progressive supranuclear palsy. For example, the disease has been linked to genetic changes on chromosome 1 and chromosome 11. However, the specific genes involved have not been identified.",progressive supranuclear palsy,0000832,GHR,https://ghr.nlm.nih.gov/condition/progressive-supranuclear-palsy,C0038868,T047,Disorders
Is progressive supranuclear palsy inherited ?,0000832-4,inheritance,"Most cases of progressive supranuclear palsy are sporadic, which means they occur in people with no history of the disorder in their family. However, some people with this disorder have had family members with related conditions, such as parkinsonism and a loss of intellectual functions (dementia).  When progressive supranuclear palsy runs in families, it can have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of an altered gene in each cell is sufficient to cause the disorder.",progressive supranuclear palsy,0000832,GHR,https://ghr.nlm.nih.gov/condition/progressive-supranuclear-palsy,C0038868,T047,Disorders
What are the treatments for progressive supranuclear palsy ?,0000832-5,treatment,"These resources address the diagnosis or management of progressive supranuclear palsy:  - Gene Review: Gene Review: MAPT-Related Disorders  - Genetic Testing Registry: Progressive supranuclear ophthalmoplegia  - NHS Choices (UK): Diagnosis of Progressive Supranuclear Palsy  - NHS Choices (UK): Treatment of Progressive Supranuclear Palsy  - Partners in Parkinson's: Movement Disorder Specialist Finder  - University of California, San Francisco (UCSF) Memory and Aging Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",progressive supranuclear palsy,0000832,GHR,https://ghr.nlm.nih.gov/condition/progressive-supranuclear-palsy,C0038868,T047,Disorders
What is (are) prolidase deficiency ?,0000833-1,information,"Prolidase deficiency is a disorder that causes a wide variety of symptoms. The disorder typically becomes apparent during infancy. Affected individuals may have enlargement of the spleen (splenomegaly); in some cases, both the spleen and liver are enlarged (hepatosplenomegaly). Diarrhea, vomiting, and dehydration may also occur. People with prolidase deficiency are susceptible to severe infections of the skin or ears, or potentially life-threatening respiratory tract infections. Some individuals with prolidase deficiency have chronic lung disease.  Characteristic facial features in people with prolidase deficiency include prominent eyes that are widely spaced (hypertelorism), a high forehead, a flat bridge of the nose, and a very small lower jaw and chin (micrognathia). Affected children may experience delayed development, and about 75 percent of people with prolidase deficiency have intellectual disability that may range from mild to severe.  People with prolidase deficiency often develop skin lesions, especially on their hands, feet, lower legs, and face. The severity of the skin involvement, which usually begins during childhood, may range from a mild rash to severe skin ulcers. Skin ulcers, especially on the legs, may not heal completely, resulting in complications including infection and amputation.  The severity of symptoms in prolidase deficiency varies greatly among affected individuals. Some people with this disorder do not have any symptoms. In these individuals the condition can be detected by laboratory tests such as newborn screening tests or tests offered to relatives of affected individuals.",prolidase deficiency,0000833,GHR,https://ghr.nlm.nih.gov/condition/prolidase-deficiency,C0268532,T047,Disorders
How many people are affected by prolidase deficiency ?,0000833-2,frequency,"Prolidase deficiency is a rare disorder. Approximately 70 individuals with this disorder have been documented in the medical literature, and researchers have estimated that the condition occurs in approximately 1 in 1 million to 1 in 2 million newborns. It is more common in certain areas in northern Israel, both among members of a religious minority called the Druze and in nearby Arab Moslem populations.",prolidase deficiency,0000833,GHR,https://ghr.nlm.nih.gov/condition/prolidase-deficiency,C0268532,T047,Disorders
What are the genetic changes related to prolidase deficiency ?,0000833-3,genetic changes,"Prolidase deficiency is caused by mutations in the PEPD gene. This gene provides instructions for making the enzyme prolidase, also called peptidase D. Prolidase helps divide certain dipeptides, which are molecules composed of two protein building blocks (amino acids). Specifically, prolidase divides dipeptides containing the amino acids proline or hydroxyproline. By freeing these amino acids, prolidase helps make them available for use in producing proteins that the body needs.  Prolidase is also involved in the final step of the breakdown of some proteins obtained through the diet and proteins that are no longer needed in the body. Prolidase is particularly important in the breakdown of collagens, a family of proteins that are rich in proline and hydroxyproline. Collagens are an important part of the extracellular matrix, which is the lattice of proteins and other molecules outside the cell. The extracellular matrix strengthens and supports connective tissues, such as skin, bone, cartilage, tendons, and ligaments. Collagen breakdown occurs during the maintenance (remodeling) of the extracellular matrix.  PEPD gene mutations that cause prolidase deficiency result in the loss of prolidase enzyme activity. It is not well understood how the absence of prolidase activity causes the various signs and symptoms of prolidase deficiency. Researchers have suggested that accumulation of dipeptides that have not been broken down may lead to cell death. When cells die, their contents are released into the surrounding tissue, which could cause inflammation and lead to the skin problems seen in prolidase deficiency. Impaired collagen breakdown during remodeling of the extracellular matrix may also contribute to the skin problems. The intellectual disability that occurs in prolidase deficiency might result from problems in processing neuropeptides, which are brain signaling proteins that are rich in proline. It is unclear how absence of prolidase activity results in the other features of prolidase deficiency.",prolidase deficiency,0000833,GHR,https://ghr.nlm.nih.gov/condition/prolidase-deficiency,C0268532,T047,Disorders
Is prolidase deficiency inherited ?,0000833-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",prolidase deficiency,0000833,GHR,https://ghr.nlm.nih.gov/condition/prolidase-deficiency,C0268532,T047,Disorders
What are the treatments for prolidase deficiency ?,0000833-5,treatment,These resources address the diagnosis or management of prolidase deficiency:  - Gene Review: Gene Review: Prolidase Deficiency  - Genetic Testing Registry: Prolidase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,prolidase deficiency,0000833,GHR,https://ghr.nlm.nih.gov/condition/prolidase-deficiency,C0268532,T047,Disorders
What is (are) proopiomelanocortin deficiency ?,0000834-1,information,"Proopiomelanocortin (POMC) deficiency causes severe obesity that begins at an early age. In addition to obesity, people with this condition have low levels of a hormone known as adrenocorticotropic hormone (ACTH) and tend to have red hair and pale skin.  Affected infants are usually a normal weight at birth, but they are constantly hungry, which leads to excessive feeding (hyperphagia). The babies continuously gain weight and are severely obese by age 1. Affected individuals experience excessive hunger and remain obese for life. It is unclear if these individuals are prone to weight-related conditions like cardiovascular disease or type 2 diabetes.  Low levels of ACTH lead to a condition called adrenal insufficiency, which occurs when the pair of small glands on top of the kidneys (the adrenal glands) do not produce enough hormones. Adrenal insufficiency often results in periods of severely low blood sugar (hypoglycemia) in people with POMC deficiency, which can cause seizures, elevated levels of a toxic substance called bilirubin in the blood (hyperbilirubinemia), and a reduced ability to produce and release a digestive fluid called bile (cholestasis). Without early treatment, adrenal insufficiency can be fatal.  Pale skin that easily burns when exposed to the sun and red hair are common in POMC deficiency, although not everyone with the condition has these characteristics.",proopiomelanocortin deficiency,0000834,GHR,https://ghr.nlm.nih.gov/condition/proopiomelanocortin-deficiency,C1857854,T047,Disorders
How many people are affected by proopiomelanocortin deficiency ?,0000834-2,frequency,POMC deficiency is a rare condition; approximately 50 cases have been reported in the medical literature.,proopiomelanocortin deficiency,0000834,GHR,https://ghr.nlm.nih.gov/condition/proopiomelanocortin-deficiency,C1857854,T047,Disorders
What are the genetic changes related to proopiomelanocortin deficiency ?,0000834-3,genetic changes,"POMC deficiency is caused by mutations in the POMC gene, which provides instructions for making the proopiomelanocortin protein. This protein is cut (cleaved) into smaller pieces called peptides that have different functions in the body. One of these peptides, ACTH, stimulates the release of another hormone called cortisol from the adrenal glands. Cortisol is involved in the maintenance of blood sugar levels. Another peptide, alpha-melanocyte stimulating hormone (-MSH), plays a role in the production of the pigment that gives skin and hair their color. The -MSH peptide and another peptide called beta-melanocyte stimulating hormone (-MSH) act in the brain to help maintain the balance between energy from food taken into the body and energy spent by the body. The correct balance is important to control eating and weight.  POMC gene mutations that cause POMC deficiency result in production of an abnormally short version of the POMC protein or no protein at all. As a result, there is a shortage of the peptides made from POMC, including ACTH, -MSH, and -MSH. Without ACTH, there is a reduction in cortisol production, leading to adrenal insufficiency. Decreased -MSH in the skin reduces pigment production, resulting in the red hair and pale skin often seen in people with POMC deficiency. Loss of -MSH and -MSH in the brain dysregulates the body's energy balance, leading to overeating and severe obesity.  POMC deficiency is a rare cause of obesity; POMC gene mutations are not frequently associated with more common, complex forms of obesity. Researchers are studying other factors that are likely involved in these forms.",proopiomelanocortin deficiency,0000834,GHR,https://ghr.nlm.nih.gov/condition/proopiomelanocortin-deficiency,C1857854,T047,Disorders
Is proopiomelanocortin deficiency inherited ?,0000834-4,inheritance,"POMC deficiency is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with this condition each carry one copy of the mutated gene. They typically do not have POMC deficiency, but they may have an increased risk of obesity.",proopiomelanocortin deficiency,0000834,GHR,https://ghr.nlm.nih.gov/condition/proopiomelanocortin-deficiency,C1857854,T047,Disorders
What are the treatments for proopiomelanocortin deficiency ?,0000834-5,treatment,These resources address the diagnosis or management of proopiomelanocortin deficiency:  - Eunice Kennedy Shriver National Institute of Child Health and Human Development: How are Obesity and Overweight Diagnosed?  - Gene Review: Gene Review: Proopiomelanocortin Deficiency  - Genetic Testing Registry: Proopiomelanocortin deficiency  - MedlinePlus Encyclopedia: ACTH  - National Heart Lung and Blood Institute: How Are Overweight and Obesity Treated?  - National Institutes of Health Clinical Center: Managing Adrenal Insufficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,proopiomelanocortin deficiency,0000834,GHR,https://ghr.nlm.nih.gov/condition/proopiomelanocortin-deficiency,C1857854,T047,Disorders
What is (are) propionic acidemia ?,0000835-1,information,"Propionic acidemia is an inherited disorder in which the body is unable to process certain parts of proteins and lipids (fats) properly. It is classified as an organic acid disorder, which is a condition that leads to an abnormal buildup of particular acids known as organic acids. Abnormal levels of organic acids in the blood (organic acidemia), urine (organic aciduria), and tissues can be toxic and can cause serious health problems.  In most cases, the features of propionic acidemia become apparent within a few days after birth. The initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These symptoms sometimes progress to more serious medical problems, including heart abnormalities, seizures, coma, and possibly death.  Less commonly, the signs and symptoms of propionic acidemia appear during childhood and may come and go over time. Some affected children experience intellectual disability or delayed development. In children with this later-onset form of the condition, episodes of more serious health problems can be triggered by prolonged periods without food (fasting), fever, or infections.",propionic acidemia,0000835,GHR,https://ghr.nlm.nih.gov/condition/propionic-acidemia,C0268579,T047,Disorders
How many people are affected by propionic acidemia ?,0000835-2,frequency,"Propionic acidemia affects about 1 in 100,000 people in the United States. The condition appears to be more common in several populations worldwide, including the Inuit population of Greenland, some Amish communities, and Saudi Arabians.",propionic acidemia,0000835,GHR,https://ghr.nlm.nih.gov/condition/propionic-acidemia,C0268579,T047,Disorders
What are the genetic changes related to propionic acidemia ?,0000835-3,genetic changes,"Mutations in the PCCA and PCCB genes cause propionic acidemia.  The PCCA and PCCB genes provide instructions for making two parts (subunits) of an enzyme called propionyl-CoA carboxylase. This enzyme plays a role in the normal breakdown of proteins. Specifically, it helps process several amino acids, which are the building blocks of proteins. Propionyl-CoA carboxylase also helps break down certain types of fat and cholesterol in the body. Mutations in the PCCA or PCCB gene disrupt the function of the enzyme and prevent the normal breakdown of these molecules. As a result, a substance called propionyl-CoA and other potentially harmful compounds can build up to toxic levels in the body. This buildup damages the brain and nervous system, causing the serious health problems associated with propionic acidemia.",propionic acidemia,0000835,GHR,https://ghr.nlm.nih.gov/condition/propionic-acidemia,C0268579,T047,Disorders
Is propionic acidemia inherited ?,0000835-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",propionic acidemia,0000835,GHR,https://ghr.nlm.nih.gov/condition/propionic-acidemia,C0268579,T047,Disorders
What are the treatments for propionic acidemia ?,0000835-5,treatment,These resources address the diagnosis or management of propionic acidemia:  - Baby's First Test  - Gene Review: Gene Review: Propionic Acidemia  - Genetic Testing Registry: Propionic acidemia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,propionic acidemia,0000835,GHR,https://ghr.nlm.nih.gov/condition/propionic-acidemia,C0268579,T047,Disorders
What is (are) prostate cancer ?,0000836-1,information,"Prostate cancer is a common disease that affects men, usually in middle age or later. In this disorder, certain cells in the prostate become abnormal and multiply without control or order to form a tumor. The prostate is a gland that surrounds the male urethra and helps produce semen, the fluid that carries sperm.  Early prostate cancer usually does not cause pain, and most affected men exhibit no noticeable symptoms. Men are often diagnosed as the result of health screenings, such as a blood test for a substance called prostate specific antigen (PSA) or a medical procedure called a digital rectal exam. As the tumor grows larger, signs and symptoms can include difficulty starting or stopping the flow of urine, a feeling of not being able to empty the bladder completely, blood in the urine or semen, or pain with ejaculation. However, these changes can also occur with many other genitourinary conditions. Having one or more of these symptoms does not necessarily mean that a man has prostate cancer.  The severity and outcome of prostate cancer varies widely. Early-stage prostate cancer can usually be treated successfully, and some older men have prostate tumors that grow so slowly that they may never cause health problems during their lifetime, even without treatment. In other men, however, the cancer is much more aggressive; in these cases, prostate cancer can be life-threatening.  Some cancerous tumors can invade surrounding tissue and spread to other parts of the body. Tumors that begin at one site and then spread to other areas of the body are called metastatic cancers. The signs and symptoms of metastatic cancer depend on where the disease has spread. If prostate cancer spreads, cancerous cells most often appear in the lymph nodes, bones, lungs, liver, or brain. Bone metastases of prostate cancer most often cause pain in the lower back, pelvis, or hips.  A small percentage of all prostate cancers cluster in families. These hereditary cancers are associated with inherited gene mutations. Hereditary prostate cancers tend to develop earlier in life than non-inherited (sporadic) cases.",prostate cancer,0000836,GHR,https://ghr.nlm.nih.gov/condition/prostate-cancer,C0376358,T191,Disorders
How many people are affected by prostate cancer ?,0000836-2,frequency,"About 1 in 7 men will be diagnosed with prostate cancer at some time during their life. In addition, studies indicate that many older men have undiagnosed prostate cancer that is non-aggressive and unlikely to cause symptoms or affect their lifespan. While most men who are diagnosed with prostate cancer do not die from it, this common cancer is still the second leading cause of cancer death among men in the United States.  More than 60 percent of prostate cancers are diagnosed after age 65, and the disorder is rare before age 40. In the United States, African Americans have a higher risk of developing prostate cancer than do men of other ethnic backgrounds, and they also have a higher risk of dying from the disease.",prostate cancer,0000836,GHR,https://ghr.nlm.nih.gov/condition/prostate-cancer,C0376358,T191,Disorders
What are the genetic changes related to prostate cancer ?,0000836-3,genetic changes,"Cancers occur when genetic mutations build up in critical genes, specifically those that control cell growth and division or the repair of damaged DNA. These changes allow cells to grow and divide uncontrollably to form a tumor. In most cases of prostate cancer, these genetic changes are acquired during a man's lifetime and are present only in certain cells in the prostate. These changes, which are called somatic mutations, are not inherited. Somatic mutations in many different genes have been found in prostate cancer cells. Less commonly, genetic changes present in essentially all of the body's cells increase the risk of developing prostate cancer. These genetic changes, which are classified as germline mutations, are usually inherited from a parent. In people with germline mutations, changes in other genes, together with environmental and lifestyle factors, also influence whether a person will develop prostate cancer.  Inherited mutations in particular genes, such as BRCA1, BRCA2, and HOXB13, account for some cases of hereditary prostate cancer. Men with mutations in these genes have a high risk of developing prostate cancer and, in some cases, other cancers during their lifetimes. In addition, men with BRCA2 or HOXB13 gene mutations may have a higher risk of developing life-threatening forms of prostate cancer.  The proteins produced from the BRCA1 and BRCA2 genes are involved in fixing damaged DNA, which helps to maintain the stability of a cell's genetic information. For this reason, the BRCA1 and BRCA2 proteins are considered to be tumor suppressors, which means that they help keep cells from growing and dividing too fast or in an uncontrolled way. Mutations in these genes impair the cell's ability to fix damaged DNA, allowing potentially damaging mutations to persist. As these defects accumulate, they can trigger cells to grow and divide uncontrollably and form a tumor.  The HOXB13 gene provides instructions for producing a protein that attaches (binds) to specific regions of DNA and regulates the activity of other genes. On the basis of this role, the protein produced from the HOXB13 gene is called a transcription factor. Like BRCA1 and BRCA2, the HOXB13 protein is thought to act as a tumor suppressor. HOXB13 gene mutations may result in impairment of the protein's tumor suppressor function, resulting in the uncontrolled cell growth and division that can lead to prostate cancer.  Inherited variations in dozens of other genes have been studied as possible risk factors for prostate cancer. Some of these genes provide instructions for making proteins that interact with the proteins produced from the BRCA1, BRCA2, or HOXB13 genes. Others act as tumor suppressors through different pathways. Changes in these genes probably make only a small contribution to overall prostate cancer risk. However, researchers suspect that the combined influence of variations in many of these genes may significantly impact a person's risk of developing this form of cancer.  In many families, the genetic changes associated with hereditary prostate cancer are unknown. Identifying additional genetic risk factors for prostate cancer is an active area of medical research.  In addition to genetic changes, researchers have identified many personal and environmental factors that may contribute to a person's risk of developing prostate cancer. These factors include a high-fat diet that includes an excess of meat and dairy and not enough vegetables, a largely inactive (sedentary) lifestyle, obesity, excessive alcohol use, or exposure to certain toxic chemicals. A history of prostate cancer in closely related family members is also an important risk factor, particularly if the cancer occurred at an early age.",prostate cancer,0000836,GHR,https://ghr.nlm.nih.gov/condition/prostate-cancer,C0376358,T191,Disorders
Is prostate cancer inherited ?,0000836-4,inheritance,"Many cases of prostate cancer are not related to inherited gene changes. These cancers are associated with somatic mutations that occur only in certain cells in the prostate.  When prostate cancer is related to inherited gene changes, the way that cancer risk is inherited depends on the gene involved. For example, mutations in the BRCA1, BRCA2, and HOXB13 genes are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase a person's chance of developing cancer. In other cases, the inheritance of prostate cancer risk is unclear. It is important to note that people inherit an increased risk of cancer, not the disease itself. Not all people who inherit mutations in these genes will develop cancer.",prostate cancer,0000836,GHR,https://ghr.nlm.nih.gov/condition/prostate-cancer,C0376358,T191,Disorders
What are the treatments for prostate cancer ?,0000836-5,treatment,"These resources address the diagnosis or management of prostate cancer:  - American College of Radiology: Prostate Cancer Radiation Treatment  - Genetic Testing Registry: Familial prostate cancer  - Genetic Testing Registry: Prostate cancer, hereditary, 2  - MedlinePlus Encyclopedia: Prostate Brachytherapy  - MedlinePlus Encyclopedia: Prostate Cancer Staging  - MedlinePlus Encyclopedia: Prostate Cancer Treatment  - MedlinePlus Encyclopedia: Prostate-Specific Antigen (PSA) Blood Test  - MedlinePlus Encyclopedia: Radical Prostatectomy  - MedlinePlus Health Topic: Prostate Cancer Screening  - National Cancer Institute: Prostate-Specific Antigen (PSA) Test  - U.S. Preventive Services Task Force   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",prostate cancer,0000836,GHR,https://ghr.nlm.nih.gov/condition/prostate-cancer,C0376358,T191,Disorders
What is (are) protein C deficiency ?,0000837-1,information,"Protein C deficiency is a disorder that increases the risk of developing abnormal blood clots; the condition can be mild or severe.  Individuals with mild protein C deficiency are at risk of a type of blood clot known as a deep vein thrombosis (DVT). These clots occur in the deep veins of the arms or legs, away from the surface of the skin. A DVT can travel through the bloodstream and lodge in the lungs, causing a life-threatening blockage of blood flow known as a pulmonary embolism (PE). While most people with mild protein C deficiency never develop abnormal blood clots, certain factors can add to the risk of their development. These factors include increased age, surgery, inactivity, or pregnancy. Having another inherited disorder of blood clotting in addition to protein C deficiency can also influence the risk of abnormal blood clotting.  In severe cases of protein C deficiency, infants develop a life-threatening blood clotting disorder called purpura fulminans soon after birth. Purpura fulminans is characterized by the formation of blood clots in the small blood vessels throughout the body. These blood clots block normal blood flow and can lead to localized death of body tissue (necrosis). Widespread blood clotting uses up all available blood clotting proteins. As a result, abnormal bleeding occurs in various parts of the body, which can cause large, purple patches on the skin. Individuals who survive the newborn period may experience recurrent episodes of purpura fulminans.",protein C deficiency,0000837,GHR,https://ghr.nlm.nih.gov/condition/protein-c-deficiency,C0398625,T047,Disorders
How many people are affected by protein C deficiency ?,0000837-2,frequency,Mild protein C deficiency affects approximately 1 in 500 individuals. Severe protein C deficiency is rare and occurs in an estimated 1 in 4 million newborns.,protein C deficiency,0000837,GHR,https://ghr.nlm.nih.gov/condition/protein-c-deficiency,C0398625,T047,Disorders
What are the genetic changes related to protein C deficiency ?,0000837-3,genetic changes,"Protein C deficiency is caused by mutations in the PROC gene. This gene provides instructions for making protein C, which is found in the bloodstream and is important for controlling blood clotting. Protein C blocks the activity of (inactivates) certain proteins that promote blood clotting.  Most of the mutations that cause protein C deficiency change single protein building blocks (amino acids) in protein C, which disrupts its ability to control blood clotting. Individuals with this condition do not have enough functional protein C to inactivate clotting proteins, which results in the increased risk of developing abnormal blood clots. Protein C deficiency can be divided into type I and type II based on how mutations in the PROC gene affect protein C. Type I is caused by PROC gene mutations that result in reduced levels of protein C, while type II is caused by PROC gene mutations that result in the production of an altered protein C with reduced activity. Both types of mutations can be associated with mild or severe protein C deficiency; the severity is determined by the number of PROC gene mutations an individual has.",protein C deficiency,0000837,GHR,https://ghr.nlm.nih.gov/condition/protein-c-deficiency,C0398625,T047,Disorders
Is protein C deficiency inherited ?,0000837-4,inheritance,"Protein C deficiency is inherited in an autosomal dominant pattern, which means one altered copy of the PROC gene in each cell is sufficient to cause mild protein C deficiency. Individuals who inherit two altered copies of this gene in each cell have severe protein C deficiency.",protein C deficiency,0000837,GHR,https://ghr.nlm.nih.gov/condition/protein-c-deficiency,C0398625,T047,Disorders
What are the treatments for protein C deficiency ?,0000837-5,treatment,"These resources address the diagnosis or management of protein C deficiency:  - Genetic Testing Registry: Thrombophilia, hereditary, due to protein C deficiency, autosomal dominant  - MedlinePlus Encyclopedia: Congenital Protein C or S Deficiency  - MedlinePlus Encyclopedia: Necrosis  - MedlinePlus Encyclopedia: Protein C  - MedlinePlus Encyclopedia: Purpura   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",protein C deficiency,0000837,GHR,https://ghr.nlm.nih.gov/condition/protein-c-deficiency,C0398625,T047,Disorders
What is (are) protein S deficiency ?,0000838-1,information,"Protein S deficiency is a disorder of blood clotting. People with this condition have an increased risk of developing abnormal blood clots.  Individuals with mild protein S deficiency are at risk of a type of clot called a deep vein thrombosis (DVT) that occurs in the deep veins of the arms or legs. If a DVT travels through the bloodstream and lodges in the lungs, it can cause a life-threatening clot known as a pulmonary embolism (PE). Other factors can raise the risk of abnormal blood clots in people with mild protein S deficiency. These factors include increasing age, surgery, immobility, or pregnancy. The combination of protein S deficiency and other inherited disorders of blood clotting can also influence risk. Many people with mild protein S deficiency never develop an abnormal blood clot, however.  In severe cases of protein S deficiency, infants develop a life-threatening blood clotting disorder called purpura fulminans soon after birth. Purpura fulminans is characterized by the formation of blood clots within small blood vessels throughout the body. These blood clots disrupt normal blood flow and can lead to death of body tissue (necrosis). Widespread blood clotting uses up all available blood clotting proteins. As a result, abnormal bleeding occurs in various parts of the body and is often noticeable as large, purple skin lesions. Individuals who survive the newborn period may experience recurrent episodes of purpura fulminans.",protein S deficiency,0000838,GHR,https://ghr.nlm.nih.gov/condition/protein-s-deficiency,C0242666,T047,Disorders
How many people are affected by protein S deficiency ?,0000838-2,frequency,"Mild protein S deficiency is estimated to occur in approximately 1 in 500 individuals. Severe protein S deficiency is rare; however, its exact prevalence is unknown.",protein S deficiency,0000838,GHR,https://ghr.nlm.nih.gov/condition/protein-s-deficiency,C0242666,T047,Disorders
What are the genetic changes related to protein S deficiency ?,0000838-3,genetic changes,"Protein S deficiency is caused by mutations in the PROS1 gene. This gene provides instructions for making protein S, which is found in the bloodstream and is important for controlling blood clotting. Protein S helps block the activity of (inactivate) certain proteins that promote the formation of blood clots.  Most mutations that cause protein S deficiency change single protein building blocks (amino acids) in protein S, which disrupts its ability to control blood clotting. Individuals with this condition do not have enough functional protein S to inactivate clotting proteins, which results in the increased risk of developing abnormal blood clots. Protein S deficiency can be divided into types I, II and III based on how mutations in the PROS1 gene affect protein S.",protein S deficiency,0000838,GHR,https://ghr.nlm.nih.gov/condition/protein-s-deficiency,C0242666,T047,Disorders
Is protein S deficiency inherited ?,0000838-4,inheritance,"Protein S deficiency is inherited in an autosomal dominant pattern, which means one altered copy of the PROS1 gene in each cell is sufficient to cause mild protein S deficiency. Individuals who inherit two altered copies of this gene in each cell have severe protein S deficiency.",protein S deficiency,0000838,GHR,https://ghr.nlm.nih.gov/condition/protein-s-deficiency,C0242666,T047,Disorders
What are the treatments for protein S deficiency ?,0000838-5,treatment,These resources address the diagnosis or management of protein S deficiency:  - Genetic Testing Registry: Protein S deficiency  - MedlinePlus Encyclopedia: Congenital Protein C or S Deficiency  - MedlinePlus Encyclopedia: Necrosis  - MedlinePlus Encyclopedia: Protein S  - MedlinePlus Encyclopedia: Purpura   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,protein S deficiency,0000838,GHR,https://ghr.nlm.nih.gov/condition/protein-s-deficiency,C0242666,T047,Disorders
What is (are) Proteus syndrome ?,0000839-1,information,"Proteus syndrome is a rare condition characterized by overgrowth of the bones, skin, and other tissues. Organs and tissues affected by the disease grow out of proportion to the rest of the body. The overgrowth is usually asymmetric, which means it affects the right and left sides of the body differently. Newborns with Proteus syndrome have few or no signs of the condition. Overgrowth becomes apparent between the ages of 6 and 18 months and gets more severe with age.  In people with Proteus syndrome, the pattern of overgrowth varies greatly but can affect almost any part of the body. Bones in the limbs, skull, and spine are often affected. The condition can also cause a variety of skin growths, particularly a thick, raised, and deeply grooved lesion known as a cerebriform connective tissue nevus. This type of skin growth usually occurs on the soles of the feet and is hardly ever seen in conditions other than Proteus syndrome. Blood vessels (vascular tissue) and fat (adipose tissue) can also grow abnormally in Proteus syndrome.  Some people with Proteus syndrome have neurological abnormalities, including intellectual disability, seizures, and vision loss. Affected individuals may also have distinctive facial features such as a long face, outside corners of the eyes that point downward (down-slanting palpebral fissures), a low nasal bridge with wide nostrils, and an open-mouth expression. For reasons that are unclear, affected people with neurological symptoms are more likely to have distinctive facial features than those without neurological symptoms. It is unclear how these signs and symptoms are related to abnormal growth.  Other potential complications of Proteus syndrome include an increased risk of developing various types of noncancerous (benign) tumors and a type of blood clot called a deep venous thrombosis (DVT). DVTs occur most often in the deep veins of the legs or arms. If these clots travel through the bloodstream, they can lodge in the lungs and cause a life-threatening complication called a pulmonary embolism. Pulmonary embolism is a common cause of death in people with Proteus syndrome.",Proteus syndrome,0000839,GHR,https://ghr.nlm.nih.gov/condition/proteus-syndrome,C0085261,T191,Disorders
How many people are affected by Proteus syndrome ?,0000839-2,frequency,"Proteus syndrome is a rare condition with an incidence of less than 1 in 1 million people worldwide. Only a few hundred affected individuals have been reported in the medical literature.  Researchers believe that Proteus syndrome may be overdiagnosed, as some individuals with other conditions featuring asymmetric overgrowth have been mistakenly diagnosed with Proteus syndrome. To make an accurate diagnosis, most doctors and researchers now follow a set of strict guidelines that define the signs and symptoms of Proteus syndrome.",Proteus syndrome,0000839,GHR,https://ghr.nlm.nih.gov/condition/proteus-syndrome,C0085261,T191,Disorders
What are the genetic changes related to Proteus syndrome ?,0000839-3,genetic changes,"Proteus syndrome results from a mutation in the AKT1 gene. This genetic change is not inherited from a parent; it arises randomly in one cell during the early stages of development before birth. As cells continue to grow and divide, some cells will have the mutation and other cells will not. This mixture of cells with and without a genetic mutation is known as mosaicism.  The AKT1 gene helps regulate cell growth and division (proliferation) and cell death. A mutation in this gene disrupts a cell's ability to regulate its own growth, allowing it to grow and divide abnormally. Increased cell proliferation in various tissues and organs leads to the abnormal growth characteristic of Proteus syndrome. Studies suggest that an AKT1 gene mutation is more common in groups of cells that experience overgrowth than in the parts of the body that grow normally.  In some published case reports, mutations in a gene called PTEN have been associated with Proteus syndrome. However, many researchers now believe that individuals with PTEN gene mutations and asymmetric overgrowth do not meet the strict guidelines for a diagnosis of Proteus syndrome. Instead, these individuals actually have condition that is considered part of a larger group of disorders called PTEN hamartoma tumor syndrome. One name that has been proposed for the condition is segmental overgrowth, lipomatosis, arteriovenous malformations, and epidermal nevus (SOLAMEN) syndrome; another is type 2 segmental Cowden syndrome. However, some scientific articles still refer to PTEN-related Proteus syndrome.",Proteus syndrome,0000839,GHR,https://ghr.nlm.nih.gov/condition/proteus-syndrome,C0085261,T191,Disorders
Is Proteus syndrome inherited ?,0000839-4,inheritance,"Because Proteus syndrome is caused by AKT1 gene mutations that occur during early development, the disorder is not inherited and does not run in families.",Proteus syndrome,0000839,GHR,https://ghr.nlm.nih.gov/condition/proteus-syndrome,C0085261,T191,Disorders
What are the treatments for Proteus syndrome ?,0000839-5,treatment,These resources address the diagnosis or management of Proteus syndrome:  - Gene Review: Gene Review: Proteus Syndrome  - Genetic Testing Registry: Proteus syndrome  - Proteus Syndrome Foundation: Diagnostic Criteria and FAQs   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Proteus syndrome,0000839,GHR,https://ghr.nlm.nih.gov/condition/proteus-syndrome,C0085261,T191,Disorders
What is (are) prothrombin deficiency ?,0000840-1,information,"Prothrombin deficiency is a bleeding disorder that slows the blood clotting process. People with this condition often experience prolonged bleeding following an injury, surgery, or having a tooth pulled. In severe cases of prothrombin deficiency, heavy bleeding occurs after minor trauma or even in the absence of injury (spontaneous bleeding). Women with prothrombin deficiency can have prolonged and sometimes abnormally heavy menstrual bleeding. Serious complications can result from bleeding into the joints, muscles, brain, or other internal organs. Milder forms of prothrombin deficiency do not involve spontaneous bleeding, and the condition may only become apparent following surgery or a serious injury.",prothrombin deficiency,0000840,GHR,https://ghr.nlm.nih.gov/condition/prothrombin-deficiency,C3203356,T047,Disorders
How many people are affected by prothrombin deficiency ?,0000840-2,frequency,Prothrombin deficiency is very rare; it is estimated to affect 1 in 2 million people in the general population.,prothrombin deficiency,0000840,GHR,https://ghr.nlm.nih.gov/condition/prothrombin-deficiency,C3203356,T047,Disorders
What are the genetic changes related to prothrombin deficiency ?,0000840-3,genetic changes,"Mutations in the F2 gene cause prothrombin deficiency. The F2 gene provides instructions for making the prothrombin protein (also called coagulation factor II), which plays a critical role in the formation of blood clots in response to injury. Prothrombin is the precursor to thrombin, a protein that initiates a series of chemical reactions to form a blood clot. After an injury, clots protect the body by sealing off damaged blood vessels and preventing further blood loss.  F2 gene mutations reduce the production of prothrombin in cells, which prevents clots from forming properly in response to injury. Problems with blood clotting can lead to excessive bleeding. Some mutations drastically reduce the activity of prothrombin and can lead to severe bleeding episodes. Other F2 gene mutations allow for a moderate amount of prothrombin activity, typically resulting in mild bleeding episodes.",prothrombin deficiency,0000840,GHR,https://ghr.nlm.nih.gov/condition/prothrombin-deficiency,C3203356,T047,Disorders
Is prothrombin deficiency inherited ?,0000840-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",prothrombin deficiency,0000840,GHR,https://ghr.nlm.nih.gov/condition/prothrombin-deficiency,C3203356,T047,Disorders
What are the treatments for prothrombin deficiency ?,0000840-5,treatment,"These resources address the diagnosis or management of prothrombin deficiency:  - Genetic Testing Registry: Prothrombin deficiency, congenital  - MedlinePlus Encyclopedia: Factor II deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",prothrombin deficiency,0000840,GHR,https://ghr.nlm.nih.gov/condition/prothrombin-deficiency,C3203356,T047,Disorders
What is (are) prothrombin thrombophilia ?,0000841-1,information,"Prothrombin thrombophilia is an inherited disorder of blood clotting. Thrombophilia is an increased tendency to form abnormal blood clots in blood vessels. People who have prothrombin thrombophilia are at somewhat higher than average risk for a type of clot called a deep venous thrombosis, which typically occurs in the deep veins of the legs. Affected people also have an increased risk of developing a pulmonary embolism, which is a clot that travels through the bloodstream and lodges in the lungs. Most people with prothrombin thrombophilia never develop abnormal blood clots, however.  Some research suggests that prothrombin thrombophilia is associated with a somewhat increased risk of pregnancy loss (miscarriage) and may also increase the risk of other complications during pregnancy. These complications may include pregnancy-induced high blood pressure (preeclampsia), slow fetal growth, and early separation of the placenta from the uterine wall (placental abruption). It is important to note, however, that most women with prothrombin thrombophilia have normal pregnancies.",prothrombin thrombophilia,0000841,GHR,https://ghr.nlm.nih.gov/condition/prothrombin-thrombophilia,C1867596,T047,Disorders
How many people are affected by prothrombin thrombophilia ?,0000841-2,frequency,"Prothrombin thrombophilia is the second most common inherited form of thrombophilia after factor V Leiden thrombophilia. Approximately 1 in 50 people in the white population in the United States and Europe has prothrombin thrombophilia. This condition is less common in other ethnic groups, occurring in less than one percent of African American, Native American, or Asian populations.",prothrombin thrombophilia,0000841,GHR,https://ghr.nlm.nih.gov/condition/prothrombin-thrombophilia,C1867596,T047,Disorders
What are the genetic changes related to prothrombin thrombophilia ?,0000841-3,genetic changes,"Prothrombin thrombophilia is caused by a particular mutation in the F2 gene. The F2 gene plays a critical role in the formation of blood clots in response to injury. The protein produced from the F2 gene, prothrombin (also called coagulation factor II), is the precursor to a protein called thrombin that initiates a series of chemical reactions in order to form a blood clot. The particular mutation that causes prothrombin thrombophilia results in an overactive F2 gene that causes too much prothrombin to be produced. An abundance of prothrombin leads to more thrombin, which promotes the formation of blood clots.  Other factors also increase the risk of blood clots in people with prothrombin thrombophilia. These factors include increasing age, obesity, trauma, surgery, smoking, the use of oral contraceptives (birth control pills) or hormone replacement therapy, and pregnancy. The combination of prothrombin thrombophilia and mutations in other genes involved in blood clotting can also influence risk.",prothrombin thrombophilia,0000841,GHR,https://ghr.nlm.nih.gov/condition/prothrombin-thrombophilia,C1867596,T047,Disorders
Is prothrombin thrombophilia inherited ?,0000841-4,inheritance,"The risk of developing an abnormal clot in a blood vessel depends on whether a person inherits one or two copies of the F2 gene mutation that causes prothrombin thrombophilia. In the general population, the risk of developing an abnormal blood clot is about 1 in 1,000 people per year. Inheriting one copy of the F2 gene mutation increases that risk to 2 to 3 in 1,000. People who inherit two copies of the mutation, one from each parent, may have a risk as high as 20 in 1,000.",prothrombin thrombophilia,0000841,GHR,https://ghr.nlm.nih.gov/condition/prothrombin-thrombophilia,C1867596,T047,Disorders
What are the treatments for prothrombin thrombophilia ?,0000841-5,treatment,These resources address the diagnosis or management of prothrombin thrombophilia:  - Gene Review: Gene Review: Prothrombin-Related Thrombophilia  - Genetic Testing Registry: Thrombophilia  - MedlinePlus Encyclopedia: Deep venous thrombosis  - MedlinePlus Encyclopedia: Pulmonary embolus   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,prothrombin thrombophilia,0000841,GHR,https://ghr.nlm.nih.gov/condition/prothrombin-thrombophilia,C1867596,T047,Disorders
What is (are) pseudoachondroplasia ?,0000842-1,information,"Pseudoachondroplasia is an inherited disorder of bone growth. It was once thought to be related to another disorder of bone growth called achondroplasia, but without that disorder's characteristic facial features. More research has demonstrated that pseudoachondroplasia is a separate disorder.  All people with pseudoachondroplasia have short stature. The average height of adult males with this condition is 120 centimeters (3 feet, 11 inches), and the average height of adult females is 116 centimeters (3 feet, 9 inches). Individuals with pseudoachondroplasia are not unusually short at birth; by the age of two, their growth rate falls below the standard growth curve.  Other characteristic features of pseudoachondroplasia include short arms and legs; a waddling walk; joint pain in childhood that progresses to a joint disease known as osteoarthritis; an unusually large range of joint movement (hyperextensibility) in the hands, knees, and ankles; and a limited range of motion at the elbows and hips. Some people with pseudoachondroplasia have legs that turn outward or inward (valgus or varus deformity). Sometimes, one leg turns outward and the other inward, which is called windswept deformity. Some affected individuals have a spine that curves to the side (scoliosis) or an abnormally curved lower back (lordosis). People with pseudoachondroplasia have normal facial features, head size, and intelligence.",pseudoachondroplasia,0000842,GHR,https://ghr.nlm.nih.gov/condition/pseudoachondroplasia,C0410538,T019,Disorders
How many people are affected by pseudoachondroplasia ?,0000842-2,frequency,"The exact prevalence of pseudoachondroplasia is unknown; it is estimated to occur in 1 in 30,000 individuals.",pseudoachondroplasia,0000842,GHR,https://ghr.nlm.nih.gov/condition/pseudoachondroplasia,C0410538,T019,Disorders
What are the genetic changes related to pseudoachondroplasia ?,0000842-3,genetic changes,"Mutations in the COMP gene cause pseudoachondroplasia. This gene provides instructions for making a protein that is essential for the normal development of cartilage and for its conversion to bone. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears.  The COMP protein is normally found in the spaces between cartilage-forming cells called chondrocytes, where it interacts with other proteins. COMP gene mutations result in the production of an abnormal COMP protein that cannot be transported out of the cell. The abnormal protein builds up inside the chondrocyte and ultimately leads to early cell death. Early death of the chondrocytes prevents normal bone growth and causes the short stature and bone abnormalities seen in pseudoachondroplasia.",pseudoachondroplasia,0000842,GHR,https://ghr.nlm.nih.gov/condition/pseudoachondroplasia,C0410538,T019,Disorders
Is pseudoachondroplasia inherited ?,0000842-4,inheritance,"Pseudoachondroplasia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In some cases, an affected person inherits the mutation from one affected parent. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",pseudoachondroplasia,0000842,GHR,https://ghr.nlm.nih.gov/condition/pseudoachondroplasia,C0410538,T019,Disorders
What are the treatments for pseudoachondroplasia ?,0000842-5,treatment,These resources address the diagnosis or management of pseudoachondroplasia:  - Gene Review: Gene Review: Pseudoachondroplasia  - Genetic Testing Registry: Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,pseudoachondroplasia,0000842,GHR,https://ghr.nlm.nih.gov/condition/pseudoachondroplasia,C0410538,T019,Disorders
What is (are) pseudocholinesterase deficiency ?,0000843-1,information,"Pseudocholinesterase deficiency is a condition that results in increased sensitivity to certain muscle relaxant drugs used during general anesthesia, called choline esters. These fast-acting drugs, such as succinylcholine and mivacurium, are given to relax the muscles used for movement (skeletal muscles), including the muscles involved in breathing. The drugs are often employed for brief surgical procedures or in emergencies when a breathing tube must be inserted quickly. Normally, these drugs are broken down (metabolized) by the body within a few minutes of being administered, at which time the muscles can move again. However, people with pseudocholinesterase deficiency may not be able to move or breathe on their own for a few hours after the drugs are administered. Affected individuals must be supported with a machine to help them breathe (mechanical ventilation) until the drugs are cleared from the body.  People with pseudocholinesterase deficiency may also have increased sensitivity to certain other drugs, including the local anesthetic procaine, and to specific agricultural pesticides. The condition causes no other signs or symptoms and is usually not discovered until an abnormal drug reaction occurs.",pseudocholinesterase deficiency,0000843,GHR,https://ghr.nlm.nih.gov/condition/pseudocholinesterase-deficiency,C0268379,T047,Disorders
How many people are affected by pseudocholinesterase deficiency ?,0000843-2,frequency,"Pseudocholinesterase deficiency occurs in 1 in 3,200 to 1 in 5,000 people. It is more common in certain populations, such as the Persian Jewish community and Alaska Natives.",pseudocholinesterase deficiency,0000843,GHR,https://ghr.nlm.nih.gov/condition/pseudocholinesterase-deficiency,C0268379,T047,Disorders
What are the genetic changes related to pseudocholinesterase deficiency ?,0000843-3,genetic changes,"Pseudocholinesterase deficiency can be caused by mutations in the BCHE gene. This gene provides instructions for making the pseudocholinesterase enzyme, also known as butyrylcholinesterase, which is produced by the liver and circulates in the blood. The pseudocholinesterase enzyme is involved in the breakdown of choline ester drugs. It is likely that the enzyme has other functions in the body, but these functions are not well understood. Studies suggest that the enzyme may be involved in the transmission of nerve signals.  Some BCHE gene mutations that cause pseudocholinesterase deficiency result in an abnormal pseudocholinesterase enzyme that does not function properly. Other mutations prevent the production of the pseudocholinesterase enzyme. A lack of functional pseudocholinesterase enzyme impairs the body's ability to break down choline ester drugs efficiently, leading to abnormally prolonged drug effects.  Pseudocholinesterase deficiency can also have nongenetic causes. In these cases, the condition is called acquired pseudocholinesterase deficiency; it is not inherited and cannot be passed to the next generation. Activity of the pseudocholinesterase enzyme can be impaired by kidney or liver disease, malnutrition, major burns, cancer, or certain drugs.",pseudocholinesterase deficiency,0000843,GHR,https://ghr.nlm.nih.gov/condition/pseudocholinesterase-deficiency,C0268379,T047,Disorders
Is pseudocholinesterase deficiency inherited ?,0000843-4,inheritance,"When due to genetic causes, this condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive disorder have one copy of the altered gene in each cell and are called carriers. They can pass on the gene mutation to their children, but they do not usually experience signs and symptoms of the disorder. In some cases, carriers of BCHE gene mutations take longer than usual to clear choline ester drugs from the body, but not as long as those with two copies of the altered gene in each cell.",pseudocholinesterase deficiency,0000843,GHR,https://ghr.nlm.nih.gov/condition/pseudocholinesterase-deficiency,C0268379,T047,Disorders
What are the treatments for pseudocholinesterase deficiency ?,0000843-5,treatment,These resources address the diagnosis or management of pseudocholinesterase deficiency:  - MedlinePlus Encyclopedia: Cholinesterase (blood test)   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,pseudocholinesterase deficiency,0000843,GHR,https://ghr.nlm.nih.gov/condition/pseudocholinesterase-deficiency,C0268379,T047,Disorders
What is (are) pseudohypoaldosteronism type 1 ?,0000844-1,information,"Pseudohypoaldosteronism type 1 (PHA1) is a condition characterized by problems regulating the amount of sodium in the body. Sodium regulation, which is important for blood pressure and fluid balance, primarily occurs in the kidneys. However, sodium can also be removed from the body through other tissues, such as the sweat glands and colon. Pseudohypoaldosteronism type 1 is named for its characteristic signs and symptoms, which mimic (pseudo) low levels (hypo) of a hormone called aldosterone that helps regulate sodium levels. However, people with PHA1 have high levels of aldosterone.  There are two types of PHA1 distinguished by their severity, the genes involved, and how they are inherited. One type, called autosomal dominant PHA1 (also known as renal PHA1) is characterized by excessive sodium loss from the kidneys. This form of the condition is relatively mild and often improves in early childhood. The other type, called autosomal recessive PHA1 (also known as generalized or systemic PHA1) is characterized by sodium loss from the kidneys and other organs, including the sweat glands, salivary glands, and colon. This type of PHA1 is more severe and does not improve with age.  The earliest signs of both types of PHA1 are usually the inability to gain weight and grow at the expected rate (failure to thrive) and dehydration, which are typically seen in infants. The characteristic features of both types of PHA1 are excessive amounts of sodium released in the urine (salt wasting), which leads to low levels of sodium in the blood (hyponatremia), and high levels of potassium in the blood (hyperkalemia). Infants with PHA1 can also have high levels of acid in the blood (metabolic acidosis). Hyponatremia, hyperkalemia, or metabolic acidosis can cause nonspecific symptoms such as nausea, vomiting, extreme tiredness (fatigue), and muscle weakness in infants with PHA1.  Infants with autosomal recessive PHA1 can have additional signs and symptoms due to the involvement of multiple organs. Affected individuals may experience episodes of abnormal heartbeat (cardiac arrhythmia) or shock because of the imbalance of salts in the body. They may also have recurrent lung infections or lesions on the skin. Although adults with autosomal recessive PHA1 can have repeated episodes of salt wasting, they do not usually have other signs and symptoms of the condition.",pseudohypoaldosteronism type 1,0000844,GHR,https://ghr.nlm.nih.gov/condition/pseudohypoaldosteronism-type-1,C0033805,T047,Disorders
How many people are affected by pseudohypoaldosteronism type 1 ?,0000844-2,frequency,"PHA1 is a rare condition that has been estimated to affect 1 in 80,000 newborns.",pseudohypoaldosteronism type 1,0000844,GHR,https://ghr.nlm.nih.gov/condition/pseudohypoaldosteronism-type-1,C0033805,T047,Disorders
What are the genetic changes related to pseudohypoaldosteronism type 1 ?,0000844-3,genetic changes,"Mutations in one of four different genes involved in sodium regulation cause autosomal dominant or autosomal recessive PHA1. Mutations in the NR3C2 gene cause autosomal dominant PHA1. This gene provides instructions for making the mineralocorticoid receptor protein. Mutations in the SCNN1A, SCNN1B, or SCNN1G genes cause autosomal recessive PHA1. Each of these three genes provides instructions for making one of the pieces (subunits) of a protein complex called the epithelial sodium channel (ENaC).  The mineralocorticoid receptor regulates specialized proteins in the cell membrane that control the transport of sodium or potassium into cells. In response to signals that sodium levels are low, such as the presence of the hormone aldosterone, the mineralocorticoid receptor increases the number and activity of these proteins at the cell membrane of certain kidney cells. One of these proteins is ENaC, which transports sodium into the cell; another protein simultaneously transports sodium out of the cell and potassium into the cell. These proteins help keep sodium in the body through a process called reabsorption and remove potassium from the body through a process called secretion.  Mutations in the NR3C2 gene lead to a nonfunctional or abnormally functioning mineralocorticoid receptor protein that cannot properly regulate the specialized proteins that transport sodium and potassium. As a result, sodium reabsorption and potassium secretion are both decreased, causing hyponatremia and hyperkalemia.  Mutations in the SCNN1A, SCNN1B, and SCNN1G genes result in reduced functioning or nonfunctioning ENaC channels. As in autosomal dominant PHA1, the reduction or absence of ENaC function in the kidneys leads to hyponatremia and hyperkalemia. In addition, nonfunctional ENaC channels in other body systems lead to additional signs and symptoms of autosomal recessive PHA1, including lung infections and skin lesions.",pseudohypoaldosteronism type 1,0000844,GHR,https://ghr.nlm.nih.gov/condition/pseudohypoaldosteronism-type-1,C0033805,T047,Disorders
Is pseudohypoaldosteronism type 1 inherited ?,0000844-4,inheritance,"PHA1 can have different inheritance patterns. When the condition is caused by mutations in the NR3C2 gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. When PHA1 is caused by mutations in the SCNN1A, SCNN1B, or SCNN1G genes, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",pseudohypoaldosteronism type 1,0000844,GHR,https://ghr.nlm.nih.gov/condition/pseudohypoaldosteronism-type-1,C0033805,T047,Disorders
What are the treatments for pseudohypoaldosteronism type 1 ?,0000844-5,treatment,These resources address the diagnosis or management of pseudohypoaldosteronism type 1:  - Genetic Testing Registry: Pseudohypoaldosteronism type 1 autosomal dominant  - Genetic Testing Registry: Pseudohypoaldosteronism type 1 autosomal recessive  - MedlinePlus Encyclopedia: Hyponatremia  - University of Maryland Medical Center: Hyperkalemia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,pseudohypoaldosteronism type 1,0000844,GHR,https://ghr.nlm.nih.gov/condition/pseudohypoaldosteronism-type-1,C0033805,T047,Disorders
What is (are) pseudohypoaldosteronism type 2 ?,0000845-1,information,"Pseudohypoaldosteronism type 2 (PHA2) is caused by problems that affect regulation of the amount of sodium and potassium in the body. Sodium and potassium are important in the control of blood pressure, and their regulation occurs primarily in the kidneys.  People with PHA2 have high blood pressure (hypertension) and high levels of potassium in their blood (hyperkalemia) despite having normal kidney function. The age of onset of PHA2 is variable and difficult to pinpoint; some affected individuals are diagnosed in infancy or childhood, and others are diagnosed in adulthood. Hyperkalemia usually occurs first, and hypertension develops later in life. Affected individuals also have high levels of chloride (hyperchloremia) and acid (metabolic acidosis) in their blood (together, referred to as hyperchloremic metabolic acidosis). People with hyperkalemia, hyperchloremia, and metabolic acidosis can have nonspecific symptoms like nausea, vomiting, extreme tiredness (fatigue), and muscle weakness. People with PHA2 may also have high levels of calcium in their urine (hypercalciuria).",pseudohypoaldosteronism type 2,0000845,GHR,https://ghr.nlm.nih.gov/condition/pseudohypoaldosteronism-type-2,C1449844,T047,Disorders
How many people are affected by pseudohypoaldosteronism type 2 ?,0000845-2,frequency,"PHA2 is a rare condition; however, the prevalence is unknown.",pseudohypoaldosteronism type 2,0000845,GHR,https://ghr.nlm.nih.gov/condition/pseudohypoaldosteronism-type-2,C1449844,T047,Disorders
What are the genetic changes related to pseudohypoaldosteronism type 2 ?,0000845-3,genetic changes,"PHA2 can be caused by mutations in the WNK1, WNK4, CUL3, or KLHL3 gene. These genes play a role in the regulation of blood pressure.  The proteins produced from the WNK1 and WNK4 genes help control the amount of sodium and potassium in the body by regulating channels in the cell membrane that control the transport of sodium or potassium into and out of cells. This process primarily occurs in the kidneys. Mutations in either of these genes disrupt control of these channels, leading to abnormal levels of sodium and potassium in the body. As a result, affected individuals develop hypertension and hyperkalemia.  The proteins produced from the CUL3 gene (called cullin-3) and the KLHL3 gene help control the amount of WNK1 and WNK4 protein available. Cullin-3 and KLHL3 are two pieces of a complex, called an E3 ubiquitin ligase, that tags certain other proteins with molecules called ubiquitin. This molecule acts as a signal for the tagged protein to be broken down when it is no longer needed. E3 ubiquitin ligases containing cullin-3 and KLHL3 are able to tag the WNK1 and WNK4 proteins with ubiquitin, leading to their breakdown. Mutations in either the CUL3 or KLHL3 gene impair breakdown of the WNK4 protein. (The effect of these mutations on the WNK1 protein is unclear.) An excess of WNK4 likely disrupts control of sodium and potassium levels, resulting in hypertension and hyperkalemia.",pseudohypoaldosteronism type 2,0000845,GHR,https://ghr.nlm.nih.gov/condition/pseudohypoaldosteronism-type-2,C1449844,T047,Disorders
Is pseudohypoaldosteronism type 2 inherited ?,0000845-4,inheritance,"This condition is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases caused by mutations in the WNK1, WNK4, or KLHL3 gene, an affected person inherits the mutation from one affected parent. While some cases caused by CUL3 gene mutations can be inherited from an affected parent, many result from new mutations in the gene and occur in people with no history of the disorder in their family.  Some cases caused by mutations in the KLHL3 gene are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",pseudohypoaldosteronism type 2,0000845,GHR,https://ghr.nlm.nih.gov/condition/pseudohypoaldosteronism-type-2,C1449844,T047,Disorders
What are the treatments for pseudohypoaldosteronism type 2 ?,0000845-5,treatment,"These resources address the diagnosis or management of pseudohypoaldosteronism type 2:  - Gene Review: Gene Review: Pseudohypoaldosteronism Type II  - Genetic Testing Registry: Pseudohypoaldosteronism, type 2   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",pseudohypoaldosteronism type 2,0000845,GHR,https://ghr.nlm.nih.gov/condition/pseudohypoaldosteronism-type-2,C1449844,T047,Disorders
What is (are) pseudoxanthoma elasticum ?,0000846-1,information,"Pseudoxanthoma elasticum (PXE) is a progressive disorder that is characterized by the accumulation of deposits of calcium and other minerals (mineralization) in elastic fibers. Elastic fibers are a component of connective tissue, which provides strength and flexibility to structures throughout the body.  In PXE, mineralization can affect elastic fibers in the skin, eyes, and blood vessels, and less frequently in other areas such as the digestive tract. People with PXE may have yellowish bumps called papules on their necks, underarms, and other areas of skin that touch when a joint bends (flexor areas). They may also have abnormalities in the eyes, such as a change in the pigmented cells of the retina (the light-sensitive layer of cells at the back of the eye) known as peau d'orange. Another eye abnormality known as angioid streaks occurs when tiny breaks form in the layer of tissue under the retina called Bruch's membrane. Bleeding and scarring of the retina may also occur, which can cause vision loss.  Mineralization of the blood vessels that carry blood from the heart to the rest of the body (arteries) may cause other signs and symptoms of PXE. For example, people with this condition can develop narrowing of the arteries (arteriosclerosis) or a condition called claudication that is characterized by cramping and pain during exercise due to decreased blood flow to the arms and legs. Rarely, bleeding from blood vessels in the digestive tract may also occur.",pseudoxanthoma elasticum,0000846,GHR,https://ghr.nlm.nih.gov/condition/pseudoxanthoma-elasticum,C0033847,T191,Disorders
How many people are affected by pseudoxanthoma elasticum ?,0000846-2,frequency,"PXE affects approximately 1 in 50,000 people worldwide. For reasons that are unclear, this disorder is diagnosed twice as frequently in females as in males.",pseudoxanthoma elasticum,0000846,GHR,https://ghr.nlm.nih.gov/condition/pseudoxanthoma-elasticum,C0033847,T191,Disorders
What are the genetic changes related to pseudoxanthoma elasticum ?,0000846-3,genetic changes,"Mutations in the ABCC6 gene cause PXE. This gene provides instructions for making a protein called MRP6 (also known as the ABCC6 protein). This protein is found primarily in cells of the liver and kidneys, with small amounts in other tissues, including the skin, stomach, blood vessels, and eyes. MRP6 is thought to transport certain substances across the cell membrane; however, the substances have not been identified. Some studies suggest that the MRP6 protein stimulates the release of a molecule called adenosine triphosphate (ATP) from cells through an unknown mechanism. ATP can be broken down into other molecules, including adenosine monophosphate (AMP) and pyrophosphate. Pyrophosphate helps control deposition of calcium and other minerals in the body. Other studies suggest that a substance transported by MRP6 is involved in the breakdown of ATP. This unidentified substance is thought to help prevent mineralization of tissues.  Mutations in the ABCC6 gene lead to an absent or nonfunctional MRP6 protein. It is unclear how a lack of properly functioning MRP6 protein leads to PXE. This shortage may impair the release of ATP from cells. As a result, little pyrophosphate is produced, and calcium and other minerals accumulate in elastic fibers of the skin, eyes, blood vessels and other tissues affected by PXE. Alternatively, a lack of functioning MRP6 may impair the transport of a substance that would normally prevent mineralization, leading to the abnormal accumulation of calcium and other minerals characteristic of PXE.",pseudoxanthoma elasticum,0000846,GHR,https://ghr.nlm.nih.gov/condition/pseudoxanthoma-elasticum,C0033847,T191,Disorders
Is pseudoxanthoma elasticum inherited ?,0000846-4,inheritance,"PXE is inherited in an autosomal recessive manner, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.  In a few cases, an affected individual has one affected parent and one parent without the signs and symptoms of the disorder. This situation resembles autosomal dominant inheritance, in which one copy of an altered gene in each cell is sufficient to cause a disorder and the mutation is typically inherited from one affected parent. In these cases of PXE, however, the parent without apparent symptoms has an ABCC6 gene mutation. The affected offspring inherits two altered genes, one from each parent. This appearance of autosomal dominant inheritance when the pattern is actually autosomal recessive is called pseudodominance.",pseudoxanthoma elasticum,0000846,GHR,https://ghr.nlm.nih.gov/condition/pseudoxanthoma-elasticum,C0033847,T191,Disorders
What are the treatments for pseudoxanthoma elasticum ?,0000846-5,treatment,These resources address the diagnosis or management of pseudoxanthoma elasticum:  - Gene Review: Gene Review: Pseudoxanthoma Elasticum  - Genetic Testing Registry: Pseudoxanthoma elasticum   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,pseudoxanthoma elasticum,0000846,GHR,https://ghr.nlm.nih.gov/condition/pseudoxanthoma-elasticum,C0033847,T191,Disorders
What is (are) psoriatic arthritis ?,0000847-1,information,"Psoriatic arthritis is a condition involving joint inflammation (arthritis) that usually occurs in combination with a skin disorder called psoriasis. Psoriasis is a chronic inflammatory condition characterized by patches of red, irritated skin that are often covered by flaky white scales. People with psoriasis may also have changes in their fingernails and toenails, such as nails that become pitted or ridged, crumble, or separate from the nail beds.  Signs and symptoms of psoriatic arthritis include stiff, painful joints with redness, heat, and swelling in the surrounding tissues. When the hands and feet are affected, swelling and redness may result in a ""sausage-like"" appearance of the fingers or toes (dactylitis).  In most people with psoriatic arthritis, psoriasis appears before joint problems develop. Psoriasis typically begins during adolescence or young adulthood, and psoriatic arthritis usually occurs between the ages of 30 and 50. However, both conditions may occur at any age. In a small number of cases, psoriatic arthritis develops in the absence of noticeable skin changes.  Psoriatic arthritis may be difficult to distinguish from other forms of arthritis, particularly when skin changes are minimal or absent. Nail changes and dactylitis are two features that are characteristic of psoriatic arthritis, although they do not occur in all cases.  Psoriatic arthritis is categorized into five types: distal interphalangeal predominant, asymmetric oligoarticular, symmetric polyarthritis, spondylitis, and arthritis mutilans.  The distal interphalangeal predominant type affects mainly the ends of the fingers and toes. The distal interphalangeal joints are those closest to the nails. Nail changes are especially frequent with this form of psoriatic arthritis.  The asymmetric oligoarticular and symmetric polyarthritis types are the most common forms of psoriatic arthritis. The asymmetric oligoarticular type of psoriatic arthritis involves different joints on each side of the body, while the symmetric polyarthritis form affects the same joints on each side. Any joint in the body may be affected in these forms of the disorder, and symptoms range from mild to severe.  Some individuals with psoriatic arthritis have joint involvement that primarily involves spondylitis, which is inflammation in the joints between the vertebrae in the spine. Symptoms of this form of the disorder involve pain and stiffness in the back or neck, and movement is often impaired. Joints in the arms, legs, hands, and feet may also be involved.  The most severe and least common type of psoriatic arthritis is called arthritis mutilans. Fewer than 5 percent of individuals with psoriatic arthritis have this form of the disorder. Arthritis mutilans involves severe inflammation that damages the joints in the hands and feet, resulting in deformation and movement problems. Bone loss (osteolysis) at the joints may lead to shortening (telescoping) of the fingers and toes. Neck and back pain may also occur.",psoriatic arthritis,0000847,GHR,https://ghr.nlm.nih.gov/condition/psoriatic-arthritis,C0003872,T047,Disorders
How many people are affected by psoriatic arthritis ?,0000847-2,frequency,"Psoriatic arthritis affects an estimated 24 in 10,000 people.  Between 5 and 10 percent of people with psoriasis develop psoriatic arthritis, according to most estimates. Some studies suggest a figure as high as 30 percent. Psoriasis itself is a common disorder, affecting approximately 2 to 3 percent of the population worldwide.",psoriatic arthritis,0000847,GHR,https://ghr.nlm.nih.gov/condition/psoriatic-arthritis,C0003872,T047,Disorders
What are the genetic changes related to psoriatic arthritis ?,0000847-3,genetic changes,"The specific cause of psoriatic arthritis is unknown. Its signs and symptoms result from excessive inflammation in and around the joints. Inflammation occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight microbial invaders and facilitate tissue repair. When this has been accomplished, the body ordinarily stops the inflammatory response to prevent damage to its own cells and tissues. Mechanical stress on the joints, such as occurs in movement, may result in an excessive inflammatory response in people with psoriatic arthritis. The reasons for this excessive inflammatory response are unclear.  Researchers have identified changes in several genes that may influence the risk of developing psoriatic arthritis. The most well-studied of these genes belong to a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Each HLA gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. Variations of several HLA genes seem to affect the risk of developing psoriatic arthritis, as well as the type, severity, and progression of the condition.  Variations in several other genes have also been associated with psoriatic arthritis. Many of these genes are thought to play roles in immune system function. However, variations in these genes probably make only a small contribution to the overall risk of developing psoriatic arthritis. Other genetic and environmental factors are also likely to influence a person's chances of developing this disorder.",psoriatic arthritis,0000847,GHR,https://ghr.nlm.nih.gov/condition/psoriatic-arthritis,C0003872,T047,Disorders
Is psoriatic arthritis inherited ?,0000847-4,inheritance,This condition has an unknown inheritance pattern. Approximately 40 percent of affected individuals have at least one close family member with psoriasis or psoriatic arthritis.,psoriatic arthritis,0000847,GHR,https://ghr.nlm.nih.gov/condition/psoriatic-arthritis,C0003872,T047,Disorders
What are the treatments for psoriatic arthritis ?,0000847-5,treatment,"These resources address the diagnosis or management of psoriatic arthritis:  - American Society for Surgery of the Hand  - Genetic Testing Registry: Psoriatic arthritis, susceptibility to  - The Johns Hopkins Arthritis Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",psoriatic arthritis,0000847,GHR,https://ghr.nlm.nih.gov/condition/psoriatic-arthritis,C0003872,T047,Disorders
What is (are) pulmonary alveolar microlithiasis ?,0000848-1,information,"Pulmonary alveolar microlithiasis is a disorder in which many tiny fragments (microliths) of a compound called calcium phosphate gradually accumulate in the small air sacs (alveoli) located throughout the lungs. These deposits eventually cause widespread damage to the alveoli and surrounding lung tissue (interstitial lung disease) that leads to breathing problems. People with this disorder can develop a persistent cough and difficulty breathing (dyspnea), especially during physical exertion. Affected individuals may also experience chest pain that worsens when coughing, sneezing, or taking deep breaths.  Pulmonary alveolar microlithiasis is usually diagnosed before age 40. Often the disorder is discovered before symptoms develop, when medical imaging is done for other reasons. The condition typically worsens slowly over many years, although some affected individuals have signs and symptoms that remain stable for long periods of time.  People with pulmonary alveolar microlithiasis can also develop calcium phosphate deposits in other organs and tissues of the body, including the kidneys, gallbladder, testes, and the valve that connects a large blood vessel called the aorta with the heart (the aortic valve). In rare cases, affected individuals have complications related to accumulation of these deposits, such as a narrowing (stenosis) of the aortic valve that can impede normal blood flow.",pulmonary alveolar microlithiasis,0000848,GHR,https://ghr.nlm.nih.gov/condition/pulmonary-alveolar-microlithiasis,C0155912,T047,Disorders
How many people are affected by pulmonary alveolar microlithiasis ?,0000848-2,frequency,"Pulmonary alveolar microlithiasis is a rare disorder; its prevalence is unknown. About 600 affected individuals have been described in the medical literature, of whom about a quarter are of Turkish descent. The remainder come from populations worldwide.",pulmonary alveolar microlithiasis,0000848,GHR,https://ghr.nlm.nih.gov/condition/pulmonary-alveolar-microlithiasis,C0155912,T047,Disorders
What are the genetic changes related to pulmonary alveolar microlithiasis ?,0000848-3,genetic changes,"Pulmonary alveolar microlithiasis is caused by mutations in the SLC34A2 gene. This gene provides instructions for making a protein called the type IIb sodium-phosphate cotransporter, which plays a role in the regulation of phosphate levels (phosphate homeostasis). Although this protein can be found in several organs and tissues in the body, it is located mainly in the lungs, specifically in cells in the alveoli called alveolar type II cells. These cells produce and recycle surfactant, which is a mixture of certain phosphate-containing fats (called phospholipids) and proteins that lines the lung tissue and makes breathing easy.  The recycling of surfactant releases phosphate into the alveoli. Research suggests that the type IIb sodium-phosphate cotransporter normally helps clear this phosphate. SLC34A2 gene mutations are thought to impair the activity of the type IIb sodium-phosphate cotransporter, resulting in the accumulation of phosphate in the alveoli. The accumulated phosphate forms the microliths that cause the signs and symptoms of pulmonary alveolar microlithiasis.",pulmonary alveolar microlithiasis,0000848,GHR,https://ghr.nlm.nih.gov/condition/pulmonary-alveolar-microlithiasis,C0155912,T047,Disorders
Is pulmonary alveolar microlithiasis inherited ?,0000848-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",pulmonary alveolar microlithiasis,0000848,GHR,https://ghr.nlm.nih.gov/condition/pulmonary-alveolar-microlithiasis,C0155912,T047,Disorders
What are the treatments for pulmonary alveolar microlithiasis ?,0000848-5,treatment,These resources address the diagnosis or management of pulmonary alveolar microlithiasis:  - Genetic Testing Registry: Pulmonary alveolar microlithiasis  - MedlinePlus Health Topic: Oxygen Therapy  - MedlinePlus Health Topic: Pulmonary Rehabilitation  - National Jewish Health: Interstitial Lung Disease  - Rare Diseases Clinical Research Network: Rare Lung Disease Consortium   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,pulmonary alveolar microlithiasis,0000848,GHR,https://ghr.nlm.nih.gov/condition/pulmonary-alveolar-microlithiasis,C0155912,T047,Disorders
What is (are) pulmonary arterial hypertension ?,0000849-1,information,"Pulmonary arterial hypertension is a progressive disorder characterized by abnormally high blood pressure (hypertension) in the pulmonary artery, the blood vessel that carries blood from the heart to the lungs. Pulmonary arterial hypertension is one form of a broader condition known as pulmonary hypertension. Pulmonary hypertension occurs when most of the very small arteries throughout the lungs narrow in diameter, which increases the resistance to blood flow through the lungs. To overcome the increased resistance, blood pressure increases in the pulmonary artery and in the right ventricle of the heart, which is the chamber that pumps blood into the pulmonary artery. Ultimately, the increased blood pressure can damage the right ventricle of the heart.  Signs and symptoms of pulmonary arterial hypertension occur when increased blood pressure cannot fully overcome the elevated resistance. As a result, the flow of oxygenated blood from the lungs to the rest of the body is insufficient. Shortness of breath (dyspnea) during exertion and fainting spells are the most common symptoms of pulmonary arterial hypertension. People with this disorder may experience additional symptoms, particularly as the condition worsens. Other symptoms include dizziness, swelling (edema) of the ankles or legs, chest pain, and a rapid heart rate.",pulmonary arterial hypertension,0000849,GHR,https://ghr.nlm.nih.gov/condition/pulmonary-arterial-hypertension,C0152171,T047,Disorders
How many people are affected by pulmonary arterial hypertension ?,0000849-2,frequency,"In the United States, about 1,000 new cases of pulmonary arterial hypertension are diagnosed each year. This disorder is twice as common in females as in males.",pulmonary arterial hypertension,0000849,GHR,https://ghr.nlm.nih.gov/condition/pulmonary-arterial-hypertension,C0152171,T047,Disorders
What are the genetic changes related to pulmonary arterial hypertension ?,0000849-3,genetic changes,"Mutations in the BMPR2 gene are the most common genetic cause of pulmonary arterial hypertension. This gene plays a role in regulating the number of cells in certain tissues. Researchers suggest that a mutation in this gene promotes cell division or prevents cell death, resulting in an overgrowth of cells in small arteries throughout the lungs. As a result, these arteries narrow in diameter, which increases the resistance to blood flow. Blood pressure in the pulmonary artery and the right ventricle of the heart increases to overcome the increased resistance to blood flow.  Mutations in several additional genes have also been found to cause pulmonary arterial hypertension, but they are much less common causes of the disorder than are BMPR2 gene mutations. Variations in other genes may increase the risk of developing pulmonary arterial hypertension or modify the course of the disease (usually making it more severe). Changes in as-yet-unidentified genes may also be associated with this condition.  Although pulmonary arterial hypertension often occurs on its own, it can also be part of syndromes that affect many parts of the body. For example, this condition is occasionally found in people with systemic scleroderma, systemic lupus erythematosus, critical congenital heart disease, or Down syndrome.  Researchers have also identified nongenetic factors that increase the risk of developing pulmonary arterial hypertension. These include certain drugs used as appetite suppressants and several illegal drugs, such as cocaine and methamphetamine. Pulmonary arterial hypertension is also a rare complication of certain infectious diseases, including HIV and schistosomiasis.",pulmonary arterial hypertension,0000849,GHR,https://ghr.nlm.nih.gov/condition/pulmonary-arterial-hypertension,C0152171,T047,Disorders
Is pulmonary arterial hypertension inherited ?,0000849-4,inheritance,"Pulmonary arterial hypertension is usually sporadic, which means it occurs in individuals with no known family history of the disorder. These non-familial cases are described as idiopathic pulmonary arterial hypertension. About 20 percent of these cases are caused by mutations in one of the genes known to be associated with the disease, but most of the time a causative gene mutation has not been identified.  Inherited cases of this disorder are known as familial pulmonary arterial hypertension. When the condition is inherited, it most often has an autosomal dominant pattern of inheritance, which means one copy of an altered gene in each cell is sufficient to cause the disorder. However, many people with an altered gene never develop pulmonary arterial hypertension; this phenomenon is called reduced penetrance.",pulmonary arterial hypertension,0000849,GHR,https://ghr.nlm.nih.gov/condition/pulmonary-arterial-hypertension,C0152171,T047,Disorders
What are the treatments for pulmonary arterial hypertension ?,0000849-5,treatment,These resources address the diagnosis or management of pulmonary arterial hypertension:  - Gene Review: Gene Review: Heritable Pulmonary Arterial Hypertension  - Genetic Testing Registry: Primary pulmonary hypertension  - Genetic Testing Registry: Primary pulmonary hypertension 2  - Genetic Testing Registry: Primary pulmonary hypertension 3  - Genetic Testing Registry: Primary pulmonary hypertension 4  - MedlinePlus Encyclopedia: Pulmonary hypertension   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,pulmonary arterial hypertension,0000849,GHR,https://ghr.nlm.nih.gov/condition/pulmonary-arterial-hypertension,C0152171,T047,Disorders
What is (are) pulmonary veno-occlusive disease ?,0000850-1,information,"Pulmonary veno-occlusive disease (PVOD) is characterized by the blockage (occlusion) of the blood vessels that carry oxygen-rich (oxygenated) blood from the lungs to the heart (the pulmonary veins). The occlusion is caused by a buildup of abnormal fibrous tissue in the small veins in the lungs, which narrows the vessels and impairs blood flow. Because blood flow through the lungs is difficult, pressure rises in the vessels that carry blood that needs to be oxygenated to the lungs from the heart (the pulmonary arteries). Increased pressure in these vessels is known as pulmonary arterial hypertension.  The problems with blood flow in PVOD also impair the delivery of oxygenated blood to the rest of the body, which leads to the signs and symptoms of the condition. Shortness of breath (dyspnea) and tiredness (fatigue) during exertion are the most common symptoms of this condition. Other common features include dizziness, a lack of energy (lethargy), difficulty breathing when lying down, and a cough that does not go away. As the condition worsens, affected individuals can develop a bluish tint to the skin (cyanosis), chest pains, fainting spells, and an accumulation of fluid in the lungs (pulmonary edema).  Certain features commonly seen in people with PVOD can be identified using a test called a CT scan. One of these features, which is seen in the lungs of affected individuals, is an abnormality described as centrilobular ground-glass opacities. Affected individuals also have abnormal thickening of certain tissues in the lungs, which is described as septal lines. In addition, lymph nodes in the chest (mediastinal lymph nodes) are abnormally enlarged in people with PVOD.  PVOD can begin at any age, and the blood flow problems worsen over time. Because of the increased blood pressure in the pulmonary arteries, the heart must work harder than normal to pump blood to the lungs, which can eventually lead to fatal heart failure. Most people with this severe disorder do not live more than 2 years after diagnosis.",pulmonary veno-occlusive disease,0000850,GHR,https://ghr.nlm.nih.gov/condition/pulmonary-veno-occlusive-disease,C0034091,T047,Disorders
How many people are affected by pulmonary veno-occlusive disease ?,0000850-2,frequency,"The exact prevalence of PVOD is unknown. Many cases are likely misdiagnosed as idiopathic pulmonary arterial hypertension, which is increased blood pressure in the pulmonary arteries without a known cause. Research suggests that 5 to 25 percent of people diagnosed with idiopathic pulmonary arterial hypertension have PVOD. Based on these numbers, PVOD is thought to affect an estimated 1 to 2 per 10 million people.",pulmonary veno-occlusive disease,0000850,GHR,https://ghr.nlm.nih.gov/condition/pulmonary-veno-occlusive-disease,C0034091,T047,Disorders
What are the genetic changes related to pulmonary veno-occlusive disease ?,0000850-3,genetic changes,"The primary genetic cause of PVOD is mutations in the EIF2AK4 gene. Mutations in other genes may cause a small percentage of cases. Other suspected causes of PVOD include viral infection and exposure to toxic chemicals, including certain chemotherapy drugs.  The protein produced from the EIF2AK4 gene helps cells respond appropriately to changes that could damage the cell. For example, when the level of protein building blocks (amino acids) in a cell falls too low, the activity of the EIF2AK4 protein helps reduce the production of other proteins, which conserves amino acids. The EIF2AK4 gene mutations involved in PVOD likely eliminate functional EIF2AK4 protein; however, it is unknown how absence of this protein's function leads to the pulmonary vessel abnormalities that underlie PVOD.",pulmonary veno-occlusive disease,0000850,GHR,https://ghr.nlm.nih.gov/condition/pulmonary-veno-occlusive-disease,C0034091,T047,Disorders
Is pulmonary veno-occlusive disease inherited ?,0000850-4,inheritance,"When caused by mutations in the EIF2AK4 gene, PVOD is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  In contrast, when caused by mutations in another gene, the condition can have an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In these cases, one parent of an affected individual typically has increased blood pressure in the vessels of the lungs.",pulmonary veno-occlusive disease,0000850,GHR,https://ghr.nlm.nih.gov/condition/pulmonary-veno-occlusive-disease,C0034091,T047,Disorders
What are the treatments for pulmonary veno-occlusive disease ?,0000850-5,treatment,These resources address the diagnosis or management of pulmonary veno-occlusive disease:  - Genetic Testing Registry: Pulmonary veno-occlusive disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,pulmonary veno-occlusive disease,0000850,GHR,https://ghr.nlm.nih.gov/condition/pulmonary-veno-occlusive-disease,C0034091,T047,Disorders
What is (are) purine nucleoside phosphorylase deficiency ?,0000851-1,information,"Purine nucleoside phosphorylase deficiency is one of several disorders that damage the immune system and cause severe combined immunodeficiency (SCID). People with SCID lack virtually all immune protection from foreign invaders such as bacteria, viruses, and fungi. Affected individuals are prone to repeated and persistent infections that can be very serious or life-threatening. These infections are often caused by ""opportunistic"" organisms that ordinarily do not cause illness in people with a normal immune system. Infants with SCID typically grow much more slowly than healthy children and experience pneumonia, chronic diarrhea, and widespread skin rashes. Without successful treatment to restore immune function, children with SCID usually do not survive past early childhood.  About two-thirds of individuals with purine nucleoside phosphorylase deficiency have neurological problems, which may include developmental delay, intellectual disability, difficulties with balance and coordination (ataxia), and muscle stiffness (spasticity). People with purine nucleoside phosphorylase deficiency are also at increased risk of developing autoimmune disorders, which occur when the immune system malfunctions and attacks the body's tissues and organs.",purine nucleoside phosphorylase deficiency,0000851,GHR,https://ghr.nlm.nih.gov/condition/purine-nucleoside-phosphorylase-deficiency,C0268125,T047,Disorders
How many people are affected by purine nucleoside phosphorylase deficiency ?,0000851-2,frequency,Purine nucleoside phosphorylase deficiency is rare; only about 70 affected individuals have been identified. This disorder accounts for approximately 4 percent of all SCID cases.,purine nucleoside phosphorylase deficiency,0000851,GHR,https://ghr.nlm.nih.gov/condition/purine-nucleoside-phosphorylase-deficiency,C0268125,T047,Disorders
What are the genetic changes related to purine nucleoside phosphorylase deficiency ?,0000851-3,genetic changes,"Purine nucleoside phosphorylase deficiency is caused by mutations in the PNP gene. The PNP gene provides instructions for making an enzyme called purine nucleoside phosphorylase. This enzyme is found throughout the body but is most active in specialized white blood cells called lymphocytes. These cells protect the body against potentially harmful invaders by making immune proteins called antibodies that tag foreign particles and germs for destruction or by directly attacking virus-infected cells. Lymphocytes are produced in specialized lymphoid tissues including the thymus and lymph nodes and then released into the blood. The thymus is a gland located behind the breastbone; lymph nodes are found throughout the body. Lymphocytes in the blood and in lymphoid tissues make up the immune system.  Purine nucleoside phosphorylase is known as a housekeeping enzyme because it clears away waste molecules that are generated when DNA is broken down. Mutations in the PNP gene reduce or eliminate the activity of purine nucleoside phosphorylase. The resulting excess of waste molecules and further reactions involving them lead to the buildup of a substance called deoxyguanosine triphosphate (dGTP) to levels that are toxic to lymphocytes. Immature lymphocytes in the thymus are particularly vulnerable to a toxic buildup of dGTP, which damages them and triggers their self-destruction (apoptosis). The number of lymphocytes in other lymphoid tissues is also greatly reduced, resulting in the immune deficiency characteristic of purine nucleoside phosphorylase deficiency.",purine nucleoside phosphorylase deficiency,0000851,GHR,https://ghr.nlm.nih.gov/condition/purine-nucleoside-phosphorylase-deficiency,C0268125,T047,Disorders
Is purine nucleoside phosphorylase deficiency inherited ?,0000851-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",purine nucleoside phosphorylase deficiency,0000851,GHR,https://ghr.nlm.nih.gov/condition/purine-nucleoside-phosphorylase-deficiency,C0268125,T047,Disorders
What are the treatments for purine nucleoside phosphorylase deficiency ?,0000851-5,treatment,These resources address the diagnosis or management of purine nucleoside phosphorylase deficiency:  - Baby's First Test: Severe Combined Immunodeficiency  - Genetic Testing Registry: Purine-nucleoside phosphorylase deficiency  - National Marrow Donor Program   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,purine nucleoside phosphorylase deficiency,0000851,GHR,https://ghr.nlm.nih.gov/condition/purine-nucleoside-phosphorylase-deficiency,C0268125,T047,Disorders
What is (are) pyridoxal 5'-phosphate-dependent epilepsy ?,0000852-1,information,"Pyridoxal 5'-phosphate-dependent epilepsy is a condition that involves seizures beginning soon after birth or, in some cases, before birth. The seizures typically involve irregular involuntary muscle contractions (myoclonus), abnormal eye movements, and convulsions. Most babies with this condition are born prematurely and may have a temporary, potentially toxic, increase in lactic acid in the blood (lactic acidosis). Additionally, some infants have a slow heart rate and a lack of oxygen during delivery (fetal distress).  Anticonvulsant drugs, which are usually given to control seizures, are ineffective in people with pyridoxal 5'-phosphate-dependent epilepsy. Instead, individuals with this type of epilepsy are medically treated with large daily doses of pyridoxal 5'-phosphate (a form of vitamin B6). If left untreated, people with this condition can develop severe brain dysfunction (encephalopathy), which can lead to death. Even though seizures can be controlled with pyridoxal 5'-phosphate, neurological problems such as developmental delay and learning disorders may still occur.",pyridoxal 5'-phosphate-dependent epilepsy,0000852,GHR,https://ghr.nlm.nih.gov/condition/pyridoxal-5-phosphate-dependent-epilepsy,C1864723,T047,Disorders
How many people are affected by pyridoxal 5'-phosphate-dependent epilepsy ?,0000852-2,frequency,Pyridoxal 5'-phosphate-dependent epilepsy is a rare condition; approximately 14 cases have been described in the scientific literature.,pyridoxal 5'-phosphate-dependent epilepsy,0000852,GHR,https://ghr.nlm.nih.gov/condition/pyridoxal-5-phosphate-dependent-epilepsy,C1864723,T047,Disorders
What are the genetic changes related to pyridoxal 5'-phosphate-dependent epilepsy ?,0000852-3,genetic changes,"Mutations in the PNPO gene cause pyridoxal 5'-phosphate-dependent epilepsy. The PNPO gene provides instructions for producing an enzyme called pyridoxine 5'-phosphate oxidase. This enzyme is involved in the conversion (metabolism) of vitamin B6 derived from food (in the form of pyridoxine and pyridoxamine) to the active form of vitamin B6 called pyridoxal 5'-phosphate (PLP). PLP is necessary for many processes in the body including protein metabolism and the production of chemicals that transmit signals in the brain (neurotransmitters).  PNPO gene mutations result in a pyridoxine 5'-phosphate oxidase enzyme that is unable to metabolize pyridoxine and pyridoxamine, leading to a deficiency of PLP. A shortage of PLP can disrupt the function of many other proteins and enzymes that need PLP in order to be effective. It is not clear how the lack of PLP affects the brain and leads to the seizures that are characteristic of pyridoxal 5'-phosphate-dependent epilepsy.",pyridoxal 5'-phosphate-dependent epilepsy,0000852,GHR,https://ghr.nlm.nih.gov/condition/pyridoxal-5-phosphate-dependent-epilepsy,C1864723,T047,Disorders
Is pyridoxal 5'-phosphate-dependent epilepsy inherited ?,0000852-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",pyridoxal 5'-phosphate-dependent epilepsy,0000852,GHR,https://ghr.nlm.nih.gov/condition/pyridoxal-5-phosphate-dependent-epilepsy,C1864723,T047,Disorders
What are the treatments for pyridoxal 5'-phosphate-dependent epilepsy ?,0000852-5,treatment,These resources address the diagnosis or management of pyridoxal 5'-phosphate-dependent epilepsy:  - Genetic Testing Registry: Pyridoxal 5'-phosphate-dependent epilepsy  - MedlinePlus Encyclopedia: Lactic acidosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,pyridoxal 5'-phosphate-dependent epilepsy,0000852,GHR,https://ghr.nlm.nih.gov/condition/pyridoxal-5-phosphate-dependent-epilepsy,C1864723,T047,Disorders
What is (are) pyridoxine-dependent epilepsy ?,0000853-1,information,"Pyridoxine-dependent epilepsy is a condition that involves seizures beginning in infancy or, in some cases, before birth. Those affected typically experience prolonged seizures lasting several minutes (status epilepticus). These seizures involve muscle rigidity, convulsions, and loss of consciousness (tonic-clonic seizures). Additional features of pyridoxine-dependent epilepsy include low body temperature (hypothermia), poor muscle tone (dystonia) soon after birth, and irritability before a seizure episode. In rare instances, children with this condition do not have seizures until they are 1 to 3 years old.  Anticonvulsant drugs, which are usually given to control seizures, are ineffective in people with pyridoxine-dependent epilepsy. Instead, people with this type of seizure are medically treated with large daily doses of pyridoxine (a type of vitamin B6 found in food). If left untreated, people with this condition can develop severe brain dysfunction (encephalopathy). Even though seizures can be controlled with pyridoxine, neurological problems such as developmental delay and learning disorders may still occur.",pyridoxine-dependent epilepsy,0000853,GHR,https://ghr.nlm.nih.gov/condition/pyridoxine-dependent-epilepsy,C1849508,T047,Disorders
How many people are affected by pyridoxine-dependent epilepsy ?,0000853-2,frequency,"Pyridoxine-dependent epilepsy occurs in 1 in 100,000 to 700,000 individuals. At least 100 cases have been reported worldwide.",pyridoxine-dependent epilepsy,0000853,GHR,https://ghr.nlm.nih.gov/condition/pyridoxine-dependent-epilepsy,C1849508,T047,Disorders
What are the genetic changes related to pyridoxine-dependent epilepsy ?,0000853-3,genetic changes,"Mutations in the ALDH7A1 gene cause pyridoxine-dependent epilepsy. The ALDH7A1 gene provides instructions for making an enzyme called -aminoadipic semialdehyde (-AASA) dehydrogenase, also known as antiquitin. This enzyme is involved in the breakdown of the protein building block (amino acid) lysine in the brain.  When antiquitin is deficient, a molecule that interferes with vitamin B6 function builds up in various tissues. Pyridoxine plays a role in many processes in the body, such as the breakdown of amino acids and the productions of chemicals that transmit signals in the brain (neurotransmitters). It is unclear how a lack of pyridoxine causes the seizures that are characteristic of this condition.  Some individuals with pyridoxine-dependent epilepsy do not have identified mutations in the ALDH7A1 gene. In these cases, the cause of the condition is unknown.",pyridoxine-dependent epilepsy,0000853,GHR,https://ghr.nlm.nih.gov/condition/pyridoxine-dependent-epilepsy,C1849508,T047,Disorders
Is pyridoxine-dependent epilepsy inherited ?,0000853-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",pyridoxine-dependent epilepsy,0000853,GHR,https://ghr.nlm.nih.gov/condition/pyridoxine-dependent-epilepsy,C1849508,T047,Disorders
What are the treatments for pyridoxine-dependent epilepsy ?,0000853-5,treatment,These resources address the diagnosis or management of pyridoxine-dependent epilepsy:  - Gene Review: Gene Review: Pyridoxine-Dependent Epilepsy  - Genetic Testing Registry: Pyridoxine-dependent epilepsy  - MedlinePlus Encyclopedia: Generalized tonic-clonic seizure   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,pyridoxine-dependent epilepsy,0000853,GHR,https://ghr.nlm.nih.gov/condition/pyridoxine-dependent-epilepsy,C1849508,T047,Disorders
What is (are) pyruvate carboxylase deficiency ?,0000854-1,information,"Pyruvate carboxylase deficiency is an inherited disorder that causes lactic acid and other potentially toxic compounds to accumulate in the blood. High levels of these substances can damage the body's organs and tissues, particularly in the nervous system.  Researchers have identified at least three types of pyruvate carboxylase deficiency, which are distinguished by the severity of their signs and symptoms. Type A, which has been identified mostly in people from North America, has moderately severe symptoms that begin in infancy. Characteristic features include developmental delay and a buildup of lactic acid in the blood (lactic acidosis). Increased acidity in the blood can lead to vomiting, abdominal pain, extreme tiredness (fatigue), muscle weakness, and difficulty breathing. In some cases, episodes of lactic acidosis are triggered by an illness or periods without food (fasting). Children with pyruvate carboxylase deficiency type A typically survive only into early childhood.  Pyruvate carboxylase deficiency type B has life-threatening signs and symptoms that become apparent shortly after birth. This form of the condition has been reported mostly in Europe, particularly France. Affected infants have severe lactic acidosis, a buildup of ammonia in the blood (hyperammonemia), and liver failure. They experience neurological problems including weak muscle tone (hypotonia), abnormal movements, seizures, and coma. Infants with this form of the condition usually survive for less than 3 months after birth.  A milder form of pyruvate carboxylase deficiency, sometimes called type C, has also been described. This type is characterized by slightly increased levels of lactic acid in the blood and minimal signs and symptoms affecting the nervous system.",pyruvate carboxylase deficiency,0000854,GHR,https://ghr.nlm.nih.gov/condition/pyruvate-carboxylase-deficiency,C0034341,T047,Disorders
How many people are affected by pyruvate carboxylase deficiency ?,0000854-2,frequency,"Pyruvate carboxylase deficiency is a rare condition, with an estimated incidence of 1 in 250,000 births worldwide. This disorder appears to be much more common in some Algonkian Indian tribes in eastern Canada.",pyruvate carboxylase deficiency,0000854,GHR,https://ghr.nlm.nih.gov/condition/pyruvate-carboxylase-deficiency,C0034341,T047,Disorders
What are the genetic changes related to pyruvate carboxylase deficiency ?,0000854-3,genetic changes,"Mutations in the PC gene cause pyruvate carboxylase deficiency.  The PC gene provides instructions for making an enzyme called pyruvate carboxylase. This enzyme is active in mitochondria, which are the energy-producing centers within cells. It is involved in several important cellular functions including the generation of glucose, a simple sugar that is the body's main energy source. Pyruvate carboxylase also plays a role in the formation of the protective sheath that surrounds certain nerve cells (myelin) and the production of brain chemicals called neurotransmitters.  Mutations in the PC gene reduce the amount of pyruvate carboxylase in cells or disrupt the enzyme's activity. The missing or altered enzyme cannot carry out its essential role in generating glucose, which impairs the body's ability to make energy in mitochondria. Additionally, a loss of pyruvate carboxylase allows potentially toxic compounds such as lactic acid and ammonia to build up and damage organs and tissues. Researchers suggest that the loss of pyruvate carboxylase function in the nervous system, particularly the role of the enzyme in myelin formation and neurotransmitter production, also contributes to the neurologic features of pyruvate carboxylase deficiency.",pyruvate carboxylase deficiency,0000854,GHR,https://ghr.nlm.nih.gov/condition/pyruvate-carboxylase-deficiency,C0034341,T047,Disorders
Is pyruvate carboxylase deficiency inherited ?,0000854-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",pyruvate carboxylase deficiency,0000854,GHR,https://ghr.nlm.nih.gov/condition/pyruvate-carboxylase-deficiency,C0034341,T047,Disorders
What are the treatments for pyruvate carboxylase deficiency ?,0000854-5,treatment,These resources address the diagnosis or management of pyruvate carboxylase deficiency:  - Gene Review: Gene Review: Pyruvate Carboxylase Deficiency  - Genetic Testing Registry: Pyruvate carboxylase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,pyruvate carboxylase deficiency,0000854,GHR,https://ghr.nlm.nih.gov/condition/pyruvate-carboxylase-deficiency,C0034341,T047,Disorders
What is (are) pyruvate dehydrogenase deficiency ?,0000855-1,information,"Pyruvate dehydrogenase deficiency is characterized by the buildup of a chemical called lactic acid in the body and a variety of neurological problems. Signs and symptoms of this condition usually first appear shortly after birth, and they can vary widely among affected individuals. The most common feature is a potentially life-threatening buildup of lactic acid (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. People with pyruvate dehydrogenase deficiency usually have neurological problems as well. Most have delayed development of mental abilities and motor skills such as sitting and walking. Other neurological problems can include intellectual disability, seizures, weak muscle tone (hypotonia), poor coordination, and difficulty walking. Some affected individuals have abnormal brain structures, such as underdevelopment of the tissue connecting the left and right halves of the brain (corpus callosum), wasting away (atrophy) of the exterior part of the brain known as the cerebral cortex, or patches of damaged tissue (lesions) on some parts of the brain. Because of the severe health effects, many individuals with pyruvate dehydrogenase deficiency do not survive past childhood, although some may live into adolescence or adulthood.",pyruvate dehydrogenase deficiency,0000855,GHR,https://ghr.nlm.nih.gov/condition/pyruvate-dehydrogenase-deficiency,C0034345,T047,Disorders
How many people are affected by pyruvate dehydrogenase deficiency ?,0000855-2,frequency,"Pyruvate dehydrogenase deficiency is believed to be a rare condition; however, its prevalence is unknown.",pyruvate dehydrogenase deficiency,0000855,GHR,https://ghr.nlm.nih.gov/condition/pyruvate-dehydrogenase-deficiency,C0034345,T047,Disorders
What are the genetic changes related to pyruvate dehydrogenase deficiency ?,0000855-3,genetic changes,"The genes involved in pyruvate dehydrogenase deficiency each provide instructions for making a protein that is a component of a group of proteins called the pyruvate dehydrogenase complex. This complex plays an important role in the pathways that convert the energy from food into a form that cells can use. The pyruvate dehydrogenase complex converts a molecule called pyruvate, which is formed from the breakdown of carbohydrates, into another molecule called acetyl-CoA. This conversion is essential to begin the series of chemical reactions that produce energy for cells.  The pyruvate dehydrogenase complex is made up of multiple copies of several enzymes called E1, E2, and E3, each of which performs part of the chemical reaction that converts pyruvate to acetyl-CoA. In addition, other proteins included in the complex ensure its proper function. One of these proteins, E3 binding protein, attaches E3 to the complex and provides the correct structure for the complex to perform its function. Other associated proteins control the activity of the complex: pyruvate dehydrogenase phosphatase turns on (activates) the complex, while pyruvate dehydrogenase kinase turns off (inhibits) the complex.  The E1 enzyme, also called pyruvate dehydrogenase, is composed of four parts (subunits): two alpha subunits (called E1 alpha) and two beta subunits (called E1 beta). Mutations in the gene that provides instructions for making E1 alpha, the PDHA1 gene, are the most common cause of pyruvate dehydrogenase deficiency, accounting for approximately 80 percent of cases. These mutations lead to a shortage of E1 alpha protein or result in an abnormal protein that cannot function properly. A decrease in functional E1 alpha leads to reduced activity of the pyruvate dehydrogenase complex.  Other components of the pyruvate dehydrogenase complex are also involved in pyruvate dehydrogenase deficiency. Mutations in the genes that provide instructions for E1 beta (the PDHB gene), the E2 enzyme (the DLAT gene), E3 binding protein (the PDHX gene), and pyruvate dehydrogenase phosphatase (the PDP1 gene) have been identified in people with this condition. Although it is unclear how mutations in each of these genes affect the complex, reduced functioning of one component of the complex appears to impair the activity of the whole complex. As with PDHA1 gene mutations, changes in these other genes lead to a reduction of pyruvate dehydrogenase complex activity.  With decreased function of this complex, pyruvate builds up and is converted in another chemical reaction to lactic acid. The excess lactic acid causes lactic acidosis in affected individuals. In addition, the production of cellular energy is diminished. The brain, which requires especially large amounts of energy, is severely affected, resulting in the neurological problems associated with pyruvate dehydrogenase deficiency.",pyruvate dehydrogenase deficiency,0000855,GHR,https://ghr.nlm.nih.gov/condition/pyruvate-dehydrogenase-deficiency,C0034345,T047,Disorders
Is pyruvate dehydrogenase deficiency inherited ?,0000855-4,inheritance,"Pyruvate dehydrogenase deficiency can have different inheritance patterns. When the condition is caused by mutations in the PDHA1 gene, it is inherited in an X-linked recessive pattern. The PDHA1 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would usually have to occur in both copies of the gene to cause the disorder. However, in pyruvate dehydrogenase deficiency, one altered copy of the PDHA1 gene is sufficient to cause the disorder, because the X chromosome with the normal copy of the PDHA1 gene is turned off through a process called X-inactivation.  Early in embryonic development in females, one of the two X chromosomes is permanently inactivated in somatic cells (cells other than egg and sperm cells). X-inactivation ensures that females, like males, have only one active copy of the X chromosome in each body cell. Usually X-inactivation occurs randomly, such that each X chromosome is active in about half of the body cells. Sometimes X-inactivation is not random, and one X chromosome is active in more than half of cells. When X-inactivation does not occur randomly, it is called skewed X-inactivation.  Research shows that females with pyruvate dehydrogenase deficiency caused by mutation of the PDHA1 gene have skewed X-inactivation, which results in the inactivation of the X chromosome with the normal copy of the PDHA1 gene in most cells of the body. This skewed X-inactivation causes the chromosome with the mutated PDHA1 gene to be expressed in more than half of cells.  When caused by mutations in the other associated genes, pyruvate dehydrogenase deficiency is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",pyruvate dehydrogenase deficiency,0000855,GHR,https://ghr.nlm.nih.gov/condition/pyruvate-dehydrogenase-deficiency,C0034345,T047,Disorders
What are the treatments for pyruvate dehydrogenase deficiency ?,0000855-5,treatment,These resources address the diagnosis or management of pyruvate dehydrogenase deficiency:  - Genetic Testing Registry: Pyruvate dehydrogenase E1-beta deficiency  - Genetic Testing Registry: Pyruvate dehydrogenase E2 deficiency  - Genetic Testing Registry: Pyruvate dehydrogenase E3-binding protein deficiency  - Genetic Testing Registry: Pyruvate dehydrogenase complex deficiency  - Genetic Testing Registry: Pyruvate dehydrogenase phosphatase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,pyruvate dehydrogenase deficiency,0000855,GHR,https://ghr.nlm.nih.gov/condition/pyruvate-dehydrogenase-deficiency,C0034345,T047,Disorders
What is (are) pyruvate kinase deficiency ?,0000856-1,information,"Pyruvate kinase deficiency is an inherited disorder that affects red blood cells, which carry oxygen to the body's tissues. People with this disorder have a condition known as chronic hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely, resulting in a shortage of red blood cells (anemia). Specifically, pyruvate kinase deficiency is a common cause of a type of inherited hemolytic anemia called hereditary nonspherocytic hemolytic anemia. In hereditary nonspherocytic hemolytic anemia, the red blood cells do not assume a spherical shape as they do in some other forms of hemolytic anemia.  Chronic hemolytic anemia can lead to unusually pale skin (pallor), yellowing of the eyes and skin (jaundice), extreme tiredness (fatigue), shortness of breath (dyspnea), and a rapid heart rate (tachycardia). An enlarged spleen (splenomegaly), an excess of iron in the blood, and small pebble-like deposits in the gallbladder or bile ducts (gallstones) are also common in this disorder.  In people with pyruvate kinase deficiency, hemolytic anemia and associated complications may range from mild to severe. Some affected individuals have few or no symptoms. Severe cases can be life-threatening in infancy, and such affected individuals may require regular blood transfusions to survive. The symptoms of this disorder may get worse during an infection or pregnancy.",pyruvate kinase deficiency,0000856,GHR,https://ghr.nlm.nih.gov/condition/pyruvate-kinase-deficiency,C0340968,T047,Disorders
How many people are affected by pyruvate kinase deficiency ?,0000856-2,frequency,"Pyruvate kinase deficiency is the most common inherited cause of nonspherocytic hemolytic anemia. More than 500 affected families have been identified, and studies suggest that the disorder may be underdiagnosed because mild cases may not be identified.  Pyruvate kinase deficiency is found in all ethnic groups. Its prevalence has been estimated at 1 in 20,000 people of European descent. It is more common in the Old Order Amish population of Pennsylvania.",pyruvate kinase deficiency,0000856,GHR,https://ghr.nlm.nih.gov/condition/pyruvate-kinase-deficiency,C0340968,T047,Disorders
What are the genetic changes related to pyruvate kinase deficiency ?,0000856-3,genetic changes,"Pyruvate kinase deficiency is caused by mutations in the PKLR gene. The PKLR gene is active in the liver and in red blood cells, where it provides instructions for making an enzyme called pyruvate kinase. The pyruvate kinase enzyme is involved in a critical energy-producing process known as glycolysis. During glycolysis, the simple sugar glucose is broken down to produce adenosine triphosphate (ATP), the cell's main energy source.  PKLR gene mutations result in reduced pyruvate kinase enzyme function, causing a shortage of ATP in red blood cells and increased levels of other molecules produced earlier in the glycolysis process. The abnormal red blood cells are gathered up by the spleen and destroyed, causing hemolytic anemia and an enlarged spleen. A shortage of red blood cells to carry oxygen throughout the body leads to fatigue, pallor, and shortness of breath. Iron and a molecule called bilirubin are released when red blood cells are destroyed, resulting in an excess of these substances circulating in the blood. Excess bilirubin in the blood causes jaundice and increases the risk of developing gallstones.  Pyruvate kinase deficiency may also occur as an effect of other blood diseases, such as leukemia. These cases are called secondary pyruvate kinase deficiency and are not inherited.",pyruvate kinase deficiency,0000856,GHR,https://ghr.nlm.nih.gov/condition/pyruvate-kinase-deficiency,C0340968,T047,Disorders
Is pyruvate kinase deficiency inherited ?,0000856-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",pyruvate kinase deficiency,0000856,GHR,https://ghr.nlm.nih.gov/condition/pyruvate-kinase-deficiency,C0340968,T047,Disorders
What are the treatments for pyruvate kinase deficiency ?,0000856-5,treatment,These resources address the diagnosis or management of pyruvate kinase deficiency:  - Cincinnati Children's Hospital Medical Center: Hemolytic Anemia  - Genetic Testing Registry: Pyruvate kinase deficiency of red cells  - Johns Hopkins Medicine: Hemolytic Anemia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,pyruvate kinase deficiency,0000856,GHR,https://ghr.nlm.nih.gov/condition/pyruvate-kinase-deficiency,C0340968,T047,Disorders
What is (are) Rabson-Mendenhall syndrome ?,0000857-1,information,"Rabson-Mendenhall syndrome is a rare disorder characterized by severe insulin resistance, a condition in which the body's tissues and organs do not respond properly to the hormone insulin. Insulin normally helps regulate blood sugar levels by controlling how much sugar (in the form of glucose) is passed from the bloodstream into cells to be used as energy. In people with Rabson-Mendenhall syndrome, insulin resistance impairs blood sugar regulation and ultimately leads to a condition called diabetes mellitus, in which blood sugar levels can become dangerously high.  Severe insulin resistance in people with Rabson-Mendenhall syndrome affects the development of many parts of the body. Affected individuals are unusually small starting before birth, and infants experience failure to thrive, which means they do not grow and gain weight at the expected rate. Additional features of the condition that become apparent early in life include a lack of fatty tissue under the skin (subcutaneous fat); wasting (atrophy) of muscles; dental abnormalities; excessive body hair growth (hirsutism); multiple cysts on the ovaries in females; and enlargement of the nipples, genitalia, kidneys, heart, and other organs. Most affected individuals also have a skin condition called acanthosis nigricans, in which the skin in body folds and creases becomes thick, dark, and velvety. Distinctive facial features in people with Rabson-Mendenhall syndrome include prominent, widely spaced eyes; a broad nose; and large, low-set ears.  Rabson-Mendenhall syndrome is one of a group of related conditions described as inherited severe insulin resistance syndromes. These disorders, which also include Donohue syndrome and type A insulin resistance syndrome, are considered part of a spectrum. Rabson-Mendenhall syndrome is intermediate in severity between Donohue syndrome (which is usually fatal before age 2) and type A insulin resistance syndrome (which is often not diagnosed until adolescence). People with Rabson-Mendenhall syndrome develop signs and symptoms early in life and live into their teens or twenties. Death usually results from complications related to diabetes mellitus, such as a toxic buildup of acids called ketones in the body (diabetic ketoacidosis).",Rabson-Mendenhall syndrome,0000857,GHR,https://ghr.nlm.nih.gov/condition/rabson-mendenhall-syndrome,C0271695,T047,Disorders
How many people are affected by Rabson-Mendenhall syndrome ?,0000857-2,frequency,Rabson-Mendenhall syndrome is estimated to affect less than 1 per million people worldwide. Several dozen cases have been reported in the medical literature.,Rabson-Mendenhall syndrome,0000857,GHR,https://ghr.nlm.nih.gov/condition/rabson-mendenhall-syndrome,C0271695,T047,Disorders
What are the genetic changes related to Rabson-Mendenhall syndrome ?,0000857-3,genetic changes,"Rabson-Mendenhall syndrome results from mutations in the INSR gene. This gene provides instructions for making a protein called an insulin receptor, which is found in many types of cells. Insulin receptors are embedded in the outer membrane surrounding the cell, where they attach (bind) to insulin circulating in the bloodstream. This binding triggers signaling pathways that influence many cell functions.  The INSR gene mutations that cause Rabson-Mendenhall syndrome reduce the number of insulin receptors that reach the cell membrane or diminish the function of these receptors. Although insulin is present in the bloodstream, without enough functional receptors it is less able to exert its effects on cells and tissues. This severe resistance to the effects of insulin impairs blood sugar regulation and affects many aspects of development in people with Rabson-Mendenhall syndrome.",Rabson-Mendenhall syndrome,0000857,GHR,https://ghr.nlm.nih.gov/condition/rabson-mendenhall-syndrome,C0271695,T047,Disorders
Is Rabson-Mendenhall syndrome inherited ?,0000857-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Rabson-Mendenhall syndrome,0000857,GHR,https://ghr.nlm.nih.gov/condition/rabson-mendenhall-syndrome,C0271695,T047,Disorders
What are the treatments for Rabson-Mendenhall syndrome ?,0000857-5,treatment,These resources address the diagnosis or management of Rabson-Mendenhall syndrome:  - Genetic Testing Registry: Pineal hyperplasia AND diabetes mellitus syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Rabson-Mendenhall syndrome,0000857,GHR,https://ghr.nlm.nih.gov/condition/rabson-mendenhall-syndrome,C0271695,T047,Disorders
What is (are) RAPADILINO syndrome ?,0000858-1,information,"RAPADILINO syndrome is a rare condition that involves many parts of the body. Bone development is especially affected, causing many of the characteristic features of the condition.  Most affected individuals have underdevelopment or absence of the bones in the forearms and the thumbs, which are known as radial ray malformations. The kneecaps (patellae) can also be underdeveloped or absent. Other features include an opening in the roof of the mouth (cleft palate) or a high arched palate; a long, slender nose; and dislocated joints.  Many infants with RAPADILINO syndrome have difficulty feeding and experience diarrhea and vomiting. The combination of impaired bone development and feeding problems leads to slow growth and short stature in affected individuals.  Some individuals with RAPADILINO syndrome have harmless light brown patches of skin that resemble a skin finding known as caf-au-lait spots. In addition, people with RAPADILINO syndrome have a slightly increased risk of developing a type of bone cancer known as osteosarcoma or a blood-related cancer called lymphoma. In individuals with RAPADILINO syndrome, osteosarcoma most often develops during childhood or adolescence, and lymphoma typically develops in young adulthood.  The condition name is an acronym for the characteristic features of the disorder: RA for radial ray malformations, PA for patella and palate abnormalities, DI for diarrhea and dislocated joints, LI for limb abnormalities and little size, and NO for slender nose and normal intelligence.  The varied signs and symptoms of RAPADILINO syndrome overlap with features of other disorders, namely Baller-Gerold syndrome and Rothmund-Thomson syndrome. These syndromes are also characterized by radial ray defects, skeletal abnormalities, and slow growth. All of these conditions can be caused by mutations in the same gene. Based on these similarities, researchers are investigating whether Baller-Gerold syndrome, Rothmund-Thomson syndrome, and RAPADILINO syndrome are separate disorders or part of a single syndrome with overlapping signs and symptoms.",RAPADILINO syndrome,0000858,GHR,https://ghr.nlm.nih.gov/condition/rapadilino-syndrome,C1849453,T047,Disorders
How many people are affected by RAPADILINO syndrome ?,0000858-2,frequency,"RAPADILINO syndrome is a rare condition, although its worldwide prevalence is unknown. The condition was first identified in Finland, where it affects an estimated 1 in 75,000 individuals, although it has since been found in other regions.",RAPADILINO syndrome,0000858,GHR,https://ghr.nlm.nih.gov/condition/rapadilino-syndrome,C1849453,T047,Disorders
What are the genetic changes related to RAPADILINO syndrome ?,0000858-3,genetic changes,"Mutations in the RECQL4 gene cause RAPADILINO syndrome. This gene provides instructions for making one member of a protein family called RecQ helicases. Helicases are enzymes that bind to DNA and temporarily unwind the two spiral strands (double helix) of the DNA molecule. This unwinding is necessary for copying (replicating) DNA in preparation for cell division and for repairing damaged DNA. The RECQL4 protein helps stabilize genetic information in the body's cells and plays a role in replicating and repairing DNA.  The most common RECQL4 gene mutation involved in RAPADILINO syndrome causes the RECQL4 protein to be pieced together incorrectly. This genetic change results in the production of a protein that is missing a region called exon 7 and is unable to act as a helicase. The loss of helicase function may prevent normal DNA replication and repair, causing widespread damage to a person's genetic information over time. These changes may result in the accumulation of DNA errors and cell death, although it is unclear exactly how RECQL4 gene mutations lead to the specific features of RAPADILINO syndrome.",RAPADILINO syndrome,0000858,GHR,https://ghr.nlm.nih.gov/condition/rapadilino-syndrome,C1849453,T047,Disorders
Is RAPADILINO syndrome inherited ?,0000858-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",RAPADILINO syndrome,0000858,GHR,https://ghr.nlm.nih.gov/condition/rapadilino-syndrome,C1849453,T047,Disorders
What are the treatments for RAPADILINO syndrome ?,0000858-5,treatment,These resources address the diagnosis or management of RAPADILINO syndrome:  - Genetic Testing Registry: Rapadilino syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,RAPADILINO syndrome,0000858,GHR,https://ghr.nlm.nih.gov/condition/rapadilino-syndrome,C1849453,T047,Disorders
What is (are) rapid-onset dystonia parkinsonism ?,0000859-1,information,"Rapid-onset dystonia parkinsonism is a rare movement disorder. ""Rapid-onset"" refers to the abrupt appearance of signs and symptoms over a period of hours to days. Dystonia is a condition characterized by involuntary, sustained muscle contractions. Parkinsonism can include tremors, unusually slow movement (bradykinesia), rigidity, an inability to hold the body upright and balanced (postural instability), and a shuffling walk that can cause recurrent falls.  Rapid-onset dystonia parkinsonism causes movement abnormalities that can make it difficult to walk, talk, and carry out other activities of daily life. In this disorder, dystonia affects the arms and legs, causing muscle cramping and spasms. Facial muscles are often affected, resulting in problems with speech and swallowing. The movement abnormalities associated with rapid-onset dystonia parkinsonism tend to begin near the top of the body and move downward, first affecting the facial muscles, then the arms, and finally the legs.  The signs and symptoms of rapid-onset dystonia parkinsonism most commonly appear in adolescence or young adulthood. In some affected individuals, signs and symptoms can be triggered by an infection, physical stress (such as prolonged exercise), emotional stress, or alcohol consumption. The signs and symptoms tend to stabilize within about a month, but they typically do not improve much after that. In some people with this condition, the movement abnormalities abruptly worsen during a second episode several years later.  Some people with rapid-onset dystonia parkinsonism have been diagnosed with anxiety, social phobias, depression, and seizures. It is unclear whether these disorders are related to the genetic changes that cause rapid-onset dystonia parkinsonism.",rapid-onset dystonia parkinsonism,0000859,GHR,https://ghr.nlm.nih.gov/condition/rapid-onset-dystonia-parkinsonism,C1868681,T047,Disorders
How many people are affected by rapid-onset dystonia parkinsonism ?,0000859-2,frequency,"Rapid-onset dystonia parkinsonism appears to be a rare disorder, although its prevalence is unknown. It has been diagnosed in individuals and families from the United States, Europe, and Korea.",rapid-onset dystonia parkinsonism,0000859,GHR,https://ghr.nlm.nih.gov/condition/rapid-onset-dystonia-parkinsonism,C1868681,T047,Disorders
What are the genetic changes related to rapid-onset dystonia parkinsonism ?,0000859-3,genetic changes,"Rapid-onset dystonia parkinsonism is caused by mutations in the ATP1A3 gene. This gene provides instructions for making one part of a larger protein called Na+/K+ ATPase, also known as the sodium pump. This protein is critical for the normal function of nerve cells (neurons) in the brain. It transports charged atoms (ions) into and out of neurons, which is an essential part of the signaling process that controls muscle movement.  Mutations in the ATP1A3 gene reduce the activity of the Na+/K+ ATPase or make the protein unstable. Studies suggest that the defective protein is unable to transport ions normally, which disrupts the electrical activity of neurons in the brain. However, it is unclear how a malfunctioning Na+/K+ ATPase causes the movement abnormalities characteristic of rapid-onset dystonia parkinsonism.  In some people with rapid-onset dystonia parkinsonism, no mutation in the ATP1A3 gene has been identified. The genetic cause of the disorder is unknown in these individuals. Researchers believe that mutations in at least one other gene, which has not been identified, can cause this disorder.",rapid-onset dystonia parkinsonism,0000859,GHR,https://ghr.nlm.nih.gov/condition/rapid-onset-dystonia-parkinsonism,C1868681,T047,Disorders
Is rapid-onset dystonia parkinsonism inherited ?,0000859-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered ATP1A3 gene in each cell is sufficient to cause the disorder.  In most cases, an affected person inherits a mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  Not everyone who has an ATP1A3 mutation will ultimately develop the signs and symptoms of rapid-onset dystonia parkinsonism. It is unclear why some people with a gene mutation develop movement abnormalities and others do not.",rapid-onset dystonia parkinsonism,0000859,GHR,https://ghr.nlm.nih.gov/condition/rapid-onset-dystonia-parkinsonism,C1868681,T047,Disorders
What are the treatments for rapid-onset dystonia parkinsonism ?,0000859-5,treatment,These resources address the diagnosis or management of rapid-onset dystonia parkinsonism:  - Gene Review: Gene Review: Rapid-Onset Dystonia-Parkinsonism  - Genetic Testing Registry: Dystonia 12   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,rapid-onset dystonia parkinsonism,0000859,GHR,https://ghr.nlm.nih.gov/condition/rapid-onset-dystonia-parkinsonism,C1868681,T047,Disorders
What is (are) recombinant 8 syndrome ?,0000860-1,information,"Recombinant 8 syndrome is a condition that involves heart and urinary tract abnormalities, moderate to severe intellectual disability, and a distinctive facial appearance. The characteristic facial features include a wide, square face; a thin upper lip; a downturned mouth; a small chin (micrognathia); wide-set eyes (hypertelorism); and low-set or unusually shaped ears. People with recombinant 8 syndrome may have overgrowth of the gums (gingival hyperplasia) and abnormal tooth development. Males with this condition frequently have undescended testes (cryptorchidism). Some affected individuals have recurrent ear infections (otitis media) or hearing loss. Many children with recombinant 8 syndrome do not survive past early childhood, usually due to complications related to their heart abnormalities.",recombinant 8 syndrome,0000860,GHR,https://ghr.nlm.nih.gov/condition/recombinant-8-syndrome,C0795822,T047,Disorders
How many people are affected by recombinant 8 syndrome ?,0000860-2,frequency,Recombinant 8 syndrome is a rare condition; its exact incidence is unknown. Most people with this condition are descended from a Hispanic population originating in the San Luis Valley area of southern Colorado and northern New Mexico. Recombinant 8 syndrome is also called San Luis Valley syndrome. Only a few cases outside this population have been found.,recombinant 8 syndrome,0000860,GHR,https://ghr.nlm.nih.gov/condition/recombinant-8-syndrome,C0795822,T047,Disorders
What are the genetic changes related to recombinant 8 syndrome ?,0000860-3,genetic changes,Recombinant 8 syndrome is caused by a rearrangement of chromosome 8 that results in a deletion of a piece of the short (p) arm and a duplication of a piece of the long (q) arm. The deletion and duplication result in the recombinant 8 chromosome. The signs and symptoms of recombinant 8 syndrome are related to the loss and addition of genetic material on these regions of chromosome 8. Researchers are working to determine which genes are involved in the deletion and duplication on chromosome 8.,recombinant 8 syndrome,0000860,GHR,https://ghr.nlm.nih.gov/condition/recombinant-8-syndrome,C0795822,T047,Disorders
Is recombinant 8 syndrome inherited ?,0000860-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the recombinant chromosome 8 in each cell is sufficient to cause the disorder.  Most people with recombinant 8 syndrome have at least one parent with a change in chromosome 8 called an inversion. An inversion involves the breakage of a chromosome in two places; the resulting piece of DNA is reversed and reinserted into the chromosome. Genetic material is typically not lost as a result of this inversion in chromosome 8, so people usually do not have any related health problems. However, genetic material can be lost or duplicated when inversions are being passed to the next generation. People with this chromosome 8 inversion are at of risk having a child with recombinant 8 syndrome.",recombinant 8 syndrome,0000860,GHR,https://ghr.nlm.nih.gov/condition/recombinant-8-syndrome,C0795822,T047,Disorders
What are the treatments for recombinant 8 syndrome ?,0000860-5,treatment,These resources address the diagnosis or management of recombinant 8 syndrome:  - Genetic Testing Registry: Recombinant chromosome 8 syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,recombinant 8 syndrome,0000860,GHR,https://ghr.nlm.nih.gov/condition/recombinant-8-syndrome,C0795822,T047,Disorders
What is (are) recurrent hydatidiform mole ?,0000861-1,information,"Recurrent hydatidiform mole occurs when women have at least two abnormal pregnancies described as hydatidiform moles. A hydatidiform mole occurs early in pregnancy when an embryo does not fully develop and the placenta develops abnormally. The placenta is a solid structure in the uterus that normally provides nutrients to a growing fetus. If a hydatidiform mole occurs once, it is known a sporadic hydatidiform mole; if it happens again, the condition is known as recurrent hydatidiform mole.  A hydatidiform mole often causes vaginal bleeding in the first trimester of the pregnancy. In an ultrasound examination, the abnormal placenta appears as numerous small sacs, often described as resembling a bunch of grapes. In some cases, the ultrasound shows no fetus, umbilical cord, or amniotic sac (a fluid-filled sac that normally surrounds the fetus).  Hydatidiform moles are not naturally discharged from the body and must be surgically removed, typically by the end of the first trimester. After removal, there is up to a 20 percent risk that any tissue left behind (persistent mole) will continue to grow and become a cancerous tumor called an invasive mole. The invasive mole can transform into a different form of cancer called gestational choriocarcinoma that can spread (metastasize) to other tissues such as the liver, lungs, or brain.",recurrent hydatidiform mole,0000861,GHR,https://ghr.nlm.nih.gov/condition/recurrent-hydatidiform-mole,C0278796,T191,Disorders
How many people are affected by recurrent hydatidiform mole ?,0000861-2,frequency,"Hydatidiform moles occur in 1 in 600 to 1,000 pregnancies in western countries and are more common in developing countries. One to six percent of previously affected women will have a recurrent hydatidiform mole.",recurrent hydatidiform mole,0000861,GHR,https://ghr.nlm.nih.gov/condition/recurrent-hydatidiform-mole,C0278796,T191,Disorders
What are the genetic changes related to recurrent hydatidiform mole ?,0000861-3,genetic changes,"Mutations in the NLRP7 or KHDC3L gene can cause recurrent hydatidiform mole, with NLRP7 gene mutations being the most common cause.  Within egg cells (oocytes), both the NLRP7 and KHDC3L proteins are thought to play a role in turning off (inactivating) certain genes based on which parent the copy of the gene came from, a phenomenon known as genomic imprinting. For most genes, both copies of the gene (one copy inherited from each parent) are active in all cells. For a small subset of genes, however, only one of the two copies is active; for some of these genes, the copy from the father is normally active, while for others, the copy from the mother is normally active. The NLRP7 and KHDC3L proteins are likely involved in imprinting multiple maternal genes in oocytes, ensuring that they will be inactive in the developing embryo; the corresponding paternal genes are active.  NLRP7 or KHDC3L gene mutations result in the production of proteins with impaired function. As a result, multiple genes that contribute to a developing embryo are not imprinted properly, leading to abnormal gene activity (expression) in all pregnancies. Because many genes that would normally be inactive are instead active, embryonic development is impaired, resulting in a hydatidiform mole.  The NLRP7 protein has also been found to play a role in cell growth and division (proliferation) and cell maturation (differentiation). Research suggests that the NLRP7 protein plays an additional role in immune responses by regulating the release of an immune protein called interleukin-1 beta. Normally, the immune system would recognize a hydatidiform mole as a non-growing pregnancy or foreign tissue and signal the body to remove it. Because the impaired NLRP7 protein slows interleukin-1 beta release, the body cannot trigger an immune response to the abnormal pregnancy. Instead, the hydatidiform mole remains in the body. The cause of the retention of the pregnancy in women with KHDC3L gene mutations is unclear.  In some cases of recurrent hydatidiform mole, no mutations in either of these genes have been identified. In these instances, the cause of the condition is unknown.  When there is only a single instance of hydatidiform mole, it is often caused by abnormal fertilization of an egg. In sporadic hydatidiform mole, the embryo either receives genetic information only from sperm cells because the egg has no DNA-containing nucleus, or the embryo receives too much genetic information because two sperm cells fertilized one egg.",recurrent hydatidiform mole,0000861,GHR,https://ghr.nlm.nih.gov/condition/recurrent-hydatidiform-mole,C0278796,T191,Disorders
Is recurrent hydatidiform mole inherited ?,0000861-4,inheritance,"This condition is often inherited in an autosomal recessive pattern, which means a woman has to have mutations in both copies of the gene in each of her cells to have recurrent hydatidiform mole pregnancies. Because the mutations are present in all of a woman's cells, including oocytes (which need these genes to promote normal embryonic development), a hydatidiform mole will develop in each pregnancy that occurs with those egg cells.",recurrent hydatidiform mole,0000861,GHR,https://ghr.nlm.nih.gov/condition/recurrent-hydatidiform-mole,C0278796,T191,Disorders
What are the treatments for recurrent hydatidiform mole ?,0000861-5,treatment,"These resources address the diagnosis or management of recurrent hydatidiform mole:  - American Cancer Society: Signs and Symptoms of Gestational Trophoblastic Disease  - Genetic Testing Registry: Hydatidiform mole  - Genetic Testing Registry: Hydatidiform mole, recurrent, 2  - MedlinePlus Encyclopedia: Choriocarcinoma  - MedlinePlus Encyclopedia: Hydatidiform Mole   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",recurrent hydatidiform mole,0000861,GHR,https://ghr.nlm.nih.gov/condition/recurrent-hydatidiform-mole,C0278796,T191,Disorders
What is (are) Refsum disease ?,0000862-1,information,"Refsum disease is an inherited condition that causes vision loss, absence of the sense of smell (anosmia), and a variety of other signs and symptoms.  The vision loss associated with Refsum disease is caused by an eye disorder called retinitis pigmentosa. This disorder affects the retina, the light-sensitive layer at the back of the eye. Vision loss occurs as the light-sensing cells of the retina gradually deteriorate. The first sign of retinitis pigmentosa is usually a loss of night vision, which often becomes apparent in childhood. Over a period of years, the disease disrupts side (peripheral) vision and may eventually lead to blindness.  Vision loss and anosmia are seen in almost everyone with Refsum disease, but other signs and symptoms vary. About one-third of affected individuals are born with bone abnormalities of the hands and feet. Features that appear later in life can include progressive muscle weakness and wasting; poor balance and coordination (ataxia); hearing loss; and dry, scaly skin (ichthyosis). Additionally, some people with Refsum disease develop an abnormal heart rhythm (arrhythmia) and related heart problems that can be life-threatening.",Refsum disease,0000862,GHR,https://ghr.nlm.nih.gov/condition/refsum-disease,C0034960,T047,Disorders
How many people are affected by Refsum disease ?,0000862-2,frequency,"The prevalence of Refsum disease is unknown, although the condition is thought to be uncommon.",Refsum disease,0000862,GHR,https://ghr.nlm.nih.gov/condition/refsum-disease,C0034960,T047,Disorders
What are the genetic changes related to Refsum disease ?,0000862-3,genetic changes,"More than 90 percent of all cases of Refsum disease result from mutations in the PHYH gene. The remaining cases are caused by mutations in a gene called PEX7.  The signs and symptoms of Refsum disease result from the abnormal buildup of a type of fatty acid called phytanic acid. This substance is obtained from the diet, particularly from beef and dairy products. It is normally broken down through a process called alpha-oxidation, which occurs in cell structures called peroxisomes. These sac-like compartments contain enzymes that process many different substances, such as fatty acids and certain toxic compounds.  Mutations in either the PHYH or PEX7 gene disrupt the usual functions of peroxisomes, including the breakdown of phytanic acid. As a result, this substance builds up in the body's tissues. The accumulation of phytanic acid is toxic to cells, although it is unclear how an excess of this substance affects vision and smell and causes the other specific features of Refsum disease.",Refsum disease,0000862,GHR,https://ghr.nlm.nih.gov/condition/refsum-disease,C0034960,T047,Disorders
Is Refsum disease inherited ?,0000862-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Refsum disease,0000862,GHR,https://ghr.nlm.nih.gov/condition/refsum-disease,C0034960,T047,Disorders
What are the treatments for Refsum disease ?,0000862-5,treatment,These resources address the diagnosis or management of Refsum disease:  - Gene Review: Gene Review: Refsum Disease  - Gene Review: Gene Review: Retinitis Pigmentosa Overview  - Genetic Testing Registry: Phytanic acid storage disease  - MedlinePlus Encyclopedia: Retinitis Pigmentosa   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Refsum disease,0000862,GHR,https://ghr.nlm.nih.gov/condition/refsum-disease,C0034960,T047,Disorders
What is (are) REN-related kidney disease ?,0000863-1,information,"REN-related kidney disease is an inherited condition that affects kidney function. This condition causes slowly progressive kidney disease that usually becomes apparent during childhood. As this condition progresses, the kidneys become less able to filter fluids and waste products from the body, resulting in kidney failure. Individuals with REN-related kidney disease typically require dialysis (to remove wastes from the blood) or a kidney transplant between ages 40 and 70.  People with REN-related kidney disease sometimes have low blood pressure. They may also have mildly increased levels of potassium in their blood (hyperkalemia). In childhood, people with REN-related kidney disease develop a shortage of red blood cells (anemia), which can cause pale skin, weakness, and fatigue. In this disorder, anemia is usually mild and begins to improve during adolescence.  Many individuals with this condition develop high blood levels of a waste product called uric acid. Normally, the kidneys remove uric acid from the blood and transfer it to urine so it can be excreted from the body. In REN-related kidney disease, the kidneys are unable to remove uric acid from the blood effectively. A buildup of uric acid can cause gout, which is a form of arthritis resulting from uric acid crystals in the joints. Individuals with REN-related kidney disease may begin to experience the signs and symptoms of gout during their twenties.",REN-related kidney disease,0000863,GHR,https://ghr.nlm.nih.gov/condition/ren-related-kidney-disease,C0022658,T047,Disorders
How many people are affected by REN-related kidney disease ?,0000863-2,frequency,REN-related kidney disease is a rare condition. At least three families with this condition have been identified.,REN-related kidney disease,0000863,GHR,https://ghr.nlm.nih.gov/condition/ren-related-kidney-disease,C0022658,T047,Disorders
What are the genetic changes related to REN-related kidney disease ?,0000863-3,genetic changes,"Mutations in the REN gene cause REN-related kidney disease. This gene provides instructions for making a protein called renin that is produced in the kidneys. Renin plays an important role in regulating blood pressure and water levels in the body.  Mutations in the REN gene that cause REN-related kidney disease result in the production of an abnormal protein that is toxic to the cells that normally produce renin. These kidney cells gradually die off, which causes progressive kidney disease.",REN-related kidney disease,0000863,GHR,https://ghr.nlm.nih.gov/condition/ren-related-kidney-disease,C0022658,T047,Disorders
Is REN-related kidney disease inherited ?,0000863-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",REN-related kidney disease,0000863,GHR,https://ghr.nlm.nih.gov/condition/ren-related-kidney-disease,C0022658,T047,Disorders
What are the treatments for REN-related kidney disease ?,0000863-5,treatment,"These resources address the diagnosis or management of REN-related kidney disease:  - Gene Review: Gene Review: Autosomal Dominant Tubulointerstitial Kidney Disease, REN-Related (ADTKD-REN)  - Genetic Testing Registry: Hyperuricemic nephropathy, familial juvenile, 2  - MedlinePlus Encyclopedia: Hyperkalemia  - MedlinePlus Encyclopedia: Renin   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",REN-related kidney disease,0000863,GHR,https://ghr.nlm.nih.gov/condition/ren-related-kidney-disease,C0022658,T047,Disorders
What is (are) renal coloboma syndrome ?,0000864-1,information,"Renal coloboma syndrome (also known as papillorenal syndrome) is a condition that primarily affects kidney (renal) and eye development. People with this condition typically have kidneys that are small and underdeveloped (hypoplastic), which can lead to end-stage renal disease (ESRD). This serious disease occurs when the kidneys are no longer able to filter fluids and waste products from the body effectively. It has been estimated that approximately ten percent of children with hypoplastic kidneys may have renal coloboma syndrome. The kidney problems can affect one or both kidneys.  Additionally, people with renal coloboma syndrome may have a malformation in the optic nerve, a structure that carries information from the eye to the brain. Optic nerve malformations are sometimes associated with a gap or hole (coloboma) in the light-sensitive tissue at the back of the eye (the retina). The vision problems caused by these abnormalities can vary depending on the size and location of the malformation. Some people have no visual problems, while others may have severely impaired vision.  Less common features of renal coloboma syndrome include backflow of urine from the bladder (vesicoureteral reflux), multiple kidney cysts, loose joints, and mild hearing loss.",renal coloboma syndrome,0000864,GHR,https://ghr.nlm.nih.gov/condition/renal-coloboma-syndrome,C1852759,T019,Disorders
How many people are affected by renal coloboma syndrome ?,0000864-2,frequency,The prevalence of renal coloboma syndrome is unknown; at least 60 cases have been reported in the scientific literature.,renal coloboma syndrome,0000864,GHR,https://ghr.nlm.nih.gov/condition/renal-coloboma-syndrome,C1852759,T019,Disorders
What are the genetic changes related to renal coloboma syndrome ?,0000864-3,genetic changes,"Renal coloboma syndrome is caused by mutations in the PAX2 gene. The PAX2 gene provides instructions for making a protein that is involved in the early development of the eyes, ears, brain and spinal cord (central nervous system), kidneys, and genital tract. The PAX2 protein attaches (binds) to specific regions of DNA and regulates the activity of other genes. On the basis of this role, the PAX2 protein is called a transcription factor. After birth, the PAX2 protein is thought to protect against cell death during periods of cellular stress.  Mutations in the PAX2 gene lead to the production of a nonfunctional PAX2 protein that is unable to aid in development, causing incomplete formation of certain tissues. Why the kidneys and eyes are specifically affected by PAX2 gene mutations is unclear.  Approximately half of those affected with renal coloboma syndrome do not have an identified mutation in the PAX2 gene. In these cases, the cause of the disorder is unknown.",renal coloboma syndrome,0000864,GHR,https://ghr.nlm.nih.gov/condition/renal-coloboma-syndrome,C1852759,T019,Disorders
Is renal coloboma syndrome inherited ?,0000864-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",renal coloboma syndrome,0000864,GHR,https://ghr.nlm.nih.gov/condition/renal-coloboma-syndrome,C1852759,T019,Disorders
What are the treatments for renal coloboma syndrome ?,0000864-5,treatment,These resources address the diagnosis or management of renal coloboma syndrome:  - Gene Review: Gene Review: Renal Coloboma Syndrome  - Genetic Testing Registry: Renal coloboma syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,renal coloboma syndrome,0000864,GHR,https://ghr.nlm.nih.gov/condition/renal-coloboma-syndrome,C1852759,T019,Disorders
What is (are) renal hypouricemia ?,0000865-1,information,"Renal hypouricemia is a kidney (renal) disorder that results in a reduced amount of uric acid in the blood. Uric acid is a byproduct of certain normal chemical reactions in the body. In the bloodstream it acts as an antioxidant, protecting cells from the damaging effects of unstable molecules called free radicals. However, having too much uric acid in the body is toxic, so excess uric acid is removed from the body in urine.  People with renal hypouricemia have little to no uric acid in their blood; they release an excessive amount of it in the urine. In many affected individuals, renal hypouricemia causes no signs or symptoms. However, some people with this condition develop kidney problems. After strenuous exercise, they can develop exercise-induced acute kidney injury, which causes pain in their sides and lower back as well as nausea and vomiting that can last several hours.  Because an excessive amount of uric acid passes through the kidneys to be excreted in urine in people with renal hypouricemia, they have an increased risk of developing kidney stones (nephrolithiasis) formed from uric acid crystals. These uric acid stones can damage the kidneys and lead to episodes of blood in the urine (hematuria). Rarely, people with renal hypouricemia develop life-threatening kidney failure.",renal hypouricemia,0000865,GHR,https://ghr.nlm.nih.gov/condition/renal-hypouricemia,C0473219,T047,Disorders
How many people are affected by renal hypouricemia ?,0000865-2,frequency,"The prevalence of renal hypouricemia is unknown; at least 150 affected individuals have been described in the scientific literature. This condition is thought to be most prevalent in Asian countries such as Japan and South Korea, although affected individuals have been found in Europe. Renal hypouricemia is likely underdiagnosed because it does not cause any symptoms in many affected individuals.",renal hypouricemia,0000865,GHR,https://ghr.nlm.nih.gov/condition/renal-hypouricemia,C0473219,T047,Disorders
What are the genetic changes related to renal hypouricemia ?,0000865-3,genetic changes,"Mutations in the SLC22A12 or SLC2A9 gene cause renal hypouricemia. These genes provide instructions for making proteins called urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9), respectively. These proteins are found in the kidneys, specifically in structures called proximal tubules. These structures help to reabsorb needed nutrients, water, and other materials into the blood and excrete unneeded substances into the urine. Within the proximal tubules, both the URAT1 and GLUT9 proteins reabsorb uric acid into the bloodstream or release it into the urine, depending on the body's needs. Most uric acid that is filtered through the kidneys is reabsorbed into the bloodstream; about 10 percent is released into urine.  Mutations that cause renal hypouricemia lead to the production of URAT1 or GLUT9 protein with a reduced ability to reabsorb uric acid into the bloodstream. Instead, large amounts of uric acid are released in the urine. The specific cause of the signs and symptoms of renal hypouricemia is unclear. Researchers suspect that when additional uric acid is produced during exercise and passed through the kidneys, it could lead to tissue damage. Alternatively, without the antioxidant properties of uric acid, free radicals could cause tissue damage in the kidneys. Another possibility is that other substances are prevented from being reabsorbed along with uric acid; accumulation of these substances in the kidneys could cause tissue damage. It is likely that individuals with renal hypouricemia who have mild or no symptoms have enough protein function to reabsorb a sufficient amount of uric acid into the bloodstream to prevent severe kidney problems.",renal hypouricemia,0000865,GHR,https://ghr.nlm.nih.gov/condition/renal-hypouricemia,C0473219,T047,Disorders
Is renal hypouricemia inherited ?,0000865-4,inheritance,"This condition is typically inherited in an autosomal recessive pattern, which means both copies of the SLC22A12 or SLC2A9 gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they usually do not show signs and symptoms of the condition.  Sometimes, individuals with one SLC2A9 gene mutation in each cell have reduced levels of uric acid. The levels usually are not as low as they are in people who have mutations in both copies of the gene, and they often do not cause any signs or symptoms. Rarely, people who carry one copy of the mutated gene will develop uric acid kidney stones.",renal hypouricemia,0000865,GHR,https://ghr.nlm.nih.gov/condition/renal-hypouricemia,C0473219,T047,Disorders
What are the treatments for renal hypouricemia ?,0000865-5,treatment,These resources address the diagnosis or management of renal hypouricemia:  - Genetic Testing Registry: Familial renal hypouricemia  - Genetic Testing Registry: Renal hypouricemia 2  - KidsHealth from Nemours: Blood Test: Uric Acid  - MedlinePlus Encyclopedia: Uric Acid--Blood   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,renal hypouricemia,0000865,GHR,https://ghr.nlm.nih.gov/condition/renal-hypouricemia,C0473219,T047,Disorders
What is (are) renal tubular acidosis with deafness ?,0000866-1,information,"Renal tubular acidosis with deafness is a disorder characterized by kidney (renal) problems and hearing loss. The kidneys normally filter fluid and waste products from the body and remove them in urine; however, in people with this disorder, the kidneys do not remove enough acidic compounds from the body. Instead, the acids are absorbed back into the bloodstream, and the blood becomes too acidic. This chemical imbalance, called metabolic acidosis, can result in a range of signs and symptoms that vary in severity. Metabolic acidosis often causes nausea, vomiting, and dehydration; affected infants tend to have problems feeding and gaining weight (failure to thrive). Most children and adults with renal tubular acidosis with deafness have short stature, and many develop kidney stones.  The metabolic acidosis that occurs in renal tubular acidosis with deafness may also lead to softening and weakening of the bones, called rickets in children and osteomalacia in adults. This bone disorder is characterized by bone pain, bowed legs, and difficulty walking. Rarely, people with renal tubular acidosis with deafness have episodes of hypokalemic paralysis, a condition that causes extreme muscle weakness associated with low levels of potassium in the blood (hypokalemia).  In people with renal tubular acidosis with deafness, hearing loss caused by changes in the inner ear (sensorineural hearing loss) usually begins between childhood and young adulthood, and gradually gets worse. An inner ear abnormality affecting both ears occurs in most people with this disorder. This feature, which is called enlarged vestibular aqueduct, can be seen with medical imaging. The vestibular aqueduct is a bony canal that runs from the inner ear into the temporal bone of the skull and toward the brain. The relationship between enlarged vestibular aqueduct and hearing loss is unclear. In renal tubular acidosis with deafness, enlarged vestibular aqueduct typically occurs in individuals whose hearing loss begins in childhood.",renal tubular acidosis with deafness,0000866,GHR,https://ghr.nlm.nih.gov/condition/renal-tubular-acidosis-with-deafness,C0001122,T046,Disorders
How many people are affected by renal tubular acidosis with deafness ?,0000866-2,frequency,Renal tubular acidosis with deafness is a rare disorder; its prevalence is unknown.,renal tubular acidosis with deafness,0000866,GHR,https://ghr.nlm.nih.gov/condition/renal-tubular-acidosis-with-deafness,C0001122,T046,Disorders
What are the genetic changes related to renal tubular acidosis with deafness ?,0000866-3,genetic changes,"Renal tubular acidosis with deafness is caused by mutations in the ATP6V1B1 or ATP6V0A4 gene. These genes provide instructions for making proteins that are parts (subunits) of a large protein complex known as vacuolar H+-ATPase (V-ATPase). V-ATPases are a group of similar complexes that act as pumps to move positively charged hydrogen atoms (protons) across membranes. Because acids are substances that can ""donate"" protons to other molecules, this movement of protons helps regulate the relative acidity (pH) of cells and their surrounding environment. Tight control of pH is necessary for most biological reactions to proceed properly.  The V-ATPase that includes subunits produced from the ATP6V1B1 and ATP6V0A4 genes is found in the inner ear and in nephrons, which are the functional structures within the kidneys. Each nephron consists of two parts: a renal corpuscle (also known as a glomerulus) that filters the blood, and a renal tubule that reabsorbs substances that are needed and eliminates unneeded substances in urine. The V-ATPase is involved in regulating the amount of acid that is removed from the blood into the urine, and also in maintaining the proper pH of the fluid in the inner ear (endolymph).  Mutations in the ATP6V1B1 or ATP6V0A4 gene impair the function of the V-ATPase complex and reduce the body's capability to control the pH of the blood and the fluid in the inner ear, resulting in the signs and symptoms of renal tubular acidosis with deafness.",renal tubular acidosis with deafness,0000866,GHR,https://ghr.nlm.nih.gov/condition/renal-tubular-acidosis-with-deafness,C0001122,T046,Disorders
Is renal tubular acidosis with deafness inherited ?,0000866-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",renal tubular acidosis with deafness,0000866,GHR,https://ghr.nlm.nih.gov/condition/renal-tubular-acidosis-with-deafness,C0001122,T046,Disorders
What are the treatments for renal tubular acidosis with deafness ?,0000866-5,treatment,These resources address the diagnosis or management of renal tubular acidosis with deafness:  - Genetic Testing Registry: Renal tubular acidosis with progressive nerve deafness  - MedlinePlus Encyclopedia: Audiometry  - MedlinePlus Encyclopedia: Kidney Function Tests   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,renal tubular acidosis with deafness,0000866,GHR,https://ghr.nlm.nih.gov/condition/renal-tubular-acidosis-with-deafness,C0001122,T046,Disorders
What is (are) renal tubular dysgenesis ?,0000867-1,information,"Renal tubular dysgenesis is a severe kidney disorder characterized by abnormal development of the kidneys before birth. In particular, kidney structures called proximal tubules are absent or underdeveloped. These structures help to reabsorb needed nutrients, water, and other materials into the blood and excrete everything else into the urine. Without functional proximal tubules, the kidneys cannot produce urine (a condition called anuria).  Fetal urine is the major component of the fluid that surrounds the fetus (amniotic fluid), and anuria leads to decreased amniotic fluid levels (oligohydramnios). Amniotic fluid helps cushion and protect the fetus and plays a role in the development of many organs, including the lungs. Oligohydramnios causes a set of abnormalities called the Potter sequence, which includes distinctive facial features such as a flattened nose and large, low-set ears; excess skin; inward- and upward-turning feet (clubfeet); and underdeveloped lungs.  Renal tubular dysgenesis also causes severe low blood pressure (hypotension). In addition, bone development in the skull is abnormal in some affected individuals, causing a large space between the bones of the skull (fontanels).  As a result of the serious health problems caused by renal tubular dysgenesis, affected individuals usually die before birth, are stillborn, or die soon after birth from respiratory failure. Rarely, with treatment, affected individuals survive into childhood. Their blood pressure usually normalizes, but they quickly develop chronic kidney disease, which is characterized by reduced kidney function that worsens over time.",renal tubular dysgenesis,0000867,GHR,https://ghr.nlm.nih.gov/condition/renal-tubular-dysgenesis,C0266313,T047,Disorders
How many people are affected by renal tubular dysgenesis ?,0000867-2,frequency,"Renal tubular dysgenesis is a rare disorder, but its prevalence is unknown.",renal tubular dysgenesis,0000867,GHR,https://ghr.nlm.nih.gov/condition/renal-tubular-dysgenesis,C0266313,T047,Disorders
What are the genetic changes related to renal tubular dysgenesis ?,0000867-3,genetic changes,"Mutations in the ACE, AGT, AGTR1, or REN gene can cause renal tubular dysgenesis. These genes are involved in the renin-angiotensin system, which regulates blood pressure and the balance of fluids and salts in the body and plays a role in kidney development before birth.  The renin-angiotensin system consists of several proteins that are involved in a series of steps to produce a protein called angiotensin II. In the first step, the renin protein (produced from the REN gene) converts a protein called angiotensinogen (produced from the AGT gene) to angiotensin I. In the next step, angiotensin-converting enzyme (produced from the ACE gene) converts angiotensin I to angiotensin II. Angiotensin II attaches (binds) to the angiotensin II receptor type 1 (AT1 receptor; produced from the AGTR1 gene), stimulating chemical signaling.  By binding to the AT1 receptor, angiotensin II causes blood vessels to narrow (constrict), which results in increased blood pressure. This protein also stimulates production of the hormone aldosterone, which triggers the absorption of salt and water by the kidneys. The increased amount of fluid in the body also increases blood pressure. Proper blood pressure, which delivers oxygen to the developing tissues during fetal growth, is required for normal development of the kidneys (particularly of the proximal tubules) and other tissues.  Mutations in the ACE, AGT, AGTR1, or REN gene impair the production or function of angiotensin II, leading to a nonfunctional renin-angiotensin system. Without this system, the kidneys cannot control blood pressure. Because of low blood pressure, the flow of blood is reduced (hypoperfusion), and the fetal tissues do not get enough oxygen during development. As a result, kidney development is impaired, leading to the features of renal tubular dysgenesis. Hypoperfusion also causes the skull abnormalities found in individuals with this condition.  Medications that block the activity of the angiotensin-converting enzyme or the AT1 receptor are used to treat high blood pressure. Because these drugs impair the renin-angiotensin system, they can cause an acquired (non-inherited) form of renal tubular dysgenesis in fetuses of pregnant women who take them. Acquired renal tubular dysgenesis can also result from other conditions that cause renal hypoperfusion during fetal development. These include heart problems, congenital hemochromatosis, and a complication that can occur in twin pregnancies called twin-to-twin transfusion syndrome.",renal tubular dysgenesis,0000867,GHR,https://ghr.nlm.nih.gov/condition/renal-tubular-dysgenesis,C0266313,T047,Disorders
Is renal tubular dysgenesis inherited ?,0000867-4,inheritance,"Renal tubular dysgenesis is inherited in an autosomal recessive pattern, which means both copies of the affected gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",renal tubular dysgenesis,0000867,GHR,https://ghr.nlm.nih.gov/condition/renal-tubular-dysgenesis,C0266313,T047,Disorders
What are the treatments for renal tubular dysgenesis ?,0000867-5,treatment,These resources address the diagnosis or management of renal tubular dysgenesis:  - Genetic Testing Registry: Renal dysplasia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,renal tubular dysgenesis,0000867,GHR,https://ghr.nlm.nih.gov/condition/renal-tubular-dysgenesis,C0266313,T047,Disorders
What is (are) Renpenning syndrome ?,0000868-1,information,"Renpenning syndrome is a disorder that almost exclusively affects males, causing developmental delay, moderate to severe intellectual disability, and distinctive physical features. Individuals with Renpenning syndrome typically have short stature and a small head size (microcephaly). Facial features characteristic of this disorder include a long, narrow face; outside corners of the eyes that point upward (upslanting palpebral fissures); a long, bulbous nose with a low-hanging separation between the nostrils (overhanging columella); a shortened space between the nose and mouth (philtrum); and cup-shaped ears. Males with Renpenning syndrome generally have small testes. Seizures and wasting away (atrophy) of muscles used for movement (skeletal muscles) may also occur in this disorder.  About 20 percent of individuals with Renpenning syndrome also have other features, which may include a gap or split in structures that make up the eye (coloboma), an opening in the roof of the mouth (cleft palate), heart abnormalities, or malformations of the anus.  Certain combinations of the features that often occur in Renpenning syndrome are sometimes called by other names, such as Golabi-Ito-Hall syndrome or Sutherland-Haan syndrome. However, all these syndromes, which have the same genetic cause, are now generally grouped under the term Renpenning syndrome.",Renpenning syndrome,0000868,GHR,https://ghr.nlm.nih.gov/condition/renpenning-syndrome,C0039082,T047,Disorders
How many people are affected by Renpenning syndrome ?,0000868-2,frequency,Renpenning syndrome is a rare disorder; its prevalence is unknown. More than 60 affected individuals in at least 15 families have been identified.,Renpenning syndrome,0000868,GHR,https://ghr.nlm.nih.gov/condition/renpenning-syndrome,C0039082,T047,Disorders
What are the genetic changes related to Renpenning syndrome ?,0000868-3,genetic changes,"Renpenning syndrome is caused by mutations in the PQBP1 gene. This gene provides instructions for making a protein called polyglutamine-binding protein 1. This protein attaches (binds) to stretches of multiple copies of a protein building block (amino acid) called glutamine in certain other proteins.  While the specific function of polyglutamine-binding protein 1 is not well understood, it is believed to play a role in processing and transporting RNA, a chemical cousin of DNA that serves as the genetic blueprint for the production of proteins.  In nerve cells (neurons) such as those in the brain, polyglutamine-binding protein 1 is found in structures called RNA granules. These granules allow the transport and storage of RNA within the cell. The RNA is held within the granules until the genetic information it carries is translated to produce proteins or until cellular signals or environmental factors trigger the RNA to be degraded. Through these mechanisms, polyglutamine-binding protein 1 is thought to help control the way genetic information is used (gene expression) in neurons. This control is important for normal brain development.  Most of the mutations in the PQBP1 gene that cause Renpenning syndrome result in an abnormally short polyglutamine-binding protein 1. The function of a shortened or otherwise abnormal protein is likely impaired and interferes with normal gene expression in neurons, resulting in abnormal development of the brain and the signs and symptoms of Renpenning syndrome.",Renpenning syndrome,0000868,GHR,https://ghr.nlm.nih.gov/condition/renpenning-syndrome,C0039082,T047,Disorders
Is Renpenning syndrome inherited ?,0000868-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation typically has to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",Renpenning syndrome,0000868,GHR,https://ghr.nlm.nih.gov/condition/renpenning-syndrome,C0039082,T047,Disorders
What are the treatments for Renpenning syndrome ?,0000868-5,treatment,These resources address the diagnosis or management of Renpenning syndrome:  - Genetic Testing Registry: Renpenning syndrome 1  - Greenwood Genetics Center: X-Linked Intellectual Disability  - Kennedy Krieger Institute: Center for Genetic Disorders of Cognition and Behavior   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Renpenning syndrome,0000868,GHR,https://ghr.nlm.nih.gov/condition/renpenning-syndrome,C0039082,T047,Disorders
What is (are) restless legs syndrome ?,0000869-1,information,"Restless legs syndrome is a neurological condition that causes an irresistible urge to move the legs. The movement is triggered by strange or uncomfortable feelings, often described as crawling, pulling, or itching, deep within both legs. The feelings usually occur while the affected person is sitting or lying down and are worse at night. Movement, such as kicking, stretching, rubbing, or pacing, make the discomfort go away, at least temporarily. The unpleasant feelings and the resulting need to move the legs often make it difficult for an affected person to fall asleep or stay asleep.  The signs and symptoms of restless legs syndrome range from mild to severe; people with mild cases may experience symptoms a few times a month, while those with more severe cases may have symptoms every night. In severe cases, the uncomfortable feelings can affect the arms or other parts of the body in addition to the legs.  Many people with restless legs syndrome also experience uncontrollable, repetitive leg movements that occur while they are sleeping or while relaxed or drowsy. When these movements occur during sleep, they are called periodic limb movements of sleep (PLMS); when they occur while a person is awake, they are called periodic limb movements of wakefulness (PLMW). It is unclear whether PLMS and PLMW are features of restless legs syndrome itself or represent similar, but separate, conditions.  Restless legs syndrome and PLMS can affect the quality and amount of sleep. As a result of these conditions, affected individuals may have difficulty concentrating during the day, and some develop mood swings, depression, or other health problems.  Researchers have described early-onset and late-onset forms of restless legs syndrome. The early-onset form begins before age 45, and sometimes as early as childhood. The signs and symptoms of this form usually worsen slowly with time. The late-onset form begins after age 45, and its signs and symptoms tend to worsen more rapidly.",restless legs syndrome,0000869,GHR,https://ghr.nlm.nih.gov/condition/restless-legs-syndrome,C0035258,T047,Disorders
How many people are affected by restless legs syndrome ?,0000869-2,frequency,"Restless legs syndrome is one of the most common sleep and movement disorders. It affects an estimated 5 to 10 percent of adults and 2 to 4 percent of children in the United States. For unknown reasons, the disorder affects women more often than men. The prevalence of restless legs syndrome increases with age.",restless legs syndrome,0000869,GHR,https://ghr.nlm.nih.gov/condition/restless-legs-syndrome,C0035258,T047,Disorders
What are the genetic changes related to restless legs syndrome ?,0000869-3,genetic changes,"Restless legs syndrome likely results from a combination of genetic and environmental factors, many of which are unknown.  Studies suggest that restless legs syndrome is related to a shortage (deficiency) of iron in certain parts of the brain. Iron is involved in several critical activities in brain cells, including the production of a chemical messenger (neurotransmitter) called dopamine. Among its many functions, dopamine triggers signals within the nervous system that help the brain control physical movement. Researchers believe that malfunction of the dopamine signaling system may underlie the abnormal movements in people with restless legs syndrome. However, it is unclear how iron deficiency is related to abnormal dopamine signaling, or how these changes in the brain lead to the particular signs and symptoms of the condition.  Variations in several genes have been studied as risk factors for restless legs syndrome. Most of these genes are thought to be involved in the development of nerve cells (neurons) before birth. It is unclear whether any of the genes play roles in brain iron levels or in dopamine signaling. Variations in known genes appear to account for only a small percentage of the risk of developing restless legs syndrome. Changes in other genes, which have not been identified, probably also contribute to this complex disorder. Researchers suspect that the early-onset form of restless legs syndrome is more likely than the late-onset form to have a genetic basis.  Nongenetic factors are also thought to play a role in restless legs syndrome. For example, several other disorders increase the risk of developing the condition. These include a life-threatening failure of kidney function called end-stage renal disease, diabetes mellitus, multiple sclerosis, rheumatoid arthritis, and Parkinson disease. People with low iron levels associated with a shortage of red blood cells (anemia) and women who are pregnant are also more likely to develop restless legs syndrome. In these cases, the condition usually improves or goes away when iron levels increase or after the woman gives birth.  Restless legs syndrome can be triggered by medications, including certain drugs used to treat nausea, depression and other mental health disorders, colds and allergies, heart problems, and high blood pressure. Use of caffeine, nicotine, or alcohol can also trigger restless legs syndrome or make the signs and symptoms worse. In these cases, the condition usually improves or goes away once a person stops using these medications or substances.",restless legs syndrome,0000869,GHR,https://ghr.nlm.nih.gov/condition/restless-legs-syndrome,C0035258,T047,Disorders
Is restless legs syndrome inherited ?,0000869-4,inheritance,"The inheritance pattern of restless legs syndrome is usually unclear because many genetic and environmental factors can be involved. The disorder often runs in families: 40 to 90 percent of affected individuals report having at least one affected first-degree relative, such as a parent or sibling, and many families have multiple affected family members. Studies suggest that the early-onset form of the disorder is more likely to run in families than the late-onset form.  In some affected families, restless legs syndrome appears to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance suggests that one copy of an altered gene in each cell is sufficient to cause the disorder. However, the genetic changes associated with restless legs syndrome in these families have not been identified.",restless legs syndrome,0000869,GHR,https://ghr.nlm.nih.gov/condition/restless-legs-syndrome,C0035258,T047,Disorders
What are the treatments for restless legs syndrome ?,0000869-5,treatment,"These resources address the diagnosis or management of restless legs syndrome:  - Agency for Healthcare Research and Quality: Options for Treating Restless Legs Syndrome  - Genetic Testing Registry: Restless legs syndrome, susceptibility to, 8  - National Heart, Lung, and Blood Institute: How is Restless Legs Syndrome Diagnosed?  - National Heart, Lung, and Blood Institute: How is Restless Legs Syndrome Treated?  - Restless Leg Syndrome Foundation: Diagnosis  - Restless Leg Syndrome Foundation: Treatment Options   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",restless legs syndrome,0000869,GHR,https://ghr.nlm.nih.gov/condition/restless-legs-syndrome,C0035258,T047,Disorders
What is (are) retinal arterial macroaneurysm with supravalvular pulmonic stenosis ?,0000870-1,information,"Retinal arterial macroaneurysm with supravalvular pulmonic stenosis (RAMSVPS) is a disorder that affects blood vessels in the eyes and heart. The condition generally becomes apparent in infancy or childhood.  RAMSVPS damages the arteries in the light-sensitive tissue at the back of the eye (the retina). These arteries gradually develop multiple small bulges called beading. Eventually, larger bulges in the blood vessel walls (macroaneurysms) occur. These macroaneurysms can tear (rupture), leading to bleeding that can spread into other areas of the eye and cause vision loss.  People with RAMSVPS also have a heart condition called supravalvular pulmonic stenosis. Pulmonic stenosis is a narrowing that affects the pulmonic valve between the heart and the lungs. The term ""supravalvular"" means that the narrowing occurs just above the valve, in a blood vessel called the pulmonary artery. Supravalvular pulmonic stenosis impairs blood flow into the lungs, where blood normally picks up oxygen for distribution to cells and tissues throughout the body. As a result, less oxygen is carried through the bloodstream, leading to signs and symptoms that include shortness of breath; a rapid heartbeat; fatigue; and swelling in the face, feet, or abdomen.",retinal arterial macroaneurysm with supravalvular pulmonic stenosis,0000870,GHR,https://ghr.nlm.nih.gov/condition/retinal-arterial-macroaneurysm-with-supravalvular-pulmonic-stenosis,C3280205,T047,Disorders
How many people are affected by retinal arterial macroaneurysm with supravalvular pulmonic stenosis ?,0000870-2,frequency,"RAMSVPS is a rare disorder. Only a small number of affected individuals and families, all from Saudi Arabia, have been described in the medical literature.",retinal arterial macroaneurysm with supravalvular pulmonic stenosis,0000870,GHR,https://ghr.nlm.nih.gov/condition/retinal-arterial-macroaneurysm-with-supravalvular-pulmonic-stenosis,C3280205,T047,Disorders
What are the genetic changes related to retinal arterial macroaneurysm with supravalvular pulmonic stenosis ?,0000870-3,genetic changes,"RAMSVPS is caused by a mutation in the IGFBP7 gene. This gene provides instructions for making a protein called insulin-like growth factor-binding protein 7 (IGFBP7). The IGFBP7 protein is active in the lining of blood vessels (the vascular endothelium). It is thought to help stop a pathway called BRAF signaling, which is involved in directing cell growth.  The IGFBP7 gene mutation that causes RAMSVPS results in an abnormally short IGFBP7 protein that does not function properly. Without normally functioning IGFBP7 protein to control BRAF signaling, this signaling is increased. It is unknown how this increase is related to the specific blood vessel abnormalities that occur in RAMSVPS, or why these abnormalities are confined to the eyes and the pulmonary artery. Researchers suggest that differences in normal levels of IGFBP7 protein in various parts of the body or the presence of other proteins with a similar function in different tissues may account for the specific signs and symptoms of this disorder.",retinal arterial macroaneurysm with supravalvular pulmonic stenosis,0000870,GHR,https://ghr.nlm.nih.gov/condition/retinal-arterial-macroaneurysm-with-supravalvular-pulmonic-stenosis,C3280205,T047,Disorders
Is retinal arterial macroaneurysm with supravalvular pulmonic stenosis inherited ?,0000870-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",retinal arterial macroaneurysm with supravalvular pulmonic stenosis,0000870,GHR,https://ghr.nlm.nih.gov/condition/retinal-arterial-macroaneurysm-with-supravalvular-pulmonic-stenosis,C3280205,T047,Disorders
What are the treatments for retinal arterial macroaneurysm with supravalvular pulmonic stenosis ?,0000870-5,treatment,These resources address the diagnosis or management of RAMSVPS:  - Calgary Retina Consultants: Retinal Arterial Macroaneurysm  - Genetic Testing Registry: Retinal arterial macroaneurysm with supravalvular pulmonic stenosis  - MedlinePlus Encyclopedia: Fluorescein Angiography  - University of Rochester Medical Center: Pulmonary Stenosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,retinal arterial macroaneurysm with supravalvular pulmonic stenosis,0000870,GHR,https://ghr.nlm.nih.gov/condition/retinal-arterial-macroaneurysm-with-supravalvular-pulmonic-stenosis,C3280205,T047,Disorders
What is (are) retinitis pigmentosa ?,0000871-1,information,"Retinitis pigmentosa is a group of related eye disorders that cause progressive vision loss. These disorders affect the retina, which is the layer of light-sensitive tissue at the back of the eye. In people with retinitis pigmentosa, vision loss occurs as the light-sensing cells of the retina gradually deteriorate.  The first sign of retinitis pigmentosa is usually a loss of night vision, which becomes apparent in childhood. Problems with night vision can make it difficult to navigate in low light. Later, the disease causes blind spots to develop in the side (peripheral) vision. Over time, these blind spots merge to produce tunnel vision. The disease progresses over years or decades to affect central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. In adulthood, many people with retinitis pigmentosa become legally blind.  The signs and symptoms of retinitis pigmentosa are most often limited to vision loss. When the disorder occurs by itself, it is described as nonsyndromic. Researchers have identified several major types of nonsyndromic retinitis pigmentosa, which are usually distinguished by their pattern of inheritance: autosomal dominant, autosomal recessive, or X-linked.  Less commonly, retinitis pigmentosa occurs as part of syndromes that affect other organs and tissues in the body. These forms of the disease are described as syndromic. The most common form of syndromic retinitis pigmentosa is Usher syndrome, which is characterized by the combination of vision loss and hearing loss beginning early in life. Retinitis pigmentosa is also a feature of several other genetic syndromes, including Bardet-Biedl syndrome; Refsum disease; and neuropathy, ataxia, and retinitis pigmentosa (NARP).",retinitis pigmentosa,0000871,GHR,https://ghr.nlm.nih.gov/condition/retinitis-pigmentosa,C0035334,T047,Disorders
How many people are affected by retinitis pigmentosa ?,0000871-2,frequency,"Retinitis pigmentosa is one of the most common inherited diseases of the retina (retinopathies). It is estimated to affect 1 in 3,500 to 1 in 4,000 people in the United States and Europe.",retinitis pigmentosa,0000871,GHR,https://ghr.nlm.nih.gov/condition/retinitis-pigmentosa,C0035334,T047,Disorders
What are the genetic changes related to retinitis pigmentosa ?,0000871-3,genetic changes,"Mutations in more than 60 genes are known to cause nonsyndromic retinitis pigmentosa. More than 20 of these genes are associated with the autosomal dominant form of the disorder. Mutations in the RHO gene are the most common cause of autosomal dominant retinitis pigmentosa, accounting for 20 to 30 percent of all cases. At least 35 genes have been associated with the autosomal recessive form of the disorder. The most common of these is USH2A; mutations in this gene are responsible for 10 to 15 percent of all cases of autosomal recessive retinitis pigmentosa. Changes in at least six genes are thought to cause the X-linked form of the disorder. Together, mutations in the RPGR and RP2 genes account for most cases of X-linked retinitis pigmentosa.  The genes associated with retinitis pigmentosa play essential roles in the structure and function of specialized light receptor cells (photoreceptors) in the retina. The retina contains two types of photoreceptors, rods and cones. Rods are responsible for vision in low light, while cones provide vision in bright light, including color vision.  Mutations in any of the genes responsible for retinitis pigmentosa lead to a gradual loss of rods and cones in the retina. The progressive degeneration of these cells causes the characteristic pattern of vision loss that occurs in people with retinitis pigmentosa. Rods typically break down before cones, which is why night vision impairment is usually the first sign of the disorder. Daytime vision is disrupted later, as both rods and cones are lost.  Some of the genes associated with retinitis pigmentosa are also associated with other eye diseases, including a condition called cone-rod dystrophy. Cone-rod dystrophy has signs and symptoms similar to those of retinitis pigmentosa. However, cone-rod dystrophy is characterized by deterioration of the cones first, followed by the rods, so daylight and color vision are affected before night vision.",retinitis pigmentosa,0000871,GHR,https://ghr.nlm.nih.gov/condition/retinitis-pigmentosa,C0035334,T047,Disorders
Is retinitis pigmentosa inherited ?,0000871-4,inheritance,"Retinitis pigmentosa often has an autosomal dominant inheritance pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. Most people with autosomal dominant retinitis pigmentosa have an affected parent and other family members with the disorder.  Retinitis pigmentosa can also have an autosomal recessive pattern of inheritance, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  This condition can also be inherited in an X-linked pattern. The genes associated with X-linked retinitis pigmentosa are located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females, (who have two X chromosomes), mutations usually have to occur in both copes of the gene to cause the disorder. However, at least 20 percent of females who carry only one mutated copy of the gene develop retinal degeneration and associated vision loss. In most cases, males experience more severe symptoms of the disorder than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In 10 to 40 percent of all cases of retinitis pigmentosa, only one person in a family is affected. In these families, the disorder is described as simplex. It can be difficult to determine the inheritance pattern of simplex cases because affected individuals may have no affected relatives or may be unaware of other family members with the disease. Simplex cases can also result from a new gene mutation that is not present in other family members.",retinitis pigmentosa,0000871,GHR,https://ghr.nlm.nih.gov/condition/retinitis-pigmentosa,C0035334,T047,Disorders
What are the treatments for retinitis pigmentosa ?,0000871-5,treatment,These resources address the diagnosis or management of retinitis pigmentosa:  - American Foundation for the Blind: Living with Vision Loss  - Foundation Fighting Blindness: Treatment of Retinitis Pigmentosa  - Gene Review: Gene Review: Retinitis Pigmentosa Overview  - Genetic Testing Registry: Retinitis pigmentosa  - RP Fighting Blindness: Treatment of Retinitis Pigmentosa   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,retinitis pigmentosa,0000871,GHR,https://ghr.nlm.nih.gov/condition/retinitis-pigmentosa,C0035334,T047,Disorders
What is (are) retinoblastoma ?,0000872-1,information,"Retinoblastoma is a rare type of eye cancer that usually develops in early childhood, typically before the age of 5. This form of cancer develops in the retina, which is the specialized light-sensitive tissue at the back of the eye that detects light and color.  In most children with retinoblastoma, the disease affects only one eye. However, one out of three children with retinoblastoma develops cancer in both eyes. The most common first sign of retinoblastoma is a visible whiteness in the pupil called ""cat's eye reflex"" or leukocoria. This unusual whiteness is particularly noticeable in photographs taken with a flash. Other signs and symptoms of retinoblastoma include crossed eyes or eyes that do not point in the same direction (strabismus); persistent eye pain, redness, or irritation; and blindness or poor vision in the affected eye(s).  Retinoblastoma is often curable when it is diagnosed early. However, if it is not treated promptly, this cancer can spread beyond the eye to other parts of the body. This advanced form of retinoblastoma can be life-threatening.  When retinoblastoma is associated with a gene mutation that occurs in all of the body's cells, it is known as germinal retinoblastoma. People with this form of retinoblastoma also have an increased risk of developing several other cancers outside the eye. Specifically, they are more likely to develop a cancer of the pineal gland in the brain (pinealoma), a type of bone cancer known as osteosarcoma, cancers of soft tissues such as muscle, and an aggressive form of skin cancer called melanoma.",retinoblastoma,0000872,GHR,https://ghr.nlm.nih.gov/condition/retinoblastoma,C0035335,T191,Disorders
How many people are affected by retinoblastoma ?,0000872-2,frequency,Retinoblastoma is diagnosed in 250 to 350 children per year in the United States. It accounts for about 4 percent of all cancers in children younger than 15 years.,retinoblastoma,0000872,GHR,https://ghr.nlm.nih.gov/condition/retinoblastoma,C0035335,T191,Disorders
What are the genetic changes related to retinoblastoma ?,0000872-3,genetic changes,"Mutations in the RB1 gene are responsible for most cases of retinoblastoma. RB1 is a tumor suppressor gene, which means that it normally regulates cell growth and keeps cells from dividing too rapidly or in an uncontrolled way. Most mutations in the RB1 gene prevent it from making any functional protein, so it is unable to regulate cell division effectively. As a result, certain cells in the retina can divide uncontrollably to form a cancerous tumor. Some studies suggest that additional genetic changes can influence the development of retinoblastoma; these changes may help explain variations in the development and growth of tumors in different people.  A small percentage of retinoblastomas are caused by deletions in the region of chromosome 13 that contains the RB1 gene. Because these chromosomal changes involve several genes in addition to RB1, affected children usually also have intellectual disability, slow growth, and distinctive facial features (such as prominent eyebrows, a short nose with a broad nasal bridge, and ear abnormalities).",retinoblastoma,0000872,GHR,https://ghr.nlm.nih.gov/condition/retinoblastoma,C0035335,T191,Disorders
Is retinoblastoma inherited ?,0000872-4,inheritance,"Researchers estimate that 40 percent of all retinoblastomas are germinal, which means that RB1 mutations occur in all of the body's cells, including reproductive cells (sperm or eggs). People with germinal retinoblastoma may have a family history of the disease, and they are at risk of passing on the mutated RB1 gene to the next generation. The other 60 percent of retinoblastomas are non-germinal, which means that RB1 mutations occur only in the eye and cannot be passed to the next generation.  In germinal retinoblastoma, mutations in the RB1 gene appear to be inherited in an autosomal dominant pattern. Autosomal dominant inheritance suggests that one copy of the altered gene in each cell is sufficient to increase cancer risk. A person with germinal retinoblastoma may inherit an altered copy of the gene from one parent, or the altered gene may be the result of a new mutation that occurs in an egg or sperm cell or just after fertilization. For retinoblastoma to develop, a mutation involving the other copy of the RB1 gene must occur in retinal cells during the person's lifetime. This second mutation usually occurs in childhood, typically leading to the development of retinoblastoma in both eyes.  In the non-germinal form of retinoblastoma, typically only one eye is affected and there is no family history of the disease. Affected individuals are born with two normal copies of the RB1 gene. Then, usually in early childhood, both copies of the RB1 gene in retinal cells acquire mutations or are lost. People with non-germinal retinoblastoma are not at risk of passing these RB1 mutations to their children. However, without genetic testing it can be difficult to tell whether a person with retinoblastoma in one eye has the germinal or the non-germinal form of the disease.",retinoblastoma,0000872,GHR,https://ghr.nlm.nih.gov/condition/retinoblastoma,C0035335,T191,Disorders
What are the treatments for retinoblastoma ?,0000872-5,treatment,These resources address the diagnosis or management of retinoblastoma:  - Gene Review: Gene Review: Retinoblastoma  - Genetic Testing Registry: Retinoblastoma  - Genomics Education Programme (UK)  - MedlinePlus Encyclopedia: Retinoblastoma  - National Cancer Institute: Genetic Testing for Hereditary Cancer Syndromes   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,retinoblastoma,0000872,GHR,https://ghr.nlm.nih.gov/condition/retinoblastoma,C0035335,T191,Disorders
What is (are) retroperitoneal fibrosis ?,0000873-1,information,"Retroperitoneal fibrosis is a disorder in which inflammation and extensive scar tissue (fibrosis) occur in the back of the abdominal cavity, behind (retro-) the membrane that surrounds the organs of the digestive system (the peritoneum). This area is known as the retroperitoneal space. Retroperitoneal fibrosis can occur at any age but appears most frequently between the ages of 40 and 60.  The inflamed tissue characteristic of retroperitoneal fibrosis typically causes gradually increasing pain in the lower abdomen, back, or side. Other symptoms arise from blockage of blood flow to and from various parts of the lower body, due to the development of scar tissue around blood vessels. The fibrosis usually develops first around the aorta, which is the large blood vessel that distributes blood from the heart to the rest of the body. Additional blood vessels including the inferior vena cava, which returns blood from the lower part of the body to the heart, may also be involved. Obstruction of blood flow to and from the legs can result in pain, changes in color, and swelling in these limbs. Impairment of blood flow in the intestines may lead to death (necrosis) of intestinal tissue, severe pain, and excessive bleeding (hemorrhage). In men, reduced blood flow back toward the heart (venous flow) may cause swelling of the scrotum.  Because the kidneys are located in the retroperitoneal space, retroperitoneal fibrosis may result in blockage of the ureters, which are tubes that carry urine from each kidney to the bladder. Such blockages can lead to decreased or absent urine flow and kidney failure. When the kidneys fail, toxic substances build up in the blood and tissues, leading to nausea, vomiting, weight loss, itching, a low number of red blood cells (anemia), and changes in brain function.",retroperitoneal fibrosis,0000873,GHR,https://ghr.nlm.nih.gov/condition/retroperitoneal-fibrosis,C0035357,T046,Disorders
How many people are affected by retroperitoneal fibrosis ?,0000873-2,frequency,"Retroperitoneal fibrosis occurs in 1 in 200,000 to 500,000 people per year. The disorder occurs approximately twice as often in men as it does in women, but the reason for this difference is unclear.",retroperitoneal fibrosis,0000873,GHR,https://ghr.nlm.nih.gov/condition/retroperitoneal-fibrosis,C0035357,T046,Disorders
What are the genetic changes related to retroperitoneal fibrosis ?,0000873-3,genetic changes,"No genes associated with retroperitoneal fibrosis have been identified.  Retroperitoneal fibrosis occasionally occurs with autoimmune disorders, which result when the immune system malfunctions and attacks the body's own organs and tissues. Researchers suggest that the immune system may be involved in the development of retroperitoneal fibrosis. They propose that the immune system may be reacting abnormally to blood vessels damaged by fatty buildup (atherosclerosis) or to certain drugs, infections, or trauma. In many cases, the reason for the abnormal immune system reaction is unknown. Such cases are described as idiopathic.",retroperitoneal fibrosis,0000873,GHR,https://ghr.nlm.nih.gov/condition/retroperitoneal-fibrosis,C0035357,T046,Disorders
Is retroperitoneal fibrosis inherited ?,0000873-4,inheritance,"Most cases of retroperitoneal fibrosis are sporadic, which means that they occur in people with no apparent history of the disorder in their family. In rare cases, the condition has been reported to occur in a few members of the same family, but the inheritance pattern is unknown.",retroperitoneal fibrosis,0000873,GHR,https://ghr.nlm.nih.gov/condition/retroperitoneal-fibrosis,C0035357,T046,Disorders
What are the treatments for retroperitoneal fibrosis ?,0000873-5,treatment,These resources address the diagnosis or management of retroperitoneal fibrosis:  - Johns Hopkins Medicine   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,retroperitoneal fibrosis,0000873,GHR,https://ghr.nlm.nih.gov/condition/retroperitoneal-fibrosis,C0035357,T046,Disorders
What is (are) Rett syndrome ?,0000874-1,information,"Rett syndrome is a brain disorder that occurs almost exclusively in girls. The most common form of the condition is known as classic Rett syndrome. After birth, girls with classic Rett syndrome have 6 to 18 months of apparently normal development before developing severe problems with language and communication, learning, coordination, and other brain functions. Early in childhood, affected girls lose purposeful use of their hands and begin making repeated hand wringing, washing, or clapping motions. They tend to grow more slowly than other children and have a small head size (microcephaly). Other signs and symptoms that can develop include breathing abnormalities, seizures, an abnormal side-to-side curvature of the spine (scoliosis), and sleep disturbances.  Researchers have described several variant or atypical forms of Rett syndrome, which can be milder or more severe than the classic form.",Rett syndrome,0000874,GHR,https://ghr.nlm.nih.gov/condition/rett-syndrome,C0035372,T047,Disorders
How many people are affected by Rett syndrome ?,0000874-2,frequency,"This condition affects an estimated 1 in 8,500 females.",Rett syndrome,0000874,GHR,https://ghr.nlm.nih.gov/condition/rett-syndrome,C0035372,T047,Disorders
What are the genetic changes related to Rett syndrome ?,0000874-3,genetic changes,"Classic Rett syndrome and some variant forms of the condition are caused by mutations in the MECP2 gene. This gene provides instructions for making a protein (MeCP2) that is critical for normal brain function. Although the exact function of the MeCP2 protein is unclear, it is likely involved in maintaining connections (synapses) between nerve cells (neurons). It may also be necessary for the normal function of other types of brain cells.  The MeCP2 protein is thought to help regulate the activity of genes in the brain. This protein may also control the production of different versions of certain proteins in brain cells. Mutations in the MECP2 gene alter the MeCP2 protein or result in the production of less protein, which appears to disrupt the normal function of neurons and other cells in the brain. Specifically, studies suggest that changes in the MeCP2 protein may reduce the activity of certain neurons and impair their ability to communicate with one another. It is unclear how these changes lead to the specific features of Rett syndrome.  Several conditions with signs and symptoms overlapping those of Rett syndrome have been found to result from mutations in other genes. These conditions, including FOXG1 syndrome, were previously thought to be variant forms of Rett syndrome. However, doctors and researchers have identified some important differences between the conditions, so they are now usually considered to be separate disorders.",Rett syndrome,0000874,GHR,https://ghr.nlm.nih.gov/condition/rett-syndrome,C0035372,T047,Disorders
Is Rett syndrome inherited ?,0000874-4,inheritance,"In more than 99 percent of people with Rett syndrome, there is no history of the disorder in their family. Many of these cases result from new mutations in the MECP2 gene.  A few families with more than one affected family member have been described. These cases helped researchers determine that classic Rett syndrome and variants caused by MECP2 gene mutations have an X-linked dominant pattern of inheritance. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. The inheritance is dominant if one copy of the altered gene in each cell is sufficient to cause the condition.  Males with mutations in the MECP2 gene often die in infancy. However, a small number of males with a genetic change involving MECP2 have developed signs and symptoms similar to those of Rett syndrome, including intellectual disability, seizures, and movement problems. In males, this condition is described as MECP2-related severe neonatal encephalopathy.",Rett syndrome,0000874,GHR,https://ghr.nlm.nih.gov/condition/rett-syndrome,C0035372,T047,Disorders
What are the treatments for Rett syndrome ?,0000874-5,treatment,These resources address the diagnosis or management of Rett syndrome:  - Boston Children's Hospital  - Cleveland Clinic  - Gene Review: Gene Review: MECP2-Related Disorders  - Genetic Testing Registry: Rett syndrome  - International Rett Syndrome Foundation: Living with Rett Syndrome  - MedlinePlus Encyclopedia: Rett Syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Rett syndrome,0000874,GHR,https://ghr.nlm.nih.gov/condition/rett-syndrome,C0035372,T047,Disorders
What is (are) rheumatoid arthritis ?,0000875-1,information,"Rheumatoid arthritis is a disease that causes chronic abnormal inflammation, primarily affecting the joints. The most common signs and symptoms are pain, swelling, and stiffness of the joints. Small joints in the hands and feet are involved most often, although larger joints (such as the shoulders, hips, and knees) may become involved later in the disease. Joints are typically affected in a symmetrical pattern; for example, if joints in the hand are affected, both hands tend to be involved. People with rheumatoid arthritis often report that their joint pain and stiffness is worse when getting out of bed in the morning or after a long rest.  Rheumatoid arthritis can also cause inflammation of other tissues and organs, including the eyes, lungs, and blood vessels. Additional signs and symptoms of the condition can include a loss of energy, a low fever, weight loss, and a shortage of red blood cells (anemia). Some affected individuals develop rheumatoid nodules, which are firm lumps of noncancerous tissue that can grow under the skin and elsewhere in the body.  The signs and symptoms of rheumatoid arthritis usually appear in mid- to late adulthood. Many affected people have episodes of symptoms (flares) followed by periods with no symptoms (remissions) for the rest of their lives. In severe cases, affected individuals have continuous health problems related to the disease for many years. The abnormal inflammation can lead to severe joint damage, which limits movement and can cause significant disability.",rheumatoid arthritis,0000875,GHR,https://ghr.nlm.nih.gov/condition/rheumatoid-arthritis,C0003873,T047,Disorders
How many people are affected by rheumatoid arthritis ?,0000875-2,frequency,"Rheumatoid arthritis affects about 1.3 million adults in the United States. Worldwide, it is estimated to occur in up to 1 percent of the population. The disease is two to three times more common in women than in men, which may be related to hormonal factors.",rheumatoid arthritis,0000875,GHR,https://ghr.nlm.nih.gov/condition/rheumatoid-arthritis,C0003873,T047,Disorders
What are the genetic changes related to rheumatoid arthritis ?,0000875-3,genetic changes,"Rheumatoid arthritis probably results from a combination of genetic and environmental factors, many of which are unknown.  Rheumatoid arthritis is classified as an autoimmune disorder, one of a large group of conditions that occur when the immune system attacks the body's own tissues and organs. In people with rheumatoid arthritis, the immune system triggers abnormal inflammation in the membrane that lines the joints (the synovium). When the synovium is inflamed, it causes pain, swelling, and stiffness of the joint. In severe cases, the inflammation also affects the bone, cartilage, and other tissues within the joint, causing more serious damage. Abnormal immune reactions also underlie the features of rheumatoid arthritis affecting other parts of the body.  Variations in dozens of genes have been studied as risk factors for rheumatoid arthritis. Most of these genes are known or suspected to be involved in immune system function. The most significant genetic risk factors for rheumatoid arthritis are variations in human leukocyte antigen (HLA) genes, especially the HLA-DRB1 gene. The proteins produced from HLA genes help the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Changes in other genes appear to have a smaller impact on a person's overall risk of developing the condition.  Other, nongenetic factors are also believed to play a role in rheumatoid arthritis. These factors may trigger the condition in people who are at risk, although the mechanism is unclear. Potential triggers include changes in sex hormones (particularly in women), occupational exposure to certain kinds of dust or fibers, and viral or bacterial infections. Long-term smoking is a well-established risk factor for developing rheumatoid arthritis; it is also associated with more severe signs and symptoms in people who have the disease.",rheumatoid arthritis,0000875,GHR,https://ghr.nlm.nih.gov/condition/rheumatoid-arthritis,C0003873,T047,Disorders
Is rheumatoid arthritis inherited ?,0000875-4,inheritance,"The inheritance pattern of rheumatoid arthritis is unclear because many genetic and environmental factors appear to be involved. However, having a close relative with rheumatoid arthritis likely increases a person's risk of developing the condition.",rheumatoid arthritis,0000875,GHR,https://ghr.nlm.nih.gov/condition/rheumatoid-arthritis,C0003873,T047,Disorders
What are the treatments for rheumatoid arthritis ?,0000875-5,treatment,These resources address the diagnosis or management of rheumatoid arthritis:  - American College of Rheumatology: ACR-Endorsed Criteria for Rheumatic Diseases  - American College of Rheumatology: Treatment for Rheumatic Diseases  - Genetic Testing Registry: Rheumatoid arthritis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,rheumatoid arthritis,0000875,GHR,https://ghr.nlm.nih.gov/condition/rheumatoid-arthritis,C0003873,T047,Disorders
What is (are) rhizomelic chondrodysplasia punctata ?,0000876-1,information,"Rhizomelic chondrodysplasia punctata is a condition that impairs the normal development of many parts of the body. The major features of this disorder include skeletal abnormalities, distinctive facial features, intellectual disability, and respiratory problems.  Rhizomelic chondrodysplasia punctata is characterized by shortening of the bones in the upper arms and thighs (rhizomelia). Affected individuals also have a specific bone abnormality called chondrodysplasia punctata, which affects the growth of the long bones and can be seen on x-rays. People with rhizomelic chondrodysplasia punctata often develop joint deformities (contractures) that make the joints stiff and painful.  Distinctive facial features are also seen with rhizomelic chondrodysplasia punctata. These include a prominent forehead, widely set eyes (hypertelorism), a sunken appearance of the middle of the face (midface hypoplasia), a small nose with upturned nostrils, and full cheeks. Additionally, almost all affected individuals have clouding of the lenses of the eyes (cataracts). The cataracts are apparent at birth (congenital) or develop in early infancy.  Rhizomelic chondrodysplasia punctata is associated with significantly delayed development and severe intellectual disability. Most children with this condition do not achieve developmental milestones such as sitting without support, feeding themselves, or speaking in phrases. Affected infants grow much more slowly than other children their age, and many also have seizures. Recurrent respiratory infections and life-threatening breathing problems are common. Because of their severe health problems, most people with rhizomelic chondrodysplasia punctata survive only into childhood. It is rare for affected children to live past age 10. However, a few individuals with milder features of the condition have lived into early adulthood.  Researchers have described three types of rhizomelic chondrodysplasia punctata: type 1 (RCDP1), type 2 (RCDP2), and type 3 (RCDP3). The types have similar features and are distinguished by their genetic cause.",rhizomelic chondrodysplasia punctata,0000876,GHR,https://ghr.nlm.nih.gov/condition/rhizomelic-chondrodysplasia-punctata,C0282529,T047,Disorders
How many people are affected by rhizomelic chondrodysplasia punctata ?,0000876-2,frequency,"Rhizomelic chondrodysplasia punctata affects fewer than 1 in 100,000 people worldwide. RCDP1 is more common than RCDP2 or RCDP3.",rhizomelic chondrodysplasia punctata,0000876,GHR,https://ghr.nlm.nih.gov/condition/rhizomelic-chondrodysplasia-punctata,C0282529,T047,Disorders
What are the genetic changes related to rhizomelic chondrodysplasia punctata ?,0000876-3,genetic changes,"Rhizomelic chondrodysplasia punctata results from mutations in one of three genes. Mutations in the PEX7 gene, which are most common, cause RCDP1. Changes in the GNPAT gene lead to RCDP2, while AGPS gene mutations result in RCDP3.  The genes associated with rhizomelic chondrodysplasia punctata are involved in the formation and function of structures called peroxisomes. Peroxisomes are sac-like compartments within cells that contain enzymes needed to break down many different substances, including fatty acids and certain toxic compounds. They are also important for the production of fats (lipids) used in digestion and in the nervous system.  Within peroxisomes, the proteins produced from the PEX7, GNPAT, and AGPS genes play roles in the formation (synthesis) of lipid molecules called plasmalogens. Plasmalogens are found in cell membranes throughout the body, although little is known about their function. Mutations in the PEX7, GNPAT, or AGPS genes prevent peroxisomes from making plasmalogens. Researchers are working to determine how problems with plasmalogen synthesis lead to the specific signs and symptoms of rhizomelic chondrodysplasia punctata.",rhizomelic chondrodysplasia punctata,0000876,GHR,https://ghr.nlm.nih.gov/condition/rhizomelic-chondrodysplasia-punctata,C0282529,T047,Disorders
Is rhizomelic chondrodysplasia punctata inherited ?,0000876-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",rhizomelic chondrodysplasia punctata,0000876,GHR,https://ghr.nlm.nih.gov/condition/rhizomelic-chondrodysplasia-punctata,C0282529,T047,Disorders
What are the treatments for rhizomelic chondrodysplasia punctata ?,0000876-5,treatment,These resources address the diagnosis or management of rhizomelic chondrodysplasia punctata:  - Gene Review: Gene Review: Rhizomelic Chondrodysplasia Punctata Type 1  - Genetic Testing Registry: Rhizomelic chondrodysplasia punctata type 1  - Genetic Testing Registry: Rhizomelic chondrodysplasia punctata type 2  - Genetic Testing Registry: Rhizomelic chondrodysplasia punctata type 3   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,rhizomelic chondrodysplasia punctata,0000876,GHR,https://ghr.nlm.nih.gov/condition/rhizomelic-chondrodysplasia-punctata,C0282529,T047,Disorders
What is (are) ring chromosome 14 syndrome ?,0000878-1,information,"Ring chromosome 14 syndrome is a condition characterized by seizures and intellectual disability. Recurrent seizures (epilepsy) develop in infancy or early childhood. In many cases, the seizures are resistant to treatment with anti-epileptic drugs. Most people with ring chromosome 14 syndrome also have some degree of intellectual disability or learning problems. Development may be delayed, particularly the development of speech and of motor skills such as sitting, standing, and walking.  Additional features of ring chromosome 14 syndrome can include slow growth and short stature, a small head (microcephaly), puffy hands and/or feet caused by a buildup of fluid (lymphedema), and subtle differences in facial features. Some affected individuals have problems with their immune system that lead to recurrent infections, especially involving the respiratory system. Abnormalities of the retina, the specialized tissue at the back of the eye that detects light and color, have also been reported in some people with this condition. These changes typically do not affect vision. Major birth defects are rarely seen with ring chromosome 14 syndrome.",ring chromosome 14 syndrome,0000878,GHR,https://ghr.nlm.nih.gov/condition/ring-chromosome-14-syndrome,C2930916,T049,Disorders
How many people are affected by ring chromosome 14 syndrome ?,0000878-2,frequency,"Ring chromosome 14 syndrome appears to be a rare condition, although its prevalence is unknown. More than 50 affected individuals have been reported in the medical literature.",ring chromosome 14 syndrome,0000878,GHR,https://ghr.nlm.nih.gov/condition/ring-chromosome-14-syndrome,C2930916,T049,Disorders
What are the genetic changes related to ring chromosome 14 syndrome ?,0000878-3,genetic changes,"Ring chromosome 14 syndrome is caused by a chromosomal abnormality known as a ring chromosome 14, sometimes written as r(14). A ring chromosome is a circular structure that occurs when a chromosome breaks in two places and its broken ends fuse together. People with ring chromosome 14 syndrome have one copy of this abnormal chromosome in some or all of their cells.  Researchers believe that several critical genes near the end of the long (q) arm of chromosome 14 are lost when the ring chromosome forms. The loss of these genes is likely responsible for several of the major features of ring chromosome 14 syndrome, including intellectual disability and delayed development. Researchers are still working to determine which missing genes contribute to the signs and symptoms of this disorder.  Epilepsy is a common feature of ring chromosome syndromes, including ring chromosome 14. There may be something about the ring structure itself that causes epilepsy. Seizures may occur because certain genes on the ring chromosome 14 are less active than those on the normal chromosome 14. Alternately, seizures might result from instability of the ring chromosome in some cells.",ring chromosome 14 syndrome,0000878,GHR,https://ghr.nlm.nih.gov/condition/ring-chromosome-14-syndrome,C2930916,T049,Disorders
Is ring chromosome 14 syndrome inherited ?,0000878-4,inheritance,"Ring chromosome 14 syndrome is almost never inherited. A ring chromosome typically occurs as a random event during the formation of reproductive cells (eggs or sperm) or in early embryonic development. In some cases, the ring chromosome is present in only some of a person's cells. This situation is known as mosaicism.  Most affected individuals have no history of the disorder in their families. However, at least two families have been reported in which a ring chromosome 14 was passed from a mother to her children.",ring chromosome 14 syndrome,0000878,GHR,https://ghr.nlm.nih.gov/condition/ring-chromosome-14-syndrome,C2930916,T049,Disorders
What are the treatments for ring chromosome 14 syndrome ?,0000878-5,treatment,These resources address the diagnosis or management of ring chromosome 14 syndrome:  - Genetic Testing Registry: Ring chromosome 14  - MedlinePlus Encyclopedia: Chromosome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,ring chromosome 14 syndrome,0000878,GHR,https://ghr.nlm.nih.gov/condition/ring-chromosome-14-syndrome,C2930916,T049,Disorders
What is (are) ring chromosome 20 syndrome ?,0000879-1,information,"Ring chromosome 20 syndrome is a condition that affects the normal development and function of the brain. The most common feature of this condition is recurrent seizures (epilepsy) in childhood. The seizures may occur during the day or at night during sleep. They are described as partial seizures because they affect only one area of the brain, a region called the frontal lobe. In many cases, the seizures are complex and resistant to treatment with anti-epileptic drugs. Prolonged seizure episodes known as non-convulsive status epilepticus also appear to be characteristic of ring chromosome 20 syndrome. These episodes involve confusion and behavioral changes.  Most people with ring chromosome 20 syndrome also have some degree of intellectual disability and behavioral difficulties. Although these problems can appear either before or after the onset of epilepsy, they tend to worsen after seizures develop. Additional features of this condition can include slow growth and short stature, a small head (microcephaly), and subtle differences in facial features. Major birth defects are rarely seen with ring chromosome 20 syndrome.",ring chromosome 20 syndrome,0000879,GHR,https://ghr.nlm.nih.gov/condition/ring-chromosome-20-syndrome,C0265482,T019,Disorders
How many people are affected by ring chromosome 20 syndrome ?,0000879-2,frequency,"Ring chromosome 20 syndrome appears to be a rare condition, although its prevalence is unknown. More than 60 affected individuals have been reported in the medical literature.",ring chromosome 20 syndrome,0000879,GHR,https://ghr.nlm.nih.gov/condition/ring-chromosome-20-syndrome,C0265482,T019,Disorders
What are the genetic changes related to ring chromosome 20 syndrome ?,0000879-3,genetic changes,"Ring chromosome 20 syndrome is caused by a chromosomal abnormality known as a ring chromosome 20 or r(20). A ring chromosome is a circular structure that occurs when a chromosome breaks in two places and its broken ends fuse together. People with ring chromosome 20 syndrome have one copy of this abnormal chromosome in some or all of their cells.  It is not well understood how the ring chromosome causes the signs and symptoms of this syndrome. In some affected individuals, genes near the ends of chromosome 20 are deleted when the ring chromosome forms. Researchers suspect that the loss of these genes may be responsible for epilepsy and other health problems. However, other affected individuals do not have gene deletions associated with the ring chromosome. In these people, the ring chromosome may change the activity of certain genes on chromosome 20, or it may be unable to copy (replicate) itself normally during cell division. Researchers are still working to determine the precise relationship between the ring chromosome 20 and the characteristic features of the syndrome.",ring chromosome 20 syndrome,0000879,GHR,https://ghr.nlm.nih.gov/condition/ring-chromosome-20-syndrome,C0265482,T019,Disorders
Is ring chromosome 20 syndrome inherited ?,0000879-4,inheritance,"Ring chromosome 20 syndrome is almost never inherited. A ring chromosome typically occurs as a random event during the formation of reproductive cells (eggs or sperm) or in early embryonic development. Often, the ring chromosome is present in only some of a person's cells. This situation is known as mosaicism.  Most affected individuals have no history of the disorder in their families. However, at least one family has been reported in which a ring chromosome 20 was passed from a mother to her children.",ring chromosome 20 syndrome,0000879,GHR,https://ghr.nlm.nih.gov/condition/ring-chromosome-20-syndrome,C0265482,T019,Disorders
What are the treatments for ring chromosome 20 syndrome ?,0000879-5,treatment,These resources address the diagnosis or management of ring chromosome 20 syndrome:  - Genetic Testing Registry: Ring chromosome 20 syndrome  - MedlinePlus Encyclopedia: Chromosome  - MedlinePlus Encyclopedia: Epilepsy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,ring chromosome 20 syndrome,0000879,GHR,https://ghr.nlm.nih.gov/condition/ring-chromosome-20-syndrome,C0265482,T019,Disorders
What is (are) rippling muscle disease ?,0000880-1,information,"Rippling muscle disease is a condition in which the muscles are unusually sensitive to movement or pressure (irritable). The muscles near the center of the body (proximal muscles) are most affected, especially the thighs. In most people with this condition, stretching the muscle causes visible ripples to spread across the muscle, lasting 5 to 20 seconds. A bump or other sudden impact on the muscle causes it to bunch up (percussion-induced muscle mounding) or exhibit repetitive tensing (percussion-induced rapid contraction). The rapid contractions can continue for up to 30 seconds and may be painful.  People with rippling muscle disease may have overgrowth (hypertrophy) of some muscles, especially in the calf. Some affected individuals have an abnormal pattern of walking (gait), such as walking on tiptoe. They may experience fatigue, cramps, or muscle stiffness, especially after exercise or in cold temperatures.  The age of onset of rippling muscle disease varies widely, but it often begins in late childhood or adolescence. Rippling muscles may also occur as a feature of other muscle disorders such as limb-girdle muscular dystrophy.",rippling muscle disease,0000880,GHR,https://ghr.nlm.nih.gov/condition/rippling-muscle-disease,C0026848,T047,Disorders
How many people are affected by rippling muscle disease ?,0000880-2,frequency,The prevalence of rippling muscle disease is unknown.,rippling muscle disease,0000880,GHR,https://ghr.nlm.nih.gov/condition/rippling-muscle-disease,C0026848,T047,Disorders
What are the genetic changes related to rippling muscle disease ?,0000880-3,genetic changes,"Rippling muscle disease can be caused by mutations in the CAV3 gene. Muscle conditions caused by CAV3 gene mutations are called caveolinopathies. The CAV3 gene provides instructions for making a protein called caveolin-3, which is found in the membrane surrounding muscle cells. This protein is the main component of caveolae, which are small pouches in the muscle cell membrane. Within the caveolae, the caveolin-3 protein acts as a scaffold to organize other molecules that are important for cell signaling and maintenance of the cell structure. It may also help regulate calcium levels in muscle cells, which play a role in controlling muscle contraction and relaxation.  CAV3 gene mutations that cause rippling muscle disease result in a shortage of caveolin-3 protein in the muscle cell membrane. Researchers suggest that the reduction in caveolin-3 protein disrupts the normal control of calcium levels in muscle cells, leading to abnormal muscle contractions in response to stimulation.  In addition to rippling muscle disease, CAV3 gene mutations can cause other caveolinopathies including CAV3-related distal myopathy, limb-girdle muscular dystrophy, isolated hyperCKemia, and a heart disorder called hypertrophic cardiomyopathy. Several CAV3 gene mutations have been found to cause different caveolinopathies in different individuals. It is unclear why a single CAV3 gene mutation may cause different patterns of signs and symptoms, even within the same family.  Some people with rippling muscle disease do not have mutations in the CAV3 gene. The cause of the disorder in these individuals is unknown.",rippling muscle disease,0000880,GHR,https://ghr.nlm.nih.gov/condition/rippling-muscle-disease,C0026848,T047,Disorders
Is rippling muscle disease inherited ?,0000880-4,inheritance,"Rippling muscle disease is usually inherited in an autosomal dominant pattern, but it is occasionally inherited in an autosomal recessive pattern.  Autosomal dominant inheritance means that one copy of an altered CAV3 gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with rippling muscle disease or another caveolinopathy. Rare cases result from new mutations in the gene and occur in people with no history of caveolinopathies in their family.  Autosomal recessive inheritance means that both copies of the CAV3 gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. People with autosomal recessive rippling muscle disease generally have more severe signs and symptoms than do people with the autosomal dominant form.",rippling muscle disease,0000880,GHR,https://ghr.nlm.nih.gov/condition/rippling-muscle-disease,C0026848,T047,Disorders
What are the treatments for rippling muscle disease ?,0000880-5,treatment,These resources address the diagnosis or management of rippling muscle disease:  - Gene Review: Gene Review: Caveolinopathies  - Genetic Testing Registry: Rippling muscle disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,rippling muscle disease,0000880,GHR,https://ghr.nlm.nih.gov/condition/rippling-muscle-disease,C0026848,T047,Disorders
What is (are) Roberts syndrome ?,0000881-1,information,"Roberts syndrome is a genetic disorder characterized by limb and facial abnormalities. Affected individuals also grow slowly before and after birth. Mild to severe intellectual impairment occurs in half of all people with Roberts syndrome.  Children with Roberts syndrome are born with abnormalities of all four limbs. They have shortened arm and leg bones (hypomelia), particularly the bones in their forearms and lower legs. In severe cases, the limbs may be so short that the hands and feet are located very close to the body (phocomelia). People with Roberts syndrome may also have abnormal or missing fingers and toes, and joint deformities (contractures) commonly occur at the elbows and knees. The limb abnormalities are very similar on the right and left sides of the body, but arms are usually more severely affected than legs.  Individuals with Roberts syndrome typically have numerous facial abnormalities, including an opening in the lip (a cleft lip) with or without an opening in the roof of the mouth (cleft palate), a small chin (micrognathia), ear abnormalities, wide-set eyes (hypertelorism), outer corners of the eyes that point downward (down-slanting palpebral fissures), small nostrils, and a beaked nose. They may have a small head size (microcephaly), and in severe cases affected individuals have a sac-like protrusion of the brain (encephalocele) at the front of their head. In addition, people with Roberts syndrome may have heart, kidney, and genital abnormalities.  Infants with a severe form of Roberts syndrome are often stillborn or die shortly after birth. Mildly affected individuals may live into adulthood. A condition called SC phocomelia syndrome was originally thought to be distinct from Roberts syndrome; however, it is now considered to be a mild variant. ""SC"" represents the first letters of the surnames of the two families first diagnosed with this disorder.",Roberts syndrome,0000881,GHR,https://ghr.nlm.nih.gov/condition/roberts-syndrome,C0392475,T019,Disorders
How many people are affected by Roberts syndrome ?,0000881-2,frequency,Roberts syndrome is a rare disorder; approximately 150 affected individuals have been reported.,Roberts syndrome,0000881,GHR,https://ghr.nlm.nih.gov/condition/roberts-syndrome,C0392475,T019,Disorders
What are the genetic changes related to Roberts syndrome ?,0000881-3,genetic changes,"Mutations in the ESCO2 gene cause Roberts syndrome. This gene provides instructions for making a protein that is important for proper chromosome separation during cell division. Before cells divide, they must copy all of their chromosomes. The copied DNA from each chromosome is arranged into two identical structures, called sister chromatids. The ESCO2 protein plays an important role in establishing the glue that holds the sister chromatids together until the chromosomes are ready to separate.  All identified mutations in the ESCO2 gene prevent the cell from producing any functional ESCO2 protein, which causes some of the glue between sister chromatids to be missing around the chromosome's constriction point (centromere). In Roberts syndrome, cells respond to abnormal sister chromatid attachment by delaying cell division. Delayed cell division can be a signal that the cell should undergo self-destruction. The signs and symptoms of Roberts syndrome may result from the loss of cells from various tissues during early development. Because both mildly and severely affected individuals lack any functional ESCO2 protein, the underlying cause of the variation in disease severity remains unknown. Researchers suspect that other genetic and environmental factors may be involved.",Roberts syndrome,0000881,GHR,https://ghr.nlm.nih.gov/condition/roberts-syndrome,C0392475,T019,Disorders
Is Roberts syndrome inherited ?,0000881-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Roberts syndrome,0000881,GHR,https://ghr.nlm.nih.gov/condition/roberts-syndrome,C0392475,T019,Disorders
What are the treatments for Roberts syndrome ?,0000881-5,treatment,These resources address the diagnosis or management of Roberts syndrome:  - Gene Review: Gene Review: Roberts Syndrome  - Genetic Testing Registry: Roberts-SC phocomelia syndrome  - MedlinePlus Encyclopedia: Contracture deformity  - MedlinePlus Encyclopedia: Microcephaly   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Roberts syndrome,0000881,GHR,https://ghr.nlm.nih.gov/condition/roberts-syndrome,C0392475,T019,Disorders
What is (are) Robinow syndrome ?,0000882-1,information,"Robinow syndrome is a rare disorder that affects the development of many parts of the body, particularly the bones. Researchers have identified two major types of Robinow syndrome. The types are distinguished by the severity of their signs and symptoms and by their pattern of inheritance, autosomal recessive or autosomal dominant.  Autosomal recessive Robinow syndrome is characterized by skeletal abnormalities including shortening of the long bones in the arms and legs, particularly the forearms; abnormally short fingers and toes (brachydactyly); wedge-shaped spinal bones (hemivertebrae) leading to an abnormal curvature of the spine (kyphoscoliosis); fused or missing ribs; and short stature. Affected individuals also have distinctive facial features, such as a broad forehead, prominent and widely spaced eyes, a short nose with an upturned tip, a wide nasal bridge, and a broad and triangle-shaped mouth. Together, these facial features are sometimes described as ""fetal facies"" because they resemble the facial structure of a developing fetus. Other common features of autosomal recessive Robinow syndrome include underdeveloped genitalia in both males and females, and dental problems such as crowded teeth and overgrowth of the gums. Kidney and heart defects are also possible. Delayed development occurs in 10 to 15 percent of people with this condition, although intelligence is usually normal.  Autosomal dominant Robinow syndrome has signs and symptoms that are similar to, but tend to be milder than, those of the autosomal recessive form. Abnormalities of the spine and ribs are rarely seen in the autosomal dominant form, and short stature is less pronounced. A variant form of autosomal dominant Robinow syndrome features increased bone mineral density (osteosclerosis) in addition to the signs and symptoms listed above. This variant is called the osteosclerotic form of Robinow syndrome.",Robinow syndrome,0000882,GHR,https://ghr.nlm.nih.gov/condition/robinow-syndrome,C0265205,T019,Disorders
How many people are affected by Robinow syndrome ?,0000882-2,frequency,"Both the autosomal recessive and autosomal dominant forms of Robinow syndrome are rare.  Fewer than 200 people with autosomal recessive Robinow syndrome have been described in the medical literature. This form of the condition has been identified in families from several countries, including Turkey, Oman, Pakistan, and Brazil.  Autosomal dominant Robinow syndrome has been diagnosed in fewer than 50 families; about 10 of these families have had the osteosclerotic form.",Robinow syndrome,0000882,GHR,https://ghr.nlm.nih.gov/condition/robinow-syndrome,C0265205,T019,Disorders
What are the genetic changes related to Robinow syndrome ?,0000882-3,genetic changes,"Autosomal recessive Robinow syndrome results from mutations in the ROR2 gene. This gene provides instructions for making a protein whose function is not well understood, although it is involved in chemical signaling pathways that are essential for normal development before birth. In particular, the ROR2 protein appears to play a critical role in the formation of the skeleton, heart, and genitals. Mutations in the ROR2 gene prevent cells from making any functional ROR2 protein, which disrupts development starting before birth and leads to the characteristic features of Robinow syndrome.  Autosomal dominant Robinow syndrome can be caused by mutations in the WNT5A or DVL1 gene, with the osteosclerotic form of the condition resulting from DVL1 gene mutations. The proteins produced from these genes appear to be part of the same chemical signaling pathways as the ROR2 protein. Mutations in either of these genes alter the production or function of their respective proteins, which impairs chemical signaling that is important for early development.  Some people with the characteristic signs and symptoms of Robinow syndrome do not have an identified mutation in the ROR2, WNT5A, or DVL1 gene. In these cases, the cause of the condition is unknown.",Robinow syndrome,0000882,GHR,https://ghr.nlm.nih.gov/condition/robinow-syndrome,C0265205,T019,Disorders
Is Robinow syndrome inherited ?,0000882-4,inheritance,"As discussed above, Robinow syndrome can have either an autosomal recessive or an autosomal dominant pattern of inheritance.  Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Autosomal dominant inheritance means one copy of an altered gene in each cell is sufficient to cause the disorder. In some cases of Robinow syndrome, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",Robinow syndrome,0000882,GHR,https://ghr.nlm.nih.gov/condition/robinow-syndrome,C0265205,T019,Disorders
What are the treatments for Robinow syndrome ?,0000882-5,treatment,These resources address the diagnosis or management of Robinow syndrome:  - Gene Review: Gene Review: Autosomal Dominant Robinow Syndrome  - Gene Review: Gene Review: ROR2-Related Robinow Syndrome  - Genetic Testing Registry: Robinow syndrome  - University of Chicago: Genetic Testing for Robinow Syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Robinow syndrome,0000882,GHR,https://ghr.nlm.nih.gov/condition/robinow-syndrome,C0265205,T019,Disorders
What is (are) Romano-Ward syndrome ?,0000883-1,information,"Romano-Ward syndrome is a condition that causes a disruption of the heart's normal rhythm (arrhythmia). This disorder is a form of long QT syndrome, which is a heart condition that causes the heart (cardiac) muscle to take longer than usual to recharge between beats. The irregular heartbeats can lead to fainting (syncope) or cardiac arrest and sudden death.",Romano-Ward syndrome,0000883,GHR,https://ghr.nlm.nih.gov/condition/romano-ward-syndrome,C0035828,T047,Disorders
How many people are affected by Romano-Ward syndrome ?,0000883-2,frequency,"Romano-Ward syndrome is the most common form of inherited long QT syndrome, affecting an estimated 1 in 7,000 people worldwide. The disorder may actually be more common than this estimate, however, because some people never experience any symptoms associated with arrhythmia and therefore may not have been diagnosed.",Romano-Ward syndrome,0000883,GHR,https://ghr.nlm.nih.gov/condition/romano-ward-syndrome,C0035828,T047,Disorders
What are the genetic changes related to Romano-Ward syndrome ?,0000883-3,genetic changes,"Mutations in the KCNE1, KCNE2, KCNH2, KCNQ1, and SCN5A genes cause Romano-Ward syndrome. These genes provide instructions for making proteins that act as channels across the cell membrane. These channels transport positively charged atoms (ions), such as potassium and sodium, into and out of cells. In cardiac muscle, ion channels play critical roles in maintaining the heart's normal rhythm. Mutations in any of these genes alter the structure or function of these channels, which changes the flow of ions between cells. A disruption in ion transport alters the way the heart beats, leading to the abnormal heart rhythm characteristic of Romano-Ward syndrome.  Unlike most genes related to Romano-Ward syndrome, the ANK2 gene does not provide instructions for making an ion channel. The ANK2 protein, ankyrin-2, ensures that certain other proteins (particularly ion channels) are inserted into the cell membrane appropriately. A mutation in the ANK2 gene likely alters the flow of ions between cells in the heart, which disrupts the heart's normal rhythm. ANK2 mutations can cause a variety of heart problems, including the irregular heartbeat often found in Romano-Ward syndrome. It is unclear whether mutations in the ANK2 gene cause Romano-Ward syndrome or lead to another heart condition with some of the same signs and symptoms.",Romano-Ward syndrome,0000883,GHR,https://ghr.nlm.nih.gov/condition/romano-ward-syndrome,C0035828,T047,Disorders
Is Romano-Ward syndrome inherited ?,0000883-4,inheritance,"This condition is typically inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent. A small percentage of cases result from new mutations in one of the genes described above. These cases occur in people with no history of Romano-Ward syndrome in their family.",Romano-Ward syndrome,0000883,GHR,https://ghr.nlm.nih.gov/condition/romano-ward-syndrome,C0035828,T047,Disorders
What are the treatments for Romano-Ward syndrome ?,0000883-5,treatment,These resources address the diagnosis or management of Romano-Ward syndrome:  - Gene Review: Gene Review: Long QT Syndrome  - Genetic Testing Registry: Long QT syndrome 1  - Genetic Testing Registry: Romano-Ward syndrome  - MedlinePlus Encyclopedia: Arrhythmias   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Romano-Ward syndrome,0000883,GHR,https://ghr.nlm.nih.gov/condition/romano-ward-syndrome,C0035828,T047,Disorders
What is (are) Rothmund-Thomson syndrome ?,0000884-1,information,"Rothmund-Thomson syndrome is a rare condition that affects many parts of the body, especially the skin. People with this condition typically develop redness on the cheeks between ages 3 months and 6 months. Over time the rash spreads to the arms and legs, causing patchy changes in skin coloring, areas of thinning skin (atrophy), and small clusters of blood vessels just under the skin (telangiectases). These skin problems persist for life and are collectively known as poikiloderma.  Rothmund-Thomson syndrome is also characterized by sparse hair, eyebrows, and eyelashes; slow growth and small stature; abnormalities of the teeth and nails; and gastrointestinal problems in infancy, such as chronic diarrhea and vomiting. Some affected children develop a clouding of the lens of the eye (cataract), which affects vision. Many people with this disorder have skeletal abnormalities including absent or malformed bones, fused bones, and low bone mineral density (osteopenia or osteoporosis). Some of these abnormalities affect the development of bones in the forearms and the thumbs, and are known as radial ray malformations.  People with Rothmund-Thomson syndrome have an increased risk of developing cancer, particularly a form of bone cancer called osteosarcoma. These bone tumors most often develop during childhood or adolescence. Several types of skin cancer, including basal cell carcinoma and squamous cell carcinoma, are also more common in people with this disorder.  The varied signs and symptoms of Rothmund-Thomson syndrome overlap with features of other disorders, namely Baller-Gerold syndrome and RAPADILINO syndrome. These syndromes are also characterized by radial ray defects, skeletal abnormalities, and slow growth. All of these conditions can be caused by mutations in the same gene. Based on these similarities, researchers are investigating whether Rothmund-Thomson syndrome, Baller-Gerold syndrome, and RAPADILINO syndrome are separate disorders or part of a single syndrome with overlapping signs and symptoms.",Rothmund-Thomson syndrome,0000884,GHR,https://ghr.nlm.nih.gov/condition/rothmund-thomson-syndrome,C0032339,T047,Disorders
How many people are affected by Rothmund-Thomson syndrome ?,0000884-2,frequency,Rothmund-Thomson syndrome is a rare disorder; its incidence is unknown. About 300 people with this condition have been reported worldwide in scientific studies.,Rothmund-Thomson syndrome,0000884,GHR,https://ghr.nlm.nih.gov/condition/rothmund-thomson-syndrome,C0032339,T047,Disorders
What are the genetic changes related to Rothmund-Thomson syndrome ?,0000884-3,genetic changes,"Mutations in the RECQL4 gene cause about two-thirds of all cases of Rothmund-Thomson syndrome. This gene provides instructions for making one member of a protein family called RecQ helicases. Helicases are enzymes that bind to DNA and temporarily unwind the two spiral strands (double helix) of the DNA molecule. This unwinding is necessary for copying (replicating) DNA in preparation for cell division, and for repairing damaged DNA. The RECQL4 protein helps stabilize genetic information in the body's cells and plays a role in replicating and repairing DNA.  RECQL4 mutations lead to the production of an abnormally short, nonfunctional version of the RECQL4 protein or prevent cells from making any of this protein. A shortage of the RECQL4 protein may prevent normal DNA replication and repair, causing widespread damage to a person's genetic information over time. It is unclear how a loss of this protein's activity leads to the specific features of Rothmund-Thomson syndrome.  In about one-third of individuals with Rothmund-Thomson syndrome, no mutation in the RECQL4 gene has been found. The cause of the condition in these individuals is unknown; however, researchers suspect that these cases may result from mutations in a gene related to the RECQL4 gene.  In some cases, chromosomal abnormalities have been identified in people with Rothmund-Thomson syndrome. These abnormalities include extra or missing genetic material, usually from chromosome 7 or chromosome 8, in some of an affected person's cells. Researchers believe that these chromosomal changes arise because of the overall instability of an affected person's genetic information; they do not cause the disorder.",Rothmund-Thomson syndrome,0000884,GHR,https://ghr.nlm.nih.gov/condition/rothmund-thomson-syndrome,C0032339,T047,Disorders
Is Rothmund-Thomson syndrome inherited ?,0000884-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Rothmund-Thomson syndrome,0000884,GHR,https://ghr.nlm.nih.gov/condition/rothmund-thomson-syndrome,C0032339,T047,Disorders
What are the treatments for Rothmund-Thomson syndrome ?,0000884-5,treatment,These resources address the diagnosis or management of Rothmund-Thomson syndrome:  - Gene Review: Gene Review: Rothmund-Thomson Syndrome  - Genetic Testing Registry: Rothmund-Thomson syndrome  - MedlinePlus Encyclopedia: Cataract  - MedlinePlus Encyclopedia: Osteosarcoma   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Rothmund-Thomson syndrome,0000884,GHR,https://ghr.nlm.nih.gov/condition/rothmund-thomson-syndrome,C0032339,T047,Disorders
What is (are) Rotor syndrome ?,0000885-1,information,"Rotor syndrome is a relatively mild condition characterized by elevated levels of a substance called bilirubin in the blood (hyperbilirubinemia). Bilirubin is produced when red blood cells are broken down. It has an orange-yellow tint, and buildup of this substance can cause yellowing of the skin or whites of the eyes (jaundice). In people with Rotor syndrome, jaundice is usually evident shortly after birth or in childhood and may come and go; yellowing of the whites of the eyes (also called conjunctival icterus) is often the only symptom.  There are two forms of bilirubin in the body: a toxic form called unconjugated bilirubin and a nontoxic form called conjugated bilirubin. People with Rotor syndrome have a buildup of both unconjugated and conjugated bilirubin in their blood, but the majority is conjugated.",Rotor syndrome,0000885,GHR,https://ghr.nlm.nih.gov/condition/rotor-syndrome,C0220991,T047,Disorders
How many people are affected by Rotor syndrome ?,0000885-2,frequency,"Rotor syndrome is a rare condition, although its prevalence is unknown.",Rotor syndrome,0000885,GHR,https://ghr.nlm.nih.gov/condition/rotor-syndrome,C0220991,T047,Disorders
What are the genetic changes related to Rotor syndrome ?,0000885-3,genetic changes,"The SLCO1B1 and SLCO1B3 genes are involved in Rotor syndrome. Mutations in both genes are required for the condition to occur. The SLCO1B1 and SLCO1B3 genes provide instructions for making similar proteins, called organic anion transporting polypeptide 1B1 (OATP1B1) and organic anion transporting polypeptide 1B3 (OATP1B3), respectively. Both proteins are found in liver cells; they transport bilirubin and other compounds from the blood into the liver so that they can be cleared from the body. In the liver, bilirubin is dissolved in a digestive fluid called bile and then excreted from the body.  The SLCO1B1 and SLCO1B3 gene mutations that cause Rotor syndrome lead to abnormally short, nonfunctional OATP1B1 and OATP1B3 proteins or an absence of these proteins. Without the function of either transport protein, bilirubin is less efficiently taken up by the liver and removed from the body. The buildup of this substance leads to jaundice in people with Rotor syndrome.",Rotor syndrome,0000885,GHR,https://ghr.nlm.nih.gov/condition/rotor-syndrome,C0220991,T047,Disorders
Is Rotor syndrome inherited ?,0000885-4,inheritance,"This condition is inherited in an autosomal recessive pattern. In autosomal recessive inheritance, both copies of a gene in each cell have mutations. In Rotor syndrome, an affected individual must have mutations in both the SLCO1B1 and the SLCO1B3 gene, so both copies of the two genes are altered. The parents of an individual with this condition each carry one altered copy of both genes, but they do not show signs and symptoms of the condition.",Rotor syndrome,0000885,GHR,https://ghr.nlm.nih.gov/condition/rotor-syndrome,C0220991,T047,Disorders
What are the treatments for Rotor syndrome ?,0000885-5,treatment,These resources address the diagnosis or management of Rotor syndrome:  - Centers for Disease Control and Prevention: Facts About Jaundice and Kernicterus  - Gene Review: Gene Review: Rotor Syndrome  - Genetic Testing Registry: Rotor syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Rotor syndrome,0000885,GHR,https://ghr.nlm.nih.gov/condition/rotor-syndrome,C0220991,T047,Disorders
What is (are) Rubinstein-Taybi syndrome ?,0000886-1,information,"Rubinstein-Taybi syndrome is a condition characterized by short stature, moderate to severe intellectual disability, distinctive facial features, and broad thumbs and first toes. Additional features of the disorder can include eye abnormalities, heart and kidney defects, dental problems, and obesity. These signs and symptoms vary among affected individuals. People with this condition have an increased risk of developing noncancerous and cancerous tumors, including certain kinds of brain tumors. Cancer of blood-forming tissue (leukemia) also occurs more frequently in people with Rubinstein-Taybi syndrome.  Rarely, Rubinstein-Taybi syndrome can involve serious complications such as a failure to gain weight and grow at the expected rate (failure to thrive) and life-threatening infections. Infants born with this severe form of the disorder usually survive only into early childhood.",Rubinstein-Taybi syndrome,0000886,GHR,https://ghr.nlm.nih.gov/condition/rubinstein-taybi-syndrome,C0035934,T019,Disorders
How many people are affected by Rubinstein-Taybi syndrome ?,0000886-2,frequency,"This condition is uncommon; it occurs in an estimated 1 in 100,000 to 125,000 newborns.",Rubinstein-Taybi syndrome,0000886,GHR,https://ghr.nlm.nih.gov/condition/rubinstein-taybi-syndrome,C0035934,T019,Disorders
What are the genetic changes related to Rubinstein-Taybi syndrome ?,0000886-3,genetic changes,"Mutations in the CREBBP gene are responsible for some cases of Rubinstein-Taybi syndrome. The CREBBP gene provides instructions for making a protein that helps control the activity of many other genes. This protein, called CREB binding protein, plays an important role in regulating cell growth and division and is essential for normal fetal development. If one copy of the CREBBP gene is deleted or mutated, cells make only half of the normal amount of CREB binding protein. Although a reduction in the amount of this protein disrupts normal development before and after birth, researchers have not determined how it leads to the specific signs and symptoms of Rubinstein-Taybi syndrome.  Mutations in the EP300 gene cause a small percentage of cases of Rubinstein-Taybi syndrome. Like the CREBBP gene, this gene provides instructions for making a protein that helps control the activity of other genes. It also appears to be important for development before and after birth. EP300 mutations inactivate one copy of the gene in each cell, which interferes with normal development and causes the typical features of Rubinstein-Taybi syndrome. The signs and symptoms of this disorder in people with EP300 mutations are similar to those with mutations in the CREBBP gene; however, studies suggest that EP300 mutations may be associated with milder skeletal changes in the hands and feet.  Some cases of severe Rubinstein-Taybi syndrome have resulted from a deletion of genetic material from the short (p) arm of chromosome 16. Several genes, including the CREBBP gene, are missing as a result of this deletion. Researchers believe that the loss of multiple genes in this region probably accounts for the serious complications associated with severe Rubinstein-Taybi syndrome.  About half of people with Rubinstein-Taybi syndrome do not have an identified mutation in the CREBBP or EP300 gene or a deletion in chromosome 16. The cause of the condition is unknown in these cases. Researchers predict that mutations in other genes are also responsible for the disorder.",Rubinstein-Taybi syndrome,0000886,GHR,https://ghr.nlm.nih.gov/condition/rubinstein-taybi-syndrome,C0035934,T019,Disorders
Is Rubinstein-Taybi syndrome inherited ?,0000886-4,inheritance,"This condition is considered to have an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",Rubinstein-Taybi syndrome,0000886,GHR,https://ghr.nlm.nih.gov/condition/rubinstein-taybi-syndrome,C0035934,T019,Disorders
What are the treatments for Rubinstein-Taybi syndrome ?,0000886-5,treatment,These resources address the diagnosis or management of Rubinstein-Taybi syndrome:  - Gene Review: Gene Review: Rubinstein-Taybi Syndrome  - Genetic Testing Registry: Rubinstein-Taybi syndrome  - MedlinePlus Encyclopedia: Rubinstein-Taybi syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Rubinstein-Taybi syndrome,0000886,GHR,https://ghr.nlm.nih.gov/condition/rubinstein-taybi-syndrome,C0035934,T019,Disorders
What is (are) Russell-Silver syndrome ?,0000887-1,information,"Russell-Silver syndrome is a growth disorder characterized by slow growth before and after birth. Babies with this condition have a low birth weight and often fail to grow and gain weight at the expected rate (failure to thrive). Head growth is normal, however, so the head may appear unusually large compared to the rest of the body. Affected children are thin and have poor appetites, and some develop low blood sugar (hypoglycemia) as a result of feeding difficulties. Adults with Russell-Silver syndrome are short; the average height for affected males is about 151 centimeters (4 feet, 11 inches) and the average height for affected females is about 140 centimeters (4 feet, 7 inches).  Many children with Russell-Silver syndrome have a small, triangular face with distinctive facial features including a prominent forehead, a narrow chin, a small jaw, and downturned corners of the mouth. Other features of this disorder can include an unusual curving of the fifth finger (clinodactyly), asymmetric or uneven growth of some parts of the body, and digestive system abnormalities. Russell-Silver syndrome is also associated with an increased risk of delayed development and learning disabilities.",Russell-Silver syndrome,0000887,GHR,https://ghr.nlm.nih.gov/condition/russell-silver-syndrome,C0175693,T047,Disorders
How many people are affected by Russell-Silver syndrome ?,0000887-2,frequency,"The exact incidence of Russell-Silver syndrome is unknown, but the condition is estimated to affect 1 in 75,000 to 100,000 people.",Russell-Silver syndrome,0000887,GHR,https://ghr.nlm.nih.gov/condition/russell-silver-syndrome,C0175693,T047,Disorders
What are the genetic changes related to Russell-Silver syndrome ?,0000887-3,genetic changes,"The genetic causes of Russell-Silver syndrome are complex. The disorder often results from the abnormal regulation of certain genes that control growth. Research has focused on genes located in particular regions of chromosome 7 and chromosome 11.  People normally inherit one copy of each chromosome from their mother and one copy from their father. For most genes, both copies are expressed, or ""turned on,"" in cells. For some genes, however, only the copy inherited from a person's father (the paternal copy) is expressed. For other genes, only the copy inherited from a person's mother (the maternal copy) is expressed. These parent-specific differences in gene expression are caused by a phenomenon called genomic imprinting. Both chromosome 7 and chromosome 11 contain groups of genes that normally undergo genomic imprinting. Abnormalities involving these genes appear to be responsible for many cases of Russell-Silver syndrome.  Researchers suspect that at least one third of all cases of Russell-Silver syndrome result from changes in a process called methylation. Methylation is a chemical reaction that attaches small molecules called methyl groups to certain segments of DNA. In genes that undergo genomic imprinting, methylation is one way that a gene's parent of origin is marked during the formation of egg and sperm cells. Russell-Silver syndrome has been associated with changes in methylation involving the H19 and IGF2 genes, which are located near one another on chromosome 11. These genes are thought to be involved in directing normal growth. A loss of methylation disrupts the regulation of these genes, which leads to slow growth and the other characteristic features of this disorder.  Abnormalities involving genes on chromosome 7 also cause Russell-Silver syndrome. In 7 percent to 10 percent of cases, people inherit both copies of chromosome 7 from their mother instead of one copy from each parent. This phenomenon is called maternal uniparental disomy (UPD). Maternal UPD causes people to have two active copies of maternally expressed imprinted genes rather than one active copy from the mother and one inactive copy from the father. These individuals do not have a paternal copy of chromosome 7 and therefore do not have any copies of genes that are active only on the paternal copy. In cases of Russell-Silver syndrome caused by maternal UPD, an imbalance in active paternal and maternal genes on chromosome 7 underlies the signs and symptoms of the disorder.  In at least 40 percent of people with Russell-Silver syndrome, the cause of the condition is unknown. It is possible that changes in chromosomes other than 7 and 11 may play a role. Researchers are working to identify additional genetic changes that underlie this disorder.",Russell-Silver syndrome,0000887,GHR,https://ghr.nlm.nih.gov/condition/russell-silver-syndrome,C0175693,T047,Disorders
Is Russell-Silver syndrome inherited ?,0000887-4,inheritance,"Most cases of Russell-Silver syndrome are sporadic, which means they occur in people with no history of the disorder in their family.  Less commonly, Russell-Silver syndrome can run in families. In some affected families, the condition appears to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of a genetic change in each cell is sufficient to cause the disorder. In other families, the condition has an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of a gene are altered in each cell. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Russell-Silver syndrome,0000887,GHR,https://ghr.nlm.nih.gov/condition/russell-silver-syndrome,C0175693,T047,Disorders
What are the treatments for Russell-Silver syndrome ?,0000887-5,treatment,These resources address the diagnosis or management of Russell-Silver syndrome:  - Gene Review: Gene Review: Russell-Silver Syndrome  - Genetic Testing Registry: Russell-Silver syndrome  - MedlinePlus Encyclopedia: Russell-Silver syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Russell-Silver syndrome,0000887,GHR,https://ghr.nlm.nih.gov/condition/russell-silver-syndrome,C0175693,T047,Disorders
What is (are) SADDAN ?,0000888-1,information,"SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans) is a rare disorder of bone growth characterized by skeletal, brain, and skin abnormalities.  All people with this condition have extremely short stature with particularly short arms and legs. Other features include unusual bowing of the leg bones; a small chest with short ribs and curved collar bones; short, broad fingers; and folds of extra skin on the arms and legs. Structural abnormalities of the brain cause seizures, profound developmental delay, and intellectual disability. Several affected individuals also have had episodes in which their breathing slows or stops for short periods (apnea). Acanthosis nigricans, a progressive skin disorder characterized by thick, dark, velvety skin, is another characteristic feature of SADDAN that develops in infancy or early childhood.",SADDAN,0000888,GHR,https://ghr.nlm.nih.gov/condition/saddan,C2674173,T047,Disorders
How many people are affected by SADDAN ?,0000888-2,frequency,This disorder is very rare; it has been described in only a small number of individuals worldwide.,SADDAN,0000888,GHR,https://ghr.nlm.nih.gov/condition/saddan,C2674173,T047,Disorders
What are the genetic changes related to SADDAN ?,0000888-3,genetic changes,"Mutations in the FGFR3 gene cause SADDAN. The FGFR3 gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. A mutation in this gene may cause the FGFR3 protein to be overly active, which leads to the disturbances in bone growth that are characteristic of this disorder. Researchers have not determined how the mutation disrupts brain development or causes acanthosis nigricans.",SADDAN,0000888,GHR,https://ghr.nlm.nih.gov/condition/saddan,C2674173,T047,Disorders
Is SADDAN inherited ?,0000888-4,inheritance,"SADDAN is considered an autosomal dominant disorder because one mutated copy of the FGFR3 gene in each cell is sufficient to cause the condition. The few described cases of SADDAN have been caused by new mutations in the FGFR3 gene and occurred in people with no history of the disorder in their family. No individuals with this disorder are known to have had children; therefore, the disorder has not been passed to the next generation.",SADDAN,0000888,GHR,https://ghr.nlm.nih.gov/condition/saddan,C2674173,T047,Disorders
What are the treatments for SADDAN ?,0000888-5,treatment,These resources address the diagnosis or management of SADDAN:  - Gene Review: Gene Review: Achondroplasia  - Genetic Testing Registry: Severe achondroplasia with developmental delay and acanthosis nigricans  - MedlinePlus Encyclopedia: Acanthosis Nigricans   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,SADDAN,0000888,GHR,https://ghr.nlm.nih.gov/condition/saddan,C2674173,T047,Disorders
What is (are) Saethre-Chotzen syndrome ?,0000889-1,information,"Saethre-Chotzen syndrome is a genetic condition characterized by the premature fusion of certain skull bones (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face.  Most people with Saethre-Chotzen syndrome have prematurely fused skull bones along the coronal suture, the growth line that goes over the head from ear to ear. Other parts of the skull may be malformed as well. These changes can result in an abnormally shaped head, a high forehead, a low frontal hairline, droopy eyelids (ptosis), widely spaced eyes, and a broad nasal bridge. One side of the face may appear noticeably different from the other (facial asymmetry). Most people with Saethre-Chotzen syndrome also have small, unusually shaped ears.  The signs and symptoms of Saethre-Chotzen syndrome vary widely, even among affected individuals in the same family. This condition can cause mild abnormalities of the hands and feet, such as fusion of the skin between the second and third fingers on each hand and a broad or duplicated first (big) toe. Delayed development and learning difficulties have been reported, although most people with this condition are of normal intelligence. Less common signs and symptoms of Saethre-Chotzen syndrome include short stature, abnormalities of the bones of the spine (the vertebra), hearing loss, and heart defects.  Robinow-Sorauf syndrome is a condition with features similar to those of Saethre-Chotzen syndrome, including craniosynostosis and broad or duplicated great toes. It was once considered a separate disorder, but was found to result from mutations in the same gene and is now thought to be a mild variant of Saethre-Chotzen syndrome.",Saethre-Chotzen syndrome,0000889,GHR,https://ghr.nlm.nih.gov/condition/saethre-chotzen-syndrome,C0175699,T019,Disorders
How many people are affected by Saethre-Chotzen syndrome ?,0000889-2,frequency,"Saethre-Chotzen syndrome has an estimated prevalence of 1 in 25,000 to 50,000 people.",Saethre-Chotzen syndrome,0000889,GHR,https://ghr.nlm.nih.gov/condition/saethre-chotzen-syndrome,C0175699,T019,Disorders
What are the genetic changes related to Saethre-Chotzen syndrome ?,0000889-3,genetic changes,"Mutations in the TWIST1 gene cause Saethre-Chotzen syndrome. The TWIST1 gene provides instructions for making a protein that plays an important role in early development. This protein is a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of particular genes. The TWIST1 protein is active in cells that give rise to bones, muscles, and other tissues in the head and face. It is also involved in the development of the limbs.  Mutations in the TWIST1 gene prevent one copy of the gene in each cell from making any functional protein. A shortage of the TWIST1 protein affects the development and maturation of cells in the skull, face, and limbs. These abnormalities underlie the signs and symptoms of Saethre-Chotzen syndrome, including the premature fusion of certain skull bones.  A small number of cases of Saethre-Chotzen syndrome have resulted from a structural chromosomal abnormality, such as a deletion or rearrangement of genetic material, in the region of chromosome 7 that contains the TWIST1 gene. When Saethre-Chotzen syndrome is caused by a chromosomal deletion instead of a mutation within the TWIST1 gene, affected children are much more likely to have intellectual disability, developmental delay, and learning difficulties. These features are typically not seen in classic cases of Saethre-Chotzen syndrome. Researchers believe that a loss of other genes on chromosome 7 may be responsible for these additional features.",Saethre-Chotzen syndrome,0000889,GHR,https://ghr.nlm.nih.gov/condition/saethre-chotzen-syndrome,C0175699,T019,Disorders
Is Saethre-Chotzen syndrome inherited ?,0000889-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.  Some people with a TWIST1 mutation do not have any of the obvious features of Saethre-Chotzen syndrome. These people are still at risk of passing on the gene mutation and may have a child with craniosynostosis and the other typical signs and symptoms of the condition.",Saethre-Chotzen syndrome,0000889,GHR,https://ghr.nlm.nih.gov/condition/saethre-chotzen-syndrome,C0175699,T019,Disorders
What are the treatments for Saethre-Chotzen syndrome ?,0000889-5,treatment,These resources address the diagnosis or management of Saethre-Chotzen syndrome:  - Gene Review: Gene Review: Saethre-Chotzen Syndrome  - Genetic Testing Registry: Robinow Sorauf syndrome  - Genetic Testing Registry: Saethre-Chotzen syndrome  - MedlinePlus Encyclopedia: Craniosynostosis  - MedlinePlus Encyclopedia: Skull of a Newborn (image)   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Saethre-Chotzen syndrome,0000889,GHR,https://ghr.nlm.nih.gov/condition/saethre-chotzen-syndrome,C0175699,T019,Disorders
What is (are) Salih myopathy ?,0000890-1,information,"Salih myopathy is an inherited muscle disease that affects the skeletal muscles, which are used for movement, and the heart (cardiac) muscle. This condition is characterized by skeletal muscle weakness that becomes apparent in early infancy. Affected individuals have delayed development of motor skills, such as sitting, standing, and walking. Beginning later in childhood, people with Salih myopathy may also develop joint deformities called contractures that restrict the movement of the neck and back. Scoliosis, which is an abnormal side-to-side curvature of the spine, also develops in late childhood.  A form of heart disease called dilated cardiomyopathy is another feature of Salih myopathy. Dilated cardiomyopathy enlarges and weakens the cardiac muscle, preventing the heart from pumping blood efficiently. Signs and symptoms of this condition can include an irregular heartbeat (arrhythmia), shortness of breath, extreme tiredness (fatigue), and swelling of the legs and feet. The heart abnormalities associated with Salih myopathy usually become apparent in childhood, after the skeletal muscle abnormalities. The heart disease worsens quickly, and it often causes heart failure and sudden death in adolescence or early adulthood.",Salih myopathy,0000890,GHR,https://ghr.nlm.nih.gov/condition/salih-myopathy,C2673677,T047,Disorders
How many people are affected by Salih myopathy ?,0000890-2,frequency,"Salih myopathy appears to be a rare disorder, although its prevalence is unknown. It has been reported in a small number of families of Moroccan and Sudanese descent.",Salih myopathy,0000890,GHR,https://ghr.nlm.nih.gov/condition/salih-myopathy,C2673677,T047,Disorders
What are the genetic changes related to Salih myopathy ?,0000890-3,genetic changes,"Salih myopathy is caused by mutations in the TTN gene. This gene provides instructions for making a protein called titin, which plays an important role in skeletal and cardiac muscle function.  Within muscle cells, titin is an essential component of structures called sarcomeres. Sarcomeres are the basic units of muscle contraction; they are made of proteins that generate the mechanical force needed for muscles to contract. Titin has several functions within sarcomeres. One of this protein's most important jobs is to provide structure, flexibility, and stability to these cell structures. Titin also plays a role in chemical signaling and in assembling new sarcomeres.  The TTN gene mutations responsible for Salih myopathy lead to the production of an abnormally short version of titin. The defective protein disrupts the function of sarcomeres, which prevents skeletal and cardiac muscle from contracting normally. These muscle abnormalities underlie the features of Salih myopathy, including skeletal muscle weakness and dilated cardiomyopathy.",Salih myopathy,0000890,GHR,https://ghr.nlm.nih.gov/condition/salih-myopathy,C2673677,T047,Disorders
Is Salih myopathy inherited ?,0000890-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Salih myopathy,0000890,GHR,https://ghr.nlm.nih.gov/condition/salih-myopathy,C2673677,T047,Disorders
What are the treatments for Salih myopathy ?,0000890-5,treatment,"These resources address the diagnosis or management of Salih myopathy:  - Gene Review: Gene Review: Salih Myopathy  - Genetic Testing Registry: Myopathy, early-onset, with fatal cardiomyopathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Salih myopathy,0000890,GHR,https://ghr.nlm.nih.gov/condition/salih-myopathy,C2673677,T047,Disorders
What is (are) Sandhoff disease ?,0000891-1,information,"Sandhoff disease is a rare inherited disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord.  The most common and severe form of Sandhoff disease becomes apparent in infancy. Infants with this disorder typically appear normal until the age of 3 to 6 months, when their development slows and muscles used for movement weaken. Affected infants lose motor skills such as turning over, sitting, and crawling. They also develop an exaggerated startle reaction to loud noises. As the disease progresses, children with Sandhoff disease experience seizures, vision and hearing loss, intellectual disability, and paralysis. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. Some affected children also have enlarged organs (organomegaly) or bone abnormalities. Children with the severe infantile form of Sandhoff disease usually live only into early childhood.  Other forms of Sandhoff disease are very rare. Signs and symptoms can begin in childhood, adolescence, or adulthood and are usually milder than those seen with the infantile form. Characteristic features include muscle weakness, loss of muscle coordination (ataxia) and other problems with movement, speech problems, and mental illness. These signs and symptoms vary widely among people with late-onset forms of Sandhoff disease.",Sandhoff disease,0000891,GHR,https://ghr.nlm.nih.gov/condition/sandhoff-disease,C0036161,T047,Disorders
How many people are affected by Sandhoff disease ?,0000891-2,frequency,"Sandhoff disease is a rare disorder; its frequency varies among populations. This condition appears to be more common in the Creole population of northern Argentina; the Metis Indians in Saskatchewan, Canada; and people from Lebanon.",Sandhoff disease,0000891,GHR,https://ghr.nlm.nih.gov/condition/sandhoff-disease,C0036161,T047,Disorders
What are the genetic changes related to Sandhoff disease ?,0000891-3,genetic changes,"Mutations in the HEXB gene cause Sandhoff disease. The HEXB gene provides instructions for making a protein that is part of two critical enzymes in the nervous system, beta-hexosaminidase A and beta-hexosaminidase B. These enzymes are located in lysosomes, which are structures in cells that break down toxic substances and act as recycling centers. Within lysosomes, these enzymes break down fatty substances, complex sugars, and molecules that are linked to sugars. In particular, beta-hexosaminidase A helps break down a fatty substance called GM2 ganglioside.  Mutations in the HEXB gene disrupt the activity of beta-hexosaminidase A and beta-hexosaminidase B, which prevents these enzymes from breaking down GM2 ganglioside and other molecules. As a result, these compounds can accumulate to toxic levels, particularly in neurons of the brain and spinal cord. A buildup of GM2 ganglioside leads to the progressive destruction of these neurons, which causes many of the signs and symptoms of Sandhoff disease.  Because Sandhoff disease impairs the function of lysosomal enzymes and involves the buildup of GM2 ganglioside, this condition is sometimes referred to as a lysosomal storage disorder or a GM2-gangliosidosis.",Sandhoff disease,0000891,GHR,https://ghr.nlm.nih.gov/condition/sandhoff-disease,C0036161,T047,Disorders
Is Sandhoff disease inherited ?,0000891-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Sandhoff disease,0000891,GHR,https://ghr.nlm.nih.gov/condition/sandhoff-disease,C0036161,T047,Disorders
What are the treatments for Sandhoff disease ?,0000891-5,treatment,These resources address the diagnosis or management of Sandhoff disease:  - Genetic Testing Registry: Sandhoff disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Sandhoff disease,0000891,GHR,https://ghr.nlm.nih.gov/condition/sandhoff-disease,C0036161,T047,Disorders
What is (are) Schimke immuno-osseous dysplasia ?,0000892-1,information,"Schimke immuno-osseous dysplasia is a condition characterized by short stature, kidney disease, and a weakened immune system. In people with this condition, short stature is caused by flattened spinal bones (vertebrae), resulting in a shortened neck and trunk. Adult height is typically between 3 and 5 feet. Kidney (renal) disease often leads to life-threatening renal failure and end-stage renal disease (ESRD). Affected individuals also have a shortage of certain immune system cells called T cells. T cells identify foreign substances and defend the body against infection. A shortage of T cells causes a person to be more susceptible to illness.  Other features frequently seen in people with this condition include an exaggerated curvature of the lower back (lordosis); darkened patches of skin (hyperpigmentation), typically on the chest and back; and a broad nasal bridge with a rounded tip of the nose.  Less common signs and symptoms of Schimke immuno-osseous dysplasia include an accumulation of fatty deposits and scar-like tissue in the lining of the arteries (atherosclerosis), reduced blood flow to the brain (cerebral ischemia), migraine-like headaches, an underactive thyroid gland (hypothyroidism), decreased numbers of white blood cells (lymphopenia), underdeveloped hip bones (hypoplastic pelvis), abnormally small head size (microcephaly), a lack of sperm (azoospermia) in males, and irregular menstruation in females.  In severe cases, many signs of Schimke immuno-osseous dysplasia can be present at birth. People with mild cases of this disorder may not develop signs or symptoms until late childhood.",Schimke immuno-osseous dysplasia,0000892,GHR,https://ghr.nlm.nih.gov/condition/schimke-immuno-osseous-dysplasia,C0877024,T019,Disorders
How many people are affected by Schimke immuno-osseous dysplasia ?,0000892-2,frequency,Schimke immuno-osseous dysplasia is a very rare condition. The prevalence in North America is estimated to be one in 1 million to 3 million people.,Schimke immuno-osseous dysplasia,0000892,GHR,https://ghr.nlm.nih.gov/condition/schimke-immuno-osseous-dysplasia,C0877024,T019,Disorders
What are the genetic changes related to Schimke immuno-osseous dysplasia ?,0000892-3,genetic changes,"Mutations in the SMARCAL1 gene increase the risk of Schimke immuno-osseous dysplasia. The SMARCAL1 gene provides instructions for producing a protein whose specific function is unknown. The SMARCAL1 protein can attach (bind) to chromatin, which is the complex of DNA and protein that packages DNA into chromosomes. Based on the function of similar proteins, SMARCAL1 is thought to influence the activity (expression) of other genes through a process known as chromatin remodeling. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. Chromatin remodeling is one way gene expression is regulated during development. When DNA is tightly packed, gene expression is lower than when DNA is loosely packed.  Mutations in the SMARCAL1 gene are thought to lead to disease by affecting protein activity, protein stability, or the protein's ability to bind to chromatin. It is not clear if mutations in the SMARCAL1 gene interfere with chromatin remodeling and the expression of other genes.  The mutations associated with Schimke immuno-osseous dysplasia disrupt the usual functions of the SMARCAL1 protein or prevent the production of any functional protein. People who have mutations that cause a complete lack of functional protein tend to have a more severe form of this disorder than those who have mutations that lead to an active but malfunctioning protein. However, in order for people with SMARCAL1 gene mutations to develop Schimke immuno-osseous dysplasia, other currently unknown genetic or environmental factors must also be present.  Approximately half of all people with Schimke immuno-osseous dysplasia do not have identified mutations in the SMARCAL1 gene. In these cases, the cause of the disease is unknown.",Schimke immuno-osseous dysplasia,0000892,GHR,https://ghr.nlm.nih.gov/condition/schimke-immuno-osseous-dysplasia,C0877024,T019,Disorders
Is Schimke immuno-osseous dysplasia inherited ?,0000892-4,inheritance,"Mutations in the SMARCAL1 gene are inherited in an autosomal recessive pattern, which means that an increased risk of Schimke immuno-osseous dysplasia results from mutations in both copies of the SMARCAL1 gene in each cell. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Schimke immuno-osseous dysplasia,0000892,GHR,https://ghr.nlm.nih.gov/condition/schimke-immuno-osseous-dysplasia,C0877024,T019,Disorders
What are the treatments for Schimke immuno-osseous dysplasia ?,0000892-5,treatment,These resources address the diagnosis or management of Schimke immuno-osseous dysplasia:  - Gene Review: Gene Review: Schimke Immunoosseous Dysplasia  - Genetic Testing Registry: Schimke immunoosseous dysplasia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Schimke immuno-osseous dysplasia,0000892,GHR,https://ghr.nlm.nih.gov/condition/schimke-immuno-osseous-dysplasia,C0877024,T019,Disorders
What is (are) Schindler disease ?,0000893-1,information,"Schindler disease is an inherited disorder that primarily causes neurological problems.  There are three types of Schindler disease. Schindler disease type I, also called the infantile type, is the most severe form. Babies with Schindler disease type I appear healthy at birth, but by the age of 8 to 15 months they stop developing new skills and begin losing skills they had already acquired (developmental regression). As the disorder progresses, affected individuals develop blindness and seizures, and eventually they lose awareness of their surroundings and become unresponsive. People with this form of the disorder usually do not survive past early childhood.  Schindler disease type II, also called Kanzaki disease, is a milder form of the disorder that usually appears in adulthood. Affected individuals may develop mild cognitive impairment and hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss). They may experience weakness and loss of sensation due to problems with the nerves connecting the brain and spinal cord to muscles and sensory cells (peripheral nervous system). Clusters of enlarged blood vessels that form small, dark red spots on the skin (angiokeratomas) are characteristic of this form of the disorder.  Schindler disease type III is intermediate in severity between types I and II. Affected individuals may exhibit signs and symptoms beginning in infancy, including developmental delay, seizures, a weakened and enlarged heart (cardiomyopathy), and an enlarged liver (hepatomegaly). In other cases, people with this form of the disorder exhibit behavioral problems beginning in early childhood, with some features of autism spectrum disorders. Autism spectrum disorders are characterized by impaired communication and socialization skills.",Schindler disease,0000893,GHR,https://ghr.nlm.nih.gov/condition/schindler-disease,C1836544,T047,Disorders
How many people are affected by Schindler disease ?,0000893-2,frequency,Schindler disease is very rare. Only a few individuals with each type of the disorder have been identified.,Schindler disease,0000893,GHR,https://ghr.nlm.nih.gov/condition/schindler-disease,C1836544,T047,Disorders
What are the genetic changes related to Schindler disease ?,0000893-3,genetic changes,"Mutations in the NAGA gene cause Schindler disease. The NAGA gene provides instructions for making the enzyme alpha-N-acetylgalactosaminidase. This enzyme works in the lysosomes, which are compartments within cells that digest and recycle materials. Within lysosomes, the enzyme helps break down complexes called glycoproteins and glycolipids, which consist of sugar molecules attached to certain proteins and fats. Specifically, alpha-N-acetylgalactosaminidase helps remove a molecule called alpha-N-acetylgalactosamine from sugars in these complexes.  Mutations in the NAGA gene interfere with the ability of the alpha-N-acetylgalactosaminidase enzyme to perform its role in breaking down glycoproteins and glycolipids. These substances accumulate in the lysosomes and cause cells to malfunction and eventually die. Cell damage in the nervous system and other tissues and organs of the body leads to the signs and symptoms of Schindler disease.",Schindler disease,0000893,GHR,https://ghr.nlm.nih.gov/condition/schindler-disease,C1836544,T047,Disorders
Is Schindler disease inherited ?,0000893-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Schindler disease,0000893,GHR,https://ghr.nlm.nih.gov/condition/schindler-disease,C1836544,T047,Disorders
What are the treatments for Schindler disease ?,0000893-5,treatment,"These resources address the diagnosis or management of Schindler disease:  - Genetic Testing Registry: Kanzaki disease  - Genetic Testing Registry: Schindler disease, type 1   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Schindler disease,0000893,GHR,https://ghr.nlm.nih.gov/condition/schindler-disease,C1836544,T047,Disorders
What is (are) Schinzel-Giedion syndrome ?,0000894-1,information,"Schinzel-Giedion syndrome is a severe condition that is apparent at birth and affects many body systems. Signs and symptoms of this condition include distinctive facial features, neurological problems, and organ and bone abnormalities. Because of their serious health problems, most affected individuals do not survive past childhood.  Children with Schinzel-Giedion syndrome can have a variety of distinctive features. In most affected individuals, the middle of the face looks as though it has been drawn inward (midface retraction). Other facial features include a large or bulging forehead; wide-set eyes (ocular hypertelorism); a short, upturned nose; and a wide mouth with a large tongue (macroglossia). Affected individuals can have other distinctive features, including larger than normal gaps between the bones of the skull in infants (fontanelles), a short neck, ear malformations, an inability to secrete tears (alacrima), and excessive hairiness (hypertrichosis). Hypertrichosis often disappears in infancy.  Children with Schinzel-Giedion syndrome have severe developmental delay. Other neurological problems can include severe feeding problems, seizures, or visual or hearing impairment.  Affected individuals can also have abnormalities of organs such as the heart, kidneys, or genitals. Heart defects include problems with the heart valves, which control blood flow in the heart; the chambers of the heart that pump blood to the body (ventricles); or the dividing wall between the sides of the heart (the septum). Most children with Schinzel-Giedion syndrome have accumulation of urine in the kidneys (hydronephrosis), which can occur in one or both kidneys. Affected individuals can have genital abnormalities such as underdevelopment (hypoplasia) of the genitals. Affected boys may have the opening of the urethra on the underside of the penis (hypospadias).  Bone abnormalities are common in people with Schinzel-Giedion syndrome. The bones at the base of the skull are often abnormally hard or thick (sclerotic), or the joint between the bones at the base of the skull (occipital synchondrosis) can be abnormally wide. In addition, affected individuals may have broad ribs, abnormal collarbones (clavicles), or shortened bones at the ends of the fingers (hypoplastic distal phalanges).  Children with this condition who survive past infancy have a higher than normal risk of developing certain types of tumors called neuroepithelial tumors.",Schinzel-Giedion syndrome,0000894,GHR,https://ghr.nlm.nih.gov/condition/schinzel-giedion-syndrome,C0265227,T019,Disorders
How many people are affected by Schinzel-Giedion syndrome ?,0000894-2,frequency,"Schinzel-Giedion syndrome is very rare, although the exact prevalence is unknown.",Schinzel-Giedion syndrome,0000894,GHR,https://ghr.nlm.nih.gov/condition/schinzel-giedion-syndrome,C0265227,T019,Disorders
What are the genetic changes related to Schinzel-Giedion syndrome ?,0000894-3,genetic changes,"Schinzel-Giedion syndrome is caused by mutations in the SETBP1 gene. This gene provides instructions for making a protein called SET binding protein 1 (SETBP1), which is known to attach (bind) to another protein called SET. However, the function of the SETBP1 protein and the effect of its binding to the SET protein are unknown.  The SETBP1 gene mutations that have been identified in Schinzel-Giedion syndrome cluster in one region of the gene known as exon 4. However, the effects of the mutations on the function of the gene or the protein are unknown. Researchers are working to understand how mutations in the SETBP1 gene cause the signs and symptoms of Schinzel-Giedion syndrome.",Schinzel-Giedion syndrome,0000894,GHR,https://ghr.nlm.nih.gov/condition/schinzel-giedion-syndrome,C0265227,T019,Disorders
Is Schinzel-Giedion syndrome inherited ?,0000894-4,inheritance,Schinzel-Giedion syndrome results from new mutations in the SETBP1 gene and occurs in people with no history of the disorder in their family. One copy of the altered gene in each cell is sufficient to cause the disorder.,Schinzel-Giedion syndrome,0000894,GHR,https://ghr.nlm.nih.gov/condition/schinzel-giedion-syndrome,C0265227,T019,Disorders
What are the treatments for Schinzel-Giedion syndrome ?,0000894-5,treatment,These resources address the diagnosis or management of Schinzel-Giedion syndrome:  - Genetic Testing Registry: Schinzel-Giedion syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Schinzel-Giedion syndrome,0000894,GHR,https://ghr.nlm.nih.gov/condition/schinzel-giedion-syndrome,C0265227,T019,Disorders
What is (are) Schwartz-Jampel syndrome ?,0000895-1,information,"Schwartz-Jampel syndrome is a rare condition characterized by permanent muscle stiffness (myotonia) and bone abnormalities known as chondrodysplasia. The signs and symptoms of this condition become apparent sometime after birth, usually in early childhood. Either muscle stiffness or chondrodysplasia can appear first. The muscle and bone abnormalities worsen in childhood, although most affected individuals have a normal lifespan. The specific features of Schwartz-Jampel syndrome vary widely.  Myotonia involves continuous tensing (contraction) of muscles used for movement (skeletal muscles) throughout the body. This sustained muscle contraction causes stiffness that interferes with eating, sitting, walking, and other movements. Sustained contraction of muscles in the face leads to a fixed, ""mask-like"" facial expression with narrow eye openings (blepharophimosis) and pursed lips. This facial appearance is very specific to Schwartz-Jampel syndrome. Affected individuals may also be nearsighted and experience abnormal blinking or spasms of the eyelids (blepharospasm).  Chondrodysplasia affects the development of the skeleton, particularly the long bones in the arms and legs and the bones of the hips. These bones are shortened and unusually wide at the ends, so affected individuals have short stature. The long bones may also be abnormally curved (bowed). Other bone abnormalities associated with Schwartz-Jampel syndrome include a protruding chest (pectus carinatum), abnormal curvature of the spine, flattened bones of the spine (platyspondyly), and joint abnormalities called contractures that further restrict movement.  Researchers originally described two types of Schwartz-Jampel syndrome. Type 1 has the signs and symptoms described above, while type 2 has more severe bone abnormalities and other health problems and is usually life-threatening in early infancy. Researchers have since discovered that the condition they thought was Schwartz-Jampel syndrome type 2 is actually part of another disorder, Stve-Wiedemann syndrome, which is caused by mutations in a different gene. They have recommended that the designation Schwartz-Jampel syndrome type 2 no longer be used.",Schwartz-Jampel syndrome,0000895,GHR,https://ghr.nlm.nih.gov/condition/schwartz-jampel-syndrome,C0036391,T019,Disorders
How many people are affected by Schwartz-Jampel syndrome ?,0000895-2,frequency,Schwartz-Jampel syndrome appears to be a rare condition. About 150 cases have been reported in the medical literature.,Schwartz-Jampel syndrome,0000895,GHR,https://ghr.nlm.nih.gov/condition/schwartz-jampel-syndrome,C0036391,T019,Disorders
What are the genetic changes related to Schwartz-Jampel syndrome ?,0000895-3,genetic changes,"Schwartz-Jampel syndrome is caused by mutations in the HSPG2 gene. This gene provides instructions for making a protein known as perlecan. This protein is found in the extracellular matrix, which is the intricate lattice of proteins and other molecules that forms in the spaces between cells. Specifically, it is found in part of the extracellular matrix called the basement membrane, which is a thin, sheet-like structure that separates and supports cells in many tissues. Perlecan is also found in cartilage, a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears.  Perlecan has multiple functions, including cell signaling and the normal maintenance of basement membranes and cartilage. The protein also plays a critical role at the neuromuscular junction, which is the area between the ends of nerve cells and muscle cells where signals are relayed to trigger muscle contraction.  The mutations that cause Schwartz-Jampel syndrome reduce the amount of perlecan that is produced or lead to a version of perlecan that is only partially functional. A reduction in the amount or function of this protein disrupts the normal development of cartilage and bone tissue, which underlies chondrodysplasia in affected individuals. A reduced amount of functional perlecan at the neuromuscular junction likely alters the balance of other molecules that signal when muscles should contract and when they should relax. As a result, muscle contraction is triggered continuously, leading to myotonia.",Schwartz-Jampel syndrome,0000895,GHR,https://ghr.nlm.nih.gov/condition/schwartz-jampel-syndrome,C0036391,T019,Disorders
Is Schwartz-Jampel syndrome inherited ?,0000895-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Schwartz-Jampel syndrome,0000895,GHR,https://ghr.nlm.nih.gov/condition/schwartz-jampel-syndrome,C0036391,T019,Disorders
What are the treatments for Schwartz-Jampel syndrome ?,0000895-5,treatment,These resources address the diagnosis or management of Schwartz-Jampel syndrome:  - Genetic Testing Registry: Schwartz Jampel syndrome type 1  - National Institute of Neurological Disorders and Stroke: Myotonia Information Page   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Schwartz-Jampel syndrome,0000895,GHR,https://ghr.nlm.nih.gov/condition/schwartz-jampel-syndrome,C0036391,T019,Disorders
What is (are) Senior-Lken syndrome ?,0000896-1,information,"Senior-Lken syndrome is a rare disorder characterized by the combination of two specific features: a kidney condition called nephronophthisis and an eye condition known as Leber congenital amaurosis.  Nephronophthisis causes fluid-filled cysts to develop in the kidneys beginning in childhood. These cysts impair kidney function, initially causing increased urine production (polyuria), excessive thirst (polydipsia), general weakness, and extreme tiredness (fatigue). Nephronophthisis leads to end-stage renal disease (ESRD) later in childhood or in adolescence. ESRD is a life-threatening failure of kidney function that occurs when the kidneys are no longer able to filter fluids and waste products from the body effectively.  Leber congenital amaurosis primarily affects the retina, which is the specialized tissue at the back of the eye that detects light and color. This condition causes vision problems, including an increased sensitivity to light (photophobia), involuntary movements of the eyes (nystagmus), and extreme farsightedness (hyperopia). Some people with Senior-Lken syndrome develop the signs of Leber congenital amaurosis within the first few years of life, while others do not develop vision problems until later in childhood.",Senior-Lken syndrome,0000896,GHR,https://ghr.nlm.nih.gov/condition/senior-loken-syndrome,C0039082,T047,Disorders
How many people are affected by Senior-Lken syndrome ?,0000896-2,frequency,"Senior-Lken syndrome is a rare disorder, with an estimated prevalence of about 1 in 1 million people worldwide. Only a few families with the condition have been described in the medical literature.",Senior-Lken syndrome,0000896,GHR,https://ghr.nlm.nih.gov/condition/senior-loken-syndrome,C0039082,T047,Disorders
What are the genetic changes related to Senior-Lken syndrome ?,0000896-3,genetic changes,"Senior-Lken syndrome can be caused by mutations in one of at least five genes. The proteins produced from these genes are known or suspected to play roles in cell structures called cilia. Cilia are microscopic, finger-like projections that stick out from the surface of cells; they are involved in signaling pathways that transmit information between cells. Cilia are important for the structure and function of many types of cells, including certain cells in the kidneys. They are also necessary for the perception of sensory input (such as vision, hearing, and smell).  Mutations in the genes associated with Senior-Lken syndrome likely lead to problems with the structure and function of cilia. Defects in these cell structures probably disrupt important chemical signaling pathways within cells. Although researchers believe that defective cilia are responsible for the features of this disorder, it remains unclear how they lead specifically to nephronophthisis and Leber congenital amaurosis.  Some people with Senior-Lken syndrome do not have identified mutations in one of the five genes known to be associated with the condition. In these cases, the genetic cause of the disorder is unknown.",Senior-Lken syndrome,0000896,GHR,https://ghr.nlm.nih.gov/condition/senior-loken-syndrome,C0039082,T047,Disorders
Is Senior-Lken syndrome inherited ?,0000896-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Senior-Lken syndrome,0000896,GHR,https://ghr.nlm.nih.gov/condition/senior-loken-syndrome,C0039082,T047,Disorders
What are the treatments for Senior-Lken syndrome ?,0000896-5,treatment,These resources address the diagnosis or management of Senior-Lken syndrome:  - Genetic Testing Registry: Senior-Loken syndrome 1  - Genetic Testing Registry: Senior-Loken syndrome 3  - Genetic Testing Registry: Senior-Loken syndrome 4  - Genetic Testing Registry: Senior-Loken syndrome 5  - Genetic Testing Registry: Senior-Loken syndrome 6  - Genetic Testing Registry: Senior-Loken syndrome 7   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Senior-Lken syndrome,0000896,GHR,https://ghr.nlm.nih.gov/condition/senior-loken-syndrome,C0039082,T047,Disorders
What is (are) sensorineural deafness and male infertility ?,0000897-1,information,"Sensorineural deafness and male infertility is a condition characterized by hearing loss and an inability to father children. Affected individuals have moderate to severe sensorineural hearing loss, which is caused by abnormalities in the inner ear. The hearing loss is typically diagnosed in early childhood and does not worsen over time. Males with this condition produce sperm that have decreased movement (motility), causing affected males to be infertile.",sensorineural deafness and male infertility,0000897,GHR,https://ghr.nlm.nih.gov/condition/sensorineural-deafness-and-male-infertility,C2048468,T047,Disorders
How many people are affected by sensorineural deafness and male infertility ?,0000897-2,frequency,The prevalence of sensorineural deafness and male infertility is unknown.,sensorineural deafness and male infertility,0000897,GHR,https://ghr.nlm.nih.gov/condition/sensorineural-deafness-and-male-infertility,C2048468,T047,Disorders
What are the genetic changes related to sensorineural deafness and male infertility ?,0000897-3,genetic changes,"Sensorineural deafness and male infertility is caused by a deletion of genetic material on the long (q) arm of chromosome 15. The signs and symptoms of sensorineural deafness and male infertility are related to the loss of multiple genes in this region. The size of the deletion varies among affected individuals. Researchers have determined that the loss of a particular gene on chromosome 15, the STRC gene, is responsible for hearing loss in affected individuals. The loss of another gene, CATSPER2, in the same region of chromosome 15 is responsible for the sperm abnormalities and infertility in affected males. Researchers are working to determine how the loss of additional genes in the deleted region affects people with sensorineural deafness and male infertility.",sensorineural deafness and male infertility,0000897,GHR,https://ghr.nlm.nih.gov/condition/sensorineural-deafness-and-male-infertility,C2048468,T047,Disorders
Is sensorineural deafness and male infertility inherited ?,0000897-4,inheritance,"Sensorineural deafness and male infertility is inherited in an autosomal recessive pattern, which means both copies of chromosome 15 in each cell have a deletion. The parents of an individual with sensorineural deafness and male infertility each carry one copy of the chromosome 15 deletion, but they do not show symptoms of the condition.  Males with two chromosome 15 deletions in each cell have sensorineural deafness and infertility. Females with two chromosome 15 deletions in each cell have sensorineural deafness as their only symptom because the CATSPER2 gene deletions affect sperm function, and women do not produce sperm.",sensorineural deafness and male infertility,0000897,GHR,https://ghr.nlm.nih.gov/condition/sensorineural-deafness-and-male-infertility,C2048468,T047,Disorders
What are the treatments for sensorineural deafness and male infertility ?,0000897-5,treatment,"These resources address the diagnosis or management of sensorineural deafness and male infertility:  - Cleveland Clinic: Male Infertility  - Gene Review: Gene Review: CATSPER-Related Male Infertility  - Genetic Testing Registry: Deafness, sensorineural, and male infertility  - MedlinePlus Health Topic: Assisted Reproductive Technology  - RESOLVE: The National Infertility Association: Semen Analysis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",sensorineural deafness and male infertility,0000897,GHR,https://ghr.nlm.nih.gov/condition/sensorineural-deafness-and-male-infertility,C2048468,T047,Disorders
What is (are) sepiapterin reductase deficiency ?,0000898-1,information,"Sepiapterin reductase deficiency is a condition characterized by movement problems, most often a pattern of involuntary, sustained muscle contractions known as dystonia. Other movement problems can include muscle stiffness (spasticity), tremors, problems with coordination and balance (ataxia), and involuntary jerking movements (chorea). People with sepiapterin reductase deficiency can experience episodes called oculogyric crises. These episodes involve abnormal rotation of the eyeballs; extreme irritability and agitation; and pain, muscle spasms, and uncontrolled movements, especially of the head and neck. Movement abnormalities are often worse late in the day. Most affected individuals have delayed development of motor skills such as sitting and crawling, and they typically are not able to walk unassisted. The problems with movement tend to worsen over time.  People with sepiapterin reductase deficiency may have additional signs and symptoms including an unusually small head size (microcephaly), intellectual disability, seizures, excessive sleeping, and mood swings.",sepiapterin reductase deficiency,0000898,GHR,https://ghr.nlm.nih.gov/condition/sepiapterin-reductase-deficiency,C1291316,T047,Disorders
How many people are affected by sepiapterin reductase deficiency ?,0000898-2,frequency,Sepiapterin reductase deficiency appears to be a rare condition. At least 30 cases have been described in the scientific literature.,sepiapterin reductase deficiency,0000898,GHR,https://ghr.nlm.nih.gov/condition/sepiapterin-reductase-deficiency,C1291316,T047,Disorders
What are the genetic changes related to sepiapterin reductase deficiency ?,0000898-3,genetic changes,"Mutations in the SPR gene cause sepiapterin reductase deficiency. The SPR gene provides instructions for making the sepiapterin reductase enzyme. This enzyme is involved in the production of a molecule called tetrahydrobiopterin (also known as BH4). Specifically, sepiapterin reductase is responsible for the last step in the production of tetrahydrobiopterin. Tetrahydrobiopterin helps process several building blocks of proteins (amino acids), and is involved in the production of chemicals called neurotransmitters, which transmit signals between nerve cells in the brain.  SPR gene mutations disrupt the production of sepiapterin reductase. Most SPR gene mutations result in an enzyme with little or no function. A nonfunctional sepiapterin reductase leads to a lack of tetrahydrobiopterin. In most parts of the body, there are alternate pathways that do not use sepiapterin reductase for the production of tetrahydrobiopterin, but these pathways are not found in the brain. Therefore, people with sepiapterin reductase deficiency have a lack of tetrahydrobiopterin in the brain. When no tetrahydrobiopterin is produced in the brain, production of dopamine and serotonin is greatly reduced. Among their many functions, dopamine transmits signals within the brain to produce smooth physical movements, and serotonin regulates mood, emotion, sleep, and appetite. The lack of these two neurotransmitters causes the problems with movement and other features of sepiapterin reductase deficiency.",sepiapterin reductase deficiency,0000898,GHR,https://ghr.nlm.nih.gov/condition/sepiapterin-reductase-deficiency,C1291316,T047,Disorders
Is sepiapterin reductase deficiency inherited ?,0000898-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",sepiapterin reductase deficiency,0000898,GHR,https://ghr.nlm.nih.gov/condition/sepiapterin-reductase-deficiency,C1291316,T047,Disorders
What are the treatments for sepiapterin reductase deficiency ?,0000898-5,treatment,These resources address the diagnosis or management of sepiapterin reductase deficiency:  - Gene Review: Gene Review: Sepiapterin Reductase Deficiency  - Genetic Testing Registry: Sepiapterin reductase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,sepiapterin reductase deficiency,0000898,GHR,https://ghr.nlm.nih.gov/condition/sepiapterin-reductase-deficiency,C1291316,T047,Disorders
What is (are) septo-optic dysplasia ?,0000899-1,information,"Septo-optic dysplasia is a disorder of early brain development. Although its signs and symptoms vary, this condition is traditionally defined by three characteristic features: underdevelopment (hypoplasia) of the optic nerves, abnormal formation of structures along the midline of the brain, and pituitary hypoplasia.  The first major feature, optic nerve hypoplasia, is the underdevelopment of the optic nerves, which carry visual information from the eyes to the brain. In affected individuals, the optic nerves are abnormally small and make fewer connections than usual between the eyes and the brain. As a result, people with optic nerve hypoplasia have impaired vision in one or both eyes. Optic nerve hypoplasia can also be associated with unusual side-to-side eye movements (nystagmus) and other eye abnormalities.  The second characteristic feature of septo-optic dysplasia is the abnormal development of structures separating the right and left halves of the brain. These structures include the corpus callosum, which is a band of tissue that connects the two halves of the brain, and the septum pellucidum, which separates the fluid-filled spaces called ventricles in the brain. In the early stages of brain development, these structures may form abnormally or fail to develop at all. Depending on which structures are affected, abnormal brain development can lead to intellectual disability and other neurological problems.  The third major feature of this disorder is pituitary hypoplasia. The pituitary is a gland at the base of the brain that produces several hormones. These hormones help control growth, reproduction, and other critical body functions. Underdevelopment of the pituitary can lead to a shortage (deficiency) of many essential hormones. Most commonly, pituitary hypoplasia causes growth hormone deficiency, which results in slow growth and unusually short stature. Severe cases cause panhypopituitarism, a condition in which the pituitary produces no hormones. Panhypopituitarism is associated with slow growth, low blood sugar (hypoglycemia), genital abnormalities, and problems with sexual development.  The signs and symptoms of septo-optic dysplasia can vary significantly. Some researchers suggest that septo-optic dysplasia should actually be considered a group of related conditions rather than a single disorder. About one-third of people diagnosed with septo-optic dysplasia have all three major features; most affected individuals have two of the major features. In rare cases, septo-optic dysplasia is associated with additional signs and symptoms, including recurrent seizures (epilepsy), delayed development, and abnormal movements.",septo-optic dysplasia,0000899,GHR,https://ghr.nlm.nih.gov/condition/septo-optic-dysplasia,C0338503,T019,Disorders
How many people are affected by septo-optic dysplasia ?,0000899-2,frequency,"Septo-optic dysplasia has a reported incidence of 1 in 10,000 newborns.",septo-optic dysplasia,0000899,GHR,https://ghr.nlm.nih.gov/condition/septo-optic-dysplasia,C0338503,T019,Disorders
What are the genetic changes related to septo-optic dysplasia ?,0000899-3,genetic changes,"In most cases of septo-optic dysplasia, the cause of the disorder is unknown. Researchers suspect that a combination of genetic and environmental factors may play a role in causing this disorder. Proposed environmental risk factors include viral infections, specific medications, and a disruption in blood flow to certain areas of the brain during critical periods of development.  At least three genes have been associated with septo-optic dysplasia, although mutations in these genes appear to be rare causes of this disorder. The three genes, HESX1, OTX2, and SOX2, all play important roles in embryonic development. In particular, they are essential for the formation of the eyes, the pituitary gland, and structures at the front of the brain (the forebrain) such as the optic nerves. Mutations in any of these genes disrupt the early development of these structures, which leads to the major features of septo-optic dysplasia.  Researchers are looking for additional genetic changes that contribute to septo-optic dysplasia.",septo-optic dysplasia,0000899,GHR,https://ghr.nlm.nih.gov/condition/septo-optic-dysplasia,C0338503,T019,Disorders
Is septo-optic dysplasia inherited ?,0000899-4,inheritance,"Septo-optic dysplasia is usually sporadic, which means that the condition typically occurs in people with no history of the disorder in their family.  Less commonly, septo-optic dysplasia has been found to run in families. Most familial cases appear to have an autosomal recessive pattern of inheritance, which means that both copies of an associated gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. In a few affected families, the disorder has had an autosomal dominant pattern of inheritance, which means one copy of an altered gene in each cell is sufficient to cause the condition.",septo-optic dysplasia,0000899,GHR,https://ghr.nlm.nih.gov/condition/septo-optic-dysplasia,C0338503,T019,Disorders
What are the treatments for septo-optic dysplasia ?,0000899-5,treatment,These resources address the diagnosis or management of septo-optic dysplasia:  - Genetic Testing Registry: Septo-optic dysplasia sequence  - MedlinePlus Encyclopedia: Growth Hormone Deficiency  - MedlinePlus Encyclopedia: Hypopituitarism   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,septo-optic dysplasia,0000899,GHR,https://ghr.nlm.nih.gov/condition/septo-optic-dysplasia,C0338503,T019,Disorders
What is (are) severe congenital neutropenia ?,0000900-1,information,"Severe congenital neutropenia is a condition that causes affected individuals to be prone to recurrent infections. People with this condition have a shortage (deficiency) of neutrophils, a type of white blood cell that plays a role in inflammation and in fighting infection. The deficiency of neutrophils, called neutropenia, is apparent at birth or soon afterward. It leads to recurrent infections beginning in infancy, including infections of the sinuses, lungs, and liver. Affected individuals can also develop fevers and inflammation of the gums (gingivitis) and skin. Approximately 40 percent of affected people have decreased bone density (osteopenia) and may develop osteoporosis, a condition that makes bones progressively more brittle and prone to fracture. In people with severe congenital neutropenia, these bone disorders can begin at any time from infancy through adulthood.  Approximately 20 percent of people with severe congenital neutropenia develop cancer of the blood-forming tissue (leukemia) or a disease of the blood and bone marrow (myelodysplastic syndrome) during adolescence.  Some people with severe congenital neutropenia have additional health problems such as seizures, developmental delay, or heart and genital abnormalities.",severe congenital neutropenia,0000900,GHR,https://ghr.nlm.nih.gov/condition/severe-congenital-neutropenia,C1853118,T019,Disorders
How many people are affected by severe congenital neutropenia ?,0000900-2,frequency,"The incidence of severe congenital neutropenia is estimated to be 1 in 200,000 individuals.",severe congenital neutropenia,0000900,GHR,https://ghr.nlm.nih.gov/condition/severe-congenital-neutropenia,C1853118,T019,Disorders
What are the genetic changes related to severe congenital neutropenia ?,0000900-3,genetic changes,"Severe congenital neutropenia can result from mutations in at least five different genes. These genes play a role in the maturation and function of neutrophils, which are cells produced by the bone marrow. Neutrophils secrete immune molecules and ingest and break down foreign invaders.  Gene mutations that cause severe congenital neutropenia lead to the production of neutrophils that die off quickly or do not function properly. Some gene mutations result in unstable proteins that build up in neutrophils, leading to cell death. Other gene mutations result in proteins that impair the maturation or function of neutrophils, preventing these cells from responding appropriately to immune signals.  About half of all cases of severe congenital neutropenia are caused by mutations in the ELANE gene. Another 15 percent are caused by mutations in the HAX1 gene. The other genes each account for only a small percentage of all cases of this condition. In about one-third of people with severe congenital neutropenia, the cause of the disorder is unknown.",severe congenital neutropenia,0000900,GHR,https://ghr.nlm.nih.gov/condition/severe-congenital-neutropenia,C1853118,T019,Disorders
Is severe congenital neutropenia inherited ?,0000900-4,inheritance,"Most cases of severe congenital neutropenia are classified as sporadic and occur in people with no apparent history of the disorder in their family. Some of these cases are associated with changes in specific genes; however in some cases the cause of the disorder is unknown.  Many cases of severe congenital neutropenia are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  Less often, this condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  In rare cases, severe congenital neutropenia is inherited in an X-linked recessive pattern. In these cases, the gene that causes the condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",severe congenital neutropenia,0000900,GHR,https://ghr.nlm.nih.gov/condition/severe-congenital-neutropenia,C1853118,T019,Disorders
What are the treatments for severe congenital neutropenia ?,0000900-5,treatment,"These resources address the diagnosis or management of severe congenital neutropenia:  - Cincinnati Children's Hospital: The Severe Congenital Neutropenia International Registry  - Gene Review: Gene Review: ELANE-Related Neutropenia  - Gene Review: Gene Review: G6PC3 Deficiency  - Genetic Testing Registry: Severe congenital neutropenia  - Genetic Testing Registry: Severe congenital neutropenia 2, autosomal dominant  - Genetic Testing Registry: Severe congenital neutropenia 4, autosomal recessive  - Genetic Testing Registry: Severe congenital neutropenia X-linked  - Genetic Testing Registry: Severe congenital neutropenia autosomal dominant  - MedlinePlus Encyclopedia: Neutropenia--infants   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",severe congenital neutropenia,0000900,GHR,https://ghr.nlm.nih.gov/condition/severe-congenital-neutropenia,C1853118,T019,Disorders
What is (are) Sheldon-Hall syndrome ?,0000901-1,information,"Sheldon-Hall syndrome, also known as distal arthrogryposis type 2B, is a disorder characterized by joint deformities (contractures) that restrict movement in the hands and feet. The term ""arthrogryposis"" comes from the Greek words for joint (arthro-) and crooked or hooked (gryposis). ""Distal"" refers to areas of the body away from the center. The characteristic features of this condition include permanently bent fingers and toes (camptodactyly), overlapping fingers, and a hand deformity called ulnar deviation in which all of the fingers are angled outward toward the fifth (pinky) finger. Inward- and upward-turning feet (a condition called clubfoot) is also commonly seen in Sheldon-Hall syndrome. The specific hand and foot abnormalities vary among affected individuals; the abnormalities are present at birth and generally do not get worse over time.  People with Sheldon-Hall syndrome also usually have distinctive facial features, which include a triangular face; outside corners of the eyes that point downward (down-slanting palpebral fissures); deep folds in the skin between the nose and lips (nasolabial folds); and a small mouth with a high, arched roof of the mouth (palate). Other features that may occur in Sheldon-Hall syndrome include extra folds of skin on the neck (webbed neck) and short stature.  Sheldon-Hall syndrome does not usually affect other parts of the body, and intelligence and life expectancy are normal in this disorder.",Sheldon-Hall syndrome,0000901,GHR,https://ghr.nlm.nih.gov/condition/sheldon-hall-syndrome,C0039082,T047,Disorders
How many people are affected by Sheldon-Hall syndrome ?,0000901-2,frequency,"The prevalence of Sheldon-Hall syndrome is unknown; however, it is thought to be the most common type of distal arthrogryposis. About 100 affected individuals have been described in the medical literature.",Sheldon-Hall syndrome,0000901,GHR,https://ghr.nlm.nih.gov/condition/sheldon-hall-syndrome,C0039082,T047,Disorders
What are the genetic changes related to Sheldon-Hall syndrome ?,0000901-3,genetic changes,"Sheldon-Hall syndrome can be caused by mutations in the MYH3, TNNI2, TNNT3, or TPM2 gene. These genes provide instructions for making proteins that are involved in muscle tensing (contraction).  Muscle contraction occurs when thick filaments made of proteins called myosins slide past thin filaments made of proteins called actins. The MYH3 gene provides instructions for making a myosin protein that is normally active only before birth and is important for early development of the muscles.  The process of muscle contraction is controlled (regulated) by other proteins called troponins and tropomyosins, which affect the interaction of myosin and actin. Certain troponin proteins are produced from the TNNI2 and TNNT3 genes. The TPM2 gene provides instructions for making a tropomyosin protein.  Mutations in the MYH3, TNNI2, TNNT3, or TPM2 gene likely interfere with normal muscle development or prevent muscle contractions from being properly controlled, resulting in the contractures and other muscle and skeletal abnormalities associated with Sheldon-Hall syndrome. It is unknown why the contractures mainly affect the hands and feet or how these gene mutations are related to other features of this disorder.",Sheldon-Hall syndrome,0000901,GHR,https://ghr.nlm.nih.gov/condition/sheldon-hall-syndrome,C0039082,T047,Disorders
Is Sheldon-Hall syndrome inherited ?,0000901-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In about 50 percent of cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",Sheldon-Hall syndrome,0000901,GHR,https://ghr.nlm.nih.gov/condition/sheldon-hall-syndrome,C0039082,T047,Disorders
What are the treatments for Sheldon-Hall syndrome ?,0000901-5,treatment,These resources address the diagnosis or management of Sheldon-Hall syndrome:  - Gillette Children's Hospital  - NYU Langone Medical Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Sheldon-Hall syndrome,0000901,GHR,https://ghr.nlm.nih.gov/condition/sheldon-hall-syndrome,C0039082,T047,Disorders
What is (are) short QT syndrome ?,0000902-1,information,"Short QT syndrome is a condition that can cause a disruption of the heart's normal rhythm (arrhythmia). In people with this condition, the heart (cardiac) muscle takes less time than usual to recharge between beats. The term ""short QT"" refers to a specific pattern of heart activity that is detected with an electrocardiogram (EKG), which is a test used to measure the electrical activity of the heart. In people with this condition, the part of the heartbeat known as the QT interval is abnormally short.  If untreated, the arrhythmia associated with short QT syndrome can lead to a variety of signs and symptoms, from dizziness and fainting (syncope) to cardiac arrest and sudden death. These signs and symptoms can occur any time from early infancy to old age. This condition may explain some cases of sudden infant death syndrome (SIDS), which is a major cause of unexplained death in babies younger than 1 year. However, some people with short QT syndrome never experience any health problems associated with the condition.",short QT syndrome,0000902,GHR,https://ghr.nlm.nih.gov/condition/short-qt-syndrome,C2348199,T047,Disorders
How many people are affected by short QT syndrome ?,0000902-2,frequency,"Short QT syndrome appears to be rare. At least 70 cases have been identified worldwide since the condition was discovered in 2000. However, the condition may be underdiagnosed because some affected individuals never experience symptoms.",short QT syndrome,0000902,GHR,https://ghr.nlm.nih.gov/condition/short-qt-syndrome,C2348199,T047,Disorders
What are the genetic changes related to short QT syndrome ?,0000902-3,genetic changes,"Mutations in the KCNH2, KCNJ2, and KCNQ1 genes can cause short QT syndrome. These genes provide instructions for making channels that transport positively charged atoms (ions) of potassium out of cells. In cardiac muscle, these ion channels play critical roles in maintaining the heart's normal rhythm. Mutations in the KCNH2, KCNJ2, or KCNQ1 gene increase the activity of the channels, which enhances the flow of potassium ions across the membrane of cardiac muscle cells. This change in ion transport alters the electrical activity of the heart and can lead to the abnormal heart rhythms characteristic of short QT syndrome.  Some affected individuals do not have an identified mutation in the KCNH2, KCNJ2, or KCNQ1 gene. Changes in other genes that have not been identified may cause the disorder in these cases.",short QT syndrome,0000902,GHR,https://ghr.nlm.nih.gov/condition/short-qt-syndrome,C2348199,T047,Disorders
Is short QT syndrome inherited ?,0000902-4,inheritance,"Short QT syndrome appears to have an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Some affected individuals have a family history of short QT syndrome or related heart problems and sudden cardiac death. Other cases of short QT syndrome are classified as sporadic and occur in people with no apparent family history of related heart problems.",short QT syndrome,0000902,GHR,https://ghr.nlm.nih.gov/condition/short-qt-syndrome,C2348199,T047,Disorders
What are the treatments for short QT syndrome ?,0000902-5,treatment,These resources address the diagnosis or management of short QT syndrome:  - Genetic Testing Registry: Short QT syndrome 1  - Genetic Testing Registry: Short QT syndrome 2  - Genetic Testing Registry: Short QT syndrome 3  - MedlinePlus Encyclopedia: Arrhythmias   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,short QT syndrome,0000902,GHR,https://ghr.nlm.nih.gov/condition/short-qt-syndrome,C2348199,T047,Disorders
"What is (are) short stature, hyperextensibility, hernia, ocular depression, Rieger anomaly, and teething delay ?",0000903-1,information,"Short stature, hyperextensibility, hernia, ocular depression, Rieger anomaly, and teething delay, commonly known by the acronym SHORT syndrome, is a rare disorder that affects many parts of the body.  Most people with SHORT syndrome are small at birth and gain weight slowly in childhood. Affected adults tend to have short stature compared with others in their family. Many have a lack of fatty tissue under the skin (lipoatrophy), primarily in the face, arms, and chest. This lack of fat, together with thin, wrinkled skin and veins visible beneath the skin, makes affected individuals look older than their biological age. This appearance of premature aging is sometimes described as progeroid.  Most people with SHORT syndrome have distinctive facial features. These include a triangular face shape with a prominent forehead and deep-set eyes (ocular depression), thin nostrils, a downturned mouth, and a small chin. Eye abnormalities are common in affected individuals, particularly Rieger anomaly, which affects structures at the front of the eye. Rieger anomaly can be associated with increased pressure in the eye (glaucoma) and vision loss. Some people with SHORT syndrome also have dental abnormalities such as delayed appearance (eruption) of teeth in early childhood, small teeth, fewer teeth than normal (hypodontia), and a lack of protective covering (enamel) on the surface of the teeth.  Other signs and symptoms that have been reported in people with SHORT syndrome include immune system abnormalities, a kidney disorder known as nephrocalcinosis, hearing loss, loose (hyperextensible) joints, and a soft out-pouching in the lower abdomen called an inguinal hernia. A few affected individuals have developed problems with blood sugar regulation including insulin resistance and diabetes. Most people with SHORT syndrome have normal intelligence, although a few have been reported with mild cognitive impairment or delayed development of speech in childhood.","short stature, hyperextensibility, hernia, ocular depression, Rieger anomaly, and teething delay",0000903,GHR,https://ghr.nlm.nih.gov/condition/short-stature-hyperextensibility-hernia-ocular-depression-rieger-anomaly-and-teething-delay,C0265341,T019,Disorders
"How many people are affected by short stature, hyperextensibility, hernia, ocular depression, Rieger anomaly, and teething delay ?",0000903-2,frequency,SHORT syndrome is a rare condition; its prevalence is unknown. Only a few affected individuals and families have been reported worldwide.,"short stature, hyperextensibility, hernia, ocular depression, Rieger anomaly, and teething delay",0000903,GHR,https://ghr.nlm.nih.gov/condition/short-stature-hyperextensibility-hernia-ocular-depression-rieger-anomaly-and-teething-delay,C0265341,T019,Disorders
"What are the genetic changes related to short stature, hyperextensibility, hernia, ocular depression, Rieger anomaly, and teething delay ?",0000903-3,genetic changes,"SHORT syndrome results from mutations in the PIK3R1 gene. This gene provides instructions for making one part (subunit) of an enzyme called PI3K, which plays a role in chemical signaling within cells. PI3K signaling is important for many cell activities, including cell growth and division, movement (migration) of cells, production of new proteins, transport of materials within cells, and cell survival. Studies suggest that PI3K signaling may be involved in the regulation of several hormones, including insulin, which helps control blood sugar levels. PI3K signaling may also play a role in the maturation of fat cells (adipocytes).  Mutations in the PIK3R1 gene alter the structure of the subunit, which reduces the ability of PI3K to participate in cell signaling. Researchers are working to determine how these changes lead to the specific features of SHORT syndrome. PI3K's role in insulin activity may be related to the development of insulin resistance and diabetes, and problems with adipocyte maturation might contribute to lipoatrophy in affected individuals. It is unclear how reduced PI3K signaling is associated with the other features of the condition.","short stature, hyperextensibility, hernia, ocular depression, Rieger anomaly, and teething delay",0000903,GHR,https://ghr.nlm.nih.gov/condition/short-stature-hyperextensibility-hernia-ocular-depression-rieger-anomaly-and-teething-delay,C0265341,T019,Disorders
"Is short stature, hyperextensibility, hernia, ocular depression, Rieger anomaly, and teething delay inherited ?",0000903-4,inheritance,"SHORT syndrome has an autosomal dominant pattern of inheritance, which means one copy of the altered PIK3R1 gene in each cell is sufficient to cause the disorder. In most cases, the condition results from a new mutation in the gene and occurs in people with no history of the disorder in their family. In other cases, an affected person inherits the mutation from one affected parent.","short stature, hyperextensibility, hernia, ocular depression, Rieger anomaly, and teething delay",0000903,GHR,https://ghr.nlm.nih.gov/condition/short-stature-hyperextensibility-hernia-ocular-depression-rieger-anomaly-and-teething-delay,C0265341,T019,Disorders
"What are the treatments for short stature, hyperextensibility, hernia, ocular depression, Rieger anomaly, and teething delay ?",0000903-5,treatment,These resources address the diagnosis or management of SHORT syndrome:  - Gene Review: Gene Review: SHORT Syndrome  - Genetic Testing Registry: SHORT syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,"short stature, hyperextensibility, hernia, ocular depression, Rieger anomaly, and teething delay",0000903,GHR,https://ghr.nlm.nih.gov/condition/short-stature-hyperextensibility-hernia-ocular-depression-rieger-anomaly-and-teething-delay,C0265341,T019,Disorders
What is (are) short-chain acyl-CoA dehydrogenase deficiency ?,0000904-1,information,"Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is a condition that prevents the body from converting certain fats into energy, especially during periods without food (fasting).  Signs and symptoms of SCAD deficiency may appear during infancy or early childhood and can include vomiting, low blood sugar (hypoglycemia), a lack of energy (lethargy), poor feeding, and failure to gain weight and grow at the expected rate (failure to thrive). Other features of this disorder may include poor muscle tone (hypotonia), seizures, developmental delay, and a small head size (microcephaly).  The symptoms of SCAD deficiency may be triggered by fasting or illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe condition that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.  In some people with SCAD deficiency, signs and symptoms do not appear until adulthood. These individuals are more likely to have problems related to muscle weakness and wasting.  The severity of this condition varies widely, even among members of the same family. Some individuals are diagnosed with SCAD deficiency based on laboratory testing but never develop any symptoms of the condition.",short-chain acyl-CoA dehydrogenase deficiency,0000904,GHR,https://ghr.nlm.nih.gov/condition/short-chain-acyl-coa-dehydrogenase-deficiency,C0342783,T047,Disorders
How many people are affected by short-chain acyl-CoA dehydrogenase deficiency ?,0000904-2,frequency,"This disorder is thought to affect approximately 1 in 35,000 to 50,000 newborns.",short-chain acyl-CoA dehydrogenase deficiency,0000904,GHR,https://ghr.nlm.nih.gov/condition/short-chain-acyl-coa-dehydrogenase-deficiency,C0342783,T047,Disorders
What are the genetic changes related to short-chain acyl-CoA dehydrogenase deficiency ?,0000904-3,genetic changes,"Mutations in the ACADS gene cause SCAD deficiency. This gene provides instructions for making an enzyme called short-chain acyl-CoA dehydrogenase, which is required to break down (metabolize) a group of fats called short-chain fatty acids. Fatty acids are a major source of energy for the heart and muscles. During periods of fasting, fatty acids are also an important energy source for the liver and other tissues.  Mutations in the ACADS gene lead to a shortage (deficiency) of the SCAD enzyme within cells. Without sufficient amounts of this enzyme, short-chain fatty acids are not metabolized properly. As a result, these fats are not converted into energy, which can lead to the signs and symptoms of this disorder, such as lethargy, hypoglycemia, and muscle weakness. It remains unclear why some people with SCAD deficiency never develop any symptoms.",short-chain acyl-CoA dehydrogenase deficiency,0000904,GHR,https://ghr.nlm.nih.gov/condition/short-chain-acyl-coa-dehydrogenase-deficiency,C0342783,T047,Disorders
Is short-chain acyl-CoA dehydrogenase deficiency inherited ?,0000904-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",short-chain acyl-CoA dehydrogenase deficiency,0000904,GHR,https://ghr.nlm.nih.gov/condition/short-chain-acyl-coa-dehydrogenase-deficiency,C0342783,T047,Disorders
What are the treatments for short-chain acyl-CoA dehydrogenase deficiency ?,0000904-5,treatment,These resources address the diagnosis or management of SCAD deficiency:  - Baby's First Test  - Gene Review: Gene Review: Short-Chain Acyl-CoA Dehydrogenase Deficiency  - Genetic Testing Registry: Deficiency of butyryl-CoA dehydrogenase  - MedlinePlus Encyclopedia: Newborn Screening Tests   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,short-chain acyl-CoA dehydrogenase deficiency,0000904,GHR,https://ghr.nlm.nih.gov/condition/short-chain-acyl-coa-dehydrogenase-deficiency,C0342783,T047,Disorders
What is (are) Shprintzen-Goldberg syndrome ?,0000905-1,information,"Shprintzen-Goldberg syndrome is a disorder that affects many parts of the body. Affected individuals have a combination of distinctive facial features and skeletal and neurological abnormalities.  A common feature in people with Shprintzen-Goldberg syndrome is craniosynostosis, which is the premature fusion of certain skull bones. This early fusion prevents the skull from growing normally. Affected individuals can also have distinctive facial features, including a long, narrow head; widely spaced eyes (hypertelorism); protruding eyes (exophthalmos); outside corners of the eyes that point downward (downslanting palpebral fissures); a high, narrow palate; a small lower jaw (micrognathia); and low-set ears that are rotated backward.  People with Shprintzen-Goldberg syndrome are often said to have a marfanoid habitus, because their bodies resemble those of people with a genetic condition called Marfan syndrome. For example, they may have long, slender fingers (arachnodactyly), unusually long limbs, a sunken chest (pectus excavatum) or protruding chest (pectus carinatum), and an abnormal side-to-side curvature of the spine (scoliosis). People with Shprintzen-Goldberg syndrome can have other skeletal abnormalities, such as one or more fingers that are permanently bent (camptodactyly) and an unusually large range of joint movement (hypermobility).  People with Shprintzen-Goldberg syndrome often have delayed development and mild to moderate intellectual disability.  Other common features of Shprintzen-Goldberg syndrome include heart or brain abnormalities, weak muscle tone (hypotonia) in infancy, and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia).  Shprintzen-Goldberg syndrome has signs and symptoms similar to those of Marfan syndrome and another genetic condition called Loeys-Dietz syndrome. However, intellectual disability is more likely to occur in Shprintzen-Goldberg syndrome than in the other two conditions. In addition, heart abnormalities are more common and usually more severe in Marfan syndrome and Loeys-Dietz syndrome.",Shprintzen-Goldberg syndrome,0000905,GHR,https://ghr.nlm.nih.gov/condition/shprintzen-goldberg-syndrome,C1321551,T019,Disorders
How many people are affected by Shprintzen-Goldberg syndrome ?,0000905-2,frequency,"Shprintzen-Goldberg syndrome is a rare condition, although its prevalence is unknown. It is difficult to identify the number of affected individuals, because some cases diagnosed as Shprintzen-Goldberg syndrome may instead be Marfan syndrome or Loeys-Dietz syndrome, which have overlapping signs and symptoms.",Shprintzen-Goldberg syndrome,0000905,GHR,https://ghr.nlm.nih.gov/condition/shprintzen-goldberg-syndrome,C1321551,T019,Disorders
What are the genetic changes related to Shprintzen-Goldberg syndrome ?,0000905-3,genetic changes,"Shprintzen-Goldberg syndrome is often caused by mutations in the SKI gene. This gene provides instructions for making a protein that regulates the transforming growth factor beta (TGF-) signaling pathway. The TGF- pathway regulates many processes, including cell growth and division (proliferation), the process by which cells mature to carry out special functions (differentiation), cell movement (motility), and the self-destruction of cells (apoptosis). By attaching to certain proteins in the pathway, the SKI protein blocks TGF- signaling. The SKI protein is found in many cell types throughout the body and appears to play a role in the development of many tissues, including the skull, other bones, skin, and brain.  SKI gene mutations involved in Shprintzen-Goldberg syndrome alter the SKI protein. The altered protein is no longer able to attach to proteins in the TGF- pathway and block signaling. As a result, the pathway is abnormally active. Excess TGF- signaling changes the regulation of gene activity and likely disrupts development of many body systems, including the bones and brain, resulting in the wide range of signs and symptoms of Shprintzen-Goldberg syndrome.  Not all cases of Shprintzen-Goldberg syndrome are caused by mutations in the SKI gene. Other genes may be involved in this condition, and in some cases, the genetic cause is unknown.",Shprintzen-Goldberg syndrome,0000905,GHR,https://ghr.nlm.nih.gov/condition/shprintzen-goldberg-syndrome,C1321551,T019,Disorders
Is Shprintzen-Goldberg syndrome inherited ?,0000905-4,inheritance,"Shprintzen-Goldberg syndrome is described as autosomal dominant, which means one copy of the altered gene in each cell is sufficient to cause the disorder. The condition almost always results from new (de novo) gene mutations and occurs in people with no history of the disorder in their family. Very rarely, people with Shprintzen-Goldberg syndrome have inherited the altered gene from an unaffected parent who has a gene mutation only in their sperm or egg cells. When a mutation is present only in reproductive cells, it is known as germline mosaicism.",Shprintzen-Goldberg syndrome,0000905,GHR,https://ghr.nlm.nih.gov/condition/shprintzen-goldberg-syndrome,C1321551,T019,Disorders
What are the treatments for Shprintzen-Goldberg syndrome ?,0000905-5,treatment,These resources address the diagnosis or management of Shprintzen-Goldberg syndrome:  - Gene Review: Gene Review: Shprintzen-Goldberg Syndrome  - Genetic Testing Registry: Shprintzen-Goldberg syndrome  - Johns Hopkins Medicine: Diagnosis of Craniosynostosis  - MedlinePlus Encyclopedia: Craniosynostosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Shprintzen-Goldberg syndrome,0000905,GHR,https://ghr.nlm.nih.gov/condition/shprintzen-goldberg-syndrome,C1321551,T019,Disorders
What is (are) Shwachman-Diamond syndrome ?,0000906-1,information,"Shwachman-Diamond syndrome is an inherited condition that affects many parts of the body, particularly the bone marrow, pancreas, and skeletal system.  The major function of bone marrow is to produce new blood cells. These include red blood cells, which carry oxygen to the body's tissues; white blood cells, which fight infection; and platelets, which are necessary for normal blood clotting. In Shwachman-Diamond syndrome, the bone marrow malfunctions and does not make some or all types of white blood cells. A shortage of neutrophils, the most common type of white blood cell, causes a condition called neutropenia. Most people with Shwachman-Diamond syndrome have at least occasional episodes of neutropenia, which makes them more vulnerable to infections such as pneumonia, recurrent ear infections (otitis media), and skin infections. Less commonly, bone marrow abnormalities lead to a shortage of red blood cells (anemia), which causes fatigue and weakness, or a reduction in the amount of platelets (thrombocytopenia), which can result in easy bruising and abnormal bleeding.  People with Shwachman-Diamond syndrome have an increased risk of several serious complications related to their malfunctioning bone marrow. Specifically, they have a higher-than-average chance of developing myelodysplastic syndrome (MDS) and aplastic anemia, which are disorders that affect blood cell production, and a cancer of blood-forming tissue known as acute myeloid leukemia (AML).  Shwachman-Diamond syndrome also affects the pancreas, which is an organ that plays an essential role in digestion. One of this organ's main functions is to produce enzymes that help break down and use the nutrients from food. In most infants with Shwachman-Diamond syndrome, the pancreas does not produce enough of these enzymes. This condition is known as pancreatic insufficiency. Infants with pancreatic insufficiency have trouble digesting food and absorbing nutrients that are needed for growth. As a result, they often have fatty, foul-smelling stools (steatorrhea); are slow to grow and gain weight (failure to thrive); and experience malnutrition. Pancreatic insufficiency often improves with age in people with Shwachman-Diamond syndrome.  Skeletal abnormalities are another common feature of Shwachman-Diamond syndrome. Many affected individuals have problems with bone formation and growth, most often affecting the hips and knees. Low bone density is also frequently associated with this condition. Some infants are born with a narrow rib cage and short ribs, which can cause life-threatening problems with breathing. The combination of skeletal abnormalities and slow growth results in short stature in most people with this disorder.  The complications of this condition can affect several other parts of the body, including the liver, heart, endocrine system (which produces hormones), eyes, teeth, and skin. Additionally, studies suggest that Shwachman-Diamond syndrome may be associated with delayed speech and the delayed development of motor skills such as sitting, standing, and walking.",Shwachman-Diamond syndrome,0000906,GHR,https://ghr.nlm.nih.gov/condition/shwachman-diamond-syndrome,C0272170,T047,Disorders
How many people are affected by Shwachman-Diamond syndrome ?,0000906-2,frequency,Researchers are not sure how common Shwachman-Diamond syndrome is. Several hundred cases have been reported in scientific studies.,Shwachman-Diamond syndrome,0000906,GHR,https://ghr.nlm.nih.gov/condition/shwachman-diamond-syndrome,C0272170,T047,Disorders
What are the genetic changes related to Shwachman-Diamond syndrome ?,0000906-3,genetic changes,"Mutations in the SBDS gene have been identified in about 90 percent of people with the characteristic features of Shwachman-Diamond syndrome. This gene provides instructions for making a protein whose function is unknown, although it is active in cells throughout the body. Researchers suspect that the SBDS protein may play a role in processing RNA (a molecule that is a chemical cousin of DNA). This protein may also be involved in building ribosomes, which are cellular structures that process the cell's genetic instructions to create proteins. It is unclear how SBDS mutations lead to the major signs and symptoms of Shwachman-Diamond syndrome.  In cases where no SBDS mutation is found, the cause of this disorder is unknown.",Shwachman-Diamond syndrome,0000906,GHR,https://ghr.nlm.nih.gov/condition/shwachman-diamond-syndrome,C0272170,T047,Disorders
Is Shwachman-Diamond syndrome inherited ?,0000906-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Shwachman-Diamond syndrome,0000906,GHR,https://ghr.nlm.nih.gov/condition/shwachman-diamond-syndrome,C0272170,T047,Disorders
What are the treatments for Shwachman-Diamond syndrome ?,0000906-5,treatment,These resources address the diagnosis or management of Shwachman-Diamond syndrome:  - Gene Review: Gene Review: Shwachman-Diamond Syndrome  - Genetic Testing Registry: Shwachman syndrome  - MedlinePlus Encyclopedia: Malabsorption   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Shwachman-Diamond syndrome,0000906,GHR,https://ghr.nlm.nih.gov/condition/shwachman-diamond-syndrome,C0272170,T047,Disorders
What is (are) sialic acid storage disease ?,0000907-1,information,"Sialic acid storage disease is an inherited disorder that primarily affects the nervous system. People with sialic acid storage disease have signs and symptoms that may vary widely in severity. This disorder is generally classified into one of three forms: infantile free sialic acid storage disease, Salla disease, and intermediate severe Salla disease.  Infantile free sialic acid storage disease (ISSD) is the most severe form of this disorder. Babies with this condition have severe developmental delay, weak muscle tone (hypotonia), and failure to gain weight and grow at the expected rate (failure to thrive). They may have unusual facial features that are often described as ""coarse,"" seizures, bone malformations, an enlarged liver and spleen (hepatosplenomegaly), and an enlarged heart (cardiomegaly). The abdomen may be swollen due to the enlarged organs and an abnormal buildup of fluid in the abdominal cavity (ascites). Affected infants may have a condition called hydrops fetalis in which excess fluid accumulates in the body before birth. Children with this severe form of the condition usually live only into early childhood.  Salla disease is a less severe form of sialic acid storage disease. Babies with Salla disease usually begin exhibiting hypotonia during the first year of life and go on to experience progressive neurological problems. Signs and symptoms of Salla disease include intellectual disability and developmental delay, seizures, problems with movement and balance (ataxia), abnormal tensing of the muscles (spasticity), and involuntary slow, sinuous movements of the limbs (athetosis). Individuals with Salla disease usually survive into adulthood.  People with intermediate severe Salla disease have signs and symptoms that fall between those of ISSD and Salla disease in severity.",sialic acid storage disease,0000907,GHR,https://ghr.nlm.nih.gov/condition/sialic-acid-storage-disease,C0342853,T047,Disorders
How many people are affected by sialic acid storage disease ?,0000907-2,frequency,Sialic acid storage disease is a very rare disorder. ISSD has been identified in only a few dozen infants worldwide. Salla disease occurs mainly in Finland and Sweden and has been reported in approximately 150 people. A few individuals have been identified as having intermediate severe Salla disease.,sialic acid storage disease,0000907,GHR,https://ghr.nlm.nih.gov/condition/sialic-acid-storage-disease,C0342853,T047,Disorders
What are the genetic changes related to sialic acid storage disease ?,0000907-3,genetic changes,"Mutations in the SLC17A5 gene cause all forms of sialic acid storage disease. This gene provides instructions for producing a protein called sialin that is located mainly on the membranes of lysosomes, compartments in the cell that digest and recycle materials. Sialin moves a molecule called free sialic acid, which is produced when certain proteins and fats are broken down, out of the lysosomes to other parts of the cell. Free sialic acid means that the sialic acid is not attached (bound) to other molecules. Researchers believe that sialin may also have other functions in brain cells, in addition to those associated with the lysosomes, but these additional functions are not well understood.  Approximately 20 mutations that cause sialic acid storage disease have been identified in the SLC17A5 gene. Some of these mutations result in sialin that does not function normally; others prevent sialin from being produced. In a few cases, sialin is produced but not routed properly to the lysosomal membrane.  SLC17A5 gene mutations that reduce or eliminate sialin activity result in a buildup of free sialic acid in the lysosomes. It is not known how this buildup, or the disruption of other possible functions of sialin in the brain, causes the specific signs and symptoms of sialic acid storage disease.",sialic acid storage disease,0000907,GHR,https://ghr.nlm.nih.gov/condition/sialic-acid-storage-disease,C0342853,T047,Disorders
Is sialic acid storage disease inherited ?,0000907-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",sialic acid storage disease,0000907,GHR,https://ghr.nlm.nih.gov/condition/sialic-acid-storage-disease,C0342853,T047,Disorders
What are the treatments for sialic acid storage disease ?,0000907-5,treatment,"These resources address the diagnosis or management of sialic acid storage disease:  - Gene Review: Gene Review: Free Sialic Acid Storage Disorders  - Genetic Testing Registry: Salla disease  - Genetic Testing Registry: Sialic acid storage disease, severe infantile type   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",sialic acid storage disease,0000907,GHR,https://ghr.nlm.nih.gov/condition/sialic-acid-storage-disease,C0342853,T047,Disorders
What is (are) sialidosis ?,0000908-1,information,"Sialidosis is a severe inherited disorder that affects many organs and tissues, including the nervous system. This disorder is divided into two types, which are distinguished by the age at which symptoms appear and the severity of features.  Sialidosis type I, also referred to as cherry-red spot myoclonus syndrome, is the less severe form of this condition. People with type I develop signs and symptoms of sialidosis in their teens or twenties. Initially, affected individuals experience problems walking (gait disturbance) and/or a loss of sharp vision (reduced visual acuity). Individuals with sialidosis type I also experience muscle twitches (myoclonus), difficulty coordinating movements (ataxia), leg tremors, and seizures. The myoclonus worsens over time, causing difficulty sitting, standing, or walking. People with sialidosis type I eventually require wheelchair assistance. Affected individuals have progressive vision problems, including impaired color vision or night blindness. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. Sialidosis type I does not affect intelligence or life expectancy.  Sialidosis type II, the more severe type of the disorder, is further divided into congenital, infantile, and juvenile forms. The features of congenital sialidosis type II can develop before birth. This form of sialidosis is associated with an abnormal buildup of fluid in the abdominal cavity (ascites) or widespread swelling before birth caused by fluid accumulation (hydrops fetalis). Affected infants may also have an enlarged liver and spleen (hepatosplenomegaly), abnormal bone development (dysostosis multiplex), and distinctive facial features that are often described as ""coarse."" As a result of these serious health problems, individuals with congenital sialidosis type II usually are stillborn or die soon after birth.  Infantile sialidosis type II shares some features with the congenital form, although the signs and symptoms are slightly less severe and begin within the first year of life. Features of the infantile form include hepatosplenomegaly, dysostosis multiplex, ""coarse"" facial features, short stature, and intellectual disability. As children with infantile sialidosis type II get older, they may develop myoclonus and cherry-red spots. Other signs and symptoms include hearing loss, overgrowth of the gums (gingival hyperplasia), and widely spaced teeth. Affected individuals may survive into childhood or adolescence.  The juvenile form has the least severe signs and symptoms of the different forms of sialidosis type II. Features of this condition usually appear in late childhood and may include mildly ""coarse"" facial features, mild bone abnormalities, cherry-red spots, myoclonus, intellectual disability, and dark red spots on the skin (angiokeratomas). The life expectancy of individuals with juvenile sialidosis type II varies depending on the severity of symptoms.",sialidosis,0000908,GHR,https://ghr.nlm.nih.gov/condition/sialidosis,C0268226,T047,Disorders
How many people are affected by sialidosis ?,0000908-2,frequency,The overall prevalence of sialidosis is unknown. Sialidosis type I appears to be more common in people with Italian ancestry.,sialidosis,0000908,GHR,https://ghr.nlm.nih.gov/condition/sialidosis,C0268226,T047,Disorders
What are the genetic changes related to sialidosis ?,0000908-3,genetic changes,"Mutations in the NEU1 gene cause sialidosis. This gene provides instructions for making an enzyme called neuraminidase 1 (NEU1), which is found in lysosomes. Lysosomes are compartments within the cell that use enzymes to digest and recycle materials. The NEU1 enzyme helps break down large sugar molecules attached to certain proteins by removing a substance known as sialic acid.  Mutations in the NEU1 gene lead to a shortage (deficiency) of the NEU1 enzyme. When this enzyme is lacking, sialic acid-containing compounds accumulate inside lysosomes. Conditions such as sialidosis that cause molecules to build up inside lysosomes are called lysosomal storage disorders. People with sialidosis type II have mutations that severely reduce or eliminate NEU1 enzyme activity. Individuals with sialidosis type I have mutations that result in some functional NEU1 enzyme. It is unclear exactly how the accumulation of large molecules within lysosomes leads to the signs and symptoms of sialidosis.",sialidosis,0000908,GHR,https://ghr.nlm.nih.gov/condition/sialidosis,C0268226,T047,Disorders
Is sialidosis inherited ?,0000908-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",sialidosis,0000908,GHR,https://ghr.nlm.nih.gov/condition/sialidosis,C0268226,T047,Disorders
What are the treatments for sialidosis ?,0000908-5,treatment,"These resources address the diagnosis or management of sialidosis:  - Genetic Testing Registry: Sialidosis type I  - Genetic Testing Registry: Sialidosis, type II  - MedlinePlus Encyclopedia: Ascites  - MedlinePlus Encyclopedia: Hydrops Fetalis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",sialidosis,0000908,GHR,https://ghr.nlm.nih.gov/condition/sialidosis,C0268226,T047,Disorders
What is (are) sialuria ?,0000909-1,information,"Sialuria is a rare disorder that has variable effects on development. Affected infants are often born with a yellow tint to the skin and the whites of the eyes (neonatal jaundice), an enlarged liver and spleen (hepatosplenomegaly), and unusually small red blood cells (microcytic anemia). They may develop a somewhat flat face and distinctive-looking facial features that are described as ""coarse."" Temporarily delayed development and weak muscle tone (hypotonia) have also been reported.  Young children with sialuria tend to have frequent upper respiratory infections and episodes of dehydration and stomach upset (gastroenteritis). Older children may have seizures and learning difficulties. In some affected children, intellectual development is nearly normal.  The features of sialuria vary widely among affected people. Many of the problems associated with this disorder appear to improve with age, although little is known about the long-term effects of the disease. It is likely that some adults with sialuria never come to medical attention because they have very mild signs and symptoms or no health problems related to the condition.",sialuria,0000909,GHR,https://ghr.nlm.nih.gov/condition/sialuria,C0342853,T047,Disorders
How many people are affected by sialuria ?,0000909-2,frequency,"Fewer than 10 people worldwide have been diagnosed with sialuria. There are probably more people with the disorder who have not been diagnosed, as sialuria can be difficult to detect because of its variable features.",sialuria,0000909,GHR,https://ghr.nlm.nih.gov/condition/sialuria,C0342853,T047,Disorders
What are the genetic changes related to sialuria ?,0000909-3,genetic changes,"Mutations in the GNE gene cause sialuria. The GNE gene provides instructions for making an enzyme found in cells and tissues throughout the body. This enzyme is involved in a chemical pathway that produces sialic acid, which is a simple sugar that attaches to the ends of more complex molecules on the surface of cells. By modifying these molecules, sialic acid influences a wide variety of cellular functions including cell movement (migration), attachment of cells to one another (adhesion), signaling between cells, and inflammation.  The enzyme produced from the GNE gene is carefully controlled to ensure that cells produce an appropriate amount of sialic acid. A feedback system shuts off the enzyme when no more sialic acid is needed. The mutations responsible for sialuria disrupt this feedback mechanism, resulting in an overproduction of sialic acid. This simple sugar builds up within cells and is excreted in urine. Researchers are working to determine how an accumulation of sialic acid in the body interferes with normal development in people with sialuria.",sialuria,0000909,GHR,https://ghr.nlm.nih.gov/condition/sialuria,C0342853,T047,Disorders
Is sialuria inherited ?,0000909-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most reported cases have occurred in people with no known history of the disorder in their family and may result from new mutations in the gene.",sialuria,0000909,GHR,https://ghr.nlm.nih.gov/condition/sialuria,C0342853,T047,Disorders
What are the treatments for sialuria ?,0000909-5,treatment,These resources address the diagnosis or management of sialuria:  - Gene Review: Gene Review: Sialuria  - Genetic Testing Registry: Sialuria  - MedlinePlus Encyclopedia: Hepatosplenomegaly (image)  - MedlinePlus Encyclopedia: Newborn Jaundice   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,sialuria,0000909,GHR,https://ghr.nlm.nih.gov/condition/sialuria,C0342853,T047,Disorders
What is (are) sick sinus syndrome ?,0000910-1,information,"Sick sinus syndrome (also known as sinus node dysfunction) is a group of related heart conditions that can affect how the heart beats. ""Sick sinus"" refers to the sino-atrial (SA) node, which is an area of specialized cells in the heart that functions as a natural pacemaker. The SA node generates electrical impulses that start each heartbeat. These signals travel from the SA node to the rest of the heart, signaling the heart (cardiac) muscle to contract and pump blood. In people with sick sinus syndrome, the SA node does not function normally. In some cases, it does not produce the right signals to trigger a regular heartbeat. In others, abnormalities disrupt the electrical impulses and prevent them from reaching the rest of the heart.  Sick sinus syndrome tends to cause the heartbeat to be too slow (bradycardia), although occasionally the heartbeat is too fast (tachycardia). In some cases, the heartbeat rapidly switches from being too fast to being too slow, a condition known as tachycardia-bradycardia syndrome. Symptoms related to abnormal heartbeats can include dizziness, light-headedness, fainting (syncope), a sensation of fluttering or pounding in the chest (palpitations), and confusion or memory problems. During exercise, many affected individuals experience chest pain, difficulty breathing, or excessive tiredness (fatigue). Once symptoms of sick sinus syndrome appear, they usually worsen with time. However, some people with the condition never experience any related health problems.  Sick sinus syndrome occurs most commonly in older adults, although it can be diagnosed in people of any age. The condition increases the risk of several life-threatening problems involving the heart and blood vessels. These include a heart rhythm abnormality called atrial fibrillation, heart failure, cardiac arrest, and stroke.",sick sinus syndrome,0000910,GHR,https://ghr.nlm.nih.gov/condition/sick-sinus-syndrome,C1963235,T047,Disorders
How many people are affected by sick sinus syndrome ?,0000910-2,frequency,Sick sinus syndrome accounts for 1 in 600 patients with heart disease who are over age 65. The incidence of this condition increases with age.,sick sinus syndrome,0000910,GHR,https://ghr.nlm.nih.gov/condition/sick-sinus-syndrome,C1963235,T047,Disorders
What are the genetic changes related to sick sinus syndrome ?,0000910-3,genetic changes,"Sick sinus syndrome can result from genetic or environmental factors. In many cases, the cause of the condition is unknown.  Genetic changes are an uncommon cause of sick sinus syndrome. Mutations in two genes, SCN5A and HCN4, have been found to cause the condition in a small number of families. These genes provide instructions for making proteins called ion channels that transport positively charged atoms (ions) into cardiac cells, including cells that make up the SA node. The flow of these ions is essential for creating the electrical impulses that start each heartbeat and coordinate contraction of the cardiac muscle. Mutations in these genes reduce the flow of ions, which alters the SA node's ability to create and spread electrical signals. These changes lead to abnormal heartbeats and the other symptoms of sick sinus syndrome.  A particular variation in another gene, MYH6, appears to increase the risk of developing sick sinus syndrome. The protein produced from the MYH6 gene forms part of a larger protein called myosin, which generates the mechanical force needed for cardiac muscle to contract. Researchers believe that the MYH6 gene variation changes the structure of myosin, which can affect cardiac muscle contraction and increase the likelihood of developing an abnormal heartbeat.  More commonly, sick sinus syndrome is caused by other factors that alter the structure or function of the SA node. These include a variety of heart conditions, other disorders such as muscular dystrophy, abnormal inflammation, or a shortage of oxygen (hypoxia). Certain medications, such as drugs given to treat abnormal heart rhythms or high blood pressure, can also disrupt SA node function. One of the most common causes of sick sinus syndrome in children is trauma to the SA node, such as damage that occurs during heart surgery.  In older adults, sick sinus syndrome is often associated with age-related changes in the heart. Over time, the SA node may harden and develop scar-like damage (fibrosis) that prevents it from working properly.",sick sinus syndrome,0000910,GHR,https://ghr.nlm.nih.gov/condition/sick-sinus-syndrome,C1963235,T047,Disorders
Is sick sinus syndrome inherited ?,0000910-4,inheritance,"Most cases of sick sinus syndrome are not inherited. They are described as sporadic, which means they occur in people with no history of the disorder in their family.  When sick sinus syndrome results from mutations in the HCN4 gene, it has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.  When sick sinus syndrome is caused by mutations in the SCN5A gene, it is inherited in an autosomal recessive pattern. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",sick sinus syndrome,0000910,GHR,https://ghr.nlm.nih.gov/condition/sick-sinus-syndrome,C1963235,T047,Disorders
What are the treatments for sick sinus syndrome ?,0000910-5,treatment,"These resources address the diagnosis or management of sick sinus syndrome:  - Cleveland Clinic: Management of Arrhythmias  - Genetic Testing Registry: Sick sinus syndrome 1, autosomal recessive  - Genetic Testing Registry: Sick sinus syndrome 2, autosomal dominant  - Genetic Testing Registry: Sick sinus syndrome 3, susceptibility to  - National Heart Lung and Blood Institute: What Is a Pacemaker?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",sick sinus syndrome,0000910,GHR,https://ghr.nlm.nih.gov/condition/sick-sinus-syndrome,C1963235,T047,Disorders
What is (are) sickle cell disease ?,0000911-1,information,"Sickle cell disease is a group of disorders that affects hemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body. People with this disorder have atypical hemoglobin molecules called hemoglobin S, which can distort red blood cells into a sickle, or crescent, shape.  Signs and symptoms of sickle cell disease usually begin in early childhood. Characteristic features of this disorder include a low number of red blood cells (anemia), repeated infections, and periodic episodes of pain. The severity of symptoms varies from person to person. Some people have mild symptoms, while others are frequently hospitalized for more serious complications.  The signs and symptoms of sickle cell disease are caused by the sickling of red blood cells. When red blood cells sickle, they break down prematurely, which can lead to anemia. Anemia can cause shortness of breath, fatigue, and delayed growth and development in children. The rapid breakdown of red blood cells may also cause yellowing of the eyes and skin, which are signs of jaundice. Painful episodes can occur when sickled red blood cells, which are stiff and inflexible, get stuck in small blood vessels. These episodes deprive tissues and organs of oxygen-rich blood and can lead to organ damage, especially in the lungs, kidneys, spleen, and brain. A particularly serious complication of sickle cell disease is high blood pressure in the blood vessels that supply the lungs (pulmonary hypertension). Pulmonary hypertension occurs in about one-third of adults with sickle cell disease and can lead to heart failure.",sickle cell disease,0000911,GHR,https://ghr.nlm.nih.gov/condition/sickle-cell-disease,C0002895,T047,Disorders
How many people are affected by sickle cell disease ?,0000911-2,frequency,"Sickle cell disease affects millions of people worldwide. It is most common among people whose ancestors come from Africa; Mediterranean countries such as Greece, Turkey, and Italy; the Arabian Peninsula; India; and Spanish-speaking regions in South America, Central America, and parts of the Caribbean.  Sickle cell disease is the most common inherited blood disorder in the United States, affecting 70,000 to 80,000 Americans. The disease is estimated to occur in 1 in 500 African Americans and 1 in 1,000 to 1,400 Hispanic Americans.",sickle cell disease,0000911,GHR,https://ghr.nlm.nih.gov/condition/sickle-cell-disease,C0002895,T047,Disorders
What are the genetic changes related to sickle cell disease ?,0000911-3,genetic changes,"Mutations in the HBB gene cause sickle cell disease.  Hemoglobin consists of four protein subunits, typically, two subunits called alpha-globin and two subunits called beta-globin. The HBB gene provides instructions for making beta-globin. Various versions of beta-globin result from different mutations in the HBB gene. One particular HBB gene mutation produces an abnormal version of beta-globin known as hemoglobin S (HbS). Other mutations in the HBB gene lead to additional abnormal versions of beta-globin such as hemoglobin C (HbC) and hemoglobin E (HbE). HBB gene mutations can also result in an unusually low level of beta-globin; this abnormality is called beta thalassemia.  In people with sickle cell disease, at least one of the beta-globin subunits in hemoglobin is replaced with hemoglobin S. In sickle cell anemia, which is a common form of sickle cell disease, hemoglobin S replaces both beta-globin subunits in hemoglobin. In other types of sickle cell disease, just one beta-globin subunit in hemoglobin is replaced with hemoglobin S. The other beta-globin subunit is replaced with a different abnormal variant, such as hemoglobin C. For example, people with sickle-hemoglobin C (HbSC) disease have hemoglobin molecules with hemoglobin S and hemoglobin C instead of beta-globin. If mutations that produce hemoglobin S and beta thalassemia occur together, individuals have hemoglobin S-beta thalassemia (HbSBetaThal) disease.  Abnormal versions of beta-globin can distort red blood cells into a sickle shape. The sickle-shaped red blood cells die prematurely, which can lead to anemia. Sometimes the inflexible, sickle-shaped cells get stuck in small blood vessels and can cause serious medical complications.",sickle cell disease,0000911,GHR,https://ghr.nlm.nih.gov/condition/sickle-cell-disease,C0002895,T047,Disorders
Is sickle cell disease inherited ?,0000911-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",sickle cell disease,0000911,GHR,https://ghr.nlm.nih.gov/condition/sickle-cell-disease,C0002895,T047,Disorders
What are the treatments for sickle cell disease ?,0000911-5,treatment,"These resources address the diagnosis or management of sickle cell disease:  - Baby's First Test: S, Beta-Thalassemia  - Baby's First Test: S, C Disease  - Baby's First Test: Sickle Cell Anemia  - Gene Review: Gene Review: Sickle Cell Disease  - Genetic Testing Registry: Hb SS disease  - Genomics Education Programme (UK)  - Howard University Hospital Center for Sickle Cell Disease  - MedlinePlus Encyclopedia: Sickle Cell Anemia  - MedlinePlus Encyclopedia: Sickle Cell Test   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",sickle cell disease,0000911,GHR,https://ghr.nlm.nih.gov/condition/sickle-cell-disease,C0002895,T047,Disorders
What is (are) Silver syndrome ?,0000912-1,information,"Silver syndrome belongs to a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and, frequently, development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. Both types involve the lower limbs; the complex types may also involve the upper limbs, although to a lesser degree. In addition, the complex types may affect the brain and parts of the nervous system involved in muscle movement and sensations. Silver syndrome is a complex hereditary spastic paraplegia.  The first sign of Silver syndrome is usually weakness in the muscles of the hands. These muscles waste away (amyotrophy), resulting in abnormal positioning of the thumbs and difficulty using the fingers and hands for tasks such as handwriting. People with Silver syndrome often have high-arched feet (pes cavus) and spasticity in the legs. The signs and symptoms of Silver syndrome typically begin in late childhood but can start anytime from early childhood to late adulthood. The muscle problems associated with Silver syndrome slowly worsen with age, but affected individuals can remain active throughout life.",Silver syndrome,0000912,GHR,https://ghr.nlm.nih.gov/condition/silver-syndrome,C0175693,T047,Disorders
How many people are affected by Silver syndrome ?,0000912-2,frequency,"Although Silver syndrome appears to be a rare condition, its exact prevalence is unknown.",Silver syndrome,0000912,GHR,https://ghr.nlm.nih.gov/condition/silver-syndrome,C0175693,T047,Disorders
What are the genetic changes related to Silver syndrome ?,0000912-3,genetic changes,"Mutations in the BSCL2 gene cause Silver syndrome. The BSCL2 gene provides instructions for making a protein called seipin, whose function is unknown. The BSCL2 gene is active (expressed) in cells throughout the body, particularly in nerve cells that control muscle movement (motor neurons) and in brain cells. Within cells, seipin is found in the membrane of a cell structure called the endoplasmic reticulum, which is involved in protein processing and transport.  BSCL2 gene mutations that cause Silver syndrome likely lead to an alteration in the structure of seipin, causing it to fold into an incorrect 3-dimensional shape. Research findings indicate that misfolded seipin proteins accumulate in the endoplasmic reticulum. This accumulation likely damages and kills motor neurons, which leads to muscle weakness and spasticity. In Silver syndrome, only specific motor neurons are involved, resulting in the hand and leg muscles being solely affected.  Some people with Silver syndrome do not have an identified mutation in the BSCL2 gene. The cause of the condition in these individuals is unknown.",Silver syndrome,0000912,GHR,https://ghr.nlm.nih.gov/condition/silver-syndrome,C0175693,T047,Disorders
Is Silver syndrome inherited ?,0000912-4,inheritance,"Silver syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In these cases, the affected person inherits the mutation from one affected parent. However, some people who inherit the altered gene never develop features of Silver syndrome. (This situation is known as reduced penetrance.) It is unclear why some people with a mutated gene develop the disease and other people with a mutated gene do not.  Rarely, Silver syndrome is caused by new mutations in the gene and occurs in people with no history of the disorder in their family.",Silver syndrome,0000912,GHR,https://ghr.nlm.nih.gov/condition/silver-syndrome,C0175693,T047,Disorders
What are the treatments for Silver syndrome ?,0000912-5,treatment,"These resources address the diagnosis or management of Silver syndrome:  - Gene Review: Gene Review: BSCL2-Related Neurologic Disorders/Seipinopathy  - Gene Review: Gene Review: Hereditary Spastic Paraplegia Overview  - Genetic Testing Registry: Spastic paraplegia 17  - Spastic Paraplegia Foundation, Inc.: Treatments and Therapies   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Silver syndrome,0000912,GHR,https://ghr.nlm.nih.gov/condition/silver-syndrome,C0175693,T047,Disorders
What is (are) Simpson-Golabi-Behmel syndrome ?,0000913-1,information,"Simpson-Golabi-Behmel syndrome is a condition that affects many parts of the body and occurs primarily in males. This condition is classified as an overgrowth syndrome, which means that affected infants are considerably larger than normal at birth (macrosomia) and continue to grow and gain weight at an unusual rate. The other signs and symptoms of Simpson-Golabi-Behmel syndrome vary widely. The most severe cases are life-threatening before birth or in infancy, whereas people with milder cases often live into adulthood.  People with Simpson-Golabi-Behmel syndrome have distinctive facial features including widely spaced eyes (ocular hypertelorism), an unusually large mouth (macrostomia), a large tongue (macroglossia) that may have a deep groove or furrow down the middle, a broad nose with an upturned tip, and abnormalities affecting the roof of the mouth (the palate). The facial features are often described as ""coarse"" in older children and adults with this condition.  Other features of Simpson-Golabi-Behmel syndrome involve the chest and abdomen. Affected infants may be born with one or more extra nipples, an abnormal opening in the muscle covering the abdomen (diastasis recti), a soft out-pouching around the belly-button (an umbilical hernia), or a hole in the diaphragm (a diaphragmatic hernia) that allows the stomach and intestines to move into the chest and crowd the developing heart and lungs.  Simpson-Golabi-Behmel syndrome can also cause heart defects, malformed or abnormally large kidneys, an enlarged liver and spleen (hepatosplenomegaly), and skeletal abnormalities. Additionally, the syndrome can affect the development of the gastrointestinal system, urinary system, and genitalia. Some people with this condition have mild to severe intellectual disability, while others have normal intelligence.  About 10 percent of people with Simpson-Golabi-Behmel syndrome develop cancerous or noncancerous tumors in early childhood. The most common tumors are a rare form of kidney cancer called Wilms tumor and a cancerous tumor called a neuroblastoma that arises in developing nerve cells.",Simpson-Golabi-Behmel syndrome,0000913,GHR,https://ghr.nlm.nih.gov/condition/simpson-golabi-behmel-syndrome,C0796154,T019,Disorders
How many people are affected by Simpson-Golabi-Behmel syndrome ?,0000913-2,frequency,The incidence of Simpson-Golabi-Behmel syndrome is unknown. At least 130 people worldwide have been diagnosed with this disorder.,Simpson-Golabi-Behmel syndrome,0000913,GHR,https://ghr.nlm.nih.gov/condition/simpson-golabi-behmel-syndrome,C0796154,T019,Disorders
What are the genetic changes related to Simpson-Golabi-Behmel syndrome ?,0000913-3,genetic changes,"Mutations in the GPC3 gene are responsible for some cases of Simpson-Golabi-Behmel syndrome. This gene provides instructions for making a protein called glypican 3, which is involved in the regulation of cell growth and division (cell proliferation). Researchers believe that the GPC3 protein can also cause certain cells to self-destruct (undergo apoptosis) when they are no longer needed, which can help establish the body's shape.  GPC3 mutations can delete part or all of the gene, or alter the structure of glypican 3. These mutations prevent the protein from performing its usual functions, which may contribute to an increased rate of cell growth and cell division starting before birth. It is unclear, however, how a shortage of functional glypican 3 causes overgrowth of the entire body and the other abnormalities characteristic of Simpson-Golabi-Behmel syndrome.  Some individuals with Simpson-Golabi-Behmel syndrome do not have identified mutations in the GPC3 gene. In these cases, the cause of the condition is unknown.",Simpson-Golabi-Behmel syndrome,0000913,GHR,https://ghr.nlm.nih.gov/condition/simpson-golabi-behmel-syndrome,C0796154,T019,Disorders
Is Simpson-Golabi-Behmel syndrome inherited ?,0000913-4,inheritance,"This condition is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. Because females have two copies of the X chromosome, one altered copy of the gene in each cell usually leads to less severe symptoms in females than in males, or it may cause no symptoms at all.  Some females who have one altered copy of the GPC3 gene have distinctive facial features including an upturned nose, a wide mouth, and a prominent chin. Their fingernails may be malformed and they can have extra nipples. Skeletal abnormalities, including extra spinal bones (vertebrae), are also possible in affected females. Other females who carry one altered copy of the GPC3 gene do not have these features or any other medical problems associated with Simpson-Golabi-Behmel syndrome.",Simpson-Golabi-Behmel syndrome,0000913,GHR,https://ghr.nlm.nih.gov/condition/simpson-golabi-behmel-syndrome,C0796154,T019,Disorders
What are the treatments for Simpson-Golabi-Behmel syndrome ?,0000913-5,treatment,These resources address the diagnosis or management of Simpson-Golabi-Behmel syndrome:  - Gene Review: Gene Review: Simpson-Golabi-Behmel Syndrome Type 1  - Genetic Testing Registry: Simpson-Golabi-Behmel syndrome  - MedlinePlus Encyclopedia: Diastasis Recti  - MedlinePlus Encyclopedia: Macrosomia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Simpson-Golabi-Behmel syndrome,0000913,GHR,https://ghr.nlm.nih.gov/condition/simpson-golabi-behmel-syndrome,C0796154,T019,Disorders
What is (are) sitosterolemia ?,0000914-1,information,"Sitosterolemia is a condition in which fatty substances (lipids) from vegetable oils, nuts, and other plant-based foods accumulate in the blood and tissues. These lipids are called plant sterols (or phytosterols). Sitosterol is one of several plant sterols that accumulate in this disorder, with a blood level 30 to 100 times greater than normal. Cholesterol, a similar fatty substance found in animal products, is mildly to moderately elevated in many people with sitosterolemia. Cholesterol levels are particularly high in some affected children.  Plant sterols are not produced by the body; they are taken in as components of foods. Signs and symptoms of sitosterolemia begin to appear early in life after foods containing plant sterols are introduced into the diet.  An accumulation of fatty deposits on the artery walls (atherosclerosis) may occur by adolescence or early adulthood in people with sitosterolemia. The deposits narrow the arteries and can eventually block blood flow, increasing the chance of a heart attack, stroke, or sudden death.  People with sitosterolemia typically develop small yellowish growths called xanthomas beginning in childhood. The xanthomas consist of accumulated lipids and may be located anywhere on or just under the skin, typically on the heels, knees, elbows, and buttocks. They may also occur in the bands that connect muscles to bones (tendons), including tendons of the hand and the tendon that connects the heel of the foot to the calf muscles (the Achilles tendon). Large xanthomas can cause pain, difficulty with movement, and cosmetic problems.  Joint stiffness and pain resulting from plant sterol deposits may also occur in individuals with sitosterolemia. Less often, affected individuals have blood abnormalities. Occasionally the blood abnormalities are the only signs of the disorder. The red blood cells may be broken down (undergo hemolysis) prematurely, resulting in a shortage of red blood cells (anemia). This type of anemia is called hemolytic anemia. Affected individuals sometimes have abnormally shaped red blood cells called stomatocytes. In addition, the blood cells involved in clotting, called platelets or thrombocytes, may be abnormally large (macrothrombocytopenia).",sitosterolemia,0000914,GHR,https://ghr.nlm.nih.gov/condition/sitosterolemia,C0342907,T046,Disorders
How many people are affected by sitosterolemia ?,0000914-2,frequency,"Only 80 to 100 individuals with sitosterolemia have been described in the medical literature. However, researchers believe that this condition is likely underdiagnosed because mild cases often do not come to medical attention. Studies suggest that the prevalence may be at least 1 in 50,000 people.",sitosterolemia,0000914,GHR,https://ghr.nlm.nih.gov/condition/sitosterolemia,C0342907,T046,Disorders
What are the genetic changes related to sitosterolemia ?,0000914-3,genetic changes,"Sitosterolemia is caused by mutations in the ABCG5 or ABCG8 gene. These genes provide instructions for making the two halves of a protein called sterolin. This protein is involved in eliminating plant sterols, which cannot be used by human cells.  Sterolin is a transporter protein, which is a type of protein that moves substances across cell membranes. It is found mostly in cells of the intestines and liver. After plant sterols in food are taken into intestinal cells, the sterolin transporters in these cells pump them back into the intestinal tract, decreasing absorption. Sterolin transporters in liver cells pump the plant sterols into a fluid called bile that is released into the intestine. From the intestine, the plant sterols are eliminated with the feces. This process removes most of the dietary plant sterols, and allows only about 5 percent of these substances to get into the bloodstream. Sterolin also helps regulate cholesterol levels in a similar fashion; normally about 50 percent of cholesterol in the diet is absorbed by the body.  Mutations in the ABCG5 or ABCG8 gene that cause sitosterolemia result in a defective sterolin transporter and impair the elimination of plant sterols and, to a lesser degree, cholesterol from the body. These fatty substances build up in the arteries, skin, and other tissues, resulting in atherosclerosis, xanthomas, and the additional signs and symptoms of sitosterolemia. Excess plant sterols, such as sitosterol, in red blood cells likely make their cell membranes stiff and prone to rupture, leading to hemolytic anemia. Changes in the lipid composition of the membranes of red blood cells and platelets may account for the other blood abnormalities that sometimes occur in sitosterolemia.",sitosterolemia,0000914,GHR,https://ghr.nlm.nih.gov/condition/sitosterolemia,C0342907,T046,Disorders
Is sitosterolemia inherited ?,0000914-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",sitosterolemia,0000914,GHR,https://ghr.nlm.nih.gov/condition/sitosterolemia,C0342907,T046,Disorders
What are the treatments for sitosterolemia ?,0000914-5,treatment,These resources address the diagnosis or management of sitosterolemia:  - Gene Review: Gene Review: Sitosterolemia  - Genetic Testing Registry: Sitosterolemia  - Massachusetts General Hospital: Lipid Metabolism   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,sitosterolemia,0000914,GHR,https://ghr.nlm.nih.gov/condition/sitosterolemia,C0342907,T046,Disorders
What is (are) Sjgren syndrome ?,0000915-1,information,"Sjgren syndrome is a disorder whose main features are dry eyes and a dry mouth. The condition typically develops gradually beginning in middle adulthood, but can occur at any age.  Sjgren syndrome is classified as an autoimmune disorder, one of a large group of conditions that occur when the immune system attacks the body's own tissues and organs. In Sjgren syndrome, the immune system primarily attacks the glands that produce tears (the lacrimal glands) and saliva (the salivary glands), impairing the glands' ability to secrete these fluids.  Dry eyes may lead to itching, burning, a feeling of sand in the eyes, blurry vision, or intolerance of bright or fluorescent lighting. A dry mouth can feel chalky or full of cotton, and affected individuals may have difficulty speaking, tasting food, or swallowing. Because saliva helps protect the teeth and the tissues of the oral cavity, people with Sjgren syndrome are at increased risk of tooth decay and infections in the mouth.  In most people with Sjgren syndrome, dry eyes and dry mouth are the primary features of the disorder, and general health and life expectancy are largely unaffected. However, in some cases the immune system also attacks and damages other organs and tissues. This complication is known as extraglandular involvement. Affected individuals may develop inflammation in connective tissues, which provide strength and flexibility to structures throughout the body. Disorders involving connective tissue inflammation are sometimes called rheumatic conditions. In Sjgren syndrome, extraglandular involvement may result in painful inflammation of the joints and muscles; dry, itchy skin and skin rashes; chronic cough; a hoarse voice; kidney and liver problems; numbness or tingling in the hands and feet; and, in women, vaginal dryness. Prolonged and extreme tiredness (fatigue) severe enough to affect activities of daily living may also occur in this disorder. A small number of people with Sjgren syndrome develop lymphoma, a blood-related cancer that causes tumor formation in the lymph nodes.  When Sjgren syndrome first occurs on its own, it is called primary Sjgren syndrome. Some individuals who are first diagnosed with another rheumatic disorder, such as rheumatoid arthritis or systemic lupus erythematosus, later develop the dry eyes and dry mouth characteristic of Sjgren syndrome. In such cases, the individual is said to have secondary Sjgren syndrome. Other autoimmune disorders can also develop after the onset of primary Sjgren syndrome. In all, about half of all individuals with Sjgren syndrome also have another autoimmune disorder.",Sjgren syndrome,0000915,GHR,https://ghr.nlm.nih.gov/condition/sjogren-syndrome,C0039082,T047,Disorders
How many people are affected by Sjgren syndrome ?,0000915-2,frequency,"Sjgren syndrome is a relatively common disorder; it occurs in 0.1 to 4 percent of the population. It is difficult to determine the exact prevalence because the characteristic features of this disorder, dry eyes and dry mouth, can also be caused by many other conditions. Women develop Sjgren syndrome about 10 times more often than men; the specific reason for this difference is unknown but likely involves the effects of sex hormones on immune system function.",Sjgren syndrome,0000915,GHR,https://ghr.nlm.nih.gov/condition/sjogren-syndrome,C0039082,T047,Disorders
What are the genetic changes related to Sjgren syndrome ?,0000915-3,genetic changes,"Sjgren syndrome is thought to result from a combination of genetic and environmental factors; however, no associations between specific genetic changes and the development of Sjgren syndrome have been confirmed. Researchers believe that variations in many genes affect the risk of developing Sjgren syndrome, but that development of the condition may be triggered by something in the environment. In particular, viral or bacterial infections, which activate the immune system, may have the potential to encourage the development of Sjgren syndrome in susceptible individuals. The genetic variations that increase susceptibility may reduce the body's ability to turn off the immune response when it is no longer needed.",Sjgren syndrome,0000915,GHR,https://ghr.nlm.nih.gov/condition/sjogren-syndrome,C0039082,T047,Disorders
Is Sjgren syndrome inherited ?,0000915-4,inheritance,"A predisposition to develop autoimmune disorders can be passed through generations in families. Relatives of people with Sjgren syndrome are at an increased risk of developing autoimmune diseases, although they are not necessarily more likely to develop Sjgren syndrome in particular. The inheritance pattern of this predisposition is unknown.",Sjgren syndrome,0000915,GHR,https://ghr.nlm.nih.gov/condition/sjogren-syndrome,C0039082,T047,Disorders
What are the treatments for Sjgren syndrome ?,0000915-5,treatment,These resources address the diagnosis or management of Sjgren syndrome:  - Genetic Testing Registry: Sjgren's syndrome  - MedlinePlus Encyclopedia: Schirmer's Test  - National Institute of Dental and Craniofacial Research: Sjgren's Syndrome Clinic  - Sjgren's Syndrome Foundation: Treatments   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Sjgren syndrome,0000915,GHR,https://ghr.nlm.nih.gov/condition/sjogren-syndrome,C0039082,T047,Disorders
What is (are) Sjgren-Larsson syndrome ?,0000916-1,information,"Sjgren-Larsson syndrome is a condition characterized by dry, scaly skin (ichthyosis); neurological problems; and eye problems. These symptoms are apparent by early childhood and usually do not worsen with age.  Affected infants tend to be born prematurely. At birth the skin is red (erythema), but later in infancy the skin becomes dry, rough, and scaly with a brownish or yellowish tone. Mild to severe itchiness (pruritus) is also common. These skin abnormalities are generally dispersed over the whole body, most severely affecting the nape of the neck, the torso, and the extremities. The skin of the face is usually not affected.  People with this condition may also have neurological signs and symptoms. Most affected individuals have leukoencephalopathy, which is a change in a type of brain tissue called white matter. White matter consists of nerve fibers covered by a substance (myelin) that insulates and protects the nerves. The leukoencephalopathy is thought to contribute to many of the neurological signs and symptoms in people with Sjgren-Larsson syndrome. Most affected individuals have intellectual disability that varies from mild to profound and is usually apparent by early childhood. People with Sjgren-Larsson syndrome have speech difficulties (dysarthria) and delayed speech. Usually they are able to produce only short sentences with poorly formed words. Rarely, people with this condition have normal intelligence. In addition, approximately 40 percent of people with Sjgren-Larsson syndrome have seizures.  Children with this condition often experience delayed development of motor skills (such as crawling and walking) due to abnormal muscle stiffness (spasticity) that is typically in their legs and, less commonly, also in their arms. About one-half of people with Sjgren-Larsson syndrome require wheelchair assistance and many others need some form of support to walk.  Affected individuals have tiny crystals in the light-sensitive tissue at the back of the eye (retina) that can be seen during an eye exam. Based on their appearance, these retinal crystals are often called glistening white dots. These white dots are usually apparent by early childhood, and it is unclear if they affect normal vision. People with Sjgren-Larsson syndrome may also have nearsightedness (myopia) or an increased sensitivity to light (photophobia).",Sjgren-Larsson syndrome,0000916,GHR,https://ghr.nlm.nih.gov/condition/sjogren-larsson-syndrome,C0039082,T047,Disorders
How many people are affected by Sjgren-Larsson syndrome ?,0000916-2,frequency,"Sjgren-Larsson syndrome was first observed in Sweden, where the prevalence of this condition is 1 per 250,000 individuals. Outside Sweden, the prevalence of this condition is unknown.",Sjgren-Larsson syndrome,0000916,GHR,https://ghr.nlm.nih.gov/condition/sjogren-larsson-syndrome,C0039082,T047,Disorders
What are the genetic changes related to Sjgren-Larsson syndrome ?,0000916-3,genetic changes,"Mutations in the ALDH3A2 gene cause Sjgren-Larsson syndrome. The ALDH3A2 gene provides instructions for making an enzyme called fatty aldehyde dehydrogenase (FALDH). The FALDH enzyme is part of a multistep process called fatty acid oxidation in which fats are broken down and converted into energy. Specifically, the FALDH enzyme breaks down molecules called fatty aldehydes to fatty acids.  ALDH3A2 gene mutations disrupt the normal process of fatty acid oxidation. Most mutations result in the production of a FALDH enzyme that is unable to break down fatty aldehyde molecules. As a result, fats that cannot be broken down build up in cells. Within skin cells, excess fat accumulation can interfere with the formation of membranes that act as protective barriers to control water loss. As a result of the loss of these protective barriers, the skin has difficulty maintaining its water balance, resulting in dry, scaly skin. In the brain, the consequences of excess fat accumulation are unclear, but it is likely that an abundance of fat disrupts the formation of myelin. Myelin is the covering that protects nerves and promotes the efficient transmission of nerve impulses. A lack of myelin can lead to neurological problems such as intellectual disability and walking difficulties. The cause of the eye problems is unclear, but it is also likely related to a disruption in the breakdown of fats.",Sjgren-Larsson syndrome,0000916,GHR,https://ghr.nlm.nih.gov/condition/sjogren-larsson-syndrome,C0039082,T047,Disorders
Is Sjgren-Larsson syndrome inherited ?,0000916-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Sjgren-Larsson syndrome,0000916,GHR,https://ghr.nlm.nih.gov/condition/sjogren-larsson-syndrome,C0039082,T047,Disorders
What are the treatments for Sjgren-Larsson syndrome ?,0000916-5,treatment,These resources address the diagnosis or management of Sjgren-Larsson syndrome:  - Genetic Testing Registry: Sjgren-Larsson syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Sjgren-Larsson syndrome,0000916,GHR,https://ghr.nlm.nih.gov/condition/sjogren-larsson-syndrome,C0039082,T047,Disorders
What is (are) SLC4A1-associated distal renal tubular acidosis ?,0000917-1,information,"SLC4A1-associated distal renal tubular acidosis is a kidney (renal) disorder that sometimes includes blood cell abnormalities. The kidneys normally filter fluid and waste products from the body and remove them in urine; however, in people with distal renal tubular acidosis, the kidneys are unable to remove enough acid from the body, and the blood becomes too acidic. This chemical imbalance is called metabolic acidosis. The inability to remove acids from the body often results in slowed growth and may also lead to softening and weakening of the bones, called rickets in children and osteomalacia in adults. This bone disorder is characterized by bone pain, bowed legs, and difficulty walking. In addition, most children and adults with SLC4A1-associated distal renal tubular acidosis have excess calcium in the urine (hypercalciuria), calcium deposits in the kidneys (nephrocalcinosis), and kidney stones (nephrolithiasis). In rare cases, these kidney abnormalities lead to life-threatening kidney failure. Affected individuals may also have low levels of potassium in the blood (hypokalemia).  Individuals with the features described above have complete distal renal tubular acidosis, which usually becomes apparent in childhood. Some people do not develop metabolic acidosis even though their kidneys have trouble removing acids; these individuals are said to have incomplete distal renal tubular acidosis. Additionally, these individuals may have other features of distal renal tubular acidosis, such as bone problems and kidney stones. Often, people who initially have incomplete distal renal tubular acidosis develop metabolic acidosis later in life.  Some people with SLC4A1-associated distal renal tubular acidosis also have blood cell abnormalities. These can vary in severity from no symptoms to a condition called hemolytic anemia, in which red blood cells prematurely break down (undergo hemolysis), causing a shortage of red blood cells (anemia). Hemolytic anemia can lead to unusually pale skin (pallor), extreme tiredness (fatigue), shortness of breath (dyspnea), and an enlarged spleen (splenomegaly).  There are two forms of SLC4A1-associated distal renal tubular acidosis; they are distinguished by their inheritance pattern (described below). The autosomal dominant form is more common and is usually less severe than the autosomal recessive form. The autosomal dominant form can be associated with incomplete or complete distal renal tubular acidosis and is rarely associated with blood cell abnormalities. The autosomal recessive form is always associated with complete distal renal tubular acidosis and is more commonly associated with blood cell abnormalities, although not everyone with this form has abnormal blood cells.",SLC4A1-associated distal renal tubular acidosis,0000917,GHR,https://ghr.nlm.nih.gov/condition/slc4a1-associated-distal-renal-tubular-acidosis,C0259810,T047,Disorders
How many people are affected by SLC4A1-associated distal renal tubular acidosis ?,0000917-2,frequency,"The prevalence of SLC4A1-associated distal renal tubular acidosis is unknown. The condition is most common in Southeast Asia, especially Thailand.",SLC4A1-associated distal renal tubular acidosis,0000917,GHR,https://ghr.nlm.nih.gov/condition/slc4a1-associated-distal-renal-tubular-acidosis,C0259810,T047,Disorders
What are the genetic changes related to SLC4A1-associated distal renal tubular acidosis ?,0000917-3,genetic changes,"Both the autosomal dominant and autosomal recessive forms of SLC4A1-associated distal renal tubular acidosis are caused by mutations in the SLC4A1 gene. This gene provides instructions for making the anion exchanger 1 (AE1) protein, which transports negatively charged atoms (anions) across cell membranes. Specifically, AE1 exchanges negatively charged atoms of chlorine (chloride ions) for negatively charged bicarbonate molecules (bicarbonate ions). The AE1 protein is found in the cell membrane of kidney cells and red blood cells. In kidney cells, the exchange of bicarbonate through AE1 allows acid to be released from the cell into the urine. In red blood cells, AE1 attaches to other proteins that make up the structural framework (the cytoskeleton) of the cells, helping to maintain their structure.  The SLC4A1 gene mutations involved in either form of SLC4A1-associated distal renal tubular acidosis lead to production of altered AE1 proteins that cannot get to the correct location in the cell membrane. In the autosomal dominant form of the condition, gene mutations affect only one copy of the SLC4A1 gene, and normal AE1 protein is produced from the other copy. However, the altered protein attaches to the normal protein and keeps it from getting to the correct location, leading to a severe reduction or absence of AE1 protein in the cell membrane. In autosomal recessive distal renal tubular acidosis, both copies of the SLC4A1 gene are mutated, so all of the protein produced from this gene is altered and not able to get to the correct location. Improper location or absence of AE1 in kidney cell membranes disrupts bicarbonate exchange, and as a result, acid cannot be released into the urine. Instead, the acid builds up in the blood in most affected individuals, leading to metabolic acidosis and the other features of complete distal renal tubular acidosis. It is not clear why some people develop metabolic acidosis and others do not. Researchers suggest that in individuals with incomplete distal renal tubular acidosis, another mechanism is able to help regulate blood acidity (pH) and keep metabolic acidosis from developing.  In red blood cells, interaction with a protein called glycophorin A can often help the altered AE1 protein get to the cell membrane where it can perform its function, which explains why most people with SLC4A1-associated distal renal tubular acidosis do not have blood cell abnormalities. However, some altered AE1 proteins cannot be helped by glycophorin A and are not found in the cell membrane. Without AE1, the red blood cells are unstable; breakdown of these abnormal red blood cells may lead to hemolytic anemia.  Some people have nonhereditary forms of distal renal tubular acidosis; these forms can be caused by immune system problems or other conditions that damage the kidneys. These individuals often have additional signs and symptoms related to the original condition.",SLC4A1-associated distal renal tubular acidosis,0000917,GHR,https://ghr.nlm.nih.gov/condition/slc4a1-associated-distal-renal-tubular-acidosis,C0259810,T047,Disorders
Is SLC4A1-associated distal renal tubular acidosis inherited ?,0000917-4,inheritance,"SLC4A1-associated distal renal tubular acidosis can have different patterns of inheritance. It is usually inherited in an autosomal dominant pattern, which means one copy of the altered SLC4A1 gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  Less commonly, SLC4A1-associated distal renal tubular acidosis has an autosomal recessive pattern of inheritance, which means a mutation must occur in both copies of the SLC4A1 gene for the condition to develop. This pattern occurs with certain types of SLC4A1 gene mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",SLC4A1-associated distal renal tubular acidosis,0000917,GHR,https://ghr.nlm.nih.gov/condition/slc4a1-associated-distal-renal-tubular-acidosis,C0259810,T047,Disorders
What are the treatments for SLC4A1-associated distal renal tubular acidosis ?,0000917-5,treatment,"These resources address the diagnosis or management of SLC4A1-associated distal renal tubular acidosis:  - Genetic Testing Registry: Renal tubular acidosis, distal, autosomal dominant  - Genetic Testing Registry: Renal tubular acidosis, distal, with hemolytic anemia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",SLC4A1-associated distal renal tubular acidosis,0000917,GHR,https://ghr.nlm.nih.gov/condition/slc4a1-associated-distal-renal-tubular-acidosis,C0259810,T047,Disorders
What is (are) small fiber neuropathy ?,0000918-1,information,"Small fiber neuropathy is a condition characterized by severe pain attacks that typically begin in the feet or hands. As a person ages, the pain attacks can affect other regions. Some people initially experience a more generalized, whole-body pain. The attacks usually consist of pain described as stabbing or burning, or abnormal skin sensations such as tingling or itchiness. In some individuals, the pain is more severe during times of rest or at night. The signs and symptoms of small fiber neuropathy usually begin in adolescence to mid-adulthood.  Individuals with small fiber neuropathy cannot feel pain that is concentrated in a very small area, such as the prick of a pin. However, they have an increased sensitivity to pain in general (hyperalgesia) and experience pain from stimulation that typically does not cause pain (hypoesthesia). People affected with this condition may also have a reduced ability to differentiate between hot and cold. However, in some individuals, the pain attacks are provoked by cold or warm triggers.  Some affected individuals have urinary or bowel problems, episodes of rapid heartbeat (palpitations), dry eyes or mouth, or abnormal sweating. They can also experience a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting.  Small fiber neuropathy is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and pain.",small fiber neuropathy,0000918,GHR,https://ghr.nlm.nih.gov/condition/small-fiber-neuropathy,C3276706,T047,Disorders
How many people are affected by small fiber neuropathy ?,0000918-2,frequency,The prevalence of small fiber neuropathy is unknown.,small fiber neuropathy,0000918,GHR,https://ghr.nlm.nih.gov/condition/small-fiber-neuropathy,C3276706,T047,Disorders
What are the genetic changes related to small fiber neuropathy ?,0000918-3,genetic changes,"Mutations in the SCN9A or SCN10A gene can cause small fiber neuropathy. These genes provide instructions for making pieces (the alpha subunits) of sodium channels. The SCN9A gene instructs the production of the alpha subunit for the NaV1.7 sodium channel and the SCN10A gene instructs the production of the alpha subunit for the NaV1.8 sodium channel. Sodium channels transport positively charged sodium atoms (sodium ions) into cells and play a key role in a cell's ability to generate and transmit electrical signals. The NaV1.7 and NaV1.8 sodium channels are found in nerve cells called nociceptors that transmit pain signals to the spinal cord and brain.  The SCN9A gene mutations that cause small fiber neuropathy result in NaV1.7 sodium channels that do not close completely when the channel is turned off. Many SCN10A gene mutations result in NaV1.8 sodium channels that open more easily than usual. The altered channels allow sodium ions to flow abnormally into nociceptors. This increase in sodium ions enhances transmission of pain signals, causing individuals to be more sensitive to stimulation that might otherwise not cause pain. In this condition, the small fibers that extend from the nociceptors through which pain signals are transmitted (axons) degenerate over time. The cause of this degeneration is unknown, but it likely accounts for signs and symptoms such as the loss of temperature differentiation and pinprick sensation. The combination of increased pain signaling and degeneration of pain-transmitting fibers leads to a variable condition with signs and symptoms that can change over time.  SCN9A gene mutations have been found in approximately 30 percent of individuals with small fiber neuropathy; SCN10A gene mutations are responsible for about 5 percent of cases. In some instances, other health conditions cause this disorder. Diabetes mellitus and impaired glucose tolerance are the most common diseases that lead to this disorder, with 6 to 50 percent of diabetics or pre-diabetics developing small fiber neuropathy. Other causes of this condition include a metabolic disorder called Fabry disease, immune disorders such as celiac disease or Sjogren syndrome, an inflammatory condition called sarcoidosis, and human immunodeficiency virus (HIV) infection.",small fiber neuropathy,0000918,GHR,https://ghr.nlm.nih.gov/condition/small-fiber-neuropathy,C3276706,T047,Disorders
Is small fiber neuropathy inherited ?,0000918-4,inheritance,"Small fiber neuropathy is inherited in an autosomal dominant pattern, which means one copy of the altered SCN9A gene or SCN10A gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  When the genetic cause of small fiber neuropathy is unknown or when the condition is caused by another disorder, the inheritance pattern is unclear.",small fiber neuropathy,0000918,GHR,https://ghr.nlm.nih.gov/condition/small-fiber-neuropathy,C3276706,T047,Disorders
What are the treatments for small fiber neuropathy ?,0000918-5,treatment,These resources address the diagnosis or management of small fiber neuropathy:  - Genetic Testing Registry: Small fiber neuropathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,small fiber neuropathy,0000918,GHR,https://ghr.nlm.nih.gov/condition/small-fiber-neuropathy,C3276706,T047,Disorders
What is (are) Smith-Lemli-Opitz syndrome ?,0000919-1,information,"Smith-Lemli-Opitz syndrome is a developmental disorder that affects many parts of the body. This condition is characterized by distinctive facial features, small head size (microcephaly), intellectual disability or learning problems, and behavioral problems. Many affected children have the characteristic features of autism, a developmental condition that affects communication and social interaction. Malformations of the heart, lungs, kidneys, gastrointestinal tract, and genitalia are also common. Infants with Smith-Lemli-Opitz syndrome have weak muscle tone (hypotonia), experience feeding difficulties, and tend to grow more slowly than other infants. Most affected individuals have fused second and third toes (syndactyly), and some have extra fingers or toes (polydactyly).  The signs and symptoms of Smith-Lemli-Opitz syndrome vary widely. Mildly affected individuals may have only minor physical abnormalities with learning and behavioral problems. Severe cases can be life-threatening and involve profound intellectual disability and major physical abnormalities.",Smith-Lemli-Opitz syndrome,0000919,GHR,https://ghr.nlm.nih.gov/condition/smith-lemli-opitz-syndrome,C2936904,T019,Disorders
How many people are affected by Smith-Lemli-Opitz syndrome ?,0000919-2,frequency,"Smith-Lemli-Opitz syndrome affects an estimated 1 in 20,000 to 60,000 newborns. This condition is most common in whites of European ancestry, particularly people from Central European countries such as Slovakia and the Czech Republic. It is very rare among African and Asian populations.",Smith-Lemli-Opitz syndrome,0000919,GHR,https://ghr.nlm.nih.gov/condition/smith-lemli-opitz-syndrome,C2936904,T019,Disorders
What are the genetic changes related to Smith-Lemli-Opitz syndrome ?,0000919-3,genetic changes,"Mutations in the DHCR7 gene cause Smith-Lemli-Opitz syndrome.  The DHCR7 gene provides instructions for making an enzyme called 7-dehydrocholesterol reductase. This enzyme is responsible for the final step in the production of cholesterol. Cholesterol is a waxy, fat-like substance that is produced in the body and obtained from foods that come from animals (particularly egg yolks, meat, poultry, fish, and dairy products). Cholesterol is necessary for normal embryonic development and has important functions both before and after birth. It is a structural component of cell membranes and the protective substance covering nerve cells (myelin). Additionally, cholesterol plays a role in the production of certain hormones and digestive acids.  Mutations in the DHCR7 gene reduce or eliminate the activity of 7-dehydrocholesterol reductase, preventing cells from producing enough cholesterol. A lack of this enzyme also allows potentially toxic byproducts of cholesterol production to build up in the blood, nervous system, and other tissues. The combination of low cholesterol levels and an accumulation of other substances likely disrupts the growth and development of many body systems. It is not known, however, how this disturbance in cholesterol production leads to the specific features of Smith-Lemli-Opitz syndrome.",Smith-Lemli-Opitz syndrome,0000919,GHR,https://ghr.nlm.nih.gov/condition/smith-lemli-opitz-syndrome,C2936904,T019,Disorders
Is Smith-Lemli-Opitz syndrome inherited ?,0000919-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Smith-Lemli-Opitz syndrome,0000919,GHR,https://ghr.nlm.nih.gov/condition/smith-lemli-opitz-syndrome,C2936904,T019,Disorders
What are the treatments for Smith-Lemli-Opitz syndrome ?,0000919-5,treatment,These resources address the diagnosis or management of Smith-Lemli-Opitz syndrome:  - Gene Review: Gene Review: Smith-Lemli-Opitz Syndrome  - Genetic Testing Registry: Smith-Lemli-Opitz syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Smith-Lemli-Opitz syndrome,0000919,GHR,https://ghr.nlm.nih.gov/condition/smith-lemli-opitz-syndrome,C2936904,T019,Disorders
What is (are) Smith-Magenis syndrome ?,0000920-1,information,"Smith-Magenis syndrome is a developmental disorder that affects many parts of the body. The major features of this condition include mild to moderate intellectual disability, delayed speech and language skills, distinctive facial features, sleep disturbances, and behavioral problems.  Most people with Smith-Magenis syndrome have a broad, square-shaped face with deep-set eyes, full cheeks, and a prominent lower jaw. The middle of the face and the bridge of the nose often appear flattened. The mouth tends to turn downward with a full, outward-curving upper lip. These facial differences can be subtle in early childhood, but they usually become more distinctive in later childhood and adulthood. Dental abnormalities are also common in affected individuals.  Disrupted sleep patterns are characteristic of Smith-Magenis syndrome, typically beginning early in life. Affected people may be very sleepy during the day, but they have trouble falling asleep and awaken several times each night.  People with Smith-Magenis syndrome have affectionate, engaging personalities, but most also have behavioral problems. These include frequent temper tantrums and outbursts, aggression, anxiety, impulsiveness, and difficulty paying attention. Self-injury, including biting, hitting, head banging, and skin picking, is very common. Repetitive self-hugging is a behavioral trait that may be unique to Smith-Magenis syndrome. People with this condition also compulsively lick their fingers and flip pages of books and magazines (a behavior known as ""lick and flip"").  Other signs and symptoms of Smith-Magenis syndrome include short stature, abnormal curvature of the spine (scoliosis), reduced sensitivity to pain and temperature, and a hoarse voice. Some people with this disorder have ear abnormalities that lead to hearing loss. Affected individuals may have eye abnormalities that cause nearsightedness (myopia) and other vision problems. Although less common, heart and kidney defects also have been reported in people with Smith-Magenis syndrome.",Smith-Magenis syndrome,0000920,GHR,https://ghr.nlm.nih.gov/condition/smith-magenis-syndrome,C0795864,T047,Disorders
How many people are affected by Smith-Magenis syndrome ?,0000920-2,frequency,"Smith-Magenis syndrome affects at least 1 in 25,000 individuals worldwide. Researchers believe that many people with this condition are not diagnosed, however, so the true prevalence may be closer to 1 in 15,000 individuals.",Smith-Magenis syndrome,0000920,GHR,https://ghr.nlm.nih.gov/condition/smith-magenis-syndrome,C0795864,T047,Disorders
What are the genetic changes related to Smith-Magenis syndrome ?,0000920-3,genetic changes,"Most people with Smith-Magenis syndrome have a deletion of genetic material from a specific region of chromosome 17. Although this region contains multiple genes, researchers believe that the loss of one particular gene, RAI1, in each cell is responsible for most of the characteristic features of this condition. The loss of other genes in the deleted region may help explain why the features of Smith-Magenis syndrome vary among affected individuals.  A small percentage of people with Smith-Magenis syndrome have a mutation in the RAI1 gene instead of a chromosomal deletion. Although these individuals have many of the major features of the condition, they are less likely than people with a chromosomal deletion to have short stature, hearing loss, and heart or kidney abnormalities.  The RAI1 gene provides instructions for making a protein whose function is unknown. Mutations in one copy of this gene lead to the production of a nonfunctional version of the RAI1 protein or reduce the amount of this protein that is produced in cells. Researchers are uncertain how changes in this protein result in the physical, mental, and behavioral problems associated with Smith-Magenis syndrome.",Smith-Magenis syndrome,0000920,GHR,https://ghr.nlm.nih.gov/condition/smith-magenis-syndrome,C0795864,T047,Disorders
Is Smith-Magenis syndrome inherited ?,0000920-4,inheritance,"Smith-Magenis syndrome is typically not inherited. This condition usually results from a genetic change that occurs during the formation of reproductive cells (eggs or sperm) or in early fetal development. Most often, people with Smith-Magenis syndrome have no history of the condition in their family.",Smith-Magenis syndrome,0000920,GHR,https://ghr.nlm.nih.gov/condition/smith-magenis-syndrome,C0795864,T047,Disorders
What are the treatments for Smith-Magenis syndrome ?,0000920-5,treatment,These resources address the diagnosis or management of Smith-Magenis syndrome:  - Gene Review: Gene Review: Smith-Magenis Syndrome  - Genetic Testing Registry: Smith-Magenis syndrome  - MedlinePlus Encyclopedia: Intellectual Disability   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Smith-Magenis syndrome,0000920,GHR,https://ghr.nlm.nih.gov/condition/smith-magenis-syndrome,C0795864,T047,Disorders
What is (are) Snyder-Robinson syndrome ?,0000921-1,information,"Snyder-Robinson syndrome is a condition characterized by intellectual disability, muscle and bone abnormalities, and other problems with development. It occurs exclusively in males.  Males with Snyder-Robinson syndrome have delayed development and intellectual disability beginning in early childhood. The intellectual disability can range from mild to profound. Speech often develops late, and speech difficulties are common. Some affected individuals never develop any speech.  Most affected males are thin and have low muscle mass, a body type described as an asthenic habitus. Weakness or ""floppiness"" (hypotonia) typically becomes apparent in infancy, and the loss of muscle tissue continues with age. People with this condition often have difficulty walking; most have an unsteady gait.  Snyder-Robinson syndrome causes skeletal problems, particularly thinning of the bones (osteoporosis) that starts in early childhood. Osteoporosis causes the bones to be brittle and to break easily, often during normal activities. In people with Snyder-Robinson syndrome, broken bones occur most often in the arms and legs. Most affected individuals also develop an abnormal side-to-side and back-to-front curvature of the spine (scoliosis and kyphosis, often called kyphoscoliosis when they occur together). Affected individuals tend to be shorter than their peers and others in their family.  Snyder-Robinson syndrome is associated with distinctive facial features, including a prominent lower lip; a high, narrow roof of the mouth or an opening in the roof of the mouth (a cleft palate); and differences in the size and shape of the right and left sides of the face (facial asymmetry). Other signs and symptoms that have been reported include seizures that begin in childhood and abnormalities of the genitalia and kidneys.",Snyder-Robinson syndrome,0000921,GHR,https://ghr.nlm.nih.gov/condition/snyder-robinson-syndrome,C0796160,T047,Disorders
How many people are affected by Snyder-Robinson syndrome ?,0000921-2,frequency,Snyder-Robinson syndrome is a rare condition; its prevalence is unknown. About 10 affected families have been identified worldwide.,Snyder-Robinson syndrome,0000921,GHR,https://ghr.nlm.nih.gov/condition/snyder-robinson-syndrome,C0796160,T047,Disorders
What are the genetic changes related to Snyder-Robinson syndrome ?,0000921-3,genetic changes,"Snyder-Robinson syndrome results from mutations in the SMS gene. This gene provides instructions for making an enzyme called spermine synthase. This enzyme is involved in the production of spermine, which is a type of small molecule called a polyamine. Polyamines have many critical functions within cells. Studies suggest that these molecules play roles in cell growth and division, the production of new proteins, the repair of damaged tissues, the function of molecules called ion channels, and the controlled self-destruction of cells (apoptosis). Polyamines appear to be necessary for normal development and function of the brain and other parts of the body.  Mutations in the SMS gene greatly reduce or eliminate the activity of spermine synthase, which decreases the amount of spermine in cells. A shortage of this polyamine clearly impacts normal development, including the development of the brain, muscles, and bones, but it is unknown how it leads to the specific signs and symptoms of Snyder-Robinson syndrome.",Snyder-Robinson syndrome,0000921,GHR,https://ghr.nlm.nih.gov/condition/snyder-robinson-syndrome,C0796160,T047,Disorders
Is Snyder-Robinson syndrome inherited ?,0000921-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. No cases of Snyder-Robinson syndrome in females have been reported.",Snyder-Robinson syndrome,0000921,GHR,https://ghr.nlm.nih.gov/condition/snyder-robinson-syndrome,C0796160,T047,Disorders
What are the treatments for Snyder-Robinson syndrome ?,0000921-5,treatment,These resources address the diagnosis or management of Snyder-Robinson syndrome:  - Gene Review: Gene Review: Snyder-Robinson Syndrome  - Genetic Testing Registry: Snyder Robinson syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Snyder-Robinson syndrome,0000921,GHR,https://ghr.nlm.nih.gov/condition/snyder-robinson-syndrome,C0796160,T047,Disorders
What is (are) SOST-related sclerosing bone dysplasia ?,0000922-1,information,"SOST-related sclerosing bone dysplasia is a disorder of bone development characterized by excessive bone formation (hyperostosis). As a result of hyperostosis, bones throughout the body are denser and wider than normal, particularly the bones of the skull. Affected individuals typically have an enlarged jaw with misaligned teeth. People with this condition may also have a sunken appearance of the middle of the face (midface hypoplasia), bulging eyes with shallow eye sockets (ocular proptosis), and a prominent forehead. People with this condition often experience headaches because increased thickness of the skull bones increases pressure on the brain. The excessive bone formation seen in this condition seems to occur throughout a person's life, so the skeletal features become more pronounced over time. However, the excessive bone growth may only occur in certain areas.  Abnormal bone growth can pinch (compress) the cranial nerves, which emerge from the brain and extend to various areas of the head and neck. Compression of the cranial nerves can lead to paralyzed facial muscles (facial nerve palsy), hearing loss, vision loss, and a sense of smell that is diminished (hyposmia) or completely absent (anosmia). Abnormal bone growth can cause life-threatening complications if it compresses the part of the brain that is connected to the spinal cord (the brainstem).  There are two forms of SOST-related sclerosing bone dysplasia: sclerosteosis and van Buchem disease. The two forms are distinguished by the severity of their symptoms.  Sclerosteosis is the more severe form of the disorder. People with sclerosteosis are often tall and have webbed or fused fingers (syndactyly), most often involving the second and third fingers. The syndactyly is present from birth, while the skeletal features typically appear in early childhood. People with sclerosteosis may also have absent or malformed nails.  Van Buchem disease represents the milder form of the disorder. People with van Buchem disease are typically of average height and do not have syndactyly or nail abnormalities. Affected individuals tend to have less severe cranial nerve compression, resulting in milder neurological features. In people with van Buchem disease, the skeletal features typically appear in childhood or adolescence.",SOST-related sclerosing bone dysplasia,0000922,GHR,https://ghr.nlm.nih.gov/condition/sost-related-sclerosing-bone-dysplasia,C0432272,T019,Disorders
How many people are affected by SOST-related sclerosing bone dysplasia ?,0000922-2,frequency,SOST-related sclerosing bone dysplasia is a rare condition; its exact prevalence is unknown.  Approximately 100 individuals with sclerosteosis have been reported in the scientific literature. Sclerosteosis is most common in the Afrikaner population of South Africa.  Van Buchem disease has been reported in approximately 30 people. Most people with van Buchem disease are of Dutch ancestry.,SOST-related sclerosing bone dysplasia,0000922,GHR,https://ghr.nlm.nih.gov/condition/sost-related-sclerosing-bone-dysplasia,C0432272,T019,Disorders
What are the genetic changes related to SOST-related sclerosing bone dysplasia ?,0000922-3,genetic changes,"SOST-related sclerosing bone dysplasia is caused by mutations in or near the SOST gene. The SOST gene provides instructions for making the protein sclerostin. Sclerostin is produced in osteocytes, which are a type of bone cell. The main function of sclerostin is to stop (inhibit) bone formation.  Mutations in the SOST gene that cause sclerosteosis prevent the production of any functional sclerostin. A lack of sclerostin disrupts the inhibitory role it plays during bone formation, causing excessive bone growth.  SOST mutations that cause van Buchem disease result in a shortage of functional sclerostin. This shortage reduces the protein's ability to inhibit bone formation, causing the excessive bone growth seen in people with van Buchem disease.",SOST-related sclerosing bone dysplasia,0000922,GHR,https://ghr.nlm.nih.gov/condition/sost-related-sclerosing-bone-dysplasia,C0432272,T019,Disorders
Is SOST-related sclerosing bone dysplasia inherited ?,0000922-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",SOST-related sclerosing bone dysplasia,0000922,GHR,https://ghr.nlm.nih.gov/condition/sost-related-sclerosing-bone-dysplasia,C0432272,T019,Disorders
What are the treatments for SOST-related sclerosing bone dysplasia ?,0000922-5,treatment,These resources address the diagnosis or management of SOST-related sclerosing bone dysplasia:  - Gene Review: Gene Review: SOST-Related Sclerosing Bone Dysplasias  - Genetic Testing Registry: Hyperphosphatasemia tarda  - Genetic Testing Registry: Sclerosteosis  - MedlinePlus Encyclopedia: Facial Paralysis  - MedlinePlus Encyclopedia: Smell--Impaired   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,SOST-related sclerosing bone dysplasia,0000922,GHR,https://ghr.nlm.nih.gov/condition/sost-related-sclerosing-bone-dysplasia,C0432272,T019,Disorders
What is (are) Sotos syndrome ?,0000923-1,information,"Sotos syndrome is a disorder characterized by a distinctive facial appearance, overgrowth in childhood, and learning disabilities or delayed development of mental and movement abilities. Characteristic facial features include a long, narrow face; a high forehead; flushed (reddened) cheeks; and a small, pointed chin. In addition, the outside corners of the eyes may point downward (down-slanting palpebral fissures). This facial appearance is most notable in early childhood. Affected infants and children tend to grow quickly; they are significantly taller than their siblings and peers and have an unusually large head. However, adult height is usually in the normal range.  People with Sotos syndrome often have intellectual disability, and most also have behavioral problems. Frequent behavioral issues include attention deficit hyperactivity disorder (ADHD), phobias, obsessions and compulsions, tantrums, and impulsive behaviors. Problems with speech and language are also common. Affected individuals often have a stutter, a monotone voice, and problems with sound production. Additionally, weak muscle tone (hypotonia) may delay other aspects of early development, particularly motor skills such as sitting and crawling.  Other signs and symptoms of Sotos syndrome can include an abnormal side-to-side curvature of the spine (scoliosis), seizures, heart or kidney defects, hearing loss, and problems with vision. Some infants with this disorder experience yellowing of the skin and whites of the eyes (jaundice) and poor feeding.  A small percentage of people with Sotos syndrome have developed cancer, most often in childhood, but no single form of cancer occurs most frequently with this condition. It remains uncertain whether Sotos syndrome increases the risk of specific types of cancer. If people with this disorder have an increased cancer risk, it is only slightly greater than that of the general population.",Sotos syndrome,0000923,GHR,https://ghr.nlm.nih.gov/condition/sotos-syndrome,C0175695,T019,Disorders
How many people are affected by Sotos syndrome ?,0000923-2,frequency,"Sotos syndrome is reported to occur in 1 in 10,000 to 14,000 newborns. Because many of the features of Sotos syndrome can be attributed to other conditions, many cases of this disorder are likely not properly diagnosed, so the true incidence may be closer to 1 in 5,000.",Sotos syndrome,0000923,GHR,https://ghr.nlm.nih.gov/condition/sotos-syndrome,C0175695,T019,Disorders
What are the genetic changes related to Sotos syndrome ?,0000923-3,genetic changes,"Mutations in the NSD1 gene are the primary cause of Sotos syndrome, accounting for up to 90 percent of cases. Other genetic causes of this condition have not been identified.  The NSD1 gene provides instructions for making a protein that functions as a histone methyltransferase. Histone methyltransferases are enzymes that modify structural proteins called histones, which attach (bind) to DNA and give chromosomes their shape. By adding a molecule called a methyl group to histones (a process called methylation), histone methyltransferases regulate the activity of certain genes and can turn them on and off as needed. The NSD1 protein controls the activity of genes involved in normal growth and development, although most of these genes have not been identified.  Genetic changes involving the NSD1 gene prevent one copy of the gene from producing any functional protein. Research suggests that a reduced amount of NSD1 protein disrupts the normal activity of genes involved in growth and development. However, it remains unclear exactly how a shortage of this protein during development leads to overgrowth, learning disabilities, and the other features of Sotos syndrome.",Sotos syndrome,0000923,GHR,https://ghr.nlm.nih.gov/condition/sotos-syndrome,C0175695,T019,Disorders
Is Sotos syndrome inherited ?,0000923-4,inheritance,About 95 percent of Sotos syndrome cases occur in people with no history of the disorder in their family. Most of these cases result from new mutations involving the NSD1 gene.  A few families have been described with more than one affected family member. These cases helped researchers determine that Sotos syndrome has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder.,Sotos syndrome,0000923,GHR,https://ghr.nlm.nih.gov/condition/sotos-syndrome,C0175695,T019,Disorders
What are the treatments for Sotos syndrome ?,0000923-5,treatment,These resources address the diagnosis or management of Sotos syndrome:  - Gene Review: Gene Review: Sotos Syndrome  - Genetic Testing Registry: Sotos' syndrome  - MedlinePlus Encyclopedia: Increased Head Circumference   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Sotos syndrome,0000923,GHR,https://ghr.nlm.nih.gov/condition/sotos-syndrome,C0175695,T019,Disorders
What is (are) SOX2 anophthalmia syndrome ?,0000924-1,information,"SOX2 anophthalmia syndrome is a rare disorder characterized by abnormal development of the eyes and other parts of the body.  People with SOX2 anophthalmia syndrome are usually born without eyeballs (anophthalmia), although some individuals have small eyes (microphthalmia). The term anophthalmia is often used interchangeably with severe microphthalmia because individuals with no visible eyeballs typically have some remaining eye tissue. These eye problems can cause significant vision loss. While both eyes are usually affected in SOX2 anophthalmia syndrome, one eye may be more affected than the other.  Individuals with SOX2 anophthalmia syndrome may also have seizures, brain abnormalities, slow growth, delayed development of motor skills (such as walking), and mild to severe learning disabilities. Some people with this condition are born with a blocked esophagus (esophageal atresia), which is often accompanied by an abnormal connection between the esophagus and the trachea (tracheoesophageal fistula). Genital abnormalities have been described in affected individuals, especially males. Male genital abnormalities include undescended testes (cryptorchidism) and an unusually small penis (micropenis).",SOX2 anophthalmia syndrome,0000924,GHR,https://ghr.nlm.nih.gov/condition/sox2-anophthalmia-syndrome,C1859773,T047,Disorders
How many people are affected by SOX2 anophthalmia syndrome ?,0000924-2,frequency,"SOX2 anophthalmia syndrome is estimated to affect 1 in 250,000 individuals. About 10 percent to 15 percent of people with anophthalmia in both eyes have SOX2 anophthalmia syndrome.",SOX2 anophthalmia syndrome,0000924,GHR,https://ghr.nlm.nih.gov/condition/sox2-anophthalmia-syndrome,C1859773,T047,Disorders
What are the genetic changes related to SOX2 anophthalmia syndrome ?,0000924-3,genetic changes,"Mutations in the SOX2 gene cause SOX2 anophthalmia syndrome. This gene provides instructions for making a protein that plays a critical role in the formation of many different tissues and organs during embryonic development. The SOX2 protein regulates the activity of other genes, especially those that are important for normal development of the eyes.  Mutations in the SOX2 gene prevent the production of functional SOX2 protein. The absence of this protein disrupts the activity of genes that are essential for the development of the eyes and other parts of the body. Abnormal development of these structures causes the signs and symptoms of SOX2 anophthalmia syndrome.",SOX2 anophthalmia syndrome,0000924,GHR,https://ghr.nlm.nih.gov/condition/sox2-anophthalmia-syndrome,C1859773,T047,Disorders
Is SOX2 anophthalmia syndrome inherited ?,0000924-4,inheritance,"SOX2 anophthalmia syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the SOX2 gene and occur in people with no history of the disorder in their family. In a small number of cases, people with SOX2 anophthalmia syndrome have inherited the altered gene from an unaffected parent who has a SOX2 mutation only in their sperm or egg cells. This phenomenon is called germline mosaicism.",SOX2 anophthalmia syndrome,0000924,GHR,https://ghr.nlm.nih.gov/condition/sox2-anophthalmia-syndrome,C1859773,T047,Disorders
What are the treatments for SOX2 anophthalmia syndrome ?,0000924-5,treatment,These resources address the diagnosis or management of SOX2 anophthalmia syndrome:  - Gene Review: Gene Review: SOX2-Related Eye Disorders  - Genetic Testing Registry: Microphthalmia syndromic 3  - MedlinePlus Encyclopedia: Vision Problems   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,SOX2 anophthalmia syndrome,0000924,GHR,https://ghr.nlm.nih.gov/condition/sox2-anophthalmia-syndrome,C1859773,T047,Disorders
What is (are) spastic paraplegia type 11 ?,0000925-1,information,"Spastic paraplegia type 11 is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve the lower limbs. The complex types involve the lower limbs and can affect the upper limbs to a lesser degree. Complex spastic paraplegias also affect the structure or functioning of the brain and the peripheral nervous system, which consists of nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound. Spastic paraplegia type 11 is a complex hereditary spastic paraplegia.  Like all hereditary spastic paraplegias, spastic paraplegia type 11 involves spasticity of the leg muscles and muscle weakness. In almost all individuals with this type of spastic paraplegia, the tissue connecting the left and right halves of the brain (corpus callosum) is abnormally thin. People with this form of spastic paraplegia can also experience numbness, tingling, or pain in the arms and legs (sensory neuropathy); disturbance in the nerves used for muscle movement (motor neuropathy); intellectual disability; exaggerated reflexes (hyperreflexia) of the lower limbs; speech difficulties (dysarthria); reduced bladder control; and muscle wasting (amyotrophy). Less common features include difficulty swallowing (dysphagia), high-arched feet (pes cavus), an abnormal curvature of the spine (scoliosis), and involuntary movements of the eyes (nystagmus). The onset of symptoms varies greatly; however, abnormalities in muscle tone and difficulty walking usually become noticeable in adolescence.  Many features of spastic paraplegia type 11 are progressive. Most people experience a decline in intellectual ability and an increase in muscle weakness and nerve abnormalities over time. As the condition progresses, some people require wheelchair assistance.",spastic paraplegia type 11,0000925,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-11,C0030486,T047,Disorders
How many people are affected by spastic paraplegia type 11 ?,0000925-2,frequency,"Over 100 cases of spastic paraplegia type 11 have been reported. Although this condition is thought to be rare, its exact prevalence is unknown.",spastic paraplegia type 11,0000925,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-11,C0030486,T047,Disorders
What are the genetic changes related to spastic paraplegia type 11 ?,0000925-3,genetic changes,"Mutations in the SPG11 gene cause spastic paraplegia type 11. The SPG11 gene provides instructions for making the protein spatacsin. Spatacsin is active (expressed) throughout the nervous system, although its exact function is unknown. Researchers speculate that spatacsin may be involved in the maintenance of axons, which are specialized extensions of nerve cells (neurons) that transmit impulses throughout the nervous system.  SPG11 gene mutations typically change the structure of the spatacsin protein. The effect that the altered spatacsin protein has on the nervous system is not known. Researchers suggest that mutations in spatacsin may cause the signs and symptoms of spastic paraplegia type 11 by interfering with the protein's proposed role in the maintenance of axons.",spastic paraplegia type 11,0000925,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-11,C0030486,T047,Disorders
Is spastic paraplegia type 11 inherited ?,0000925-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",spastic paraplegia type 11,0000925,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-11,C0030486,T047,Disorders
What are the treatments for spastic paraplegia type 11 ?,0000925-5,treatment,"These resources address the diagnosis or management of spastic paraplegia type 11:  - Gene Review: Gene Review: Spastic Paraplegia 11  - Genetic Testing Registry: Spastic paraplegia 11, autosomal recessive  - Spastic Paraplegia Foundation, Inc.: Treatments and Therapies   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",spastic paraplegia type 11,0000925,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-11,C0030486,T047,Disorders
What is (are) spastic paraplegia type 15 ?,0000926-1,information,"Spastic paraplegia type 15 is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia). Spastic paraplegia type 15 is classified as a complex hereditary spastic paraplegia because it involves all four limbs as well as additional features, including abnormalities of the brain. In addition to the muscles and brain, spastic paraplegia type 15 affects the peripheral nervous system, which consists of nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound.  Spastic paraplegia type 15 usually becomes apparent in childhood or adolescence with the development of weak muscle tone (hypotonia), difficulty walking, or intellectual disability. In almost all affected individuals, the tissue connecting the left and right halves of the brain (corpus callosum) is abnormally thin and becomes thinner over time. Additionally, there is often a loss (atrophy) of nerve cells in several parts of the brain, including the cerebral cortex, which controls thinking and emotions, and the cerebellum, which coordinates movement.  People with this form of spastic paraplegia can have numbness, tingling, or pain in the arms and legs (sensory neuropathy); impairment of the nerves used for muscle movement (motor neuropathy); exaggerated reflexes (hyperreflexia) of the lower limbs; muscle wasting (amyotrophy); or reduced bladder control. Rarely, spastic paraplegia type 15 is associated with a group of movement abnormalities called parkinsonism, which includes tremors, rigidity, and unusually slow movement (bradykinesia). People with spastic paraplegia type 15 may have an eye condition called pigmentary maculopathy that often impairs vision. This condition results from the breakdown (degeneration) of tissue at the back of the eye called the macula, which is responsible for sharp central vision.  Most people with spastic paraplegia type 15 experience a decline in intellectual ability and an increase in muscle weakness and nerve abnormalities over time. As the condition progresses, many people require walking aids or wheelchair assistance in adulthood.",spastic paraplegia type 15,0000926,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-15,C0037772,T047,Disorders
How many people are affected by spastic paraplegia type 15 ?,0000926-2,frequency,"Spastic paraplegia type 15 is a rare condition, although its exact prevalence is unknown.",spastic paraplegia type 15,0000926,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-15,C0037772,T047,Disorders
What are the genetic changes related to spastic paraplegia type 15 ?,0000926-3,genetic changes,"Mutations in the ZFYVE26 gene cause spastic paraplegia type 15. This gene provides instructions for making a protein called spastizin. This protein is important in a process called autophagy, in which worn-out cell parts and unneeded proteins are recycled within cells. Specifically, spastizin is involved in the formation and maturation of sacs called autophagosomes (or autophagic vacuoles) that transport unneeded materials to be broken down. Spastizin also plays a role in the process by which dividing cells separate from one another (cytokinesis).  Many ZFYVE26 gene mutations that cause spastic paraplegia type 15 result in a shortened spastizin protein that is quickly broken down. As a result, functional autophagosomes are not produced, autophagy cannot occur, and recycling of materials within cells is decreased. An inability to break down unneeded materials, and the subsequent accumulation of these materials in cells, leads to cell dysfunction and often cell death. The loss of cells in the brain and other parts of the body is responsible for many of the features of spastic paraplegia type 15.  It is unclear whether a lack of spastizin protein interferes with normal cytokinesis and whether impaired cell division contributes to the signs and symptoms of spastic paraplegia type 15.",spastic paraplegia type 15,0000926,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-15,C0037772,T047,Disorders
Is spastic paraplegia type 15 inherited ?,0000926-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",spastic paraplegia type 15,0000926,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-15,C0037772,T047,Disorders
What are the treatments for spastic paraplegia type 15 ?,0000926-5,treatment,"These resources address the diagnosis or management of spastic paraplegia type 15:  - Gene Review: Gene Review: Hereditary Spastic Paraplegia Overview  - Spastic Paraplegia Foundation, Inc: Treatments and Therapies   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",spastic paraplegia type 15,0000926,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-15,C0037772,T047,Disorders
What is (are) spastic paraplegia type 2 ?,0000927-1,information,"Spastic paraplegia type 2 is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve the lower limbs. The complex types involve the lower limbs and can also affect the upper limbs to a lesser degree; the structure or functioning of the brain; and the nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound (the peripheral nervous system). Spastic paraplegia type 2 can occur in either the pure or complex form.  People with the pure form of spastic paraplegia type 2 experience spasticity in the lower limbs, usually without any additional features. People with the complex form of spastic paraplegia type 2 have lower limb spasticity and can also experience problems with movement and balance (ataxia); involuntary movements of the eyes (nystagmus); mild intellectual disability; involuntary, rhythmic shaking (tremor); and degeneration (atrophy) of the optic nerves, which carry information from the eyes to the brain. Symptoms usually become apparent between the ages of 1 and 5 years; those affected are typically able to walk and have a normal lifespan.",spastic paraplegia type 2,0000927,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-2,C0751604,T047,Disorders
How many people are affected by spastic paraplegia type 2 ?,0000927-2,frequency,"The prevalence of all hereditary spastic paraplegias combined is estimated to be 2 to 6 in 100,000 people worldwide. Spastic paraplegia type 2 likely accounts for only a small percentage of all spastic paraplegia cases.",spastic paraplegia type 2,0000927,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-2,C0751604,T047,Disorders
What are the genetic changes related to spastic paraplegia type 2 ?,0000927-3,genetic changes,"Mutations in the PLP1 gene cause spastic paraplegia 2. The PLP1 gene provides instructions for producing proteolipid protein 1 and a modified version (isoform) of proteolipid protein 1, called DM20. Proteolipid protein 1 and DM20 are primarily located in the brain and spinal cord (central nervous system) and are the main proteins found in myelin, the fatty covering that insulates nerve fibers. A lack of proteolipid protein 1 and DM20 can cause a reduction in the formation of myelin (dysmyelination) which can impair nervous system function, resulting in the signs and symptoms of spastic paraplegia type 2.",spastic paraplegia type 2,0000927,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-2,C0751604,T047,Disorders
Is spastic paraplegia type 2 inherited ?,0000927-4,inheritance,"This condition is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. Because females have two copies of the X chromosome, one altered copy of the gene in each cell usually leads to less severe symptoms in females than in males, or may cause no symptoms at all. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In X-linked recessive inheritance, a female with one altered copy of the gene in each cell is called a carrier. She can pass on the gene, but generally does not experience signs and symptoms of the disorder. Some females who carry a PLP1 mutation, however, may experience muscle stiffness and a decrease in intellectual function. Females with one PLP1 mutation have an increased risk of experiencing progressive deterioration of cognitive functions (dementia) later in life.",spastic paraplegia type 2,0000927,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-2,C0751604,T047,Disorders
What are the treatments for spastic paraplegia type 2 ?,0000927-5,treatment,"These resources address the diagnosis or management of spastic paraplegia type 2:  - Gene Review: Gene Review: Hereditary Spastic Paraplegia Overview  - Gene Review: Gene Review: PLP1-Related Disorders  - Genetic Testing Registry: Spastic paraplegia 2  - Spastic Paraplegia Foundation, Inc.: Treatments and Therapies   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",spastic paraplegia type 2,0000927,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-2,C0751604,T047,Disorders
What is (are) spastic paraplegia type 31 ?,0000928-1,information,"Spastic paraplegia type 31 is one of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia) caused by degeneration of nerve cells (neurons) that trigger muscle movement. Hereditary spastic paraplegias are divided into two types: pure and complicated. The pure types involve only the lower limbs, while the complicated types also involve the upper limbs and other areas of the body, including the brain. Spastic paraplegia type 31 is usually a pure hereditary spastic paraplegia, although a few complicated cases have been reported.  The first signs and symptoms of spastic paraplegia type 31 usually appear before age 20 or after age 30. An early feature is difficulty walking due to spasticity and weakness, which typically affect both legs equally. People with spastic paraplegia type 31 can also experience progressive muscle wasting (amyotrophy) in the lower limbs, exaggerated reflexes (hyperreflexia), a decreased ability to feel vibrations, reduced bladder control, and high-arched feet (pes cavus). As the condition progresses, some individuals require walking support.",spastic paraplegia type 31,0000928,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-31,C0037772,T047,Disorders
How many people are affected by spastic paraplegia type 31 ?,0000928-2,frequency,"Spastic paraplegia type 31 is one of a subgroup of hereditary spastic paraplegias known as autosomal dominant hereditary spastic paraplegia, which has an estimated prevalence of one to 12 per 100,000 individuals. Spastic paraplegia type 31 accounts for 3 to 9 percent of all autosomal dominant hereditary spastic paraplegia cases.",spastic paraplegia type 31,0000928,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-31,C0037772,T047,Disorders
What are the genetic changes related to spastic paraplegia type 31 ?,0000928-3,genetic changes,"Spastic paraplegia type 31 is caused by mutations in the REEP1 gene. This gene provides instructions for making a protein called receptor expression-enhancing protein 1 (REEP1), which is found in neurons in the brain and spinal cord. The REEP1 protein is located within cell compartments called mitochondria, which are the energy-producing centers in cells, and the endoplasmic reticulum, which helps with protein processing and transport. The REEP1 protein plays a role in regulating the size of the endoplasmic reticulum and determining how many proteins it can process. The function of the REEP1 protein in the mitochondria is unknown.  REEP1 gene mutations that cause spastic paraplegia type 31 result in a short, nonfunctional protein that is usually broken down quickly. As a result, there is a reduction in functional REEP1 protein. It is unclear how REEP1 gene mutations lead to the signs and symptoms of spastic paraplegia type 31. Researchers have shown that mitochondria in cells of affected individuals are less able to produce energy, which may contribute to the death of neurons and lead to the progressive movement problems of spastic paraplegia type 31; however, the exact mechanism that causes this condition is unknown.",spastic paraplegia type 31,0000928,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-31,C0037772,T047,Disorders
Is spastic paraplegia type 31 inherited ?,0000928-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",spastic paraplegia type 31,0000928,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-31,C0037772,T047,Disorders
What are the treatments for spastic paraplegia type 31 ?,0000928-5,treatment,"These resources address the diagnosis or management of spastic paraplegia type 31:  - Gene Review: Gene Review: Hereditary Spastic Paraplegia Overview  - Genetic Testing Registry: Spastic paraplegia 31, autosomal dominant  - Spastic Paraplegia Foundation, Inc.: Treatments and Therapies   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",spastic paraplegia type 31,0000928,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-31,C0037772,T047,Disorders
What is (are) spastic paraplegia type 3A ?,0000929-1,information,"Spastic paraplegia type 3A is one of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by muscle stiffness (spasticity) and weakness in the lower limbs (paraplegia). Hereditary spastic paraplegias are often divided into two types: pure and complex. The pure types involve only the lower limbs, while the complex types also involve other areas of the body; additional features can include changes in vision, changes in intellectual functioning, difficulty walking, and disturbances in nerve function (neuropathy). Spastic paraplegia type 3A is usually a pure hereditary spastic paraplegia, although a few complex cases have been reported.  In addition to spasticity and weakness, which typically affect both legs equally, people with spastic paraplegia type 3A can also experience progressive muscle wasting (amyotrophy) in the lower limbs, reduced bladder control, an abnormal curvature of the spine (scoliosis), loss of sensation in the feet (peripheral neuropathy), or high arches of the feet (pes cavus). The signs and symptoms of spastic paraplegia type 3A usually appear before the age of 10; the average age of onset is 4 years. In some affected individuals the condition slowly worsens over time, sometimes leading to a need for walking support.",spastic paraplegia type 3A,0000929,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-3a,C0030486,T047,Disorders
How many people are affected by spastic paraplegia type 3A ?,0000929-2,frequency,"Spastic paraplegia type 3A belongs to a subgroup of hereditary spastic paraplegias known as autosomal dominant hereditary spastic paraplegia, which has an estimated prevalence of 2 to 9 per 100,000 individuals. Spastic paraplegia type 3A accounts for 10 to 15 percent of all autosomal dominant hereditary spastic paraplegia cases.",spastic paraplegia type 3A,0000929,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-3a,C0030486,T047,Disorders
What are the genetic changes related to spastic paraplegia type 3A ?,0000929-3,genetic changes,"Mutations in the ATL1 gene cause spastic paraplegia type 3A. The ATL1 gene provides instructions for producing a protein called atlastin-1. Atlastin-1 is produced primarily in the brain and spinal cord (central nervous system), particularly in nerve cells (neurons) that extend down the spinal cord (corticospinal tracts). These neurons send electrical signals that lead to voluntary muscle movement. Atlastin-1 is involved in the growth of specialized extensions of neurons, called axons, which transmit nerve impulses that signal muscle movement. The protein also likely plays a role in the normal functioning of multiple structures within neurons and in distributing materials within these cells.  ATL1 gene mutations likely lead to a shortage of normal atlastin-1 protein, which impairs the functioning of neurons, including the distribution of materials within these cells. This lack of functional atlastin-1 protein may also restrict the growth of axons. These problems can lead to the abnormal functioning or death of the long neurons of the corticospinal tracts. As a result, the neurons are unable to transmit nerve impulses, particularly to other neurons and muscles in the lower extremities. This impaired nerve function leads to the signs and symptoms of spastic paraplegia type 3A.",spastic paraplegia type 3A,0000929,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-3a,C0030486,T047,Disorders
Is spastic paraplegia type 3A inherited ?,0000929-4,inheritance,"Spastic paraplegia type 3A is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In approximately 95 percent of cases, an affected person inherits the mutation from one affected parent.",spastic paraplegia type 3A,0000929,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-3a,C0030486,T047,Disorders
What are the treatments for spastic paraplegia type 3A ?,0000929-5,treatment,"These resources address the diagnosis or management of spastic paraplegia type 3A:  - Gene Review: Gene Review: Hereditary Spastic Paraplegia Overview  - Gene Review: Gene Review: Spastic Paraplegia 3A  - Genetic Testing Registry: Spastic paraplegia 3  - Spastic Paraplegia Foundation, Inc.: Treatments and Therapies   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",spastic paraplegia type 3A,0000929,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-3a,C0030486,T047,Disorders
What is (are) spastic paraplegia type 4 ?,0000930-1,information,"Spastic paraplegia type 4 is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve only the lower limbs, whereas the complex types also involve the upper limbs (to a lesser degree) and the nervous system. Spastic paraplegia type 4 is a pure hereditary spastic paraplegia.  Like all hereditary spastic paraplegias, spastic paraplegia type 4 involves spasticity of the leg muscles and muscle weakness. People with this condition can also experience exaggerated reflexes (hyperreflexia), ankle spasms, high-arched feet (pes cavus), and reduced bladder control. Spastic paraplegia type 4 generally affects nerve and muscle function in the lower half of the body only.",spastic paraplegia type 4,0000930,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-4,C0030486,T047,Disorders
How many people are affected by spastic paraplegia type 4 ?,0000930-2,frequency,"The prevalence of spastic paraplegia type 4 is estimated to be 2 to 6 in 100,000 people worldwide.",spastic paraplegia type 4,0000930,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-4,C0030486,T047,Disorders
What are the genetic changes related to spastic paraplegia type 4 ?,0000930-3,genetic changes,"Mutations in the SPAST gene cause spastic paraplegia type 4. The SPAST gene provides instructions for producing a protein called spastin. Spastin is found throughout the body, particularly in certain nerve cells (neurons). The spastin protein plays a role in the function of microtubules, which are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). Microtubules are also involved in transporting cell components and facilitating cell division. Spastin likely helps restrict microtubule length and disassemble microtubule structures when they are no longer needed. Mutations in spastin impair the microtubules' ability to transport cell components, especially in nerve cells; researchers believe this contributes to the major signs and symptoms of spastic paraplegia type 4.",spastic paraplegia type 4,0000930,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-4,C0030486,T047,Disorders
Is spastic paraplegia type 4 inherited ?,0000930-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In most cases, an affected person inherits the mutation from one affected parent. The remaining cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.",spastic paraplegia type 4,0000930,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-4,C0030486,T047,Disorders
What are the treatments for spastic paraplegia type 4 ?,0000930-5,treatment,"These resources address the diagnosis or management of spastic paraplegia type 4:  - Gene Review: Gene Review: Hereditary Spastic Paraplegia Overview  - Gene Review: Gene Review: Spastic Paraplegia 4  - Genetic Testing Registry: Spastic paraplegia 4, autosomal dominant  - Spastic Paraplegia Foundation, Inc.: Treatments and Therapies   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",spastic paraplegia type 4,0000930,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-4,C0030486,T047,Disorders
What is (are) spastic paraplegia type 7 ?,0000931-1,information,"Spastic paraplegia type 7 is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve the lower limbs. The complex types involve the lower limbs and can also affect the upper limbs to a lesser degree; the structure or functioning of the brain; and the nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound (the peripheral nervous system). Spastic paraplegia type 7 can occur in either the pure or complex form.  Like all hereditary spastic paraplegias, spastic paraplegia type 7 involves spasticity of the leg muscles and increased muscle weakness. People with this form of spastic paraplegia can also experience exaggerated reflexes (hyperreflexia) in the arms; speech difficulties (dysarthria); difficulty swallowing (dysphagia); involuntary movements of the eyes (nystagmus); mild hearing loss; abnormal curvature of the spine (scoliosis); high-arched feet (pes cavus); numbness, tingling, or pain in the arms and legs (sensory neuropathy); disturbance in the nerves used for muscle movement (motor neuropathy); and muscle wasting (amyotrophy). The onset of symptoms varies greatly among those with spastic paraplegia type 7; however, abnormalities in muscle tone and other features are usually noticeable in adulthood.",spastic paraplegia type 7,0000931,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-7,C3711370,T047,Disorders
How many people are affected by spastic paraplegia type 7 ?,0000931-2,frequency,"The prevalence of all hereditary spastic paraplegias combined is estimated to be 2 to 6 in 100,000 people worldwide. Spastic paraplegia type 7 likely accounts for only a small percentage of all spastic paraplegia cases.",spastic paraplegia type 7,0000931,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-7,C3711370,T047,Disorders
What are the genetic changes related to spastic paraplegia type 7 ?,0000931-3,genetic changes,"Mutations in the SPG7 gene cause spastic paraplegia type 7. The SPG7 gene provides instructions for producing a protein called paraplegin. Located within the inner membrane of the energy-producing centers of cells (mitochondria), paraplegin is one of the proteins that form a complex called the m-AAA protease. The m-AAA protease is responsible for assembling ribosomes (cellular structures that process the cell's genetic instructions to create proteins) and removing nonfunctional proteins in the mitochondria. When there is a mutation in paraplegin, the m-AAA protease cannot function correctly. Nonfunctional m-AAA proteases cause a build up of unusable proteins in the mitochondria of nerve cells, which can result in swelling of the cell, reduced cell signaling, and impaired cell movement, leading to the major signs and symptoms of spastic paraplegia type 7.",spastic paraplegia type 7,0000931,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-7,C3711370,T047,Disorders
Is spastic paraplegia type 7 inherited ?,0000931-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",spastic paraplegia type 7,0000931,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-7,C3711370,T047,Disorders
What are the treatments for spastic paraplegia type 7 ?,0000931-5,treatment,"These resources address the diagnosis or management of spastic paraplegia type 7:  - Gene Review: Gene Review: Hereditary Spastic Paraplegia Overview  - Gene Review: Gene Review: Spastic Paraplegia 7  - Genetic Testing Registry: Spastic paraplegia 7  - Spastic Paraplegia Foundation, Inc.: Treatments and Therapies   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",spastic paraplegia type 7,0000931,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-7,C3711370,T047,Disorders
What is (are) spastic paraplegia type 8 ?,0000932-1,information,"Spastic paraplegia type 8 is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve only the nerves and muscles controlling the lower limbs and bladder, whereas the complex types also have significant involvement of the nervous system in other parts of the body. Spastic paraplegia type 8 is a pure hereditary spastic paraplegia.  Like all hereditary spastic paraplegias, spastic paraplegia type 8 involves spasticity of the leg muscles and muscle weakness. People with this condition can also experience exaggerated reflexes (hyperreflexia), a decreased ability to feel vibrations, muscle wasting (amyotrophy), and reduced bladder control. The signs and symptoms of spastic paraplegia type 8 usually appear in early to mid-adulthood. As the muscle weakness and spasticity get worse, some people may need the aid of a cane, walker, or wheelchair.",spastic paraplegia type 8,0000932,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-8,C1863704,T047,Disorders
How many people are affected by spastic paraplegia type 8 ?,0000932-2,frequency,"The prevalence of all hereditary spastic paraplegias combined is estimated to be 1 to 18 in 100,000 people worldwide. Spastic paraplegia type 8 likely accounts for only a small percentage of all spastic paraplegia cases.",spastic paraplegia type 8,0000932,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-8,C1863704,T047,Disorders
What are the genetic changes related to spastic paraplegia type 8 ?,0000932-3,genetic changes,"Mutations in the KIAA0196 gene cause spastic paraplegia type 8. The KIAA0196 gene provides instructions for making a protein called strumpellin. Strumpellin is active (expressed) throughout the body, although its exact function is unknown. The protein's structure suggests that strumpellin may interact with the structural framework inside cells (the cytoskeleton) and may attach (bind) to other proteins.  KIAA0196 gene mutations are thought to change the structure of the strumpellin protein. It is unknown how the altered strumpellin protein causes the signs and symptoms of spastic paraplegia type 8.",spastic paraplegia type 8,0000932,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-8,C1863704,T047,Disorders
Is spastic paraplegia type 8 inherited ?,0000932-4,inheritance,"Spastic paraplegia type 8 is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",spastic paraplegia type 8,0000932,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-8,C1863704,T047,Disorders
What are the treatments for spastic paraplegia type 8 ?,0000932-5,treatment,"These resources address the diagnosis or management of spastic paraplegia type 8:  - Gene Review: Gene Review: Spastic Paraplegia 8  - Genetic Testing Registry: Spastic paraplegia 8  - Spastic Paraplegia Foundation, Inc.: Treatments and Therapies   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",spastic paraplegia type 8,0000932,GHR,https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-8,C1863704,T047,Disorders
What is (are) spina bifida ?,0000933-1,information,"Spina bifida is a condition in which the neural tube, a layer of cells that ultimately develops into the brain and spinal cord, fails to close completely during the first few weeks of embryonic development. As a result, when the spine forms, the bones of the spinal column do not close completely around the developing nerves of the spinal cord. Part of the spinal cord may stick out through an opening in the spine, leading to permanent nerve damage. Because spina bifida is caused by abnormalities of the neural tube, it is classified as a neural tube defect.  Children born with spina bifida often have a fluid-filled sac on their back that is covered by skin, called a meningocele. If the sac contains part of the spinal cord and its protective covering, it is known as a myelomeningocele. The signs and symptoms of these abnormalities range from mild to severe, depending on where the opening in the spinal column is located and how much of the spinal cord is affected. Related problems can include a loss of feeling below the level of the opening, weakness or paralysis of the feet or legs, and problems with bladder and bowel control. Some affected individuals have additional complications, including a buildup of excess fluid around the brain (hydrocephalus) and learning problems. With surgery and other forms of treatment, many people with spina bifida live into adulthood.  In a milder form of the condition, called spina bifida occulta, the bones of the spinal column are abnormally formed, but the nerves of the spinal cord usually develop normally. Unlike in the more severe form of spina bifida, the nerves do not stick out through an opening in the spine. Spina bifida occulta most often causes no health problems, although rarely it can cause back pain or changes in bladder function.",spina bifida,0000933,GHR,https://ghr.nlm.nih.gov/condition/spina-bifida,C0080178,T019,Disorders
How many people are affected by spina bifida ?,0000933-2,frequency,"Spina bifida is one of the most common types of neural tube defect, affecting an estimated 1 in 2,500 newborns worldwide. For unknown reasons, the prevalence of spina bifida varies among different geographic regions and ethnic groups. In the United States, this condition occurs more frequently in Hispanics and non-Hispanic whites than in African Americans.",spina bifida,0000933,GHR,https://ghr.nlm.nih.gov/condition/spina-bifida,C0080178,T019,Disorders
What are the genetic changes related to spina bifida ?,0000933-3,genetic changes,"Spina bifida is a complex condition that is likely caused by the interaction of multiple genetic and environmental factors. Some of these factors have been identified, but many remain unknown.  Changes in dozens of genes in individuals with spina bifida and in their mothers may influence the risk of developing this type of neural tube defect. The best-studied of these genes is MTHFR, which provides instructions for making a protein that is involved in processing the vitamin folate (also called vitamin B9). A shortage (deficiency) of this vitamin is an established risk factor for neural tube defects. Changes in other genes related to folate processing and genes involved in the development of the neural tube have also been studied as potential risk factors for spina bifida. However, none of these genes appears to play a major role in causing the condition.  Researchers have also examined environmental factors that could contribute to the risk of spina bifida. As mentioned above, folate deficiency appears to play a significant role. Studies have shown that women who take supplements containing folic acid (the synthetic form of folate) before they get pregnant and very early in their pregnancy are significantly less likely to have a baby with spina bifida or a related neural tube defect. Other possible maternal risk factors for spina bifida include diabetes mellitus, obesity, exposure to high heat (such as a fever or use of a hot tub or sauna) in early pregnancy, and the use of certain anti-seizure medications during pregnancy. However, it is unclear how these factors may influence the risk of spina bifida.",spina bifida,0000933,GHR,https://ghr.nlm.nih.gov/condition/spina-bifida,C0080178,T019,Disorders
Is spina bifida inherited ?,0000933-4,inheritance,"Most cases of spina bifida are sporadic, which means they occur in people with no history of the disorder in their family. A small percentage of cases have been reported to run in families; however, the condition does not have a clear pattern of inheritance. First-degree relatives (such as siblings and children) of people with spina bifida have an increased risk of the condition compared with people in the general population.",spina bifida,0000933,GHR,https://ghr.nlm.nih.gov/condition/spina-bifida,C0080178,T019,Disorders
What are the treatments for spina bifida ?,0000933-5,treatment,"These resources address the diagnosis or management of spina bifida:  - Benioff Children's Hospital, University of California, San Francisco: Treatment of Spina Bifida  - Centers for Disease Control and Prevention: Living with Spina Bifida  - GeneFacts: Spina Bifida: Diagnosis  - GeneFacts: Spina Bifida: Management  - Genetic Testing Registry: Neural tube defect  - Genetic Testing Registry: Neural tube defects, folate-sensitive  - Spina Bifida Association: Urologic Care and Management  - University of California, San Francisco Fetal Treatment Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",spina bifida,0000933,GHR,https://ghr.nlm.nih.gov/condition/spina-bifida,C0080178,T019,Disorders
What is (are) spinal and bulbar muscular atrophy ?,0000934-1,information,"Spinal and bulbar muscular atrophy, also known as Kennedy disease, is a disorder of specialized nerve cells that control muscle movement (motor neurons). These nerve cells originate in the spinal cord and the part of the brain that is connected to the spinal cord (the brainstem).  Spinal and bulbar muscular atrophy mainly affects males and is characterized by muscle weakness and wasting (atrophy) that usually begins in adulthood and worsens slowly over time. Muscle wasting in the arms and legs results in cramping; leg muscle weakness can also lead to difficulty walking and a tendency to fall. Certain muscles in the face and throat (bulbar muscles) are also affected, which causes progressive problems with swallowing and speech. Additionally, muscle twitches (fasciculations) are common. Some males with the disorder experience unusual breast development (gynecomastia) and may be unable to father a child (infertile).",spinal and bulbar muscular atrophy,0000934,GHR,https://ghr.nlm.nih.gov/condition/spinal-and-bulbar-muscular-atrophy,C0026846,T047,Disorders
How many people are affected by spinal and bulbar muscular atrophy ?,0000934-2,frequency,"This condition affects fewer than 1 in 150,000 males and is very rare in females.",spinal and bulbar muscular atrophy,0000934,GHR,https://ghr.nlm.nih.gov/condition/spinal-and-bulbar-muscular-atrophy,C0026846,T047,Disorders
What are the genetic changes related to spinal and bulbar muscular atrophy ?,0000934-3,genetic changes,"Spinal and bulbar muscular atrophy results from a particular type of mutation in the AR gene. This gene provides instructions for making a protein called an androgen receptor. This receptor attaches (binds) to a class of hormones called androgens, which are involved in male sexual development. Androgens and androgen receptors also have other important functions in both males and females, such as regulating hair growth and sex drive.  The AR gene mutation that causes spinal and bulbar muscular atrophy is the abnormal expansion of a DNA segment called a CAG triplet repeat. Normally, this DNA segment is repeated up to about 36 times. In people with spinal and bulbar muscular atrophy, the CAG segment is repeated at least 38 times, and it may be two or three times its usual length. Although the extended CAG region changes the structure of the androgen receptor, it is unclear how the altered protein disrupts nerve cells in the brain and spinal cord. Researchers believe that a fragment of the androgen receptor protein containing the CAG segment accumulates within these cells and interferes with normal cell functions. The nerve cells gradually die, leading to the muscle weakness and wasting seen in this condition. People with a higher number of CAG repeats tend to develop signs and symptoms of spinal and bulbar muscular atrophy at an earlier age.",spinal and bulbar muscular atrophy,0000934,GHR,https://ghr.nlm.nih.gov/condition/spinal-and-bulbar-muscular-atrophy,C0026846,T047,Disorders
Is spinal and bulbar muscular atrophy inherited ?,0000934-4,inheritance,"This condition is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In most cases, males experience more severe symptoms of the disorder than females (who have two X chromosomes). Females with a mutation in one copy of the AR gene in each cell are typically unaffected. A few females with mutations in both copies of the gene have had mild features related to the condition, including muscle cramps and occasional tremors. Researchers believe that the milder signs and symptoms in females may be related to lower androgen levels.  A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",spinal and bulbar muscular atrophy,0000934,GHR,https://ghr.nlm.nih.gov/condition/spinal-and-bulbar-muscular-atrophy,C0026846,T047,Disorders
What are the treatments for spinal and bulbar muscular atrophy ?,0000934-5,treatment,These resources address the diagnosis or management of spinal and bulbar muscular atrophy:  - Gene Review: Gene Review: Spinal and Bulbar Muscular Atrophy  - Genetic Testing Registry: Bulbo-spinal atrophy X-linked  - MedlinePlus Encyclopedia: Muscle Atrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,spinal and bulbar muscular atrophy,0000934,GHR,https://ghr.nlm.nih.gov/condition/spinal-and-bulbar-muscular-atrophy,C0026846,T047,Disorders
What is (are) spinal muscular atrophy ?,0000935-1,information,"Spinal muscular atrophy is a genetic disorder that affects the control of muscle movement. It is caused by a loss of specialized nerve cells, called motor neurons, in the spinal cord and the part of the brain that is connected to the spinal cord (the brainstem). The loss of motor neurons leads to weakness and wasting (atrophy) of muscles used for activities such as crawling, walking, sitting up, and controlling head movement. In severe cases of spinal muscular atrophy, the muscles used for breathing and swallowing are affected. There are many types of spinal muscular atrophy distinguished by the pattern of features, severity of muscle weakness, and age when the muscle problems begin.  Type I spinal muscular atrophy (also called Werdnig-Hoffman disease) is a severe form of the disorder that is evident at birth or within the first few months of life. Affected infants are developmentally delayed; most are unable to support their head or sit unassisted. Children with this type have breathing and swallowing problems that may lead to choking or gagging.  Type II spinal muscular atrophy is characterized by muscle weakness that develops in children between ages 6 and 12 months. Children with type II can sit without support, although they may need help getting to a seated position. Individuals with this type of spinal muscular atrophy cannot stand or walk unaided.  Type III spinal muscular atrophy (also called Kugelberg-Welander disease or juvenile type) has milder features that typically develop between early childhood and adolescence. Individuals with type III spinal muscular atrophy can stand and walk unaided, but walking and climbing stairs may become increasingly difficult. Many affected individuals will require wheelchair assistance later in life.  The signs and symptoms of type IV spinal muscular atrophy often occur after age 30. Affected individuals usually experience mild to moderate muscle weakness, tremor, twitching, or mild breathing problems. Typically, only muscles close to the center of the body (proximal muscles), such as the upper arms and legs, are affected in type IV spinal muscular atrophy.  The features of X-linked spinal muscular atrophy appear in infancy and include severe muscle weakness and difficulty breathing. Children with this type often have joint deformities (contractures) that impair movement. In severe cases, affected infants are born with broken bones. Poor muscle tone before birth may contribute to the contractures and broken bones seen in these children.  Spinal muscular atrophy, lower extremity, dominant (SMA-LED) is characterized by leg muscle weakness that is most severe in the thigh muscles (quadriceps). This weakness begins in infancy or early childhood and progresses slowly. Affected individuals often have a waddling or unsteady walk and have difficulty rising from a seated position and climbing stairs.  An adult-onset form of spinal muscular atrophy that begins in early to mid-adulthood affects the proximal muscles and is characterized by muscle cramping of the limbs and abdomen, weakness in the leg muscles, involuntary muscle contractions, tremors, and a protrusion of the abdomen thought to be related to muscle weakness. Some affected individuals experience difficulty swallowing and problems with bladder and bowel function.",spinal muscular atrophy,0000935,GHR,https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy,C0026847,T047,Disorders
How many people are affected by spinal muscular atrophy ?,0000935-2,frequency,"Spinal muscular atrophy affects 1 in 6,000 to 1 in 10,000 people.",spinal muscular atrophy,0000935,GHR,https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy,C0026847,T047,Disorders
What are the genetic changes related to spinal muscular atrophy ?,0000935-3,genetic changes,"Mutations in the SMN1, UBA1, DYNC1H1, and VAPB genes cause spinal muscular atrophy. Extra copies of the SMN2 gene modify the severity of spinal muscular atrophy.  The SMN1 and SMN2 genes provide instructions for making a protein called the survival motor neuron (SMN) protein. The SMN protein is important for the maintenance of specialized nerve cells called motor neurons. Motor neurons are located in the spinal cord and the brainstem; they control muscle movement. Most functional SMN protein is produced from the SMN1 gene, with a small amount produced from the SMN2 gene. Several different versions of the SMN protein are produced from the SMN2 gene, but only one version is full size and functional.  Mutations in the SMN1 gene cause spinal muscular atrophy types I, II, III, and IV. SMN1 gene mutations lead to a shortage of the SMN protein. Without SMN protein, motor neurons die, and nerve impulses are not passed between the brain and muscles. As a result, some muscles cannot perform their normal functions, leading to weakness and impaired movement.  Some people with type II, III, or IV spinal muscular atrophy have three or more copies of the SMN2 gene in each cell. Having multiple copies of the SMN2 gene can modify the course of spinal muscular atrophy. The additional SMN proteins produced from the extra copies of the SMN2 gene can help replace some of the SMN protein that is lost due to mutations in the SMN1 gene. In general, symptoms are less severe and begin later in life as the number of copies of the SMN2 gene increases.  Mutations in the UBA1 gene cause X-linked spinal muscular atrophy. The UBA1 gene provides instructions for making the ubiquitin-activating enzyme E1. This enzyme is involved in a process that targets proteins to be broken down (degraded) within cells. UBA1 gene mutations lead to reduced or absent levels of functional enzyme, which disrupts the process of protein degradation. A buildup of proteins in the cell can cause it to die; motor neurons are particularly susceptible to damage from protein buildup.  The DYNC1H1 gene provides instructions for making a protein that is part of a group (complex) of proteins called dynein. This complex is found in the fluid inside cells (cytoplasm), where it is part of a network that moves proteins and other materials. In neurons, dynein moves cellular materials away from the junctions between neurons (synapses) to the center of the cell. This process helps transmit chemical messages from one neuron to another. DYNC1H1 gene mutations that cause SMA-LED disrupt the function of the dynein complex. As a result, the movement of proteins, cellular structures, and other materials within cells are impaired. A decrease in chemical messaging between neurons that control muscle movement is thought to contribute to the muscle weakness experienced by people with SMA-LED. It is unclear why this condition affects only the lower extremities.  The adult-onset form of spinal muscular atrophy is caused by a mutation in the VAPB gene. The VAPB gene provides instructions for making a protein that is found in cells throughout the body. Researchers suggest that this protein may play a role in preventing the buildup of unfolded or misfolded proteins within cells. It is unclear how a VAPB gene mutation leads to the loss of motor neurons. An impaired VAPB protein might cause misfolded and unfolded proteins to accumulate and impair the normal function of motor neurons.  Other types of spinal muscular atrophy that primarily affect the lower legs and feet and the lower arms and hands are caused by the dysfunction of neurons in the spinal cord. When spinal muscular atrophy shows this pattern of signs and symptoms, it is also known as distal hereditary motor neuropathy. The various types of this condition are caused by mutations in other genes.",spinal muscular atrophy,0000935,GHR,https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy,C0026847,T047,Disorders
Is spinal muscular atrophy inherited ?,0000935-4,inheritance,"Types I, II, III, and IV spinal muscular atrophy are inherited in an autosomal recessive pattern, which means both copies of the SMN1 gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Extra copies of the SMN2 gene are due to a random error when making new copies of DNA (replication) in an egg or sperm cell or just after fertilization.  SMA-LED and the late-onset form of spinal muscular atrophy caused by VAPB gene mutations are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  X-linked spinal muscular atrophy is inherited in an X-linked pattern. The UBA1 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",spinal muscular atrophy,0000935,GHR,https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy,C0026847,T047,Disorders
What are the treatments for spinal muscular atrophy ?,0000935-5,treatment,"These resources address the diagnosis or management of spinal muscular atrophy:  - Gene Review: Gene Review: Spinal Muscular Atrophy  - Gene Review: Gene Review: Spinal Muscular Atrophy, X-Linked Infantile  - Genetic Testing Registry: Adult proximal spinal muscular atrophy, autosomal dominant  - Genetic Testing Registry: Arthrogryposis multiplex congenita, distal, X-linked  - Genetic Testing Registry: Kugelberg-Welander disease  - Genetic Testing Registry: Spinal muscular atrophy type 4  - Genetic Testing Registry: Spinal muscular atrophy, lower extremity predominant 1, autosomal dominant  - Genetic Testing Registry: Spinal muscular atrophy, type II  - Genetic Testing Registry: Werdnig-Hoffmann disease  - Genomics Education Programme (UK)  - MedlinePlus Encyclopedia: Spinal Muscular Atrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",spinal muscular atrophy,0000935,GHR,https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy,C0026847,T047,Disorders
What is (are) spinal muscular atrophy with progressive myoclonic epilepsy ?,0000936-1,information,"Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is a neurological condition that causes muscle weakness and wasting (atrophy) and a combination of seizures and uncontrollable muscle jerks (myoclonic epilepsy).  In individuals with SMA-PME, spinal muscular atrophy results from a loss of specialized nerve cells, called motor neurons, in the spinal cord and the part of the brain that is connected to the spinal cord (the brainstem). After a few years of normal development, affected children begin experiencing muscle weakness and atrophy in the lower limbs, causing difficulty walking and frequent falls. The muscles in the upper limbs are later affected, and soon the muscle weakness and atrophy spreads throughout the body. Once weakness reaches the muscles used for breathing and swallowing, it leads to life-threatening breathing problems and increased susceptibility to pneumonia.  A few years after the muscle weakness begins, affected individuals start to experience recurrent seizures (epilepsy). Most people with SMA-PME have a variety of seizure types. In addition to myoclonic epilepsy, they may have generalized tonic-clonic seizures (also known as grand mal seizures), which cause muscle rigidity, convulsions, and loss of consciousness. Affected individuals can also have absence seizures, which cause loss of consciousness for a short period that may or may not be accompanied by muscle jerks. In SMA-PME, seizures often increase in frequency over time and are usually not well-controlled with medication. Individuals with SMA-PME may also have episodes of rhythmic shaking (tremors), usually in the hands; these tremors are not thought to be related to epilepsy.  Some people with SMA-PME develop hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss).  Individuals with SMA-PME have a shortened lifespan; they generally live into late childhood or early adulthood. The cause of death is often respiratory failure or pneumonia.",spinal muscular atrophy with progressive myoclonic epilepsy,0000936,GHR,https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy-with-progressive-myoclonic-epilepsy,C1834569,T047,Disorders
How many people are affected by spinal muscular atrophy with progressive myoclonic epilepsy ?,0000936-2,frequency,SMA-PME is a rare disorder; approximately a dozen affected families have been described in the scientific literature.,spinal muscular atrophy with progressive myoclonic epilepsy,0000936,GHR,https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy-with-progressive-myoclonic-epilepsy,C1834569,T047,Disorders
What are the genetic changes related to spinal muscular atrophy with progressive myoclonic epilepsy ?,0000936-3,genetic changes,"SMA-PME is caused by mutations in the ASAH1 gene. This gene provides instructions for making an enzyme called acid ceramidase. This enzyme is found in lysosomes, which are cell compartments that digest and recycle materials. Within lysosomes, acid ceramidase breaks down fats called ceramides into a fat called sphingosine and a fatty acid. These two breakdown products are recycled to create new ceramides for the body to use. Ceramides have several roles within cells. For example, they are a component of a fatty substance called myelin that insulates and protects nerve cells.  ASAH1 gene mutations that cause SMA-PME result in a reduction of acid ceramidase activity to a level less than one-third of normal. Inefficient breakdown of ceramides and impaired production of its breakdown products likely play a role in the nerve cell damage that leads to the features of SMA-PME, but the exact mechanism is unknown.",spinal muscular atrophy with progressive myoclonic epilepsy,0000936,GHR,https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy-with-progressive-myoclonic-epilepsy,C1834569,T047,Disorders
Is spinal muscular atrophy with progressive myoclonic epilepsy inherited ?,0000936-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",spinal muscular atrophy with progressive myoclonic epilepsy,0000936,GHR,https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy-with-progressive-myoclonic-epilepsy,C1834569,T047,Disorders
What are the treatments for spinal muscular atrophy with progressive myoclonic epilepsy ?,0000936-5,treatment,These resources address the diagnosis or management of spinal muscular atrophy with progressive myoclonic epilepsy:  - Genetic Testing Registry: Jankovic Rivera syndrome  - Muscular Dystrophy Association: Spinal Muscular Atrophy Types   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,spinal muscular atrophy with progressive myoclonic epilepsy,0000936,GHR,https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy-with-progressive-myoclonic-epilepsy,C1834569,T047,Disorders
What is (are) spinal muscular atrophy with respiratory distress type 1 ?,0000937-1,information,"Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is an inherited condition that causes muscle weakness and respiratory failure typically beginning in infancy. Early features of this condition are difficult and noisy breathing, especially when inhaling; a weak cry; problems feeding; and recurrent episodes of pneumonia. Typically between the ages of 6 weeks and 6 months, infants with this condition will experience a sudden inability to breathe due to paralysis of the muscle that separates the abdomen from the chest cavity (the diaphragm). Normally, the diaphragm contracts and moves downward during inhalation to allow the lungs to expand. With diaphragm paralysis, affected individuals require life-long support with a machine to help them breathe (mechanical ventilation). Rarely, children with SMARD1 develop signs or symptoms of the disorder later in childhood.  Soon after respiratory failure occurs, individuals with SMARD1 develop muscle weakness in their distal muscles. These are the muscles farther from the center of the body, such as muscles in the hands and feet. The weakness soon spreads to all muscles; however, within 2 years, the muscle weakness typically stops getting worse. Some individuals may retain a low level of muscle function, while others lose all ability to move their muscles. Muscle weakness severely impairs motor development, such as sitting, standing, and walking. Some affected children develop an abnormal side-to-side and back-to-front curvature of the spine (scoliosis and kyphosis, often called kyphoscoliosis when they occur together). After approximately the first year of life, individuals with SMARD1 may lose their deep tendon reflexes, such as the reflex being tested when a doctor taps the knee with a hammer.  Other features of SMARD1 can include reduced pain sensitivity, excessive sweating (hyperhidrosis), loss of bladder and bowel control, and an irregular heartbeat (arrhythmia).",spinal muscular atrophy with respiratory distress type 1,0000937,GHR,https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy-with-respiratory-distress-type-1,C1858517,T047,Disorders
How many people are affected by spinal muscular atrophy with respiratory distress type 1 ?,0000937-2,frequency,"SMARD1 appears to be a rare condition, but its prevalence is unknown. More than 60 cases have been reported in the scientific literature.",spinal muscular atrophy with respiratory distress type 1,0000937,GHR,https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy-with-respiratory-distress-type-1,C1858517,T047,Disorders
What are the genetic changes related to spinal muscular atrophy with respiratory distress type 1 ?,0000937-3,genetic changes,"Mutations in the IGHMBP2 gene cause SMARD1. The IGHMBP2 gene provides instructions for making a protein involved in copying (replicating) DNA; producing RNA, a chemical cousin of DNA; and producing proteins. IGHMBP2 gene mutations that cause SMARD1 lead to the production of a protein with reduced ability to aid in DNA replication and the production of RNA and proteins. These problems particularly affect alpha-motor neurons, which are specialized cells in the brainstem and spinal cord that control muscle movements. Although the mechanism is unknown, altered IGHMBP2 proteins contribute to the damage of these neurons and their death over time. The cumulative death of alpha-motor neurons leads to breathing problems and progressive muscle weakness in children with SMARD1.  Research suggests that the amount of functional protein that is produced from the mutated IGHMBP2 gene may play a role in the severity of SMARD1. Individuals who have some functional protein are more likely to develop signs and symptoms later in childhood and retain a greater level of muscle function.",spinal muscular atrophy with respiratory distress type 1,0000937,GHR,https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy-with-respiratory-distress-type-1,C1858517,T047,Disorders
Is spinal muscular atrophy with respiratory distress type 1 inherited ?,0000937-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",spinal muscular atrophy with respiratory distress type 1,0000937,GHR,https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy-with-respiratory-distress-type-1,C1858517,T047,Disorders
What are the treatments for spinal muscular atrophy with respiratory distress type 1 ?,0000937-5,treatment,These resources address the diagnosis or management of SMARD1:  - Genetic Testing Registry: Spinal muscular atrophy with respiratory distress 1   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,spinal muscular atrophy with respiratory distress type 1,0000937,GHR,https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy-with-respiratory-distress-type-1,C1858517,T047,Disorders
What is (are) spinocerebellar ataxia type 1 ?,0000938-1,information,"Spinocerebellar ataxia type 1 (SCA1) is a condition characterized by progressive problems with movement. People with this condition initially experience problems with coordination and balance (ataxia). Other signs and symptoms of SCA1 include speech and swallowing difficulties, muscle stiffness (spasticity), and weakness in the muscles that control eye movement (ophthalmoplegia). Eye muscle weakness leads to rapid, involuntary eye movements (nystagmus). Individuals with SCA1 may have difficulty processing, learning, and remembering information (cognitive impairment).  Over time, individuals with SCA1 may develop numbness, tingling, or pain in the arms and legs (sensory neuropathy); uncontrolled muscle tensing (dystonia); muscle wasting (atrophy); and muscle twitches (fasciculations). Rarely, rigidity, tremors, and involuntary jerking movements (chorea) have been reported in people who have been affected for many years.  Signs and symptoms of the disorder typically begin in early adulthood but can appear anytime from childhood to late adulthood. People with SCA1 typically survive 10 to 20 years after symptoms first appear.",spinocerebellar ataxia type 1,0000938,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-1,C0752120,T047,Disorders
How many people are affected by spinocerebellar ataxia type 1 ?,0000938-2,frequency,"SCA1 affects 1 to 2 per 100,000 people worldwide.",spinocerebellar ataxia type 1,0000938,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-1,C0752120,T047,Disorders
What are the genetic changes related to spinocerebellar ataxia type 1 ?,0000938-3,genetic changes,"Mutations in the ATXN1 gene cause SCA1. The ATXN1 gene provides instructions for making a protein called ataxin-1. This protein is found throughout the body, but its function is unknown. Within cells, ataxin-1 is located in the nucleus. Researchers believe that ataxin-1 may be involved in regulating various aspects of producing proteins, including the first stage of protein production (transcription) and processing RNA, a chemical cousin of DNA.  The ATXN1 gene mutations that cause SCA1 involve a DNA segment known as a CAG trinucleotide repeat. This segment is made up of a series of three DNA building blocks (cytosine, adenine, and guanine) that appear multiple times in a row. Normally, the CAG segment is repeated 4 to 39 times within the gene. In people with SCA1, the CAG segment is repeated 40 to more than 80 times. People with 40 to 50 repeats tend to first experience signs and symptoms of SCA1 in mid-adulthood, while people with more than 70 repeats usually have signs and symptoms by their teens.  An increase in the length of the CAG segment leads to the production of an abnormally long version of the ataxin-1 protein that folds into the wrong 3-dimensional shape. This abnormal protein clusters with other proteins to form clumps (aggregates) within the nucleus of the cells. These aggregates prevent the ataxin-1 protein from functioning normally, which damages cells and leads to cell death. For reasons that are unclear, aggregates of ataxin-1 are found only in the brain and spinal cord (central nervous system). Cells within the cerebellum, which is the part of the brain that coordinates movement, are particularly sensitive to changes in ataxin-1 shape and function. Over time, the loss of the cells of the cerebellum causes the movement problems characteristic of SCA1.",spinocerebellar ataxia type 1,0000938,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-1,C0752120,T047,Disorders
Is spinocerebellar ataxia type 1 inherited ?,0000938-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. An affected person usually inherits the altered gene from one affected parent. However, some people with SCA1 do not have a parent with the disorder.  As the altered ATXN1 gene is passed down from one generation to the next, the length of the CAG trinucleotide repeat often increases. A larger number of repeats is usually associated with an earlier onset of signs and symptoms. This phenomenon is called anticipation. Anticipation tends to be more prominent when the ATXN1 gene is inherited from a person's father (paternal inheritance) than when it is inherited from a person's mother (maternal inheritance).  Individuals who have around 35 CAG repeats in the ATXN1 gene do not develop SCA1, but they are at risk of having children who will develop the disorder. As the gene is passed from parent to child, the size of the CAG trinucleotide repeat may lengthen into the range associated with SCA1 (40 repeats or more).",spinocerebellar ataxia type 1,0000938,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-1,C0752120,T047,Disorders
What are the treatments for spinocerebellar ataxia type 1 ?,0000938-5,treatment,These resources address the diagnosis or management of SCA1:  - Gene Review: Gene Review: Spinocerebellar Ataxia Type 1  - Genetic Testing Registry: Spinocerebellar ataxia 1   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,spinocerebellar ataxia type 1,0000938,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-1,C0752120,T047,Disorders
What is (are) spinocerebellar ataxia type 2 ?,0000939-1,information,"Spinocerebellar ataxia type 2 (SCA2) is a condition characterized by progressive problems with movement. People with this condition initially experience problems with coordination and balance (ataxia). Other early signs and symptoms of SCA2 include speech and swallowing difficulties, rigidity, tremors, and weakness in the muscles that control eye movement (ophthalmoplegia). Eye muscle weakness leads to a decreased ability to make rapid eye movements (saccadic slowing).  Over time, individuals with SCA2 may develop loss of sensation and weakness in the limbs (peripheral neuropathy), muscle wasting (atrophy), uncontrolled muscle tensing (dystonia), and involuntary jerking movements (chorea). Individuals with SCA2 may have problems with short term memory, planning, and problem solving, or experience an overall decline in intellectual function (dementia).  Signs and symptoms of the disorder typically begin in mid-adulthood but can appear anytime from childhood to late adulthood. People with SCA2 usually survive 10 to 20 years after symptoms first appear.",spinocerebellar ataxia type 2,0000939,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-2,C0752121,T047,Disorders
How many people are affected by spinocerebellar ataxia type 2 ?,0000939-2,frequency,"The prevalence of SCA2 is unknown. This condition is estimated to be one of the most common types of spinocerebellar ataxia; however, all types of spinocerebellar ataxia are relatively rare. SCA2 is more common in Cuba, particularly in the Holgun province, where approximately 40 per 100,000 individuals are affected.",spinocerebellar ataxia type 2,0000939,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-2,C0752121,T047,Disorders
What are the genetic changes related to spinocerebellar ataxia type 2 ?,0000939-3,genetic changes,"Mutations in the ATXN2 gene cause SCA2. The ATXN2 gene provides instructions for making a protein called ataxin-2. This protein is found throughout the body, but its function is unknown. Ataxin-2 is found in the fluid inside cells (cytoplasm), where it appears to interact with a cell structure called the endoplasmic reticulum. The endoplasmic reticulum is involved in protein production, processing, and transport. Researchers believe that ataxin-2 may be involved in processing RNA, a chemical cousin of DNA. Ataxin-2 is also thought to play a role in the production of proteins from RNA (translation of DNA's genetic information).  The ATXN2 gene mutations that cause SCA2 involve a DNA segment known as a CAG trinucleotide repeat. This segment is made up of a series of three DNA building blocks (cytosine, adenine, and guanine) that appear multiple times in a row. Normally, the CAG segment is repeated approximately 22 times within the gene, but it can be repeated up to 31 times without causing any health problems. Individuals with 32 or more CAG repeats in the ATXN2 gene develop SCA2. People with 32 or 33 repeats tend to first experience signs and symptoms of SCA2 in late adulthood, while people with more than 45 repeats usually have signs and symptoms by their teens.  It is unclear how the abnormally long CAG segment affects the function of the ataxin-2 protein. The abnormal protein apparently leads to cell death, as people with SCA2 show loss of brain cells in different parts of the brain. Over time, the loss of brain cells causes the movement problems characteristic of SCA2.",spinocerebellar ataxia type 2,0000939,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-2,C0752121,T047,Disorders
Is spinocerebellar ataxia type 2 inherited ?,0000939-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. An affected person usually inherits the altered gene from one affected parent. However, some people with SCA2 do not have a parent with the disorder. Individuals who have an increase in the number of CAG repeats in the ATXN2 gene, but do not develop SCA2, are at risk of having children who will develop the disorder.  As the altered ATXN2 gene is passed down from one generation to the next, the length of the CAG trinucleotide repeat often increases. A larger number of repeats is usually associated with an earlier onset of signs and symptoms. This phenomenon is called anticipation. Anticipation tends to be more prominent when the ATXN2 gene is inherited from a person's father (paternal inheritance) than when it is inherited from a person's mother (maternal inheritance).",spinocerebellar ataxia type 2,0000939,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-2,C0752121,T047,Disorders
What are the treatments for spinocerebellar ataxia type 2 ?,0000939-5,treatment,These resources address the diagnosis or management of SCA2:  - Gene Review: Gene Review: Spinocerebellar Ataxia Type 2  - Genetic Testing Registry: Spinocerebellar ataxia 2   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,spinocerebellar ataxia type 2,0000939,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-2,C0752121,T047,Disorders
What is (are) spinocerebellar ataxia type 3 ?,0000940-1,information,"Spinocerebellar ataxia type 3 (SCA3) is a condition characterized by progressive problems with movement. People with this condition initially experience problems with coordination and balance (ataxia). Other early signs and symptoms of SCA3 include speech difficulties, uncontrolled muscle tensing (dystonia), muscle stiffness (spasticity), rigidity, tremors, bulging eyes, and double vision. People with this condition may experience sleep disorders such as restless leg syndrome or REM sleep behavior disorder. Restless leg syndrome is a condition characterized by numbness or tingling in the legs accompanied by an urge to move the legs to stop the sensations. REM sleep behavior disorder is a condition in which the muscles are active during the dream (REM) stage of sleep, so an affected person often acts out his or her dreams. These sleep disorders tend to leave affected individuals feeling tired during the day.  Over time, individuals with SCA3 may develop loss of sensation and weakness in the limbs (peripheral neuropathy), muscle cramps, muscle twitches (fasciculations), and swallowing difficulties. Individuals with SCA3 may have problems with memory, planning, and problem solving.  Signs and symptoms of the disorder typically begin in mid-adulthood but can appear anytime from childhood to late adulthood. People with SCA3 eventually require wheelchair assistance. They usually survive 10 to 20 years after symptoms first appear.",spinocerebellar ataxia type 3,0000940,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-3,C0024408,T047,Disorders
How many people are affected by spinocerebellar ataxia type 3 ?,0000940-2,frequency,"The prevalence of SCA3 is unknown. This condition is thought to be the most common type of spinocerebellar ataxia; however, all types of spinocerebellar ataxia are relatively rare.",spinocerebellar ataxia type 3,0000940,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-3,C0024408,T047,Disorders
What are the genetic changes related to spinocerebellar ataxia type 3 ?,0000940-3,genetic changes,"Mutations in the ATXN3 gene cause SCA3. The ATXN3 gene provides instructions for making an enzyme called ataxin-3, which is found in cells throughout the body. Ataxin-3 is involved in a mechanism called the ubiquitin-proteasome system that destroys and gets rid of excess or damaged proteins. The molecule ubiquitin is attached (bound) to unneeded proteins, which tags them to be broken down (degraded) within cells. Ataxin-3 removes the ubiquitin from these unwanted proteins just before they are degraded so that the ubiquitin can be used again. Researchers believe that ataxin-3 also may be involved in regulating the first stage of protein production (transcription).  The ATXN3 gene mutations that cause SCA3 involve a DNA segment known as a CAG trinucleotide repeat. This segment is made up of a series of three DNA building blocks (cytosine, adenine, and guanine) that appear multiple times in a row. Normally, the CAG segment is repeated 12 to 43 times within the gene. Most people have fewer than 31 CAG repeats. In people with SCA3, the CAG segment is repeated more than 50 times. People who have 44 to 52 CAG repeats are described as having an ""intermediate repeat."" These individuals may or may not develop SCA3. People with 75 or fewer repeats tend to first experience signs and symptoms of SCA3 in mid-adulthood, while people with around 80 repeats usually have signs and symptoms by their teens.  An increase in the length of the CAG segment leads to the production of an abnormally long version of the ataxin-3 enzyme that folds into the wrong 3-dimensional shape. This nonfunctional ataxin-3 enzyme cannot remove ubiquitin from proteins that are no longer needed. As a result, these unwanted proteins, along with ubiquitin and ataxin-3, cluster together to form clumps (aggregates) within the nucleus of the cells. It is unclear how these aggregates affect cell function, because they are found in healthy cells as well as those that die.  Nerve cells (neurons) and other types of brain cells are most affected by mutations in the ATXN3 gene. SCA3 is associated with cell death in the part of the brain that is connected to the spinal cord (the brainstem), the part of the brain involved in coordinating movements (the cerebellum), and other areas of the brain. This condition is also associated with the death of neurons in the spinal cord. Over time, the loss of cells in the brain and spinal cord cause the signs and symptoms characteristic of SCA3.",spinocerebellar ataxia type 3,0000940,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-3,C0024408,T047,Disorders
Is spinocerebellar ataxia type 3 inherited ?,0000940-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.  As the altered ATXN3 gene is passed down from one generation to the next, the length of the CAG trinucleotide repeat often increases. A larger number of repeats is usually associated with an earlier onset of signs and symptoms. This phenomenon is called anticipation. Anticipation tends to be more prominent when the ATXN3 gene is inherited from a person's father (paternal inheritance) than when it is inherited from a person's mother (maternal inheritance).  In rare cases, individuals have been reported with expanded CAG repeats on both copies of the ATXN3 gene in each cell. These people have more severe signs and symptoms than people with only one mutation, and features of the condition appear in childhood.",spinocerebellar ataxia type 3,0000940,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-3,C0024408,T047,Disorders
What are the treatments for spinocerebellar ataxia type 3 ?,0000940-5,treatment,These resources address the diagnosis or management of SCA3:  - Gene Review: Gene Review: Spinocerebellar Ataxia Type 3  - Genetic Testing Registry: Azorean disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,spinocerebellar ataxia type 3,0000940,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-3,C0024408,T047,Disorders
What is (are) spinocerebellar ataxia type 36 ?,0000941-1,information,"Spinocerebellar ataxia type 36 (SCA36) is a condition characterized by progressive problems with movement that typically begin in mid-adulthood. People with this condition initially experience problems with coordination and balance (ataxia). Affected individuals often have exaggerated reflexes (hyperreflexia) and problems with speech (dysarthria). They also usually develop muscle twitches (fasciculations) of the tongue and over time, the muscles in the tongue waste away (atrophy). These tongue problems can cause difficulties swallowing liquids. As the condition progresses, individuals with SCA36 develop muscle atrophy in the legs, forearms, and hands. Another common feature of SCA36 is the atrophy of specialized nerve cells that control muscle movement (motor neurons), which can contribute to the tongue and limb muscle atrophy in affected individuals.  Some people with SCA36 have abnormalities of the eye muscles, which can lead to involuntary eye movements (nystagmus), rapid eye movements (saccades), trouble moving the eyes side-to-side (oculomotor apraxia), and droopy eyelids (ptosis). Sensorineural hearing loss, which is hearing loss caused by changes in the inner ear, may also occur in people with SCA36.  Brain imaging of people with SCA36 shows progressive atrophy of various parts of the brain, particularly within the cerebellum, which is the area of the brain involved in coordinating movements. Over time, the loss of cells in the cerebellum causes the movement problems characteristic of SCA36. In older affected individuals, the frontal lobes of the brain may show atrophy resulting in loss of executive function, which is the ability to plan and implement actions and develop problem-solving strategies.  Signs and symptoms of SCA36 typically begin in a person's forties or fifties but can appear anytime during adulthood. People with SCA36 have a normal lifespan and are usually mobile for 15 to 20 years after they are diagnosed.",spinocerebellar ataxia type 36,0000941,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-36,C0087012,T047,Disorders
How many people are affected by spinocerebellar ataxia type 36 ?,0000941-2,frequency,"Approximately 100 individuals with SCA36 have been reported in the scientific literature. Almost all of these individuals have been from two regions: western Japan and the Costa de Morte in Galicia, Spain.",spinocerebellar ataxia type 36,0000941,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-36,C0087012,T047,Disorders
What are the genetic changes related to spinocerebellar ataxia type 36 ?,0000941-3,genetic changes,"SCA36 is caused by mutations in the NOP56 gene. The NOP56 gene provides instructions for making a protein called nucleolar protein 56, which is primarily found in the nucleus of nerve cells (neurons), particularly those in the cerebellum. This protein is one part (subunit) of the ribonucleoprotein complex, which is composed of proteins and molecules of RNA, DNA's chemical cousin. The ribonucleoprotein complex is needed to make cellular structures called ribosomes, which process the cell's genetic instructions to create proteins.  The NOP56 gene mutations that cause SCA36 involve a string of six DNA building blocks (nucleotides) located in an area of the gene known as intron 1. This string of six nucleotides (known as a hexanucleotide) is represented by the letters GGCCTG and normally appears multiple times in a row. In healthy individuals, GGCCTG is repeated 3 to 14 times within the gene. In people with SCA36, GGCCTG is repeated at least 650 times. It is unclear if 15 to 649 repeats of this hexanucleotide cause any signs or symptoms.  To make proteins from the genetic instructions carried in genes, a molecule called messenger RNA (mRNA) is formed. This molecule acts as a genetic blueprint for protein production. However, a large increase in the number of GGCCTG repeats in the NOP56 gene disrupts the normal structure of NOP56 mRNA. Abnormal NOP56 mRNA molecules form clumps called RNA foci within the nucleus of neurons. Other proteins become trapped in the RNA foci, where they cannot function. These proteins may be important for controlling gene activity or protein production.  Additionally, researchers believe that the large expansion of the hexanucleotide repeat in the NOP56 gene may reduce the activity of a nearby gene called MIR1292. The MIR1292 gene provides instructions for making a type of RNA that regulates the activity (expression) of genes that produce proteins called glutamate receptors. These proteins are found on the surface of neurons and allow these cells to communicate with one another. A decrease in the production of Mir1292 RNA can lead to an increase in the production of glutamate receptors. The increased receptor activity may overexcite neurons, which disrupts normal communication between cells and can contribute to ataxia.  The combination of RNA foci and overly excited neurons likely leads to the death of these cells over time. Because the NOP56 gene is especially active in neurons in the cerebellum, these cells are particularly affected by expansion of the gene, leading to cerebellar atrophy. Deterioration in this part of the brain leads to ataxia and the other signs and symptoms of SCA36.",spinocerebellar ataxia type 36,0000941,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-36,C0087012,T047,Disorders
Is spinocerebellar ataxia type 36 inherited ?,0000941-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In most cases, an affected person has one parent with the condition.  In conditions that are caused by repeated segments of DNA, the number of repeats often increases when the altered gene is passed down from one generation to the next. Additionally, a larger number of repeats is usually associated with an earlier onset of signs and symptoms. This phenomenon is called anticipation. Some families affected by SCA36 have demonstrated anticipation while others have not. When anticipation is observed in SCA36, the mutation is most often passed down from the affected father.",spinocerebellar ataxia type 36,0000941,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-36,C0087012,T047,Disorders
What are the treatments for spinocerebellar ataxia type 36 ?,0000941-5,treatment,These resources address the diagnosis or management of spinocerebellar ataxia type 36:  - Ataxia Center at the University of Minnesota: Dominant Spinocerebellar Ataxias  - Baylor College of Medicine: Parkinson's Disease Center and Movement Disorders Clinic: Ataxia  - Gene Review: Gene Review: Spinocerebellar Ataxia Type 36  - Genetic Testing Registry: Spinocerebellar ataxia 36  - Johns Hopkins Medicine: Ataxia  - The Ataxia Center at the University of Chicago: Autosomal Dominant Spinocerebellar Ataxia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,spinocerebellar ataxia type 36,0000941,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-36,C0087012,T047,Disorders
What is (are) spinocerebellar ataxia type 6 ?,0000942-1,information,"Spinocerebellar ataxia type 6 (SCA6) is a condition characterized by progressive problems with movement. People with this condition initially experience problems with coordination and balance (ataxia). Other early signs and symptoms of SCA6 include speech difficulties, involuntary eye movements (nystagmus), and double vision. Over time, individuals with SCA6 may develop loss of coordination in their arms, tremors, and uncontrolled muscle tensing (dystonia).  Signs and symptoms of SCA6 typically begin in a person's forties or fifties but can appear anytime from childhood to late adulthood. Most people with this disorder require wheelchair assistance by the time they are in their sixties.",spinocerebellar ataxia type 6,0000942,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-6,C0752124,T047,Disorders
How many people are affected by spinocerebellar ataxia type 6 ?,0000942-2,frequency,"The worldwide prevalence of SCA6 is estimated to be less than 1 in 100,000 individuals.",spinocerebellar ataxia type 6,0000942,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-6,C0752124,T047,Disorders
What are the genetic changes related to spinocerebellar ataxia type 6 ?,0000942-3,genetic changes,"Mutations in the CACNA1A gene cause SCA6. The CACNA1A gene provides instructions for making a protein that forms a part of some calcium channels. These channels transport positively charged calcium atoms (calcium ions) across cell membranes. The movement of these ions is critical for normal signaling between nerve cells (neurons) in the brain and other parts of the nervous system. The CACNA1A gene provides instructions for making one part (the alpha-1 subunit) of a calcium channel called CaV2.1. CaV2.1 channels play an essential role in communication between neurons in the brain.  The CACNA1A gene mutations that cause SCA6 involve a DNA segment known as a CAG trinucleotide repeat. This segment is made up of a series of three DNA building blocks (cytosine, adenine, and guanine) that appear multiple times in a row. Normally, the CAG segment is repeated 4 to 18 times within the gene. In people with SCA6, the CAG segment is repeated 20 to 33 times. People with 20 repeats tend to experience signs and symptoms of SCA6 beginning in late adulthood, while people with a larger number of repeats usually have signs and symptoms from mid-adulthood.  An increase in the length of the CAG segment leads to the production of an abnormally long version of the alpha-1 subunit. This version of the subunit alters the location and function of the CaV2.1 channels. Normally the alpha-1 subunit is located within the cell membrane; the abnormal subunit is found in the cell membrane as well as in the fluid inside cells (cytoplasm), where it clusters together and forms clumps (aggregates). The effect these aggregates have on cell functioning is unknown. The lack of normal calcium channels in the cell membrane impairs cell communication between neurons in the brain. Diminished cell communication leads to cell death. Cells within the cerebellum, which is the part of the brain that coordinates movement, are particularly sensitive to the accumulation of these aggregates. Over time, a loss of cells in the cerebellum causes the movement problems characteristic of SCA6.",spinocerebellar ataxia type 6,0000942,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-6,C0752124,T047,Disorders
Is spinocerebellar ataxia type 6 inherited ?,0000942-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In most cases, an affected person has one parent with the condition.  As the altered CACNA1A gene is passed down from one generation to the next, the length of the CAG trinucleotide repeat often slightly increases. A larger number of repeats is usually associated with an earlier onset of signs and symptoms. This phenomenon is called anticipation.",spinocerebellar ataxia type 6,0000942,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-6,C0752124,T047,Disorders
What are the treatments for spinocerebellar ataxia type 6 ?,0000942-5,treatment,These resources address the diagnosis or management of SCA6:  - Gene Review: Gene Review: Spinocerebellar Ataxia Type 6  - Genetic Testing Registry: Spinocerebellar ataxia 6   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,spinocerebellar ataxia type 6,0000942,GHR,https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-6,C0752124,T047,Disorders
What is (are) spondylocarpotarsal synostosis syndrome ?,0000943-1,information,"Spondylocarpotarsal synostosis syndrome is a disorder that affects the development of bones throughout the body. Newborns with this disorder are of approximately normal length, but impaired growth of the trunk results in short stature over time. The bones of the spine (vertebrae) are misshapen and abnormally joined together (fused). The vertebral abnormalities may result in an abnormally curved lower back (lordosis) and a spine that curves to the side (scoliosis).  Affected individuals also have abnormalities of the wrist (carpal) and ankle (tarsal) bones and inward- and upward-turning feet (clubfeet). Characteristic facial features include a round face, a large forehead (frontal bossing), and nostrils that open to the front rather than downward (anteverted nares).  Some people with spondylocarpotarsal synostosis syndrome have an opening in the roof of the mouth (a cleft palate), hearing loss, thin tooth enamel, flat feet, or an unusually large range of joint movement (hypermobility). Individuals with this disorder can survive into adulthood. Intelligence is generally unaffected, although mild developmental delay has been reported in some affected individuals.",spondylocarpotarsal synostosis syndrome,0000943,GHR,https://ghr.nlm.nih.gov/condition/spondylocarpotarsal-synostosis-syndrome,C1368355,T019,Disorders
How many people are affected by spondylocarpotarsal synostosis syndrome ?,0000943-2,frequency,Spondylocarpotarsal synostosis syndrome is a rare disorder; its prevalence is unknown. At least 25 affected individuals have been identified.,spondylocarpotarsal synostosis syndrome,0000943,GHR,https://ghr.nlm.nih.gov/condition/spondylocarpotarsal-synostosis-syndrome,C1368355,T019,Disorders
What are the genetic changes related to spondylocarpotarsal synostosis syndrome ?,0000943-3,genetic changes,"Mutations in the FLNB gene cause spondylocarpotarsal synostosis syndrome. The FLNB gene provides instructions for making a protein called filamin B. This protein helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. Filamin B attaches (binds) to another protein called actin and helps the actin to form the branching network of filaments that makes up the cytoskeleton. It also links actin to many other proteins to perform various functions within the cell, including the cell signaling that helps determine how the cytoskeleton will change as tissues grow and take shape during development.  Filamin B is especially important in the development of the skeleton before birth. It is active (expressed) in the cell membranes of cartilage-forming cells (chondrocytes). Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone (a process called ossification), except for the cartilage that continues to cover and protect the ends of bones and is present in the nose, airways (trachea and bronchi), and external ears. Filamin B appears to be important for normal cell growth and division (proliferation) and maturation (differentiation) of chondrocytes and for the ossification of cartilage.  FLNB gene mutations that cause spondylocarpotarsal synostosis syndrome result in the production of an abnormally short filamin B protein that is unstable and breaks down rapidly. Loss of the filamin B protein appears to result in out-of-place (ectopic) ossification, resulting in fusion of the bones in the spine, wrists, and ankles and other signs and symptoms of spondylocarpotarsal synostosis syndrome.  A few individuals who have been diagnosed with spondylocarpotarsal synostosis syndrome do not have mutations in the FLNB gene. In these cases, the genetic cause of the disorder is unknown.",spondylocarpotarsal synostosis syndrome,0000943,GHR,https://ghr.nlm.nih.gov/condition/spondylocarpotarsal-synostosis-syndrome,C1368355,T019,Disorders
Is spondylocarpotarsal synostosis syndrome inherited ?,0000943-4,inheritance,"Spondylocarpotarsal synostosis syndrome caused by FLNB gene mutations is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  In a few individuals with signs and symptoms similar to those of spondylocarpotarsal synostosis syndrome but without FLNB gene mutations, the condition appears to have been inherited in an autosomal dominant pattern. Autosomal dominant means one copy of the altered gene in each cell is sufficient to cause the disorder.",spondylocarpotarsal synostosis syndrome,0000943,GHR,https://ghr.nlm.nih.gov/condition/spondylocarpotarsal-synostosis-syndrome,C1368355,T019,Disorders
What are the treatments for spondylocarpotarsal synostosis syndrome ?,0000943-5,treatment,These resources address the diagnosis or management of spondylocarpotarsal synostosis syndrome:  - Gene Review: Gene Review: FLNB-Related Disorders  - Genetic Testing Registry: Spondylocarpotarsal synostosis syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,spondylocarpotarsal synostosis syndrome,0000943,GHR,https://ghr.nlm.nih.gov/condition/spondylocarpotarsal-synostosis-syndrome,C1368355,T019,Disorders
What is (are) spondylocostal dysostosis ?,0000944-1,information,"Spondylocostal dysostosis is a group of conditions characterized by abnormal development of bones in the spine and ribs. The bones of the spine (vertebrae) are misshapen and abnormally joined together (fused). Many people with this condition have abnormal side-to-side curvature of the spine (scoliosis) due to malformation of the vertebrae. In addition to spine abnormalities, some of the rib bones may be fused together or missing. Affected individuals have short, rigid necks and short midsections because of the bone malformations. As a result, people with spondylocostal dysostosis have short bodies but normal length arms and legs, called short-trunk dwarfism.  The spine and rib abnormalities cause other signs and symptoms of spondylocostal dysostosis. Infants with this condition are born with small chests that cannot expand adequately, often leading to life-threatening breathing problems. As the lungs expand in the narrow chest, the muscle that separates the abdomen from the chest cavity (the diaphragm) is forced down and the abdomen is pushed out. The increased pressure in the abdomen can cause a soft out-pouching around the lower abdomen (inguinal hernia), particularly in males with spondylocostal dysostosis.  There are several types of spondylocostal dysostosis, designated types 1 through 4 and the autosomal dominant (AD) type. These types have similar features and are distinguished by their genetic cause and inheritance pattern. Spondylocostal dysostosis has often been grouped with a similar condition called spondylothoracic dysostosis, and both are called Jarcho-Levin syndrome; however, they are now considered distinct conditions.",spondylocostal dysostosis,0000944,GHR,https://ghr.nlm.nih.gov/condition/spondylocostal-dysostosis,C0265343,T047,Disorders
How many people are affected by spondylocostal dysostosis ?,0000944-2,frequency,"Spondylocostal dysostosis is a rare condition, although its exact prevalence is unknown.",spondylocostal dysostosis,0000944,GHR,https://ghr.nlm.nih.gov/condition/spondylocostal-dysostosis,C0265343,T047,Disorders
What are the genetic changes related to spondylocostal dysostosis ?,0000944-3,genetic changes,"Mutations in at least four genes are known to cause spondylocostal dysostosis: Mutations in the DLL3 gene cause spondylocostal dysostosis type 1; mutations in the MESP2 gene cause spondylocostal dysostosis type 2; mutations in the LFNG gene cause spondylocostal dysostosis type 3; and mutations in the HES7 gene cause spondylocostal dysostosis type 4. The genetic cause of AD spondylocostal dysostosis is unknown.  The DLL3, MESP2, LFNG, and HES7 genes play a role in the Notch signaling pathway, an important pathway in embryonic development. One of the functions of the Notch pathway is separating future vertebrae from one another during early development, a process called somite segmentation. When this pathway is disrupted, somite segmentation does not occur properly, resulting in the malformation and fusion of the bones of the spine and ribs seen in spondylocostal dysostosis.  Mutations in the four identified genes account for approximately 25 percent of diagnosed spondylocostal dysostosis. Researchers suggest that additional genes in the Notch signaling pathway might also be involved.",spondylocostal dysostosis,0000944,GHR,https://ghr.nlm.nih.gov/condition/spondylocostal-dysostosis,C0265343,T047,Disorders
Is spondylocostal dysostosis inherited ?,0000944-4,inheritance,"Spondylocostal dysostosis can have different inheritance patterns. Types 1, 2, 3, and 4 are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. AD spondylocostal dysostosis is inherited in an autosomal dominant pattern. Autosomal dominant inheritance means that one copy of an altered gene in each cell is sufficient to cause the disorder, although in these cases no causative genes have been identified. The signs and symptoms of spondylocostal dysostosis are typically more severe with autosomal recessive inheritance.",spondylocostal dysostosis,0000944,GHR,https://ghr.nlm.nih.gov/condition/spondylocostal-dysostosis,C0265343,T047,Disorders
What are the treatments for spondylocostal dysostosis ?,0000944-5,treatment,"These resources address the diagnosis or management of spondylocostal dysostosis:  - Gene Review: Gene Review: Spondylocostal Dysostosis, Autosomal Recessive  - Genetic Testing Registry: Jarcho-Levin syndrome  - Genetic Testing Registry: Spondylocostal dysostosis 1  - Genetic Testing Registry: Spondylocostal dysostosis 2  - Genetic Testing Registry: Spondylocostal dysostosis 3  - Genetic Testing Registry: Spondylocostal dysostosis 4, autosomal recessive  - KidsHealth: X-Ray Exam (Scoliosis)  - MedlinePlus Encyclopedia: Scoliosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",spondylocostal dysostosis,0000944,GHR,https://ghr.nlm.nih.gov/condition/spondylocostal-dysostosis,C0265343,T047,Disorders
What is (are) spondyloenchondrodysplasia with immune dysregulation ?,0000945-1,information,"Spondyloenchondrodysplasia with immune dysregulation (SPENCDI) is an inherited condition that primarily affects bone growth and immune system function. The signs and symptoms of SPENCDI can become apparent anytime from infancy to adolescence.  Bone abnormalities in individuals with SPENCDI include flattened spinal bones (platyspondyly), abnormalities at the ends of long bones in the limbs (metaphyseal dysplasia), and areas of damage (lesions) on the long bones and spinal bones that can be seen on x-rays. Additional skeletal problems occur because of abnormalities of the tough, flexible tissue called cartilage that makes up much of the skeleton during early development. Individuals with SPENCDI often have areas where cartilage did not convert to bone. They may also have noncancerous growths of cartilage (enchondromas). The bone and cartilage problems contribute to short stature in people with SPENCDI.  Individuals with SPENCDI have a combination of immune system problems. Many affected individuals have malfunctioning immune systems that attack the body's own tissues and organs, which is known as an autoimmune reaction. The malfunctioning immune system can lead to a variety of disorders, such as a decrease in blood cells called platelets (thrombocytopenia), premature destruction of red blood cells (hemolytic anemia), an underactive thyroid gland (hypothyroidism), or chronic inflammatory disorders such as systemic lupus erythematosus or rheumatoid arthritis. In addition, affected individuals often have abnormal immune cells that cannot grow and divide in response to harmful invaders such as bacteria and viruses. As a result of this immune deficiency, these individuals have frequent fevers and recurrent respiratory infections.  Some people with SPENCDI have neurological problems such as abnormal muscle stiffness (spasticity), difficulty with coordinating movements (ataxia), and intellectual disability. They may also have abnormal deposits of calcium (calcification) in the brain.  Due to the range of immune system problems, people with SPENCDI typically have a shortened life expectancy, but figures vary widely.",spondyloenchondrodysplasia with immune dysregulation,0000945,GHR,https://ghr.nlm.nih.gov/condition/spondyloenchondrodysplasia-with-immune-dysregulation,C1842763,T047,Disorders
How many people are affected by spondyloenchondrodysplasia with immune dysregulation ?,0000945-2,frequency,"SPENCDI appears to be a rare condition, although its prevalence is unknown.",spondyloenchondrodysplasia with immune dysregulation,0000945,GHR,https://ghr.nlm.nih.gov/condition/spondyloenchondrodysplasia-with-immune-dysregulation,C1842763,T047,Disorders
What are the genetic changes related to spondyloenchondrodysplasia with immune dysregulation ?,0000945-3,genetic changes,"Mutations in the ACP5 gene cause SPENCDI. This gene provides instructions for making an enzyme called tartrate-resistant acid phosphatase type 5 (TRAP). The TRAP enzyme primarily regulates the activity of a protein called osteopontin, which is produced in bone cells called osteoclasts and in immune cells. Osteopontin performs a variety of functions in these cells.  Osteoclasts are specialized cells that break down and remove (resorb) bone tissue that is no longer needed. These cells are involved in bone remodeling, which is a normal process that replaces old bone tissue with new bone. During bone remodeling, osteopontin is turned on (activated), allowing osteoclasts to attach (bind) to bones. When the breakdown of bone is complete, TRAP turns off (inactivates) osteopontin, causing the osteoclasts to release themselves from bone.  In immune system cells, osteopontin helps fight infection by promoting inflammation, regulating immune cell activity, and turning on various immune system cells that are necessary to fight off foreign invaders. As in bone cells, the TRAP enzyme inactivates osteopontin in immune cells when it is no longer needed.  The ACP5 gene mutations that cause SPENCDI impair or eliminate TRAP's ability to inactivate osteopontin. As a result, osteopontin is abnormally active, prolonging bone breakdown by osteoclasts and triggering abnormal inflammation and immune responses by immune cells. In people with SPENCDI, increased bone remodeling contributes to the skeletal abnormalities, including irregularly shaped bones and short stature. An overactive immune system leads to increased susceptibility to autoimmune disorders and impairs the body's normal immune response to harmful invaders, resulting in frequent infections. The mechanism that leads to the other features of SPENCDI, including movement disorders and intellectual disability, is currently unknown.",spondyloenchondrodysplasia with immune dysregulation,0000945,GHR,https://ghr.nlm.nih.gov/condition/spondyloenchondrodysplasia-with-immune-dysregulation,C1842763,T047,Disorders
Is spondyloenchondrodysplasia with immune dysregulation inherited ?,0000945-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",spondyloenchondrodysplasia with immune dysregulation,0000945,GHR,https://ghr.nlm.nih.gov/condition/spondyloenchondrodysplasia-with-immune-dysregulation,C1842763,T047,Disorders
What are the treatments for spondyloenchondrodysplasia with immune dysregulation ?,0000945-5,treatment,These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,spondyloenchondrodysplasia with immune dysregulation,0000945,GHR,https://ghr.nlm.nih.gov/condition/spondyloenchondrodysplasia-with-immune-dysregulation,C1842763,T047,Disorders
"What is (are) spondyloepimetaphyseal dysplasia, Strudwick type ?",0000946-1,information,"Spondyloepimetaphyseal dysplasia, Strudwick type is an inherited disorder of bone growth that results in short stature (dwarfism), skeletal abnormalities, and problems with vision. This condition affects the bones of the spine (spondylo-) and two regions (epiphyses and metaphyses) near the ends of long bones in the arms and legs. The Strudwick type was named after the first reported patient with the disorder.  People with this condition have short stature from birth, with a very short trunk and shortened limbs. Their hands and feet, however, are usually average-sized. Affected individuals may have an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). This abnormal spinal curvature may be severe and can cause problems with breathing. Instability of the spinal bones (vertebrae) in the neck may increase the risk of spinal cord damage. Other skeletal features include flattened vertebrae (platyspondyly), severe protrusion of the breastbone (pectus carinatum), an abnormality of the hip joint that causes the upper leg bones to turn inward (coxa vara), and an inward- and upward-turning foot (clubfoot). Arthritis may develop early in life.  People with spondyloepimetaphyseal dysplasia, Strudwick type have mild changes in their facial features. Some infants are born with an opening in the roof of the mouth (a cleft palate) and their cheekbones may appear flattened. Eye problems that can impair vision are common, such as severe nearsightedness (high myopia) and tearing of the lining of the eye (retinal detachment).","spondyloepimetaphyseal dysplasia, Strudwick type",0000946,GHR,https://ghr.nlm.nih.gov/condition/spondyloepimetaphyseal-dysplasia-strudwick-type,C0700635,T046,Disorders
"How many people are affected by spondyloepimetaphyseal dysplasia, Strudwick type ?",0000946-2,frequency,This condition is rare; only a few affected individuals have been reported worldwide.,"spondyloepimetaphyseal dysplasia, Strudwick type",0000946,GHR,https://ghr.nlm.nih.gov/condition/spondyloepimetaphyseal-dysplasia-strudwick-type,C0700635,T046,Disorders
"What are the genetic changes related to spondyloepimetaphyseal dysplasia, Strudwick type ?",0000946-3,genetic changes,"Spondyloepimetaphyseal dysplasia, Strudwick type is one of a spectrum of skeletal disorders caused by mutations in the COL2A1 gene. This gene provides instructions for making a protein that forms type II collagen. This type of collagen is found mostly in the clear gel that fills the eyeball (the vitreous) and cartilage. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Type II collagen is essential for the normal development of bones and other connective tissues that form the body's supportive framework.  Most mutations in the COL2A1 gene that cause spondyloepimetaphyseal dysplasia, Strudwick type interfere with the assembly of type II collagen molecules. Abnormal collagen prevents bones and other connective tissues from developing properly, which leads to the signs and symptoms of spondyloepimetaphyseal dysplasia, Strudwick type.","spondyloepimetaphyseal dysplasia, Strudwick type",0000946,GHR,https://ghr.nlm.nih.gov/condition/spondyloepimetaphyseal-dysplasia-strudwick-type,C0700635,T046,Disorders
"Is spondyloepimetaphyseal dysplasia, Strudwick type inherited ?",0000946-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.","spondyloepimetaphyseal dysplasia, Strudwick type",0000946,GHR,https://ghr.nlm.nih.gov/condition/spondyloepimetaphyseal-dysplasia-strudwick-type,C0700635,T046,Disorders
"What are the treatments for spondyloepimetaphyseal dysplasia, Strudwick type ?",0000946-5,treatment,"These resources address the diagnosis or management of spondyloepimetaphyseal dysplasia, Strudwick type:  - Genetic Testing Registry: Spondyloepimetaphyseal dysplasia Strudwick type  - MedlinePlus Encyclopedia: Clubfoot  - MedlinePlus Encyclopedia: Retinal Detachment  - MedlinePlus Encyclopedia: Scoliosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","spondyloepimetaphyseal dysplasia, Strudwick type",0000946,GHR,https://ghr.nlm.nih.gov/condition/spondyloepimetaphyseal-dysplasia-strudwick-type,C0700635,T046,Disorders
What is (are) spondyloepiphyseal dysplasia congenita ?,0000947-1,information,"Spondyloepiphyseal dysplasia congenita is an inherited bone growth disorder that results in short stature (dwarfism), skeletal abnormalities, and problems with vision and hearing. This condition affects the bones of the spine (spondylo-) and the ends (epiphyses) of long bones in the arms and legs. Congenita indicates that the condition is present from birth.  People with spondyloepiphyseal dysplasia congenita have short stature from birth, with a very short trunk and neck and shortened limbs. Their hands and feet, however, are usually average-sized. Adult height ranges from 3 feet to just over 4 feet. Abnormal curvature of the spine (kyphoscoliosis and lordosis) becomes more severe during childhood. Instability of the spinal bones (vertebrae) in the neck may increase the risk of spinal cord damage. Other skeletal features include flattened vertebrae (platyspondyly); an abnormality of the hip joint that causes the upper leg bones to turn inward (coxa vara); a foot deformity called a clubfoot; and a broad, barrel-shaped chest. Abnormal development of the chest can cause problems with breathing. Arthritis and decreased joint mobility often develop early in life.  People with spondyloepiphyseal dysplasia congenita have mild changes in their facial features. The cheekbones close to the nose may appear flattened. Some infants are born with an opening in the roof of the mouth (a cleft palate). Severe nearsightedness (high myopia) is common, as are other eye problems that can impair vision. About one quarter of people with this condition have hearing loss.",spondyloepiphyseal dysplasia congenita,0000947,GHR,https://ghr.nlm.nih.gov/condition/spondyloepiphyseal-dysplasia-congenita,C0334044,T019,Disorders
How many people are affected by spondyloepiphyseal dysplasia congenita ?,0000947-2,frequency,This condition is rare; the exact incidence is unknown. More than 175 cases have been reported in the scientific literature.,spondyloepiphyseal dysplasia congenita,0000947,GHR,https://ghr.nlm.nih.gov/condition/spondyloepiphyseal-dysplasia-congenita,C0334044,T019,Disorders
What are the genetic changes related to spondyloepiphyseal dysplasia congenita ?,0000947-3,genetic changes,"Spondyloepiphyseal dysplasia congenita is one of a spectrum of skeletal disorders caused by mutations in the COL2A1 gene. This gene provides instructions for making a protein that forms type II collagen. This type of collagen is found mostly in cartilage and in the clear gel that fills the eyeball (the vitreous). The COL2A1 gene is essential for the normal development of bones and other tissues that form the body's supportive framework (connective tissues). Mutations in the COL2A1 gene interfere with the assembly of type II collagen molecules, which prevents bones and other connective tissues from developing properly.",spondyloepiphyseal dysplasia congenita,0000947,GHR,https://ghr.nlm.nih.gov/condition/spondyloepiphyseal-dysplasia-congenita,C0334044,T019,Disorders
Is spondyloepiphyseal dysplasia congenita inherited ?,0000947-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",spondyloepiphyseal dysplasia congenita,0000947,GHR,https://ghr.nlm.nih.gov/condition/spondyloepiphyseal-dysplasia-congenita,C0334044,T019,Disorders
What are the treatments for spondyloepiphyseal dysplasia congenita ?,0000947-5,treatment,These resources address the diagnosis or management of spondyloepiphyseal dysplasia congenita:  - Genetic Testing Registry: Spondyloepiphyseal dysplasia congenita  - MedlinePlus Encyclopedia: Clubfoot  - MedlinePlus Encyclopedia: Lordosis  - MedlinePlus Encyclopedia: Retinal Detachment  - MedlinePlus Encyclopedia: Scoliosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,spondyloepiphyseal dysplasia congenita,0000947,GHR,https://ghr.nlm.nih.gov/condition/spondyloepiphyseal-dysplasia-congenita,C0334044,T019,Disorders
What is (are) spondyloperipheral dysplasia ?,0000948-1,information,"Spondyloperipheral dysplasia is a disorder that impairs bone growth. This condition is characterized by flattened bones of the spine (platyspondyly) and unusually short fingers and toes (brachydactyly), with the exception of the first (big) toes. Other skeletal abnormalities associated with spondyloperipheral dysplasia include short stature, shortened long bones of the arms and legs, exaggerated curvature of the lower back (lordosis), and an inward- and upward-turning foot (clubfoot). Additionally, some affected individuals have nearsightedness (myopia), hearing loss, and intellectual disability.",spondyloperipheral dysplasia,0000948,GHR,https://ghr.nlm.nih.gov/condition/spondyloperipheral-dysplasia,C0796173,T019,Disorders
How many people are affected by spondyloperipheral dysplasia ?,0000948-2,frequency,This condition is rare; only a few affected individuals have been reported worldwide.,spondyloperipheral dysplasia,0000948,GHR,https://ghr.nlm.nih.gov/condition/spondyloperipheral-dysplasia,C0796173,T019,Disorders
What are the genetic changes related to spondyloperipheral dysplasia ?,0000948-3,genetic changes,"Spondyloperipheral dysplasia is one of a spectrum of skeletal disorders caused by mutations in the COL2A1 gene. This gene provides instructions for making a protein that forms type II collagen. This type of collagen is found mostly in the clear gel that fills the eyeball (the vitreous) and in cartilage. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Type II collagen is essential for the normal development of bones and other connective tissues that form the body's supportive framework.  Mutations in the COL2A1 gene interfere with the assembly of type II collagen molecules, reducing the amount of this type of collagen in the body. Instead of forming collagen molecules, the abnormal COL2A1 protein builds up in cartilage cells (chondrocytes). These changes disrupt the normal development of bones and other connective tissues, leading to the signs and symptoms of spondyloperipheral dysplasia.",spondyloperipheral dysplasia,0000948,GHR,https://ghr.nlm.nih.gov/condition/spondyloperipheral-dysplasia,C0796173,T019,Disorders
Is spondyloperipheral dysplasia inherited ?,0000948-4,inheritance,"This condition is probably inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",spondyloperipheral dysplasia,0000948,GHR,https://ghr.nlm.nih.gov/condition/spondyloperipheral-dysplasia,C0796173,T019,Disorders
What are the treatments for spondyloperipheral dysplasia ?,0000948-5,treatment,These resources address the diagnosis or management of spondyloperipheral dysplasia:  - Genetic Testing Registry: Spondyloperipheral dysplasia  - MedlinePlus Encyclopedia: Nearsightedness   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,spondyloperipheral dysplasia,0000948,GHR,https://ghr.nlm.nih.gov/condition/spondyloperipheral-dysplasia,C0796173,T019,Disorders
What is (are) spondylothoracic dysostosis ?,0000949-1,information,"Spondylothoracic dysostosis is a condition characterized by the malformation of the bones of the spine and ribs. The bones of the spine (vertebrae) do not develop properly, which causes them to be misshapen and abnormally joined together (fused). The ribs are also fused at the part nearest the spine (posteriorly), which gives the rib cage its characteristic fan-like or ""crab"" appearance in x-rays. Affected individuals have short, rigid necks and short midsections because of the bone malformations. As a result, people with spondylothoracic dysostosis have short bodies but normal length arms and legs, called short-trunk dwarfism.  The spine and rib abnormalities cause other signs and symptoms of spondylothoracic dysostosis. Infants with this condition are born with a small chest that cannot expand adequately, often leading to life-threatening breathing problems. As the lungs expand, the narrow chest forces the muscle that separates the abdomen from the chest cavity (the diaphragm) down and the abdomen is pushed out. The increased pressure in the abdomen can cause a soft out-pouching around the lower abdomen (inguinal hernia) or belly-button (umbilical hernia).  Spondylothoracic dysostosis is sometimes called spondylocostal dysostosis, a similar condition with abnormalities of the spine and ribs. The two conditions have been grouped in the past, and both are referred to as Jarcho-Levin syndrome; however, they are now considered distinct conditions.",spondylothoracic dysostosis,0000949,GHR,https://ghr.nlm.nih.gov/condition/spondylothoracic-dysostosis,C0265343,T047,Disorders
How many people are affected by spondylothoracic dysostosis ?,0000949-2,frequency,"Spondylothoracic dysostosis affects about one in 200,000 people worldwide. However, it is much more common in people of Puerto Rican ancestry, affecting approximately one in 12,000 people.",spondylothoracic dysostosis,0000949,GHR,https://ghr.nlm.nih.gov/condition/spondylothoracic-dysostosis,C0265343,T047,Disorders
What are the genetic changes related to spondylothoracic dysostosis ?,0000949-3,genetic changes,"The MESP2 gene provides instructions for a protein that plays a critical role in the development of vertebrae. Specifically, it is involved in separating vertebrae from one another during early development, a process called somite segmentation. Mutations in the MESP2 gene prevent the production of any protein or lead to the production of an abnormally short, nonfunctional protein. When the MESP2 protein is nonfunctional or absent, somite segmentation does not occur properly, which results in the malformation and fusion of the bones of the spine and ribs seen in spondylothoracic dysostosis.",spondylothoracic dysostosis,0000949,GHR,https://ghr.nlm.nih.gov/condition/spondylothoracic-dysostosis,C0265343,T047,Disorders
Is spondylothoracic dysostosis inherited ?,0000949-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",spondylothoracic dysostosis,0000949,GHR,https://ghr.nlm.nih.gov/condition/spondylothoracic-dysostosis,C0265343,T047,Disorders
What are the treatments for spondylothoracic dysostosis ?,0000949-5,treatment,"These resources address the diagnosis or management of spondylothoracic dysostosis:  - Cleveland Clinic: Spine X-ray  - Gene Review: Gene Review: Spondylocostal Dysostosis, Autosomal Recessive   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",spondylothoracic dysostosis,0000949,GHR,https://ghr.nlm.nih.gov/condition/spondylothoracic-dysostosis,C0265343,T047,Disorders
What is (are) sporadic hemiplegic migraine ?,0000950-1,information,"Sporadic hemiplegic migraine is a rare form of migraine headache. Migraines typically cause intense, throbbing pain in one area of the head. Some people with migraines also experience nausea, vomiting, and sensitivity to light and sound. These recurrent headaches typically begin in childhood or adolescence and can be triggered by certain foods, emotional stress, and minor head trauma. Each headache may last from a few hours to a few days.  In sporadic hemiplegic migraine and some other types of migraine, a pattern of neurological symptoms called an aura occurs before onset of the headache. An aura commonly includes temporary visual changes such as blind spots (scotomas), flashing lights, zig-zagging lines, and double vision. In people with sporadic hemiplegic migraine, auras are also characterized by temporary numbness or weakness, often affecting one side of the body (hemiparesis). Additional features of an aura can include difficulty with speech, confusion, and drowsiness. An aura typically develops gradually over a few minutes and lasts about an hour.  Some people with sporadic hemiplegic migraine experience unusually severe migraine episodes. These episodes can include fever, prolonged weakness, seizures, and coma. Although most people with sporadic hemiplegic migraine recover completely between episodes, neurological symptoms such as memory loss and problems with attention can last for weeks or months. Some affected individuals develop mild but permanent difficulty coordinating movements (ataxia), which may worsen with time, and rapid, involuntary eye movements called nystagmus. Mild to severe intellectual disability has been reported in some people with sporadic hemiplegic migraine.",sporadic hemiplegic migraine,0000950,GHR,https://ghr.nlm.nih.gov/condition/sporadic-hemiplegic-migraine,C2367445,T047,Disorders
How many people are affected by sporadic hemiplegic migraine ?,0000950-2,frequency,"The worldwide prevalence of sporadic hemiplegic migraine is unknown. Studies suggest that in Denmark about 1 in 10,000 people have hemiplegic migraine and that the condition occurs equally in families with multiple affected individuals (familial hemiplegic migraine) and in individuals with no family history of the condition (sporadic hemiplegic migraine).",sporadic hemiplegic migraine,0000950,GHR,https://ghr.nlm.nih.gov/condition/sporadic-hemiplegic-migraine,C2367445,T047,Disorders
What are the genetic changes related to sporadic hemiplegic migraine ?,0000950-3,genetic changes,"Mutations in the ATP1A2 and CACNA1A genes have been found to cause sporadic hemiplegic migraine. The proteins produced from these genes transport charged atoms (ions) across cell membranes. The movement of these ions is critical for normal signaling between nerve cells (neurons) in the brain and other parts of the nervous system. Signaling between neurons relies on chemicals called neurotransmitters, which are released from one neuron and taken up by neighboring neurons. Mutations in the ATP1A2 and CACNA1A genes disrupt the transport of ions in neurons, which is thought to impair the normal release and uptake of certain neurotransmitters in the brain. The resulting abnormal signaling may lead to the severe headaches and auras characteristic of sporadic hemiplegic migraine.  Many people with sporadic hemiplegic migraine do not have a mutation in one of the known genes. Researchers believe that mutations in other genes are also involved in the condition, although these genes have not been identified.  There is little evidence that mutations in the CACNA1A and ATP1A2 genes play a role in common migraines, which affect millions of people each year. Researchers are searching for additional genetic changes that may underlie rare types of migraine, such as sporadic hemiplegic migraine, as well as the more common forms of migraine.",sporadic hemiplegic migraine,0000950,GHR,https://ghr.nlm.nih.gov/condition/sporadic-hemiplegic-migraine,C2367445,T047,Disorders
Is sporadic hemiplegic migraine inherited ?,0000950-4,inheritance,"Sporadic means that the condition occurs in individuals with no history of the disorder in their family. While most cases result from new (de novo) mutations that likely occur during early embryonic development, some affected individuals inherit the genetic change that causes the condition from an unaffected parent. (When some people with the mutation have no signs and symptoms of the disorder, the condition is said to have reduced penetrance.) Although family members of an affected individual do not have sporadic hemiplegic migraine, some experience migraine headaches without hemiparesis. A related condition, familial hemiplegic migraine, has signs and symptoms identical to those in sporadic hemiplegic migraine but occurs in multiple members of a family.",sporadic hemiplegic migraine,0000950,GHR,https://ghr.nlm.nih.gov/condition/sporadic-hemiplegic-migraine,C2367445,T047,Disorders
What are the treatments for sporadic hemiplegic migraine ?,0000950-5,treatment,"These resources address the diagnosis or management of sporadic hemiplegic migraine:  - Genetic Testing Registry: Migraine, sporadic hemiplegic  - Journal of the American Medical Association Patient Page: Migraine Headache   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",sporadic hemiplegic migraine,0000950,GHR,https://ghr.nlm.nih.gov/condition/sporadic-hemiplegic-migraine,C2367445,T047,Disorders
What is (are) Stargardt macular degeneration ?,0000951-1,information,"Stargardt macular degeneration is a genetic eye disorder that causes progressive vision loss. This disorder affects the retina, the specialized light-sensitive tissue that lines the back of the eye. Specifically, Stargardt macular degeneration affects a small area near the center of the retina called the macula. The macula is responsible for sharp central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. In most people with Stargardt macular degeneration, a fatty yellow pigment (lipofuscin) builds up in cells underlying the macula. Over time, the abnormal accumulation of this substance can damage cells that are critical for clear central vision. In addition to central vision loss, people with Stargardt macular degeneration have problems with night vision that can make it difficult to navigate in low light. Some affected individuals also have impaired color vision. The signs and symptoms of Stargardt macular degeneration typically appear in late childhood to early adulthood and worsen over time.",Stargardt macular degeneration,0000951,GHR,https://ghr.nlm.nih.gov/condition/stargardt-macular-degeneration,C0271093,T033,Disorders
How many people are affected by Stargardt macular degeneration ?,0000951-2,frequency,"Stargardt macular degeneration is the most common form of juvenile macular degeneration, the signs and symptoms of which begin in childhood. The estimated prevalence of Stargardt macular degeneration is 1 in 8,000 to 10,000 individuals.",Stargardt macular degeneration,0000951,GHR,https://ghr.nlm.nih.gov/condition/stargardt-macular-degeneration,C0271093,T033,Disorders
What are the genetic changes related to Stargardt macular degeneration ?,0000951-3,genetic changes,"In most cases, Stargardt macular degeneration is caused by mutations in the ABCA4 gene. Less often, mutations in the ELOVL4 gene cause this condition. The ABCA4 and ELOVL4 genes provide instructions for making proteins that are found in light-sensing (photoreceptor) cells in the retina.  The ABCA4 protein transports potentially toxic substances out of photoreceptor cells. These substances form after phototransduction, the process by which light entering the eye is converted into electrical signals that are transmitted to the brain. Mutations in the ABCA4 gene prevent the ABCA4 protein from removing toxic byproducts from photoreceptor cells. These toxic substances build up and form lipofuscin in the photoreceptor cells and the surrounding cells of the retina, eventually causing cell death. Loss of cells in the retina causes the progressive vision loss characteristic of Stargardt macular degeneration.  The ELOVL4 protein plays a role in making a group of fats called very long-chain fatty acids. The ELOVL4 protein is primarily active (expressed) in the retina, but is also expressed in the brain and skin. The function of very long-chain fatty acids within the retina is unknown. Mutations in the ELOVL4 gene lead to the formation of ELOVL4 protein clumps (aggregates) that build up and may interfere with retinal cell functions, ultimately leading to cell death.",Stargardt macular degeneration,0000951,GHR,https://ghr.nlm.nih.gov/condition/stargardt-macular-degeneration,C0271093,T033,Disorders
Is Stargardt macular degeneration inherited ?,0000951-4,inheritance,"Stargardt macular degeneration can have different inheritance patterns.  When mutations in the ABCA4 gene cause this condition, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  When this condition is caused by mutations in the ELOVL4 gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Stargardt macular degeneration,0000951,GHR,https://ghr.nlm.nih.gov/condition/stargardt-macular-degeneration,C0271093,T033,Disorders
What are the treatments for Stargardt macular degeneration ?,0000951-5,treatment,These resources address the diagnosis or management of Stargardt macular degeneration:  - Genetic Testing Registry: Stargardt Disease 3  - Genetic Testing Registry: Stargardt disease 1  - Genetic Testing Registry: Stargardt disease 4   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Stargardt macular degeneration,0000951,GHR,https://ghr.nlm.nih.gov/condition/stargardt-macular-degeneration,C0271093,T033,Disorders
What is (are) steatocystoma multiplex ?,0000952-1,information,"Steatocystoma multiplex is a skin disorder characterized by the development of multiple noncancerous (benign) cysts known as steatocystomas. These growths begin in the skin's sebaceous glands, which normally produce an oily substance called sebum that lubricates the skin and hair. Steatocystomas are filled with sebum.  In affected individuals, steatocystomas typically first appear during adolescence and are found most often on the torso, neck, upper arms, and upper legs. In most people with steatocystoma multiplex, these cysts are the only sign of the condition. However, some affected individuals also have mild abnormalities involving the teeth or the fingernails and toenails.",steatocystoma multiplex,0000952,GHR,https://ghr.nlm.nih.gov/condition/steatocystoma-multiplex,C0259771,T191,Disorders
How many people are affected by steatocystoma multiplex ?,0000952-2,frequency,"Although the prevalence of steatocystoma multiplex is unknown, it appears to be rare.",steatocystoma multiplex,0000952,GHR,https://ghr.nlm.nih.gov/condition/steatocystoma-multiplex,C0259771,T191,Disorders
What are the genetic changes related to steatocystoma multiplex ?,0000952-3,genetic changes,"Steatocystoma multiplex can be caused by mutations in the KRT17 gene. This gene provides instructions for making a protein called keratin 17, which is produced in the nails, the hair follicles, and the skin on the palms of the hands and soles of the feet. It is also found in the skin's sebaceous glands. Keratin 17 partners with a similar protein called keratin 6b to form networks that provide strength and resilience to the skin, nails, and other tissues.  The KRT17 gene mutations that cause steatocystoma multiplex alter the structure of keratin 17, preventing it from forming strong, stable networks within cells. The defective keratin network disrupts the growth and function of cells in the skin and nails, including cells that make up the sebaceous glands. These abnormalities lead to the growth of sebum-containing cysts in people with steatocystoma multiplex. However, it is unclear why steatocystomas are typically the only feature of this disorder.  Many researchers believe that steatocystoma multiplex is a variant form of a disorder called pachyonychia congenita, which can also result from mutations in the KRT17 gene. Like steatocystoma multiplex, pachyonychia congenita involves the growth of steatocystomas. Pachyonychia congenita is also associated with more severe skin and nail abnormalities not usually found in people with steatocystoma multiplex.  In some cases, people with steatocystoma multiplex do not have an identified mutation in the KRT17 gene. The cause of the condition in these individuals is unknown.",steatocystoma multiplex,0000952,GHR,https://ghr.nlm.nih.gov/condition/steatocystoma-multiplex,C0259771,T191,Disorders
Is steatocystoma multiplex inherited ?,0000952-4,inheritance,"When steatocystoma multiplex is caused by mutations in the KRT17 gene, it is inherited in an autosomal dominant pattern. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the condition from an affected parent.  In people with steatocystoma multiplex who do not have identified KRT17 gene mutations, there is usually no family history of the disorder.",steatocystoma multiplex,0000952,GHR,https://ghr.nlm.nih.gov/condition/steatocystoma-multiplex,C0259771,T191,Disorders
What are the treatments for steatocystoma multiplex ?,0000952-5,treatment,These resources address the diagnosis or management of steatocystoma multiplex:  - Genetic Testing Registry: Steatocystoma multiplex   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,steatocystoma multiplex,0000952,GHR,https://ghr.nlm.nih.gov/condition/steatocystoma-multiplex,C0259771,T191,Disorders
What is (are) Stevens-Johnson syndrome/toxic epidermal necrolysis ?,0000953-1,information,"Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe skin reaction most often triggered by particular medications. Although Stevens-Johnson syndrome and toxic epidermal necrolysis were once thought to be separate conditions, they are now considered part of a continuum. Stevens-Johnson syndrome represents the less severe end of the disease spectrum, and toxic epidermal necrolysis represents the more severe end.  SJS/TEN often begins with a fever and flu-like symptoms. Within a few days, the skin begins to blister and peel, forming very painful raw areas called erosions that resemble a severe hot-water burn. The skin erosions usually start on the face and chest before spreading to other parts of the body. In most affected individuals, the condition also damages the mucous membranes, including the lining of the mouth and the airways, which can cause trouble with swallowing and breathing. The painful blistering can also affect the urinary tract and genitals. SJS/TEN often affects the eyes as well, causing irritation and redness of the conjunctiva, which are the mucous membranes that protect the white part of the eye and line the eyelids, and damage to the clear front covering of the eye (the cornea).  Severe damage to the skin and mucous membranes makes SJS/TEN a life-threatening disease. Because the skin normally acts as a protective barrier, extensive skin damage can lead to a dangerous loss of fluids and allow infections to develop. Serious complications can include pneumonia, overwhelming bacterial infections (sepsis), shock, multiple organ failure, and death. About 10 percent of people with Stevens-Johnson syndrome die from the disease, while the condition is fatal in up to 50 percent of those with toxic epidermal necrolysis.  Among people who survive, long-term effects of SJS/TEN can include changes in skin coloring (pigmentation), dryness of the skin and mucous membranes (xerosis), excess sweating (hyperhidrosis), hair loss (alopecia), and abnormal growth or loss of the fingernails and toenails. Other long-term problems can include impaired taste, difficulty urinating, and genital abnormalities. A small percentage of affected individuals develop chronic dryness or inflammation of the eyes, which can lead to increased sensitivity to light (photophobia) and vision impairment.",Stevens-Johnson syndrome/toxic epidermal necrolysis,0000953,GHR,https://ghr.nlm.nih.gov/condition/stevens-johnson-syndrome-toxic-epidermal-necrolysis,C0038325,T047,Disorders
How many people are affected by Stevens-Johnson syndrome/toxic epidermal necrolysis ?,0000953-2,frequency,"SJS/TEN is a rare disease, affecting 1 to 2 per million people each year. Stevens-Johnson syndrome (the less severe form of the condition) is more common than toxic epidermal necrolysis.  People who are HIV-positive and those with a chronic inflammatory disease called systemic lupus erythematosus are more likely to develop SJS/TEN than the general population. The reason for the increased risk is unclear, but immune system factors and exposure to multiple medications may play a role.",Stevens-Johnson syndrome/toxic epidermal necrolysis,0000953,GHR,https://ghr.nlm.nih.gov/condition/stevens-johnson-syndrome-toxic-epidermal-necrolysis,C0038325,T047,Disorders
What are the genetic changes related to Stevens-Johnson syndrome/toxic epidermal necrolysis ?,0000953-3,genetic changes,"Several genetic changes have been found to increase the risk of SJS/TEN in response to triggering factors such as medications. Most of these changes occur in genes that are involved in the normal function of the immune system.  The genetic variations most strongly associated with SJS/TEN occur in the HLA-B gene. This gene is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). The HLA-B gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. Certain variations in this gene occur much more often in people with SJS/TEN than in people without the condition.  Studies suggest that the HLA-B gene variations associated with SJS/TEN cause the immune system to react abnormally to certain medications. In a process that is not well understood, the drug causes immune cells called cytotoxic T cells and natural killer (NK) cells to release a substance called granulysin that destroys cells in the skin and mucous membranes. The death of these cells causes the blistering and peeling that is characteristic of SJS/TEN.  Variations in several other HLA and non-HLA genes have also been studied as potential risk factors for SJS/TEN. However, most people with genetic variations that increase the risk of SJS/TEN never develop the disease, even if they are exposed to drugs that can trigger it. Researchers believe that additional genetic and nongenetic factors, many of which are unknown, likely play a role in whether a particular individual develops SJS/TEN.  The drugs most frequently associated with SJS/TEN include several medications that are used to treat seizures (particularly carbamazepine, lamotrigine, and phenytoin); allopurinol, which is used to treat kidney stones and a form of arthritis called gout; a class of antibiotic drugs called sulfonamides; nevirapine, which is used to treat HIV infection; and a type of non-steroidal anti-inflammatory drugs (NSAIDs) called oxicams. Other factors may also trigger SJS/TEN. In particular, these skin reactions have occurred in people with an unusual form of pneumonia caused by infection with Mycoplasma pneumoniae and in people with viral infections, including cytomegalovirus. Researchers suspect that a combination of infections and drugs could contribute to the disease in some individuals. In many cases, no definitive trigger for an individual's SJS/TEN is ever discovered.",Stevens-Johnson syndrome/toxic epidermal necrolysis,0000953,GHR,https://ghr.nlm.nih.gov/condition/stevens-johnson-syndrome-toxic-epidermal-necrolysis,C0038325,T047,Disorders
Is Stevens-Johnson syndrome/toxic epidermal necrolysis inherited ?,0000953-4,inheritance,"SJS/TEN is not an inherited condition. However, the genetic changes that increase the risk of developing SJS/TEN can be passed from one generation to the next.",Stevens-Johnson syndrome/toxic epidermal necrolysis,0000953,GHR,https://ghr.nlm.nih.gov/condition/stevens-johnson-syndrome-toxic-epidermal-necrolysis,C0038325,T047,Disorders
What are the treatments for Stevens-Johnson syndrome/toxic epidermal necrolysis ?,0000953-5,treatment,These resources address the diagnosis or management of Stevens-Johnson syndrome/toxic epidermal necrolysis:  - Genetic Testing Registry: Stevens-Johnson syndrome  - Genetic Testing Registry: Toxic epidermal necrolysis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Stevens-Johnson syndrome/toxic epidermal necrolysis,0000953,GHR,https://ghr.nlm.nih.gov/condition/stevens-johnson-syndrome-toxic-epidermal-necrolysis,C0038325,T047,Disorders
What is (are) Stickler syndrome ?,0000954-1,information,"Stickler syndrome is a group of hereditary conditions characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and joint problems. These signs and symptoms vary widely among affected individuals.  A characteristic feature of Stickler syndrome is a somewhat flattened facial appearance. This appearance results from underdeveloped bones in the middle of the face, including the cheekbones and the bridge of the nose. A particular group of physical features called Pierre Robin sequence is also common in people with Stickler syndrome. Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate), a tongue that is placed further back than normal (glossoptosis), and a small lower jaw (micrognathia). This combination of features can lead to feeding problems and difficulty breathing.  Many people with Stickler syndrome have severe nearsightedness (high myopia). In some cases, the clear gel that fills the eyeball (the vitreous) has an abnormal appearance, which is noticeable during an eye examination. Other eye problems are also common, including increased pressure within the eye (glaucoma), clouding of the lens of the eyes (cataracts), and tearing of the lining of the eye (retinal detachment). These eye abnormalities cause impaired vision or blindness in some cases.  In people with Stickler syndrome, hearing loss varies in degree and may become more severe over time. The hearing loss may be sensorineural, meaning that it results from changes in the inner ear, or conductive, meaning that it is caused by abnormalities of the middle ear.  Most people with Stickler syndrome have skeletal abnormalities that affect the joints. The joints of affected children and young adults may be loose and very flexible (hypermobile), though joints become less flexible with age. Arthritis often appears early in life and may cause joint pain or stiffness. Problems with the bones of the spine (vertebrae) can also occur, including abnormal curvature of the spine (scoliosis or kyphosis) and flattened vertebrae (platyspondyly). These spinal abnormalities may cause back pain.  Researchers have described several types of Stickler syndrome, which are distinguished by their genetic causes and their patterns of signs and symptoms. In particular, the eye abnormalities and severity of hearing loss differ among the types. Type I has the highest risk of retinal detachment. Type II also includes eye abnormalities, but type III does not (and is often called non-ocular Stickler syndrome). Types II and III are more likely than type I to have significant hearing loss. Types IV, V, and VI are very rare and have each been diagnosed in only a few individuals.  A condition similar to Stickler syndrome, called Marshall syndrome, is characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and early-onset arthritis. Marshall syndrome can also include short stature. Some researchers have classified Marshall syndrome as a variant of Stickler syndrome, while others consider it to be a separate disorder.",Stickler syndrome,0000954,GHR,https://ghr.nlm.nih.gov/condition/stickler-syndrome,C0265253,T047,Disorders
How many people are affected by Stickler syndrome ?,0000954-2,frequency,"Stickler syndrome affects an estimated 1 in 7,500 to 9,000 newborns. Type I is the most common form of the condition.",Stickler syndrome,0000954,GHR,https://ghr.nlm.nih.gov/condition/stickler-syndrome,C0265253,T047,Disorders
What are the genetic changes related to Stickler syndrome ?,0000954-3,genetic changes,"Mutations in several genes cause the different types of Stickler syndrome. Between 80 and 90 percent of all cases are classified as type I and are caused by mutations in the COL2A1 gene. Another 10 to 20 percent of cases are classified as type II and result from mutations in the COL11A1 gene. Marshall syndrome, which may be a variant of Stickler syndrome, is also caused by COL11A1 gene mutations. Stickler syndrome types III through VI result from mutations in other, related genes.  All of the genes associated with Stickler syndrome provide instructions for making components of collagens, which are complex molecules that give structure and strength to the connective tissues that support the body's joints and organs. Mutations in any of these genes impair the production, processing, or assembly of collagen molecules. Defective collagen molecules or reduced amounts of collagen impair the development of connective tissues in many different parts of the body, leading to the varied features of Stickler syndrome.  Not all individuals with Stickler syndrome have mutations in one of the known genes. Researchers believe that mutations in other genes may also cause this condition, but those genes have not been identified.",Stickler syndrome,0000954,GHR,https://ghr.nlm.nih.gov/condition/stickler-syndrome,C0265253,T047,Disorders
Is Stickler syndrome inherited ?,0000954-4,inheritance,"Stickler syndrome types I, II, and III are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits a gene mutation from one affected parent. Other cases result from new mutations. These cases occur in people with no history of Stickler syndrome in their family.  Marshall syndrome also typically has an autosomal dominant pattern of inheritance.  Stickler syndrome types IV, V, and VI are inherited in an autosomal recessive pattern. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Stickler syndrome,0000954,GHR,https://ghr.nlm.nih.gov/condition/stickler-syndrome,C0265253,T047,Disorders
What are the treatments for Stickler syndrome ?,0000954-5,treatment,"These resources address the diagnosis or management of Stickler syndrome:  - Gene Review: Gene Review: Stickler Syndrome  - Genetic Testing Registry: Marshall syndrome  - Genetic Testing Registry: Stickler syndrome  - MedlinePlus Encyclopedia: Pierre Robin Syndrome  - Merck Manual Consumer Version: Detachment of the Retina  - Stickler Involved People: Clinical Characteristics & Diagnostic Criteria  - Stickler Involved People: Stickler Syndrome Recognition, Diagnosis, Treatment   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Stickler syndrome,0000954,GHR,https://ghr.nlm.nih.gov/condition/stickler-syndrome,C0265253,T047,Disorders
What is (are) STING-associated vasculopathy with onset in infancy ?,0000955-1,information,"STING-associated vasculopathy with onset in infancy (SAVI) is a disorder involving abnormal inflammation throughout the body, especially in the skin, blood vessels, and lungs. Inflammation normally occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight microbial invaders and help with tissue repair. Excessive inflammation damages the body's own cells and tissues. Disorders such as SAVI that result from abnormally increased inflammation are known as autoinflammatory diseases.  The signs and symptoms of SAVI begin in the first few months of life, and most are related to problems with blood vessels (vasculopathy) and damage to the tissues that rely on these vessels for their blood supply. Affected infants develop areas of severely damaged skin (lesions), particularly on the face, ears, nose, fingers, and toes. These lesions begin as rashes and can progress to become wounds (ulcers) and dead tissue (necrosis). The skin problems, which worsen in cold weather, can lead to complications such as scarred ears, a hole in the tissue that separates the two nostrils (nasal septum perforation), or fingers or toes that require amputation. Individuals with SAVI also have a purplish skin discoloration (livedo reticularis) caused by abnormalities in the tiny blood vessels of the skin. Affected individuals may also experience episodes of Raynaud phenomenon, in which the fingers and toes turn white or blue in response to cold temperature or other stresses. This effect occurs because of problems with the small vessels that carry blood to the extremities.  In addition to problems affecting the skin, people with SAVI have recurrent low-grade fevers and swollen lymph nodes. They may also develop widespread lung damage (interstitial lung disease) that can lead to the formation of scar tissue in the lungs (pulmonary fibrosis) and difficulty breathing; these respiratory complications can become life-threatening. Rarely, muscle inflammation (myositis) and joint stiffness also occur.",STING-associated vasculopathy with onset in infancy,0000955,GHR,https://ghr.nlm.nih.gov/condition/sting-associated-vasculopathy-with-onset-in-infancy,C1864921,T047,Disorders
How many people are affected by STING-associated vasculopathy with onset in infancy ?,0000955-2,frequency,The prevalence of this condition is unknown. Only a few affected individuals have been described in the medical literature.,STING-associated vasculopathy with onset in infancy,0000955,GHR,https://ghr.nlm.nih.gov/condition/sting-associated-vasculopathy-with-onset-in-infancy,C1864921,T047,Disorders
What are the genetic changes related to STING-associated vasculopathy with onset in infancy ?,0000955-3,genetic changes,"SAVI is caused by mutations in the TMEM173 gene. This gene provides instructions for making a protein called STING, which is involved in immune system function. STING helps produce beta-interferon, a member of a class of proteins called cytokines that promote inflammation.  The TMEM173 gene mutations that cause SAVI are described as ""gain-of-function"" mutations because they enhance the activity of the STING protein, leading to overproduction of beta-interferon. Abnormally high beta-interferon levels cause excessive inflammation that results in tissue damage, leading to the signs and symptoms of SAVI.",STING-associated vasculopathy with onset in infancy,0000955,GHR,https://ghr.nlm.nih.gov/condition/sting-associated-vasculopathy-with-onset-in-infancy,C1864921,T047,Disorders
Is STING-associated vasculopathy with onset in infancy inherited ?,0000955-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, this condition likely results from new (de novo) mutations in the gene that occur during the formation of reproductive cells (eggs or sperm) or in early embryonic development. These cases occur in people with no history of the disorder in their family.",STING-associated vasculopathy with onset in infancy,0000955,GHR,https://ghr.nlm.nih.gov/condition/sting-associated-vasculopathy-with-onset-in-infancy,C1864921,T047,Disorders
What are the treatments for STING-associated vasculopathy with onset in infancy ?,0000955-5,treatment,"These resources address the diagnosis or management of SAVI:  - Beth Israel Deaconess Medical Center: Autoinflammatory Disease Center  - Eurofever Project  - Genetic Testing Registry: Sting-associated vasculopathy, infantile-onset  - University College London: Vasculitis and Autoinflammation Research Group   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",STING-associated vasculopathy with onset in infancy,0000955,GHR,https://ghr.nlm.nih.gov/condition/sting-associated-vasculopathy-with-onset-in-infancy,C1864921,T047,Disorders
What is (are) Stormorken syndrome ?,0000956-1,information,"Stormorken syndrome is a rare condition that affects many body systems. Affected individuals usually have thrombocytopenia, in which there are abnormally low numbers of blood cells called platelets. Platelets are involved in normal blood clotting; a shortage of platelets typically results in easy bruising and abnormal bleeding. In addition, affected individuals often have a muscle disorder, called tubular aggregate myopathy, that leads to muscle weakness. Another feature of Stormorken syndrome is permanent constriction of the pupils of the eyes (miosis), which may be caused by abnormalities in the muscles that control the size of the pupils. Other features include lack of a functioning spleen (asplenia), scaly skin (ichthyosis), headaches, and difficulty with reading and spelling (dyslexia).",Stormorken syndrome,0000956,GHR,https://ghr.nlm.nih.gov/condition/stormorken-syndrome,C1861451,T047,Disorders
How many people are affected by Stormorken syndrome ?,0000956-2,frequency,Stormorken syndrome is a rare disorder. Approximately a dozen cases have been reported in the medical literature.,Stormorken syndrome,0000956,GHR,https://ghr.nlm.nih.gov/condition/stormorken-syndrome,C1861451,T047,Disorders
What are the genetic changes related to Stormorken syndrome ?,0000956-3,genetic changes,"Stormorken syndrome is caused by a mutation in the STIM1 gene. The protein produced from this gene is involved in controlling the entry of positively charged calcium atoms (calcium ions) into cells. The STIM1 protein recognizes when calcium ion levels are low and stimulates the flow of ions into the cell through special channels in the cell membrane called calcium-release activated calcium (CRAC) channels. The flow of calcium ions through CRAC channels triggers signaling within cells that helps control gene activity, cell growth and division, and immune function.  The STIM1 gene mutation involved in Stormorken syndrome leads to production of a STIM1 protein that is constantly turned on (constitutively active), which means it continually stimulates calcium ion entry through CRAC channels regardless of ion levels. Researchers suggest that the abnormal ion flow in platelets causes the cells to die earlier than usual, leading to thrombocytopenia and bleeding problems in people with Stormorken syndrome. It is unknown how constitutively active STIM1 leads to the other features of the disorder.",Stormorken syndrome,0000956,GHR,https://ghr.nlm.nih.gov/condition/stormorken-syndrome,C1861451,T047,Disorders
Is Stormorken syndrome inherited ?,0000956-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",Stormorken syndrome,0000956,GHR,https://ghr.nlm.nih.gov/condition/stormorken-syndrome,C1861451,T047,Disorders
What are the treatments for Stormorken syndrome ?,0000956-5,treatment,These resources address the diagnosis or management of Stormorken syndrome:  - Genetic Testing Registry: Stormorken syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Stormorken syndrome,0000956,GHR,https://ghr.nlm.nih.gov/condition/stormorken-syndrome,C1861451,T047,Disorders
What is (are) Stve-Wiedemann syndrome ?,0000957-1,information,"Stve-Wiedemann syndrome is a severe condition characterized by bone abnormalities and dysfunction of the autonomic nervous system, which controls involuntary body processes such as the regulation of breathing rate and body temperature. The condition is apparent from birth, and its key features include abnormal curvature (bowing) of the long bones in the legs, difficulty feeding and swallowing, and episodes of dangerously high body temperature (hyperthermia).  In addition to bowed legs, affected infants can have bowed arms, permanently bent fingers and toes (camptodactyly), and joint deformities (contractures) in the elbows and knees that restrict their movement. Other features include abnormalities of the pelvic bones (the ilia) and reduced bone mineral density (osteopenia).  In infants with Stve-Wiedemann syndrome, dysfunction of the autonomic nervous system typically leads to difficulty feeding and swallowing, breathing problems, and episodes of hyperthermia. Affected infants may also sweat excessively, even when the body temperature is not elevated, or have a reduced ability to feel pain. Many babies with this condition do not survive past infancy because of the problems regulating breathing and body temperature; however, some people with Stve-Wiedemann syndrome live into adolescence or later.  Problems with breathing and swallowing usually improve in affected children who survive infancy; however, they still have difficulty regulating body temperature. In addition, the leg bowing worsens, and children with Stve-Wiedemann syndrome may develop prominent joints, an abnormal curvature of the spine (scoliosis), and spontaneous bone fractures. Some affected individuals have a smooth tongue that lacks the bumps that house taste buds (fungiform papillae). Affected children may also lose certain reflexes, particularly the reflex to blink when something touches the eye (corneal reflex) and the knee-jerk reflex (patellar reflex).  Another condition once known as Schwartz-Jampel syndrome type 2 is now considered to be part of Stve-Wiedemann syndrome. Researchers have recommended that the designation Schwartz-Jampel syndrome type 2 no longer be used.",Stve-Wiedemann syndrome,0000957,GHR,https://ghr.nlm.nih.gov/condition/stuve-wiedemann-syndrome,C0004903,T019,Disorders
How many people are affected by Stve-Wiedemann syndrome ?,0000957-2,frequency,Stve-Wiedemann syndrome is a rare condition that has been found worldwide. Its prevalence is unknown.,Stve-Wiedemann syndrome,0000957,GHR,https://ghr.nlm.nih.gov/condition/stuve-wiedemann-syndrome,C0004903,T019,Disorders
What are the genetic changes related to Stve-Wiedemann syndrome ?,0000957-3,genetic changes,"Stve-Wiedemann syndrome is usually caused by mutations in the LIFR gene. This gene provides instructions for making a protein called leukemia inhibitory factor receptor (LIFR). Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. Together, ligands and their receptors trigger signals that affect cell development and function.  The LIFR protein acts as a receptor for a ligand known as leukemia inhibitory factor (LIF). LIFR signaling can control several cellular processes, including growth and division (proliferation), maturation (differentiation), and survival. First found to be important in blocking (inhibiting) growth of blood cancer (leukemia) cells, this signaling is also involved in the formation of bone and the development of nerve cells. It appears to play an important role in normal development and functioning of the autonomic nervous system.  Most LIFR gene mutations that cause Stve-Wiedemann syndrome prevent production of any LIFR protein. Other mutations lead to production of an altered protein that likely cannot function. Without functional LIFR, signaling is impaired. The lack of LIFR signaling disrupts normal bone formation, leading to osteopenia, bowed legs, and other skeletal problems common in Stve-Wiedemann syndrome. In addition, development of nerve cells, particularly those involved in the autonomic nervous system, is abnormal, leading to the problems with breathing, feeding, and regulating body temperature characteristic of this condition.  A small number of people with Stve-Wiedemann syndrome do not have an identified mutation in the LIFR gene. Researchers suggest that other genes that have not been identified may be involved in this condition.",Stve-Wiedemann syndrome,0000957,GHR,https://ghr.nlm.nih.gov/condition/stuve-wiedemann-syndrome,C0004903,T019,Disorders
Is Stve-Wiedemann syndrome inherited ?,0000957-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Stve-Wiedemann syndrome,0000957,GHR,https://ghr.nlm.nih.gov/condition/stuve-wiedemann-syndrome,C0004903,T019,Disorders
What are the treatments for Stve-Wiedemann syndrome ?,0000957-5,treatment,These resources address the diagnosis or management of Stve-Wiedemann syndrome:  - Genetic Testing Registry: Stuve-Wiedemann syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Stve-Wiedemann syndrome,0000957,GHR,https://ghr.nlm.nih.gov/condition/stuve-wiedemann-syndrome,C0004903,T019,Disorders
What is (are) succinate-CoA ligase deficiency ?,0000958-1,information,"Succinate-CoA ligase deficiency is an inherited disorder that affects the early development of the brain and other body systems. One of the earliest signs of the disorder is very weak muscle tone (severe hypotonia), which appears in the first few months of life. Severe hypotonia delays the development of motor skills such as holding up the head and rolling over. Many affected children also have muscle weakness and reduced muscle mass, which prevents them from standing and walking independently.  Additional features of succinate-CoA ligase deficiency can include progressive abnormal curvature of the spine (scoliosis or kyphosis), uncontrolled movements (dystonia), severe hearing loss, and seizures beginning in childhood. In most affected children, a substance called methylmalonic acid builds up abnormally in the body and is excreted in urine (methylmalonic aciduria). Most children with succinate-CoA ligase deficiency also experience a failure to thrive, which means that they gain weight and grow more slowly than expected.  Succinate-CoA ligase deficiency causes breathing difficulties that often lead to recurrent infections of the respiratory tract. These infections can be life-threatening, and most people with succinate-CoA ligase deficiency live only into childhood or adolescence.  A few individuals with succinate-CoA ligase deficiency have had an even more severe form of the disorder known as fatal infantile lactic acidosis. Affected infants develop a toxic buildup of lactic acid in the body (lactic acidosis) in the first day of life, which leads to muscle weakness and breathing difficulties. Children with fatal infantile lactic acidosis usually live only a few days after birth.",succinate-CoA ligase deficiency,0000958,GHR,https://ghr.nlm.nih.gov/condition/succinate-coa-ligase-deficiency,C1291575,T047,Disorders
How many people are affected by succinate-CoA ligase deficiency ?,0000958-2,frequency,"Although the exact prevalence of succinate-CoA ligase deficiency is unknown, it appears to be very rare. This condition occurs more frequently among people from the Faroe Islands in the North Atlantic Ocean.",succinate-CoA ligase deficiency,0000958,GHR,https://ghr.nlm.nih.gov/condition/succinate-coa-ligase-deficiency,C1291575,T047,Disorders
What are the genetic changes related to succinate-CoA ligase deficiency ?,0000958-3,genetic changes,"Succinate-CoA ligase deficiency results from mutations in the SUCLA2 or SUCLG1 gene. SUCLG1 gene mutations can cause fatal infantile lactic acidosis, while mutations in either gene can cause the somewhat less severe form of the condition.  The SUCLA2 and SUCLG1 genes each provide instructions for making one part (subunit) of an enzyme called succinate-CoA ligase. This enzyme plays a critical role in mitochondria, which are structures within cells that convert the energy from food into a form that cells can use. Mitochondria each contain a small amount of DNA, known as mitochondrial DNA or mtDNA, which is essential for the normal function of these structures. Succinate-CoA ligase is involved in producing and maintaining the building blocks of mitochondrial DNA.  Mutations in either the SUCLA2 or SUCLG1 gene disrupt the normal function of succinate-CoA ligase. A shortage (deficiency) of this enzyme leads to problems with the production and maintenance of mitochondrial DNA. A reduction in the amount of mitochondrial DNA (known as mitochondrial DNA depletion) impairs mitochondrial function in many of the body's cells and tissues. These problems lead to hypotonia, muscle weakness, and the other characteristic features of succinate-CoA ligase deficiency.",succinate-CoA ligase deficiency,0000958,GHR,https://ghr.nlm.nih.gov/condition/succinate-coa-ligase-deficiency,C1291575,T047,Disorders
Is succinate-CoA ligase deficiency inherited ?,0000958-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",succinate-CoA ligase deficiency,0000958,GHR,https://ghr.nlm.nih.gov/condition/succinate-coa-ligase-deficiency,C1291575,T047,Disorders
What are the treatments for succinate-CoA ligase deficiency ?,0000958-5,treatment,"These resources address the diagnosis or management of succinate-CoA ligase deficiency:  - Gene Review: Gene Review: SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form, with Mild Methylmalonic Aciduria  - Genetic Testing Registry: Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria)  - Genetic Testing Registry: Mitochondrial DNA depletion syndrome 9 (encephalomyopathic with methylmalonic aciduria)  - MedlinePlus Encyclopedia: Hypotonia  - MedlinePlus Encyclopedia: Lactic Acidosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",succinate-CoA ligase deficiency,0000958,GHR,https://ghr.nlm.nih.gov/condition/succinate-coa-ligase-deficiency,C1291575,T047,Disorders
What is (are) succinic semialdehyde dehydrogenase deficiency ?,0000959-1,information,"Succinic semialdehyde dehydrogenase deficiency is a disorder that can cause a variety of neurological problems. People with this condition typically have developmental delay, especially involving speech development; intellectual disability; and decreased muscle tone (hypotonia) soon after birth. About half of those affected experience seizures, difficulty coordinating movements (ataxia), decreased reflexes (hyporeflexia), and behavioral problems. The most common behavioral problems associated with this condition are sleep disturbances, hyperactivity, difficulty maintaining attention, and anxiety. Less frequently, affected individuals may have increased aggression, hallucinations, obsessive-compulsive disorder (OCD), and self-injurious behavior, including biting and head banging. People with this condition can also have problems controlling eye movements. Less common features of succinic semialdehyde dehydrogenase deficiency include uncontrollable movements of the limbs (choreoathetosis), involuntary tensing of the muscles (dystonia), muscle twitches (myoclonus), and a progressive worsening of ataxia.",succinic semialdehyde dehydrogenase deficiency,0000959,GHR,https://ghr.nlm.nih.gov/condition/succinic-semialdehyde-dehydrogenase-deficiency,C0268631,T047,Disorders
How many people are affected by succinic semialdehyde dehydrogenase deficiency ?,0000959-2,frequency,Approximately 350 people with succinic semialdehyde dehydrogenase deficiency have been reported worldwide.,succinic semialdehyde dehydrogenase deficiency,0000959,GHR,https://ghr.nlm.nih.gov/condition/succinic-semialdehyde-dehydrogenase-deficiency,C0268631,T047,Disorders
What are the genetic changes related to succinic semialdehyde dehydrogenase deficiency ?,0000959-3,genetic changes,"Mutations in the ALDH5A1 gene cause succinic semialdehyde dehydrogenase deficiency. The ALDH5A1 gene provides instructions for producing the succinic semialdehyde dehydrogenase enzyme. This enzyme is involved in the breakdown of a chemical that transmits signals in the brain (neurotransmitter) called gamma-amino butyric acid (GABA). The primary role of GABA is to prevent the brain from being overloaded with too many signals.  A shortage (deficiency) of succinic semialdehyde dehydrogenase leads to an increase in the amount of GABA and a related molecule called gamma-hydroxybutyrate (GHB) in the body, particularly the brain and spinal cord (central nervous system). It is unclear how an increase in GABA and GHB causes developmental delay, seizures, and other signs and symptoms of succinic semialdehyde dehydrogenase deficiency.",succinic semialdehyde dehydrogenase deficiency,0000959,GHR,https://ghr.nlm.nih.gov/condition/succinic-semialdehyde-dehydrogenase-deficiency,C0268631,T047,Disorders
Is succinic semialdehyde dehydrogenase deficiency inherited ?,0000959-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",succinic semialdehyde dehydrogenase deficiency,0000959,GHR,https://ghr.nlm.nih.gov/condition/succinic-semialdehyde-dehydrogenase-deficiency,C0268631,T047,Disorders
What are the treatments for succinic semialdehyde dehydrogenase deficiency ?,0000959-5,treatment,These resources address the diagnosis or management of succinic semialdehyde dehydrogenase deficiency:  - Gene Review: Gene Review: Succinic Semialdehyde Dehydrogenase Deficiency  - Genetic Testing Registry: Succinate-semialdehyde dehydrogenase deficiency  - MedlinePlus Encyclopedia: Hyperactivity   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,succinic semialdehyde dehydrogenase deficiency,0000959,GHR,https://ghr.nlm.nih.gov/condition/succinic-semialdehyde-dehydrogenase-deficiency,C0268631,T047,Disorders
What is (are) succinyl-CoA:3-ketoacid CoA transferase deficiency ?,0000960-1,information,"Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency is an inherited disorder that impairs the body's ability to break down ketones, which are molecules produced in the liver during the breakdown of fats.  The signs and symptoms of SCOT deficiency typically appear within the first few years of life. Affected individuals experience episodes of extreme tiredness (lethargy), appetite loss, vomiting, rapid breathing, and, occasionally, seizures. These episodes, which are called ketoacidotic attacks, sometimes lead to coma. About half of affected individuals have a ketoacidotic attack within the first 4 days of life. Affected individuals have no symptoms of the disorder between ketoacidotic attacks.  People with SCOT deficiency usually have a permanently elevated level of ketones in their blood (persistent ketosis). If the level of ketones gets too high, which can be brought on by infections, fevers, or periods without food (fasting), a ketoacidotic attack can occur. The frequency of ketoacidotic attacks varies among affected individuals.",succinyl-CoA:3-ketoacid CoA transferase deficiency,0000960,GHR,https://ghr.nlm.nih.gov/condition/succinyl-coa3-ketoacid-coa-transferase-deficiency,C1291317,T047,Disorders
How many people are affected by succinyl-CoA:3-ketoacid CoA transferase deficiency ?,0000960-2,frequency,The prevalence of SCOT deficiency is unknown. More than 20 cases of this condition have been reported in the scientific literature.,succinyl-CoA:3-ketoacid CoA transferase deficiency,0000960,GHR,https://ghr.nlm.nih.gov/condition/succinyl-coa3-ketoacid-coa-transferase-deficiency,C1291317,T047,Disorders
What are the genetic changes related to succinyl-CoA:3-ketoacid CoA transferase deficiency ?,0000960-3,genetic changes,"Mutations in the OXCT1 gene cause SCOT deficiency. The OXCT1 gene provides instructions for making an enzyme called succinyl-CoA:3-ketoacid CoA transferase (SCOT). The SCOT enzyme is made in the energy-producing centers of cells (mitochondria). The enzyme plays a role in the breakdown of ketones, which are an important source of energy during fasting or when energy demands are increased, such as during illness or when exercising.  OXCT1 gene mutations result in the production of a SCOT enzyme with little or no function. A reduction in the amount of functional enzyme leads to an inability to break down ketones, resulting in decreased energy production and an elevated level of ketones in the blood. If these signs become severe, a ketoacidotic attack can occur. Individuals with mutations that create an enzyme with partial function are still prone to ketoacidotic attacks, but are less likely to have persistent ketosis.",succinyl-CoA:3-ketoacid CoA transferase deficiency,0000960,GHR,https://ghr.nlm.nih.gov/condition/succinyl-coa3-ketoacid-coa-transferase-deficiency,C1291317,T047,Disorders
Is succinyl-CoA:3-ketoacid CoA transferase deficiency inherited ?,0000960-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",succinyl-CoA:3-ketoacid CoA transferase deficiency,0000960,GHR,https://ghr.nlm.nih.gov/condition/succinyl-coa3-ketoacid-coa-transferase-deficiency,C1291317,T047,Disorders
What are the treatments for succinyl-CoA:3-ketoacid CoA transferase deficiency ?,0000960-5,treatment,These resources address the diagnosis or management of succinyl-CoA:3-ketoacid CoA transferase deficiency:  - Genetic Testing Registry: Succinyl-CoA acetoacetate transferase deficiency  - MedlinePlus Encyclopedia: Ketones--Urine  - MedlinePlus Encyclopedia: Serum Ketones Test   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,succinyl-CoA:3-ketoacid CoA transferase deficiency,0000960,GHR,https://ghr.nlm.nih.gov/condition/succinyl-coa3-ketoacid-coa-transferase-deficiency,C1291317,T047,Disorders
What is (are) sudden infant death with dysgenesis of the testes syndrome ?,0000961-1,information,"Sudden infant death with dysgenesis of the testes syndrome (SIDDT) is a rare condition that is fatal in the first year of life; its major features include abnormalities of the reproductive system in males, feeding difficulties, and breathing problems.  Infants with SIDDT who are genetically male, with one X chromosome and one Y chromosome in each cell, have underdeveloped or abnormal testes. They may also have external genitalia that appear female or that do not look clearly male or clearly female (ambiguous genitalia). In affected infants who are genetically female, with two X chromosomes in each cell, development of the internal and external reproductive organs is normal.  SIDDT is associated with abnormal development of the brain, particularly the brainstem, which is the part of the brain that is connected to the spinal cord. The brainstem regulates many basic body functions, including heart rate, breathing, eating, and sleeping. It also relays information about movement and the senses between the brain and the rest of the body. Many features of SIDDT appear to be related to brainstem malfunction, including a slow or uneven heart rate, abnormal breathing patterns, difficulty controlling body temperature, unusual tongue and eye movements, abnormal reflexes, seizures, and feeding difficulties. Affected infants also have an unusual cry that has been described as similar to the bleating of a goat, which is probably a result of abnormal nerve connections between the brain and the voicebox (larynx).  The brainstem abnormalities lead to death in the first year of life, when affected infants suddenly stop breathing or their heart stops beating (cardiorespiratory arrest).",sudden infant death with dysgenesis of the testes syndrome,0000961,GHR,https://ghr.nlm.nih.gov/condition/sudden-infant-death-with-dysgenesis-of-the-testes-syndrome,C0038644,T019,Disorders
How many people are affected by sudden infant death with dysgenesis of the testes syndrome ?,0000961-2,frequency,SIDDT has been diagnosed in more than 20 infants from a single Old Order Amish community in Pennsylvania. The condition has not been reported outside this community.,sudden infant death with dysgenesis of the testes syndrome,0000961,GHR,https://ghr.nlm.nih.gov/condition/sudden-infant-death-with-dysgenesis-of-the-testes-syndrome,C0038644,T019,Disorders
What are the genetic changes related to sudden infant death with dysgenesis of the testes syndrome ?,0000961-3,genetic changes,"A single mutation in the TSPYL1 gene has caused all identified cases of SIDDT. This gene provides instructions for making a protein called TSPY-like 1, whose function is unknown. Based on its role in SIDDT, researchers propose that TSPY-like 1 is involved in the development of the male reproductive system and the brain.  The TSPYL1 gene mutation that causes SIDDT eliminates the function of TSPY-like 1. The loss of this protein's function appears to cause the major features of the disorder by disrupting the normal development of the male reproductive system and the brain, particularly the brainstem.  Research findings suggest that mutations in the TSPYL1 gene are not associated with sudden infant death syndrome (SIDS) in the general population. SIDS is a major cause of death in children younger than 1 year.",sudden infant death with dysgenesis of the testes syndrome,0000961,GHR,https://ghr.nlm.nih.gov/condition/sudden-infant-death-with-dysgenesis-of-the-testes-syndrome,C0038644,T019,Disorders
Is sudden infant death with dysgenesis of the testes syndrome inherited ?,0000961-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",sudden infant death with dysgenesis of the testes syndrome,0000961,GHR,https://ghr.nlm.nih.gov/condition/sudden-infant-death-with-dysgenesis-of-the-testes-syndrome,C0038644,T019,Disorders
What are the treatments for sudden infant death with dysgenesis of the testes syndrome ?,0000961-5,treatment,"These resources address the diagnosis or management of SIDDT:  - Clinic for Special Children (Strasburg, Pennsylvania)  - Genetic Testing Registry: Sudden infant death with dysgenesis of the testes syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",sudden infant death with dysgenesis of the testes syndrome,0000961,GHR,https://ghr.nlm.nih.gov/condition/sudden-infant-death-with-dysgenesis-of-the-testes-syndrome,C0038644,T019,Disorders
What is (are) supravalvular aortic stenosis ?,0000962-1,information,"Supravalvular aortic stenosis (SVAS) is a heart defect that develops before birth. This defect is a narrowing (stenosis) of the large blood vessel that carries blood from the heart to the rest of the body (the aorta). The condition is described as supravalvular because the section of the aorta that is narrowed is located just above the valve that connects the aorta with the heart (the aortic valve). Some people with SVAS also have defects in other blood vessels, most commonly stenosis of the artery from the heart to the lungs (the pulmonary artery). An abnormal heart sound during a heartbeat (heart murmur) can often be heard during a chest exam. If SVAS is not treated, the aortic narrowing can lead to shortness of breath, chest pain, and ultimately heart failure.  The severity of SVAS varies considerably, even among family members. Some affected individuals die in infancy, while others never experience symptoms of the disorder.",supravalvular aortic stenosis,0000962,GHR,https://ghr.nlm.nih.gov/condition/supravalvular-aortic-stenosis,C0003499,T047,Disorders
How many people are affected by supravalvular aortic stenosis ?,0000962-2,frequency,"SVAS occurs in 1 in 20,000 newborns worldwide.",supravalvular aortic stenosis,0000962,GHR,https://ghr.nlm.nih.gov/condition/supravalvular-aortic-stenosis,C0003499,T047,Disorders
What are the genetic changes related to supravalvular aortic stenosis ?,0000962-3,genetic changes,"Mutations in the ELN gene cause SVAS. The ELN gene provides instructions for making a protein called tropoelastin. Multiple copies of the tropoelastin protein attach to one another and are processed to form a mature protein called elastin. Elastin is the major component of elastic fibers, which are slender bundles of proteins that provide strength and flexibility to connective tissue (tissue that supports the body's joints and organs). Elastic fibers are found in the intricate lattice that forms in the spaces between cells (the extracellular matrix), where they give structural support to organs and tissues such as the heart, skin, lungs, ligaments, and blood vessels. Elastic fibers make up approximately 50 percent of the aorta, the rest being primarily muscle cells called vascular smooth muscle cells that line the aorta. Together, elastic fibers and vascular smooth muscle cells provide flexibility and resilience to the aorta.  Most of the ELN gene mutations that cause SVAS lead to a decrease in the production of tropoelastin. A shortage of tropoelastin reduces the amount of mature elastin protein that is processed and available for forming elastic fibers. As a result, elastic fibers that make up the aorta are thinner than normal. To compensate, the smooth muscle cells that line the aorta increase in number, making the aorta thicker and narrower than usual. A thickened aorta is less flexible and resilient to the stress of constant blood flow and pumping of the heart. Over time, the wall of the aorta can become damaged. Aortic narrowing causes the heart to work harder to pump blood through the aorta, resulting in the signs and symptoms of SVAS.",supravalvular aortic stenosis,0000962,GHR,https://ghr.nlm.nih.gov/condition/supravalvular-aortic-stenosis,C0003499,T047,Disorders
Is supravalvular aortic stenosis inherited ?,0000962-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. However, some people who inherit the altered gene never develop features of SVAS. (This situation is known as reduced penetrance.)  In some cases, a person inherits the mutation from one parent who has the mutation. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",supravalvular aortic stenosis,0000962,GHR,https://ghr.nlm.nih.gov/condition/supravalvular-aortic-stenosis,C0003499,T047,Disorders
What are the treatments for supravalvular aortic stenosis ?,0000962-5,treatment,These resources address the diagnosis or management of supravalvular aortic stenosis:  - Children's Hospital of Philadelphia  - Genetic Testing Registry: Supravalvar aortic stenosis  - Monroe Carell Jr. Children's Hospital at Vanderbilt   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,supravalvular aortic stenosis,0000962,GHR,https://ghr.nlm.nih.gov/condition/supravalvular-aortic-stenosis,C0003499,T047,Disorders
What is (are) surfactant dysfunction ?,0000963-1,information,"Surfactant dysfunction is a lung disorder that causes breathing problems. This condition results from abnormalities in the composition or function of surfactant, a mixture of certain fats (called phospholipids) and proteins that lines the lung tissue and makes breathing easy. Without normal surfactant, the tissue surrounding the air sacs in the lungs (the alveoli) sticks together (because of a force called surface tension) after exhalation, causing the alveoli to collapse. As a result, filling the lungs with air on each breath becomes very difficult, and the delivery of oxygen to the body is impaired.  The signs and symptoms of surfactant dysfunction can vary in severity. The most severe form of this condition causes respiratory distress syndrome in newborns. Affected babies have extreme difficulty breathing and are unable to get enough oxygen. The lack of oxygen can damage the baby's brain and other organs. This syndrome leads to respiratory failure, and most babies with this form of the condition do not survive more than a few months.  Less severe forms of surfactant dysfunction cause gradual onset of breathing problems in children or adults. Signs and symptoms of these milder forms are abnormally rapid breathing (tachypnea); low concentrations of oxygen in the blood (hypoxemia); and an inability to grow or gain weight at the expected rate (failure to thrive).  There are several types of surfactant dysfunction, which are identified by the genetic cause of the condition. One type, called SP-B deficiency, causes respiratory distress syndrome in newborns. Other types, known as SP-C dysfunction and ABCA3 deficiency, have signs and symptoms that range from mild to severe.",surfactant dysfunction,0000963,GHR,https://ghr.nlm.nih.gov/condition/surfactant-dysfunction,C3711368,T047,Disorders
How many people are affected by surfactant dysfunction ?,0000963-2,frequency,"One type of surfactant dysfunction, SP-B deficiency, is estimated to occur in 1 in 1 million newborns worldwide. The prevalence of surfactant dysfunction due to other causes is unknown.",surfactant dysfunction,0000963,GHR,https://ghr.nlm.nih.gov/condition/surfactant-dysfunction,C3711368,T047,Disorders
What are the genetic changes related to surfactant dysfunction ?,0000963-3,genetic changes,"Surfactant dysfunction is caused by mutations in one of several genes, including SFTPB, SFTPC, and ABCA3. Each of these genes is involved in the production of surfactant. The production and release of surfactant is a complex process. The phospholipids and proteins that make up surfactant are packaged in cellular structures known as lamellar bodies. These structures are also important for some processing of surfactant proteins, which is necessary for the proteins to mature and become functional. Surfactant is released from the lung cells and spreads across the tissue that surrounds alveoli. This substance lowers surface tension, which keeps the alveoli from collapsing after exhalation and makes breathing easy.  The SFTPB and SFTPC genes provide instructions for making surfactant protein-B (SP-B) and surfactant protein-C (SP-C), respectively, two of the four proteins in surfactant. These two proteins help spread the surfactant across the surface of the lung tissue, aiding in the surface tension-lowering property of surfactant. In addition, SP-B plays a role in the formation of lamellar bodies.  Mutations in the SFTPB gene cause a type of surfactant dysfunction sometimes referred to as SP-B deficiency. These mutations lead to a reduction in or absence of mature SP-B. In addition, SFTPB gene mutations cause abnormal processing of SP-C, resulting in a lack of mature SP-C and a buildup of unprocessed forms of SP-C. These changes lead to abnormal surfactant composition and decreased surfactant function. The loss of functional surfactant raises surface tension in the alveoli, causing severe breathing problems. The combination of SP-B and SP-C dysfunction may explain why the signs and symptoms of SP-B deficiency are so severe.  Mutations in the SFTPC gene are involved in a type of surfactant dysfunction sometimes called SP-C dysfunction. These mutations result in a reduction or absence of mature SP-C and the buildup of abnormal forms of SP-C. It is unclear which of these outcomes causes the signs and symptoms of SP-C dysfunction. Lack of mature SP-C can lead to abnormal composition of surfactant and decreased surfactant function. Alternatively, research suggests that abnormally processed SP-C proteins form the wrong three-dimensional shape and accumulate inside the lung cells. These misfolded proteins may trigger a cellular response that results in cell damage and death. This damage may disrupt surfactant production and release.  The ABCA3 gene provides instructions for making a protein that is found in the membrane that surrounds lamellar bodies. The ABCA3 protein transports phospholipids into lamellar bodies where they form surfactant. The ABCA3 protein also appears to be involved in the formation of lamellar bodies.  ABCA3 gene mutations, which cause a type of surfactant dysfunction sometimes referred to as ABCA3 deficiency, lead to reduction or absence of the protein's function. Without ABCA3 protein function, the transport of surfactant phospholipids is decreased. In addition, lamellar body formation is impaired, which causes abnormal processing of SP-B and SP-C. ABCA3 gene mutations result in abnormal surfactant composition and function. It has been suggested that mutations that eliminate ABCA3 protein function cause severe forms of surfactant dysfunction, and mutations that leave some residual ABCA3 activity cause milder forms of the condition.",surfactant dysfunction,0000963,GHR,https://ghr.nlm.nih.gov/condition/surfactant-dysfunction,C3711368,T047,Disorders
Is surfactant dysfunction inherited ?,0000963-4,inheritance,"Surfactant dysfunction can have different inheritance patterns depending on its genetic cause.  When caused by mutations in the SFTPB or ABCA3 gene, this condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  When caused by mutations in the SFTPC gene, this condition has an autosomal dominant inheritance pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In about half of cases caused by changes in the SFTPC gene, an affected person inherits the mutation from one affected parent. The remainder result from new mutations in the gene and occur in people with no history of the disorder in their family.",surfactant dysfunction,0000963,GHR,https://ghr.nlm.nih.gov/condition/surfactant-dysfunction,C3711368,T047,Disorders
What are the treatments for surfactant dysfunction ?,0000963-5,treatment,"These resources address the diagnosis or management of surfactant dysfunction:  - Children's Interstitial and Diffuse Lung Disease (chILD) Foundation: Surfactant Deficiency  - Genetic Testing Registry: Surfactant metabolism dysfunction, pulmonary, 1  - Genetic Testing Registry: Surfactant metabolism dysfunction, pulmonary, 2  - Genetic Testing Registry: Surfactant metabolism dysfunction, pulmonary, 4  - Genetic Testing Registry: Surfactant metabolism dysfunction, pulmonary, 5  - National Heart Lung and Blood Institute: How is Respiratory Distress Syndrome Diagnosed?  - National Heart Lung and Blood Institute: How is Respiratory Distress Syndrome Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",surfactant dysfunction,0000963,GHR,https://ghr.nlm.nih.gov/condition/surfactant-dysfunction,C3711368,T047,Disorders
What is (are) Swyer syndrome ?,0000964-1,information,"Swyer syndrome is a condition that affects sexual development. Sexual development is usually determined by an individual's chromosomes; however, in Swyer syndrome, sexual development does not match the affected individual's chromosomal makeup.  People usually have 46 chromosomes in each cell. Two of the 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male or female sex characteristics. Girls and women typically have two X chromosomes (46,XX karyotype), while boys and men usually have one X chromosome and one Y chromosome (46,XY karyotype). In Swyer syndrome, individuals with one X chromosome and one Y chromosome in each cell, the pattern typically found in boys and men, have female reproductive structures.  People with Swyer syndrome have typical female external genitalia. The uterus and fallopian tubes are normally-formed, but the gonads (ovaries or testes) are not functional; affected individuals have undeveloped clumps of tissue called streak gonads. Because of the lack of development of the gonads, Swyer syndrome is also called 46,XY complete gonadal dysgenesis. The residual gonadal tissue often becomes cancerous, so it is usually removed surgically early in life.  People with Swyer syndrome are typically raised as girls and have a female gender identity. Because they do not have functional ovaries, affected individuals usually begin hormone replacement therapy during adolescence to induce menstruation and development of female secondary sex characteristics such as breast enlargement and uterine growth. Hormone replacement therapy also helps reduce the risk of reduced bone density (osteopenia and osteoporosis). Women with this disorder do not produce eggs (ova), but they may be able to become pregnant with a donated egg or embryo.  Swyer syndrome usually affects only sexual development; such cases are called isolated Swyer syndrome. However, depending on the genetic cause, Swyer syndrome may also occur along with health conditions such as nerve problems (neuropathy) or as part of a syndrome such as campomelic dysplasia, which causes severe skeletal abnormalities.",Swyer syndrome,0000964,GHR,https://ghr.nlm.nih.gov/condition/swyer-syndrome,C2936694,T019,Disorders
How many people are affected by Swyer syndrome ?,0000964-2,frequency,"Swyer syndrome occurs in approximately 1 in 80,000 people.",Swyer syndrome,0000964,GHR,https://ghr.nlm.nih.gov/condition/swyer-syndrome,C2936694,T019,Disorders
What are the genetic changes related to Swyer syndrome ?,0000964-3,genetic changes,"Mutations in the SRY gene have been identified in approximately 15 percent of individuals with Swyer syndrome. The SRY gene, located on the Y chromosome, provides instructions for making the sex-determining region Y protein. This protein is a transcription factor, which means it attaches (binds) to specific regions of DNA and helps control the activity of particular genes. The sex-determining region Y protein starts processes that are involved in male sexual development. These processes cause a fetus to develop male gonads (testes) and prevent the development of female reproductive structures (uterus and fallopian tubes). SRY gene mutations that cause Swyer syndrome prevent production of the sex-determining region Y protein or result in the production of a nonfunctioning protein. A fetus whose cells do not produce functional sex-determining region Y protein will not develop testes but will develop a uterus and fallopian tubes, despite having a typically male karyotype.  Swyer syndrome can also be caused by mutations in the MAP3K1 gene; research indicates that mutations in this gene may account for up to 18 percent of cases. The MAP3K1 gene provides instructions for making a protein that helps regulate signaling pathways that control various processes in the body. These include the processes of determining sexual characteristics before birth. The mutations in this gene that cause Swyer syndrome decrease signaling that leads to male sexual differentiation and enhance signaling that leads to female sexual differentiation, preventing the development of testes and allowing the development of a uterus and fallopian tubes.  Mutations in the DHH and NR5A1 genes have also been identified in small numbers of people with Swyer syndrome. The DHH gene provides instructions for making a protein that is important for early development of tissues in many parts of the body. The NR5A1 gene provides instructions for producing another transcription factor called the steroidogenic factor 1 (SF1). This protein helps control the activity of several genes related to the production of sex hormones and sexual differentiation. Mutations in the DHH and NR5A1 genes affect the process of sexual differentiation, preventing affected individuals with a typically male karyotype from developing testes and causing them to develop a uterus and fallopian tubes.  Changes affecting other genes have also been identified in a small number of people with Swyer syndrome. Nongenetic factors, such as hormonal medications taken by the mother during pregnancy, have also been associated with this condition. However, in most individuals with Swyer syndrome, the cause is unknown.",Swyer syndrome,0000964,GHR,https://ghr.nlm.nih.gov/condition/swyer-syndrome,C2936694,T019,Disorders
Is Swyer syndrome inherited ?,0000964-4,inheritance,"Most cases of Swyer syndrome are not inherited; they occur in people with no history of the condition in their family. These cases result either from nongenetic causes or from new (de novo) mutations in a gene that occur during the formation of reproductive cells (eggs or sperm) or in early embryonic development.  SRY-related Swyer syndrome is usually caused by a new mutation. However, some individuals with Swyer syndrome inherit an altered SRY gene from an unaffected father who is mosaic for the mutation. Mosaic means that an individual has the mutation in some cells (including some reproductive cells) but not in others. In rare cases, a father may carry the mutation in every cell of the body but also has other genetic variations that prevent him from being affected by the condition. Because the SRY gene is on the Y chromosome, Swyer syndrome caused by SRY gene mutations is described as having a Y-linked inheritance pattern.  When Swyer syndrome is associated with an MAP3K1 or NR5A1 gene mutation, the condition is also usually caused by a new mutation. In the rare inherited cases, the mutation may be inherited from either parent, since these genes are not on the Y chromosome. In these cases, the condition has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the condition.  Swyer syndrome caused by mutations in the DHH gene is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition are carriers of one copy of the altered gene. Female carriers of a DHH gene mutation generally have typical sex development. Male carriers of a DHH gene mutation may also be unaffected, or they may have genital differences such as the urethra opening on the underside of the penis (hypospadias).",Swyer syndrome,0000964,GHR,https://ghr.nlm.nih.gov/condition/swyer-syndrome,C2936694,T019,Disorders
What are the treatments for Swyer syndrome ?,0000964-5,treatment,"These resources address the diagnosis or management of Swyer syndrome:  - Gene Review: Gene Review: 46,XY Disorder of Sex Development and 46,XY Complete Gonadal Dysgenesis  - Genetic Testing Registry: Pure gonadal dysgenesis 46,XY  - MedlinePlus Encyclopedia: Intersex  - University College London Hospitals: Disorders of Sexual Development   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Swyer syndrome,0000964,GHR,https://ghr.nlm.nih.gov/condition/swyer-syndrome,C2936694,T019,Disorders
What is (are) SYNGAP1-related intellectual disability ?,0000965-1,information,"SYNGAP1-related intellectual disability is a neurological disorder characterized by moderate to severe intellectual disability that is evident in early childhood. The earliest features are typically delayed development of speech and motor skills, such as sitting, standing, and walking. Many people with this condition have weak muscle tone (hypotonia), which contributes to the difficulty with motor skills. Some affected individuals lose skills they had already acquired (developmental regression). Other features of SYNGAP1-related intellectual disability include recurrent seizures (epilepsy), hyperactivity, and autism spectrum disorders, which are conditions characterized by impaired communication and social interaction; almost everyone with SYNGAP1-related intellectual disability develops epilepsy, and about half have an autism spectrum disorder.",SYNGAP1-related intellectual disability,0000965,GHR,https://ghr.nlm.nih.gov/condition/syngap1-related-intellectual-disability,C0445223,T048,Disorders
How many people are affected by SYNGAP1-related intellectual disability ?,0000965-2,frequency,SYNGAP1-related intellectual disability is a relatively common form of cognitive impairment. It is estimated to account for 1 to 2 percent of intellectual disability cases.,SYNGAP1-related intellectual disability,0000965,GHR,https://ghr.nlm.nih.gov/condition/syngap1-related-intellectual-disability,C0445223,T048,Disorders
What are the genetic changes related to SYNGAP1-related intellectual disability ?,0000965-3,genetic changes,"SYNGAP1-related intellectual disability is caused by mutations in the SYNGAP1 gene. The protein produced from this gene, called SynGAP, plays an important role in nerve cells in the brain. It is found at the junctions between nerve cells (synapses) and helps regulate changes in synapses that are critical for learning and memory. Mutations involved in this condition prevent the production of functional SynGAP protein from one copy of the gene, reducing the protein's activity in cells. Studies show that a reduction of SynGAP activity can have multiple effects in nerve cells, including pushing synapses to develop too early. The resulting abnormalities disrupt the synaptic changes in the brain that underlie learning and memory, leading to cognitive impairment and other neurological problems characteristic of SYNGAP1-related intellectual disability.",SYNGAP1-related intellectual disability,0000965,GHR,https://ghr.nlm.nih.gov/condition/syngap1-related-intellectual-disability,C0445223,T048,Disorders
Is SYNGAP1-related intellectual disability inherited ?,0000965-4,inheritance,"SYNGAP1-related intellectual disability is classified as an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Almost all cases result from new mutations in the gene and occur in people with no history of the disorder in their family. In at least one case, an affected person inherited the mutation from one affected parent.",SYNGAP1-related intellectual disability,0000965,GHR,https://ghr.nlm.nih.gov/condition/syngap1-related-intellectual-disability,C0445223,T048,Disorders
What are the treatments for SYNGAP1-related intellectual disability ?,0000965-5,treatment,"These resources address the diagnosis or management of SYNGAP1-related intellectual disability:  - Eunice Kennedy Shriver National Institute of Child Health and Human Development: What Are Treatments for Intellectual and Developmental Disabilities?  - Genetic Testing Registry: Mental retardation, autosomal dominant 5   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",SYNGAP1-related intellectual disability,0000965,GHR,https://ghr.nlm.nih.gov/condition/syngap1-related-intellectual-disability,C0445223,T048,Disorders
What is (are) systemic lupus erythematosus ?,0000966-1,information,"Systemic lupus erythematosus (SLE) is a chronic disease that causes inflammation in connective tissues, such as cartilage and the lining of blood vessels, which provide strength and flexibility to structures throughout the body. The signs and symptoms of SLE vary among affected individuals, and can involve many organs and systems, including the skin, joints, kidneys, lungs, central nervous system, and blood-forming (hematopoietic) system. SLE is one of a large group of conditions called autoimmune disorders that occur when the immune system attacks the body's own tissues and organs.  SLE may first appear as extreme tiredness (fatigue), a vague feeling of discomfort or illness (malaise), fever, loss of appetite, and weight loss. Most affected individuals also have joint pain, typically affecting the same joints on both sides of the body, and muscle pain and weakness. Skin problems are common in SLE. A characteristic feature is a flat red rash across the cheeks and bridge of the nose, called a ""butterfly rash"" because of its shape. The rash, which generally does not hurt or itch, often appears or becomes more pronounced when exposed to sunlight. Other skin problems that may occur in SLE include calcium deposits under the skin (calcinosis), damaged blood vessels (vasculitis) in the skin, and tiny red spots called petechiae. Petechiae are caused by a shortage of blood clotting cells called platelets that leads to bleeding under the skin. Affected individuals may also have hair loss (alopecia) and open sores (ulcerations) in the moist lining (mucosae) of the mouth, nose, or, less commonly, the genitals.  About a third of people with SLE develop kidney disease (nephritis). Heart problems may also occur in SLE, including inflammation of the sac-like membrane around the heart (pericarditis) and abnormalities of the heart valves, which control blood flow in the heart. Heart disease caused by fatty buildup in the blood vessels (atherosclerosis), which is very common in the general population, is even more common in people with SLE. The inflammation characteristic of SLE can also damage the nervous system, and may result in abnormal sensation and weakness in the limbs (peripheral neuropathy); seizures; stroke; and difficulty processing, learning, and remembering information (cognitive impairment). Anxiety and depression are also common in SLE.  People with SLE have episodes in which the condition gets worse (exacerbations) and other times when it gets better (remissions). Overall, SLE gradually gets worse over time, and damage to the major organs of the body can be life-threatening.",systemic lupus erythematosus,0000966,GHR,https://ghr.nlm.nih.gov/condition/systemic-lupus-erythematosus,C0024141,T047,Disorders
How many people are affected by systemic lupus erythematosus ?,0000966-2,frequency,"For unknown reasons, in industrialized Western countries SLE has become 10 times more common over the past 50 years. While estimates of its prevalence vary, SLE is believed to affect 14.6 to 68 per 100,000 people in the United States, with females developing SLE more often than males. It is most common in younger women; however, 20 percent of SLE cases occur in people over age 50. Because many of the signs and symptoms of SLE resemble those of other disorders, diagnosis may be delayed for years, and the condition may never be diagnosed in some affected individuals.  In industrialized Western countries, people of African and Asian descent are two to four times more likely to develop SLE than are people of European descent. However, while the prevalence of SLE in Africa and Asia is unknown, it is believed to be much lower than in Western nations. Researchers suggest that factors such as ethnic mixing, tobacco use in industrialized countries, and the different types of infections people acquire in different regions may help account for the discrepancy. For example malaria, which occurs often in tropical regions, is thought to be protective against SLE, while the Epstein-Barr virus, more common in the West, increases SLE risk.",systemic lupus erythematosus,0000966,GHR,https://ghr.nlm.nih.gov/condition/systemic-lupus-erythematosus,C0024141,T047,Disorders
What are the genetic changes related to systemic lupus erythematosus ?,0000966-3,genetic changes,"Normal variations (polymorphisms) in many genes can affect the risk of developing SLE, and in most cases multiple genetic factors are thought to be involved. In rare cases, SLE is caused by mutations in single genes. Most of the genes associated with SLE are involved in immune system function, and variations in these genes likely affect proper targeting and control of the immune response. Sex hormones and a variety of environmental factors including viral infections, diet, stress, chemical exposures, and sunlight are also thought to play a role in triggering this complex disorder. About 10 percent of SLE cases are thought to be triggered by drug exposure, and more than 80 drugs that may be involved have been identified.  In people with SLE, cells that have undergone self-destruction (apoptosis) because they are damaged or no longer needed are not cleared away properly. The relationship of this loss of function to the cause or features of SLE is unclear. Researchers suggest that these dead cells may release substances that cause the immune system to react inappropriately and attack the body's tissues, resulting in the signs and symptoms of SLE.",systemic lupus erythematosus,0000966,GHR,https://ghr.nlm.nih.gov/condition/systemic-lupus-erythematosus,C0024141,T047,Disorders
Is systemic lupus erythematosus inherited ?,0000966-4,inheritance,"SLE and other autoimmune disorders tend to run in families, but the inheritance pattern is usually unknown. People may inherit a gene variation that increases or decreases the risk of SLE, but in most cases do not inherit the condition itself. Not all people with SLE have a gene variation that increases the risk, and not all people with such a gene variation will develop the disorder.  In rare cases, SLE can be inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",systemic lupus erythematosus,0000966,GHR,https://ghr.nlm.nih.gov/condition/systemic-lupus-erythematosus,C0024141,T047,Disorders
What are the treatments for systemic lupus erythematosus ?,0000966-5,treatment,These resources address the diagnosis or management of systemic lupus erythematosus:  - MedlinePlus Encyclopedia: Antinuclear Antibody Panel   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,systemic lupus erythematosus,0000966,GHR,https://ghr.nlm.nih.gov/condition/systemic-lupus-erythematosus,C0024141,T047,Disorders
What is (are) systemic scleroderma ?,0000967-1,information,"Systemic scleroderma is an autoimmune disorder that affects the skin and internal organs. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. The word ""scleroderma"" means hard skin in Greek, and the condition is characterized by the buildup of scar tissue (fibrosis) in the skin and other organs. The condition is also called systemic sclerosis because the fibrosis can affect organs other than the skin. Fibrosis is due to the excess production of a tough protein called collagen, which normally strengthens and supports connective tissues throughout the body.  The signs and symptoms of systemic scleroderma usually begin with episodes of Raynaud phenomenon, which can occur weeks to years before fibrosis. In Raynaud phenomenon, the fingers and toes of affected individuals turn white or blue in response to cold temperature or other stresses. This effect occurs because of problems with the small vessels that carry blood to the extremities. Another early sign of systemic scleroderma is puffy or swollen hands before thickening and hardening of the skin due to fibrosis. Skin thickening usually occurs first in the fingers (called sclerodactyly) and may also involve the hands and face. In addition, people with systemic scleroderma often have open sores (ulcers) on their fingers, painful bumps under the skin (calcinosis), or small clusters of enlarged blood vessels just under the skin (telangiectasia).  Fibrosis can also affect internal organs and can lead to impairment or failure of the affected organs. The most commonly affected organs are the esophagus, heart, lungs, and kidneys. Internal organ involvement may be signaled by heartburn, difficulty swallowing (dysphagia), high blood pressure (hypertension), kidney problems, shortness of breath, diarrhea, or impairment of the muscle contractions that move food through the digestive tract (intestinal pseudo-obstruction).  There are three types of systemic scleroderma, defined by the tissues affected in the disorder. In one type of systemic scleroderma, known as limited cutaneous systemic scleroderma, fibrosis usually affects only the hands, arms, and face. Limited cutaneous systemic scleroderma used to be known as CREST syndrome, which is named for the common features of the condition: calcinosis, Raynaud phenomenon, esophageal motility dysfunction, sclerodactyly, and telangiectasia. In another type of systemic scleroderma, known as diffuse cutaneous systemic scleroderma, the fibrosis affects large areas of skin, including the torso and the upper arms and legs, and often involves internal organs. In diffuse cutaneous systemic scleroderma, the condition worsens quickly and organ damage occurs earlier than in other types of the condition. In the third type of systemic scleroderma, called systemic sclerosis sine scleroderma (""sine"" means without in Latin), fibrosis affects one or more internal organs but not the skin.  Approximately 15 percent to 25 percent of people with features of systemic scleroderma also have signs and symptoms of another condition that affects connective tissue, such as polymyositis, dermatomyositis, rheumatoid arthritis, Sjgren syndrome, or systemic lupus erythematosus. The combination of systemic scleroderma with other connective tissue abnormalities is known as scleroderma overlap syndrome.",systemic scleroderma,0000967,GHR,https://ghr.nlm.nih.gov/condition/systemic-scleroderma,C0036421,T047,Disorders
How many people are affected by systemic scleroderma ?,0000967-2,frequency,"The prevalence of systemic scleroderma is estimated to range from 50 to 300 cases per 1 million people. For reasons that are unknown, women are four times more likely to develop the condition than men.",systemic scleroderma,0000967,GHR,https://ghr.nlm.nih.gov/condition/systemic-scleroderma,C0036421,T047,Disorders
What are the genetic changes related to systemic scleroderma ?,0000967-3,genetic changes,"Researchers have identified variations in several genes that may influence the risk of developing systemic scleroderma. The most commonly associated genes belong to a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Each HLA gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. Specific normal variations of several HLA genes seem to affect the risk of developing systemic scleroderma.  Normal variations in other genes related to the body's immune function, such as IRF5 and STAT4, are also associated with an increased risk of developing systemic scleroderma. Variations in the IRF5 gene are specifically associated with diffuse cutaneous systemic scleroderma, and a variation in the STAT4 gene is associated with limited cutaneous systemic scleroderma. The IRF5 and STAT4 genes both play a role in initiating an immune response when the body detects a foreign invader (pathogen) such as a virus.  It is not known how variations in the associated genes contribute to the increased risk of systemic scleroderma. Variations in multiple genes may work together to increase the risk of developing the condition, and researchers are working to identify and confirm other genes associated with increased risk. In addition, a combination of genetic and environmental factors seems to play a role in developing systemic scleroderma.",systemic scleroderma,0000967,GHR,https://ghr.nlm.nih.gov/condition/systemic-scleroderma,C0036421,T047,Disorders
Is systemic scleroderma inherited ?,0000967-4,inheritance,"Most cases of systemic scleroderma are sporadic, which means they occur in people with no history of the condition in their family. However, some people with systemic scleroderma have close relatives with other autoimmune disorders.  A small percentage of all cases of systemic scleroderma have been reported to run in families; however, the condition does not have a clear pattern of inheritance. Multiple genetic and environmental factors likely play a part in determining the risk of developing this condition. As a result, inheriting a genetic variation linked with systemic scleroderma does not mean that a person will develop the condition.",systemic scleroderma,0000967,GHR,https://ghr.nlm.nih.gov/condition/systemic-scleroderma,C0036421,T047,Disorders
What are the treatments for systemic scleroderma ?,0000967-5,treatment,"These resources address the diagnosis or management of systemic scleroderma:  - Cedars-Sinai Medical Center  - Genetic Testing Registry: Scleroderma, familial progressive  - University of Maryland Medical Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",systemic scleroderma,0000967,GHR,https://ghr.nlm.nih.gov/condition/systemic-scleroderma,C0036421,T047,Disorders
"What is (are) T-cell immunodeficiency, congenital alopecia, and nail dystrophy ?",0000968-1,information,"T-cell immunodeficiency, congenital alopecia, and nail dystrophy is a type of severe combined immunodeficiency (SCID), which is a group of disorders characterized by an almost total lack of immune protection from foreign invaders such as bacteria and viruses. People with this form of SCID are missing functional immune cells called T cells, which normally recognize and attack foreign invaders to prevent infection. Without functional T cells, affected individuals develop repeated and persistent infections starting early in life. The infections result in slow growth and can be life-threatening; without effective treatment, most affected individuals live only into infancy or early childhood.  T-cell immunodeficiency, congenital alopecia, and nail dystrophy also affects growth of the hair and nails. Congenital alopecia refers to an absence of hair that is apparent from birth. Affected individuals have no scalp hair, eyebrows, or eyelashes. Nail dystrophy is a general term that describes malformed fingernails and toenails; in this condition, the nails are often ridged, pitted, or abnormally curved.  Researchers have described abnormalities of the brain and spinal cord (central nervous system) in at least two cases of this condition. However, it is not yet known whether central nervous system abnormalities are a common feature of T-cell immunodeficiency, congenital alopecia, and nail dystrophy.","T-cell immunodeficiency, congenital alopecia, and nail dystrophy",0000968,GHR,https://ghr.nlm.nih.gov/condition/t-cell-immunodeficiency-congenital-alopecia-and-nail-dystrophy,C1274233,T019,Disorders
"How many people are affected by T-cell immunodeficiency, congenital alopecia, and nail dystrophy ?",0000968-2,frequency,"T-cell immunodeficiency, congenital alopecia, and nail dystrophy is a rare disorder. It has been diagnosed in only a few individuals, almost all of whom are members of a large extended family from a community in southern Italy.","T-cell immunodeficiency, congenital alopecia, and nail dystrophy",0000968,GHR,https://ghr.nlm.nih.gov/condition/t-cell-immunodeficiency-congenital-alopecia-and-nail-dystrophy,C1274233,T019,Disorders
"What are the genetic changes related to T-cell immunodeficiency, congenital alopecia, and nail dystrophy ?",0000968-3,genetic changes,"T-cell immunodeficiency, congenital alopecia, and nail dystrophy results from mutations in the FOXN1 gene. This gene provides instructions for making a protein that is important for development of the skin, hair, nails, and immune system. Studies suggest that this protein helps guide the formation of hair follicles and the growth of fingernails and toenails. The FOXN1 protein also plays a critical role in the formation of the thymus, which is a gland located behind the breastbone where T cells mature and become functional. Researchers suspect that the FOXN1 protein is also involved in the development of the central nervous system, although its role is unclear.  Mutations in the FOXN1 gene prevent cells from making any functional FOXN1 protein. Without this protein, hair and nails cannot grow normally. A lack of FOXN1 protein also prevents the formation of the thymus. When this gland is not present, the immune system cannot produce mature, functional T cells to fight infections. As a result, people with T-cell immunodeficiency, congenital alopecia, and nail dystrophy develop recurrent serious infections starting early in life.","T-cell immunodeficiency, congenital alopecia, and nail dystrophy",0000968,GHR,https://ghr.nlm.nih.gov/condition/t-cell-immunodeficiency-congenital-alopecia-and-nail-dystrophy,C1274233,T019,Disorders
"Is T-cell immunodeficiency, congenital alopecia, and nail dystrophy inherited ?",0000968-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. However, some people who carry one copy of a mutated FOXN1 gene have abnormal fingernails or toenails.","T-cell immunodeficiency, congenital alopecia, and nail dystrophy",0000968,GHR,https://ghr.nlm.nih.gov/condition/t-cell-immunodeficiency-congenital-alopecia-and-nail-dystrophy,C1274233,T019,Disorders
"What are the treatments for T-cell immunodeficiency, congenital alopecia, and nail dystrophy ?",0000968-5,treatment,"These resources address the diagnosis or management of T-cell immunodeficiency, congenital alopecia, and nail dystrophy:  - Be The Match: What is a Bone Marrow Transplant?  - Genetic Testing Registry: T-cell immunodeficiency, congenital alopecia and nail dystrophy  - MedlinePlus Encyclopedia: Bone Marrow Transplant   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","T-cell immunodeficiency, congenital alopecia, and nail dystrophy",0000968,GHR,https://ghr.nlm.nih.gov/condition/t-cell-immunodeficiency-congenital-alopecia-and-nail-dystrophy,C1274233,T019,Disorders
What is (are) Tangier disease ?,0000969-1,information,"Tangier disease is an inherited disorder characterized by significantly reduced levels of high-density lipoprotein (HDL) in the blood. HDL transports cholesterol and certain fats called phospholipids from the body's tissues to the liver, where they are removed from the blood. HDL is often referred to as ""good cholesterol"" because high levels of this substance reduce the chances of developing heart and blood vessel (cardiovascular) disease. Because people with Tangier disease have very low levels of HDL, they have a moderately increased risk of cardiovascular disease.  Additional signs and symptoms of Tangier disease include a slightly elevated amount of fat in the blood (mild hypertriglyceridemia); disturbances in nerve function (neuropathy); and enlarged, orange-colored tonsils. Affected individuals often develop atherosclerosis, which is an accumulation of fatty deposits and scar-like tissue in the lining of the arteries. Other features of this condition may include an enlarged spleen (splenomegaly), an enlarged liver (hepatomegaly), clouding of the clear covering of the eye (corneal clouding), and type 2 diabetes.",Tangier disease,0000969,GHR,https://ghr.nlm.nih.gov/condition/tangier-disease,C0039292,T047,Disorders
How many people are affected by Tangier disease ?,0000969-2,frequency,Tangier disease is a rare disorder with approximately 100 cases identified worldwide. More cases are likely undiagnosed. This condition is named after an island off the coast of Virginia where the first affected individuals were identified.,Tangier disease,0000969,GHR,https://ghr.nlm.nih.gov/condition/tangier-disease,C0039292,T047,Disorders
What are the genetic changes related to Tangier disease ?,0000969-3,genetic changes,"Mutations in the ABCA1 gene cause Tangier disease. This gene provides instructions for making a protein that releases cholesterol and phospholipids from cells. These substances are used to make HDL, which transports them to the liver.  Mutations in the ABCA1 gene prevent the release of cholesterol and phospholipids from cells. As a result, these substances accumulate within cells, causing certain body tissues to enlarge and the tonsils to acquire a yellowish-orange color. A buildup of cholesterol can be toxic to cells, leading to impaired cell function or cell death. In addition, the inability to transport cholesterol and phospholipids out of cells results in very low HDL levels, which increases the risk of cardiovascular disease. These combined factors cause the signs and symptoms of Tangier disease.",Tangier disease,0000969,GHR,https://ghr.nlm.nih.gov/condition/tangier-disease,C0039292,T047,Disorders
Is Tangier disease inherited ?,0000969-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Tangier disease,0000969,GHR,https://ghr.nlm.nih.gov/condition/tangier-disease,C0039292,T047,Disorders
What are the treatments for Tangier disease ?,0000969-5,treatment,These resources address the diagnosis or management of Tangier disease:  - Genetic Testing Registry: Tangier disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Tangier disease,0000969,GHR,https://ghr.nlm.nih.gov/condition/tangier-disease,C0039292,T047,Disorders
What is (are) tarsal-carpal coalition syndrome ?,0000970-1,information,"Tarsal-carpal coalition syndrome is a rare, inherited bone disorder that affects primarily the hands and feet. Several individual bones make up each wrist (carpal bones) and ankle (tarsal bones). In tarsal-carpal coalition syndrome, the carpal bones fuse together, as do the tarsal bones, which causes stiffness and immobility of the hands and feet. Symptoms of the condition can become apparent in infancy, and they worsen with age. The severity of the symptoms can vary, even among members of the same family.  In this condition, fusion at the joints between the bones that make up each finger and toe (symphalangism) can also occur. Consequently, the fingers and toes become stiff and difficult to bend. Stiffness of the pinky fingers and toes (fifth digits) is usually noticeable first. The joints at the base of the pinky fingers and toes fuse first, and slowly, the other joints along the length of these digits may also be affected. Progressively, the bones in the fourth, third, and second digits (the ring finger, middle finger, and forefinger, and the corresponding toes) become fused. The thumb and big toe are usually not involved. Affected individuals have increasing trouble forming a fist, and walking often becomes painful and difficult. Occasionally, there is also fusion of bones in the upper and lower arm at the elbow joint (humeroradial fusion). Less common features of tarsal-carpal coalition syndrome include short stature or the development of hearing loss.",tarsal-carpal coalition syndrome,0000970,GHR,https://ghr.nlm.nih.gov/condition/tarsal-carpal-coalition-syndrome,C1861305,T019,Disorders
How many people are affected by tarsal-carpal coalition syndrome ?,0000970-2,frequency,"This condition is very rare; however, the exact prevalence is unknown.",tarsal-carpal coalition syndrome,0000970,GHR,https://ghr.nlm.nih.gov/condition/tarsal-carpal-coalition-syndrome,C1861305,T019,Disorders
What are the genetic changes related to tarsal-carpal coalition syndrome ?,0000970-3,genetic changes,"Tarsal-carpal coalition syndrome is caused by mutations in the NOG gene, which provides instructions for making a protein called noggin. This protein plays an important role in proper bone and joint development by blocking (inhibiting) signals that stimulate bone formation. The noggin protein attaches (binds) to proteins called bone morphogenetic proteins (BMPs), which keeps the BMPs from triggering signals for the development of bone.  NOG gene mutations that cause tarsal-carpal coalition syndrome reduce the amount of functional noggin protein. With decreased noggin function, BMPs abnormally stimulate bone formation in joint areas, where there should be no bone, causing the bone fusions seen in people with tarsal-carpal coalition syndrome.  Mutations in the NOG gene are involved in several disorders with overlapping signs and symptoms. Because of a shared genetic cause and overlapping features, researchers have suggested that these conditions, including tarsal-carpal coalition syndrome, represent a spectrum of related conditions referred to as NOG-related-symphalangism spectrum disorder (NOG-SSD).",tarsal-carpal coalition syndrome,0000970,GHR,https://ghr.nlm.nih.gov/condition/tarsal-carpal-coalition-syndrome,C1861305,T019,Disorders
Is tarsal-carpal coalition syndrome inherited ?,0000970-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",tarsal-carpal coalition syndrome,0000970,GHR,https://ghr.nlm.nih.gov/condition/tarsal-carpal-coalition-syndrome,C1861305,T019,Disorders
What are the treatments for tarsal-carpal coalition syndrome ?,0000970-5,treatment,These resources address the diagnosis or management of tarsal-carpal coalition syndrome:  - Foot Health Facts: Tarsal Coalition  - Genetic Testing Registry: Tarsal carpal coalition syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,tarsal-carpal coalition syndrome,0000970,GHR,https://ghr.nlm.nih.gov/condition/tarsal-carpal-coalition-syndrome,C1861305,T019,Disorders
What is (are) task-specific focal dystonia ?,0000971-1,information,"Task-specific focal dystonia is a movement disorder that interferes with the performance of particular tasks, such as writing, playing a musical instrument, or participating in a sport. Dystonias are a group of movement problems characterized by involuntary, sustained muscle contractions, tremors, and other uncontrolled movements. The term ""focal"" refers to a type of dystonia that affects a single part of the body, such as the hand or jaw.  Researchers have described several forms of task-specific focal dystonia. The most common is writer's cramp, in which muscle cramps or spasms in the hand, wrist, or forearm interfere with holding a pen or pencil. Writer's cramp begins in the hand used for writing (the dominant hand) and is usually limited to that task, but with time it can spread to the other hand and affect other fine-motor activities such as shaving or typing.  Musician's dystonia is a form of task-specific focal dystonia characterized by muscle cramps and spasms that occur while playing a musical instrument. This condition can affect amateur or professional musicians, and the location of the dystonia depends on the instrument. Some musicians (such as piano, guitar, and violin players) develop focal hand dystonia, which causes loss of fine-motor control in the hand and wrist muscles. This condition reduces finger coordination, speed, and endurance while playing. Musicians who play woodwind or brass instruments can develop what is known as embouchure dystonia. This condition causes muscle cramps or spasms involving the lips, tongue, or jaw, which prevents normal positioning of the mouth around the instrument's mouthpiece. Musician's dystonia often occurs only when playing a particular instrument. However, over time focal hand dystonia may impair other activities, and embouchure dystonia can worsen to affect eating and speech.  Task-specific focal dystonia can affect people who play sports and engage in other occupations involving repetitive, highly practiced movements. For example, some golfers experience involuntary jerking of the wrists during putting, a condition known informally as ""the yips."" Cramps and spasms of the hand and arm muscles can also affect tennis players, billiards players, dart throwers, and other athletes. Additionally, task-specific dystonia has been reported in tailors, shoemakers, hair stylists, and people who frequently type or use a computer mouse.  The abnormal movements associated with task-specific focal dystonia are usually painless, although they can cause anxiety when they interfere with musical performance and other activities. Severe cases can cause professional disability.",task-specific focal dystonia,0000971,GHR,https://ghr.nlm.nih.gov/condition/task-specific-focal-dystonia,C1969807,T047,Disorders
How many people are affected by task-specific focal dystonia ?,0000971-2,frequency,Task-specific focal dystonia affects an estimated 7 to 69 per million people in the general population. Musician's dystonia that is severe enough to impact performance occurs in about 1 percent of musicians.,task-specific focal dystonia,0000971,GHR,https://ghr.nlm.nih.gov/condition/task-specific-focal-dystonia,C1969807,T047,Disorders
What are the genetic changes related to task-specific focal dystonia ?,0000971-3,genetic changes,"The causes of task-specific focal dystonia are unknown, although the disorder likely results from a combination of genetic and environmental factors. Certain genetic changes probably increase the likelihood of developing this condition, and environmental factors may trigger the onset of symptoms in people who are at risk. It is possible that the different forms of task-specific focal dystonia have different underlying causes.  Having a family history of dystonia, particularly focal dystonia, is one of the only established risk factors for task-specific focal dystonia. Studies suggest that previous injury, changes in practice routine, and exposure to anti-psychotic drugs (which can cause other types of dystonia) are not major risk factors. Nor does the condition appear to be a form of performance anxiety. Task-specific focal dystonia may be associated with dysfunction in areas of the brain that regulate movement. In particular, researchers have found that at least some cases of the condition are related to malfunction of the basal ganglia, which are structures deep within the brain that help start and control movement.  Although genetic factors are almost certainly involved in task-specific focal dystonia, no genes have been clearly associated with the condition. Researchers have looked for mutations in several genes known to be involved in other forms of dystonia, but these genetic changes do not appear to be a major cause of task-specific focal dystonia. Researchers are working to determine which genetic factors are related to this disorder.",task-specific focal dystonia,0000971,GHR,https://ghr.nlm.nih.gov/condition/task-specific-focal-dystonia,C1969807,T047,Disorders
Is task-specific focal dystonia inherited ?,0000971-4,inheritance,"Most cases of task-specific focal dystonia are sporadic, which means they occur in people with no history of the condition in their family. However, at least 10 percent of affected individuals have a family history of focal dystonia. (For example, writer's cramp and musician's dystonia have been reported to occur in the same family.) The dystonia often appears to have an autosomal dominant pattern of inheritance, based on the observation that some affected people have a parent with the condition.",task-specific focal dystonia,0000971,GHR,https://ghr.nlm.nih.gov/condition/task-specific-focal-dystonia,C1969807,T047,Disorders
What are the treatments for task-specific focal dystonia ?,0000971-5,treatment,These resources address the diagnosis or management of task-specific focal dystonia:  - Dystonia Medical Research Foundation: How Is Dystonia Diagnosed?  - Dystonia Medical Research Foundation: Treatments  - Gene Review: Gene Review: Dystonia Overview  - Genetic Testing Registry: Focal dystonia  - Merck Manual Home Health Handbook: Dystonias   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,task-specific focal dystonia,0000971,GHR,https://ghr.nlm.nih.gov/condition/task-specific-focal-dystonia,C1969807,T047,Disorders
What is (are) Tay-Sachs disease ?,0000972-1,information,"Tay-Sachs disease is a rare inherited disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord.  The most common form of Tay-Sachs disease becomes apparent in infancy. Infants with this disorder typically appear normal until the age of 3 to 6 months, when their development slows and muscles used for movement weaken. Affected infants lose motor skills such as turning over, sitting, and crawling. They also develop an exaggerated startle reaction to loud noises. As the disease progresses, children with Tay-Sachs disease experience seizures, vision and hearing loss, intellectual disability, and paralysis. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. Children with this severe infantile form of Tay-Sachs disease usually live only into early childhood.  Other forms of Tay-Sachs disease are very rare. Signs and symptoms can appear in childhood, adolescence, or adulthood and are usually milder than those seen with the infantile form. Characteristic features include muscle weakness, loss of muscle coordination (ataxia) and other problems with movement, speech problems, and mental illness. These signs and symptoms vary widely among people with late-onset forms of Tay-Sachs disease.",Tay-Sachs disease,0000972,GHR,https://ghr.nlm.nih.gov/condition/tay-sachs-disease,C0039373,T047,Disorders
How many people are affected by Tay-Sachs disease ?,0000972-2,frequency,"Tay-Sachs disease is very rare in the general population. The genetic mutations that cause this disease are more common in people of Ashkenazi (eastern and central European) Jewish heritage than in those with other backgrounds. The mutations responsible for this disease are also more common in certain French-Canadian communities of Quebec, the Old Order Amish community in Pennsylvania, and the Cajun population of Louisiana.",Tay-Sachs disease,0000972,GHR,https://ghr.nlm.nih.gov/condition/tay-sachs-disease,C0039373,T047,Disorders
What are the genetic changes related to Tay-Sachs disease ?,0000972-3,genetic changes,"Mutations in the HEXA gene cause Tay-Sachs disease. The HEXA gene provides instructions for making part of an enzyme called beta-hexosaminidase A, which plays a critical role in the brain and spinal cord. This enzyme is located in lysosomes, which are structures in cells that break down toxic substances and act as recycling centers. Within lysosomes, beta-hexosaminidase A helps break down a fatty substance called GM2 ganglioside.  Mutations in the HEXA gene disrupt the activity of beta-hexosaminidase A, which prevents the enzyme from breaking down GM2 ganglioside. As a result, this substance accumulates to toxic levels, particularly in neurons in the brain and spinal cord. Progressive damage caused by the buildup of GM2 ganglioside leads to the destruction of these neurons, which causes the signs and symptoms of Tay-Sachs disease.  Because Tay-Sachs disease impairs the function of a lysosomal enzyme and involves the buildup of GM2 ganglioside, this condition is sometimes referred to as a lysosomal storage disorder or a GM2-gangliosidosis.",Tay-Sachs disease,0000972,GHR,https://ghr.nlm.nih.gov/condition/tay-sachs-disease,C0039373,T047,Disorders
Is Tay-Sachs disease inherited ?,0000972-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Tay-Sachs disease,0000972,GHR,https://ghr.nlm.nih.gov/condition/tay-sachs-disease,C0039373,T047,Disorders
What are the treatments for Tay-Sachs disease ?,0000972-5,treatment,These resources address the diagnosis or management of Tay-Sachs disease:  - Gene Review: Gene Review: Hexosaminidase A Deficiency  - Genetic Testing Registry: Tay-Sachs disease  - MedlinePlus Encyclopedia: Tay-Sachs Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Tay-Sachs disease,0000972,GHR,https://ghr.nlm.nih.gov/condition/tay-sachs-disease,C0039373,T047,Disorders
What is (are) tetra-amelia syndrome ?,0000973-1,information,"Tetra-amelia syndrome is a very rare disorder characterized by the absence of all four limbs. (""Tetra"" is the Greek word for ""four,"" and ""amelia"" refers to the failure of an arm or leg to develop before birth.) This syndrome can also cause severe malformations of other parts of the body, including the face and head, heart, nervous system, skeleton, and genitalia. The lungs are underdeveloped in many cases, which makes breathing difficult or impossible. Because children with tetra-amelia syndrome have such serious medical problems, most are stillborn or die shortly after birth.",tetra-amelia syndrome,0000973,GHR,https://ghr.nlm.nih.gov/condition/tetra-amelia-syndrome,C3814160,T019,Disorders
How many people are affected by tetra-amelia syndrome ?,0000973-2,frequency,Tetra-amelia syndrome has been reported in only a few families worldwide.,tetra-amelia syndrome,0000973,GHR,https://ghr.nlm.nih.gov/condition/tetra-amelia-syndrome,C3814160,T019,Disorders
What are the genetic changes related to tetra-amelia syndrome ?,0000973-3,genetic changes,"Researchers have found a mutation in the WNT3 gene in people with tetra-amelia syndrome from one large family. This gene is part of a family of WNT genes that play critical roles in development before birth. The protein produced from the WNT3 gene is involved in the formation of the limbs and other body systems during embryonic development. Mutations in the WNT3 gene prevent cells from producing functional WNT3 protein, which disrupts normal limb formation and leads to the other serious birth defects associated with tetra-amelia syndrome.  In other affected families, the cause of tetra-amelia syndrome has not been determined. Researchers believe that unidentified mutations in WNT3 or other genes involved in limb development are probably responsible for the disorder in these cases.",tetra-amelia syndrome,0000973,GHR,https://ghr.nlm.nih.gov/condition/tetra-amelia-syndrome,C3814160,T019,Disorders
Is tetra-amelia syndrome inherited ?,0000973-4,inheritance,"In most of the families reported so far, tetra-amelia syndrome appears to have an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with tetra-amelia syndrome each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.",tetra-amelia syndrome,0000973,GHR,https://ghr.nlm.nih.gov/condition/tetra-amelia-syndrome,C3814160,T019,Disorders
What are the treatments for tetra-amelia syndrome ?,0000973-5,treatment,"These resources address the diagnosis or management of tetra-amelia syndrome:  - Gene Review: Gene Review: Tetra-Amelia Syndrome  - Genetic Testing Registry: Tetraamelia, autosomal recessive   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",tetra-amelia syndrome,0000973,GHR,https://ghr.nlm.nih.gov/condition/tetra-amelia-syndrome,C3814160,T019,Disorders
What is (are) tetrahydrobiopterin deficiency ?,0000974-1,information,"Tetrahydrobiopterin deficiency is a rare disorder characterized by a shortage (deficiency) of a molecule called tetrahydrobiopterin or BH4. This condition alters the levels of several substances in the body, including phenylalanine. Phenylalanine is a building block of proteins (an amino acid) that is obtained through the diet. It is found in foods that contain protein and in some artificial sweeteners. High levels of phenylalanine are present from early infancy in people with untreated tetrahydrobiopterin deficiency. This condition also alters the levels of chemicals called neurotransmitters, which transmit signals between nerve cells in the brain.  Infants with tetrahydrobiopterin deficiency appear normal at birth, but medical problems ranging from mild to severe become apparent over time. Signs and symptoms of this condition can include intellectual disability, progressive problems with development, movement disorders, difficulty swallowing, seizures, behavioral problems, and an inability to control body temperature.",tetrahydrobiopterin deficiency,0000974,GHR,https://ghr.nlm.nih.gov/condition/tetrahydrobiopterin-deficiency,C0751436,T047,Disorders
How many people are affected by tetrahydrobiopterin deficiency ?,0000974-2,frequency,"This condition is rare, affecting an estimated 1 in 500,000 to 1 in 1 million newborns. In most parts of the world, tetrahydrobiopterin deficiency accounts for 1 to 3 percent of all cases of elevated phenylalanine levels. The remaining cases are caused by a similar condition called phenylketonuria (PKU). In certain countries, including Saudi Arabia, Taiwan, China, and Turkey, it is more common for elevated levels of phenylalanine to be caused by tetrahydrobiopterin deficiency than by PKU.",tetrahydrobiopterin deficiency,0000974,GHR,https://ghr.nlm.nih.gov/condition/tetrahydrobiopterin-deficiency,C0751436,T047,Disorders
What are the genetic changes related to tetrahydrobiopterin deficiency ?,0000974-3,genetic changes,"Tetrahydrobiopterin deficiency can be caused by mutations in one of several genes, including GCH1, PCBD1, PTS, and QDPR. These genes provide instructions for making enzymes that help produce and recycle tetrahydrobiopterin in the body. Tetrahydrobiopterin normally helps process several amino acids, including phenylalanine. It is also involved in the production of neurotransmitters.  If one of the enzymes fails to function correctly because of a gene mutation, little or no tetrahydrobiopterin is available to help process phenylalanine. As a result, phenylalanine can build up in the blood and other tissues. Because nerve cells in the brain are particularly sensitive to phenylalanine levels, excessive amounts of this substance can cause brain damage. Tetrahydrobiopterin deficiency can also alter the levels of certain neurotransmitters, which disrupts normal brain function. These abnormalities underlie the intellectual disability and other characteristic features of the condition.",tetrahydrobiopterin deficiency,0000974,GHR,https://ghr.nlm.nih.gov/condition/tetrahydrobiopterin-deficiency,C0751436,T047,Disorders
Is tetrahydrobiopterin deficiency inherited ?,0000974-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",tetrahydrobiopterin deficiency,0000974,GHR,https://ghr.nlm.nih.gov/condition/tetrahydrobiopterin-deficiency,C0751436,T047,Disorders
What are the treatments for tetrahydrobiopterin deficiency ?,0000974-5,treatment,"These resources address the diagnosis or management of tetrahydrobiopterin deficiency:  - Baby's First Test: Biopterin Defect in Cofactor Biosynthesis  - Baby's First Test: Biopterin Defect in Cofactor Regeneration  - Genetic Testing Registry: 6-pyruvoyl-tetrahydropterin synthase deficiency  - Genetic Testing Registry: Dihydropteridine reductase deficiency  - Genetic Testing Registry: GTP cyclohydrolase I deficiency  - Genetic Testing Registry: Hyperphenylalaninemia, BH4-deficient, D  - MedlinePlus Encyclopedia: Serum Phenylalanine Screening   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",tetrahydrobiopterin deficiency,0000974,GHR,https://ghr.nlm.nih.gov/condition/tetrahydrobiopterin-deficiency,C0751436,T047,Disorders
What is (are) tetrasomy 18p ?,0000975-1,information,"Tetrasomy 18p is a chromosomal condition that affects many parts of the body. This condition usually causes feeding difficulties in infancy, delayed development, intellectual disability that is often mild to moderate but can be severe, changes in muscle tone, distinctive facial features, and other birth defects. However, the signs and symptoms vary among affected individuals.  Babies with tetrasomy 18p often have trouble feeding and may vomit frequently, which makes it difficult for them to gain weight. Some affected infants also have breathing problems and jaundice, which is a yellowing of the skin and the whites of the eyes.  Changes in muscle tone are commonly seen with tetrasomy 18p. Some affected children have weak muscle tone (hypotonia), while others have increased muscle tone (hypertonia) and stiffness (spasticity). These changes contribute to delayed development of motor skills, including sitting, crawling, and walking.  Tetrasomy 18p is associated with a distinctive facial appearance that can include unusually shaped and low-set ears, a small mouth, a flat area between the upper lip and the nose (philtrum), and a thin upper lip. Many affected individuals also have a high, arched roof of the mouth (palate), and a few have had a split in the roof of the mouth (cleft palate).  Additional features of tetrasomy 18p can include seizures, vision problems, recurrent ear infections, mild to moderate hearing loss, constipation and other gastrointestinal problems, abnormal curvature of the spine (scoliosis or kyphosis), a shortage of growth hormone, and birth defects affecting the heart and other organs. Males with tetrasomy 18p may be born with undescended testes (cryptorchidism) or the opening of the urethra on the underside of the penis (hypospadias). Psychiatric conditions, such as attention deficit hyperactivity disorder (ADHD) and anxiety, as well as social and behavioral challenges have also been reported in some people with tetrasomy 18p.",tetrasomy 18p,0000975,GHR,https://ghr.nlm.nih.gov/condition/tetrasomy-18p,C0795868,T047,Disorders
How many people are affected by tetrasomy 18p ?,0000975-2,frequency,Tetrasomy 18p is a rare disorder. It is known to affect about 250 families worldwide.,tetrasomy 18p,0000975,GHR,https://ghr.nlm.nih.gov/condition/tetrasomy-18p,C0795868,T047,Disorders
What are the genetic changes related to tetrasomy 18p ?,0000975-3,genetic changes,"Tetrasomy 18p results from the presence of an abnormal extra chromosome, called an isochromosome 18p, in each cell. An isochromosome is a chromosome with two identical arms. Normal chromosomes have one long (q) arm and one short (p) arm, but isochromosomes have either two q arms or two p arms. Isochromosome 18p is a version of chromosome 18 made up of two p arms.  Cells normally have two copies of each chromosome, one inherited from each parent. In people with tetrasomy 18p, cells have the usual two copies of chromosome 18 plus an isochromosome 18p. As a result, each cell has four copies of the short arm of chromosome 18. (The word ""tetrasomy"" is derived from ""tetra,"" the Greek word for ""four."") The extra genetic material from the isochromosome disrupts the normal course of development, causing the characteristic features of this disorder.",tetrasomy 18p,0000975,GHR,https://ghr.nlm.nih.gov/condition/tetrasomy-18p,C0795868,T047,Disorders
Is tetrasomy 18p inherited ?,0000975-4,inheritance,"Tetrasomy 18p is usually not inherited. The chromosomal change responsible for the disorder typically occurs as a random event during the formation of reproductive cells (eggs or sperm) in a parent of the affected individual, usually the mother. Most affected individuals have no history of the disorder in their family. However, rare inherited cases of tetrasomy 18p have been reported.",tetrasomy 18p,0000975,GHR,https://ghr.nlm.nih.gov/condition/tetrasomy-18p,C0795868,T047,Disorders
What are the treatments for tetrasomy 18p ?,0000975-5,treatment,"These resources address the diagnosis or management of tetrasomy 18p:  - Chromosome 18 Clinical Research Center, University of Texas Health Science Center at San Antonio  - Genetic Testing Registry: Chromosome 18, tetrasomy 18p   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",tetrasomy 18p,0000975,GHR,https://ghr.nlm.nih.gov/condition/tetrasomy-18p,C0795868,T047,Disorders
What is (are) thanatophoric dysplasia ?,0000976-1,information,"Thanatophoric dysplasia is a severe skeletal disorder characterized by extremely short limbs and folds of extra (redundant) skin on the arms and legs. Other features of this condition include a narrow chest, short ribs, underdeveloped lungs, and an enlarged head with a large forehead and prominent, wide-spaced eyes.  Researchers have described two major forms of thanatophoric dysplasia, type I and type II. Type I thanatophoric dysplasia is distinguished by the presence of curved thigh bones and flattened bones of the spine (platyspondyly). Type II thanatophoric dysplasia is characterized by straight thigh bones and a moderate to severe skull abnormality called a cloverleaf skull.  The term thanatophoric is Greek for ""death bearing."" Infants with thanatophoric dysplasia are usually stillborn or die shortly after birth from respiratory failure; however, a few affected individuals have survived into childhood with extensive medical help.",thanatophoric dysplasia,0000976,GHR,https://ghr.nlm.nih.gov/condition/thanatophoric-dysplasia,C0334044,T019,Disorders
How many people are affected by thanatophoric dysplasia ?,0000976-2,frequency,"This condition occurs in 1 in 20,000 to 50,000 newborns. Type I thanatophoric dysplasia is more common than type II.",thanatophoric dysplasia,0000976,GHR,https://ghr.nlm.nih.gov/condition/thanatophoric-dysplasia,C0334044,T019,Disorders
What are the genetic changes related to thanatophoric dysplasia ?,0000976-3,genetic changes,"Mutations in the FGFR3 gene cause thanatophoric dysplasia. Both types of this condition result from mutations in the FGFR3 gene. This gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. Mutations in this gene cause the FGFR3 protein to be overly active, which leads to the severe disturbances in bone growth that are characteristic of thanatophoric dysplasia. It is not known how FGFR3 mutations cause the brain and skin abnormalities associated with this disorder.",thanatophoric dysplasia,0000976,GHR,https://ghr.nlm.nih.gov/condition/thanatophoric-dysplasia,C0334044,T019,Disorders
Is thanatophoric dysplasia inherited ?,0000976-4,inheritance,"Thanatophoric dysplasia is considered an autosomal dominant disorder because one mutated copy of the FGFR3 gene in each cell is sufficient to cause the condition. Virtually all cases of thanatophoric dysplasia are caused by new mutations in the FGFR3 gene and occur in people with no history of the disorder in their family. No affected individuals are known to have had children; therefore, the disorder has not been passed to the next generation.",thanatophoric dysplasia,0000976,GHR,https://ghr.nlm.nih.gov/condition/thanatophoric-dysplasia,C0334044,T019,Disorders
What are the treatments for thanatophoric dysplasia ?,0000976-5,treatment,"These resources address the diagnosis or management of thanatophoric dysplasia:  - Gene Review: Gene Review: Thanatophoric Dysplasia  - Genetic Testing Registry: Thanatophoric dysplasia type 1  - Genetic Testing Registry: Thanatophoric dysplasia, type 2   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",thanatophoric dysplasia,0000976,GHR,https://ghr.nlm.nih.gov/condition/thanatophoric-dysplasia,C0334044,T019,Disorders
What is (are) thiamine-responsive megaloblastic anemia syndrome ?,0000977-1,information,"Thiamine-responsive megaloblastic anemia syndrome is a rare condition characterized by hearing loss, diabetes, and a blood disorder called megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number of red blood cells (anemia), and the remaining red blood cells are larger than normal (megaloblastic). The symptoms of this blood disorder may include decreased appetite, lack of energy, headaches, pale skin, diarrhea, and tingling or numbness in the hands and feet. Individuals with thiamine-responsive megaloblastic anemia syndrome begin to show symptoms of megaloblastic anemia between infancy and adolescence. This syndrome is called ""thiamine-responsive"" because the anemia can be treated with high doses of vitamin B1 (thiamine).  People with thiamine-responsive megaloblastic anemia syndrome develop hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss) during early childhood. It remains unclear whether thiamine treatment can improve hearing or prevent hearing loss.  Diabetes becomes apparent in affected individuals sometime between infancy and adolescence. Although these individuals develop diabetes during childhood, they do not have the form of the disease that develops most often in children, called type 1 (autoimmune) diabetes. People with thiamine-responsive megaloblastic anemia syndrome usually require insulin to treat their diabetes. In some cases, treatment with thiamine can reduce the amount of insulin a person needs.  Some individuals with thiamine-responsive megaloblastic anemia syndrome develop optic atrophy, which is the degeneration (atrophy) of the nerves that carry information from the eyes to the brain. Heart and blood vessel (cardiovascular) problems such as heart rhythm abnormalities and heart defects have also been reported in some people with this syndrome.",thiamine-responsive megaloblastic anemia syndrome,0000977,GHR,https://ghr.nlm.nih.gov/condition/thiamine-responsive-megaloblastic-anemia-syndrome,C0342287,T019,Disorders
How many people are affected by thiamine-responsive megaloblastic anemia syndrome ?,0000977-2,frequency,Thiamine-responsive megaloblastic anemia syndrome has been reported in approximately 30 families worldwide. Its prevalence is unknown.,thiamine-responsive megaloblastic anemia syndrome,0000977,GHR,https://ghr.nlm.nih.gov/condition/thiamine-responsive-megaloblastic-anemia-syndrome,C0342287,T019,Disorders
What are the genetic changes related to thiamine-responsive megaloblastic anemia syndrome ?,0000977-3,genetic changes,"Mutations in the SLC19A2 gene cause thiamine-responsive megaloblastic anemia syndrome. This gene provides instructions for making a protein called thiamine transporter 1, which transports thiamine into cells. Thiamine is found in many different foods and is important for numerous body functions.  Most mutations in the SLC19A2 gene lead to the production of an abnormally short, nonfunctional thiamine transporter 1. Other mutations change single protein building blocks (amino acids) in this protein. All of these mutations prevent thiamine transporter 1 from bringing thiamine into the cell. It remains unclear how the absence of this protein leads to the seemingly unrelated symptoms of megaloblastic anemia, diabetes, and hearing loss. Research suggests that an alternative method for transporting thiamine is present in all the cells of the body, except where blood cells and insulin are formed (in the bone marrow and pancreas, respectively) and cells in the inner ear.",thiamine-responsive megaloblastic anemia syndrome,0000977,GHR,https://ghr.nlm.nih.gov/condition/thiamine-responsive-megaloblastic-anemia-syndrome,C0342287,T019,Disorders
Is thiamine-responsive megaloblastic anemia syndrome inherited ?,0000977-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",thiamine-responsive megaloblastic anemia syndrome,0000977,GHR,https://ghr.nlm.nih.gov/condition/thiamine-responsive-megaloblastic-anemia-syndrome,C0342287,T019,Disorders
What are the treatments for thiamine-responsive megaloblastic anemia syndrome ?,0000977-5,treatment,"These resources address the diagnosis or management of thiamine-responsive megaloblastic anemia syndrome:  - Gene Review: Gene Review: Thiamine-Responsive Megaloblastic Anemia Syndrome  - Genetic Testing Registry: Megaloblastic anemia, thiamine-responsive, with diabetes mellitus and sensorineural deafness  - MedlinePlus Encyclopedia: Optic nerve atrophy  - MedlinePlus Encyclopedia: Thiamine   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",thiamine-responsive megaloblastic anemia syndrome,0000977,GHR,https://ghr.nlm.nih.gov/condition/thiamine-responsive-megaloblastic-anemia-syndrome,C0342287,T019,Disorders
What is (are) thiopurine S-methyltransferase deficiency ?,0000978-1,information,"Thiopurine S-methyltransferase (TPMT) deficiency is a condition characterized by significantly reduced activity of an enzyme that helps the body process drugs called thiopurines. These drugs, which include 6-thioguanine, 6-mercaptopurine, and azathioprine, inhibit (suppress) the body's immune system. Thiopurine drugs are used to treat some autoimmune disorders, including Crohn disease and rheumatoid arthritis, which occur when the immune system malfunctions. These drugs are also used to treat several forms of cancer, particularly cancers of blood-forming tissue (leukemias) and cancers of immune system cells (lymphomas). Additionally, thiopurine drugs are used in organ transplant recipients to help prevent the immune system from attacking the transplanted organ.  A potential complication of treatment with thiopurine drugs is damage to the bone marrow (hematopoietic toxicity). Although this complication can occur in anyone who takes these drugs, people with TPMT deficiency are at highest risk. Bone marrow normally makes several types of blood cells, including red blood cells, which carry oxygen; white blood cells, which help protect the body from infection; and platelets, which are involved in blood clotting. Damage to the bone marrow results in myelosuppression, a condition in which the bone marrow is unable to make enough of these cells. A shortage of red blood cells (anemia) can cause pale skin (pallor), weakness, shortness of breath, and extreme tiredness (fatigue). Low numbers of white blood cells (neutropenia) can lead to frequent and potentially life-threatening infections. A shortage of platelets (thrombocytopenia) can cause easy bruising and bleeding.  Many healthcare providers recommend that patients' TPMT activity levels be tested before thiopurine drugs are prescribed. In people who are found to have reduced enzyme activity, the drugs may be given at a significantly lower dose or different medications can be used to reduce the risk of hematopoietic toxicity.  TPMT deficiency does not appear to cause any health problems other than those associated with thiopurine drug treatment.",thiopurine S-methyltransferase deficiency,0000978,GHR,https://ghr.nlm.nih.gov/condition/thiopurine-s-methyltransferase-deficiency,C0342801,T047,Disorders
How many people are affected by thiopurine S-methyltransferase deficiency ?,0000978-2,frequency,Studies suggest that less than 1 percent of individuals in the general population have TPMT deficiency. Another 11 percent have moderately reduced levels of TPMT activity that increase their risk of hematopoietic toxicity with thiopurine drug treatment.,thiopurine S-methyltransferase deficiency,0000978,GHR,https://ghr.nlm.nih.gov/condition/thiopurine-s-methyltransferase-deficiency,C0342801,T047,Disorders
What are the genetic changes related to thiopurine S-methyltransferase deficiency ?,0000978-3,genetic changes,"TPMT deficiency results from changes in the TPMT gene. This gene provides instructions for making the TPMT enzyme, which plays a critical role in breaking down (metabolizing) thiopurine drugs. Once inside the body, these drugs are converted to toxic compounds that kill immune system cells in the bone marrow. The TPMT enzyme ""turns off"" thiopurine drugs by breaking them down into inactive, nontoxic compounds. Changes in the TPMT gene reduce the stability and activity of the TPMT enzyme. Without enough of this enzyme, the drugs cannot be ""turned off,"" so they stay in the body longer and continue to destroy cells unchecked. The resulting damage to the bone marrow leads to potentially life-threatening myelosuppression.",thiopurine S-methyltransferase deficiency,0000978,GHR,https://ghr.nlm.nih.gov/condition/thiopurine-s-methyltransferase-deficiency,C0342801,T047,Disorders
Is thiopurine S-methyltransferase deficiency inherited ?,0000978-4,inheritance,"The activity of the TPMT enzyme is inherited in a pattern described as autosomal codominant. Codominance means that two different versions of the gene are active (expressed), and both versions influence the genetic trait.  The TPMT gene can be classified as either low-activity or high-activity. When the gene is altered in a way that impairs the activity of the TPMT enzyme, it is described as low-activity. When the gene is unaltered and TPMT activity is normal, it is described as high-activity. Because two copies of the gene are present in each cell, each person can have two low-activity copies, one low-activity copy and one high-activity copy, or two high-activity copies.  People with two low-activity copies of the TPMT gene in each cell have TPMT deficiency and are at the greatest risk of developing hematopoietic toxicity when treated with thiopurine drugs unless they are given much less than the usual dose. People with one high-activity copy and one low-activity copy have moderately reduced enzyme activity and are also at increased risk of this complication unless given a significantly lower dose of the drug. People with two high-activity copies have normal TPMT activity and do not have an increased risk of hematopoietic toxicity with thiopurine drug treatment.",thiopurine S-methyltransferase deficiency,0000978,GHR,https://ghr.nlm.nih.gov/condition/thiopurine-s-methyltransferase-deficiency,C0342801,T047,Disorders
What are the treatments for thiopurine S-methyltransferase deficiency ?,0000978-5,treatment,These resources address the diagnosis or management of thiopurine S-methyltransferase deficiency:  - MedlinePlus Drug: Azathioprine  - MedlinePlus Drug: Mercaptopurine  - MedlinePlus Drug: Thioguanine   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,thiopurine S-methyltransferase deficiency,0000978,GHR,https://ghr.nlm.nih.gov/condition/thiopurine-s-methyltransferase-deficiency,C0342801,T047,Disorders
What is (are) thrombocytopenia-absent radius syndrome ?,0000979-1,information,"Thrombocytopenia-absent radius (TAR) syndrome is characterized by the absence of a bone called the radius in each forearm. Affected individuals also have a shortage (deficiency) of blood cells involved in clotting (platelets). This platelet deficiency (thrombocytopenia) usually appears during infancy and becomes less severe over time; in some cases the platelet levels become normal.  Thrombocytopenia prevents normal blood clotting, resulting in easy bruising and frequent nosebleeds. Potentially life-threatening episodes of severe bleeding (hemorrhages) may occur in the brain and other organs, especially during the first year of life. Hemorrhages can damage the brain and lead to intellectual disability. Affected children who survive this period and do not have damaging hemorrhages in the brain usually have a normal life expectancy and normal intellectual development.  TAR syndrome is unusual among similar malformations in that affected individuals have thumbs, while people with other conditions involving an absent radius typically do not. TAR syndrome is also associated with short stature and additional skeletal abnormalities, including underdevelopment of other bones in the arms and legs. Affected individuals may also have malformations of the heart and kidneys. TAR syndrome is associated with unusual facial features including a small lower jaw (micrognathia), a prominent forehead, and low-set ears. About half of affected individuals have allergic reactions to cow's milk that may worsen the thrombocytopenia associated with this disorder.",thrombocytopenia-absent radius syndrome,0000979,GHR,https://ghr.nlm.nih.gov/condition/thrombocytopenia-absent-radius-syndrome,C1405984,T190,Disorders
How many people are affected by thrombocytopenia-absent radius syndrome ?,0000979-2,frequency,"TAR syndrome is a rare disorder, affecting fewer than 1 in 100,000 newborns.",thrombocytopenia-absent radius syndrome,0000979,GHR,https://ghr.nlm.nih.gov/condition/thrombocytopenia-absent-radius-syndrome,C1405984,T190,Disorders
What are the genetic changes related to thrombocytopenia-absent radius syndrome ?,0000979-3,genetic changes,"Mutations in the RBM8A gene cause TAR syndrome. The RBM8A gene provides instructions for making a protein called RNA-binding motif protein 8A. This protein is believed to be involved in several important cellular functions involving the production of other proteins.  Most people with TAR syndrome have a mutation in one copy of the RBM8A gene and a deletion of genetic material from chromosome 1 that includes the other copy of the RBM8A gene in each cell. A small number of affected individuals have mutations in both copies of the RBM8A gene in each cell and do not have a deletion on chromosome 1. RBM8A gene mutations that cause TAR syndrome reduce the amount of RNA-binding motif protein 8A in cells. The deletions involved in TAR syndrome eliminate at least 200,000 DNA building blocks (200 kilobases, or 200 kb) from the long (q) arm of chromosome 1 in a region called 1q21.1. The deletion eliminates one copy of the RBM8A gene in each cell and the RNA-binding motif protein 8A that would have been produced from it.  People with either an RBM8A gene mutation and a chromosome 1 deletion or with two gene mutations have a decreased amount of RNA-binding motif protein 8A. This reduction is thought to cause problems in the development of certain tissues, but it is unknown how it causes the specific signs and symptoms of TAR syndrome. No cases have been reported in which a deletion that includes the RBM8A gene occurs on both copies of chromosome 1; studies indicate that the complete loss of RNA-binding motif protein 8A is not compatible with life.  Researchers sometimes refer to the deletion in chromosome 1 associated with TAR syndrome as the 200-kb deletion to distinguish it from another chromosomal abnormality called a 1q21.1 microdeletion. People with a 1q21.1 microdeletion are missing a different, larger DNA segment in the chromosome 1q21.1 region near the area where the 200-kb deletion occurs. The chromosomal change related to 1q21.1 microdeletion is often called the recurrent distal 1.35-Mb deletion.",thrombocytopenia-absent radius syndrome,0000979,GHR,https://ghr.nlm.nih.gov/condition/thrombocytopenia-absent-radius-syndrome,C1405984,T190,Disorders
Is thrombocytopenia-absent radius syndrome inherited ?,0000979-4,inheritance,"TAR syndrome is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell are altered. In this disorder, either both copies of the RBM8A gene in each cell have mutations or, more commonly, one copy of the gene has a mutation and the other is lost as part of a deleted segment on chromosome 1. The affected individual usually inherits an RBM8A gene mutation from one parent. In about 75 percent of cases, the affected person inherits a copy of chromosome 1 with the 200-kb deletion from the other parent. In the remaining cases, the deletion occurs during the formation of reproductive cells (eggs and sperm) or in early fetal development. Although parents of an individual with TAR syndrome can carry an RBM8A gene mutation or a 200-kb deletion, they typically do not show signs and symptoms of the condition.",thrombocytopenia-absent radius syndrome,0000979,GHR,https://ghr.nlm.nih.gov/condition/thrombocytopenia-absent-radius-syndrome,C1405984,T190,Disorders
What are the treatments for thrombocytopenia-absent radius syndrome ?,0000979-5,treatment,These resources address the diagnosis or management of TAR syndrome:  - Gene Review: Gene Review: Thrombocytopenia Absent Radius Syndrome  - Genetic Testing Registry: Radial aplasia-thrombocytopenia syndrome  - MedlinePlus Encyclopedia: Skeletal Limb Abnormalities   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,thrombocytopenia-absent radius syndrome,0000979,GHR,https://ghr.nlm.nih.gov/condition/thrombocytopenia-absent-radius-syndrome,C1405984,T190,Disorders
What is (are) thrombotic thrombocytopenic purpura ?,0000980-1,information,"Thrombotic thrombocytopenic purpura is a rare disorder that causes blood clots (thrombi) to form in small blood vessels throughout the body. These clots can cause serious medical problems if they block vessels and restrict blood flow to organs such as the brain, kidneys, and heart. Resulting complications can include neurological problems (such as personality changes, headaches, confusion, and slurred speech), fever, abnormal kidney function, abdominal pain, and heart problems.  Blood clots normally form to prevent excess blood loss at the site of an injury. In people with thrombotic thrombocytopenic purpura, clots develop in blood vessels even in the absence of injury. Blood clots are formed from clumps of cell fragments called platelets, which circulate in the blood and assist with clotting. Because a large number of platelets are used to make clots in people with thrombotic thrombocytopenic purpura, fewer platelets are available in the bloodstream. A reduced level of circulating platelets is known as thrombocytopenia. Thrombocytopenia can lead to small areas of bleeding just under the surface of the skin, resulting in purplish spots called purpura.  This disorder also causes red blood cells to break down (undergo hemolysis) prematurely. As blood squeezes past clots within blood vessels, red blood cells can break apart. A condition called hemolytic anemia occurs when red blood cells are destroyed faster than the body can replace them. This type of anemia leads to paleness, yellowing of the eyes and skin (jaundice), fatigue, shortness of breath, and a rapid heart rate.  There are two major forms of thrombotic thrombocytopenic purpura, an acquired (noninherited) form and a familial form. The acquired form usually appears in late childhood or adulthood. Affected individuals may have a single episode of signs and symptoms, or they may recur over time. The familial form of this disorder is much rarer and typically appears in infancy or early childhood. In people with the familial form, signs and symptoms often recur on a regular basis.",thrombotic thrombocytopenic purpura,0000980,GHR,https://ghr.nlm.nih.gov/condition/thrombotic-thrombocytopenic-purpura,C0034150,T047,Disorders
How many people are affected by thrombotic thrombocytopenic purpura ?,0000980-2,frequency,"The precise incidence of thrombotic thrombocytopenic purpura is unknown. Researchers estimate that, depending on geographic location, the condition affects 1.7 to 11 per million people each year in the United States. For unknown reasons, the disorder occurs more frequently in women than in men. The acquired form of thrombotic thrombocytopenic purpura is much more common than the familial form.",thrombotic thrombocytopenic purpura,0000980,GHR,https://ghr.nlm.nih.gov/condition/thrombotic-thrombocytopenic-purpura,C0034150,T047,Disorders
What are the genetic changes related to thrombotic thrombocytopenic purpura ?,0000980-3,genetic changes,"Mutations in the ADAMTS13 gene cause the familial form of thrombotic thrombocytopenic purpura. The ADAMTS13 gene provides instructions for making an enzyme that is involved in the normal process of blood clotting. Mutations in this gene lead to a severe reduction in the activity of this enzyme. The acquired form of thrombotic thrombocytopenic purpura also results from a reduction in ADAMTS13 enzyme activity; however, people with the acquired form do not have mutations in the ADAMTS13 gene. Instead, their immune systems often produce specific proteins called autoantibodies that block the activity of the enzyme.  A lack of ADAMTS13 enzyme activity disrupts the usual balance between bleeding and clotting. Normally, blood clots form at the site of an injury to seal off damaged blood vessels and prevent excess blood loss. In people with thrombotic thrombocytopenic purpura, clots form throughout the body as platelets bind together abnormally and stick to the walls of blood vessels. These clots can block small blood vessels, causing organ damage and the other features of thrombotic thrombocytopenic purpura.  Researchers believe that other genetic or environmental factors may contribute to the signs and symptoms of thrombotic thrombocytopenic purpura. In people with reduced ADAMTS13 enzyme activity, factors such as pregnancy, surgery, and infection may trigger abnormal blood clotting and its associated complications.",thrombotic thrombocytopenic purpura,0000980,GHR,https://ghr.nlm.nih.gov/condition/thrombotic-thrombocytopenic-purpura,C0034150,T047,Disorders
Is thrombotic thrombocytopenic purpura inherited ?,0000980-4,inheritance,"The familial form of thrombotic thrombocytopenic purpura is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  The acquired form of thrombotic thrombocytopenic purpura is not inherited.",thrombotic thrombocytopenic purpura,0000980,GHR,https://ghr.nlm.nih.gov/condition/thrombotic-thrombocytopenic-purpura,C0034150,T047,Disorders
What are the treatments for thrombotic thrombocytopenic purpura ?,0000980-5,treatment,These resources address the diagnosis or management of thrombotic thrombocytopenic purpura:  - Genetic Testing Registry: Upshaw-Schulman syndrome  - MedlinePlus Encyclopedia: Blood Clots  - MedlinePlus Encyclopedia: Hemolytic anemia  - MedlinePlus Encyclopedia: Purpura  - MedlinePlus Encyclopedia: Thrombocytopenia  - MedlinePlus Encyclopedia: Thrombotic thrombocytopenic purpura   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,thrombotic thrombocytopenic purpura,0000980,GHR,https://ghr.nlm.nih.gov/condition/thrombotic-thrombocytopenic-purpura,C0034150,T047,Disorders
What is (are) tibial muscular dystrophy ?,0000981-1,information,"Tibial muscular dystrophy is a condition that affects the muscles at the front of the lower leg. The signs and symptoms of this condition typically appear after age 35. The first sign is usually weakness and wasting (atrophy) of a muscle in the lower leg called the tibialis anterior. This muscle helps control up-and-down movement of the foot. Weakness in the tibialis anterior muscle makes it difficult or impossible to walk on the heels, but it usually does not interfere significantly with regular walking.  Muscle weakness worsens very slowly in people with tibial muscular dystrophy. Ten to 20 years after the onset of symptoms, weakness may develop in muscles that help extend the toes (long-toe extensors). Weakness in these muscles makes it difficult to lift the toes while walking, a condition known as foot drop. Later in life, about one third of people with tibial muscular dystrophy experience mild to moderate difficulty with walking because of weakness in other leg muscles. However, most affected individuals remain able to walk throughout their lives.  A small percentage of people with tibial muscular dystrophy have a somewhat different pattern of signs and symptoms than those described above. Starting in childhood, these individuals may have generalized muscle weakness, weakness and atrophy of the thigh muscles (quadriceps) or other muscles in the legs, and weakness affecting muscles in the arms.",tibial muscular dystrophy,0000981,GHR,https://ghr.nlm.nih.gov/condition/tibial-muscular-dystrophy,C1450052,T047,Disorders
How many people are affected by tibial muscular dystrophy ?,0000981-2,frequency,"Tibial muscular dystrophy is most common in Finland, where it is estimated to affect at least 10 per 100,000 people. This condition has also been found in people of Finnish descent living in other countries.  Additionally, tibial muscular dystrophy has been identified in several European families without Finnish ancestry.",tibial muscular dystrophy,0000981,GHR,https://ghr.nlm.nih.gov/condition/tibial-muscular-dystrophy,C1450052,T047,Disorders
What are the genetic changes related to tibial muscular dystrophy ?,0000981-3,genetic changes,"Mutations in the TTN gene cause tibial muscular dystrophy. This gene provides instructions for making a protein called titin. Titin plays an important role in muscles the body uses for movement (skeletal muscles) and in heart (cardiac) muscle.  Within muscle cells, titin is an essential component of structures called sarcomeres. Sarcomeres are the basic units of muscle contraction; they are made of proteins that generate the mechanical force needed for muscles to contract. Titin has several functions within sarcomeres. One of its most important jobs is to provide structure, flexibility, and stability to these cell structures. Titin also plays a role in chemical signaling and in assembling new sarcomeres.  Mutations in the TTN gene alter the structure and function of titin. Researchers suspect that these changes may disrupt titin's interactions with other proteins within sarcomeres. Mutations may also interfere with the protein's role in chemical signaling. The altered titin protein disrupts normal muscle contraction, which causes muscles to weaken and waste away over time. It is unclear why these effects are usually limited to muscles in the lower legs.",tibial muscular dystrophy,0000981,GHR,https://ghr.nlm.nih.gov/condition/tibial-muscular-dystrophy,C1450052,T047,Disorders
Is tibial muscular dystrophy inherited ?,0000981-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",tibial muscular dystrophy,0000981,GHR,https://ghr.nlm.nih.gov/condition/tibial-muscular-dystrophy,C1450052,T047,Disorders
What are the treatments for tibial muscular dystrophy ?,0000981-5,treatment,These resources address the diagnosis or management of tibial muscular dystrophy:  - Gene Review: Gene Review: Udd Distal Myopathy  - Genetic Testing Registry: Distal myopathy Markesbery-Griggs type   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,tibial muscular dystrophy,0000981,GHR,https://ghr.nlm.nih.gov/condition/tibial-muscular-dystrophy,C1450052,T047,Disorders
What is (are) Tietz syndrome ?,0000982-1,information,"Tietz syndrome is a disorder characterized by profound hearing loss from birth, fair skin, and light-colored hair. The hearing loss in affected individuals is caused by abnormalities of the inner ear (sensorineural hearing loss) and is present from birth. Although people with Tietz syndrome are born with white hair and very pale skin, their hair color often darkens over time to blond or red. The skin of affected individuals, which sunburns very easily, may tan slightly or develop reddish freckles with limited sun exposure; however, their skin and hair color remain lighter than those of other members of their family.  Tietz syndrome also affects the eyes. The colored part of the eye (the iris) in affected individuals is blue, and specialized cells in the eye called retinal pigment epithelial cells lack their normal pigment. The retinal pigment epithelium nourishes the retina, the part of the eye that detects light and color. The changes to the retinal pigment epithelium are generally detectable only by an eye examination; it is unclear whether the changes affect vision.",Tietz syndrome,0000982,GHR,https://ghr.nlm.nih.gov/condition/tietz-syndrome,C0391816,T047,Disorders
How many people are affected by Tietz syndrome ?,0000982-2,frequency,Tietz syndrome is a rare disorder; its exact prevalence is unknown. Only a few affected families have been described in the medical literature.,Tietz syndrome,0000982,GHR,https://ghr.nlm.nih.gov/condition/tietz-syndrome,C0391816,T047,Disorders
What are the genetic changes related to Tietz syndrome ?,0000982-3,genetic changes,"Tietz syndrome is caused by mutations in the MITF gene. This gene provides instructions for making a protein that plays a role in the development, survival, and function of certain types of cells. Molecules of the MITF protein attach (bind) to each other or with other proteins that have a similar structure, creating a two-protein unit (dimer). The dimer attaches to specific areas of DNA and helps control the activity of particular genes. On the basis of this action, the MITF protein is called a transcription factor.  The MITF protein helps control the development and function of pigment-producing cells called melanocytes. Within these cells, this protein controls production of the pigment melanin, which contributes to hair, eye, and skin color. Melanocytes are also found in the inner ear and play an important role in hearing. Additionally, the MITF protein regulates the development of the retinal pigment epithelium.  MITF gene mutations that cause Tietz syndrome either delete or change a single protein building block (amino acid) in an area of the MITF protein known as the basic motif region. Dimers incorporating the abnormal MITF protein cannot be transported into the cell nucleus to bind with DNA. As a result, most of the dimers are unavailable to bind to DNA, which affects the development of melanocytes and the production of melanin. The resulting reduction or absence of melanocytes in the inner ear leads to hearing loss. Decreased melanin production (hypopigmentation) accounts for the light skin and hair color and the retinal pigment epithelium changes that are characteristic of Tietz syndrome.  Researchers suggest that Tietz syndrome may represent a severe form of a disorder called Waardenburg syndrome, which can also be caused by MITF gene mutations.",Tietz syndrome,0000982,GHR,https://ghr.nlm.nih.gov/condition/tietz-syndrome,C0391816,T047,Disorders
Is Tietz syndrome inherited ?,0000982-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.",Tietz syndrome,0000982,GHR,https://ghr.nlm.nih.gov/condition/tietz-syndrome,C0391816,T047,Disorders
What are the treatments for Tietz syndrome ?,0000982-5,treatment,These resources address the diagnosis or management of Tietz syndrome:  - Genetic Testing Registry: Tietz syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Tietz syndrome,0000982,GHR,https://ghr.nlm.nih.gov/condition/tietz-syndrome,C0391816,T047,Disorders
What is (are) Timothy syndrome ?,0000983-1,information,"Timothy syndrome is a rare disorder that affects many parts of the body including the heart, digits (fingers and toes), and the nervous system.  Timothy syndrome is characterized by a heart condition called long QT syndrome, which causes the heart (cardiac) muscle to take longer than usual to recharge between beats. This abnormality in the heart's electrical system can cause irregular heartbeats (arrhythmia), which can lead to sudden death. Many people with Timothy syndrome are also born with structural heart defects that affect the heart's ability to pump blood effectively. As a result of these serious heart problems, many people with Timothy syndrome live only into childhood. The most common cause of death is a form of arrhythmia called ventricular tachyarrhythmia, in which the lower chambers of the heart (the ventricles) beat abnormally fast and lead to cardiac arrest.  Timothy syndrome is also characterized by webbing or fusion of the skin between some fingers or toes (cutaneous syndactyly). About half of affected people have distinctive facial features such as a flattened nasal bridge, low-set ears, a small upper jaw, and a thin upper lip. Children with this condition have small, misplaced teeth and frequent cavities (dental caries). Additional signs and symptoms of Timothy syndrome can include baldness at birth, frequent infections, episodes of low blood sugar (hypoglycemia), and an abnormally low body temperature (hypothermia).  Researchers have found that many children with Timothy syndrome have the characteristic features of autism or similar conditions known as autistic spectrum disorders. Affected children tend to have impaired communication and socialization skills, as well as delayed development of speech and language. Other nervous system abnormalities, including intellectual disability and seizures, can also occur in children with Timothy syndrome.  Researchers have identified two forms of Timothy syndrome. Type 1, which is also known as the classic type, includes all of the characteristic features described above. Type 2, or the atypical type, causes a more severe form of long QT syndrome and a greater risk of arrhythmia and sudden death. Unlike the classic type, the atypical type does not appear to cause webbing of the fingers or toes.",Timothy syndrome,0000983,GHR,https://ghr.nlm.nih.gov/condition/timothy-syndrome,C1832916,T047,Disorders
How many people are affected by Timothy syndrome ?,0000983-2,frequency,"Timothy syndrome is a rare condition; fewer than 20 people with this disorder have been reported worldwide. The classic type of Timothy syndrome appears to be more common than the atypical type, which has been identified in only two individuals.",Timothy syndrome,0000983,GHR,https://ghr.nlm.nih.gov/condition/timothy-syndrome,C1832916,T047,Disorders
What are the genetic changes related to Timothy syndrome ?,0000983-3,genetic changes,"Mutations in the CACNA1C gene are responsible for all reported cases of Timothy syndrome. This gene provides instructions for making a protein that acts as a channel across cell membranes. This channel, known as CaV1.2, is one of several channels that transport positively charged calcium atoms (calcium ions) into cells. Calcium ions are involved in many different cellular functions, including cell-to-cell communication, the tensing of muscle fibers (muscle contraction), and the regulation of certain genes. CaV1.2 calcium channels are particularly important for the normal function of heart and brain cells. In cardiac muscle, these channels play a critical role in maintaining the heart's normal rhythm. Their role in the brain and in other tissues is less clear.  Mutations in the CACNA1C gene change the structure of CaV1.2 channels. The altered channels stay open much longer than usual, which allows calcium ions to continue flowing into cells abnormally. The resulting overload of calcium ions within cardiac muscle cells changes the way the heart beats and can cause arrhythmia. Researchers are working to determine how an increase in calcium ion transport in other tissues, including cells in the brain, underlies the other features of Timothy syndrome.",Timothy syndrome,0000983,GHR,https://ghr.nlm.nih.gov/condition/timothy-syndrome,C1832916,T047,Disorders
Is Timothy syndrome inherited ?,0000983-4,inheritance,"This condition is considered to have an autosomal dominant pattern of inheritance, which means one copy of the altered CACNA1C gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the gene, and occur in people with no history of the disorder in their family. Less commonly, people with Timothy syndrome inherit the altered gene from an unaffected parent who is mosaic for a CACNA1C mutation. Mosaicism means that the parent has the mutation in some cells (including egg or sperm cells), but not in others.",Timothy syndrome,0000983,GHR,https://ghr.nlm.nih.gov/condition/timothy-syndrome,C1832916,T047,Disorders
What are the treatments for Timothy syndrome ?,0000983-5,treatment,These resources address the diagnosis or management of Timothy syndrome:  - Gene Review: Gene Review: Timothy Syndrome  - Genetic Testing Registry: Timothy syndrome  - MedlinePlus Encyclopedia: Arrhythmias  - MedlinePlus Encyclopedia: Congenital Heart Disease  - MedlinePlus Encyclopedia: Webbing of the Fingers or Toes   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Timothy syndrome,0000983,GHR,https://ghr.nlm.nih.gov/condition/timothy-syndrome,C1832916,T047,Disorders
"What is (are) TK2-related mitochondrial DNA depletion syndrome, myopathic form ?",0000984-1,information,"TK2-related mitochondrial DNA depletion syndrome, myopathic form (TK2-MDS) is an inherited condition that causes progressive muscle weakness (myopathy).  The signs and symptoms of TK2-MDS typically begin in early childhood. Development is usually normal early in life, but as muscle weakness progresses, people with TK2-MDS lose motor skills such as standing, walking, eating, and talking. Some affected individuals have increasing weakness in the muscles that control eye movement, leading to droopy eyelids (progressive external ophthalmoplegia).  Most often in TK2-MDS, the muscles are the only affected tissues; however, the liver may be enlarged (hepatomegaly), seizures can occur, and hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss) may be present. Intelligence is usually not affected.  As the disorder worsens, the muscles that control breathing become weakened and affected individuals frequently have to rely on mechanical ventilation. Respiratory failure is the most common cause of death in people with TK2-MDS, often occurring in childhood. Rarely, the disorder progresses slowly and affected individuals survive into adolescence or adulthood.","TK2-related mitochondrial DNA depletion syndrome, myopathic form",0000984,GHR,https://ghr.nlm.nih.gov/condition/tk2-related-mitochondrial-dna-depletion-syndrome-myopathic-form,C3501891,T047,Disorders
"How many people are affected by TK2-related mitochondrial DNA depletion syndrome, myopathic form ?",0000984-2,frequency,The prevalence of TK2-MDS is unknown. Approximately 45 cases have been described.,"TK2-related mitochondrial DNA depletion syndrome, myopathic form",0000984,GHR,https://ghr.nlm.nih.gov/condition/tk2-related-mitochondrial-dna-depletion-syndrome-myopathic-form,C3501891,T047,Disorders
"What are the genetic changes related to TK2-related mitochondrial DNA depletion syndrome, myopathic form ?",0000984-3,genetic changes,"As the condition name suggests, mutations in the TK2 gene cause TK2-MDS. The TK2 gene provides instructions for making an enzyme called thymidine kinase 2 that functions within cell structures called mitochondria, which are found in all tissues. Mitochondria are involved in a wide variety of cellular activities, including energy production; chemical signaling; and regulation of cell growth, cell division, and cell death. Mitochondria contain their own genetic material, known as mitochondrial DNA (mtDNA), which is essential for the normal function of these structures. Thymidine kinase 2 is involved in the production and maintenance of mtDNA. Specifically, this enzyme plays a role in recycling mtDNA building blocks (nucleotides) so that errors in mtDNA sequencing can be repaired and new mtDNA molecules can be produced.  Mutations in the TK2 gene reduce the production or activity of thymidine kinase 2. A decrease in enzyme activity impairs recycling of mtDNA nucleotides, causing a shortage of nucleotides available for the repair and production of mtDNA molecules. A reduction in the amount of mtDNA (known as mtDNA depletion) impairs mitochondrial function. Greater mtDNA depletion tends to cause more severe signs and symptoms. The muscle cells of people with TK2-MDS have very low amounts of mtDNA, ranging from 5 to 30 percent of normal. Other tissues can have 60 percent of normal to normal amounts of mtDNA.  It is unclear why TK2 gene mutations typically affect only muscle tissue, but the high energy demands of muscle cells may make them the most susceptible to cell death when mtDNA is lost and less energy is produced in cells. The brain and the liver also have high energy demands, which may explain why these organs are affected in severe cases of TK2-MDS.","TK2-related mitochondrial DNA depletion syndrome, myopathic form",0000984,GHR,https://ghr.nlm.nih.gov/condition/tk2-related-mitochondrial-dna-depletion-syndrome-myopathic-form,C3501891,T047,Disorders
"Is TK2-related mitochondrial DNA depletion syndrome, myopathic form inherited ?",0000984-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.","TK2-related mitochondrial DNA depletion syndrome, myopathic form",0000984,GHR,https://ghr.nlm.nih.gov/condition/tk2-related-mitochondrial-dna-depletion-syndrome-myopathic-form,C3501891,T047,Disorders
"What are the treatments for TK2-related mitochondrial DNA depletion syndrome, myopathic form ?",0000984-5,treatment,"These resources address the diagnosis or management of TK2-related mitochondrial DNA depletion syndrome, myopathic form:  - Cincinnati Children's Hospital: Mitochondrial Diseases Program  - Gene Review: Gene Review: TK2-Related Mitochondrial DNA Depletion Syndrome, Myopathic Form   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","TK2-related mitochondrial DNA depletion syndrome, myopathic form",0000984,GHR,https://ghr.nlm.nih.gov/condition/tk2-related-mitochondrial-dna-depletion-syndrome-myopathic-form,C3501891,T047,Disorders
What is (are) Tourette syndrome ?,0000985-1,information,"Tourette syndrome is a complex disorder characterized by repetitive, sudden, and involuntary movements or noises called tics. Tics usually appear in childhood, and their severity varies over time. In most cases, tics become milder and less frequent in late adolescence and adulthood.  Tourette syndrome involves both motor tics, which are uncontrolled body movements, and vocal or phonic tics, which are outbursts of sound. Some motor tics are simple and involve only one muscle group. Simple motor tics, such as rapid eye blinking, shoulder shrugging, or nose twitching, are usually the first signs of Tourette syndrome. Motor tics also can be complex (involving multiple muscle groups), such as jumping, kicking, hopping, or spinning.  Vocal tics, which generally appear later than motor tics, also can be simple or complex. Simple vocal tics include grunting, sniffing, and throat-clearing. More complex vocalizations include repeating the words of others (echolalia) or repeating one's own words (palilalia). The involuntary use of inappropriate or obscene language (coprolalia) is possible, but uncommon, among people with Tourette syndrome.  In addition to frequent tics, people with Tourette syndrome are at risk for associated problems including attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, depression, and problems with sleep.",Tourette syndrome,0000985,GHR,https://ghr.nlm.nih.gov/condition/tourette-syndrome,C0040517,T047,Disorders
How many people are affected by Tourette syndrome ?,0000985-2,frequency,"Although the exact incidence of Tourette syndrome is uncertain, it is estimated to affect 1 to 10 in 1,000 children. This disorder occurs in populations and ethnic groups worldwide, and it is more common in males than in females.",Tourette syndrome,0000985,GHR,https://ghr.nlm.nih.gov/condition/tourette-syndrome,C0040517,T047,Disorders
What are the genetic changes related to Tourette syndrome ?,0000985-3,genetic changes,"A variety of genetic and environmental factors likely play a role in causing Tourette syndrome. Most of these factors are unknown, and researchers are studying risk factors before and after birth that may contribute to this complex disorder. Scientists believe that tics may result from changes in brain chemicals (neurotransmitters) that are responsible for producing and controlling voluntary movements.  Mutations involving the SLITRK1 gene have been identified in a small number of people with Tourette syndrome. This gene provides instructions for making a protein that is active in the brain. The SLITRK1 protein probably plays a role in the development of nerve cells, including the growth of specialized extensions (axons and dendrites) that allow each nerve cell to communicate with nearby cells. It is unclear how mutations in the SLITRK1 gene can lead to this disorder.  Most people with Tourette syndrome do not have a mutation in the SLITRK1 gene. Because mutations have been reported in so few people with this condition, the association of the SLITRK1 gene with this disorder has not been confirmed. Researchers suspect that changes in other genes, which have not been identified, are also associated with Tourette syndrome.",Tourette syndrome,0000985,GHR,https://ghr.nlm.nih.gov/condition/tourette-syndrome,C0040517,T047,Disorders
Is Tourette syndrome inherited ?,0000985-4,inheritance,"The inheritance pattern of Tourette syndrome is unclear. Although the features of this condition can cluster in families, many genetic and environmental factors are likely to be involved. Among family members of an affected person, it is difficult to predict who else may be at risk of developing the condition.  Tourette syndrome was previously thought to have an autosomal dominant pattern of inheritance, which suggests that one mutated copy of a gene in each cell would be sufficient to cause the condition. Several decades of research have shown that this is not the case. Almost all cases of Tourette syndrome probably result from a variety of genetic and environmental factors, not changes in a single gene.",Tourette syndrome,0000985,GHR,https://ghr.nlm.nih.gov/condition/tourette-syndrome,C0040517,T047,Disorders
What are the treatments for Tourette syndrome ?,0000985-5,treatment,These resources address the diagnosis or management of Tourette syndrome:  - Gene Review: Gene Review: Tourette Disorder Overview  - Genetic Testing Registry: Tourette Syndrome  - MedlinePlus Encyclopedia: Gilles de la Tourette syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Tourette syndrome,0000985,GHR,https://ghr.nlm.nih.gov/condition/tourette-syndrome,C0040517,T047,Disorders
What is (are) Townes-Brocks Syndrome ?,0000986-1,information,"Townes-Brocks syndrome is a genetic condition that affects several parts of the body. The most common features of this condition are an obstruction of the anal opening (imperforate anus), abnormally shaped ears, and hand malformations that most often affect the thumb. Most people with this condition have at least two of these three major features.  Other possible signs and symptoms of Townes-Brocks syndrome include kidney abnormalities, mild to profound hearing loss, heart defects, and genital malformations. These features vary among affected individuals, even within the same family. Intellectual disability or learning problems have also been reported in about 10 percent of people with Townes-Brocks syndrome.",Townes-Brocks Syndrome,0000986,GHR,https://ghr.nlm.nih.gov/condition/townes-brocks-syndrome,C0265246,T019,Disorders
How many people are affected by Townes-Brocks Syndrome ?,0000986-2,frequency,"The prevalence of this condition is unknown, although one study estimated that it may affect 1 in 250,000 people. It is difficult to determine how frequently Townes-Brocks syndrome occurs because the varied signs and symptoms of this disorder overlap with those of other genetic syndromes.",Townes-Brocks Syndrome,0000986,GHR,https://ghr.nlm.nih.gov/condition/townes-brocks-syndrome,C0265246,T019,Disorders
What are the genetic changes related to Townes-Brocks Syndrome ?,0000986-3,genetic changes,"Mutations in the SALL1 gene cause Townes-Brocks Syndrome. The SALL1 gene is part of a group of genes called the SALL family. These genes provide instructions for making proteins that are involved in the formation of tissues and organs before birth. SALL proteins act as transcription factors, which means they attach (bind) to specific regions of DNA and help control the activity of particular genes. Some mutations in the SALL1 gene lead to the production of an abnormally short version of the SALL1 protein that malfunctions within the cell. Other mutations prevent one copy of the gene in each cell from making any protein. It is unclear how these genetic changes disrupt normal development and cause the birth defects associated with Townes-Brocks syndrome.",Townes-Brocks Syndrome,0000986,GHR,https://ghr.nlm.nih.gov/condition/townes-brocks-syndrome,C0265246,T019,Disorders
Is Townes-Brocks Syndrome inherited ?,0000986-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Townes-Brocks Syndrome,0000986,GHR,https://ghr.nlm.nih.gov/condition/townes-brocks-syndrome,C0265246,T019,Disorders
What are the treatments for Townes-Brocks Syndrome ?,0000986-5,treatment,These resources address the diagnosis or management of Townes-Brocks Syndrome:  - Gene Review: Gene Review: Townes-Brocks Syndrome  - Genetic Testing Registry: Townes syndrome  - MedlinePlus Encyclopedia: Ear Disorders (image)  - MedlinePlus Encyclopedia: Imperforate Anus   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Townes-Brocks Syndrome,0000986,GHR,https://ghr.nlm.nih.gov/condition/townes-brocks-syndrome,C0265246,T019,Disorders
What is (are) transthyretin amyloidosis ?,0000988-1,information,"Transthyretin amyloidosis is a slowly progressive condition characterized by the buildup of abnormal deposits of a protein called amyloid (amyloidosis) in the body's organs and tissues. These protein deposits most frequently occur in the peripheral nervous system, which is made up of nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound. Protein deposits in these nerves result in a loss of sensation in the extremities (peripheral neuropathy). The autonomic nervous system, which controls involuntary body functions such as blood pressure, heart rate, and digestion, may also be affected by amyloidosis. In some cases, the brain and spinal cord (central nervous system) are affected. Other areas of amyloidosis include the heart, kidneys, eyes, and gastrointestinal tract. The age at which symptoms begin to develop varies widely among individuals with this condition, and is typically between ages 20 and 70.  There are three major forms of transthyretin amyloidosis, which are distinguished by their symptoms and the body systems they affect.  The neuropathic form of transthyretin amyloidosis primarily affects the peripheral and autonomic nervous systems, resulting in peripheral neuropathy and difficulty controlling bodily functions. Impairments in bodily functions can include sexual impotence, diarrhea, constipation, problems with urination, and a sharp drop in blood pressure upon standing (orthostatic hypotension). Some people experience heart and kidney problems as well. Various eye problems may occur, such as cloudiness of the clear gel that fills the eyeball (vitreous opacity), dry eyes, increased pressure in the eyes (glaucoma), or pupils with an irregular or ""scalloped"" appearance. Some people with this form of transthyretin amyloidosis develop carpal tunnel syndrome, which is characterized by numbness, tingling, and weakness in the hands and fingers.  The leptomeningeal form of transthyretin amyloidosis primarily affects the central nervous system. In people with this form, amyloidosis occurs in the leptomeninges, which are two thin layers of tissue that cover the brain and spinal cord. A buildup of protein in this tissue can cause stroke and bleeding in the brain, an accumulation of fluid in the brain (hydrocephalus), difficulty coordinating movements (ataxia), muscle stiffness and weakness (spastic paralysis), seizures, and loss of intellectual function (dementia). Eye problems similar to those in the neuropathic form may also occur. When people with leptomeningeal transthyretin amyloidosis have associated eye problems, they are said to have the oculoleptomeningeal form.  The cardiac form of transthyretin amyloidosis affects the heart. People with cardiac amyloidosis may have an abnormal heartbeat (arrhythmia), an enlarged heart (cardiomegaly), or orthostatic hypertension. These abnormalities can lead to progressive heart failure and death. Occasionally, people with the cardiac form of transthyretin amyloidosis have mild peripheral neuropathy.",transthyretin amyloidosis,0000988,GHR,https://ghr.nlm.nih.gov/condition/transthyretin-amyloidosis,C2751492,T047,Disorders
How many people are affected by transthyretin amyloidosis ?,0000988-2,frequency,"The exact incidence of transthyretin amyloidosis is unknown. In northern Portugal, the incidence of this condition is thought to be one in 538 people. Transthyretin amyloidosis is less common among Americans of European descent, where it is estimated to affect one in 100,000 people. The cardiac form of transthyretin amyloidosis is more common among people with African ancestry. It is estimated that this form affects between 3 percent and 3.9 percent of African Americans and approximately 5 percent of people in some areas of West Africa.",transthyretin amyloidosis,0000988,GHR,https://ghr.nlm.nih.gov/condition/transthyretin-amyloidosis,C2751492,T047,Disorders
What are the genetic changes related to transthyretin amyloidosis ?,0000988-3,genetic changes,"Mutations in the TTR gene cause transthyretin amyloidosis. The TTR gene provides instructions for producing a protein called transthyretin. Transthyretin transports vitamin A (retinol) and a hormone called thyroxine throughout the body. To transport retinol and thyroxine, four transthyretin proteins must be attached (bound) to each other to form a four-protein unit (tetramer). Transthyretin is produced primarily in the liver. A small amount of this protein is produced in an area of the brain called the choroid plexus and in the light-sensitive tissue that lines the back of the eye (the retina).  TTR gene mutations are thought to alter the structure of transthyretin, impairing its ability to bind to other transthyretin proteins and altering its normal function.",transthyretin amyloidosis,0000988,GHR,https://ghr.nlm.nih.gov/condition/transthyretin-amyloidosis,C2751492,T047,Disorders
Is transthyretin amyloidosis inherited ?,0000988-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In most cases, an affected person inherits the mutation from one affected parent. Rarely, cases result from new mutations in the gene and occur in people with no history of the disorder in their family. Not all people who have a TTR gene mutation will develop transthyretin amyloidosis.",transthyretin amyloidosis,0000988,GHR,https://ghr.nlm.nih.gov/condition/transthyretin-amyloidosis,C2751492,T047,Disorders
What are the treatments for transthyretin amyloidosis ?,0000988-5,treatment,These resources address the diagnosis or management of transthyretin amyloidosis:  - Boston University: Amyloid Treatment & Research Program  - Gene Review: Gene Review: Familial Transthyretin Amyloidosis  - Genetic Testing Registry: Amyloidogenic transthyretin amyloidosis  - MedlinePlus Encyclopedia: Autonomic neuropathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,transthyretin amyloidosis,0000988,GHR,https://ghr.nlm.nih.gov/condition/transthyretin-amyloidosis,C2751492,T047,Disorders
What is (are) Treacher Collins syndrome ?,0000989-1,information,"Treacher Collins syndrome is a condition that affects the development of bones and other tissues of the face. The signs and symptoms of this disorder vary greatly, ranging from almost unnoticeable to severe. Most affected individuals have underdeveloped facial bones, particularly the cheek bones, and a very small jaw and chin (micrognathia). Some people with this condition are also born with an opening in the roof of the mouth called a cleft palate. In severe cases, underdevelopment of the facial bones may restrict an affected infant's airway, causing potentially life-threatening respiratory problems.  People with Treacher Collins syndrome often have eyes that slant downward, sparse eyelashes, and a notch in the lower eyelids called an eyelid coloboma. Some affected individuals have additional eye abnormalities that can lead to vision loss. This condition is also characterized by absent, small, or unusually formed ears. Hearing loss occurs in about half of all affected individuals; hearing loss is caused by defects of the three small bones in the middle ear, which transmit sound, or by underdevelopment of the ear canal. People with Treacher Collins syndrome usually have normal intelligence.",Treacher Collins syndrome,0000989,GHR,https://ghr.nlm.nih.gov/condition/treacher-collins-syndrome,C0242387,T019,Disorders
How many people are affected by Treacher Collins syndrome ?,0000989-2,frequency,"This condition affects an estimated 1 in 50,000 people.",Treacher Collins syndrome,0000989,GHR,https://ghr.nlm.nih.gov/condition/treacher-collins-syndrome,C0242387,T019,Disorders
What are the genetic changes related to Treacher Collins syndrome ?,0000989-3,genetic changes,"Mutations in the TCOF1, POLR1C, or POLR1D gene can cause Treacher Collins syndrome. TCOF1 gene mutations are the most common cause of the disorder, accounting for 81 to 93 percent of all cases. POLR1C and POLR1D gene mutations cause an additional 2 percent of cases. In individuals without an identified mutation in one of these genes, the genetic cause of the condition is unknown.  The proteins produced from the TCOF1, POLR1C, and POLR1D genes all appear to play important roles in the early development of bones and other tissues of the face. These proteins are involved in the production of a molecule called ribosomal RNA (rRNA), a chemical cousin of DNA. Ribosomal RNA helps assemble protein building blocks (amino acids) into new proteins, which is essential for the normal functioning and survival of cells. Mutations in the TCOF1, POLR1C, or POLR1D gene reduce the production of rRNA. Researchers speculate that a decrease in the amount of rRNA may trigger the self-destruction (apoptosis) of certain cells involved in the development of facial bones and tissues. The abnormal cell death could lead to the specific problems with facial development found in Treacher Collins syndrome. However, it is unclear why the effects of a reduction in rRNA are limited to facial development.",Treacher Collins syndrome,0000989,GHR,https://ghr.nlm.nih.gov/condition/treacher-collins-syndrome,C0242387,T019,Disorders
Is Treacher Collins syndrome inherited ?,0000989-4,inheritance,"When Treacher Collins syndrome results from mutations in the TCOF1 or POLR1D gene, it is considered an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. About 60 percent of these cases result from new mutations in the gene and occur in people with no history of the disorder in their family. In the remaining autosomal dominant cases, a person with Treacher Collins syndrome inherits the altered gene from an affected parent.  When Treacher Collins syndrome is caused by mutations in the POLR1C gene, the condition has an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Treacher Collins syndrome,0000989,GHR,https://ghr.nlm.nih.gov/condition/treacher-collins-syndrome,C0242387,T019,Disorders
What are the treatments for Treacher Collins syndrome ?,0000989-5,treatment,"These resources address the diagnosis or management of Treacher Collins syndrome:  - Gene Review: Gene Review: Treacher Collins Syndrome  - Genetic Testing Registry: Mandibulofacial dysostosis, Treacher Collins type, autosomal recessive  - Genetic Testing Registry: Treacher Collins syndrome  - Genetic Testing Registry: Treacher collins syndrome 1  - Genetic Testing Registry: Treacher collins syndrome 2  - MedlinePlus Encyclopedia: Micrognathia  - MedlinePlus Encyclopedia: Pinna Abnormalities and Low-Set Ears  - MedlinePlus Encyclopedia: Treacher-Collins Syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Treacher Collins syndrome,0000989,GHR,https://ghr.nlm.nih.gov/condition/treacher-collins-syndrome,C0242387,T019,Disorders
What is (are) trichohepatoenteric syndrome ?,0000990-1,information,"Trichohepatoenteric syndrome is a condition that affects the hair (tricho-), liver (hepato-), and intestines (enteric), as well as other tissues and organs in the body. This condition is also known as syndromic diarrhea because chronic, difficult-to-treat diarrhea is one of its major features. Within the first few weeks of life, affected infants develop watery diarrhea that occurs multiple times per day. Even with nutritional support through intravenous feedings (parenteral nutrition), many of these children experience failure to thrive, which means they do not gain weight or grow at the expected rate. Most children with trichohepatoenteric syndrome are small at birth, and they remain shorter than their peers throughout life.  Abnormal hair is another feature of trichohepatoenteric syndrome. Hair in affected individuals is described as wooly, brittle, patchy, and easily pulled out. Under a microscope, some strands of hair can be seen to vary in diameter, with thicker and thinner spots. This feature is known as trichorrhexis nodosa.  Other signs and symptoms of trichohepatoenteric syndrome can include liver disease; skin abnormalities; and distinctive facial features, including a wide forehead, a broad base of the nose, and widely spaced eyes. Overall, the facial features are described as ""coarse."" Most affected individuals also experience immune system abnormalities that can make them prone to developing infections. Less commonly, trichohepatoenteric syndrome is associated with heart (cardiac) abnormalities. Mild intellectual disability has been reported in at least half of all children with the condition.  Trichohepatoenteric syndrome is often life-threatening in childhood, particularly in children who develop liver disease or severe infections.",trichohepatoenteric syndrome,0000990,GHR,https://ghr.nlm.nih.gov/condition/trichohepatoenteric-syndrome,C1857276,T047,Disorders
How many people are affected by trichohepatoenteric syndrome ?,0000990-2,frequency,Trichohepatoenteric syndrome is a rare condition with an estimated prevalence of about 1 in 1 million people. At least 44 cases have been reported in the medical literature.,trichohepatoenteric syndrome,0000990,GHR,https://ghr.nlm.nih.gov/condition/trichohepatoenteric-syndrome,C1857276,T047,Disorders
What are the genetic changes related to trichohepatoenteric syndrome ?,0000990-3,genetic changes,"Trichohepatoenteric syndrome can be caused by mutations in the TTC37 or SKIV2L gene. These genes provide instructions for making proteins whose functions have not been confirmed. Researchers speculate that they work together with other proteins within cells to help recognize and break down excess or abnormal messenger RNA (mRNA) molecules. mRNA is a chemical cousin of DNA that serves as the genetic blueprint for protein production. Studies suggest that getting rid of excess and abnormal mRNA is important for cell growth.  Mutations in the TTC37 or SKIV2L gene likely eliminate the function of their respective proteins, which is hypothesized to impair the breakdown of unneeded mRNA. However, it is unknown how these changes could lead to chronic diarrhea and the other features of trichohepatoenteric syndrome.",trichohepatoenteric syndrome,0000990,GHR,https://ghr.nlm.nih.gov/condition/trichohepatoenteric-syndrome,C1857276,T047,Disorders
Is trichohepatoenteric syndrome inherited ?,0000990-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",trichohepatoenteric syndrome,0000990,GHR,https://ghr.nlm.nih.gov/condition/trichohepatoenteric-syndrome,C1857276,T047,Disorders
What are the treatments for trichohepatoenteric syndrome ?,0000990-5,treatment,These resources address the diagnosis or management of trichohepatoenteric syndrome:  - American Society for Parenteral and Enteral Nutrition: What is Parenteral Nutrition?  - Genetic Testing Registry: Trichohepatoenteric syndrome  - Genetic Testing Registry: Trichohepatoenteric syndrome 2  - MedlinePlus Health Topic: Nutritional Support   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,trichohepatoenteric syndrome,0000990,GHR,https://ghr.nlm.nih.gov/condition/trichohepatoenteric-syndrome,C1857276,T047,Disorders
What is (are) trichothiodystrophy ?,0000991-1,information,"Trichothiodystrophy, which is commonly called TTD, is a rare inherited condition that affects many parts of the body. The hallmark of this condition is brittle hair that is sparse and easily broken. Tests show that the hair is lacking sulfur, an element that normally gives hair its strength.  The signs and symptoms of trichothiodystrophy vary widely. Mild cases may involve only the hair. More severe cases also cause delayed development, significant intellectual disability, and recurrent infections; severely affected individuals may survive only into infancy or early childhood.  Mothers of children with trichothiodystrophy may experience problems during pregnancy including pregnancy-induced high blood pressure (preeclampsia) and a related condition called HELLP syndrome that can damage the liver. Babies with trichothiodystrophy are at increased risk of premature birth, low birth weight, and slow growth.  Most affected children have short stature compared to others their age. Intellectual disability and delayed development are common, although most affected individuals are highly social with an outgoing and engaging personality. Some have brain abnormalities that can be seen with imaging tests. Trichothiodystrophy is also associated with recurrent infections, particularly respiratory infections, which can be life-threatening. Other features of trichothiodystrophy can include dry, scaly skin (ichthyosis); abnormalities of the fingernails and toenails; clouding of the lens in both eyes from birth (congenital cataracts); poor coordination; and skeletal abnormalities.  About half of all people with trichothiodystrophy have a photosensitive form of the disorder, which causes them to be extremely sensitive to ultraviolet (UV) rays from sunlight. They develop a severe sunburn after spending just a few minutes in the sun. However, for reasons that are unclear, they do not develop other sun-related problems such as excessive freckling of the skin or an increased risk of skin cancer. Many people with trichothiodystrophy report that they do not sweat.",trichothiodystrophy,0000991,GHR,https://ghr.nlm.nih.gov/condition/trichothiodystrophy,C1955934,T047,Disorders
How many people are affected by trichothiodystrophy ?,0000991-2,frequency,Trichothiodystrophy has an estimated incidence of about 1 in 1 million newborns in the United States and Europe. About 100 affected individuals have been reported worldwide.,trichothiodystrophy,0000991,GHR,https://ghr.nlm.nih.gov/condition/trichothiodystrophy,C1955934,T047,Disorders
What are the genetic changes related to trichothiodystrophy ?,0000991-3,genetic changes,"Most cases of the photosensitive form of trichothiodystrophy result from mutations in one of three genes: ERCC2, ERCC3, or GTF2H5. The proteins produced from these genes work together as part of a group of proteins called the general transcription factor IIH (TFIIH) complex. This complex is involved in the repair of DNA damage, which can be caused by UV radiation from the sun. The TFIIH complex also plays an important role in gene transcription, which is the first step in protein production.  Mutations in the ERCC2, ERCC3, or GTF2H5 genes reduce the amount of TFIIH complex within cells, which impairs both DNA repair and gene transcription. An inability to repair DNA damage probably underlies the sun sensitivity in affected individuals. Studies suggest that many of the other features of trichothiodystrophy may result from problems with the transcription of genes needed for normal development before and after birth.  Mutations in at least one gene, MPLKIP, have been reported to cause a non-photosensitive form of trichothiodystrophy. Mutations in this gene account for fewer than 20 percent of all cases of non-photosensitive trichothiodystrophy. Little is known about the protein produced from the MPLKIP gene, although it does not appear to be involved in DNA repair. It is unclear how mutations in the MPLKIP gene lead to the varied features of trichothiodystrophy.  In some cases, the genetic cause of trichothiodystrophy is unknown.",trichothiodystrophy,0000991,GHR,https://ghr.nlm.nih.gov/condition/trichothiodystrophy,C1955934,T047,Disorders
Is trichothiodystrophy inherited ?,0000991-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",trichothiodystrophy,0000991,GHR,https://ghr.nlm.nih.gov/condition/trichothiodystrophy,C1955934,T047,Disorders
What are the treatments for trichothiodystrophy ?,0000991-5,treatment,"These resources address the diagnosis or management of trichothiodystrophy:  - Genetic Testing Registry: BIDS brittle hair-impaired intellect-decreased fertility-short stature syndrome  - Genetic Testing Registry: Photosensitive trichothiodystrophy  - Genetic Testing Registry: Trichothiodystrophy, nonphotosensitive 1  - The Merck Manual Home Edition for Patients and Caregivers: Photosensitivity Reactions  - The Merck Manual for Healthcare Professionals: Ichthyosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",trichothiodystrophy,0000991,GHR,https://ghr.nlm.nih.gov/condition/trichothiodystrophy,C1955934,T047,Disorders
What is (are) trimethylaminuria ?,0000992-1,information,"Trimethylaminuria is a disorder in which the body is unable to break down trimethylamine, a chemical compound that has a pungent odor. Trimethylamine has been described as smelling like rotting fish, rotting eggs, garbage, or urine. As this compound builds up in the body, it causes affected people to give off a strong odor in their sweat, urine, and breath. The intensity of the odor may vary over time. The odor can interfere with many aspects of daily life, affecting a person's relationships, social life, and career. Some people with trimethylaminuria experience depression and social isolation as a result of this condition.",trimethylaminuria,0000992,GHR,https://ghr.nlm.nih.gov/condition/trimethylaminuria,C0342739,T047,Disorders
How many people are affected by trimethylaminuria ?,0000992-2,frequency,Trimethylaminuria is an uncommon genetic disorder; its incidence is unknown.,trimethylaminuria,0000992,GHR,https://ghr.nlm.nih.gov/condition/trimethylaminuria,C0342739,T047,Disorders
What are the genetic changes related to trimethylaminuria ?,0000992-3,genetic changes,"Mutations in the FMO3 gene cause trimethylaminuria. This gene provides instructions for making an enzyme that breaks down nitrogen-containing compounds from the diet, including trimethylamine. This compound is produced by bacteria in the intestine during the digestion of proteins from eggs, liver, legumes (such as soybeans and peas), certain kinds of fish, and other foods. Normally, the FMO3 enzyme converts strong-smelling trimethylamine into another molecule that has no odor. If the enzyme is missing or its activity is reduced because of a mutation in the FMO3 gene, trimethylamine is not processed properly and can build up in the body. As excess trimethylamine is released in a person's sweat, urine, and breath, it causes the odor characteristic of trimethylaminuria. Researchers believe that stress and diet also play a role in triggering symptoms.  Although FMO3 gene mutations account for most cases of trimethylaminuria, the condition can also be caused by other factors. The strong body odor may result from an excess of certain proteins in the diet or from an abnormal increase in bacteria that produce trimethylamine in the digestive system. A few cases of the disorder have been identified in adults with liver or kidney disease. Temporary symptoms of this condition have been reported in a small number of premature infants and in some healthy women at the start of menstruation.",trimethylaminuria,0000992,GHR,https://ghr.nlm.nih.gov/condition/trimethylaminuria,C0342739,T047,Disorders
Is trimethylaminuria inherited ?,0000992-4,inheritance,"Most cases of trimethylaminuria appear to be inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but typically do not show signs and symptoms of the condition. Carriers of an FMO3 mutation, however, may have mild symptoms of trimethylaminuria or experience temporary episodes of strong body odor.",trimethylaminuria,0000992,GHR,https://ghr.nlm.nih.gov/condition/trimethylaminuria,C0342739,T047,Disorders
What are the treatments for trimethylaminuria ?,0000992-5,treatment,These resources address the diagnosis or management of trimethylaminuria:  - Gene Review: Gene Review: Primary Trimethylaminuria  - Genetic Testing Registry: Trimethylaminuria  - Monell Chemical Senses Center: TMAU & Body Malodors  - National Human Genome Research Institute: Diagnosis and Treatment of Trimethylaminuria   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,trimethylaminuria,0000992,GHR,https://ghr.nlm.nih.gov/condition/trimethylaminuria,C0342739,T047,Disorders
What is (are) triosephosphate isomerase deficiency ?,0000993-1,information,"Triosephosphate isomerase deficiency is a disorder characterized by a shortage of red blood cells (anemia), movement problems, increased susceptibility to infection, and muscle weakness that can affect breathing and heart function.  The anemia in this condition begins in infancy. Since the anemia results from the premature breakdown of red blood cells (hemolysis), it is known as hemolytic anemia. A shortage of red blood cells to carry oxygen throughout the body leads to extreme tiredness (fatigue), pale skin (pallor), and shortness of breath. When the red cells are broken down, iron and a molecule called bilirubin are released; individuals with triosephosphate isomerase deficiency have an excess of these substances circulating in the blood. Excess bilirubin in the blood causes jaundice, which is a yellowing of the skin and the whites of the eyes.  Movement problems typically become apparent by age 2 in people with triosephosphate isomerase deficiency. The movement problems are caused by impairment of motor neurons, which are specialized nerve cells in the brain and spinal cord that control muscle movement. This impairment leads to muscle weakness and wasting (atrophy) and causes the movement problems typical of triosephosphate isomerase deficiency, including involuntary muscle tensing (dystonia), tremors, and weak muscle tone (hypotonia). Affected individuals may also develop seizures.  Weakness of other muscles, such as the heart (a condition known as cardiomyopathy) and the muscle that separates the abdomen from the chest cavity (the diaphragm) can also occur in triosephosphate isomerase deficiency. Diaphragm weakness can cause breathing problems and ultimately leads to respiratory failure.  Individuals with triosephosphate isomerase deficiency are at increased risk of developing infections because they have poorly functioning white blood cells. These immune system cells normally recognize and attack foreign invaders, such as viruses and bacteria, to prevent infection. The most common infections in people with triosephosphate isomerase deficiency are bacterial infections of the respiratory tract.  People with triosephosphate isomerase deficiency often do not survive past childhood due to respiratory failure. In a few rare cases, affected individuals without severe nerve damage or muscle weakness have lived into adulthood.",triosephosphate isomerase deficiency,0000993,GHR,https://ghr.nlm.nih.gov/condition/triosephosphate-isomerase-deficiency,C1860808,T047,Disorders
How many people are affected by triosephosphate isomerase deficiency ?,0000993-2,frequency,Triosephosphate isomerase deficiency is likely a rare condition; approximately 40 cases have been reported in the scientific literature.,triosephosphate isomerase deficiency,0000993,GHR,https://ghr.nlm.nih.gov/condition/triosephosphate-isomerase-deficiency,C1860808,T047,Disorders
What are the genetic changes related to triosephosphate isomerase deficiency ?,0000993-3,genetic changes,"Mutations in the TPI1 gene cause triosephosphate isomerase deficiency. This gene provides instructions for making an enzyme called triosephosphate isomerase 1. This enzyme is involved in a critical energy-producing process known as glycolysis. During glycolysis, the simple sugar glucose is broken down to produce energy for cells.  TPI1 gene mutations lead to the production of unstable enzymes or enzymes with decreased activity. As a result, glycolysis is impaired and cells have a decreased supply of energy. Red blood cells depend solely on the breakdown of glucose for energy, and without functional glycolysis, red blood cells die earlier than normal. Cells with high energy demands, such as nerve cells in the brain, white blood cells, and heart (cardiac) muscle cells are also susceptible to cell death due to reduced energy caused by impaired glycolysis. Nerve cells in the part of the brain involved in coordinating movements (the cerebellum) are particularly affected in people with triosephosphate isomerase deficiency.  Death of red and white blood cells, nerve cells in the brain, and cardiac muscle cells leads to the signs and symptoms of triosephosphate isomerase deficiency.",triosephosphate isomerase deficiency,0000993,GHR,https://ghr.nlm.nih.gov/condition/triosephosphate-isomerase-deficiency,C1860808,T047,Disorders
Is triosephosphate isomerase deficiency inherited ?,0000993-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",triosephosphate isomerase deficiency,0000993,GHR,https://ghr.nlm.nih.gov/condition/triosephosphate-isomerase-deficiency,C1860808,T047,Disorders
What are the treatments for triosephosphate isomerase deficiency ?,0000993-5,treatment,"These resources address the diagnosis or management of triosephosphate isomerase deficiency:  - Genetic Testing Registry: Triosephosphate isomerase deficiency  - MedlinePlus Encyclopedia: Hemolytic Anemia  - National Heart, Lung, and Blood Institute: How is Hemolytic Anemia Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",triosephosphate isomerase deficiency,0000993,GHR,https://ghr.nlm.nih.gov/condition/triosephosphate-isomerase-deficiency,C1860808,T047,Disorders
What is (are) triple A syndrome ?,0000994-1,information,"Triple A syndrome is an inherited condition characterized by three specific features: achalasia, Addison disease, and alacrima. Achalasia is a disorder that affects the ability to move food through the esophagus, the tube that carries food from the throat to the stomach. It can lead to severe feeding difficulties and low blood sugar (hypoglycemia). Addison disease, also known as primary adrenal insufficiency, is caused by abnormal function of the small hormone-producing glands on top of each kidney (adrenal glands). The main features of Addison disease include fatigue, loss of appetite, weight loss, low blood pressure, and darkening of the skin. The third major feature of triple A syndrome is a reduced or absent ability to secrete tears (alacrima). Most people with triple A syndrome have all three of these features, although some have only two.  Many of the features of triple A syndrome are caused by dysfunction of the autonomic nervous system. This part of the nervous system controls involuntary body processes such as digestion, blood pressure, and body temperature. People with triple A syndrome often experience abnormal sweating, difficulty regulating blood pressure, unequal pupil size (anisocoria), and other signs and symptoms of autonomic nervous system dysfunction (dysautonomia).  People with this condition may have other neurological abnormalities, such as developmental delay, intellectual disability, speech problems (dysarthria), and a small head size (microcephaly). In addition, affected individuals commonly experience muscle weakness, movement problems, and nerve abnormalities in their extremities (peripheral neuropathy). Some develop optic atrophy, which is the degeneration (atrophy) of the nerves that carry information from the eyes to the brain. Many of the neurological symptoms of triple A syndrome worsen over time.  People with triple A syndrome frequently develop a thickening of the outer layer of skin (hyperkeratosis) on the palms of their hands and the soles of their feet. Other skin abnormalities may also be present in people with this condition.  Alacrima is usually the first noticeable sign of triple A syndrome, as it becomes apparent early in life that affected children produce little or no tears while crying. They develop Addison disease and achalasia during childhood or adolescence, and most of the neurologic features of triple A syndrome begin during adulthood. The signs and symptoms of this condition vary among affected individuals, even among members of the same family.",triple A syndrome,0000994,GHR,https://ghr.nlm.nih.gov/condition/triple-a-syndrome,C0271742,T047,Disorders
How many people are affected by triple A syndrome ?,0000994-2,frequency,"Triple A syndrome is a rare condition, although its exact prevalence is unknown.",triple A syndrome,0000994,GHR,https://ghr.nlm.nih.gov/condition/triple-a-syndrome,C0271742,T047,Disorders
What are the genetic changes related to triple A syndrome ?,0000994-3,genetic changes,"Mutations in the AAAS gene cause triple A syndrome. This gene provides instructions for making a protein called ALADIN whose function is not well understood. Within cells, ALADIN is found in the nuclear envelope, the structure that surrounds the nucleus and separates it from the rest of the cell. Based on its location, ALADIN is thought to be involved in the movement of molecules into and out of the nucleus.  Mutations in the AAAS gene change the structure of ALADIN in different ways; however, almost all mutations prevent this protein from reaching its proper location in the nuclear envelope. The absence of ALADIN in the nuclear envelope likely disrupts the movement of molecules across this membrane. Researchers suspect that DNA repair proteins may be unable to enter the nucleus if ALADIN is missing from the nuclear envelope. DNA damage that is not repaired can cause the cell to become unstable and lead to cell death. Although the nervous system is particularly vulnerable to DNA damage, it remains unknown exactly how mutations in the AAAS gene lead to the signs and symptoms of triple A syndrome.  Some individuals with triple A syndrome do not have an identified mutation in the AAAS gene. The genetic cause of the disorder is unknown in these individuals.",triple A syndrome,0000994,GHR,https://ghr.nlm.nih.gov/condition/triple-a-syndrome,C0271742,T047,Disorders
Is triple A syndrome inherited ?,0000994-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",triple A syndrome,0000994,GHR,https://ghr.nlm.nih.gov/condition/triple-a-syndrome,C0271742,T047,Disorders
What are the treatments for triple A syndrome ?,0000994-5,treatment,These resources address the diagnosis or management of triple A syndrome:  - Genetic Testing Registry: Glucocorticoid deficiency with achalasia  - MedlinePlus Encyclopedia: Achalasia  - MedlinePlus Encyclopedia: Anisocoria   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,triple A syndrome,0000994,GHR,https://ghr.nlm.nih.gov/condition/triple-a-syndrome,C0271742,T047,Disorders
What is (are) triple X syndrome ?,0000995-1,information,"Triple X syndrome, also called trisomy X or 47,XXX, is characterized by the presence of an additional X chromosome in each of a female's cells. Although females with this condition may be taller than average, this chromosomal change typically causes no unusual physical features. Most females with triple X syndrome have normal sexual development and are able to conceive children.  Triple X syndrome is associated with an increased risk of learning disabilities and delayed development of speech and language skills. Delayed development of motor skills (such as sitting and walking), weak muscle tone (hypotonia), and behavioral and emotional difficulties are also possible, but these characteristics vary widely among affected girls and women. Seizures or kidney abnormalities occur in about 10 percent of affected females.",triple X syndrome,0000995,GHR,https://ghr.nlm.nih.gov/condition/triple-x-syndrome,C0221033,T019,Disorders
How many people are affected by triple X syndrome ?,0000995-2,frequency,"This condition occurs in about 1 in 1,000 newborn girls. Five to 10 girls with triple X syndrome are born in the United States each day.",triple X syndrome,0000995,GHR,https://ghr.nlm.nih.gov/condition/triple-x-syndrome,C0221033,T019,Disorders
What are the genetic changes related to triple X syndrome ?,0000995-3,genetic changes,"People normally have 46 chromosomes in each cell. Two of the 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male or female sex characteristics. Females typically have two X chromosomes (46,XX), and males have one X chromosome and one Y chromosome (46,XY).  Triple X syndrome results from an extra copy of the X chromosome in each of a female's cells. As a result of the extra X chromosome, each cell has a total of 47 chromosomes (47,XXX) instead of the usual 46. An extra copy of the X chromosome is associated with tall stature, learning problems, and other features in some girls and women.  Some females with triple X syndrome have an extra X chromosome in only some of their cells. This phenomenon is called 46,XX/47,XXX mosaicism.",triple X syndrome,0000995,GHR,https://ghr.nlm.nih.gov/condition/triple-x-syndrome,C0221033,T019,Disorders
Is triple X syndrome inherited ?,0000995-4,inheritance,"Most cases of triple X syndrome are not inherited. The chromosomal change usually occurs as a random event during the formation of reproductive cells (eggs and sperm). An error in cell division called nondisjunction can result in reproductive cells with an abnormal number of chromosomes. For example, an egg or sperm cell may gain an extra copy of the X chromosome as a result of nondisjunction. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have an extra X chromosome in each of the body's cells.  46,XX/47,XXX mosaicism is also not inherited. It occurs as a random event during cell division in early embryonic development. As a result, some of an affected person's cells have two X chromosomes (46,XX), and other cells have three X chromosomes (47,XXX).",triple X syndrome,0000995,GHR,https://ghr.nlm.nih.gov/condition/triple-x-syndrome,C0221033,T019,Disorders
What are the treatments for triple X syndrome ?,0000995-5,treatment,These resources address the diagnosis or management of triple X syndrome:  - Association for X and Y Chromosome Variations (AXYS): Trisomy X Syndrome  - Genetic Testing Registry: Trisomy X syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,triple X syndrome,0000995,GHR,https://ghr.nlm.nih.gov/condition/triple-x-syndrome,C0221033,T019,Disorders
What is (are) trisomy 13 ?,0000996-1,information,"Trisomy 13, also called Patau syndrome, is a chromosomal condition associated with severe intellectual disability and physical abnormalities in many parts of the body. Individuals with trisomy 13 often have heart defects, brain or spinal cord abnormalities, very small or poorly developed eyes (microphthalmia), extra fingers or toes, an opening in the lip (a cleft lip) with or without an opening in the roof of the mouth (a cleft palate), and weak muscle tone (hypotonia). Due to the presence of several life-threatening medical problems, many infants with trisomy 13 die within their first days or weeks of life. Only five percent to 10 percent of children with this condition live past their first year.",trisomy 13,0000996,GHR,https://ghr.nlm.nih.gov/condition/trisomy-13,C0152095,T019,Disorders
How many people are affected by trisomy 13 ?,0000996-2,frequency,"Trisomy 13 occurs in about 1 in 16,000 newborns. Although women of any age can have a child with trisomy 13, the chance of having a child with this condition increases as a woman gets older.",trisomy 13,0000996,GHR,https://ghr.nlm.nih.gov/condition/trisomy-13,C0152095,T019,Disorders
What are the genetic changes related to trisomy 13 ?,0000996-3,genetic changes,"Most cases of trisomy 13 result from having three copies of chromosome 13 in each cell in the body instead of the usual two copies. The extra genetic material disrupts the normal course of development, causing the characteristic features of trisomy 13.  Trisomy 13 can also occur when part of chromosome 13 becomes attached (translocated) to another chromosome during the formation of reproductive cells (eggs and sperm) or very early in fetal development. Affected people have two normal copies of chromosome 13, plus an extra copy of chromosome 13 attached to another chromosome. In rare cases, only part of chromosome 13 is present in three copies. The physical signs and symptoms in these cases may be different than those found in full trisomy 13.  A small percentage of people with trisomy 13 have an extra copy of chromosome 13 in only some of the body's cells. In these people, the condition is called mosaic trisomy 13. The severity of mosaic trisomy 13 depends on the type and number of cells that have the extra chromosome. The physical features of mosaic trisomy 13 are often milder than those of full trisomy 13.",trisomy 13,0000996,GHR,https://ghr.nlm.nih.gov/condition/trisomy-13,C0152095,T019,Disorders
Is trisomy 13 inherited ?,0000996-4,inheritance,"Most cases of trisomy 13 are not inherited and result from random events during the formation of eggs and sperm in healthy parents. An error in cell division called nondisjunction results in a reproductive cell with an abnormal number of chromosomes. For example, an egg or sperm cell may gain an extra copy of chromosome 13. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have an extra chromosome 13 in each cell of the body.  Translocation trisomy 13 can be inherited. An unaffected person can carry a rearrangement of genetic material between chromosome 13 and another chromosome. These rearrangements are called balanced translocations because there is no extra material from chromosome 13. A person with a balanced translocation involving chromosome 13 has an increased chance of passing extra material from chromosome 13 to their children.",trisomy 13,0000996,GHR,https://ghr.nlm.nih.gov/condition/trisomy-13,C0152095,T019,Disorders
What are the treatments for trisomy 13 ?,0000996-5,treatment,These resources address the diagnosis or management of trisomy 13:  - Genetic Testing Registry: Complete trisomy 13 syndrome  - MedlinePlus Encyclopedia: Trisomy 13   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,trisomy 13,0000996,GHR,https://ghr.nlm.nih.gov/condition/trisomy-13,C0152095,T019,Disorders
What is (are) trisomy 18 ?,0000997-1,information,"Trisomy 18, also called Edwards syndrome, is a chromosomal condition associated with abnormalities in many parts of the body. Individuals with trisomy 18 often have slow growth before birth (intrauterine growth retardation) and a low birth weight. Affected individuals may have heart defects and abnormalities of other organs that develop before birth. Other features of trisomy 18 include a small, abnormally shaped head; a small jaw and mouth; and clenched fists with overlapping fingers. Due to the presence of several life-threatening medical problems, many individuals with trisomy 18 die before birth or within their first month. Five to 10 percent of children with this condition live past their first year, and these children often have severe intellectual disability.",trisomy 18,0000997,GHR,https://ghr.nlm.nih.gov/condition/trisomy-18,C0152096,T019,Disorders
How many people are affected by trisomy 18 ?,0000997-2,frequency,"Trisomy 18 occurs in about 1 in 5,000 live-born infants; it is more common in pregnancy, but many affected fetuses do not survive to term. Although women of all ages can have a child with trisomy 18, the chance of having a child with this condition increases as a woman gets older.",trisomy 18,0000997,GHR,https://ghr.nlm.nih.gov/condition/trisomy-18,C0152096,T019,Disorders
What are the genetic changes related to trisomy 18 ?,0000997-3,genetic changes,"Most cases of trisomy 18 result from having three copies of chromosome 18 in each cell in the body instead of the usual two copies. The extra genetic material disrupts the normal course of development, causing the characteristic features of trisomy 18.  Approximately 5 percent of people with trisomy 18 have an extra copy of chromosome 18 in only some of the body's cells. In these people, the condition is called mosaic trisomy 18. The severity of mosaic trisomy 18 depends on the type and number of cells that have the extra chromosome. The development of individuals with this form of trisomy 18 may range from normal to severely affected.  Very rarely, part of the long (q) arm of chromosome 18 becomes attached (translocated) to another chromosome during the formation of reproductive cells (eggs and sperm) or very early in embryonic development. Affected individuals have two copies of chromosome 18, plus the extra material from chromosome 18 attached to another chromosome. People with this genetic change are said to have partial trisomy 18. If only part of the q arm is present in three copies, the physical signs of partial trisomy 18 may be less severe than those typically seen in trisomy 18. If the entire q arm is present in three copies, individuals may be as severely affected as if they had three full copies of chromosome 18.",trisomy 18,0000997,GHR,https://ghr.nlm.nih.gov/condition/trisomy-18,C0152096,T019,Disorders
Is trisomy 18 inherited ?,0000997-4,inheritance,"Most cases of trisomy 18 are not inherited, but occur as random events during the formation of eggs and sperm. An error in cell division called nondisjunction results in a reproductive cell with an abnormal number of chromosomes. For example, an egg or sperm cell may gain an extra copy of chromosome 18. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have an extra chromosome 18 in each of the body's cells.  Mosaic trisomy 18 is also not inherited. It occurs as a random event during cell division early in embryonic development. As a result, some of the body's cells have the usual two copies of chromosome 18, and other cells have three copies of this chromosome.  Partial trisomy 18 can be inherited. An unaffected person can carry a rearrangement of genetic material between chromosome 18 and another chromosome. This rearrangement is called a balanced translocation because there is no extra material from chromosome 18. Although they do not have signs of trisomy 18, people who carry this type of balanced translocation are at an increased risk of having children with the condition.",trisomy 18,0000997,GHR,https://ghr.nlm.nih.gov/condition/trisomy-18,C0152096,T019,Disorders
What are the treatments for trisomy 18 ?,0000997-5,treatment,These resources address the diagnosis or management of trisomy 18:  - Genetic Testing Registry: Complete trisomy 18 syndrome  - MedlinePlus Encyclopedia: Trisomy 18   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,trisomy 18,0000997,GHR,https://ghr.nlm.nih.gov/condition/trisomy-18,C0152096,T019,Disorders
What is (are) Troyer syndrome ?,0000998-1,information,"Troyer syndrome is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve the lower limbs. The complex types involve the lower limbs and can also affect the upper limbs to a lesser degree; the structure or functioning of the brain; and the nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound (the peripheral nervous system). Troyer syndrome is a complex hereditary spastic paraplegia.  People with Troyer syndrome can experience a variety of signs and symptoms. The most common characteristics of Troyer syndrome are spasticity of the leg muscles, progressive muscle weakness, paraplegia, muscle wasting in the hands and feet (distal amyotrophy), small stature, developmental delay, learning disorders, speech difficulties (dysarthria), and mood swings. Other characteristics can include exaggerated reflexes (hyperreflexia) in the lower limbs, uncontrollable movements of the limbs (choreoathetosis), skeletal abnormalities, and a bending outward (valgus) of the knees.  Troyer syndrome causes the degeneration and death of muscle cells and motor neurons (specialized nerve cells that control muscle movement) throughout a person's lifetime, leading to a slow progressive decline in muscle and nerve function. The severity of impairment related to Troyer syndrome increases as a person ages. Most affected individuals require a wheelchair by the time they are in their fifties or sixties.",Troyer syndrome,0000998,GHR,https://ghr.nlm.nih.gov/condition/troyer-syndrome,C0393559,T047,Disorders
How many people are affected by Troyer syndrome ?,0000998-2,frequency,About 20 cases of Troyer syndrome have been reported in the Old Order Amish population of Ohio. It has not been found outside this population.,Troyer syndrome,0000998,GHR,https://ghr.nlm.nih.gov/condition/troyer-syndrome,C0393559,T047,Disorders
What are the genetic changes related to Troyer syndrome ?,0000998-3,genetic changes,"Troyer syndrome is caused by a mutation in the SPG20 gene. The SPG20 gene provides instructions for producing a protein called spartin, whose function is not entirely understood. Researchers believe that spartin may be involved in a variety of cell functions, from breaking down proteins to transporting materials from the cell surface into the cell (endocytosis). Spartin is found in a wide range of body tissues, including the nervous system.",Troyer syndrome,0000998,GHR,https://ghr.nlm.nih.gov/condition/troyer-syndrome,C0393559,T047,Disorders
Is Troyer syndrome inherited ?,0000998-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Troyer syndrome,0000998,GHR,https://ghr.nlm.nih.gov/condition/troyer-syndrome,C0393559,T047,Disorders
What are the treatments for Troyer syndrome ?,0000998-5,treatment,"These resources address the diagnosis or management of Troyer syndrome:  - Gene Review: Gene Review: Hereditary Spastic Paraplegia Overview  - Gene Review: Gene Review: Troyer Syndrome  - Genetic Testing Registry: Troyer syndrome  - Spastic Paraplegia Foundation, Inc.: Treatments and Therapies   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Troyer syndrome,0000998,GHR,https://ghr.nlm.nih.gov/condition/troyer-syndrome,C0393559,T047,Disorders
What is (are) tuberous sclerosis complex ?,0000999-1,information,"Tuberous sclerosis complex is a genetic disorder characterized by the growth of numerous noncancerous (benign) tumors in many parts of the body. These tumors can occur in the skin, brain, kidneys, and other organs, in some cases leading to significant health problems. Tuberous sclerosis complex also causes developmental problems, and the signs and symptoms of the condition vary from person to person.  Virtually all affected people have skin abnormalities, including patches of unusually light-colored skin, areas of raised and thickened skin, and growths under the nails. Tumors on the face called facial angiofibromas are also common beginning in childhood.  Tuberous sclerosis complex often affects the brain, causing seizures, behavioral problems such as hyperactivity and aggression, and intellectual disability or learning problems. Some affected children have the characteristic features of autism, a developmental disorder that affects communication and social interaction. Benign brain tumors can also develop in people with tuberous sclerosis complex; these tumors can cause serious or life-threatening complications.  Kidney tumors are common in people with tuberous sclerosis complex; these growths can cause severe problems with kidney function and may be life-threatening in some cases. Additionally, tumors can develop in the heart, lungs, and the light-sensitive tissue at the back of the eye (the retina).",tuberous sclerosis complex,0000999,GHR,https://ghr.nlm.nih.gov/condition/tuberous-sclerosis-complex,C0041341,T191,Disorders
How many people are affected by tuberous sclerosis complex ?,0000999-2,frequency,"Tuberous sclerosis complex affects about 1 in 6,000 people.",tuberous sclerosis complex,0000999,GHR,https://ghr.nlm.nih.gov/condition/tuberous-sclerosis-complex,C0041341,T191,Disorders
What are the genetic changes related to tuberous sclerosis complex ?,0000999-3,genetic changes,"Mutations in the TSC1 or TSC2 gene can cause tuberous sclerosis complex. The TSC1 and TSC2 genes provide instructions for making the proteins hamartin and tuberin, respectively. Within cells, these two proteins likely work together to help regulate cell growth and size. The proteins act as tumor suppressors, which normally prevent cells from growing and dividing too fast or in an uncontrolled way.  People with tuberous sclerosis complex are born with one mutated copy of the TSC1 or TSC2 gene in each cell. This mutation prevents the cell from making functional hamartin or tuberin from the altered copy of the gene. However, enough protein is usually produced from the other, normal copy of the gene to regulate cell growth effectively. For some types of tumors to develop, a second mutation involving the other copy of the TSC1 or TSC2 gene must occur in certain cells during a person's lifetime.  When both copies of the TSC1 gene are mutated in a particular cell, that cell cannot produce any functional hamartin; cells with two altered copies of the TSC2 gene are unable to produce any functional tuberin. The loss of these proteins allows the cell to grow and divide in an uncontrolled way to form a tumor. In people with tuberous sclerosis complex, a second TSC1 or TSC2 mutation typically occurs in multiple cells over an affected person's lifetime. The loss of hamartin or tuberin in different types of cells leads to the growth of tumors in many different organs and tissues.",tuberous sclerosis complex,0000999,GHR,https://ghr.nlm.nih.gov/condition/tuberous-sclerosis-complex,C0041341,T191,Disorders
Is tuberous sclerosis complex inherited ?,0000999-4,inheritance,"Tuberous sclerosis complex has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing tumors and other problems with development. In about one-third of cases, an affected person inherits an altered TSC1 or TSC2 gene from a parent who has the disorder. The remaining two-thirds of people with tuberous sclerosis complex are born with new mutations in the TSC1 or TSC2 gene. These cases, which are described as sporadic, occur in people with no history of tuberous sclerosis complex in their family. TSC1 mutations appear to be more common in familial cases of tuberous sclerosis complex, while mutations in the TSC2 gene occur more frequently in sporadic cases.",tuberous sclerosis complex,0000999,GHR,https://ghr.nlm.nih.gov/condition/tuberous-sclerosis-complex,C0041341,T191,Disorders
What are the treatments for tuberous sclerosis complex ?,0000999-5,treatment,These resources address the diagnosis or management of tuberous sclerosis complex:  - Gene Review: Gene Review: Tuberous Sclerosis Complex  - Genetic Testing Registry: Tuberous sclerosis syndrome  - MedlinePlus Encyclopedia: Tuberous Sclerosis  - Tuberous Sclerosis Alliance: TSC Clinics   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,tuberous sclerosis complex,0000999,GHR,https://ghr.nlm.nih.gov/condition/tuberous-sclerosis-complex,C0041341,T191,Disorders
What is (are) tubular aggregate myopathy ?,0001000-1,information,"Tubular aggregate myopathy is a disorder that primarily affects the skeletal muscles, which are muscles the body uses for movement. This disorder causes muscle pain, cramping, or weakness that begins in childhood and worsens over time. The muscles of the lower limbs are most often affected, although the upper limbs can also be involved. Affected individuals can have difficulty running, climbing stairs, or getting up from a squatting position. The weakness may also lead to an unusual walking style (gait). Some people with this condition develop joint deformities (contractures) in the arms and legs.  Skeletal muscles are normally made up of two types of fibers, called type I and type II fibers, in approximately equal quantities. Type I fibers, also called slow twitch fibers, are used for long, sustained activity, such as walking long distances. Type II fibers, also known as fast twitch fibers, are used for short bursts of strength, which are needed for activities such as running up stairs or sprinting. In people with tubular aggregate myopathy, type II fibers waste away (atrophy), so affected individuals have mostly type I fibers. In addition, proteins build up abnormally in both type I and type II fibers, forming clumps of tube-like structures called tubular aggregates. Tubular aggregates can occur in other muscle disorders, but they are the primary muscle cell abnormality in tubular aggregate myopathy.",tubular aggregate myopathy,0001000,GHR,https://ghr.nlm.nih.gov/condition/tubular-aggregate-myopathy,C0410207,T047,Disorders
How many people are affected by tubular aggregate myopathy ?,0001000-2,frequency,Tubular aggregate myopathy is a rare disorder. Its prevalence is unknown.,tubular aggregate myopathy,0001000,GHR,https://ghr.nlm.nih.gov/condition/tubular-aggregate-myopathy,C0410207,T047,Disorders
What are the genetic changes related to tubular aggregate myopathy ?,0001000-3,genetic changes,"Tubular aggregate myopathy can be caused by mutations in the STIM1 gene. The protein produced from this gene is involved in controlling the entry of positively charged calcium atoms (calcium ions) into cells. The STIM1 protein recognizes when calcium ion levels are low and stimulates the flow of ions into the cell through special channels in the cell membrane called calcium-release activated calcium (CRAC) channels. In muscle cells, the activation of CRAC channels by STIM1 is thought to help replenish calcium stores in a structure called the sarcoplasmic reticulum. STIM1 may also be involved in the release of calcium ions from the sarcoplasmic reticulum. This release of ions stimulates muscle tensing (contraction).  The STIM1 gene mutations involved in tubular aggregate myopathy lead to production of a STIM1 protein that is constantly turned on (constitutively active), which means it continually stimulates calcium ion entry through CRAC channels regardless of ion levels. It is unknown how constitutively active STIM1 leads to the muscle weakness characteristic of tubular aggregate myopathy. Evidence suggests that the tubular aggregates are composed of proteins that are normally part of the sarcoplasmic reticulum. Although the mechanism is unknown, some researchers speculate that the aggregates are the result of uncontrolled calcium levels in muscle cells, possibly due to abnormal STIM1 activity.  Mutations in other genes, some of which have not been identified, are also thought to cause some cases of tubular aggregate myopathy.",tubular aggregate myopathy,0001000,GHR,https://ghr.nlm.nih.gov/condition/tubular-aggregate-myopathy,C0410207,T047,Disorders
Is tubular aggregate myopathy inherited ?,0001000-4,inheritance,"Most cases of tubular aggregate myopathy, including those caused by STIM1 gene mutations, are inherited in an autosomal dominant pattern. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, the mutation is passed through generations in a family. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  Rarely, tubular aggregate myopathy is inherited in an autosomal recessive pattern, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Researchers are still working to determine which gene or genes are associated with autosomal recessive tubular aggregate myopathy.",tubular aggregate myopathy,0001000,GHR,https://ghr.nlm.nih.gov/condition/tubular-aggregate-myopathy,C0410207,T047,Disorders
What are the treatments for tubular aggregate myopathy ?,0001000-5,treatment,These resources address the diagnosis or management of tubular aggregate myopathy:  - Genetic Testing Registry: Myopathy with tubular aggregates   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,tubular aggregate myopathy,0001000,GHR,https://ghr.nlm.nih.gov/condition/tubular-aggregate-myopathy,C0410207,T047,Disorders
What is (are) tumor necrosis factor receptor-associated periodic syndrome ?,0001001-1,information,"Tumor necrosis factor receptor-associated periodic syndrome (commonly known as TRAPS) is a condition characterized by recurrent episodes of fever. These fevers typically last about 3 weeks but can last from a few days to a few months. The frequency of the episodes varies greatly among affected individuals; fevers can occur anywhere between every 6 weeks to every few years. Some individuals can go many years without having a fever episode. Fever episodes usually occur spontaneously, but sometimes they can be brought on by a variety of triggers, such as minor injury, infection, stress, exercise, or hormonal changes.  During episodes of fever, people with TRAPS can have additional signs and symptoms. These include abdominal and muscle pain and a spreading skin rash, typically found on the limbs. Affected individuals may also experience puffiness or swelling in the skin around the eyes (periorbital edema); joint pain; and inflammation in various areas of the body including the eyes, heart muscle, certain joints, throat, or mucous membranes such as the moist lining of the mouth and digestive tract. Occasionally, people with TRAPS develop amyloidosis, an abnormal buildup of a protein called amyloid in the kidneys that can lead to kidney failure. It is estimated that 15 to 20 percent of people with TRAPS develop amyloidosis, typically in mid-adulthood.  The fever episodes characteristic of TRAPS can begin at any age, from infancy to late adulthood, but most people have their first episode in childhood.",tumor necrosis factor receptor-associated periodic syndrome,0001001,GHR,https://ghr.nlm.nih.gov/condition/tumor-necrosis-factor-receptor-associated-periodic-syndrome,C0585274,T047,Disorders
How many people are affected by tumor necrosis factor receptor-associated periodic syndrome ?,0001001-2,frequency,"TRAPS has an estimated prevalence of one per million individuals; it is the second most common inherited recurrent fever syndrome, following a similar condition called familial Mediterranean fever. More than 1,000 people worldwide have been diagnosed with TRAPS.",tumor necrosis factor receptor-associated periodic syndrome,0001001,GHR,https://ghr.nlm.nih.gov/condition/tumor-necrosis-factor-receptor-associated-periodic-syndrome,C0585274,T047,Disorders
What are the genetic changes related to tumor necrosis factor receptor-associated periodic syndrome ?,0001001-3,genetic changes,"TRAPS is caused by mutations in the TNFRSF1A gene. This gene provides instructions for making a protein called tumor necrosis factor receptor 1 (TNFR1). This protein is found within the membrane of cells, where it attaches (binds) to another protein called tumor necrosis factor (TNF). This binding sends signals that can trigger the cell either to initiate inflammation or to self-destruct. Signaling within the cell initiates a pathway that turns on a protein called nuclear factor kappa B that triggers inflammation and leads to the production of immune system proteins called cytokines. The self-destruction of the cell (apoptosis) is initiated when the TNFR1 protein, bound to the TNF protein, is brought into the cell and triggers a process known as the caspase cascade.  Most TNFRSF1A gene mutations that cause TRAPS result in a TNFR1 protein that is folded into an incorrect 3-dimensional shape. These misfolded proteins are trapped within the cell and are not able to get to the cell surface to interact with TNF. Inside the cell, these proteins clump together and are thought to trigger alternative pathways that initiate inflammation. The clumps of protein constantly activate these alternative inflammation pathways, leading to excess inflammation in people with TRAPS. Additionally, because only one copy of the TNFRSF1A gene has a mutation, some normal TNFR1 proteins are produced and can bind to the TNF protein, leading to additional inflammation. It is unclear if disruption of the apoptosis pathway plays a role in the signs and symptoms of TRAPS.",tumor necrosis factor receptor-associated periodic syndrome,0001001,GHR,https://ghr.nlm.nih.gov/condition/tumor-necrosis-factor-receptor-associated-periodic-syndrome,C0585274,T047,Disorders
Is tumor necrosis factor receptor-associated periodic syndrome inherited ?,0001001-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. However, some people who inherit the altered gene never develop features of TRAPS. (This situation is known as reduced penetrance.) It is unclear why some people with a mutated gene develop the disease and other people with the mutated gene do not.  In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",tumor necrosis factor receptor-associated periodic syndrome,0001001,GHR,https://ghr.nlm.nih.gov/condition/tumor-necrosis-factor-receptor-associated-periodic-syndrome,C0585274,T047,Disorders
What are the treatments for tumor necrosis factor receptor-associated periodic syndrome ?,0001001-5,treatment,These resources address the diagnosis or management of TRAPS:  - Genetic Testing Registry: TNF receptor-associated periodic fever syndrome (TRAPS)  - University College London: National Amyloidosis Center (UK)   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,tumor necrosis factor receptor-associated periodic syndrome,0001001,GHR,https://ghr.nlm.nih.gov/condition/tumor-necrosis-factor-receptor-associated-periodic-syndrome,C0585274,T047,Disorders
What is (are) Turner syndrome ?,0001002-1,information,"Turner syndrome is a chromosomal condition that affects development in females. The most common feature of Turner syndrome is short stature, which becomes evident by about age 5. An early loss of ovarian function (ovarian hypofunction or premature ovarian failure) is also very common. The ovaries develop normally at first, but egg cells (oocytes) usually die prematurely and most ovarian tissue degenerates before birth. Many affected girls do not undergo puberty unless they receive hormone therapy, and most are unable to conceive (infertile). A small percentage of females with Turner syndrome retain normal ovarian function through young adulthood.  About 30 percent of females with Turner syndrome have extra folds of skin on the neck (webbed neck), a low hairline at the back of the neck, puffiness or swelling (lymphedema) of the hands and feet, skeletal abnormalities, or kidney problems. One third to one half of individuals with Turner syndrome are born with a heart defect, such as a narrowing of the large artery leaving the heart (coarctation of the aorta) or abnormalities of the valve that connects the aorta with the heart (the aortic valve). Complications associated with these heart defects can be life-threatening.  Most girls and women with Turner syndrome have normal intelligence. Developmental delays, nonverbal learning disabilities, and behavioral problems are possible, although these characteristics vary among affected individuals.",Turner syndrome,0001002,GHR,https://ghr.nlm.nih.gov/condition/turner-syndrome,C0041408,T019,Disorders
How many people are affected by Turner syndrome ?,0001002-2,frequency,"This condition occurs in about 1 in 2,500 newborn girls worldwide, but it is much more common among pregnancies that do not survive to term (miscarriages and stillbirths).",Turner syndrome,0001002,GHR,https://ghr.nlm.nih.gov/condition/turner-syndrome,C0041408,T019,Disorders
What are the genetic changes related to Turner syndrome ?,0001002-3,genetic changes,"Turner syndrome is related to the X chromosome, which is one of the two sex chromosomes. People typically have two sex chromosomes in each cell: females have two X chromosomes, while males have one X chromosome and one Y chromosome. Turner syndrome results when one normal X chromosome is present in a female's cells and the other sex chromosome is missing or structurally altered. The missing genetic material affects development before and after birth.  About half of individuals with Turner syndrome have monosomy X, which means each cell in the individual's body has only one copy of the X chromosome instead of the usual two sex chromosomes. Turner syndrome can also occur if one of the sex chromosomes is partially missing or rearranged rather than completely absent. Some women with Turner syndrome have a chromosomal change in only some of their cells, which is known as mosaicism. Women with Turner syndrome caused by X chromosome mosaicism are said to have mosaic Turner syndrome.  Researchers have not determined which genes on the X chromosome are associated with most of the features of Turner syndrome. They have, however, identified one gene called SHOX that is important for bone development and growth. The loss of one copy of this gene likely causes short stature and skeletal abnormalities in women with Turner syndrome.",Turner syndrome,0001002,GHR,https://ghr.nlm.nih.gov/condition/turner-syndrome,C0041408,T019,Disorders
Is Turner syndrome inherited ?,0001002-4,inheritance,"Most cases of Turner syndrome are not inherited. When this condition results from monosomy X, the chromosomal abnormality occurs as a random event during the formation of reproductive cells (eggs and sperm) in the affected person's parent. An error in cell division called nondisjunction can result in reproductive cells with an abnormal number of chromosomes. For example, an egg or sperm cell may lose a sex chromosome as a result of nondisjunction. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have a single X chromosome in each cell and will be missing the other sex chromosome.  Mosaic Turner syndrome is also not inherited. In an affected individual, it occurs as a random event during cell division in early fetal development. As a result, some of an affected person's cells have the usual two sex chromosomes, and other cells have only one copy of the X chromosome. Other sex chromosome abnormalities are also possible in females with X chromosome mosaicism.  Rarely, Turner syndrome caused by a partial deletion of the X chromosome can be passed from one generation to the next.",Turner syndrome,0001002,GHR,https://ghr.nlm.nih.gov/condition/turner-syndrome,C0041408,T019,Disorders
What are the treatments for Turner syndrome ?,0001002-5,treatment,These resources address the diagnosis or management of Turner syndrome:  - Genetic Testing Registry: Turner syndrome  - MedlinePlus Encyclopedia: Ovarian Hypofunction  - MedlinePlus Encyclopedia: Turner Syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Turner syndrome,0001002,GHR,https://ghr.nlm.nih.gov/condition/turner-syndrome,C0041408,T019,Disorders
What is (are) type 1 diabetes ?,0001003-1,information,"Type 1 diabetes is a disorder characterized by abnormally high blood sugar levels. In this form of diabetes, specialized cells in the pancreas called beta cells stop producing insulin. Insulin controls how much glucose (a type of sugar) is passed from the blood into cells for conversion to energy. Lack of insulin results in the inability to use glucose for energy or to control the amount of sugar in the blood.  Type 1 diabetes can occur at any age; however, it usually develops by early adulthood, most often starting in adolescence. The first signs and symptoms of the disorder are caused by high blood sugar and may include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, tingling or loss of feeling in the hands and feet, and weight loss. These symptoms may recur during the course of the disorder if blood sugar is not well controlled by insulin replacement therapy. Improper control can also cause blood sugar levels to become too low (hypoglycemia). This may occur when the body's needs change, such as during exercise or if eating is delayed. Hypoglycemia can cause headache, dizziness, hunger, shaking, sweating, weakness, and agitation.  Uncontrolled type 1 diabetes can lead to a life-threatening complication called diabetic ketoacidosis. Without insulin, cells cannot take in glucose. A lack of glucose in cells prompts the liver to try to compensate by releasing more glucose into the blood, and blood sugar can become extremely high. The cells, unable to use the glucose in the blood for energy, respond by using fats instead. Breaking down fats to obtain energy produces waste products called ketones, which can build up to toxic levels in people with type 1 diabetes, resulting in diabetic ketoacidosis. Affected individuals may begin breathing rapidly; develop a fruity odor in the breath; and experience nausea, vomiting, facial flushing, stomach pain, and dryness of the mouth (xerostomia). In severe cases, diabetic ketoacidosis can lead to coma and death.  Over many years, the chronic high blood sugar associated with diabetes may cause damage to blood vessels and nerves, leading to complications affecting many organs and tissues. The retina, which is the light-sensitive tissue at the back of the eye, can be damaged (diabetic retinopathy), leading to vision loss and eventual blindness. Kidney damage (diabetic nephropathy) may also occur and can lead to kidney failure and end-stage renal disease (ESRD). Pain, tingling, and loss of normal sensation (diabetic neuropathy) often occur, especially in the feet. Impaired circulation and absence of the normal sensations that prompt reaction to injury can result in permanent damage to the feet; in severe cases, the damage can lead to amputation. People with type 1 diabetes are also at increased risk of heart attacks, strokes, and problems with urinary and sexual function.",type 1 diabetes,0001003,GHR,https://ghr.nlm.nih.gov/condition/type-1-diabetes,C0011854,T047,Disorders
How many people are affected by type 1 diabetes ?,0001003-2,frequency,"Type 1 diabetes occurs in 10 to 20 per 100,000 people per year in the United States. By age 18, approximately 1 in 300 people in the United States develop type 1 diabetes. The disorder occurs with similar frequencies in Europe, the United Kingdom, Canada, and New Zealand. Type 1 diabetes occurs much less frequently in Asia and South America, with reported incidences as low as 1 in 1 million per year. For unknown reasons, during the past 20 years the worldwide incidence of type 1 diabetes has been increasing by 2 to 5 percent each year.  Type 1 diabetes accounts for 5 to 10 percent of cases of diabetes worldwide. Most people with diabetes have type 2 diabetes, in which the body continues to produce insulin but becomes less able to use it.",type 1 diabetes,0001003,GHR,https://ghr.nlm.nih.gov/condition/type-1-diabetes,C0011854,T047,Disorders
What are the genetic changes related to type 1 diabetes ?,0001003-3,genetic changes,"The causes of type 1 diabetes are unknown, although several risk factors have been identified. The risk of developing type 1 diabetes is increased by certain variants of the HLA-DQA1, HLA-DQB1, and HLA-DRB1 genes. These genes provide instructions for making proteins that play a critical role in the immune system. The HLA-DQA1, HLA-DQB1, and HLA-DRB1 genes belong to a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders such as viruses and bacteria.  Type 1 diabetes is generally considered to be an autoimmune disorder. Autoimmune disorders occur when the immune system attacks the body's own tissues and organs. For unknown reasons, in people with type 1 diabetes the immune system damages the insulin-producing beta cells in the pancreas. Damage to these cells impairs insulin production and leads to the signs and symptoms of type 1 diabetes.  HLA genes, including HLA-DQA1, HLA-DQB1, and HLA-DRB1, have many variations, and individuals have a certain combination of these variations, called a haplotype. Certain HLA haplotypes are associated with a higher risk of developing type 1 diabetes, with particular combinations of HLA-DQA1, HLA-DQB1, and HLA-DRB1 gene variations resulting in the highest risk. These haplotypes seem to increase the risk of an inappropriate immune response to beta cells. However, these variants are also found in the general population, and only about 5 percent of individuals with the gene variants develop type 1 diabetes. HLA variations account for approximately 40 percent of the genetic risk for the condition. Other HLA variations appear to be protective against the disease. Additional contributors, such as environmental factors and variations in other genes, are also thought to influence the development of this complex disorder.",type 1 diabetes,0001003,GHR,https://ghr.nlm.nih.gov/condition/type-1-diabetes,C0011854,T047,Disorders
Is type 1 diabetes inherited ?,0001003-4,inheritance,"A predisposition to develop type 1 diabetes is passed through generations in families, but the inheritance pattern is unknown.",type 1 diabetes,0001003,GHR,https://ghr.nlm.nih.gov/condition/type-1-diabetes,C0011854,T047,Disorders
What are the treatments for type 1 diabetes ?,0001003-5,treatment,"These resources address the diagnosis or management of type 1 diabetes:  - Food and Drug Administration: Blood Glucose Measuring Devices  - Food and Drug Administration: Insulin  - Genetic Testing Registry: Diabetes mellitus type 1  - Genetic Testing Registry: Diabetes mellitus, insulin-dependent, 10  - Genetic Testing Registry: Diabetes mellitus, insulin-dependent, 11  - Genetic Testing Registry: Diabetes mellitus, insulin-dependent, 12  - Genetic Testing Registry: Diabetes mellitus, insulin-dependent, 13  - Genetic Testing Registry: Diabetes mellitus, insulin-dependent, 15  - Genetic Testing Registry: Diabetes mellitus, insulin-dependent, 17  - Genetic Testing Registry: Diabetes mellitus, insulin-dependent, 18  - Genetic Testing Registry: Diabetes mellitus, insulin-dependent, 19  - Genetic Testing Registry: Diabetes mellitus, insulin-dependent, 2  - Genetic Testing Registry: Diabetes mellitus, insulin-dependent, 20  - Genetic Testing Registry: Diabetes mellitus, insulin-dependent, 21  - Genetic Testing Registry: Diabetes mellitus, insulin-dependent, 22  - Genetic Testing Registry: Diabetes mellitus, insulin-dependent, 23  - Genetic Testing Registry: Diabetes mellitus, insulin-dependent, 24  - Genetic Testing Registry: Diabetes mellitus, insulin-dependent, 3  - Genetic Testing Registry: Diabetes mellitus, insulin-dependent, 4  - Genetic Testing Registry: Diabetes mellitus, insulin-dependent, 5  - Genetic Testing Registry: Diabetes mellitus, insulin-dependent, 6  - Genetic Testing Registry: Diabetes mellitus, insulin-dependent, 7  - Genetic Testing Registry: Diabetes mellitus, insulin-dependent, 8  - Genetic Testing Registry: Diabetes mellitus, insulin-dependent, X-linked, susceptibility to  - MedlinePlus Encyclopedia: Anti-Insulin Antibody Test  - MedlinePlus Encyclopedia: Home Blood Sugar Testing  - MedlinePlus Health Topic: Islet Cell Transplantation  - MedlinePlus Health Topic: Pancreas Transplantation  - Type 1 Diabetes in Adults: National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care (2004)  - Type 1 Diabetes: Diagnosis and Management of Type 1 Diabetes in Children and Young People (2004)   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",type 1 diabetes,0001003,GHR,https://ghr.nlm.nih.gov/condition/type-1-diabetes,C0011854,T047,Disorders
What is (are) type A insulin resistance syndrome ?,0001004-1,information,"Type A insulin resistance syndrome is a rare disorder characterized by severe insulin resistance, a condition in which the body's tissues and organs do not respond properly to the hormone insulin. Insulin normally helps regulate blood sugar levels by controlling how much sugar (in the form of glucose) is passed from the bloodstream into cells to be used as energy. In people with type A insulin resistance syndrome, insulin resistance impairs blood sugar regulation and ultimately leads to a condition called diabetes mellitus, in which blood sugar levels can become dangerously high.  Severe insulin resistance also underlies the other signs and symptoms of type A insulin resistance syndrome. In affected females, the major features of the condition become apparent in adolescence. Many affected females do not begin menstruation by age 16 (primary amenorrhea) or their periods may be light and irregular (oligomenorrhea). They develop cysts on the ovaries and excessive body hair growth (hirsutism). Most affected females also develop a skin condition called acanthosis nigricans, in which the skin in body folds and creases becomes thick, dark, and velvety. Unlike most people with insulin resistance, females with type A insulin resistance syndrome are usually not overweight.  The features of type A insulin resistance syndrome are more subtle in affected males. Some males have low blood sugar (hypoglycemia) as the only sign; others may also have acanthosis nigricans. In many cases, males with this condition come to medical attention only when they develop diabetes mellitus in adulthood.  Type A insulin resistance syndrome is one of a group of related conditions described as inherited severe insulin resistance syndromes. These disorders, which also include Donohue syndrome and Rabson-Mendenhall syndrome, are considered part of a spectrum. Type A insulin resistance syndrome represents the mildest end of the spectrum: its features often do not become apparent until puberty or later, and it is generally not life-threatening.",type A insulin resistance syndrome,0001004,GHR,https://ghr.nlm.nih.gov/condition/type-a-insulin-resistance-syndrome,C0342336,T047,Disorders
How many people are affected by type A insulin resistance syndrome ?,0001004-2,frequency,"Type A insulin resistance syndrome is estimated to affect about 1 in 100,000 people worldwide. Because females have more health problems associated with the condition, it is diagnosed more often in females than in males.",type A insulin resistance syndrome,0001004,GHR,https://ghr.nlm.nih.gov/condition/type-a-insulin-resistance-syndrome,C0342336,T047,Disorders
What are the genetic changes related to type A insulin resistance syndrome ?,0001004-3,genetic changes,"Type A insulin resistance syndrome results from mutations in the INSR gene. This gene provides instructions for making a protein called an insulin receptor, which is found in many types of cells. Insulin receptors are embedded in the outer membrane surrounding the cell, where they attach (bind) to insulin circulating in the bloodstream. This binding triggers signaling pathways that influence many cell functions.  Most of the INSR gene mutations that cause type A insulin resistance syndrome lead to the production of a faulty insulin receptor that cannot transmit signals properly. Although insulin is present in the bloodstream, the defective receptors make it less able to exert its effects on cells and tissues. This severe resistance to the effects of insulin impairs blood sugar regulation and leads to diabetes mellitus. In females with type A insulin resistance syndrome, excess insulin in the bloodstream interacts with hormonal factors during adolescence to cause abnormalities of the menstrual cycle, ovarian cysts, and other features of the disorder.  This condition is designated as type A to distinguish it from type B insulin resistance syndrome. Although the two disorders have similar signs and symptoms, type B is not caused by INSR gene mutations; instead, it results from an abnormality of the immune system that blocks insulin receptor function.",type A insulin resistance syndrome,0001004,GHR,https://ghr.nlm.nih.gov/condition/type-a-insulin-resistance-syndrome,C0342336,T047,Disorders
Is type A insulin resistance syndrome inherited ?,0001004-4,inheritance,"Type A insulin resistance syndrome can have either an autosomal dominant or, less commonly, an autosomal recessive pattern of inheritance.  In autosomal dominant inheritance, one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  In autosomal recessive inheritance, both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",type A insulin resistance syndrome,0001004,GHR,https://ghr.nlm.nih.gov/condition/type-a-insulin-resistance-syndrome,C0342336,T047,Disorders
What are the treatments for type A insulin resistance syndrome ?,0001004-5,treatment,These resources address the diagnosis or management of type A insulin resistance syndrome:  - Genetic Testing Registry: Insulin-resistant diabetes mellitus AND acanthosis nigricans   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,type A insulin resistance syndrome,0001004,GHR,https://ghr.nlm.nih.gov/condition/type-a-insulin-resistance-syndrome,C0342336,T047,Disorders
What is (are) tyrosine hydroxylase deficiency ?,0001005-1,information,"Tyrosine hydroxylase (TH) deficiency is a disorder that primarily affects movement, with symptoms that may range from mild to severe.  The mild form of this disorder is called TH-deficient dopa-responsive dystonia (DRD). Symptoms usually appear during childhood. Affected individuals may exhibit unusual limb positioning and a lack of coordination when walking or running. In some cases, people with TH-deficient DRD have additional movement problems such as shaking when holding a position (postural tremor) or involuntary upward-rolling movements of the eyes. The movement difficulties may slowly increase with age but almost always get better with medical treatment.  The severe forms of TH deficiency are called infantile parkinsonism and progressive infantile encephalopathy. These forms of the disorder appear soon after birth and are more difficult to treat effectively.  Babies with infantile parkinsonism have delayed development of motor skills such as sitting unsupported or reaching for a toy. They may have stiff muscles, especially in the arms and legs; unusual body positioning; droopy eyelids (ptosis); and involuntary upward-rolling eye movements. The autonomic nervous system, which controls involuntary body functions, may also be affected. Resulting signs and symptoms can include constipation, backflow of stomach acids into the esophagus (gastroesophageal reflux), and difficulty regulating blood sugar, body temperature, and blood pressure. People with the infantile parkinsonism form of the disorder may have intellectual disability, speech problems, attention deficit disorder, and psychiatric conditions such as depression, anxiety, or obsessive-compulsive behaviors.  Progressive infantile encephalopathy is an uncommon severe form of TH deficiency. It is characterized by brain dysfunction and structural abnormalities leading to profound physical and intellectual disability.",tyrosine hydroxylase deficiency,0001005,GHR,https://ghr.nlm.nih.gov/condition/tyrosine-hydroxylase-deficiency,C1291314,T047,Disorders
How many people are affected by tyrosine hydroxylase deficiency ?,0001005-2,frequency,The prevalence of TH deficiency is unknown.,tyrosine hydroxylase deficiency,0001005,GHR,https://ghr.nlm.nih.gov/condition/tyrosine-hydroxylase-deficiency,C1291314,T047,Disorders
What are the genetic changes related to tyrosine hydroxylase deficiency ?,0001005-3,genetic changes,"Mutations in the TH gene cause TH deficiency. The TH gene provides instructions for making the enzyme tyrosine hydroxylase, which is important for normal functioning of the nervous system. Tyrosine hydroxylase takes part in the pathway that produces a group of chemical messengers (hormones) called catecholamines. Tyrosine hydroxylase helps convert the protein building block (amino acid) tyrosine to a catecholamine called dopamine. Dopamine transmits signals to help the brain control physical movement and emotional behavior. Other catecholamines called norepinephrine and epinephrine are produced from dopamine. Norepinephrine and epinephrine are involved in the autonomic nervous system.  Mutations in the TH gene result in reduced activity of the tyrosine hydroxylase enzyme. As a result, the body produces less dopamine, norepinephrine and epinephrine. These catecholamines are necessary for normal nervous system function, and changes in their levels contribute to the abnormal movements, autonomic dysfunction, and other neurological problems seen in people with TH deficiency.",tyrosine hydroxylase deficiency,0001005,GHR,https://ghr.nlm.nih.gov/condition/tyrosine-hydroxylase-deficiency,C1291314,T047,Disorders
Is tyrosine hydroxylase deficiency inherited ?,0001005-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",tyrosine hydroxylase deficiency,0001005,GHR,https://ghr.nlm.nih.gov/condition/tyrosine-hydroxylase-deficiency,C1291314,T047,Disorders
What are the treatments for tyrosine hydroxylase deficiency ?,0001005-5,treatment,"These resources address the diagnosis or management of TH deficiency:  - Gene Review: Gene Review: Tyrosine Hydroxylase Deficiency  - Genetic Testing Registry: Segawa syndrome, autosomal recessive   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",tyrosine hydroxylase deficiency,0001005,GHR,https://ghr.nlm.nih.gov/condition/tyrosine-hydroxylase-deficiency,C1291314,T047,Disorders
What is (are) tyrosinemia ?,0001006-1,information,"Tyrosinemia is a genetic disorder characterized by disruptions in the multistep process that breaks down the amino acid tyrosine, a building block of most proteins. If untreated, tyrosine and its byproducts build up in tissues and organs, which can lead to serious health problems.  There are three types of tyrosinemia, which are each distinguished by their symptoms and genetic cause. Tyrosinemia type I, the most severe form of this disorder, is characterized by signs and symptoms that begin in the first few months of life. Affected infants fail to gain weight and grow at the expected rate (failure to thrive) due to poor food tolerance because high-protein foods lead to diarrhea and vomiting. Affected infants may also have yellowing of the skin and whites of the eyes (jaundice), a cabbage-like odor, and an increased tendency to bleed (particularly nosebleeds). Tyrosinemia type I can lead to liver and kidney failure, softening and weakening of the bones (rickets), and an increased risk of liver cancer (hepatocellular carcinoma). Some affected children have repeated neurologic crises that consist of changes in mental state, reduced sensation in the arms and legs (peripheral neuropathy), abdominal pain, and respiratory failure. These crises can last from 1 to 7 days. Untreated, children with tyrosinemia type I often do not survive past the age of 10.  Tyrosinemia type II can affect the eyes, skin, and mental development. Signs and symptoms often begin in early childhood and include eye pain and redness, excessive tearing, abnormal sensitivity to light (photophobia), and thick, painful skin on the palms of their hands and soles of their feet (palmoplantar hyperkeratosis). About 50 percent of individuals with tyrosinemia type II have some degree of intellectual disability.  Tyrosinemia type III is the rarest of the three types. The characteristic features of this type include intellectual disability, seizures, and periodic loss of balance and coordination (intermittent ataxia).  About 10 percent of newborns have temporarily elevated levels of tyrosine (transient tyrosinemia). In these cases, the cause is not genetic. The most likely causes are vitamin C deficiency or immature liver enzymes due to premature birth.",tyrosinemia,0001006,GHR,https://ghr.nlm.nih.gov/condition/tyrosinemia,C0268483,T047,Disorders
How many people are affected by tyrosinemia ?,0001006-2,frequency,"Worldwide, tyrosinemia type I affects about 1 in 100,000 individuals. This type is more common in Norway where 1 in 60,000 to 74,000 individuals are affected. Tyrosinemia type I is even more common in Quebec, Canada where it occurs in about 1 in 16,000 individuals. In the Saguenay-Lac St. Jean region of Quebec, tyrosinemia type I affects 1 in 1,846 people.  Tyrosinemia type II occurs in fewer than 1 in 250,000 individuals worldwide. Tyrosinemia type III is very rare; only a few cases have been reported.",tyrosinemia,0001006,GHR,https://ghr.nlm.nih.gov/condition/tyrosinemia,C0268483,T047,Disorders
What are the genetic changes related to tyrosinemia ?,0001006-3,genetic changes,"Mutations in the FAH, TAT, and HPD genes can cause tyrosinemia types I, II, and III, respectively.  In the liver, enzymes break down tyrosine in a five step process, resulting in molecules that are either excreted by the kidneys or used to produce energy or make other substances in the body. The FAH gene provides instructions for the fumarylacetoacetate hydrolase enzyme, which is responsible for the final step of tyrosine breakdown. The enzyme produced from the TAT gene, called tyrosine aminotransferase enzyme, is involved at the first step in the process. The HPD gene provides instructions for making the 4-hydroxyphenylpyruvate dioxygenase enzyme, which is responsible for the second step.  Mutations in the FAH, TAT, or HPD gene cause a decrease in the activity of one of the enzymes in the breakdown of tyrosine. As a result, tyrosine and its byproducts accumulate to toxic levels, which can cause damage and death to cells in the liver, kidneys, nervous system, and other organs.",tyrosinemia,0001006,GHR,https://ghr.nlm.nih.gov/condition/tyrosinemia,C0268483,T047,Disorders
Is tyrosinemia inherited ?,0001006-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",tyrosinemia,0001006,GHR,https://ghr.nlm.nih.gov/condition/tyrosinemia,C0268483,T047,Disorders
What are the treatments for tyrosinemia ?,0001006-5,treatment,"These resources address the diagnosis or management of tyrosinemia:  - Baby's First Test: Tyrosinemia, Type I  - Baby's First Test: Tyrosinemia, Type II  - Baby's First Test: Tyrosinemia, Type III  - Gene Review: Gene Review: Tyrosinemia Type I  - Genetic Testing Registry: 4-Hydroxyphenylpyruvate dioxygenase deficiency  - Genetic Testing Registry: Tyrosinemia type 2  - Genetic Testing Registry: Tyrosinemia type I  - MedlinePlus Encyclopedia: Aminoaciduria   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",tyrosinemia,0001006,GHR,https://ghr.nlm.nih.gov/condition/tyrosinemia,C0268483,T047,Disorders
What is (are) ulcerative colitis ?,0001007-1,information,"Ulcerative colitis is a chronic disorder that affects the digestive system. This condition is characterized by abnormal inflammation of the inner surface of the rectum and colon, which make up most of the length of the large intestine. The inflammation usually causes open sores (ulcers) to develop in the large intestine. Ulcerative colitis usually appears between ages 15 and 30, although it can develop at any age. The inflammation tends to flare up multiple times throughout life, which causes recurring signs and symptoms.  The most common symptoms of ulcerative colitis are abdominal pain and cramping and frequent diarrhea, often with blood, pus, or mucus in the stool. Other signs and symptoms include nausea, loss of appetite, fatigue, and fevers. Chronic bleeding from the inflamed and ulcerated intestinal tissue can cause a shortage of red blood cells (anemia) in some affected individuals. People with this disorder have difficulty absorbing enough fluids and nutrients from their diet and often experience weight loss. Affected children usually grow more slowly than normal. Less commonly, ulcerative colitis causes problems with the skin, joints, eyes, kidneys, or liver, which are most likely due to abnormal inflammation.  Toxic megacolon is a rare complication of ulcerative colitis that can be life-threatening. Toxic megacolon involves widening of the colon and an overwhelming bacterial infection (sepsis). Ulcerative colitis also increases the risk of developing colon cancer, especially in people whose entire colon is inflamed and in people who have had ulcerative colitis for 8 or more years.  Ulcerative colitis is one common form of inflammatory bowel disease (IBD). Another type of IBD, Crohn disease, also causes chronic inflammation of the intestines. Unlike ulcerative colitis, which affects only the inner surface of the large intestine, Crohn disease can cause inflammation in any part of the digestive system, and the inflammation extends deeper into the intestinal tissue.",ulcerative colitis,0001007,GHR,https://ghr.nlm.nih.gov/condition/ulcerative-colitis,C0009324,T047,Disorders
How many people are affected by ulcerative colitis ?,0001007-2,frequency,"Ulcerative colitis is most common in North America and Western Europe; however the prevalence is increasing in other regions. In North America, ulcerative colitis affects approximately 40 to 240 in 100,000 people. It is estimated that more than 750,000 North Americans are affected by this disorder. Ulcerative colitis is more common in whites and people of eastern and central European (Ashkenazi) Jewish descent than among people of other ethnic backgrounds.",ulcerative colitis,0001007,GHR,https://ghr.nlm.nih.gov/condition/ulcerative-colitis,C0009324,T047,Disorders
What are the genetic changes related to ulcerative colitis ?,0001007-3,genetic changes,"A variety of genetic and environmental factors are likely involved in the development of ulcerative colitis. Recent studies have identified variations in dozens of genes that may be linked to ulcerative colitis; however, the role of these variations is not completely understood. Researchers speculate that this condition may result from changes in the intestinal lining's protective function or an abnormal immune response to the normal bacteria in the digestive tract, both of which may be influenced by genetic variations.  Several of the genes that may be associated with ulcerative colitis are involved in the protective function of the intestines. The inner surface of the intestines provides a barrier that protects the body's tissues from the bacteria that live in the intestines and from toxins that pass through the digestive tract. Researchers speculate that a breakdown of this barrier allows contact between the intestinal tissue and the bacteria and toxins, which can trigger an immune reaction. This immune response may lead to chronic inflammation and the digestive problems characteristic of ulcerative colitis.  Other possible disease-associated genes are involved in the immune system, particularly in the maturation and function of immune cells called T cells. T cells identify foreign substances and defend the body against infection. Certain genetic variations may make some individuals more prone to an overactive immune response to the bacteria and other microbes in the intestines, which may cause the chronic inflammation that occurs in ulcerative colitis. Another possible explanation is that ulcerative colitis occurs when the immune system malfunctions and attacks the cells of the intestines, causing inflammation.",ulcerative colitis,0001007,GHR,https://ghr.nlm.nih.gov/condition/ulcerative-colitis,C0009324,T047,Disorders
Is ulcerative colitis inherited ?,0001007-4,inheritance,"The inheritance pattern of ulcerative colitis is unknown because many genetic and environmental factors are likely to be involved. Even though the inheritance pattern of this condition is unclear, having a family member with ulcerative colitis increases the risk of developing the condition.",ulcerative colitis,0001007,GHR,https://ghr.nlm.nih.gov/condition/ulcerative-colitis,C0009324,T047,Disorders
What are the treatments for ulcerative colitis ?,0001007-5,treatment,These resources address the diagnosis or management of ulcerative colitis:  - American Society of Colon and Rectal Surgeons  - Cedars-Sinai  - Crohn's & Colitis Foundation of America: Colitis Diagnosis and Testing  - Crohn's & Colitis Foundation of America: Colitis Treatment Options  - Genetic Testing Registry: Inflammatory bowel disease 1  - MedlinePlus Encyclopedia: Ulcerative Colitis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,ulcerative colitis,0001007,GHR,https://ghr.nlm.nih.gov/condition/ulcerative-colitis,C0009324,T047,Disorders
What is (are) Unverricht-Lundborg disease ?,0001008-1,information,"Unverricht-Lundborg disease is a rare inherited form of epilepsy. Affected individuals usually begin showing signs and symptoms of the disorder between the ages of 6 and 15.  Unverricht-Lundborg disease is classified as a type of progressive myoclonus epilepsy. People with this disorder experience episodes of involuntary muscle jerking or twitching (myoclonus) that increase in frequency and severity over time. Episodes of myoclonus may be brought on by physical exertion, stress, light, or other stimuli. Within 5 to 10 years, the myoclonic episodes may become severe enough to interfere with walking and other everyday activities.  Affected individuals also usually have seizures involving loss of consciousness, muscle rigidity, and convulsions (tonic-clonic or grand mal seizures). Like the myoclonic episodes, these may increase in frequency over several years but may be controlled with treatment. After several years of progression, the frequency of seizures may stabilize or decrease.  Eventually people with Unverricht-Lundborg disease may develop problems with balance and coordination (ataxia), involuntary rhythmic shaking that worsens during movement (intentional tremor), difficulty speaking (dysarthria), depression, and a slow, mild decline in intellectual functioning.  People with Unverricht-Lundborg disease typically live into adulthood. Depending on the severity of the condition and a person's response to treatment, life expectancy may be normal.",Unverricht-Lundborg disease,0001008,GHR,https://ghr.nlm.nih.gov/condition/unverricht-lundborg-disease,C0751785,T047,Disorders
How many people are affected by Unverricht-Lundborg disease ?,0001008-2,frequency,"Progressive myoclonus epilepsy is a rare condition. Unverricht-Lundborg disease is believed to be the most common cause of this type of epilepsy, but its worldwide prevalence is unknown. Unverricht-Lundborg disease occurs most frequently in Finland, where approximately 4 in 100,000 people are affected.",Unverricht-Lundborg disease,0001008,GHR,https://ghr.nlm.nih.gov/condition/unverricht-lundborg-disease,C0751785,T047,Disorders
What are the genetic changes related to Unverricht-Lundborg disease ?,0001008-3,genetic changes,"Mutations in the CSTB gene cause Unverricht-Lundborg disease. The CSTB gene provides instructions for making a protein called cystatin B. This protein reduces the activity of enzymes called cathepsins. Cathepsins help break down certain proteins in the lysosomes (compartments in the cell that digest and recycle materials). While the specific function of cystatin B is unclear, it may help protect the cells' proteins from cathepsins that leak out of the lysosomes.  In almost all affected individuals, Unverricht-Lundborg disease is caused by an increase in size of the CSTB gene. One region of the CSTB gene has a particular repeating sequence of 12 DNA building blocks (nucleotides). This sequence is normally repeated two or three times within the gene and is called a dodecamer repeat. Most people with this disorder have more than 30 repeats of the dodecamer sequence in both copies of the CSTB gene. A small number of people with Unverricht-Lundborg disease carry other mutations.  The increased number of dodecamer repeats in the CSTB gene seems to interfere with the production of the cystatin B protein. Levels of cystatin B in affected individuals are only 5 to 10 percent of normal, and cathepsin levels are significantly increased. These changes are believed to cause the signs and symptoms of Unverricht-Lundborg disease, but it is unclear how a reduction in the amount of cystatin B leads to the features of this disorder.",Unverricht-Lundborg disease,0001008,GHR,https://ghr.nlm.nih.gov/condition/unverricht-lundborg-disease,C0751785,T047,Disorders
Is Unverricht-Lundborg disease inherited ?,0001008-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Unverricht-Lundborg disease,0001008,GHR,https://ghr.nlm.nih.gov/condition/unverricht-lundborg-disease,C0751785,T047,Disorders
What are the treatments for Unverricht-Lundborg disease ?,0001008-5,treatment,These resources address the diagnosis or management of Unverricht-Lundborg disease:  - Gene Review: Gene Review: Unverricht-Lundborg Disease  - Genetic Testing Registry: Unverricht-Lundborg syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Unverricht-Lundborg disease,0001008,GHR,https://ghr.nlm.nih.gov/condition/unverricht-lundborg-disease,C0751785,T047,Disorders
What is (are) uromodulin-associated kidney disease ?,0001009-1,information,"Uromodulin-associated kidney disease is an inherited condition that affects the kidneys. The signs and symptoms of this condition vary, even among members of the same family.  Many individuals with uromodulin-associated kidney disease develop high blood levels of a waste product called uric acid. Normally, the kidneys remove uric acid from the blood and transfer it to urine. In this condition, the kidneys are unable to remove uric acid from the blood effectively. A buildup of uric acid can cause gout, which is a form of arthritis resulting from uric acid crystals in the joints. The signs and symptoms of gout may appear as early as a person's teens in uromodulin-associated kidney disease.  Uromodulin-associated kidney disease causes slowly progressive kidney disease, with the signs and symptoms usually beginning during the teenage years. The kidneys become less able to filter fluids and waste products from the body as this condition progresses, resulting in kidney failure. Individuals with uromodulin-associated kidney disease typically require either dialysis to remove wastes from the blood or a kidney transplant between the ages of 30 and 70. Occasionally, affected individuals are found to have small kidneys or kidney cysts (medullary cysts).",uromodulin-associated kidney disease,0001009,GHR,https://ghr.nlm.nih.gov/condition/uromodulin-associated-kidney-disease,C0022658,T047,Disorders
How many people are affected by uromodulin-associated kidney disease ?,0001009-2,frequency,The prevalence of uromodulin-associated kidney disease is unknown. It accounts for fewer than 1 percent of cases of kidney disease.,uromodulin-associated kidney disease,0001009,GHR,https://ghr.nlm.nih.gov/condition/uromodulin-associated-kidney-disease,C0022658,T047,Disorders
What are the genetic changes related to uromodulin-associated kidney disease ?,0001009-3,genetic changes,"Mutations in the UMOD gene cause uromodulin-associated kidney disease. This gene provides instructions for making the uromodulin protein, which is produced by the kidneys and then excreted from the body in urine. The function of uromodulin remains unclear, although it is known to be the most abundant protein in the urine of healthy individuals. Researchers have suggested that uromodulin may protect against urinary tract infections. It may also help control the amount of water in urine.  Most mutations in the UMOD gene change single protein building blocks (amino acids) used to make uromodulin. These mutations alter the structure of the protein, preventing its release from kidney cells. Abnormal buildup of uromodulin may trigger the self-destruction (apoptosis) of cells in the kidneys, causing progressive kidney disease.",uromodulin-associated kidney disease,0001009,GHR,https://ghr.nlm.nih.gov/condition/uromodulin-associated-kidney-disease,C0022658,T047,Disorders
Is uromodulin-associated kidney disease inherited ?,0001009-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",uromodulin-associated kidney disease,0001009,GHR,https://ghr.nlm.nih.gov/condition/uromodulin-associated-kidney-disease,C0022658,T047,Disorders
What are the treatments for uromodulin-associated kidney disease ?,0001009-5,treatment,"These resources address the diagnosis or management of uromodulin-associated kidney disease:  - Gene Review: Gene Review: Autosomal Dominant Tubulointerstitial Kidney Disease, UMOD-Related (ADTKD-UMOD)  - Genetic Testing Registry: Familial juvenile gout  - Genetic Testing Registry: Glomerulocystic kidney disease with hyperuricemia and isosthenuria  - Genetic Testing Registry: Medullary cystic kidney disease 2   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",uromodulin-associated kidney disease,0001009,GHR,https://ghr.nlm.nih.gov/condition/uromodulin-associated-kidney-disease,C0022658,T047,Disorders
What is (are) Usher syndrome ?,0001010-1,information,"Usher syndrome is a condition characterized by hearing loss or deafness and progressive vision loss. The loss of vision is caused by an eye disease called retinitis pigmentosa (RP), which affects the layer of light-sensitive tissue at the back of the eye (the retina). Vision loss occurs as the light-sensing cells of the retina gradually deteriorate. Night vision loss begins first, followed by blind spots that develop in the side (peripheral) vision. Over time, these blind spots enlarge and merge to produce tunnel vision. In some cases of Usher syndrome, vision is further impaired by clouding of the lens of the eye (cataracts). Many people with retinitis pigmentosa retain some central vision throughout their lives, however.  Researchers have identified three major types of Usher syndrome, designated as types I, II, and III. These types are distinguished by their severity and the age when signs and symptoms appear. Type I is further divided into seven distinct subtypes, designated as types IA through IG. Usher syndrome type II has at least three described subtypes, designated as types IIA, IIB, and IIC.  Individuals with Usher syndrome type I are typically born completely deaf or lose most of their hearing within the first year of life. Progressive vision loss caused by retinitis pigmentosa becomes apparent in childhood. This type of Usher syndrome also includes problems with the inner ear that affect balance. As a result, children with the condition begin sitting independently and walking later than usual.  Usher syndrome type II is characterized by hearing loss from birth and progressive vision loss that begins in adolescence or adulthood. The hearing loss associated with this form of Usher syndrome ranges from mild to severe and mainly affects high tones. Affected children have problems hearing high, soft speech sounds, such as those of the letters d and t. The degree of hearing loss varies within and among families with this condition. Unlike other forms of Usher syndrome, people with type II do not have difficulties with balance caused by inner ear problems.  People with Usher syndrome type III experience progressive hearing loss and vision loss beginning in the first few decades of life. Unlike the other forms of Usher syndrome, infants with Usher syndrome type III are usually born with normal hearing. Hearing loss typically begins during late childhood or adolescence, after the development of speech, and progresses over time. By middle age, most affected individuals are profoundly deaf. Vision loss caused by retinitis pigmentosa also develops in late childhood or adolescence. People with Usher syndrome type III may also experience difficulties with balance due to inner ear problems. These problems vary among affected individuals, however.",Usher syndrome,0001010,GHR,https://ghr.nlm.nih.gov/condition/usher-syndrome,C0271097,T019,Disorders
How many people are affected by Usher syndrome ?,0001010-2,frequency,"Usher syndrome is thought to be responsible for 3 percent to 6 percent of all childhood deafness and about 50 percent of deaf-blindness in adults. Usher syndrome type I is estimated to occur in at least 4 per 100,000 people. It may be more common in certain ethnic populations, such as people with Ashkenazi (central and eastern European) Jewish ancestry and the Acadian population in Louisiana. Type II is thought to be the most common form of Usher syndrome, although the frequency of this type is unknown. Type III Usher syndrome accounts for only a small percentage of all Usher syndrome cases in most populations. This form of the condition is more common in the Finnish population, however, where it accounts for about 40 percent of all cases.",Usher syndrome,0001010,GHR,https://ghr.nlm.nih.gov/condition/usher-syndrome,C0271097,T019,Disorders
What are the genetic changes related to Usher syndrome ?,0001010-3,genetic changes,"Mutations in the ADGRV1, CDH23, CLRN1, MYO7A, PCDH15, USH1C, USH1G, and USH2A genes can cause Usher syndrome.  The genes related to Usher syndrome provide instructions for making proteins that play important roles in normal hearing, balance, and vision. They function in the development and maintenance of hair cells, which are sensory cells in the inner ear that help transmit sound and motion signals to the brain. In the retina, these genes are also involved in determining the structure and function of light-sensing cells called rods and cones. In some cases, the exact role of these genes in hearing and vision is unknown. Most of the mutations responsible for Usher syndrome lead to a loss of hair cells in the inner ear and a gradual loss of rods and cones in the retina. Degeneration of these sensory cells causes hearing loss, balance problems, and vision loss characteristic of this condition.  Usher syndrome type I can result from mutations in the CDH23, MYO7A, PCDH15, USH1C, or USH1G gene. At least two other unidentified genes also cause this form of Usher syndrome.  Usher syndrome type II is caused by mutations in at least four genes. Only two of these genes, ADGRV1 and USH2A, have been identified.  Mutations in at least two genes are responsible for Usher syndrome type III; however, CLRN1 is the only gene that has been identified.",Usher syndrome,0001010,GHR,https://ghr.nlm.nih.gov/condition/usher-syndrome,C0271097,T019,Disorders
Is Usher syndrome inherited ?,0001010-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Usher syndrome,0001010,GHR,https://ghr.nlm.nih.gov/condition/usher-syndrome,C0271097,T019,Disorders
What are the treatments for Usher syndrome ?,0001010-5,treatment,"These resources address the diagnosis or management of Usher syndrome:  - Gene Review: Gene Review: Usher Syndrome Type I  - Gene Review: Gene Review: Usher Syndrome Type II  - Genetic Testing Registry: Usher syndrome type 2  - Genetic Testing Registry: Usher syndrome, type 1  - Genetic Testing Registry: Usher syndrome, type 3A  - MedlinePlus Encyclopedia: Retinitis Pigmentosa   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Usher syndrome,0001010,GHR,https://ghr.nlm.nih.gov/condition/usher-syndrome,C0271097,T019,Disorders
What is (are) UV-sensitive syndrome ?,0001011-1,information,"UV-sensitive syndrome is a condition that is characterized by sensitivity to the ultraviolet (UV) rays in sunlight. Even a small amount of sun exposure can cause a sunburn in affected individuals. In addition, these individuals can have freckles, dryness, or changes in coloring (pigmentation) on sun-exposed areas of skin after repeated exposure. Some people with UV-sensitive syndrome have small clusters of enlarged blood vessels just under the skin (telangiectasia), usually on the cheeks and nose. Although UV exposure can cause skin cancers, people with UV-sensitive syndrome do not have an increased risk of developing these forms of cancer compared with the general population.",UV-sensitive syndrome,0001011,GHR,https://ghr.nlm.nih.gov/condition/uv-sensitive-syndrome,C1833561,T047,Disorders
How many people are affected by UV-sensitive syndrome ?,0001011-2,frequency,"UV-sensitive syndrome appears to be a rare condition; only a small number of affected individuals have been reported in the scientific literature. However, this condition may be underdiagnosed.",UV-sensitive syndrome,0001011,GHR,https://ghr.nlm.nih.gov/condition/uv-sensitive-syndrome,C1833561,T047,Disorders
What are the genetic changes related to UV-sensitive syndrome ?,0001011-3,genetic changes,"UV-sensitive syndrome can result from mutations in the ERCC6 gene (also known as the CSB gene), the ERCC8 gene (also known as the CSA gene), or the UVSSA gene. These genes provide instructions for making proteins that are involved in repairing damaged DNA. DNA can be damaged by UV rays from the sun and by toxic chemicals, radiation, and unstable molecules called free radicals. Cells are usually able to fix DNA damage before it causes problems. If left uncorrected, DNA damage accumulates, which causes cells to malfunction and can lead to cell death.  Cells have several mechanisms to correct DNA damage. The CSB, CSA, and UVSSA proteins are involved in one mechanism that repairs damaged DNA within active genes (those genes undergoing gene transcription, the first step in protein production). When DNA in active genes is damaged, the enzyme that carries out gene transcription (RNA polymerase) gets stuck, and the process stalls. Researchers think that the CSB, CSA, and UVSSA proteins help remove RNA polymerase from the damaged site, so the DNA can be repaired.  Mutations in the ERCC6, ERCC8, or UVSSA genes lead to the production of an abnormal protein or the loss of the protein. If any of these proteins is not functioning normally, skin cells cannot repair DNA damage caused by UV rays, and transcription of damaged genes is blocked. However, it is unclear exactly how abnormalities in these proteins cause the signs and symptoms of UV-sensitive syndrome.",UV-sensitive syndrome,0001011,GHR,https://ghr.nlm.nih.gov/condition/uv-sensitive-syndrome,C1833561,T047,Disorders
Is UV-sensitive syndrome inherited ?,0001011-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",UV-sensitive syndrome,0001011,GHR,https://ghr.nlm.nih.gov/condition/uv-sensitive-syndrome,C1833561,T047,Disorders
What are the treatments for UV-sensitive syndrome ?,0001011-5,treatment,These resources address the diagnosis or management of UV-sensitive syndrome:  - Genetic Testing Registry: UV-sensitive syndrome  - Genetic Testing Registry: UV-sensitive syndrome 2  - Genetic Testing Registry: UV-sensitive syndrome 3  - Merck Manual Home Health Edition: Sunburn  - World Health Organization: Sun Protection   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,UV-sensitive syndrome,0001011,GHR,https://ghr.nlm.nih.gov/condition/uv-sensitive-syndrome,C1833561,T047,Disorders
What is (are) VACTERL association ?,0001012-1,information,"VACTERL association is a disorder that affects many body systems. VACTERL stands for vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. People diagnosed with VACTERL association typically have at least three of these characteristic features. Affected individuals may have additional abnormalities that are not among the characteristic features of VACTERL association.  Defects in the bones of the spine (vertebrae) are present in 60 to 80 percent of people with VACTERL association. These defects may include misshapen vertebrae, fused vertebrae, and missing or extra vertebrae. In some people, spinal problems require surgery or cause health problems, such as back pain of varying severity, throughout life. Sixty to 90 percent of individuals with VACTERL association have narrowing or blockage of the anus (anal atresia). Anal atresia may be accompanied by abnormalities of the genitalia and urinary tract (genitourinary anomalies). Heart (cardiac) defects occur in 40 to 80 percent of individuals with VACTERL association. Cardiac defects can range in severity from a life-threatening problem to a subtle defect that does not cause health problems. Fifty to 80 percent of people with VACTERL association have a tracheo-esophageal fistula, which is an abnormal connection (fistula) between the esophagus and the windpipe (trachea). Tracheo-esophageal fistula can cause problems with breathing and feeding early in life and typically requires surgical correction in infancy. Kidney (renal) anomalies occur in 50 to 80 percent of individuals with VACTERL association. Affected individuals may be missing one or both kidneys or have abnormally developed or misshapen kidneys, which can affect kidney function. Limb abnormalities are seen in 40 to 50 percent of people with VACTERL association. These abnormalities most commonly include poorly developed or missing thumbs or underdeveloped forearms and hands.  Some of the features of VACTERL association can be subtle and are not identified until late in childhood or adulthood, making diagnosis of this condition difficult.",VACTERL association,0001012,GHR,https://ghr.nlm.nih.gov/condition/vacterl-association,C1735591,T019,Disorders
How many people are affected by VACTERL association ?,0001012-2,frequency,"VACTERL association occurs in 1 in 10,000 to 40,000 newborns.",VACTERL association,0001012,GHR,https://ghr.nlm.nih.gov/condition/vacterl-association,C1735591,T019,Disorders
What are the genetic changes related to VACTERL association ?,0001012-3,genetic changes,"VACTERL association is a complex condition that may have different causes in different people. In some people, the condition is likely caused by the interaction of multiple genetic and environmental factors. Some possible genetic and environmental influences have been identified and are being studied.  The developmental abnormalities characteristic of VACTERL association develop before birth. The disruption to fetal development that causes VACTERL association likely occurs early in development, resulting in birth defects that affect multiple body systems. It is unclear why the features characteristic of VACTERL association group together in affected individuals.",VACTERL association,0001012,GHR,https://ghr.nlm.nih.gov/condition/vacterl-association,C1735591,T019,Disorders
Is VACTERL association inherited ?,0001012-4,inheritance,"Most cases of VACTERL association are sporadic, which means they occur in people with no history of the condition in their family. Rarely, families have multiple people affected with VACTERL association. A few affected individuals have family members with one or two features, but not enough signs to be diagnosed with the condition. In these families, the features of VACTERL association often do not have a clear pattern of inheritance. Multiple genetic and environmental factors likely play a part in determining the risk of developing this condition and how severe the condition will be in an individual.",VACTERL association,0001012,GHR,https://ghr.nlm.nih.gov/condition/vacterl-association,C1735591,T019,Disorders
What are the treatments for VACTERL association ?,0001012-5,treatment,These resources address the diagnosis or management of VACTERL association:  - MedlinePlus Encyclopedia: Tracheoesophageal Fistula and Esophageal Atresia Repair   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,VACTERL association,0001012,GHR,https://ghr.nlm.nih.gov/condition/vacterl-association,C1735591,T019,Disorders
What is (are) van der Woude syndrome ?,0001013-1,information,"Van der Woude syndrome is a condition that affects the development of the face. Many people with this disorder are born with a cleft lip, a cleft palate (an opening in the roof of the mouth), or both. Affected individuals usually have depressions (pits) near the center of the lower lip, which may appear moist due to the presence of salivary and mucous glands in the pits. Small mounds of tissue on the lower lip may also occur. In some cases, people with van der Woude syndrome have missing teeth.  People with van der Woude syndrome who have cleft lip and/or palate, like other individuals with these facial conditions, have an increased risk of delayed language development, learning disabilities, or other mild cognitive problems. The average IQ of individuals with van der Woude syndrome is not significantly different from that of the general population.",van der Woude syndrome,0001013,GHR,https://ghr.nlm.nih.gov/condition/van-der-woude-syndrome,C1511780,T019,Disorders
How many people are affected by van der Woude syndrome ?,0001013-2,frequency,"Van der Woude syndrome is believed to occur in 1 in 35,000 to 1 in 100,000 people, based on data from Europe and Asia. Van der Woude syndrome is the most common cause of cleft lip and palate resulting from variations in a single gene, and this condition accounts for approximately 1 in 50 such cases.",van der Woude syndrome,0001013,GHR,https://ghr.nlm.nih.gov/condition/van-der-woude-syndrome,C1511780,T019,Disorders
What are the genetic changes related to van der Woude syndrome ?,0001013-3,genetic changes,"Mutations in the IRF6 gene cause van der Woude syndrome. The IRF6 gene provides instructions for making a protein that plays an important role in early development. This protein is a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of particular genes.  The IRF6 protein is active in cells that give rise to tissues in the head and face. It is also involved in the development of other parts of the body, including the skin and genitals.  Mutations in the IRF6 gene that cause van der Woude syndrome prevent one copy of the gene in each cell from making any functional protein. A shortage of the IRF6 protein affects the development and maturation of tissues in the face, resulting in the signs and symptoms of van der Woude syndrome.",van der Woude syndrome,0001013,GHR,https://ghr.nlm.nih.gov/condition/van-der-woude-syndrome,C1511780,T019,Disorders
Is van der Woude syndrome inherited ?,0001013-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition. Occasionally, an individual who has a copy of the altered gene does not show any signs or symptoms of the disorder.",van der Woude syndrome,0001013,GHR,https://ghr.nlm.nih.gov/condition/van-der-woude-syndrome,C1511780,T019,Disorders
What are the treatments for van der Woude syndrome ?,0001013-5,treatment,These resources address the diagnosis or management of van der Woude syndrome:  - Gene Review: Gene Review: IRF6-Related Disorders  - Genetic Testing Registry: Van der Woude syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,van der Woude syndrome,0001013,GHR,https://ghr.nlm.nih.gov/condition/van-der-woude-syndrome,C1511780,T019,Disorders
What is (are) very long-chain acyl-CoA dehydrogenase deficiency ?,0001014-1,information,"Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a condition that prevents the body from converting certain fats to energy, particularly during periods without food (fasting).  Signs and symptoms of VLCAD deficiency typically appear during infancy or early childhood and can include low blood sugar (hypoglycemia), lack of energy (lethargy), and muscle weakness. Affected individuals are also at risk for serious complications such as liver abnormalities and life-threatening heart problems. When symptoms begin in adolescence or adulthood, they tend to be milder and usually do not involve the heart.  Problems related to VLCAD deficiency can be triggered by periods of fasting, illness, and exercise. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.",very long-chain acyl-CoA dehydrogenase deficiency,0001014,GHR,https://ghr.nlm.nih.gov/condition/very-long-chain-acyl-coa-dehydrogenase-deficiency,C0342784,T047,Disorders
How many people are affected by very long-chain acyl-CoA dehydrogenase deficiency ?,0001014-2,frequency,"VLCAD deficiency is estimated to affect 1 in 40,000 to 120,000 people.",very long-chain acyl-CoA dehydrogenase deficiency,0001014,GHR,https://ghr.nlm.nih.gov/condition/very-long-chain-acyl-coa-dehydrogenase-deficiency,C0342784,T047,Disorders
What are the genetic changes related to very long-chain acyl-CoA dehydrogenase deficiency ?,0001014-3,genetic changes,"Mutations in the ACADVL gene cause VLCAD deficiency. This gene provides instructions for making an enzyme called very long-chain acyl-CoA dehydrogenase, which is required to break down (metabolize) a group of fats called very long-chain fatty acids. These fatty acids are found in foods and the body's fat tissues. Fatty acids are a major source of energy for the heart and muscles. During periods of fasting, fatty acids are also an important energy source for the liver and other tissues.  Mutations in the ACADVL gene lead to a shortage (deficiency) of the VLCAD enzyme within cells. Without sufficient amounts of this enzyme, very long-chain fatty acids are not metabolized properly. As a result, these fats are not converted to energy, which can lead to the characteristic signs and symptoms of this disorder such as lethargy and hypoglycemia. Very long-chain fatty acids or partially metabolized fatty acids may also build up in tissues and damage the heart, liver, and muscles. This abnormal buildup causes the other signs and symptoms of VLCAD deficiency.",very long-chain acyl-CoA dehydrogenase deficiency,0001014,GHR,https://ghr.nlm.nih.gov/condition/very-long-chain-acyl-coa-dehydrogenase-deficiency,C0342784,T047,Disorders
Is very long-chain acyl-CoA dehydrogenase deficiency inherited ?,0001014-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",very long-chain acyl-CoA dehydrogenase deficiency,0001014,GHR,https://ghr.nlm.nih.gov/condition/very-long-chain-acyl-coa-dehydrogenase-deficiency,C0342784,T047,Disorders
What are the treatments for very long-chain acyl-CoA dehydrogenase deficiency ?,0001014-5,treatment,These resources address the diagnosis or management of VLCAD deficiency:  - Baby's First Test  - Gene Review: Gene Review: Very Long-Chain Acyl-Coenzyme A Dehydrogenase Deficiency  - Genetic Testing Registry: Very long chain acyl-CoA dehydrogenase deficiency  - MedlinePlus Encyclopedia: Newborn Screening Tests   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,very long-chain acyl-CoA dehydrogenase deficiency,0001014,GHR,https://ghr.nlm.nih.gov/condition/very-long-chain-acyl-coa-dehydrogenase-deficiency,C0342784,T047,Disorders
What is (are) vitamin D-dependent rickets ?,0001015-1,information,"Vitamin D-dependent rickets is a disorder of bone development that leads to softening and weakening of the bones (rickets). The condition is split into two major types: type 1 (VDDR1), which is also known as pseudovitamin D deficiency rickets or vitamin D 1-hydroxylase deficiency, and type 2 (VDDR2), also known as hereditary vitamin D-resistant rickets (HVDRR).  The signs and symptoms of this condition begin within months of birth, and most are the same for VDDR1 and VDDR2. The weak bones often cause bone pain and delayed growth and have a tendency to fracture. When affected children begin to walk, they may develop bowed legs because the bones are too weak to bear weight. Impaired bone development also results in widening of the areas near the ends of bones where new bone forms (metaphyses), especially in the knees, wrists, and ribs. Some people with vitamin D-dependent rickets have dental abnormalities such as thin tooth enamel and frequent cavities. Poor muscle tone (hypotonia) and muscle weakness are also common in this condition, and some affected individuals develop seizures.  In vitamin D-dependent rickets, there is an imbalance of certain substances in the blood. Both VDDR1 and VDDR2 are characterized by low levels of the minerals calcium (hypocalcemia) and phosphate (hypophosphatemia), which are essential for the normal formation of bones and teeth. Affected individuals also have high levels of a hormone involved in regulating calcium levels called parathyroid hormone (PTH), which leads to a condition called secondary hyperparathyroidism. The two forms of vitamin D-dependent rickets can be distinguished by blood levels of a hormone called calcitriol, which is the active form of vitamin D; individuals with VDDR1 have abnormally low levels of calcitriol and individuals with VDDR2 have abnormally high levels.  Hair loss (alopecia) can occur in VDDR2, although not everyone with this form of the condition has alopecia. Affected individuals can have sparse or patchy hair or no hair at all on their heads. Some affected individuals are missing body hair as well.",vitamin D-dependent rickets,0001015,GHR,https://ghr.nlm.nih.gov/condition/vitamin-d-dependent-rickets,C0221468,T047,Disorders
How many people are affected by vitamin D-dependent rickets ?,0001015-2,frequency,"Rickets affects an estimated 1 in 200,000 children. The condition is most often caused by a lack of vitamin D in the diet or insufficient sun exposure rather than genetic mutations; genetic forms of rickets, including VDDR1 and VDDR2, are much less common. The prevalence of VDDR1 and VDDR2 is unknown. VDDR1 is more common in the French Canadian population than in other populations.",vitamin D-dependent rickets,0001015,GHR,https://ghr.nlm.nih.gov/condition/vitamin-d-dependent-rickets,C0221468,T047,Disorders
What are the genetic changes related to vitamin D-dependent rickets ?,0001015-3,genetic changes,"The two types of vitamin D-dependent rickets have different genetic causes: CYP27B1 gene mutations cause VDDR1, and VDR gene mutations cause VDDR2. Both genes are involved in the body's response to vitamin D, an important vitamin that can be can be acquired from foods in the diet or made by the body with the help of sunlight. Vitamin D helps maintain the proper balance of several minerals in the body, including calcium and phosphate. One of vitamin D's major roles is to control the absorption of calcium and phosphate from the intestines into the bloodstream.  The CYP27B1 gene provides instructions for making an enzyme called 1-alpha-hydroxylase (1-hydroxylase). This enzyme carries out the final reaction to convert vitamin D to its active form, calcitriol. Once converted, calcitriol attaches (binds) to a protein called vitamin D receptor (VDR), which is produced from the VDR gene. The resulting calcitriol-VDR complex then binds to particular regions of DNA and regulates the activity of vitamin D-responsive genes. By turning these genes on or off, VDR helps control the absorption of calcium and phosphate and other processes that regulate calcium levels in the body. VDR is also involved in hair growth through a process that does not require calcitriol binding.  Mutations in either of these genes prevent the body from responding to vitamin D. CYP27B1 gene mutations reduce or eliminate 1-hydroxylase activity, which means vitamin D is not converted to its active form. The absence of calcitriol means vitamin D-responsive genes are not turned on (activated). VDR gene mutations alter the vitamin D receptor so that it cannot regulate gene activity, regardless of the presence of calcitriol in the body; often the altered receptor cannot interact with calcitriol or with DNA.  Without activation of vitamin D-responsive genes, absorption of calcium and phosphate falls, leading to hypocalcemia and hypophosphatemia. The lack of calcium and phosphate slows the deposition of these minerals in developing bones (bone mineralization), which leads to soft, weak bones and other features of vitamin D-dependent rickets. Low levels of calcium stimulate production of PTH, resulting in secondary hyperparathyroidism; hypocalcemia can also cause muscle weakness and seizures in individuals with vitamin D-dependent rickets. Certain abnormalities in the VDR protein also impair hair growth, causing alopecia in some people with VDDR2.",vitamin D-dependent rickets,0001015,GHR,https://ghr.nlm.nih.gov/condition/vitamin-d-dependent-rickets,C0221468,T047,Disorders
Is vitamin D-dependent rickets inherited ?,0001015-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",vitamin D-dependent rickets,0001015,GHR,https://ghr.nlm.nih.gov/condition/vitamin-d-dependent-rickets,C0221468,T047,Disorders
What are the treatments for vitamin D-dependent rickets ?,0001015-5,treatment,"These resources address the diagnosis or management of vitamin D-dependent rickets:  - Genetic Testing Registry: Vitamin D-dependent rickets, type 1  - Genetic Testing Registry: Vitamin D-dependent rickets, type 2  - Genetic Testing Registry: Vitamin d-dependent rickets, type 2b, with normal vitamin d receptor   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",vitamin D-dependent rickets,0001015,GHR,https://ghr.nlm.nih.gov/condition/vitamin-d-dependent-rickets,C0221468,T047,Disorders
What is (are) vitelliform macular dystrophy ?,0001016-1,information,"Vitelliform macular dystrophy is a genetic eye disorder that can cause progressive vision loss. This disorder affects the retina, the specialized light-sensitive tissue that lines the back of the eye. Specifically, vitelliform macular dystrophy disrupts cells in a small area near the center of the retina called the macula. The macula is responsible for sharp central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces.  Vitelliform macular dystrophy causes a fatty yellow pigment (lipofuscin) to build up in cells underlying the macula. Over time, the abnormal accumulation of this substance can damage cells that are critical for clear central vision. As a result, people with this disorder often lose their central vision, and their eyesight may become blurry or distorted. Vitelliform macular dystrophy typically does not affect side (peripheral) vision or the ability to see at night.  Researchers have described two forms of vitelliform macular dystrophy with similar features. The early-onset form (known as Best disease) usually appears in childhood; the onset of symptoms and the severity of vision loss vary widely. The adult-onset form begins later, usually in mid-adulthood, and tends to cause vision loss that worsens slowly over time. The two forms of vitelliform macular dystrophy each have characteristic changes in the macula that can be detected during an eye examination.",vitelliform macular dystrophy,0001016,GHR,https://ghr.nlm.nih.gov/condition/vitelliform-macular-dystrophy,C0339510,T047,Disorders
How many people are affected by vitelliform macular dystrophy ?,0001016-2,frequency,Vitelliform macular dystrophy is a rare disorder; its incidence is unknown.,vitelliform macular dystrophy,0001016,GHR,https://ghr.nlm.nih.gov/condition/vitelliform-macular-dystrophy,C0339510,T047,Disorders
What are the genetic changes related to vitelliform macular dystrophy ?,0001016-3,genetic changes,"Mutations in the BEST1 and PRPH2 genes cause vitelliform macular dystrophy. BEST1 mutations are responsible for Best disease and for some cases of the adult-onset form of vitelliform macular dystrophy. Changes in the PRPH2 gene can also cause the adult-onset form of vitelliform macular dystrophy; however, less than a quarter of all people with this form of the condition have mutations in the BEST1 or PRPH2 gene. In most cases, the cause of the adult-onset form is unknown.  The BEST1 gene provides instructions for making a protein called bestrophin. This protein acts as a channel that controls the movement of charged chlorine atoms (chloride ions) into or out of cells in the retina. Mutations in the BEST1 gene probably lead to the production of an abnormally shaped channel that cannot properly regulate the flow of chloride. Researchers have not determined how these malfunctioning channels are related to the buildup of lipofuscin in the macula and progressive vision loss.  The PRPH2 gene provides instructions for making a protein called peripherin 2. This protein is essential for the normal function of light-sensing (photoreceptor) cells in the retina. Mutations in the PRPH2 gene cause vision loss by disrupting structures in these cells that contain light-sensing pigments. It is unclear why PRPH2 mutations affect only central vision in people with adult-onset vitelliform macular dystrophy.",vitelliform macular dystrophy,0001016,GHR,https://ghr.nlm.nih.gov/condition/vitelliform-macular-dystrophy,C0339510,T047,Disorders
Is vitelliform macular dystrophy inherited ?,0001016-4,inheritance,"Best disease is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.  The inheritance pattern of adult-onset vitelliform macular dystrophy is uncertain. Some studies have suggested that this disorder may be inherited in an autosomal dominant pattern. It is difficult to be sure, however, because many affected people have no history of the disorder in their family, and only a small number of affected families have been reported.",vitelliform macular dystrophy,0001016,GHR,https://ghr.nlm.nih.gov/condition/vitelliform-macular-dystrophy,C0339510,T047,Disorders
What are the treatments for vitelliform macular dystrophy ?,0001016-5,treatment,"These resources address the diagnosis or management of vitelliform macular dystrophy:  - Gene Review: Gene Review: Best Vitelliform Macular Dystrophy  - Genetic Testing Registry: Macular dystrophy, vitelliform, adult-onset  - Genetic Testing Registry: Vitelliform dystrophy  - MedlinePlus Encyclopedia: Macula (image)   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",vitelliform macular dystrophy,0001016,GHR,https://ghr.nlm.nih.gov/condition/vitelliform-macular-dystrophy,C0339510,T047,Disorders
What is (are) vitiligo ?,0001017-1,information,"Vitiligo is a condition that causes patchy loss of skin coloring (pigmentation). The average age of onset of vitiligo is in the mid-twenties, but it can appear at any age. It tends to progress over time, with larger areas of the skin losing pigment. Some people with vitiligo also have patches of pigment loss affecting the hair on their scalp or body.  Researchers have identified several forms of vitiligo. Generalized vitiligo (also called nonsegmental vitiligo), which is the most common form, involves loss of pigment (depigmentation) in patches of skin all over the body. Depigmentation typically occurs on the face, neck, and scalp, and around body openings such as the mouth and genitals. Sometimes pigment is lost in mucous membranes, such as the lips. Loss of pigmentation is also frequently seen in areas that tend to experience rubbing, impact, or other trauma, such as the hands, arms, and places where bones are close to the skin surface (bony prominences). Another form called segmental vitiligo is associated with smaller patches of depigmented skin that appear on one side of the body in a limited area; this occurs in about 10 percent of affected individuals.  Vitiligo is generally considered to be an autoimmune disorder. Autoimmune disorders occur when the immune system attacks the body's own tissues and organs. In people with vitiligo the immune system appears to attack the pigment cells (melanocytes) in the skin. About 15 to 25 percent of people with vitiligo are also affected by at least one other autoimmune disorder, particularly autoimmune thyroid disease, rheumatoid arthritis, type 1 diabetes, psoriasis, pernicious anemia, Addison disease, or systemic lupus erythematosus.  In the absence of other autoimmune conditions, vitiligo does not affect general health or physical functioning. However, concerns about appearance and ethnic identity are significant issues for many affected individuals.",vitiligo,0001017,GHR,https://ghr.nlm.nih.gov/condition/vitiligo,C1847835,T047,Disorders
How many people are affected by vitiligo ?,0001017-2,frequency,"Vitiligo is a common disorder, affecting between 0.5 percent and 1 percent of the population worldwide. While the condition may be more noticeable in dark-skinned people, it occurs with similar frequency in all ethnic groups.",vitiligo,0001017,GHR,https://ghr.nlm.nih.gov/condition/vitiligo,C1847835,T047,Disorders
What are the genetic changes related to vitiligo ?,0001017-3,genetic changes,"Variations in over 30 genes, occurring in different combinations, have been associated with an increased risk of developing vitiligo. Two of these genes are NLRP1 and PTPN22. The NLRP1 gene provides instructions for making a protein that is involved in the immune system, helping to regulate the process of inflammation. Inflammation occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight microbial invaders and facilitate tissue repair. The body then stops (inhibits) the inflammatory response to prevent damage to its own cells and tissues.  The PTPN22 gene provides instructions for making a protein involved in signaling that helps control the activity of immune system cells called T cells. T cells identify foreign substances and defend the body against infection.  The variations in the NLRP1 and PTPN22 genes that are associated with an increased risk of developing vitiligo likely affect the activity of the NLRP1 and PTPN22 proteins, making it more difficult for the body to control inflammation and prevent the immune system from attacking its own tissues.  Studies indicate that variations in a number of other genes also affect the risk of vitiligo. Many of these genes are also involved in immune system function or melanocyte biology, and variations in each likely make only a small contribution to vitiligo risk. Some of the gene changes associated with an increased risk of vitiligo have also been associated with an increased risk of other autoimmune conditions.  It is unclear what specific circumstances trigger the immune system to attack melanocytes in the skin. Research suggests that the immune system of affected individuals may react abnormally to melanocytes that are stressed by factors such as chemicals or ultraviolet radiation. In addition, the melanocytes of people with vitiligo may be more susceptible to stress than those of the general population and therefore may be more likely to be attacked by the immune system. The condition probably results from a combination of genetic and environmental factors, most of which have not been identified.",vitiligo,0001017,GHR,https://ghr.nlm.nih.gov/condition/vitiligo,C1847835,T047,Disorders
Is vitiligo inherited ?,0001017-4,inheritance,"Vitiligo sometimes runs in families, but the inheritance pattern is complex since multiple causative factors are involved. About one-fifth of people with this condition have at least one close relative who is also affected.",vitiligo,0001017,GHR,https://ghr.nlm.nih.gov/condition/vitiligo,C1847835,T047,Disorders
What are the treatments for vitiligo ?,0001017-5,treatment,These resources address the diagnosis or management of vitiligo:  - Genetic Testing Registry: Vitiligo  - Vitiligo Support International: Vitiligo Treatments and Research   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,vitiligo,0001017,GHR,https://ghr.nlm.nih.gov/condition/vitiligo,C1847835,T047,Disorders
What is (are) VLDLR-associated cerebellar hypoplasia ?,0001018-1,information,"VLDLR-associated cerebellar hypoplasia is an inherited condition that affects the development of the brain. People with this condition have an unusually small and underdeveloped cerebellum, which is the part of the brain that coordinates movement. This brain malformation leads to problems with balance and coordination (ataxia) that become apparent in infancy and remain stable over time. Children with VLDLR-associated cerebellar hypoplasia may learn to walk later in childhood, usually after the age of 6, although some are never able to walk independently. In one Turkish family, affected people walk on their hands and feet (quadrupedal locomotion).  Additional features of VLDLR-associated cerebellar hypoplasia include moderate to profound intellectual disability, impaired speech (dysarthria) or a lack of speech, and eyes that do not look in the same direction (strabismus). Some affected individuals have also had flat feet (pes planus), seizures, and short stature. Studies suggest that VLDLR-associated cerebellar hypoplasia does not significantly affect a person's life expectancy.",VLDLR-associated cerebellar hypoplasia,0001018,GHR,https://ghr.nlm.nih.gov/condition/vldlr-associated-cerebellar-hypoplasia,C0266470,T019,Disorders
How many people are affected by VLDLR-associated cerebellar hypoplasia ?,0001018-2,frequency,VLDLR-associated cerebellar hypoplasia is rare; its prevalence is unknown. The condition was first described in the Hutterite population in Canada and the United States. This condition has also been reported in families from Iran and Turkey.,VLDLR-associated cerebellar hypoplasia,0001018,GHR,https://ghr.nlm.nih.gov/condition/vldlr-associated-cerebellar-hypoplasia,C0266470,T019,Disorders
What are the genetic changes related to VLDLR-associated cerebellar hypoplasia ?,0001018-3,genetic changes,"As its name suggests, VLDLR-associated cerebellar hypoplasia results from mutations in the VLDLR gene. This gene provides instructions for making a protein called a very low density lipoprotein (VLDL) receptor. Starting before birth, this protein plays a critical role in guiding the movement of developing nerve cells to their appropriate locations in the brain. Mutations in the VLDLR gene prevent cells from producing any functional VLDL receptor protein. Without this protein, developing nerve cells cannot reach the parts of the brain where they are needed. The resulting problems with brain development lead to ataxia and the other major features of this condition.",VLDLR-associated cerebellar hypoplasia,0001018,GHR,https://ghr.nlm.nih.gov/condition/vldlr-associated-cerebellar-hypoplasia,C0266470,T019,Disorders
Is VLDLR-associated cerebellar hypoplasia inherited ?,0001018-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",VLDLR-associated cerebellar hypoplasia,0001018,GHR,https://ghr.nlm.nih.gov/condition/vldlr-associated-cerebellar-hypoplasia,C0266470,T019,Disorders
What are the treatments for VLDLR-associated cerebellar hypoplasia ?,0001018-5,treatment,These resources address the diagnosis or management of VLDLR-associated cerebellar hypoplasia:  - Gene Review: Gene Review: Hereditary Ataxia Overview  - Gene Review: Gene Review: VLDLR-Associated Cerebellar Hypoplasia  - Genetic Testing Registry: Dysequilibrium syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,VLDLR-associated cerebellar hypoplasia,0001018,GHR,https://ghr.nlm.nih.gov/condition/vldlr-associated-cerebellar-hypoplasia,C0266470,T019,Disorders
What is (are) Vohwinkel syndrome ?,0001019-1,information,"Vohwinkel syndrome is a disorder with classic and variant forms, both of which affect the skin.  In the classic form of Vohwinkel syndrome, affected individuals have thick, honeycomb-like calluses on the palms of the hands and soles of the feet (palmoplantar keratoses) beginning in infancy or early childhood. Affected children also typically have distinctive starfish-shaped patches of thickened skin on the tops of the fingers and toes or on the knees. Within a few years they develop tight bands of abnormal fibrous tissue around their fingers and toes (pseudoainhum); the bands may cut off the circulation to the digits and result in spontaneous amputation. People with the classic form of the disorder also have hearing loss.  The variant form of Vohwinkel syndrome does not involve hearing loss, and the skin features also include widespread dry, scaly skin (ichthyosis), especially on the limbs. The ichthyosis is usually mild, and there may also be mild reddening of the skin (erythroderma). Some affected infants are born with a tight, clear sheath covering their skin called a collodion membrane. This membrane is usually shed during the first few weeks of life.",Vohwinkel syndrome,0001019,GHR,https://ghr.nlm.nih.gov/condition/vohwinkel-syndrome,C0265964,T019,Disorders
How many people are affected by Vohwinkel syndrome ?,0001019-2,frequency,Vohwinkel syndrome is a rare disorder; about 50 cases have been reported in the medical literature.,Vohwinkel syndrome,0001019,GHR,https://ghr.nlm.nih.gov/condition/vohwinkel-syndrome,C0265964,T019,Disorders
What are the genetic changes related to Vohwinkel syndrome ?,0001019-3,genetic changes,"The classic form of Vohwinkel syndrome is caused by mutations in the GJB2 gene. This gene provides instructions for making a protein called gap junction beta 2, more commonly known as connexin 26. Connexin 26 is a member of the connexin protein family. Connexin proteins form channels called gap junctions that permit the transport of nutrients, charged atoms (ions), and signaling molecules between neighboring cells that are in contact with each other. Gap junctions made with connexin 26 transport potassium ions and certain small molecules.  Connexin 26 is found in cells throughout the body, including the inner ear and the skin. In the inner ear, channels made from connexin 26 are found in a snail-shaped structure called the cochlea. These channels may help to maintain the proper level of potassium ions required for the conversion of sound waves to electrical nerve impulses. This conversion is essential for normal hearing. In addition, connexin 26 may be involved in the maturation of certain cells in the cochlea. Connexin 26 also plays a role in the growth, maturation, and stability of the outermost layer of skin (the epidermis).  The GJB2 gene mutations that cause Vohwinkel syndrome change single protein building blocks (amino acids) in connexin 26. The altered protein probably disrupts the function of normal connexin 26 in cells, and may interfere with the function of other connexin proteins. This disruption could affect skin growth and also impair hearing by disturbing the conversion of sound waves to nerve impulses.  The variant form of Vohwinkel syndrome, sometimes called loricrin keratoderma, is caused by mutations in the LOR gene. This gene provides instructions for making a protein called loricrin, which is involved in the formation and maintenance of the epidermis, particularly its tough outer surface (the stratum corneum). The stratum corneum, which is formed in a process known as cornification, provides a sturdy barrier between the body and its environment. Each cell of the stratum corneum, called a corneocyte, is surrounded by a protein shell called a cornified envelope. Loricrin is a major component of the cornified envelope. Links between loricrin and other components of the envelopes hold the corneocytes together and help give the stratum corneum its strength.  Mutations in the LOR gene change the structure of the loricrin protein; the altered protein is trapped inside the cell and cannot reach the cornified envelope. While other proteins can partially compensate for the missing loricrin, the envelope of some corneocytes is thinner than normal in affected individuals, resulting in ichthyosis and the other skin abnormalities associated with the variant form of Vohwinkel syndrome.",Vohwinkel syndrome,0001019,GHR,https://ghr.nlm.nih.gov/condition/vohwinkel-syndrome,C0265964,T019,Disorders
Is Vohwinkel syndrome inherited ?,0001019-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.",Vohwinkel syndrome,0001019,GHR,https://ghr.nlm.nih.gov/condition/vohwinkel-syndrome,C0265964,T019,Disorders
What are the treatments for Vohwinkel syndrome ?,0001019-5,treatment,"These resources address the diagnosis or management of Vohwinkel syndrome:  - Genetic Testing Registry: Mutilating keratoderma  - Genetic Testing Registry: Vohwinkel syndrome, variant form   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Vohwinkel syndrome,0001019,GHR,https://ghr.nlm.nih.gov/condition/vohwinkel-syndrome,C0265964,T019,Disorders
What is (are) von Hippel-Lindau syndrome ?,0001020-1,information,"Von Hippel-Lindau syndrome is an inherited disorder characterized by the formation of tumors and fluid-filled sacs (cysts) in many different parts of the body. Tumors may be either noncancerous or cancerous and most frequently appear during young adulthood; however, the signs and symptoms of von Hippel-Lindau syndrome can occur throughout life.  Tumors called hemangioblastomas are characteristic of von Hippel-Lindau syndrome. These growths are made of newly formed blood vessels. Although they are typically noncancerous, they can cause serious or life-threatening complications. Hemangioblastomas that develop in the brain and spinal cord can cause headaches, vomiting, weakness, and a loss of muscle coordination (ataxia). Hemangioblastomas can also occur in the light-sensitive tissue that lines the back of the eye (the retina). These tumors, which are also called retinal angiomas, may cause vision loss.  People with von Hippel-Lindau syndrome commonly develop cysts in the kidneys, pancreas, and genital tract. They are also at an increased risk of developing a type of kidney cancer called clear cell renal cell carcinoma and a type of pancreatic cancer called a pancreatic neuroendocrine tumor.  Von Hippel-Lindau syndrome is associated with a type of tumor called a pheochromocytoma, which most commonly occurs in the adrenal glands (small hormone-producing glands located on top of each kidney). Pheochromocytomas are usually noncancerous. They may cause no symptoms, but in some cases they are associated with headaches, panic attacks, excess sweating, or dangerously high blood pressure that may not respond to medication. Pheochromocytomas are particularly dangerous if they develop during pregnancy.  About 10 percent of people with von Hippel-Lindau syndrome develop endolymphatic sac tumors, which are noncancerous tumors in the inner ear. These growths can cause hearing loss in one or both ears, as well as ringing in the ears (tinnitus) and problems with balance. Without treatment, these tumors can cause sudden profound deafness.",von Hippel-Lindau syndrome,0001020,GHR,https://ghr.nlm.nih.gov/condition/von-hippel-lindau-syndrome,C1402998,T019,Disorders
How many people are affected by von Hippel-Lindau syndrome ?,0001020-2,frequency,"The incidence of von Hippel-Lindau syndrome is estimated to be 1 in 36,000 individuals.",von Hippel-Lindau syndrome,0001020,GHR,https://ghr.nlm.nih.gov/condition/von-hippel-lindau-syndrome,C1402998,T019,Disorders
What are the genetic changes related to von Hippel-Lindau syndrome ?,0001020-3,genetic changes,"Mutations in the VHL gene cause von Hippel-Lindau syndrome. The VHL gene is a tumor suppressor gene, which means it keeps cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in this gene prevent production of the VHL protein or lead to the production of an abnormal version of the protein. An altered or missing VHL protein cannot effectively regulate cell survival and division. As a result, cells grow and divide uncontrollably to form the tumors and cysts that are characteristic of von Hippel-Lindau syndrome.",von Hippel-Lindau syndrome,0001020,GHR,https://ghr.nlm.nih.gov/condition/von-hippel-lindau-syndrome,C1402998,T019,Disorders
Is von Hippel-Lindau syndrome inherited ?,0001020-4,inheritance,"Mutations in the VHL gene are inherited in an autosomal dominant pattern, which means that one copy of the altered gene in each cell is sufficient to increase the risk of developing tumors and cysts. Most people with von Hippel-Lindau syndrome inherit an altered copy of the gene from an affected parent. In about 20 percent of cases, however, the altered gene is the result of a new mutation that occurred during the formation of reproductive cells (eggs or sperm) or very early in development.  Unlike most autosomal dominant conditions, in which one altered copy of a gene in each cell is sufficient to cause the disorder, two copies of the VHL gene must be altered to trigger tumor and cyst formation in von Hippel-Lindau syndrome. A mutation in the second copy of the VHL gene occurs during a person's lifetime in certain cells within organs such as the brain, retina, and kidneys. Cells with two altered copies of this gene make no functional VHL protein, which allows tumors and cysts to develop. Almost everyone who inherits one VHL mutation will eventually acquire a mutation in the second copy of the gene in some cells, leading to the features of von Hippel-Lindau syndrome.",von Hippel-Lindau syndrome,0001020,GHR,https://ghr.nlm.nih.gov/condition/von-hippel-lindau-syndrome,C1402998,T019,Disorders
What are the treatments for von Hippel-Lindau syndrome ?,0001020-5,treatment,These resources address the diagnosis or management of von Hippel-Lindau syndrome:  - Brigham and Women's Hospital  - Gene Review: Gene Review: Von Hippel-Lindau Syndrome  - Genetic Testing Registry: Von Hippel-Lindau syndrome  - Genomics Education Programme (UK)  - MD Anderson Cancer Center  - MedlinePlus Encyclopedia: Pheochromocytoma  - MedlinePlus Encyclopedia: Renal Cell Carcinoma  - National Cancer Institute: Genetic Testing for Hereditary Cancer Syndromes   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,von Hippel-Lindau syndrome,0001020,GHR,https://ghr.nlm.nih.gov/condition/von-hippel-lindau-syndrome,C1402998,T019,Disorders
What is (are) von Willebrand disease ?,0001021-1,information,"Von Willebrand disease is a bleeding disorder that slows the blood clotting process, causing prolonged bleeding after an injury. People with this condition often experience easy bruising, long-lasting nosebleeds, and excessive bleeding or oozing following an injury, surgery, or dental work. Mild forms of von Willebrand disease may become apparent only when abnormal bleeding occurs following surgery or a serious injury. Women with this condition typically have heavy or prolonged bleeding during menstruation (menorrhagia), and some may also experience reproductive tract bleeding during pregnancy and childbirth. In severe cases of von Willebrand disease, heavy bleeding occurs after minor trauma or even in the absence of injury (spontaneous bleeding). Symptoms of von Willebrand disease may change over time. Increased age, pregnancy, exercise, and stress may cause bleeding symptoms to become less frequent.  Von Willebrand disease is divided into three types, with type 2 being further divided into four subtypes. Type 1 is the mildest and most common of the three types, accounting for 75 percent of affected individuals. Type 3 is the most severe and rarest form of the condition. The four subtypes of type 2 von Willebrand disease are intermediate in severity. Another form of the disorder, acquired von Willebrand syndrome, is not caused by inherited gene mutations. Acquired von Willebrand syndrome is typically seen along with other disorders, such as diseases that affect bone marrow or immune cell function. This rare form of the condition is characterized by abnormal bleeding into the skin and other soft tissues, usually beginning in adulthood.",von Willebrand disease,0001021,GHR,https://ghr.nlm.nih.gov/condition/von-willebrand-disease,C0042974,T047,Disorders
How many people are affected by von Willebrand disease ?,0001021-2,frequency,"Von Willebrand disease is estimated to affect 1 in 100 to 10,000 individuals. Because people with mild signs and symptoms may not come to medical attention, it is thought that this condition is underdiagnosed. Most researchers agree that von Willebrand disease is the most common genetic bleeding disorder.",von Willebrand disease,0001021,GHR,https://ghr.nlm.nih.gov/condition/von-willebrand-disease,C0042974,T047,Disorders
What are the genetic changes related to von Willebrand disease ?,0001021-3,genetic changes,"Mutations in the VWF gene cause von Willebrand disease. The VWF gene provides instructions for making a blood clotting protein called von Willebrand factor, which is essential for the formation of blood clots. After an injury, clots protect the body by sealing off damaged blood vessels and preventing further blood loss. Von Willebrand factor acts as a glue to hold blood clots together and prevents the breakdown of other blood clotting proteins. If von Willebrand factor does not function normally or too little of the protein is available, blood clots cannot form properly. Abnormally slow blood clotting causes the prolonged bleeding episodes seen in von Willebrand disease.  The three types of von Willebrand disease are based upon the amount of von Willebrand factor that is produced. Mutations in the VWF gene that reduce the amount of von Willebrand factor cause type 1 von Willebrand disease. People with type 1 have varying amounts of von Willebrand factor in their bloodstream. Some people with a mild case of type 1 never experience a prolonged bleeding episode. Mutations that disrupt the function of von Willebrand factor cause the four subtypes of type 2 von Willebrand disease. People with type 2 von Willebrand disease have bleeding episodes of varying severity depending on the extent of von Willebrand factor dysfunction, but the bleeding episodes are typically similar to those seen in type 1. Mutations that result in an abnormally short, nonfunctional von Willebrand factor generally cause type 3 von Willebrand disease. Because there is no functional protein, people with type 3 von Willebrand disease usually have severe bleeding episodes.",von Willebrand disease,0001021,GHR,https://ghr.nlm.nih.gov/condition/von-willebrand-disease,C0042974,T047,Disorders
Is von Willebrand disease inherited ?,0001021-4,inheritance,"Von Willebrand disease can have different inheritance patterns.  Most cases of type 1 and type 2 von Willebrand disease are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  Type 3, some cases of type 2, and a small number of type 1 cases of von Willebrand disease are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they do not show signs and symptoms of the condition.",von Willebrand disease,0001021,GHR,https://ghr.nlm.nih.gov/condition/von-willebrand-disease,C0042974,T047,Disorders
What are the treatments for von Willebrand disease ?,0001021-5,treatment,These resources address the diagnosis or management of von Willebrand disease:  - Gene Review: Gene Review: von Willebrand Disease  - Genetic Testing Registry: von Willebrand disorder  - MedlinePlus Encyclopedia: von Willebrand Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,von Willebrand disease,0001021,GHR,https://ghr.nlm.nih.gov/condition/von-willebrand-disease,C0042974,T047,Disorders
What is (are) Waardenburg syndrome ?,0001022-1,information,"Waardenburg syndrome is a group of genetic conditions that can cause hearing loss and changes in coloring (pigmentation) of the hair, skin, and eyes. Although most people with Waardenburg syndrome have normal hearing, moderate to profound hearing loss can occur in one or both ears. The hearing loss is present from birth (congenital). People with this condition often have very pale blue eyes or different colored eyes, such as one blue eye and one brown eye. Sometimes one eye has segments of two different colors. Distinctive hair coloring (such as a patch of white hair or hair that prematurely turns gray) is another common sign of the condition. The features of Waardenburg syndrome vary among affected individuals, even among people in the same family.  The four known types of Waardenburg syndrome are distinguished by their physical characteristics and sometimes by their genetic cause. Types I and II have very similar features, although people with type I almost always have eyes that appear widely spaced and people with type II do not. In addition, hearing loss occurs more often in people with type II than in those with type I. Type III (sometimes called Klein-Waardenburg syndrome) includes abnormalities of the upper limbs in addition to hearing loss and changes in pigmentation. Type IV (also known as Waardenburg-Shah syndrome) has signs and symptoms of both Waardenburg syndrome and Hirschsprung disease, an intestinal disorder that causes severe constipation or blockage of the intestine.",Waardenburg syndrome,0001022,GHR,https://ghr.nlm.nih.gov/condition/waardenburg-syndrome,C3266898,T019,Disorders
How many people are affected by Waardenburg syndrome ?,0001022-2,frequency,"Waardenburg syndrome affects an estimated 1 in 40,000 people. It accounts for 2 to 5 percent of all cases of congenital hearing loss. Types I and II are the most common forms of Waardenburg syndrome, while types III and IV are rare.",Waardenburg syndrome,0001022,GHR,https://ghr.nlm.nih.gov/condition/waardenburg-syndrome,C3266898,T019,Disorders
What are the genetic changes related to Waardenburg syndrome ?,0001022-3,genetic changes,"Mutations in the EDN3, EDNRB, MITF, PAX3, SNAI2, and SOX10 genes can cause Waardenburg syndrome. These genes are involved in the formation and development of several types of cells, including pigment-producing cells called melanocytes. Melanocytes make a pigment called melanin, which contributes to skin, hair, and eye color and plays an essential role in the normal function of the inner ear. Mutations in any of these genes disrupt the normal development of melanocytes, leading to abnormal pigmentation of the skin, hair, and eyes and problems with hearing.  Types I and III Waardenburg syndrome are caused by mutations in the PAX3 gene. Mutations in the MITF and SNAI2 genes are responsible for type II Waardenburg syndrome.  Mutations in the SOX10, EDN3, or EDNRB genes cause type IV Waardenburg syndrome. In addition to melanocyte development, these genes are important for the development of nerve cells in the large intestine. Mutations in any of these genes result in hearing loss, changes in pigmentation, and intestinal problems related to Hirschsprung disease.",Waardenburg syndrome,0001022,GHR,https://ghr.nlm.nih.gov/condition/waardenburg-syndrome,C3266898,T019,Disorders
Is Waardenburg syndrome inherited ?,0001022-4,inheritance,"Waardenburg syndrome is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition. A small percentage of cases result from new mutations in the gene; these cases occur in people with no history of the disorder in their family.  Some cases of type II and type IV Waardenburg syndrome appear to have an autosomal recessive pattern of inheritance, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.",Waardenburg syndrome,0001022,GHR,https://ghr.nlm.nih.gov/condition/waardenburg-syndrome,C3266898,T019,Disorders
What are the treatments for Waardenburg syndrome ?,0001022-5,treatment,These resources address the diagnosis or management of Waardenburg syndrome:  - Gene Review: Gene Review: Waardenburg Syndrome Type I  - Genetic Testing Registry: Klein-Waardenberg's syndrome  - Genetic Testing Registry: Waardenburg syndrome type 1  - Genetic Testing Registry: Waardenburg syndrome type 2A  - Genetic Testing Registry: Waardenburg syndrome type 2B  - Genetic Testing Registry: Waardenburg syndrome type 2C  - Genetic Testing Registry: Waardenburg syndrome type 2D  - Genetic Testing Registry: Waardenburg syndrome type 4A  - MedlinePlus Encyclopedia: Waardenburg Syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Waardenburg syndrome,0001022,GHR,https://ghr.nlm.nih.gov/condition/waardenburg-syndrome,C3266898,T019,Disorders
What is (are) Wagner syndrome ?,0001023-1,information,"Wagner syndrome is a hereditary disorder that causes progressive vision loss. The eye problems that lead to vision loss typically begin in childhood, although the vision impairment might not be immediately apparent.  In people with Wagner syndrome, the light-sensitive tissue that lines the back of the eye (the retina) becomes thin and may separate from the back of the eye (retinal detachment). The blood vessels within the retina (known as the choroid) may also be abnormal. The retina and the choroid progressively break down (degenerate). Some people with Wagner syndrome have blurred vision because of ectopic fovea, an abnormality in which the part of the retina responsible for sharp central vision is out of place. Additionally, the thick, clear gel that fills the eyeball (the vitreous) becomes watery and thin. People with Wagner syndrome develop a clouding of the lens of the eye (cataract). Affected individuals may also experience nearsightedness (myopia), progressive night blindness, or a narrowing of their field of vision.  Vision impairment in people with Wagner syndrome can vary from near normal vision to complete loss of vision in both eyes.",Wagner syndrome,0001023,GHR,https://ghr.nlm.nih.gov/condition/wagner-syndrome,C1840452,T047,Disorders
How many people are affected by Wagner syndrome ?,0001023-2,frequency,"Wagner syndrome is a rare disorder, although its exact prevalence is unknown. Approximately 300 affected individuals have been described worldwide; about half of these individuals are from the Netherlands.",Wagner syndrome,0001023,GHR,https://ghr.nlm.nih.gov/condition/wagner-syndrome,C1840452,T047,Disorders
What are the genetic changes related to Wagner syndrome ?,0001023-3,genetic changes,"Mutations in the VCAN gene cause Wagner syndrome. The VCAN gene provides instructions for making a protein called versican. Versican is found in the extracellular matrix, which is the intricate lattice of proteins and other molecules that forms in the spaces between cells. Versican interacts with many of these proteins and molecules to facilitate the assembly of the extracellular matrix and ensure its stability. Within the eye, versican interacts with other proteins to maintain the structure and gel-like consistency of the vitreous.  VCAN gene mutations that cause Wagner syndrome lead to insufficient levels of versican in the vitreous. Without enough versican to interact with the many proteins of the vitreous, the structure becomes unstable. This lack of stability in the vitreous affects other areas of the eye and contributes to the vision problems that occur in people with Wagner syndrome. It is unknown why VCAN gene mutations seem solely to affect vision.",Wagner syndrome,0001023,GHR,https://ghr.nlm.nih.gov/condition/wagner-syndrome,C1840452,T047,Disorders
Is Wagner syndrome inherited ?,0001023-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Wagner syndrome,0001023,GHR,https://ghr.nlm.nih.gov/condition/wagner-syndrome,C1840452,T047,Disorders
What are the treatments for Wagner syndrome ?,0001023-5,treatment,These resources address the diagnosis or management of Wagner syndrome:  - Gene Review: Gene Review: VCAN-Related Vitreoretinopathy  - Genetic Testing Registry: Wagner syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Wagner syndrome,0001023,GHR,https://ghr.nlm.nih.gov/condition/wagner-syndrome,C1840452,T047,Disorders
What is (are) WAGR syndrome ?,0001024-1,information,"WAGR syndrome is a disorder that affects many body systems and is named for its main features: Wilms tumor, anirida, genitourinary anomalies, and intellectual disability (formerly referred to as mental retardation).  People with WAGR syndrome have a 45 to 60 percent chance of developing Wilms tumor, a rare form of kidney cancer. This type of cancer is most often diagnosed in children but is sometimes seen in adults.  Most people with WAGR syndrome have aniridia, an absence of the colored part of the eye (the iris). This can cause reduction in the sharpness of vision (visual acuity) and increased sensitivity to light (photophobia). Aniridia is typically the first noticeable sign of WAGR syndrome. Other eye problems may also develop, such as clouding of the lens of the eyes (cataracts), increased pressure in the eyes (glaucoma), and involuntary eye movements (nystagmus).  Abnormalities of the genitalia and urinary tract (genitourinary anomalies) are seen more frequently in males with WAGR syndrome than in affected females. The most common genitourinary anomaly in affected males is undescended testes (cryptorchidism). Females may not have functional ovaries and instead have undeveloped clumps of tissue called streak gonads. Females may also have a heart-shaped (bicornate) uterus, which makes it difficult to carry a pregnancy to term.  Another common feature of WAGR syndrome is intellectual disability. Affected individuals often have difficulty processing, learning, and properly responding to information. Some individuals with WAGR syndrome also have psychiatric or behavioral problems including depression, anxiety, attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), or a developmental disorder called autism that affects communication and social interaction.  Other signs and symptoms of WAGR syndrome can include childhood-onset obesity, inflammation of the pancreas (pancreatitis), and kidney failure. When WAGR syndrome includes childhood-onset obesity, it is often referred to as WAGRO syndrome.",WAGR syndrome,0001024,GHR,https://ghr.nlm.nih.gov/condition/wagr-syndrome,C0206115,T047,Disorders
How many people are affected by WAGR syndrome ?,0001024-2,frequency,"The prevalence of WAGR syndrome ranges from 1 in 500,000 to one million individuals. It is estimated that one-third of people with aniridia actually have WAGR syndrome. Approximately 7 in 1,000 cases of Wilms tumor can be attributed to WAGR syndrome.",WAGR syndrome,0001024,GHR,https://ghr.nlm.nih.gov/condition/wagr-syndrome,C0206115,T047,Disorders
What are the genetic changes related to WAGR syndrome ?,0001024-3,genetic changes,"WAGR syndrome is caused by a deletion of genetic material on the short (p) arm of chromosome 11. The size of the deletion varies among affected individuals.  The signs and symptoms of WAGR syndrome are related to the loss of multiple genes on the short arm of chromosome 11. WAGR syndrome is often described as a contiguous gene deletion syndrome because it results from the loss of several neighboring genes. The PAX6 and WT1 genes are always deleted in people with the typical signs and symptoms of this disorder. Because changes in the PAX6 gene can affect eye development, researchers think that the loss of the PAX6 gene is responsible for the characteristic eye features of WAGR syndrome. The PAX6 gene may also affect brain development. Wilms tumor and genitourinary abnormalities are often the result of mutations in the WT1 gene, so deletion of the WT1 gene is very likely the cause of these features in WAGR syndrome.  In people with WAGRO syndrome, the chromosome 11 deletion includes an additional gene, BDNF. This gene is active (expressed) in the brain and plays a role in the survival of nerve cells (neurons). The protein produced from the BDNF gene is thought to be involved in the management of eating, drinking, and body weight. Loss of the BDNF gene is likely responsible for childhood-onset obesity in people with WAGRO syndrome. People with WAGRO syndrome may be at greater risk of neurological problems such as intellectual disability and autism than those with WAGR syndrome. It is unclear whether this increased risk is due to the loss of the BDNF gene or other nearby genes.  Research is ongoing to identify additional genes deleted in people with WAGR syndrome and to determine how their loss leads to the other features of the disorder.",WAGR syndrome,0001024,GHR,https://ghr.nlm.nih.gov/condition/wagr-syndrome,C0206115,T047,Disorders
Is WAGR syndrome inherited ?,0001024-4,inheritance,"Most cases of WAGR syndrome are not inherited. They result from a chromosomal deletion that occurs as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family.  Some affected individuals inherit a chromosome 11 with a deleted segment from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which no genetic material is gained or lost. Balanced translocations usually do not cause any health problems; however, they can become unbalanced as they are passed to the next generation. Children who inherit an unbalanced translocation can have a chromosomal rearrangement with extra or missing genetic material. Individuals with WAGR syndrome who inherit an unbalanced translocation are missing genetic material from the short arm of chromosome 11, which results in an increased risk of Wilms tumor, aniridia, genitourinary anomalies, and intellectual disability.",WAGR syndrome,0001024,GHR,https://ghr.nlm.nih.gov/condition/wagr-syndrome,C0206115,T047,Disorders
What are the treatments for WAGR syndrome ?,0001024-5,treatment,"These resources address the diagnosis or management of WAGR syndrome:  - Gene Review: Gene Review: Aniridia  - Gene Review: Gene Review: Wilms Tumor Overview  - Genetic Testing Registry: 11p partial monosomy syndrome  - Genetic Testing Registry: Wilms tumor, aniridia, genitourinary anomalies, mental retardation, and obesity syndrome  - MedlinePlus Encyclopedia: Undescended Testicle   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",WAGR syndrome,0001024,GHR,https://ghr.nlm.nih.gov/condition/wagr-syndrome,C0206115,T047,Disorders
What is (are) Waldenstrm macroglobulinemia ?,0001025-1,information,"Waldenstrm macroglobulinemia is a rare blood cell cancer characterized by an excess of abnormal white blood cells called lymphoplasmacytic cells in the bone marrow. This condition is classified as a lymphoplasmacytic lymphoma. The abnormal cells have characteristics of both white blood cells (lymphocytes) called B cells and of more mature cells derived from B cells known as plasma cells. These abnormal cells produce excess amounts of IgM, a type of protein known as an immunoglobulin; the overproduction of this large protein is how the condition got its name (""macroglobulinemia"").  Waldenstrm macroglobulinemia usually begins in a person's sixties and is a slow-growing (indolent) cancer. Some affected individuals have elevated levels of IgM and lymphoplasmacytic cells but no symptoms of the condition; in these cases, the disease is usually found incidentally by a blood test taken for another reason. These individuals are diagnosed with smoldering (or asymptomatic) Waldenstrm macroglobulinemia. It can be several years before this form of the condition progresses to the symptomatic form.  Individuals with symptomatic Waldenstrm macroglobulinemia can experience general symptoms such as fever, night sweats, and weight loss. Several other signs and symptoms of the condition are related to the excess IgM, which can thicken blood and impair circulation, causing a condition known as hyperviscosity syndrome. Features related to hyperviscosity syndrome include bleeding in the nose or mouth, blurring or loss of vision, headache, dizziness, and difficulty coordinating movements (ataxia). In some affected individuals, the IgM proteins clump together in the hands and feet, where the body temperature is cooler than at the center of the body. These proteins are then referred to as cryoglobulins, and their clumping causes a condition known as cryoglobulinemia. Cryoglobulinemia can lead to pain in the hands and feet or episodes of Raynaud phenomenon, in which the fingers and toes turn white or blue in response to cold temperatures. The IgM protein can also build up in organs such as the heart and kidneys, causing a condition called amyloidosis, which can lead to heart and kidney problems. Some people with Waldenstrm macroglobulinemia develop a loss of sensation and weakness in the limbs (peripheral neuropathy). Doctors are unsure why this feature occurs, although they speculate that the IgM protein attaches to the protective covering of nerve cells (myelin) and breaks it down. The damaged nerves cannot carry signals normally, leading to neuropathy.  Other features of Waldenstrm macroglobulinemia are due to the accumulation of lymphoplasmacytic cells in different tissues. For example, accumulation of these cells can lead to an enlarged liver (hepatomegaly), spleen (splenomegaly), or lymph nodes (lymphadenopathy). In the bone marrow, the lymphoplasmacytic cells interfere with normal blood cell development, causing a shortage of normal blood cells (pancytopenia). Excessive tiredness (fatigue) due to a reduction in red blood cells (anemia) is common in affected individuals.  People with Waldenstrm macroglobulinemia have an increased risk of developing other cancers of the blood or other tissues.",Waldenstrm macroglobulinemia,0001025,GHR,https://ghr.nlm.nih.gov/condition/waldenstrom-macroglobulinemia,C0024419,T191,Disorders
How many people are affected by Waldenstrm macroglobulinemia ?,0001025-2,frequency,"Waldenstrm macroglobulinemia affects an estimated 3 per million people each year in the United States. Approximately 1,500 new cases of the condition are diagnosed each year in this country, and whites are more commonly affected than African Americans. For unknown reasons, the condition occurs twice as often in men than women.",Waldenstrm macroglobulinemia,0001025,GHR,https://ghr.nlm.nih.gov/condition/waldenstrom-macroglobulinemia,C0024419,T191,Disorders
What are the genetic changes related to Waldenstrm macroglobulinemia ?,0001025-3,genetic changes,"Waldenstrm macroglobulinemia is thought to result from a combination of genetic changes. The most common known genetic change associated with this condition is a mutation in the MYD88 gene, which is found in more than 90 percent of affected individuals. Another gene commonly associated with Waldenstrm macroglobulinemia, CXCR4, is mutated in approximately 30 percent of affected individuals (most of whom also have the MYD88 gene mutation). Other genetic changes believed to be involved in Waldenstrm macroglobulinemia have not yet been identified. Studies have found that certain regions of DNA are deleted or added in some people with the condition; however, researchers are unsure which genes in these regions are important for development of the condition. The mutations that cause Waldenstrm macroglobulinemia are acquired during a person's lifetime and are present only in the abnormal blood cells.  The proteins produced from the MYD88 and CXCR4 genes are both involved in signaling within cells. The MyD88 protein relays signals that help prevent the self-destruction (apoptosis) of cells, thus aiding in cell survival. The CXCR4 protein stimulates signaling pathways inside the cell that help regulate cell growth and division (proliferation) and cell survival. Mutations in these genes lead to production of proteins that are constantly functioning (overactive). Excessive signaling through these overactive proteins allows survival and proliferation of abnormal cells that should undergo apoptosis, which likely contributes to the accumulation of lymphoplasmacytic cells in Waldenstrm macroglobulinemia.",Waldenstrm macroglobulinemia,0001025,GHR,https://ghr.nlm.nih.gov/condition/waldenstrom-macroglobulinemia,C0024419,T191,Disorders
Is Waldenstrm macroglobulinemia inherited ?,0001025-4,inheritance,"Waldenstrm macroglobulinemia is usually not inherited, and most affected people have no history of the disorder in their family. The condition usually arises from mutations that are acquired during a person's lifetime (somatic mutations), which are not inherited.  Some families seem to have a predisposition to the condition. Approximately 20 percent of people with Waldenstrm macroglobulinemia have a family member with the condition or another disorder involving abnormal B cells.",Waldenstrm macroglobulinemia,0001025,GHR,https://ghr.nlm.nih.gov/condition/waldenstrom-macroglobulinemia,C0024419,T191,Disorders
What are the treatments for Waldenstrm macroglobulinemia ?,0001025-5,treatment,These resources address the diagnosis or management of Waldenstrm macroglobulinemia:  - American Cancer Society: How is Waldenstrom Macroglobulinemia Diagnosed?  - American Cancer Society: How is Waldenstrom Macroglobulinemia Treated?  - Genetic Testing Registry: Waldenstrom macroglobulinemia  - MD Anderson Cancer Center  - MedlinePlus Encyclopedia: Macroglobulinemia of Waldenstrom   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Waldenstrm macroglobulinemia,0001025,GHR,https://ghr.nlm.nih.gov/condition/waldenstrom-macroglobulinemia,C0024419,T191,Disorders
What is (are) Walker-Warburg syndrome ?,0001026-1,information,"Walker-Warburg syndrome is an inherited disorder that affects development of the muscles, brain, and eyes. It is the most severe of a group of genetic conditions known as congenital muscular dystrophies, which cause muscle weakness and wasting (atrophy) beginning very early in life. The signs and symptoms of Walker-Warburg syndrome are present at birth or in early infancy. Because of the severity of the problems caused by Walker-Warburg syndrome, most affected individuals do not survive past age 3.  Walker-Warburg syndrome affects the skeletal muscles, which are muscles the body uses for movement. Affected babies have weak muscle tone (hypotonia) and are sometimes described as ""floppy."" The muscle weakness worsens over time.  Walker-Warburg syndrome also affects the brain; individuals with this condition typically have a brain abnormality called cobblestone lissencephaly, in which the surface of the brain lacks the normal folds and grooves and instead develops a bumpy, irregular appearance (like that of cobblestones). They may also have a buildup of fluid in the brain (hydrocephalus) or abnormalities of other parts of the brain, including a region called the cerebellum and the part of the brain that connects to the spinal cord (the brainstem). These changes in the structure of the brain lead to significantly delayed development and intellectual disability. Some individuals with Walker-Warburg syndrome experience seizures.  Eye abnormalities are also characteristic of Walker-Warburg syndrome. These can include unusually small eyeballs (microphthalmia), enlarged eyeballs caused by increased pressure in the eyes (buphthalmos), clouding of the lenses of the eyes (cataracts), and problems with the nerve that relays visual information from the eyes to the brain (the optic nerve). These eye problems lead to vision impairment in affected individuals.",Walker-Warburg syndrome,0001026,GHR,https://ghr.nlm.nih.gov/condition/walker-warburg-syndrome,C0265221,T019,Disorders
How many people are affected by Walker-Warburg syndrome ?,0001026-2,frequency,"Walker-Warburg syndrome is estimated to affect 1 in 60,500 newborns worldwide.",Walker-Warburg syndrome,0001026,GHR,https://ghr.nlm.nih.gov/condition/walker-warburg-syndrome,C0265221,T019,Disorders
What are the genetic changes related to Walker-Warburg syndrome ?,0001026-3,genetic changes,"Walker-Warburg syndrome can be caused by mutations in one of several genes, including POMT1, POMT2, ISPD, FKTN, FKRP, and LARGE. The proteins produced from these genes modify another protein called alpha ()-dystroglycan; this modification, called glycosylation, is required for -dystroglycan to function. The -dystroglycan protein helps anchor the structural framework inside each cell (cytoskeleton) to the lattice of proteins and other molecules outside the cell (extracellular matrix). In skeletal muscles, the anchoring function of -dystroglycan helps stabilize and protect muscle fibers. In the brain, it helps direct the movement (migration) of nerve cells (neurons) during early development.  Mutations in these genes prevent glycosylation of -dystroglycan, which disrupts its normal function. Without functional -dystroglycan to stabilize muscle cells, muscle fibers become damaged as they repeatedly contract and relax with use. The damaged fibers weaken and die over time, leading to progressive weakness of the skeletal muscles.  Defective -dystroglycan also affects the migration of neurons during the early development of the brain. Instead of stopping when they reach their intended destinations, some neurons migrate past the surface of the brain into the fluid-filled space that surrounds it. Researchers believe that this problem with neuronal migration causes cobblestone lissencephaly in children with Walker-Warburg syndrome. Less is known about the effects of the gene mutations in other parts of the body, including the eyes.  Mutations in the POMT1, POMT2, ISPD, FKTN, FKRP, and LARGE genes are found in only about half of individuals with Walker-Warburg syndrome. Other genes, some of which have not been identified, are likely involved in the development of this condition.  Because Walker-Warburg syndrome involves a malfunction of -dystroglycan, this condition is classified as a dystroglycanopathy.",Walker-Warburg syndrome,0001026,GHR,https://ghr.nlm.nih.gov/condition/walker-warburg-syndrome,C0265221,T019,Disorders
Is Walker-Warburg syndrome inherited ?,0001026-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Walker-Warburg syndrome,0001026,GHR,https://ghr.nlm.nih.gov/condition/walker-warburg-syndrome,C0265221,T019,Disorders
What are the treatments for Walker-Warburg syndrome ?,0001026-5,treatment,These resources address the diagnosis or management of Walker-Warburg syndrome:  - Gene Review: Gene Review: Congenital Muscular Dystrophy Overview  - Genetic Testing Registry: Walker-Warburg congenital muscular dystrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Walker-Warburg syndrome,0001026,GHR,https://ghr.nlm.nih.gov/condition/walker-warburg-syndrome,C0265221,T019,Disorders
What is (are) warfarin resistance ?,0001027-1,information,"Warfarin resistance is a condition in which individuals have a high tolerance for the drug warfarin. Warfarin is an anticoagulant, which means that it thins the blood, preventing blood clots from forming. Warfarin is often prescribed to prevent blood clots in people with heart valve disease who have replacement heart valves, people with an irregular heart beat (atrial fibrillation), or those with a history of heart attack, stroke, or a prior blood clot in the deep veins of the arms or legs (deep vein thrombosis).  There are two types of warfarin resistance: incomplete and complete. Those with incomplete warfarin resistance can achieve the benefits of warfarin treatment with a high dose of warfarin. Individuals with complete warfarin resistance do not respond to warfarin treatment, no matter how high the dose. If people with warfarin resistance require treatment with warfarin and take the average dose, they will remain at risk of developing a potentially harmful blood clot.  Both types of warfarin resistance are related to how the body processes warfarin. In some people with warfarin resistance, their blood clotting process does not react effectively to the drug. Others with this resistance rapidly break down (metabolize) warfarin, so the medication is quickly processed by their bodies; these individuals are classified as ""fast metabolizers"" or ""rapid metabolizers"" of warfarin. The severity of these abnormal processes determines whether the warfarin resistance is complete or incomplete.  Warfarin resistance does not appear to cause any health problems other than those associated with warfarin drug treatment.",warfarin resistance,0001027,GHR,https://ghr.nlm.nih.gov/condition/warfarin-resistance,C0750384,T047,Disorders
How many people are affected by warfarin resistance ?,0001027-2,frequency,"Warfarin resistance is thought to be a rare condition, although its prevalence is unknown.",warfarin resistance,0001027,GHR,https://ghr.nlm.nih.gov/condition/warfarin-resistance,C0750384,T047,Disorders
What are the genetic changes related to warfarin resistance ?,0001027-3,genetic changes,"Many genes are involved in the metabolism of warfarin and in determining the drug's effects in the body. Certain common changes (polymorphisms) in the VKORC1 gene account for 20 percent of the variation in warfarin metabolism due to genetic factors. Polymorphisms in other genes, some of which have not been identified, have a smaller effect on warfarin metabolism.  The VKORC1 gene provides instructions for making a vitamin K epoxide reductase enzyme. The VKORC1 enzyme helps turn on (activate) clotting proteins in the pathway that forms blood clots. Warfarin prevents (inhibits) the action of VKORC1 by binding to the complex and preventing it from binding to and activating the clotting proteins, stopping clot formation. Certain VKORC1 gene polymorphisms lead to the formation of a VKORC1 enzyme with a decreased ability to bind to warfarin. This reduction in warfarin binding causes incomplete warfarin resistance and results in more warfarin being needed to inhibit the VKORC1 enzyme and stop the clotting process. If no warfarin can bind to the VKORC1 enzyme, the result is complete warfarin resistance.  While changes in specific genes affect how the body reacts to warfarin, many other factors, including gender, age, weight, diet, and other medications, also play a role in the body's interaction with this drug.",warfarin resistance,0001027,GHR,https://ghr.nlm.nih.gov/condition/warfarin-resistance,C0750384,T047,Disorders
Is warfarin resistance inherited ?,0001027-4,inheritance,"The polymorphisms associated with this condition are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to result in warfarin resistance. However, different polymorphisms affect the activity of warfarin to varying degrees. Additionally, people who have more than one polymorphism in a gene or polymorphisms in multiple genes associated with warfarin resistance have a higher tolerance for the drug's effect or are able to process the drug more quickly.",warfarin resistance,0001027,GHR,https://ghr.nlm.nih.gov/condition/warfarin-resistance,C0750384,T047,Disorders
What are the treatments for warfarin resistance ?,0001027-5,treatment,These resources address the diagnosis or management of warfarin resistance:  - American Society of Hematology: Antithrombotic Therapy  - MedlinePlus Drugs & Supplements: Warfarin  - PharmGKB   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,warfarin resistance,0001027,GHR,https://ghr.nlm.nih.gov/condition/warfarin-resistance,C0750384,T047,Disorders
What is (are) warfarin sensitivity ?,0001028-1,information,"Warfarin sensitivity is a condition in which individuals have a low tolerance for the drug warfarin. Warfarin is an anticoagulant, which means that it thins the blood, preventing blood clots from forming. Warfarin is often prescribed to prevent blood clots in people with heart valve disease who have replacement heart valves, people with an irregular heart beat (atrial fibrillation), or those with a history of heart attack, stroke, or a prior blood clot in the deep veins of the arms or legs (deep vein thrombosis).  Many people with warfarin sensitivity take longer than normal to break down (metabolize) warfarin, so the medication is in their body longer than usual and they require lower doses. These individuals are classified as ""slow metabolizers"" of warfarin. Other people with warfarin sensitivity do not need as much drug to prevent clots because their clot forming process is already slower than average and can be inhibited by low warfarin doses. If people with warfarin sensitivity take the average dose (or more) of warfarin, they are at risk of an overdose, which can cause abnormal bleeding in the brain, gastrointestinal tract, or other tissues, and may lead to serious health problems or death.  Warfarin sensitivity does not appear to cause any health problems other than those associated with warfarin drug treatment.",warfarin sensitivity,0001028,GHR,https://ghr.nlm.nih.gov/condition/warfarin-sensitivity,C2608079,T047,Disorders
How many people are affected by warfarin sensitivity ?,0001028-2,frequency,"The prevalence of warfarin sensitivity is unknown. However, it appears to be more common in people who are older, those with lower body weights, and individuals of Asian ancestry.  Of the approximately 2 million people in the U.S. who are prescribed warfarin annually, 35,000 to 45,000 individuals go to hospital emergency rooms with warfarin-related adverse drug events. While it is unclear how many of these events are due to warfarin sensitivity, the most common sign is excessive internal bleeding, which is often seen when individuals with warfarin sensitivity are given too much of the medication.",warfarin sensitivity,0001028,GHR,https://ghr.nlm.nih.gov/condition/warfarin-sensitivity,C2608079,T047,Disorders
What are the genetic changes related to warfarin sensitivity ?,0001028-3,genetic changes,"Many genes are involved in the metabolism of warfarin and in determining the drug's effects in the body. Certain common changes (polymorphisms) in the CYP2C9 and VKORC1 genes account for 30 percent of the variation in warfarin metabolism due to genetic factors. Polymorphisms in other genes, some of which have not been identified, have a smaller effect on warfarin metabolism.  The CYP2C9 gene provides instructions for making an enzyme that breaks down compounds including steroids and fatty acids. The CYP2C9 enzyme also breaks down certain drugs, including warfarin. Several CYP2C9 gene polymorphisms can decrease the activity of the CYP2C9 enzyme and slow the body's metabolism of warfarin. As a result, the drug remains active in the body for a longer period of time, leading to warfarin sensitivity.  The VKORC1 gene provides instructions for making a vitamin K epoxide reductase enzyme. The VKORC1 enzyme helps turn on (activate) clotting proteins in the pathway that forms blood clots. Warfarin prevents (inhibits) the action of VKORC1 and slows the activation of clotting proteins and clot formation. Certain VKORC1 gene polymorphisms decrease the amount of functional VKORC1 enzyme available to help activate clotting proteins. Individuals develop warfarin sensitivity because less warfarin is needed to inhibit the VKORC1 enzyme, as there is less functional enzyme that needs to be suppressed.  While changes in specific genes, particularly CYP2C9 and VKORC1, affect how the body reacts to warfarin, many other factors, including gender, age, weight, diet, and other medications, also play a role in the body's interaction with this drug.",warfarin sensitivity,0001028,GHR,https://ghr.nlm.nih.gov/condition/warfarin-sensitivity,C2608079,T047,Disorders
Is warfarin sensitivity inherited ?,0001028-4,inheritance,"The polymorphisms associated with this condition are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to result in warfarin sensitivity. However, different polymorphisms affect the activity of warfarin to varying degrees. Additionally, people who have more than one polymorphism in a gene or polymorphisms in multiple genes associated with warfarin sensitivity have a lower tolerance for the drug's effect or take even longer to clear the drug from their body.",warfarin sensitivity,0001028,GHR,https://ghr.nlm.nih.gov/condition/warfarin-sensitivity,C2608079,T047,Disorders
What are the treatments for warfarin sensitivity ?,0001028-5,treatment,These resources address the diagnosis or management of warfarin sensitivity:  - Food and Drug Administration Medication Guide  - MedlinePlus Drugs & Supplements: Warfarin  - My46 Trait Profile  - PharmGKB  - WarfarinDosing.org   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,warfarin sensitivity,0001028,GHR,https://ghr.nlm.nih.gov/condition/warfarin-sensitivity,C2608079,T047,Disorders
What is (are) Warsaw breakage syndrome ?,0001029-1,information,"Warsaw breakage syndrome is a condition that can cause multiple abnormalities. People with Warsaw breakage syndrome have intellectual disability that varies from mild to severe. They also have impaired growth from birth leading to short stature and a small head size (microcephaly). Affected individuals have distinctive facial features that may include a small forehead, a short nose, a small lower jaw, a flat area between the nose and mouth (philtrum), and prominent cheeks. Other common features include hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss) and heart malformations.",Warsaw breakage syndrome,0001029,GHR,https://ghr.nlm.nih.gov/condition/warsaw-breakage-syndrome,C3150658,T047,Disorders
How many people are affected by Warsaw breakage syndrome ?,0001029-2,frequency,Warsaw breakage syndrome is a rare condition; at least four cases have been described in the medical literature.,Warsaw breakage syndrome,0001029,GHR,https://ghr.nlm.nih.gov/condition/warsaw-breakage-syndrome,C3150658,T047,Disorders
What are the genetic changes related to Warsaw breakage syndrome ?,0001029-3,genetic changes,"Mutations in the DDX11 gene cause Warsaw breakage syndrome. The DDX11 gene provides instructions for making an enzyme called ChlR1. This enzyme functions as a helicase. Helicases are enzymes that attach (bind) to DNA and temporarily unwind the two spiral strands (double helix) of the DNA molecule. This unwinding is necessary for copying (replicating) DNA in preparation for cell division, and for repairing damaged DNA and any mistakes that are made when DNA is copied. In addition, after DNA is copied, ChlR1 plays a role in ensuring proper separation of each chromosome during cell division. By helping repair mistakes in DNA and ensuring proper DNA replication, the ChlR1 enzyme is involved in maintaining the stability of a cell's genetic information.  DDX11 gene mutations severely reduce or completely eliminate ChlR1 enzyme activity. As a result, the enzyme cannot bind to DNA and cannot unwind the DNA strands to help with DNA replication and repair. A lack of functional ChlR1 impairs cell division and leads to an accumulation of DNA damage. This DNA damage can appear as breaks in the DNA, giving the condition its name. It is unclear how these problems in DNA maintenance lead to the specific abnormalities characteristic of Warsaw breakage syndrome.",Warsaw breakage syndrome,0001029,GHR,https://ghr.nlm.nih.gov/condition/warsaw-breakage-syndrome,C3150658,T047,Disorders
Is Warsaw breakage syndrome inherited ?,0001029-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Warsaw breakage syndrome,0001029,GHR,https://ghr.nlm.nih.gov/condition/warsaw-breakage-syndrome,C3150658,T047,Disorders
What are the treatments for Warsaw breakage syndrome ?,0001029-5,treatment,These resources address the diagnosis or management of Warsaw breakage syndrome:  - Centers for Disease Control and Prevention: Hearing Loss in Children  - Genetic Testing Registry: Warsaw breakage syndrome  - MedlinePlus Encyclopedia: Hearing Loss--Infants   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Warsaw breakage syndrome,0001029,GHR,https://ghr.nlm.nih.gov/condition/warsaw-breakage-syndrome,C3150658,T047,Disorders
What is (are) Weaver syndrome ?,0001030-1,information,"Weaver syndrome is a condition that involves tall stature with or without a large head size (macrocephaly), a variable degree of intellectual disability (usually mild), and characteristic facial features. These features can include a broad forehead; widely spaced eyes (hypertelorism); large, low-set ears; a dimpled chin, and a small lower jaw (micrognathia).  People with Weaver syndrome can also have joint deformities called contractures that restrict the movement of affected joints. The contractures may particularly affect the fingers and toes, resulting in permanently bent digits (camptodactyly). Other features of this disorder can include abnormal curvature of the spine (kyphoscoliosis); muscle tone that is either reduced (hypotonia) or increased (hypertonia); loose, saggy skin; and a soft-outpouching around the belly-button (umbilical hernia). Some affected individuals have abnormalities in the folds (gyri) of the brain, which can be seen by medical imaging; the relationship between these brain abnormalities and the intellectual disability associated with Weaver syndrome is unclear.  Researchers suggest that people with Weaver syndrome may have an increased risk of developing cancer, in particular a slightly increased risk of developing a tumor called neuroblastoma in early childhood, but the small number of affected individuals makes it difficult to determine the exact risk.",Weaver syndrome,0001030,GHR,https://ghr.nlm.nih.gov/condition/weaver-syndrome,C0265210,T019,Disorders
How many people are affected by Weaver syndrome ?,0001030-2,frequency,The prevalence of Weaver syndrome is unknown. About 50 affected individuals have been described in the medical literature.,Weaver syndrome,0001030,GHR,https://ghr.nlm.nih.gov/condition/weaver-syndrome,C0265210,T019,Disorders
What are the genetic changes related to Weaver syndrome ?,0001030-3,genetic changes,"Weaver syndrome is usually caused by mutations in the EZH2 gene. The EZH2 gene provides instructions for making a type of enzyme called a histone methyltransferase. Histone methyltransferases modify proteins called histones, which are structural proteins that attach (bind) to DNA and give chromosomes their shape. By adding a molecule called a methyl group to histones (methylation), histone methyltransferases can turn off the activity of certain genes, which is an essential process in normal development. It is unclear how mutations in the EZH2 gene result in the abnormalities characteristic of Weaver syndrome.",Weaver syndrome,0001030,GHR,https://ghr.nlm.nih.gov/condition/weaver-syndrome,C0265210,T019,Disorders
Is Weaver syndrome inherited ?,0001030-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family. In a small number of cases, an affected person inherits the mutation from one affected parent.",Weaver syndrome,0001030,GHR,https://ghr.nlm.nih.gov/condition/weaver-syndrome,C0265210,T019,Disorders
What are the treatments for Weaver syndrome ?,0001030-5,treatment,These resources address the diagnosis or management of Weaver syndrome:  - Genetic Testing Registry: Weaver syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Weaver syndrome,0001030,GHR,https://ghr.nlm.nih.gov/condition/weaver-syndrome,C0265210,T019,Disorders
What is (are) Weill-Marchesani syndrome ?,0001031-1,information,"Weill-Marchesani syndrome is a disorder of connective tissue. Connective tissue forms the body's supportive framework, providing structure and strength to the muscles, joints, organs, and skin.  The major signs and symptoms of Weill-Marchesani syndrome include short stature, eye abnormalities, unusually short fingers and toes (brachydactyly), and joint stiffness. Adult height for men with Weill-Marchesani syndrome ranges from 4 feet, 8 inches to 5 feet, 6 inches. Adult height for women with this condition ranges from 4 feet, 3 inches to 5 feet, 2 inches.  An eye abnormality called microspherophakia is characteristic of Weill-Marchesani syndrome. This term refers to a small, sphere-shaped lens, which is associated with nearsightedness (myopia) that worsens over time. The lens also may be positioned abnormally within the eye (ectopia lentis). Many people with Weill-Marchesani syndrome develop glaucoma, an eye disease that increases the pressure in the eye and can lead to blindness.  Occasionally, heart defects or an abnormal heart rhythm can occur in people with Weill-Marchesani syndrome.",Weill-Marchesani syndrome,0001031,GHR,https://ghr.nlm.nih.gov/condition/weill-marchesani-syndrome,C0265313,T019,Disorders
How many people are affected by Weill-Marchesani syndrome ?,0001031-2,frequency,"Weill-Marchesani syndrome appears to be rare; it has an estimated prevalence of 1 in 100,000 people.",Weill-Marchesani syndrome,0001031,GHR,https://ghr.nlm.nih.gov/condition/weill-marchesani-syndrome,C0265313,T019,Disorders
What are the genetic changes related to Weill-Marchesani syndrome ?,0001031-3,genetic changes,"Mutations in the ADAMTS10 and FBN1 genes can cause Weill-Marchesani syndrome. The ADAMTS10 gene provides instructions for making a protein whose function is unknown. This protein is important for normal growth before and after birth, and it appears to be involved in the development of the eyes, heart, and skeleton. Mutations in this gene disrupt the normal development of these structures, which leads to the specific features of Weill-Marchesani syndrome.  A mutation in the FBN1 gene has also been found to cause Weill-Marchesani syndrome. The FBN1 gene provides instructions for making a protein called fibrillin-1. This protein is needed to form threadlike filaments, called microfibrils, that help provide strength and flexibility to connective tissue. The FBN1 mutation responsible for Weill-Marchesani syndrome leads to an unstable version of fibrillin-1. Researchers believe that the unstable protein interferes with the normal assembly of microfibrils, which weakens connective tissue and causes the abnormalities associated with Weill-Marchesani syndrome.  In some people with Weill-Marchesani syndrome, no mutations in ADAMTS10 or FBN1 have been found. Researchers are looking for other genetic changes that may be responsible for the disorder in these people.",Weill-Marchesani syndrome,0001031,GHR,https://ghr.nlm.nih.gov/condition/weill-marchesani-syndrome,C0265313,T019,Disorders
Is Weill-Marchesani syndrome inherited ?,0001031-4,inheritance,"Weill-Marchesani syndrome can be inherited in either an autosomal recessive or an autosomal dominant pattern.  When Weill-Marchesani syndrome is caused by mutations in the ADAMTS10 gene, it has an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Other cases of Weill-Marchesani syndrome, including those caused by mutations in the FBN1 gene, have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the genetic change from one parent with the condition.",Weill-Marchesani syndrome,0001031,GHR,https://ghr.nlm.nih.gov/condition/weill-marchesani-syndrome,C0265313,T019,Disorders
What are the treatments for Weill-Marchesani syndrome ?,0001031-5,treatment,These resources address the diagnosis or management of Weill-Marchesani syndrome:  - Gene Review: Gene Review: Weill-Marchesani Syndrome  - Genetic Testing Registry: Weill-Marchesani syndrome  - Genetic Testing Registry: Weill-Marchesani syndrome 1  - Genetic Testing Registry: Weill-Marchesani syndrome 2  - Genetic Testing Registry: Weill-Marchesani syndrome 3   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Weill-Marchesani syndrome,0001031,GHR,https://ghr.nlm.nih.gov/condition/weill-marchesani-syndrome,C0265313,T019,Disorders
What is (are) Weissenbacher-Zweymller syndrome ?,0001032-1,information,"Weissenbacher-Zweymller syndrome is a condition that affects bone growth. It is characterized by skeletal abnormalities, hearing loss, and distinctive facial features. This condition has features that are similar to those of another skeletal disorder, otospondylomegaepiphyseal dysplasia (OSMED).  Infants born with Weissenbacher-Zweymller syndrome are smaller than average because the bones in their arms and legs are unusually short. The thigh and upper arm bones are shaped like dumbbells, and the bones of the spine (vertebrae) may also be abnormally shaped. High-tone hearing loss occurs in some cases. Distinctive facial features include wide-set protruding eyes, a small, upturned nose with a flat bridge, and a small lower jaw. Some affected infants are born with an opening in the roof of the mouth (a cleft palate).  The skeletal features of Weissenbacher-Zweymller syndrome tend to diminish during childhood. Most adults with this condition are not unusually short, but do still retain the other features of Weissenbacher-Zweymller syndrome.",Weissenbacher-Zweymller syndrome,0001032,GHR,https://ghr.nlm.nih.gov/condition/weissenbacher-zweymuller-syndrome,C0039082,T047,Disorders
How many people are affected by Weissenbacher-Zweymller syndrome ?,0001032-2,frequency,Weissenbacher-Zweymller syndrome is very rare; only a few families with the disorder have been reported worldwide.,Weissenbacher-Zweymller syndrome,0001032,GHR,https://ghr.nlm.nih.gov/condition/weissenbacher-zweymuller-syndrome,C0039082,T047,Disorders
What are the genetic changes related to Weissenbacher-Zweymller syndrome ?,0001032-3,genetic changes,"Mutations in the COL11A2 gene cause Weissenbacher-Zweymller syndrome. The COL11A2 gene is one of several genes that provide instructions for the production of type XI collagen. This type of collagen is important for the normal development of bones and other connective tissues that form the body's supportive framework. At least one mutation in the COL11A2 gene is known to cause Weissenbacher-Zweymller syndrome. This mutation disrupts the assembly of type XI collagen molecules, resulting in delayed bone development and the other features of this disorder.",Weissenbacher-Zweymller syndrome,0001032,GHR,https://ghr.nlm.nih.gov/condition/weissenbacher-zweymuller-syndrome,C0039082,T047,Disorders
Is Weissenbacher-Zweymller syndrome inherited ?,0001032-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.",Weissenbacher-Zweymller syndrome,0001032,GHR,https://ghr.nlm.nih.gov/condition/weissenbacher-zweymuller-syndrome,C0039082,T047,Disorders
What are the treatments for Weissenbacher-Zweymller syndrome ?,0001032-5,treatment,These resources address the diagnosis or management of Weissenbacher-Zweymller syndrome:  - Genetic Testing Registry: Weissenbacher-Zweymuller syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Weissenbacher-Zweymller syndrome,0001032,GHR,https://ghr.nlm.nih.gov/condition/weissenbacher-zweymuller-syndrome,C0039082,T047,Disorders
What is (are) Werner syndrome ?,0001033-1,information,"Werner syndrome is characterized by the dramatic, rapid appearance of features associated with normal aging. Individuals with this disorder typically grow and develop normally until they reach puberty. Affected teenagers usually do not have a growth spurt, resulting in short stature. The characteristic aged appearance of individuals with Werner syndrome typically begins to develop when they are in their twenties and includes graying and loss of hair; a hoarse voice; and thin, hardened skin. They may also have a facial appearance described as ""bird-like."" Many people with Werner syndrome have thin arms and legs and a thick trunk due to abnormal fat deposition.  As Werner syndrome progresses, affected individuals may develop disorders of aging early in life, such as cloudy lenses (cataracts) in both eyes, skin ulcers, type 2 diabetes, diminished fertility, severe hardening of the arteries (atherosclerosis), thinning of the bones (osteoporosis), and some types of cancer. It is not uncommon for affected individuals to develop multiple, rare cancers during their lifetime. People with Werner syndrome usually live into their late forties or early fifties. The most common causes of death are cancer and atherosclerosis.",Werner syndrome,0001033,GHR,https://ghr.nlm.nih.gov/condition/werner-syndrome,C0043119,T047,Disorders
How many people are affected by Werner syndrome ?,0001033-2,frequency,"Werner syndrome is estimated to affect 1 in 200,000 individuals in the United States. This syndrome occurs more often in Japan, affecting 1 in 20,000 to 1 in 40,000 people.",Werner syndrome,0001033,GHR,https://ghr.nlm.nih.gov/condition/werner-syndrome,C0043119,T047,Disorders
What are the genetic changes related to Werner syndrome ?,0001033-3,genetic changes,"Mutations in the WRN gene cause Werner syndrome. The WRN gene provides instructions for producing the Werner protein, which is thought to perform several tasks related to the maintenance and repair of DNA. This protein also assists in the process of copying (replicating) DNA in preparation for cell division. Mutations in the WRN gene often lead to the production of an abnormally short, nonfunctional Werner protein. Research suggests that this shortened protein is not transported to the cell's nucleus, where it normally interacts with DNA. Evidence also suggests that the altered protein is broken down more quickly in the cell than the normal Werner protein. Researchers do not fully understand how WRN mutations cause the signs and symptoms of Werner syndrome. Cells with an altered Werner protein may divide more slowly or stop dividing earlier than normal, causing growth problems. Also, the altered protein may allow DNA damage to accumulate, which could impair normal cell activities and cause the health problems associated with this condition.",Werner syndrome,0001033,GHR,https://ghr.nlm.nih.gov/condition/werner-syndrome,C0043119,T047,Disorders
Is Werner syndrome inherited ?,0001033-4,inheritance,"Werner syndrome is inherited in an autosomal recessive pattern, which means both copies of the WRN gene in each cell have mutations. The parents of an individual with Werner syndrome each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Werner syndrome,0001033,GHR,https://ghr.nlm.nih.gov/condition/werner-syndrome,C0043119,T047,Disorders
What are the treatments for Werner syndrome ?,0001033-5,treatment,These resources address the diagnosis or management of Werner syndrome:  - Gene Review: Gene Review: Werner Syndrome  - Genetic Testing Registry: Werner syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Werner syndrome,0001033,GHR,https://ghr.nlm.nih.gov/condition/werner-syndrome,C0043119,T047,Disorders
What is (are) Weyers acrofacial dysostosis ?,0001034-1,information,"Weyers acrofacial dysostosis is a disorder that affects the development of the teeth, nails, and bones. Dental abnormalities can include small, peg-shaped teeth; fewer teeth than normal (hypodontia); and one front tooth instead of two (a single central incisor). Additionally, the lower jaw (mandible) may be abnormally shaped. People with Weyers acrofacial dysostosis have abnormally small or malformed fingernails and toenails. Most people with the condition are relatively short, and they may have extra fingers or toes (polydactyly).  The features of Weyers acrofacial dysostosis overlap with those of another, more severe condition called Ellis-van Creveld syndrome. In addition to tooth and nail abnormalities, people with Ellis-van Creveld syndrome have very short stature and are often born with heart defects. The two conditions are caused by mutations in the same genes.",Weyers acrofacial dysostosis,0001034,GHR,https://ghr.nlm.nih.gov/condition/weyers-acrofacial-dysostosis,C0457013,T019,Disorders
How many people are affected by Weyers acrofacial dysostosis ?,0001034-2,frequency,Weyers acrofacial dysostosis appears to be a rare disorder. Only a few affected families have been identified worldwide.,Weyers acrofacial dysostosis,0001034,GHR,https://ghr.nlm.nih.gov/condition/weyers-acrofacial-dysostosis,C0457013,T019,Disorders
What are the genetic changes related to Weyers acrofacial dysostosis ?,0001034-3,genetic changes,"Most cases of Weyers acrofacial dysostosis result from mutations in the EVC2 gene. A mutation in a similar gene, EVC, has been found in at least one person with the characteristic features of the disorder. Little is known about the function of the EVC and EVC2 genes, although they appear to play important roles in cell-to-cell signaling during development. In particular, the proteins produced from these genes are thought to help regulate the Sonic Hedgehog signaling pathway. This pathway plays roles in cell growth, cell specialization, and the normal shaping (patterning) of many parts of the body.  The mutations that cause Weyers acrofacial dysostosis result in the production of an abnormal EVC or EVC2 protein. It is unclear how the abnormal proteins lead to the specific signs and symptoms of this condition. Studies suggest that they interfere with Sonic Hedgehog signaling in the developing embryo, disrupting the formation and growth of the teeth, nails, and bones.",Weyers acrofacial dysostosis,0001034,GHR,https://ghr.nlm.nih.gov/condition/weyers-acrofacial-dysostosis,C0457013,T019,Disorders
Is Weyers acrofacial dysostosis inherited ?,0001034-4,inheritance,"Weyers acrofacial dysostosis is inherited in an autosomal dominant pattern, which means one copy of the altered EVC or EVC2 gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the altered gene from a parent who has the condition.",Weyers acrofacial dysostosis,0001034,GHR,https://ghr.nlm.nih.gov/condition/weyers-acrofacial-dysostosis,C0457013,T019,Disorders
What are the treatments for Weyers acrofacial dysostosis ?,0001034-5,treatment,These resources address the diagnosis or management of Weyers acrofacial dysostosis:  - Genetic Testing Registry: Curry-Hall syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Weyers acrofacial dysostosis,0001034,GHR,https://ghr.nlm.nih.gov/condition/weyers-acrofacial-dysostosis,C0457013,T019,Disorders
What is (are) white sponge nevus ?,0001035-1,information,"White sponge nevus is a condition characterized by the formation of white patches of tissue called nevi (singular: nevus) that appear as thickened, velvety, sponge-like tissue. The nevi are most commonly found on the moist lining of the mouth (oral mucosa), especially on the inside of the cheeks (buccal mucosa). Affected individuals usually develop multiple nevi. Rarely, white sponge nevi also occur on the mucosae (singular: mucosa) of the nose, esophagus, genitals, or anus. The nevi are caused by a noncancerous (benign) overgrowth of cells.  White sponge nevus can be present from birth but usually first appears during early childhood. The size and location of the nevi can change over time. In the oral mucosa, both sides of the mouth are usually affected. The nevi are generally painless, but the folds of extra tissue can promote bacterial growth, which can lead to infection that may cause discomfort. The altered texture and appearance of the affected tissue, especially the oral mucosa, can be bothersome for some affected individuals.",white sponge nevus,0001035,GHR,https://ghr.nlm.nih.gov/condition/white-sponge-nevus,C1721005,T047,Disorders
How many people are affected by white sponge nevus ?,0001035-2,frequency,"The exact prevalence of white sponge nevus is unknown, but it is estimated to affect less than 1 in 200,000 individuals worldwide.",white sponge nevus,0001035,GHR,https://ghr.nlm.nih.gov/condition/white-sponge-nevus,C1721005,T047,Disorders
What are the genetic changes related to white sponge nevus ?,0001035-3,genetic changes,"Mutations in the KRT4 or KRT13 gene cause white sponge nevus. These genes provide instructions for making proteins called keratins. Keratins are a group of tough, fibrous proteins that form the structural framework of epithelial cells, which are cells that line the surfaces and cavities of the body and make up the different mucosae. The keratin 4 protein (produced from the KRT4 gene) and the keratin 13 protein (produced from the KRT13 gene) partner together to form molecules known as intermediate filaments. These filaments assemble into networks that provide strength and resilience to the different mucosae. Networks of intermediate filaments protect the mucosae from being damaged by friction or other everyday physical stresses.  Mutations in the KRT4 or KRT13 gene disrupt the structure of the keratin protein. As a result, keratin 4 and keratin 13 are mismatched and do not fit together properly, leading to the formation of irregular intermediate filaments that are easily damaged with little friction or trauma. Fragile intermediate filaments in the oral mucosa might be damaged when eating or brushing one's teeth. Damage to intermediate filaments leads to inflammation and promotes the abnormal growth and division (proliferation) of epithelial cells, causing the mucosae to thicken and resulting in white sponge nevus.",white sponge nevus,0001035,GHR,https://ghr.nlm.nih.gov/condition/white-sponge-nevus,C1721005,T047,Disorders
Is white sponge nevus inherited ?,0001035-4,inheritance,"This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell can be sufficient to cause the disorder. However, some people who have a mutation that causes white sponge nevus do not develop these abnormal growths; this phenomenon is called reduced penetrance.",white sponge nevus,0001035,GHR,https://ghr.nlm.nih.gov/condition/white-sponge-nevus,C1721005,T047,Disorders
What are the treatments for white sponge nevus ?,0001035-5,treatment,These resources address the diagnosis or management of white sponge nevus:  - Genetic Testing Registry: White sponge nevus of cannon   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,white sponge nevus,0001035,GHR,https://ghr.nlm.nih.gov/condition/white-sponge-nevus,C1721005,T047,Disorders
What is (are) Williams syndrome ?,0001036-1,information,"Williams syndrome is a developmental disorder that affects many parts of the body. This condition is characterized by mild to moderate intellectual disability or learning problems, unique personality characteristics, distinctive facial features, and heart and blood vessel (cardiovascular) problems.  People with Williams syndrome typically have difficulty with visual-spatial tasks such as drawing and assembling puzzles, but they tend to do well on tasks that involve spoken language, music, and learning by repetition (rote memorization). Affected individuals have outgoing, engaging personalities and tend to take an extreme interest in other people. Attention deficit disorder (ADD), problems with anxiety, and phobias are common among people with this disorder.  Young children with Williams syndrome have distinctive facial features including a broad forehead, a short nose with a broad tip, full cheeks, and a wide mouth with full lips. Many affected people have dental problems such as teeth that are small, widely spaced, crooked, or missing. In older children and adults, the face appears longer and more gaunt.  A form of cardiovascular disease called supravalvular aortic stenosis (SVAS) occurs frequently in people with Williams syndrome. Supravalvular aortic stenosis is a narrowing of the large blood vessel that carries blood from the heart to the rest of the body (the aorta). If this condition is not treated, the aortic narrowing can lead to shortness of breath, chest pain, and heart failure. Other problems with the heart and blood vessels, including high blood pressure (hypertension), have also been reported in people with Williams syndrome.  Additional signs and symptoms of Williams syndrome include abnormalities of connective tissue (tissue that supports the body's joints and organs) such as joint problems and soft, loose skin. Affected people may also have increased calcium levels in the blood (hypercalcemia) in infancy, developmental delays, problems with coordination, and short stature. Medical problems involving the eyes and vision, the digestive tract, and the urinary system are also possible.",Williams syndrome,0001036,GHR,https://ghr.nlm.nih.gov/condition/williams-syndrome,C0175702,T019,Disorders
How many people are affected by Williams syndrome ?,0001036-2,frequency,"Williams syndrome affects an estimated 1 in 7,500 to 10,000 people.",Williams syndrome,0001036,GHR,https://ghr.nlm.nih.gov/condition/williams-syndrome,C0175702,T019,Disorders
What are the genetic changes related to Williams syndrome ?,0001036-3,genetic changes,"Williams syndrome is caused by the deletion of genetic material from a specific region of chromosome 7. The deleted region includes 26 to 28 genes, and researchers believe that a loss of several of these genes probably contributes to the characteristic features of this disorder.  CLIP2, ELN, GTF2I, GTF2IRD1, and LIMK1 are among the genes that are typically deleted in people with Williams syndrome. Researchers have found that loss of the ELN gene is associated with the connective tissue abnormalities and cardiovascular disease (specifically supravalvular aortic stenosis) found in many people with this disease. Studies suggest that deletion of CLIP2, GTF2I, GTF2IRD1, LIMK1, and perhaps other genes may help explain the characteristic difficulties with visual-spatial tasks, unique behavioral characteristics, and other cognitive difficulties seen in people with Williams syndrome. Loss of the GTF2IRD1 gene may also contribute to the distinctive facial features often associated with this condition.  Researchers believe that the presence or absence of the NCF1 gene on chromosome 7 is related to the risk of developing hypertension in people with Williams syndrome. When the NCF1 gene is included in the part of the chromosome that is deleted, affected individuals are less likely to develop hypertension. Therefore, the loss of this gene appears to be a protective factor. People with Williams syndrome whose NCF1 gene is not deleted have a higher risk of developing hypertension.  The relationship between other genes in the deleted region of chromosome 7 and the signs and symptoms of Williams syndrome is under investigation or unknown.",Williams syndrome,0001036,GHR,https://ghr.nlm.nih.gov/condition/williams-syndrome,C0175702,T019,Disorders
Is Williams syndrome inherited ?,0001036-4,inheritance,"Most cases of Williams syndrome are not inherited but occur as random events during the formation of reproductive cells (eggs or sperm) in a parent of an affected individual. These cases occur in people with no history of the disorder in their family.  Williams syndrome is considered an autosomal dominant condition because one copy of the altered chromosome 7 in each cell is sufficient to cause the disorder. In a small percentage of cases, people with Williams syndrome inherit the chromosomal deletion from a parent with the condition.",Williams syndrome,0001036,GHR,https://ghr.nlm.nih.gov/condition/williams-syndrome,C0175702,T019,Disorders
What are the treatments for Williams syndrome ?,0001036-5,treatment,These resources address the diagnosis or management of Williams syndrome:  - Gene Review: Gene Review: Williams Syndrome  - Genetic Testing Registry: Williams syndrome  - MedlinePlus Encyclopedia: Williams Syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Williams syndrome,0001036,GHR,https://ghr.nlm.nih.gov/condition/williams-syndrome,C0175702,T019,Disorders
What is (are) Wilson disease ?,0001037-1,information,"Wilson disease is an inherited disorder in which excessive amounts of copper accumulate in the body, particularly in the liver, brain, and eyes. The signs and symptoms of Wilson disease usually first appear between the ages of 6 and 45, but they most often begin during the teenage years. The features of this condition include a combination of liver disease and neurological and psychiatric problems.  Liver disease is typically the initial feature of Wilson disease in affected children and young adults; individuals diagnosed at an older age usually do not have symptoms of liver problems, although they may have very mild liver disease. The signs and symptoms of liver disease include yellowing of the skin or whites of the eyes (jaundice), fatigue, loss of appetite, and abdominal swelling.  Nervous system or psychiatric problems are often the initial features in individuals diagnosed in adulthood and commonly occur in young adults with Wilson disease. Signs and symptoms of these problems can include clumsiness, tremors, difficulty walking, speech problems, impaired thinking ability, depression, anxiety, and mood swings.  In many individuals with Wilson disease, copper deposits in the front surface of the eye (the cornea) form a green-to-brownish ring, called the Kayser-Fleischer ring, that surrounds the colored part of the eye. Abnormalities in eye movements, such as a restricted ability to gaze upwards, may also occur.",Wilson disease,0001037,GHR,https://ghr.nlm.nih.gov/condition/wilson-disease,C0019202,T047,Disorders
How many people are affected by Wilson disease ?,0001037-2,frequency,"Wilson disease is a rare disorder that affects approximately 1 in 30,000 individuals.",Wilson disease,0001037,GHR,https://ghr.nlm.nih.gov/condition/wilson-disease,C0019202,T047,Disorders
What are the genetic changes related to Wilson disease ?,0001037-3,genetic changes,"Wilson disease is caused by mutations in the ATP7B gene. This gene provides instructions for making a protein called copper-transporting ATPase 2, which plays a role in the transport of copper from the liver to other parts of the body. Copper is necessary for many cellular functions, but it is toxic when present in excessive amounts. The copper-transporting ATPase 2 protein is particularly important for the elimination of excess copper from the body. Mutations in the ATP7B gene prevent the transport protein from functioning properly. With a shortage of functional protein, excess copper is not removed from the body. As a result, copper accumulates to toxic levels that can damage tissues and organs, particularly the liver and brain.  Research indicates that a normal variation in the PRNP gene may modify the course of Wilson disease. The PRNP gene provides instructions for making prion protein, which is active in the brain and other tissues and appears to be involved in transporting copper. Studies have focused on the effects of a PRNP gene variation that affects position 129 of the prion protein. At this position, people can have either the protein building block (amino acid) methionine or the amino acid valine. Among people who have mutations in the ATP7B gene, it appears that having methionine instead of valine at position 129 of the prion protein is associated with delayed onset of symptoms and an increased occurrence of neurological symptoms, particularly tremors. Larger studies are needed, however, before the effects of this PRNP gene variation on Wilson disease can be established.",Wilson disease,0001037,GHR,https://ghr.nlm.nih.gov/condition/wilson-disease,C0019202,T047,Disorders
Is Wilson disease inherited ?,0001037-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Wilson disease,0001037,GHR,https://ghr.nlm.nih.gov/condition/wilson-disease,C0019202,T047,Disorders
What are the treatments for Wilson disease ?,0001037-5,treatment,These resources address the diagnosis or management of Wilson disease:  - Gene Review: Gene Review: Wilson Disease  - Genetic Testing Registry: Wilson's disease  - MedlinePlus Encyclopedia: Wilson's disease  - National Human Genome Research Institute   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Wilson disease,0001037,GHR,https://ghr.nlm.nih.gov/condition/wilson-disease,C0019202,T047,Disorders
What is (are) Winchester syndrome ?,0001038-1,information,"Winchester syndrome is a rare inherited disease characterized by a loss of bone tissue (osteolysis), particularly in the hands and feet. Winchester syndrome used to be considered part of a related condition now called multicentric osteolysis, nodulosis, and arthropathy (MONA). However, because Winchester syndrome and MONA are caused by mutations in different genes, they are now thought to be separate disorders.  In most cases of Winchester syndrome, bone loss begins in the hands and feet, causing pain and limiting movement. Bone abnormalities later spread to other parts of the body, with joint problems (arthropathy) occurring in the elbows, shoulders, knees, hips, and spine. Most people with Winchester syndrome develop low bone mineral density (osteopenia) and thinning of the bones (osteoporosis) throughout the skeleton. These abnormalities make bones brittle and more prone to fracture. The bone abnormalities also lead to short stature.  Some people with Winchester syndrome have skin abnormalities including patches of dark, thick, and leathery skin. Other features of the condition can include clouding of the clear front covering of the eye (corneal opacity), excess hair growth (hypertrichosis), overgrowth of the gums, heart abnormalities, and distinctive facial features that are described as ""coarse.""",Winchester syndrome,0001038,GHR,https://ghr.nlm.nih.gov/condition/winchester-syndrome,C0432289,T019,Disorders
How many people are affected by Winchester syndrome ?,0001038-2,frequency,Winchester syndrome is a rare condition whose prevalence is unknown. It has been reported in only a few individuals worldwide.,Winchester syndrome,0001038,GHR,https://ghr.nlm.nih.gov/condition/winchester-syndrome,C0432289,T019,Disorders
What are the genetic changes related to Winchester syndrome ?,0001038-3,genetic changes,"Winchester syndrome is caused by mutations in the MMP14 gene (also known as MT1-MMP). This gene provides instructions for making a protein called matrix metallopeptidase 14, which is found on the surface of cells. Matrix metallopeptidase 14 normally helps modify and break down various components of the extracellular matrix, which is the intricate lattice of proteins and other molecules that forms in the spaces between cells. These changes influence many cell activities and functions, including promoting cell growth and stimulating cell movement (migration). Matrix metallopeptidase 14 also turns on (activates) a protein called matrix metallopeptidase 2. The activity of matrix metallopeptidase 2 appears to be important for a variety of body functions, including bone remodeling, which is a normal process in which old bone is broken down and new bone is created to replace it.  Mutations in the MMP14 gene alter matrix metallopeptidase 14 so that less of the enzyme is able to reach the cell surface. As a result, not enough of the enzyme is available to break down components of the extracellular matrix and activate matrix metallopeptidase 2. It is unclear how a shortage of this enzyme leads to the signs and symptoms of Winchester syndrome. It is possible that a loss of matrix metallopeptidase 2 activation somehow disrupts the balance of new bone creation and the breakdown of existing bone during bone remodeling, causing a progressive loss of bone tissue. How a reduced amount of matrix metallopeptidase 14 leads to the other features of Winchester syndrome is unknown.",Winchester syndrome,0001038,GHR,https://ghr.nlm.nih.gov/condition/winchester-syndrome,C0432289,T019,Disorders
Is Winchester syndrome inherited ?,0001038-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Winchester syndrome,0001038,GHR,https://ghr.nlm.nih.gov/condition/winchester-syndrome,C0432289,T019,Disorders
What are the treatments for Winchester syndrome ?,0001038-5,treatment,These resources address the diagnosis or management of Winchester syndrome:  - Genetic Testing Registry: Winchester syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Winchester syndrome,0001038,GHR,https://ghr.nlm.nih.gov/condition/winchester-syndrome,C0432289,T019,Disorders
What is (are) Wiskott-Aldrich syndrome ?,0001039-1,information,"Wiskott-Aldrich syndrome is characterized by abnormal immune system function (immune deficiency) and a reduced ability to form blood clots. This condition primarily affects males.  Individuals with Wiskott-Aldrich syndrome have microthrombocytopenia, which is a decrease in the number and size of blood cells involved in clotting (platelets). This platelet abnormality, which is typically present from birth, can lead to easy bruising or episodes of prolonged bleeding following minor trauma.  Wiskott-Aldrich syndrome causes many types of white blood cells, which are part of the immune system, to be abnormal or nonfunctional, leading to an increased risk of several immune and inflammatory disorders. Many people with this condition develop eczema, an inflammatory skin disorder characterized by abnormal patches of red, irritated skin. Affected individuals also have an increased susceptibility to infection. People with Wiskott-Aldrich syndrome are at greater risk of developing autoimmune disorders, which occur when the immune system malfunctions and attacks the body's own tissues and organs. The chance of developing some types of cancer, such as cancer of the immune system cells (lymphoma), is also greater in people with Wiskott-Aldrich syndrome.",Wiskott-Aldrich syndrome,0001039,GHR,https://ghr.nlm.nih.gov/condition/wiskott-aldrich-syndrome,C0043194,T047,Disorders
How many people are affected by Wiskott-Aldrich syndrome ?,0001039-2,frequency,The estimated incidence of Wiskott-Aldrich syndrome is between 1 and 10 cases per million males worldwide; this condition is rarer in females.,Wiskott-Aldrich syndrome,0001039,GHR,https://ghr.nlm.nih.gov/condition/wiskott-aldrich-syndrome,C0043194,T047,Disorders
What are the genetic changes related to Wiskott-Aldrich syndrome ?,0001039-3,genetic changes,"Mutations in the WAS gene cause Wiskott-Aldrich syndrome. The WAS gene provides instructions for making a protein called WASP. This protein is found in all blood cells. WASP is involved in relaying signals from the surface of blood cells to the actin cytoskeleton, which is a network of fibers that make up the cell's structural framework. WASP signaling activates the cell when it is needed and triggers its movement and attachment to other cells and tissues (adhesion). In white blood cells, this signaling allows the actin cytoskeleton to establish the interaction between cells and the foreign invaders that they target (immune synapse).  WAS gene mutations that cause Wiskott-Aldrich syndrome lead to a lack of any functional WASP. Loss of WASP signaling disrupts the function of the actin cytoskeleton in developing blood cells. White blood cells that lack WASP have a decreased ability to respond to their environment and form immune synapses. As a result, white blood cells are less able to respond to foreign invaders, causing many of the immune problems related to Wiskott-Aldrich syndrome. Similarly, a lack of functional WASP in platelets impairs their development, leading to reduced size and early cell death.",Wiskott-Aldrich syndrome,0001039,GHR,https://ghr.nlm.nih.gov/condition/wiskott-aldrich-syndrome,C0043194,T047,Disorders
Is Wiskott-Aldrich syndrome inherited ?,0001039-4,inheritance,"This condition is inherited in an X-linked pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell may or may not cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In most cases of X-linked inheritance, males experience more severe symptoms of the disorder than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",Wiskott-Aldrich syndrome,0001039,GHR,https://ghr.nlm.nih.gov/condition/wiskott-aldrich-syndrome,C0043194,T047,Disorders
What are the treatments for Wiskott-Aldrich syndrome ?,0001039-5,treatment,These resources address the diagnosis or management of Wiskott-Aldrich syndrome:  - Gene Review: Gene Review: WAS-Related Disorders  - Genetic Testing Registry: Wiskott-Aldrich syndrome  - MedlinePlus Encyclopedia: Thrombocytopenia  - National Marrow Donor Program  - Rare Disease Clinical Research Network: Primary Immune Deficiency Treatment Consortium   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Wiskott-Aldrich syndrome,0001039,GHR,https://ghr.nlm.nih.gov/condition/wiskott-aldrich-syndrome,C0043194,T047,Disorders
What is (are) Wolf-Hirschhorn syndrome ?,0001040-1,information,"Wolf-Hirschhorn syndrome is a condition that affects many parts of the body. The major features of this disorder include a characteristic facial appearance, delayed growth and development, intellectual disability, and seizures.  Almost everyone with this disorder has distinctive facial features, including a broad, flat nasal bridge and a high forehead. This combination is described as a ""Greek warrior helmet"" appearance. The eyes are widely spaced and may be protruding. Other characteristic facial features include a shortened distance between the nose and upper lip (a short philtrum), a downturned mouth, a small chin (micrognathia), and poorly formed ears with small holes (pits) or flaps of skin (tags). Additionally, affected individuals may have asymmetrical facial features and an unusually small head (microcephaly).  People with Wolf-Hirschhorn syndrome experience delayed growth and development. Slow growth begins before birth, and affected infants tend to have problems feeding and gaining weight (failure to thrive). They also have weak muscle tone (hypotonia) and underdeveloped muscles. Motor skills such as sitting, standing, and walking are significantly delayed. Most children and adults with this disorder also have short stature.  Intellectual disability ranges from mild to severe in people with Wolf-Hirschhorn syndrome. Compared to people with other forms of intellectual disability, their socialization skills are strong, while verbal communication and language skills tend to be weaker. Most affected children also have seizures, which may be resistant to treatment. Seizures tend to disappear with age.  Additional features of Wolf-Hirschhorn syndrome include skin changes such as mottled or dry skin, skeletal abnormalities such as abnormal curvature of the spine (scoliosis and kyphosis), dental problems including missing teeth, and an opening in the roof of the mouth (cleft palate) and/or in the lip (cleft lip). Wolf-Hirschhorn syndrome can also cause abnormalities of the eyes, heart, genitourinary tract, and brain.  A condition called Pitt-Rogers-Danks syndrome has features that overlap with those of Wolf-Hirschhorn syndrome. Researchers now recognize that these two conditions are actually part of a single syndrome with variable signs and symptoms.",Wolf-Hirschhorn syndrome,0001040,GHR,https://ghr.nlm.nih.gov/condition/wolf-hirschhorn-syndrome,C1956097,T047,Disorders
How many people are affected by Wolf-Hirschhorn syndrome ?,0001040-2,frequency,"The prevalence of Wolf-Hirschhorn syndrome is estimated to be 1 in 50,000 births. However, this may be an underestimate because it is likely that some affected individuals are never diagnosed.  For unknown reasons, Wolf-Hirschhorn syndrome occurs in about twice as many females as males.",Wolf-Hirschhorn syndrome,0001040,GHR,https://ghr.nlm.nih.gov/condition/wolf-hirschhorn-syndrome,C1956097,T047,Disorders
What are the genetic changes related to Wolf-Hirschhorn syndrome ?,0001040-3,genetic changes,"Wolf-Hirschhorn syndrome is caused by a deletion of genetic material near the end of the short (p) arm of chromosome 4. This chromosomal change is sometimes written as 4p-. The size of the deletion varies among affected individuals; studies suggest that larger deletions tend to result in more severe intellectual disability and physical abnormalities than smaller deletions.  The signs and symptoms of Wolf-Hirschhorn are related to the loss of multiple genes on the short arm of chromosome 4. WHSC1, LETM1, and MSX1 are the genes that are deleted in people with the typical signs and symptoms of this disorder. These genes play significant roles in early development, although many of their specific functions are unknown. Researchers believe that loss of the WHSC1 gene is associated with many of the characteristic features of Wolf-Hirschhorn syndrome, including the distinctive facial appearance and developmental delay. Deletion of the LETM1 gene appears to be associated with seizures or other abnormal electrical activity in the brain. A loss of the MSX1 gene may be responsible for the dental abnormalities and cleft lip and/or palate that are often seen with this condition.  Scientists are working to identify additional genes at the end of the short arm of chromosome 4 that contribute to the characteristic features of Wolf-Hirschhorn syndrome.",Wolf-Hirschhorn syndrome,0001040,GHR,https://ghr.nlm.nih.gov/condition/wolf-hirschhorn-syndrome,C1956097,T047,Disorders
Is Wolf-Hirschhorn syndrome inherited ?,0001040-4,inheritance,"Between 85 and 90 percent of all cases of Wolf-Hirschhorn syndrome are not inherited. They result from a chromosomal deletion that occurs as a random (de novo) event during the formation of reproductive cells (eggs or sperm) or in early embryonic development. More complex chromosomal rearrangements can also occur as de novo events, which may help explain the variability in the condition's signs and symptoms. De novo chromosomal changes occur in people with no history of the disorder in their family.  A small percentage of all people with Wolf-Hirschhorn syndrome have the disorder as a result of an unusual chromosomal abnormality such as a ring chromosome 4. Ring chromosomes occur when a chromosome breaks in two places and the ends of the chromosome arms fuse together to form a circular structure. In the process, genes near the ends of the chromosome are lost.  In the remaining cases of Wolf-Hirschhorn syndrome, an affected individual inherits a copy of chromosome 4 with a deleted segment. In these cases, one of the individual's parents carries a chromosomal rearrangement between chromosome 4 and another chromosome. This rearrangement is called a balanced translocation. No genetic material is gained or lost in a balanced translocation, so these chromosomal changes usually do not cause any health problems. However, translocations can become unbalanced as they are passed to the next generation. Some people with Wolf-Hirschhorn syndrome inherit an unbalanced translocation that deletes genes near the end of the short arm of chromosome 4. A loss of these genes results in the intellectual disability, slow growth, and other health problems characteristic of this disorder.",Wolf-Hirschhorn syndrome,0001040,GHR,https://ghr.nlm.nih.gov/condition/wolf-hirschhorn-syndrome,C1956097,T047,Disorders
What are the treatments for Wolf-Hirschhorn syndrome ?,0001040-5,treatment,These resources address the diagnosis or management of Wolf-Hirschhorn syndrome:  - Gene Review: Gene Review: Wolf-Hirschhorn Syndrome  - Genetic Testing Registry: 4p partial monosomy syndrome  - MedlinePlus Encyclopedia: Epilepsy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Wolf-Hirschhorn syndrome,0001040,GHR,https://ghr.nlm.nih.gov/condition/wolf-hirschhorn-syndrome,C1956097,T047,Disorders
What is (are) Wolff-Parkinson-White syndrome ?,0001041-1,information,"Wolff-Parkinson-White syndrome is a condition characterized by abnormal electrical pathways in the heart that cause a disruption of the heart's normal rhythm (arrhythmia).  The heartbeat is controlled by electrical signals that move through the heart in a highly coordinated way. A specialized cluster of cells called the atrioventricular node conducts electrical impulses from the heart's upper chambers (the atria) to the lower chambers (the ventricles). Impulses move through the atrioventricular node during each heartbeat, stimulating the ventricles to contract slightly later than the atria.  People with Wolff-Parkinson-White syndrome are born with an extra connection in the heart, called an accessory pathway, that allows electrical signals to bypass the atrioventricular node and move from the atria to the ventricles faster than usual. The accessory pathway may also transmit electrical impulses abnormally from the ventricles back to the atria. This extra connection can disrupt the coordinated movement of electrical signals through the heart, leading to an abnormally fast heartbeat (tachycardia) and other arrhythmias. Resulting symptoms include dizziness, a sensation of fluttering or pounding in the chest (palpitations), shortness of breath, and fainting (syncope). In rare cases, arrhythmias associated with Wolff-Parkinson-White syndrome can lead to cardiac arrest and sudden death. The most common arrhythmia associated with Wolff-Parkinson-White syndrome is called paroxysmal supraventricular tachycardia.  Complications of Wolff-Parkinson-White syndrome can occur at any age, although some individuals born with an accessory pathway in the heart never experience any health problems associated with the condition.  Wolff-Parkinson-White syndrome often occurs with other structural abnormalities of the heart or underlying heart disease. The most common heart defect associated with the condition is Ebstein anomaly, which affects the valve that allows blood to flow from the right atrium to the right ventricle (the tricuspid valve). Additionally, Wolff-Parkinson-White syndrome can be a component of several other genetic syndromes, including hypokalemic periodic paralysis (a condition that causes episodes of extreme muscle weakness), Pompe disease (a disorder characterized by the storage of excess glycogen), and tuberous sclerosis (a condition that results in the growth of noncancerous tumors in many parts of the body).",Wolff-Parkinson-White syndrome,0001041,GHR,https://ghr.nlm.nih.gov/condition/wolff-parkinson-white-syndrome,C1963282,T047,Disorders
How many people are affected by Wolff-Parkinson-White syndrome ?,0001041-2,frequency,"Wolff-Parkinson-White syndrome affects 1 to 3 in 1,000 people worldwide. Only a small fraction of these cases appear to run in families.  Wolff-Parkinson-White syndrome is a common cause of an arrhythmia known as paroxysmal supraventricular tachycardia. Wolff-Parkinson-White syndrome is the most frequent cause of this abnormal heart rhythm in the Chinese population, where it is responsible for more than 70 percent of cases.",Wolff-Parkinson-White syndrome,0001041,GHR,https://ghr.nlm.nih.gov/condition/wolff-parkinson-white-syndrome,C1963282,T047,Disorders
What are the genetic changes related to Wolff-Parkinson-White syndrome ?,0001041-3,genetic changes,"Mutations in the PRKAG2 gene cause Wolff-Parkinson-White syndrome.  A small percentage of all cases of Wolff-Parkinson-White syndrome are caused by mutations in the PRKAG2 gene. Some people with these mutations also have features of hypertrophic cardiomyopathy, a form of heart disease that enlarges and weakens the heart (cardiac) muscle. The PRKAG2 gene provides instructions for making a protein that is part of an enzyme called AMP-activated protein kinase (AMPK). This enzyme helps sense and respond to energy demands within cells. It is likely involved in the development of the heart before birth, although its role in this process is unknown.  Researchers are uncertain how PRKAG2 mutations lead to the development of Wolff-Parkinson-White syndrome and related heart abnormalities. Research suggests that these mutations alter the activity of AMP-activated protein kinase in the heart, although it is unclear whether the genetic changes overactivate the enzyme or reduce its activity. Studies indicate that changes in AMP-activated protein kinase activity allow a complex sugar called glycogen to build up abnormally within cardiac muscle cells. Other studies have found that altered AMP-activated protein kinase activity is related to changes in the regulation of certain ion channels in the heart. These channels, which transport positively charged atoms (ions) into and out of cardiac muscle cells, play critical roles in maintaining the heart's normal rhythm.  In most cases, the cause of Wolff-Parkinson-White syndrome is unknown.",Wolff-Parkinson-White syndrome,0001041,GHR,https://ghr.nlm.nih.gov/condition/wolff-parkinson-white-syndrome,C1963282,T047,Disorders
Is Wolff-Parkinson-White syndrome inherited ?,0001041-4,inheritance,"Most cases of Wolff-Parkinson-White syndrome occur in people with no apparent family history of the condition. These cases are described as sporadic and are not inherited.  Familial Wolff-Parkinson-White syndrome accounts for only a small percentage of all cases of this condition. The familial form of the disorder typically has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the condition. In most cases, a person with familial Wolff-Parkinson-White syndrome has inherited the condition from an affected parent.",Wolff-Parkinson-White syndrome,0001041,GHR,https://ghr.nlm.nih.gov/condition/wolff-parkinson-white-syndrome,C1963282,T047,Disorders
What are the treatments for Wolff-Parkinson-White syndrome ?,0001041-5,treatment,These resources address the diagnosis or management of Wolff-Parkinson-White syndrome:  - Genetic Testing Registry: Wolff-Parkinson-White pattern  - MedlinePlus Encyclopedia: Wolff-Parkinson-White syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Wolff-Parkinson-White syndrome,0001041,GHR,https://ghr.nlm.nih.gov/condition/wolff-parkinson-white-syndrome,C1963282,T047,Disorders
What is (are) Wolfram syndrome ?,0001042-1,information,"Wolfram syndrome is a condition that affects many of the body's systems. The hallmark features of Wolfram syndrome are high blood sugar levels resulting from a shortage of the hormone insulin (diabetes mellitus) and progressive vision loss due to degeneration of the nerves that carry information from the eyes to the brain (optic atrophy). People with Wolfram syndrome often also have pituitary gland dysfunction that results in the excretion of excessive amounts of urine (diabetes insipidus), hearing loss caused by changes in the inner ear (sensorineural deafness), urinary tract problems, reduced amounts of the sex hormone testosterone in males (hypogonadism), or neurological or psychiatric disorders.  Diabetes mellitus is typically the first symptom of Wolfram syndrome, usually diagnosed around age 6. Nearly everyone with Wolfram syndrome who develops diabetes mellitus requires insulin replacement therapy. Optic atrophy is often the next symptom to appear, usually around age 11. The first signs of optic atrophy are loss of color vision and side (peripheral) vision. Over time, the vision problems get worse, and people with optic atrophy are usually blind within approximately 8 years after signs of optic atrophy first begin.  In diabetes insipidus, the pituitary gland, which is located at the base of the brain, does not function normally. This abnormality disrupts the release of a hormone called vasopressin, which helps control the body's water balance and urine production. Approximately 70 percent of people with Wolfram syndrome have diabetes insipidus. Pituitary gland dysfunction can also cause hypogonadism in males. The lack of testosterone that occurs with hypogonadism affects growth and sexual development. About 65 percent of people with Wolfram syndrome have sensorineural deafness that can range in severity from deafness beginning at birth to mild hearing loss beginning in adolescence that worsens over time. Sixty to 90 percent of people with Wolfram syndrome have a urinary tract problem. Urinary tract problems include obstruction of the ducts between the kidneys and bladder (ureters), a large bladder that cannot empty normally (high-capacity atonal bladder), disrupted urination (bladder sphincter dyssynergia), and difficulty controlling the flow of urine (incontinence).  About 60 percent of people with Wolfram syndrome develop a neurological or psychiatric disorder, most commonly problems with balance and coordination (ataxia), typically beginning in early adulthood. Other neurological problems experienced by people with Wolfram syndrome include irregular breathing caused by the brain's inability to control breathing (central apnea), loss of the sense of smell, loss of the gag reflex, muscle spasms (myoclonus), seizures, reduced sensation in the lower extremities (peripheral neuropathy), and intellectual impairment. Psychiatric disorders associated with Wolfram syndrome include psychosis, episodes of severe depression, and impulsive and aggressive behavior.  There are two types of Wolfram syndrome with many overlapping features. The two types are differentiated by their genetic cause. In addition to the usual features of Wolfram syndrome, individuals with Wolfram syndrome type 2 have stomach or intestinal ulcers and excessive bleeding after an injury. The tendency to bleed excessively combined with the ulcers typically leads to abnormal bleeding in the gastrointestinal system. People with Wolfram syndrome type 2 do not develop diabetes insipidus.  Wolfram syndrome is often fatal by mid-adulthood due to complications from the many features of the condition, such as health problems related to diabetes mellitus or neurological problems.",Wolfram syndrome,0001042,GHR,https://ghr.nlm.nih.gov/condition/wolfram-syndrome,C0043207,T047,Disorders
How many people are affected by Wolfram syndrome ?,0001042-2,frequency,"The estimated prevalence of Wolfram syndrome type 1 is 1 in 500,000 people worldwide. Approximately 200 cases have been described in the scientific literature. Only a few families from Jordan have been found to have Wolfram syndrome type 2.",Wolfram syndrome,0001042,GHR,https://ghr.nlm.nih.gov/condition/wolfram-syndrome,C0043207,T047,Disorders
What are the genetic changes related to Wolfram syndrome ?,0001042-3,genetic changes,"Mutations in the WFS1 gene cause more than 90 percent of Wolfram syndrome type 1 cases. This gene provides instructions for producing a protein called wolframin that is thought to regulate the amount of calcium in cells. A proper calcium balance is important for many different cellular functions, including cell-to-cell communication, the tensing (contraction) of muscles, and protein processing. The wolframin protein is found in many different tissues, such as the pancreas, brain, heart, bones, muscles, lung, liver, and kidneys. Within cells, wolframin is located in the membrane of a cell structure called the endoplasmic reticulum that is involved in protein production, processing, and transport. Wolframin's function is important in the pancreas, where the protein is thought to help process a protein called proinsulin into the mature hormone insulin. This hormone helps control blood sugar levels.  WFS1 gene mutations lead to the production of a wolframin protein that has reduced or absent function. As a result, calcium levels within cells are not regulated and the endoplasmic reticulum does not work correctly. When the endoplasmic reticulum does not have enough functional wolframin, the cell triggers its own cell death (apoptosis). The death of cells in the pancreas, specifically cells that make insulin (beta cells), causes diabetes mellitus in people with Wolfram syndrome. The gradual loss of cells along the optic nerve eventually leads to blindness in affected individuals. The death of cells in other body systems likely causes the various signs and symptoms of Wolfram syndrome type 1.  A certain mutation in the CISD2 gene was found to cause Wolfram syndrome type 2. The CISD2 gene provides instructions for making a protein that is located in the outer membrane of cell structures called mitochondria. Mitochondria are the energy-producing centers of cells. The exact function of the CISD2 protein is unknown, but it is thought to help keep mitochondria functioning normally.  The CISD2 gene mutation that causes Wolfram syndrome type 2 results in an abnormally small, nonfunctional CISD2 protein. As a result, mitochondria are not properly maintained, and they eventually break down. Since the mitochondria provide energy to cells, the loss of mitochondria results in decreased energy for cells. Cells that do not have enough energy to function will eventually die. Cells with high energy demands such as nerve cells in the brain, eye, or gastrointestinal tract are most susceptible to cell death due to reduced energy. It is unknown why people with CISD2 gene mutations have ulcers and bleeding problems in addition to the usual Wolfram syndrome features.  Some people with Wolfram syndrome do not have an identified mutation in either the WFS1 or CISD2 gene. The cause of the condition in these individuals is unknown.",Wolfram syndrome,0001042,GHR,https://ghr.nlm.nih.gov/condition/wolfram-syndrome,C0043207,T047,Disorders
Is Wolfram syndrome inherited ?,0001042-4,inheritance,"When Wolfram syndrome is caused by mutations in the WFS1 gene, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Some studies have shown that people who carry one copy of a WFS1 gene mutation are at increased risk of developing individual features of Wolfram syndrome or related features, such as type 2 diabetes, hearing loss, or psychiatric illness. However, other studies have found no increased risk in these individuals.  Wolfram syndrome caused by mutations in the CISD2 gene is also inherited in an autosomal recessive pattern.",Wolfram syndrome,0001042,GHR,https://ghr.nlm.nih.gov/condition/wolfram-syndrome,C0043207,T047,Disorders
What are the treatments for Wolfram syndrome ?,0001042-5,treatment,"These resources address the diagnosis or management of Wolfram syndrome:  - Gene Review: Gene Review: WFS1-Related Disorders  - Genetic Testing Registry: Diabetes mellitus AND insipidus with optic atrophy AND deafness  - Genetic Testing Registry: Wolfram syndrome 2  - Johns Hopkins Medicine: Diabetes Insipidus  - MedlinePlus Encyclopedia: Diabetes Insipidus--Central  - Washington University, St. Louis: Wolfram Syndrome International Registry   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Wolfram syndrome,0001042,GHR,https://ghr.nlm.nih.gov/condition/wolfram-syndrome,C0043207,T047,Disorders
What is (are) Wolman disease ?,0001043-1,information,"Wolman disease is a rare inherited condition involving the breakdown and use of fats and cholesterol in the body (lipid metabolism). In affected individuals, harmful amounts of lipids accumulate in the spleen, liver, bone marrow, small intestine, small hormone-producing glands on top of each kidney (adrenal glands), and lymph nodes. In addition to fat deposits, calcium deposits in the adrenal glands are also seen.  Infants with Wolman disease are healthy and active at birth but soon develop signs and symptoms of the disorder. These may include an enlarged liver and spleen (hepatosplenomegaly), poor weight gain, low muscle tone, a yellow tint to the skin and the whites of the eyes (jaundice), vomiting, diarrhea, developmental delay, low amounts of iron in the blood (anemia), and poor absorption of nutrients from food. Children affected by this condition develop severe malnutrition and generally do not survive past early childhood.",Wolman disease,0001043,GHR,https://ghr.nlm.nih.gov/condition/wolman-disease,C0043208,T047,Disorders
How many people are affected by Wolman disease ?,0001043-2,frequency,"Wolman disease is estimated to occur in 1 in 350,000 newborns.",Wolman disease,0001043,GHR,https://ghr.nlm.nih.gov/condition/wolman-disease,C0043208,T047,Disorders
What are the genetic changes related to Wolman disease ?,0001043-3,genetic changes,"Mutations in the LIPA gene cause Wolman disease.  The LIPA gene provides instructions for producing an enzyme called lysosomal acid lipase. This enzyme is found in the lysosomes (compartments that digest and recycle materials in the cell), where it processes lipids such as cholesteryl esters and triglycerides so they can be used by the body.  Mutations in this gene lead to a shortage of lysosomal acid lipase and the accumulation of triglycerides, cholesteryl esters, and other kinds of fats within the cells and tissues of affected individuals. This accumulation as well as malnutrition caused by the body's inability to use lipids properly result in the signs and symptoms of Wolman disease.",Wolman disease,0001043,GHR,https://ghr.nlm.nih.gov/condition/wolman-disease,C0043208,T047,Disorders
Is Wolman disease inherited ?,0001043-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Wolman disease,0001043,GHR,https://ghr.nlm.nih.gov/condition/wolman-disease,C0043208,T047,Disorders
What are the treatments for Wolman disease ?,0001043-5,treatment,These resources address the diagnosis or management of Wolman disease:  - Genetic Testing Registry: Lysosomal acid lipase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,Wolman disease,0001043,GHR,https://ghr.nlm.nih.gov/condition/wolman-disease,C0043208,T047,Disorders
What is (are) X-linked adrenal hypoplasia congenita ?,0001044-1,information,"X-linked adrenal hypoplasia congenita is a disorder that mainly affects males. It involves many hormone-producing (endocrine) tissues in the body, particularly a pair of small glands on top of each kidney called the adrenal glands. These glands produce a variety of hormones that regulate many essential functions in the body.  One of the main signs of this disorder is adrenal insufficiency, which occurs when the adrenal glands do not produce enough hormones. Adrenal insufficiency typically begins in infancy or childhood and can cause vomiting, difficulty with feeding, dehydration, extremely low blood sugar (hypoglycemia), and shock. If untreated, these complications are often life-threatening.  Affected males may also have a shortage of male sex hormones, which leads to underdeveloped reproductive tissues, undescended testicles (cryptorchidism), delayed puberty, and an inability to father children (infertility). Together, these characteristics are known as hypogonadotropic hypogonadism.  The onset and severity of these signs and symptoms can vary, even among affected members of the same family.",X-linked adrenal hypoplasia congenita,0001044,GHR,https://ghr.nlm.nih.gov/condition/x-linked-adrenal-hypoplasia-congenita,C0220766,T019,Disorders
How many people are affected by X-linked adrenal hypoplasia congenita ?,0001044-2,frequency,"X-linked adrenal hypoplasia congenita is estimated to affect 1 in 12,500 newborns.",X-linked adrenal hypoplasia congenita,0001044,GHR,https://ghr.nlm.nih.gov/condition/x-linked-adrenal-hypoplasia-congenita,C0220766,T019,Disorders
What are the genetic changes related to X-linked adrenal hypoplasia congenita ?,0001044-3,genetic changes,"Mutations in the NR0B1 gene cause X-linked adrenal hypoplasia congenita. The NR0B1 gene provides instructions to make a protein called DAX1. This protein plays an important role in the development and function of several hormone-producing (endocrine) tissues including the adrenal glands, two hormone-secreting glands in the brain (the hypothalamus and pituitary), and the gonads (ovaries in females and testes in males). The hormones produced by these glands control many important body functions.  Some NR0B1 mutations result in the production of an inactive version of the DAX1 protein, while other mutations delete the entire gene. The resulting shortage of DAX1 disrupts the normal development and function of hormone-producing tissues in the body. The signs and symptoms of adrenal insufficiency and hypogonadotropic hypogonadism occur when endocrine glands do not produce the right amounts of certain hormones.",X-linked adrenal hypoplasia congenita,0001044,GHR,https://ghr.nlm.nih.gov/condition/x-linked-adrenal-hypoplasia-congenita,C0220766,T019,Disorders
Is X-linked adrenal hypoplasia congenita inherited ?,0001044-4,inheritance,"This condition is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In X-linked recessive inheritance, a female with one mutated copy of the gene in each cell is called a carrier. She can pass on the altered gene, but usually does not experience signs and symptoms of the disorder. In rare cases, however, females who carry a NR0B1 mutation may experience adrenal insufficiency or signs of hypogonadotropic hypogonadism such as underdeveloped reproductive tissues, delayed puberty, and an absence of menstruation.",X-linked adrenal hypoplasia congenita,0001044,GHR,https://ghr.nlm.nih.gov/condition/x-linked-adrenal-hypoplasia-congenita,C0220766,T019,Disorders
What are the treatments for X-linked adrenal hypoplasia congenita ?,0001044-5,treatment,"These resources address the diagnosis or management of X-linked adrenal hypoplasia congenita:  - Gene Review: Gene Review: X-Linked Adrenal Hypoplasia Congenita  - Genetic Testing Registry: Congenital adrenal hypoplasia, X-linked  - MedlinePlus Encyclopedia: Adrenal Glands  - MedlinePlus Encyclopedia: Hypogonadotropic Hypogonadism   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",X-linked adrenal hypoplasia congenita,0001044,GHR,https://ghr.nlm.nih.gov/condition/x-linked-adrenal-hypoplasia-congenita,C0220766,T019,Disorders
What is (are) X-linked adrenoleukodystrophy ?,0001045-1,information,"X-linked adrenoleukodystrophy is a genetic disorder that occurs primarily in males. It mainly affects the nervous system and the adrenal glands, which are small glands located on top of each kidney. In this disorder, the fatty covering (myelin) that insulates nerves in the brain and spinal cord is prone to deterioration (demyelination), which reduces the ability of the nerves to relay information to the brain. In addition, damage to the outer layer of the adrenal glands (adrenal cortex) causes a shortage of certain hormones (adrenocortical insufficiency). Adrenocortical insufficiency may cause weakness, weight loss, skin changes, vomiting, and coma.  There are three distinct types of X-linked adrenoleukodystrophy: a childhood cerebral form, an adrenomyeloneuropathy type, and a form called Addison disease only.  Children with the cerebral form of X-linked adrenoleukodystrophy experience learning and behavioral problems that usually begin between the ages of 4 and 10. Over time the symptoms worsen, and these children may have difficulty reading, writing, understanding speech, and comprehending written material. Additional signs and symptoms of the cerebral form include aggressive behavior, vision problems, difficulty swallowing, poor coordination, and impaired adrenal gland function. The rate at which this disorder progresses is variable but can be extremely rapid, often leading to total disability within a few years. The life expectancy of individuals with this type depends on the severity of the signs and symptoms and how quickly the disorder progresses. Individuals with the cerebral form of X-linked adrenoleukodystrophy usually survive only a few years after symptoms begin but may survive longer with intensive medical support.  Signs and symptoms of the adrenomyeloneuropathy type appear between early adulthood and middle age. Affected individuals develop progressive stiffness and weakness in their legs (paraparesis), experience urinary and genital tract disorders, and often show changes in behavior and thinking ability. Most people with the adrenomyeloneuropathy type also have adrenocortical insufficiency. In some severely affected individuals, damage to the brain and nervous system can lead to early death.  People with X-linked adrenoleukodystrophy whose only symptom is adrenocortical insufficiency are said to have the Addison disease only form. In these individuals, adrenocortical insufficiency can begin anytime between childhood and adulthood. However, most affected individuals develop the additional features of the adrenomyeloneuropathy type by the time they reach middle age. The life expectancy of individuals with this form depends on the severity of the signs and symptoms, but typically this is the mildest of the three types.  Rarely, individuals with X-linked adrenoleukodystrophy develop multiple features of the disorder in adolescence or early adulthood. In addition to adrenocortical insufficiency, these individuals usually have psychiatric disorders and a loss of intellectual function (dementia). It is unclear whether these individuals have a distinct form of the condition or a variation of one of the previously described types.  For reasons that are unclear, different forms of X-linked adrenoleukodystrophy can be seen in affected individuals within the same family.",X-linked adrenoleukodystrophy,0001045,GHR,https://ghr.nlm.nih.gov/condition/x-linked-adrenoleukodystrophy,C0162309,T047,Disorders
How many people are affected by X-linked adrenoleukodystrophy ?,0001045-2,frequency,"The prevalence of X-linked adrenoleukodystrophy is 1 in 20,000 to 50,000 individuals worldwide. This condition occurs with a similar frequency in all populations.",X-linked adrenoleukodystrophy,0001045,GHR,https://ghr.nlm.nih.gov/condition/x-linked-adrenoleukodystrophy,C0162309,T047,Disorders
What are the genetic changes related to X-linked adrenoleukodystrophy ?,0001045-3,genetic changes,"Mutations in the ABCD1 gene cause X-linked adrenoleukodystrophy. The ABCD1 gene provides instructions for producing the adrenoleukodystrophy protein (ALDP), which is involved in transporting certain fat molecules called very long-chain fatty acids (VLCFAs) into peroxisomes. Peroxisomes are small sacs within cells that process many types of molecules, including VLCFAs.  ABCD1 gene mutations result in a shortage (deficiency) of ALDP. When this protein is lacking, the transport and subsequent breakdown of VLCFAs is disrupted, causing abnormally high levels of these fats in the body. The accumulation of VLCFAs may be toxic to the adrenal cortex and myelin. Research suggests that the accumulation of VLCFAs triggers an inflammatory response in the brain, which could lead to the breakdown of myelin. The destruction of these tissues leads to the signs and symptoms of X-linked adrenoleukodystrophy.",X-linked adrenoleukodystrophy,0001045,GHR,https://ghr.nlm.nih.gov/condition/x-linked-adrenoleukodystrophy,C0162309,T047,Disorders
Is X-linked adrenoleukodystrophy inherited ?,0001045-4,inheritance,"X-linked adrenoleukodystrophy is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), one altered copy of the ABCD1 gene in each cell is sufficient to cause X-linked adrenoleukodystrophy. Because females have two copies of the X chromosome, one altered copy of the ABCD1 gene in each cell usually does not cause any features of X-linked adrenoleukodystrophy; however, some females with one altered copy of the gene have health problems associated with this disorder. The signs and symptoms of X-linked adrenoleukodystrophy tend to appear at a later age in females than in males. Affected women usually develop features of the adrenomyeloneuropathy type.",X-linked adrenoleukodystrophy,0001045,GHR,https://ghr.nlm.nih.gov/condition/x-linked-adrenoleukodystrophy,C0162309,T047,Disorders
What are the treatments for X-linked adrenoleukodystrophy ?,0001045-5,treatment,These resources address the diagnosis or management of X-linked adrenoleukodystrophy:  - Gene Review: Gene Review: X-Linked Adrenoleukodystrophy  - Genetic Testing Registry: Adrenoleukodystrophy  - Genomics Education Programme (UK)  - MedlinePlus Encyclopedia: Adrenoleukodystrophy  - National Marrow Donor Program  - X-linked Adrenoleukodystrophy Database: Diagnosis of X-ALD   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,X-linked adrenoleukodystrophy,0001045,GHR,https://ghr.nlm.nih.gov/condition/x-linked-adrenoleukodystrophy,C0162309,T047,Disorders
What is (are) X-linked agammaglobulinemia ?,0001046-1,information,"X-linked agammaglobulinemia (XLA) is a condition that affects the immune system and occurs almost exclusively in males. People with XLA have very few B cells, which are specialized white blood cells that help protect the body against infection. B cells can mature into the cells that produce special proteins called antibodies or immunoglobulins. Antibodies attach to specific foreign particles and germs, marking them for destruction. Individuals with XLA are more susceptible to infections because their body makes very few antibodies.  Children with XLA are usually healthy for the first 1 or 2 months of life because they are protected by antibodies acquired before birth from their mother. After this time, the maternal antibodies are cleared from the body, and the affected child begins to develop recurrent infections. In children with XLA, infections generally take longer to get better and then they come back again, even with antibiotic medications. The most common bacterial infections that occur in people with XLA are lung infections (pneumonia and bronchitis), ear infections (otitis), pink eye (conjunctivitis), and sinus infections (sinusitis). Infections that cause chronic diarrhea are also common. Recurrent infections can lead to organ damage. People with XLA can develop severe, life-threatening bacterial infections; however, affected individuals are not particularly vulnerable to infections caused by viruses. With treatment to replace antibodies, infections can usually be prevented, improving the quality of life for people with XLA.",X-linked agammaglobulinemia,0001046,GHR,https://ghr.nlm.nih.gov/condition/x-linked-agammaglobulinemia,C0221026,T047,Disorders
How many people are affected by X-linked agammaglobulinemia ?,0001046-2,frequency,"XLA occurs in approximately 1 in 200,000 newborns.",X-linked agammaglobulinemia,0001046,GHR,https://ghr.nlm.nih.gov/condition/x-linked-agammaglobulinemia,C0221026,T047,Disorders
What are the genetic changes related to X-linked agammaglobulinemia ?,0001046-3,genetic changes,"Mutations in the BTK gene cause XLA. This gene provides instructions for making the BTK protein, which is important for the development of B cells and normal functioning of the immune system. Most mutations in the BTK gene prevent the production of any BTK protein. The absence of functional BTK protein blocks B cell development and leads to a lack of antibodies. Without antibodies, the immune system cannot properly respond to foreign invaders and prevent infection.",X-linked agammaglobulinemia,0001046,GHR,https://ghr.nlm.nih.gov/condition/x-linked-agammaglobulinemia,C0221026,T047,Disorders
Is X-linked agammaglobulinemia inherited ?,0001046-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  About half of affected individuals do not have a family history of XLA. In most of these cases, the affected person's mother is a carrier of one altered BTK gene. Carriers do not have the immune system abnormalities associated with XLA, but they can pass the altered gene to their children. In other cases, the mother is not a carrier and the affected individual has a new mutation in the BTK gene.",X-linked agammaglobulinemia,0001046,GHR,https://ghr.nlm.nih.gov/condition/x-linked-agammaglobulinemia,C0221026,T047,Disorders
What are the treatments for X-linked agammaglobulinemia ?,0001046-5,treatment,These resources address the diagnosis or management of X-linked agammaglobulinemia:  - Gene Review: Gene Review: X-Linked Agammaglobulinemia  - Genetic Testing Registry: X-linked agammaglobulinemia  - MedlinePlus Encyclopedia: Agammaglobulinemia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,X-linked agammaglobulinemia,0001046,GHR,https://ghr.nlm.nih.gov/condition/x-linked-agammaglobulinemia,C0221026,T047,Disorders
What is (are) X-linked chondrodysplasia punctata 1 ?,0001047-1,information,"X-linked chondrodysplasia punctata 1 is a disorder of cartilage and bone development that occurs almost exclusively in males. Chondrodysplasia punctata is an abnormality that appears on x-rays as spots (stippling) near the ends of bones and in cartilage. In most infants with X-linked chondrodysplasia punctata 1, this stippling is seen in bones of the ankles, toes, and fingers; however, it can also appear in other bones. The stippling generally disappears in early childhood.  Other characteristic features of X-linked chondrodysplasia punctata 1 include short stature and unusually short fingertips and ends of the toes. This condition is also associated with distinctive facial features, particularly a flattened-appearing nose with crescent-shaped nostrils and a flat nasal bridge.  People with X-linked chondrodysplasia punctata 1 typically have normal intelligence and a normal life expectancy. However, some affected individuals have had serious or life-threatening complications including abnormal thickening (stenosis) of the cartilage that makes up the airways, which restricts breathing. Also, abnormalities of spinal bones in the neck can lead to pinching (compression) of the spinal cord, which can cause pain, numbness, and weakness. Other, less common features of X-linked chondrodysplasia punctata 1 include delayed development, hearing loss, vision abnormalities, and heart defects.",X-linked chondrodysplasia punctata 1,0001047,GHR,https://ghr.nlm.nih.gov/condition/x-linked-chondrodysplasia-punctata-1,C3669395,T019,Disorders
How many people are affected by X-linked chondrodysplasia punctata 1 ?,0001047-2,frequency,The prevalence of X-linked chondrodysplasia punctata 1 is unknown. Several dozen affected males have been reported in the scientific literature.,X-linked chondrodysplasia punctata 1,0001047,GHR,https://ghr.nlm.nih.gov/condition/x-linked-chondrodysplasia-punctata-1,C3669395,T019,Disorders
What are the genetic changes related to X-linked chondrodysplasia punctata 1 ?,0001047-3,genetic changes,"X-linked chondrodysplasia punctata 1 is caused by genetic changes involving the ARSE gene. This gene provides instructions for making an enzyme called arylsulfatase E. The function of this enzyme is unknown, although it appears to be important for normal skeletal development and is thought to participate in a chemical pathway involving vitamin K. Evidence suggests that vitamin K normally plays a role in bone growth and maintenance of bone density.  Between 60 and 75 percent of males with the characteristic features of X-linked chondrodysplasia punctata 1 have a mutation in the ARSE gene. These mutations reduce or eliminate the function of arylsulfatase E. Another 25 percent of affected males have a small deletion of genetic material from the region of the X chromosome that contains the ARSE gene. These individuals are missing the entire gene, so their cells produce no functional arylsulfatase E. Researchers are working to determine how a shortage of arylsulfatase E disrupts the development of bones and cartilage and leads to the characteristic features of X-linked chondrodysplasia punctata 1.  Some people with the features of X-linked chondrodysplasia punctata 1 do not have an identified mutation in the ARSE gene or a deletion involving the gene. Other, as-yet-unidentified genetic and environmental factors may also be involved in causing this disorder.",X-linked chondrodysplasia punctata 1,0001047,GHR,https://ghr.nlm.nih.gov/condition/x-linked-chondrodysplasia-punctata-1,C3669395,T019,Disorders
Is X-linked chondrodysplasia punctata 1 inherited ?,0001047-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the ARSE gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",X-linked chondrodysplasia punctata 1,0001047,GHR,https://ghr.nlm.nih.gov/condition/x-linked-chondrodysplasia-punctata-1,C3669395,T019,Disorders
What are the treatments for X-linked chondrodysplasia punctata 1 ?,0001047-5,treatment,"These resources address the diagnosis or management of X-linked chondrodysplasia punctata 1:  - Gene Review: Gene Review: Chondrodysplasia Punctata 1, X-Linked  - Genetic Testing Registry: Chondrodysplasia punctata 1, X-linked recessive   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",X-linked chondrodysplasia punctata 1,0001047,GHR,https://ghr.nlm.nih.gov/condition/x-linked-chondrodysplasia-punctata-1,C3669395,T019,Disorders
What is (are) X-linked chondrodysplasia punctata 2 ?,0001048-1,information,"X-linked chondrodysplasia punctata 2 is a disorder characterized by bone, skin, and eye abnormalities. It occurs almost exclusively in females.  Although the signs and symptoms of this condition vary widely, almost all affected individuals have chondrodysplasia punctata, an abnormality that appears on x-rays as spots (stippling) near the ends of bones and in cartilage. In this form of chondrodysplasia punctata, the stippling typically affects the long bones in the arms and legs, the ribs, the spinal bones (vertebrae), and the cartilage that makes up the windpipe (trachea). The stippling is apparent in infancy but disappears in early childhood. Other skeletal abnormalities seen in people with X-linked chondrodysplasia punctata 2 include shortening of the bones in the upper arms and thighs (rhizomelia) that is often different on the right and left sides, and progressive abnormal curvature of the spine (kyphoscoliosis). As a result of these abnormalities, people with this condition tend to have short stature.  Infants with X-linked chondrodysplasia punctata 2 are born with dry, scaly patches of skin (ichthyosis) in a linear or spiral (whorled) pattern. The scaly patches fade over time, leaving abnormally colored blotches of skin without hair (follicular atrophoderma). Most affected individuals also have sparse, coarse hair on their scalps.  Most people with X-linked chondrodysplasia punctata 2 have clouding of the lens of the eye (cataracts) from birth or early childhood. Other eye abnormalities that have been associated with this disorder include unusually small eyes (microphthalmia) and small corneas (microcornea). The cornea is the clear front surface of the eye. These eye abnormalities can impair vision.  In affected females, X-linked chondrodysplasia punctata 2 is typically associated with normal intelligence and a normal lifespan. However, a much more severe form of the condition has been reported in a small number of males. Affected males have some of the same features as affected females, as well as weak muscle tone (hypotonia), changes in the structure of the brain, moderately to profoundly delayed development, seizures, distinctive facial features, and other birth defects. The health problems associated with X-linked chondrodysplasia punctata 2 are often life-threatening in males.",X-linked chondrodysplasia punctata 2,0001048,GHR,https://ghr.nlm.nih.gov/condition/x-linked-chondrodysplasia-punctata-2,C0008445,T019,Disorders
How many people are affected by X-linked chondrodysplasia punctata 2 ?,0001048-2,frequency,"X-linked chondrodysplasia punctata 2 has been estimated to affect fewer than 1 in 400,000 newborns. However, the disorder may actually be more common than this estimate because it is likely underdiagnosed, particularly in females with mild signs and symptoms.  More than 95 percent of cases of X-linked chondrodysplasia punctata 2 occur in females. About a dozen males with the condition have been reported in the scientific literature.",X-linked chondrodysplasia punctata 2,0001048,GHR,https://ghr.nlm.nih.gov/condition/x-linked-chondrodysplasia-punctata-2,C0008445,T019,Disorders
What are the genetic changes related to X-linked chondrodysplasia punctata 2 ?,0001048-3,genetic changes,"X-linked chondrodysplasia punctata 2 is caused by mutations in the EBP gene. This gene provides instructions for making an enzyme called 3-hydroxysteroid-8,7-isomerase, which is responsible for one of the final steps in the production of cholesterol. Cholesterol is a waxy, fat-like substance that is produced in the body and obtained from foods that come from animals (particularly egg yolks, meat, poultry, fish, and dairy products). Although too much cholesterol is a risk factor for heart disease, this molecule is necessary for normal embryonic development and has important functions both before and after birth. It is a structural component of cell membranes and plays a role in the production of certain hormones and digestive acids.  Mutations in the EBP gene reduce the activity of 3-hydroxysteroid-8,7-isomerase, preventing cells from producing enough cholesterol. A shortage of this enzyme also allows potentially toxic byproducts of cholesterol production to build up in the body. The combination of low cholesterol levels and an accumulation of other substances likely disrupts the growth and development of many body systems. It is not known, however, how this disturbance in cholesterol production leads to the specific features of X-linked chondrodysplasia punctata 2.",X-linked chondrodysplasia punctata 2,0001048,GHR,https://ghr.nlm.nih.gov/condition/x-linked-chondrodysplasia-punctata-2,C0008445,T019,Disorders
Is X-linked chondrodysplasia punctata 2 inherited ?,0001048-4,inheritance,"This condition is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the EBP gene in each cell is sufficient to cause the disorder. Some cells produce a normal amount of 3-hydroxysteroid-8,7-isomerase and other cells produce none. The resulting overall reduction in the amount of this enzyme underlies the signs and symptoms of X-linked chondrodysplasia punctata 2.  In males (who have only one X chromosome), a mutation in the EBP gene can result in a total loss of 3-hydroxysteroid-8,7-isomerase. A complete lack of this enzyme is usually lethal in the early stages of development, so few males have been born with X-linked chondrodysplasia punctata 2.",X-linked chondrodysplasia punctata 2,0001048,GHR,https://ghr.nlm.nih.gov/condition/x-linked-chondrodysplasia-punctata-2,C0008445,T019,Disorders
What are the treatments for X-linked chondrodysplasia punctata 2 ?,0001048-5,treatment,"These resources address the diagnosis or management of X-linked chondrodysplasia punctata 2:  - Gene Review: Gene Review: Chondrodysplasia Punctata 2, X-Linked  - Genetic Testing Registry: Chondrodysplasia punctata 2 X-linked dominant   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",X-linked chondrodysplasia punctata 2,0001048,GHR,https://ghr.nlm.nih.gov/condition/x-linked-chondrodysplasia-punctata-2,C0008445,T019,Disorders
What is (are) X-linked congenital stationary night blindness ?,0001049-1,information,"X-linked congenital stationary night blindness is a disorder of the retina, which is the specialized tissue at the back of the eye that detects light and color. People with this condition typically have difficulty seeing in low light (night blindness). They also have other vision problems, including loss of sharpness (reduced acuity), severe nearsightedness (high myopia), involuntary movements of the eyes (nystagmus), and eyes that do not look in the same direction (strabismus). Color vision is typically not affected by this disorder.  The vision problems associated with this condition are congenital, which means they are present from birth. They tend to remain stable (stationary) over time.  Researchers have identified two major types of X-linked congenital stationary night blindness: the complete form and the incomplete form. The types have very similar signs and symptoms. However, everyone with the complete form has night blindness, while not all people with the incomplete form have night blindness. The types are distinguished by their genetic cause and by the results of a test called an electroretinogram, which measures the function of the retina.",X-linked congenital stationary night blindness,0001049,GHR,https://ghr.nlm.nih.gov/condition/x-linked-congenital-stationary-night-blindness,C0339535,T019,Disorders
How many people are affected by X-linked congenital stationary night blindness ?,0001049-2,frequency,"The prevalence of this condition is unknown. It appears to be more common in people of Dutch-German Mennonite descent. However, this disorder has been reported in families with many different ethnic backgrounds. The incomplete form is more common than the complete form.",X-linked congenital stationary night blindness,0001049,GHR,https://ghr.nlm.nih.gov/condition/x-linked-congenital-stationary-night-blindness,C0339535,T019,Disorders
What are the genetic changes related to X-linked congenital stationary night blindness ?,0001049-3,genetic changes,"Mutations in the NYX and CACNA1F genes cause the complete and incomplete forms of X-linked congenital stationary night blindness, respectively. The proteins produced from these genes play critical roles in the retina.  Within the retina, the NYX and CACNA1F proteins are located on the surface of light-detecting cells called photoreceptors. The retina contains two types of photoreceptor cells: rods and cones. Rods are needed for vision in low light. Cones are needed for vision in bright light, including color vision. The NYX and CACNA1F proteins ensure that visual signals are passed from rods and cones to other retinal cells called bipolar cells, which is an essential step in the transmission of visual information from the eyes to the brain.  Mutations in the NYX or CACNA1F gene disrupt the transmission of visual signals between photoreceptors and retinal bipolar cells, which impairs vision. In people with the complete form of X-linked congenital stationary night blindness (resulting from NYX mutations), the function of rods is severely disrupted, while the function of cones is only mildly affected. In people with the incomplete form of the condition (resulting from CACNA1F mutations), rods and cones are both affected, although they retain some ability to detect light.",X-linked congenital stationary night blindness,0001049,GHR,https://ghr.nlm.nih.gov/condition/x-linked-congenital-stationary-night-blindness,C0339535,T019,Disorders
Is X-linked congenital stationary night blindness inherited ?,0001049-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The NYX and CACNA1F genes are located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In X-linked recessive inheritance, a female with one altered copy of the gene in each cell is called a carrier. Carriers of an NYX or CACNA1F mutation can pass on the mutated gene, but most do not develop any of the vision problems associated with X-linked congenital stationary night blindness. However, carriers may have retinal changes that can be detected with an electroretinogram.",X-linked congenital stationary night blindness,0001049,GHR,https://ghr.nlm.nih.gov/condition/x-linked-congenital-stationary-night-blindness,C0339535,T019,Disorders
What are the treatments for X-linked congenital stationary night blindness ?,0001049-5,treatment,"These resources address the diagnosis or management of X-linked congenital stationary night blindness:  - American Optometric Association: Infant Vision  - Gene Review: Gene Review: X-Linked Congenital Stationary Night Blindness  - Genetic Testing Registry: Congenital stationary night blindness  - Genetic Testing Registry: Congenital stationary night blindness, type 1A  - Genetic Testing Registry: Congenital stationary night blindness, type 2A  - MedlinePlus Encyclopedia: Electroretinography  - MedlinePlus Encyclopedia: Eye movements - Uncontrollable  - MedlinePlus Encyclopedia: Nearsightedness  - MedlinePlus Encyclopedia: Strabismus  - MedlinePlus Encyclopedia: Vision - Night Blindness   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",X-linked congenital stationary night blindness,0001049,GHR,https://ghr.nlm.nih.gov/condition/x-linked-congenital-stationary-night-blindness,C0339535,T019,Disorders
What is (are) X-linked creatine deficiency ?,0001050-1,information,"X-linked creatine deficiency is an inherited disorder that primarily affects the brain. People with this disorder have intellectual disability, which can range from mild to severe, and delayed speech development. Some affected individuals develop behavioral disorders such as attention deficit hyperactivity disorder or autistic behaviors that affect communication and social interaction. They may also experience seizures. Children with X-linked creatine deficiency may experience slow growth and exhibit delayed development of motor skills such as sitting and walking. Affected individuals tend to tire easily.  A small number of people with X-linked creatine deficiency have additional signs and symptoms including abnormal heart rhythms, an unusually small head (microcephaly), or distinctive facial features such as a broad forehead and a flat or sunken appearance of the middle of the face (midface hypoplasia).",X-linked creatine deficiency,0001050,GHR,https://ghr.nlm.nih.gov/condition/x-linked-creatine-deficiency,C1845862,T047,Disorders
How many people are affected by X-linked creatine deficiency ?,0001050-2,frequency,The prevalence of X-linked creatine deficiency is unknown. More than 150 affected individuals have been identified. The disorder has been estimated to account for between 1 and 2 percent of males with intellectual disability.,X-linked creatine deficiency,0001050,GHR,https://ghr.nlm.nih.gov/condition/x-linked-creatine-deficiency,C1845862,T047,Disorders
What are the genetic changes related to X-linked creatine deficiency ?,0001050-3,genetic changes,"Mutations in the SLC6A8 gene cause X-linked creatine deficiency. The SLC6A8 gene provides instructions for making a protein that transports the compound creatine into cells. Creatine is needed for the body to store and use energy properly.  SLC6A8 gene mutations impair the ability of the transporter protein to bring creatine into cells, resulting in a creatine shortage (deficiency). The effects of creatine deficiency are most severe in organs and tissues that require large amounts of energy, especially the brain.",X-linked creatine deficiency,0001050,GHR,https://ghr.nlm.nih.gov/condition/x-linked-creatine-deficiency,C1845862,T047,Disorders
Is X-linked creatine deficiency inherited ?,0001050-4,inheritance,"This condition is inherited in an X-linked pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell may or may not cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In most cases of X-linked inheritance, males experience more severe symptoms of the disorder than females. About half of females with one mutated copy of the SLC6A8 gene in each cell have intellectual disability, learning difficulties, or behavioral problems. Other females with one mutated copy of the SLC6A8 gene in each cell have no noticeable neurological problems.",X-linked creatine deficiency,0001050,GHR,https://ghr.nlm.nih.gov/condition/x-linked-creatine-deficiency,C1845862,T047,Disorders
What are the treatments for X-linked creatine deficiency ?,0001050-5,treatment,"These resources address the diagnosis or management of X-linked creatine deficiency:  - Gene Review: Gene Review: Creatine Deficiency Syndromes  - Genetic Testing Registry: Creatine deficiency, X-linked   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",X-linked creatine deficiency,0001050,GHR,https://ghr.nlm.nih.gov/condition/x-linked-creatine-deficiency,C1845862,T047,Disorders
What is (are) X-linked dystonia-parkinsonism ?,0001051-1,information,"X-linked dystonia-parkinsonism is a movement disorder that has been found only in people of Filipino descent. This condition affects men much more often than women.  Parkinsonism is usually the first sign of X-linked dystonia-parkinsonism. Parkinsonism is a group of movement abnormalities including tremors, unusually slow movement (bradykinesia), rigidity, an inability to hold the body upright and balanced (postural instability), and a shuffling gait that can cause recurrent falls.  Later in life, many affected individuals also develop a pattern of involuntary, sustained muscle contractions known as dystonia. The dystonia associated with X-linked dystonia-parkinsonism typically starts in one area, most often the eyes, jaw, or neck, and later spreads to other parts of the body. The continuous muscle cramping and spasms can be disabling. Depending on which muscles are affected, widespread (generalized) dystonia can cause difficulty with speaking, swallowing, coordination, and walking.  The signs and symptoms of X-linked dystonia-parkinsonism vary widely. In the mildest cases, affected individuals have slowly progressive parkinsonism with little or no dystonia. More severe cases involve dystonia that rapidly becomes generalized. These individuals become dependent on others for care within a few years after signs and symptoms appear, and they may die prematurely from breathing difficulties, infections (such as aspiration pneumonia), or other complications.",X-linked dystonia-parkinsonism,0001051,GHR,https://ghr.nlm.nih.gov/condition/x-linked-dystonia-parkinsonism,C0242422,T047,Disorders
How many people are affected by X-linked dystonia-parkinsonism ?,0001051-2,frequency,"X-linked dystonia-parkinsonism has been reported in more than 500 people of Filipino descent, although it is likely that many more Filipinos are affected. Most people with this condition can trace their mother's ancestry to the island of Panay in the Philippines. The prevalence of the disorder is 5.24 per 100,000 people on the island of Panay.",X-linked dystonia-parkinsonism,0001051,GHR,https://ghr.nlm.nih.gov/condition/x-linked-dystonia-parkinsonism,C0242422,T047,Disorders
What are the genetic changes related to X-linked dystonia-parkinsonism ?,0001051-3,genetic changes,"Mutations in and near the TAF1 gene can cause X-linked dystonia-parkinsonism. The TAF1 gene provides instructions for making part of a protein called transcription factor IID (TFIID). This protein is active in cells and tissues throughout the body, where it plays an essential role in regulating the activity of most genes.  The TAF1 gene is part of a complex region of DNA known as the TAF1/DYT3 multiple transcript system. This region consists of short stretches of DNA from the TAF1 gene plus some extra segments of genetic material near the gene. These stretches of DNA can be combined in different ways to create various sets of instructions for making proteins. Researchers believe that some of these variations are critical for the normal function of nerve cells (neurons) in the brain.  Several changes in the TAF1/DYT3 multiple transcript system have been identified in people with X-linked dystonia-parkinsonism. Scientists are uncertain how these changes are related to the movement abnormalities characteristic of this disease. However, they suspect that the changes disrupt the regulation of critical genes in neurons. This defect leads to the eventual death of these cells, particularly in areas of the brain called the caudate nucleus and putamen. These regions are critical for normal movement, learning, and memory. It is unclear why the effects of changes in the TAF1/DYT3 multiple transcript system appear to be limited to dystonia and parkinsonism.",X-linked dystonia-parkinsonism,0001051,GHR,https://ghr.nlm.nih.gov/condition/x-linked-dystonia-parkinsonism,C0242422,T047,Disorders
Is X-linked dystonia-parkinsonism inherited ?,0001051-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation typically must occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In X-linked recessive inheritance, females with one altered copy of the gene in each cell are called carriers. They can pass on the gene to their children, but they usually do not experience signs and symptoms of the disorder. However, a few females carrying one altered copy of the TAF1 gene have developed movement abnormalities associated with X-linked dystonia-parkinsonism. These movement problems tend to be milder than those seen in affected men, and they are usually not progressive or disabling.",X-linked dystonia-parkinsonism,0001051,GHR,https://ghr.nlm.nih.gov/condition/x-linked-dystonia-parkinsonism,C0242422,T047,Disorders
What are the treatments for X-linked dystonia-parkinsonism ?,0001051-5,treatment,"These resources address the diagnosis or management of X-linked dystonia-parkinsonism:  - Gene Review: Gene Review: X-Linked Dystonia-Parkinsonism Syndrome  - Genetic Testing Registry: Dystonia 3, torsion, X-linked   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",X-linked dystonia-parkinsonism,0001051,GHR,https://ghr.nlm.nih.gov/condition/x-linked-dystonia-parkinsonism,C0242422,T047,Disorders
What is (are) X-linked hyper IgM syndrome ?,0001052-1,information,"X-linked hyper IgM syndrome is a condition that affects the immune system and occurs almost exclusively in males. People with this disorder have abnormal levels of proteins called antibodies or immunoglobulins. Antibodies help protect the body against infection by attaching to specific foreign particles and germs, marking them for destruction. There are several classes of antibodies, and each one has a different function in the immune system. Although the name of this condition implies that affected individuals always have high levels of immunoglobulin M (IgM), some people have normal levels of this antibody. People with X-linked hyper IgM syndrome have low levels of three other classes of antibodies: immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin E (IgE). The lack of certain antibody classes makes it difficult for people with this disorder to fight off infections.  Individuals with X-linked hyper IgM syndrome begin to develop frequent infections in infancy and early childhood. Common infections include pneumonia, sinus infections (sinusitis), and ear infections (otitis). Infections often cause these children to have chronic diarrhea and they fail to gain weight and grow at the expected rate (failure to thrive). Some people with X-linked hyper IgM syndrome have low levels of white blood cells called neutrophils (neutropenia). Affected individuals may develop autoimmune disorders, neurologic complications from brain and spinal cord (central nervous system) infections, liver disease, and gastrointestinal tumors. They also have an increased risk of lymphoma, which is a cancer of immune system cells.  The severity of X-linked hyper IgM syndrome varies among affected individuals, even among members of the same family. Without treatment, this condition can result in death during childhood or adolescence.",X-linked hyper IgM syndrome,0001052,GHR,https://ghr.nlm.nih.gov/condition/x-linked-hyper-igm-syndrome,C0398689,T047,Disorders
How many people are affected by X-linked hyper IgM syndrome ?,0001052-2,frequency,X-linked hyper IgM syndrome is estimated to occur in 2 per million newborn boys.,X-linked hyper IgM syndrome,0001052,GHR,https://ghr.nlm.nih.gov/condition/x-linked-hyper-igm-syndrome,C0398689,T047,Disorders
What are the genetic changes related to X-linked hyper IgM syndrome ?,0001052-3,genetic changes,"Mutations in the CD40LG gene cause X-linked hyper IgM syndrome. This gene provides instructions for making a protein called CD40 ligand, which is found on the surface of immune system cells known as T cells. CD40 ligand attaches like a key in a lock to its receptor protein, which is located on the surface of immune system cells called B cells. B cells are involved in the production of antibodies, and initially they are able to make only IgM antibodies. When CD40 ligand and its receptor protein are connected, they trigger a series of chemical signals that instruct the B cell to start making IgG, IgA, or IgE antibodies.  CD40 ligand is also necessary for T cells to interact with other cells of the immune system, and it plays a key role in T cell differentiation (the process by which cells mature to carry out specific functions).  Mutations in the CD40LG gene lead to the production of an abnormal CD40 ligand or prevent production of this protein. If CD40 ligand does not attach to its receptor on B cells, these cells cannot produce IgG, IgA, or IgE antibodies. Mutations in the CD40LG gene also impair the T cell's ability to differentiate and interact with other immune system cells. People with X-linked hyper IgM syndrome are more susceptible to infections because they do not have a properly functioning immune system.",X-linked hyper IgM syndrome,0001052,GHR,https://ghr.nlm.nih.gov/condition/x-linked-hyper-igm-syndrome,C0398689,T047,Disorders
Is X-linked hyper IgM syndrome inherited ?,0001052-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",X-linked hyper IgM syndrome,0001052,GHR,https://ghr.nlm.nih.gov/condition/x-linked-hyper-igm-syndrome,C0398689,T047,Disorders
What are the treatments for X-linked hyper IgM syndrome ?,0001052-5,treatment,These resources address the diagnosis or management of X-linked hyper IgM syndrome:  - Gene Review: Gene Review: X-Linked Hyper IgM Syndrome  - Genetic Testing Registry: Immunodeficiency with hyper IgM type 1  - MedlinePlus Encyclopedia: Immunodeficiency Disorders   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,X-linked hyper IgM syndrome,0001052,GHR,https://ghr.nlm.nih.gov/condition/x-linked-hyper-igm-syndrome,C0398689,T047,Disorders
"What is (are) X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia ?",0001053-1,information,"X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (typically known by the acronym XMEN) is a disorder that affects the immune system in males. In XMEN, certain types of immune system cells called T cells are reduced in number or do not function properly. Normally these cells recognize foreign invaders, such as viruses, bacteria, and fungi, and are then turned on (activated) to attack these invaders in order to prevent infection and illness. Because males with XMEN do not have enough functional T cells, they have frequent infections, such as ear infections, sinus infections, and pneumonia.  In particular, affected individuals are vulnerable to the Epstein-Barr virus (EBV). EBV is a very common virus that infects more than 90 percent of the general population and in most cases goes unnoticed. Normally, after initial infection, EBV remains in the body for the rest of a person's life. However, the virus is generally inactive (latent) because it is controlled by T cells. In males with XMEN, however, the T cells cannot control the virus, and EBV infection can lead to cancers of immune system cells (lymphomas). The word ""neoplasia"" in the condition name refers to these lymphomas; neoplasia is a general term meaning abnormal growths of tissue. The EBV infection itself usually does not cause any other symptoms in males with XMEN, and affected individuals may not come to medical attention until they develop lymphoma.","X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia",0001053,GHR,https://ghr.nlm.nih.gov/condition/x-linked-immunodeficiency-with-magnesium-defect-epstein-barr-virus-infection-and-neoplasia,C0021051,T191,Disorders
"How many people are affected by X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia ?",0001053-2,frequency,The prevalence of XMEN is unknown. Only a few affected individuals have been described in the medical literature.,"X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia",0001053,GHR,https://ghr.nlm.nih.gov/condition/x-linked-immunodeficiency-with-magnesium-defect-epstein-barr-virus-infection-and-neoplasia,C0021051,T191,Disorders
"What are the genetic changes related to X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia ?",0001053-3,genetic changes,"XMEN is caused by mutations in the MAGT1 gene. This gene provides instructions for making a protein called a magnesium transporter, which moves charged atoms (ions) of magnesium (Mg2+) into certain T cells. Specifically, the magnesium transporter produced from the MAGT1 gene is active in CD8+ T cells, which are especially important in controlling viral infections such as the Epstein-Barr virus (EBV). These cells normally take in magnesium when they detect a foreign invader, and the magnesium is involved in activating the T cell's response.  Researchers suggest that magnesium transport may also be involved in the production of another type of T cell called helper T cells (CD4+ T cells) in a gland called the thymus. CD4+ T cells direct and assist the functions of the immune system by influencing the activities of other immune system cells.  Mutations in the MAGT1 gene impair the magnesium transporter's function, reducing the amount of magnesium that gets into T cells. This magnesium deficiency prevents the efficient activation of the T cells to target EBV and other infections. Uncontrolled EBV infection increases the likelihood of developing lymphoma. Impaired production of CD4+ T cells resulting from abnormal magnesium transport likely accounts for the deficiency of this type of T cell in people with XMEN, contributing to the decreased ability to prevent infection and illness.","X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia",0001053,GHR,https://ghr.nlm.nih.gov/condition/x-linked-immunodeficiency-with-magnesium-defect-epstein-barr-virus-infection-and-neoplasia,C0021051,T191,Disorders
"Is X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia inherited ?",0001053-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.","X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia",0001053,GHR,https://ghr.nlm.nih.gov/condition/x-linked-immunodeficiency-with-magnesium-defect-epstein-barr-virus-infection-and-neoplasia,C0021051,T191,Disorders
"What are the treatments for X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia ?",0001053-5,treatment,These resources address the diagnosis or management of XMEN:  - MedlinePlus Encyclopedia: Epstein-Barr Virus Test  - MedlinePlus Encyclopedia: T Cell Count   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,"X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia",0001053,GHR,https://ghr.nlm.nih.gov/condition/x-linked-immunodeficiency-with-magnesium-defect-epstein-barr-virus-infection-and-neoplasia,C0021051,T191,Disorders
What is (are) X-linked infantile nystagmus ?,0001054-1,information,"X-linked infantile nystagmus is a condition characterized by abnormal eye movements. Nystagmus is a term that refers to involuntary side-to-side movements of the eyes. In people with this condition, nystagmus is present at birth or develops within the first six months of life. The abnormal eye movements may worsen when an affected person is feeling anxious or tries to stare directly at an object. The severity of nystagmus varies, even among affected individuals within the same family. Sometimes, affected individuals will turn or tilt their head to compensate for the irregular eye movements.",X-linked infantile nystagmus,0001054,GHR,https://ghr.nlm.nih.gov/condition/x-linked-infantile-nystagmus,C2673809,T019,Disorders
How many people are affected by X-linked infantile nystagmus ?,0001054-2,frequency,"The incidence of all forms of infantile nystagmus is estimated to be 1 in 5,000 newborns; however, the precise incidence of X-linked infantile nystagmus is unknown.",X-linked infantile nystagmus,0001054,GHR,https://ghr.nlm.nih.gov/condition/x-linked-infantile-nystagmus,C2673809,T019,Disorders
What are the genetic changes related to X-linked infantile nystagmus ?,0001054-3,genetic changes,"Mutations in the FRMD7 gene cause X-linked infantile nystagmus. The FRMD7 gene provides instructions for making a protein whose exact function is unknown. This protein is found mostly in areas of the brain that control eye movement and in the light-sensitive tissue at the back of the eye (retina). Research suggests that FRMD7 gene mutations cause nystagmus by disrupting the development of certain nerve cells in the brain and retina.  In some people with X-linked infantile nystagmus, no mutation in the FRMD7 gene has been found. The genetic cause of the disorder is unknown in these individuals. Researchers believe that mutations in at least one other gene, which has not been identified, can cause this disorder.",X-linked infantile nystagmus,0001054,GHR,https://ghr.nlm.nih.gov/condition/x-linked-infantile-nystagmus,C2673809,T019,Disorders
Is X-linked infantile nystagmus inherited ?,0001054-4,inheritance,"This condition is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two copies of the X chromosome), one altered copy of the gene in each cell can cause the condition, although affected females may experience less severe symptoms than affected males. Approximately half of the females with only one altered copy of the FRMD7 gene in each cell have no symptoms of this condition.",X-linked infantile nystagmus,0001054,GHR,https://ghr.nlm.nih.gov/condition/x-linked-infantile-nystagmus,C2673809,T019,Disorders
What are the treatments for X-linked infantile nystagmus ?,0001054-5,treatment,"These resources address the diagnosis or management of X-linked infantile nystagmus:  - Gene Review: Gene Review: FRMD7-Related Infantile Nystagmus  - Genetic Testing Registry: Infantile nystagmus, X-linked  - MedlinePlus Encyclopedia: Nystagmus   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",X-linked infantile nystagmus,0001054,GHR,https://ghr.nlm.nih.gov/condition/x-linked-infantile-nystagmus,C2673809,T019,Disorders
What is (are) X-linked infantile spasm syndrome ?,0001055-1,information,"X-linked infantile spasm syndrome is a seizure disorder characterized by a type of seizure known as infantile spasms. The spasms usually appear before the age of 1. Several types of spasms have been described, but the most commonly reported involves bending at the waist and neck with extension of the arms and legs (sometimes called a jackknife spasm). Each spasm lasts only seconds, but they occur in clusters several minutes long. Although individuals are not usually affected while they are sleeping, the spasms commonly occur just after awakening. Infantile spasms usually disappear by age 5, but many children then develop other types of seizures that recur throughout their lives.  Most babies with X-linked infantile spasm syndrome have characteristic results on an electroencephalogram (EEG), a test used to measure the electrical activity of the brain. The EEG of these individuals typically shows an irregular pattern known as hypsarrhythmia, and this finding can help differentiate infantile spasms from other types of seizures.  Because of the recurrent seizures, babies with X-linked infantile spasm syndrome stop developing normally and begin to lose skills they have acquired (developmental regression), such as sitting, rolling over, and babbling. Subsequently, development in affected children is delayed. Most affected individuals also have intellectual disability throughout their lives.",X-linked infantile spasm syndrome,0001055,GHR,https://ghr.nlm.nih.gov/condition/x-linked-infantile-spasm-syndrome,C0037769,T047,Disorders
How many people are affected by X-linked infantile spasm syndrome ?,0001055-2,frequency,"Infantile spasms are estimated to affect 1 to 1.6 in 100,000 individuals. This estimate includes X-linked infantile spasm syndrome as well as infantile spasms that have other causes.",X-linked infantile spasm syndrome,0001055,GHR,https://ghr.nlm.nih.gov/condition/x-linked-infantile-spasm-syndrome,C0037769,T047,Disorders
What are the genetic changes related to X-linked infantile spasm syndrome ?,0001055-3,genetic changes,"X-linked infantile spasm syndrome is caused by mutations in either the ARX gene or the CDKL5 gene. The proteins produced from these genes play a role in the normal functioning of the brain. The ARX protein is involved in the regulation of other genes that contribute to brain development. The CDKL5 protein is thought to regulate the activity of at least one protein that is critical for normal brain function. Researchers are working to determine how mutations in either of these genes lead to seizures and intellectual disability.  Infantile spasms can have nongenetic causes, such as brain malformations, other disorders that affect brain function, or brain damage. In addition, changes in genes that are not located on the X chromosome cause infantile spasms in rare cases.",X-linked infantile spasm syndrome,0001055,GHR,https://ghr.nlm.nih.gov/condition/x-linked-infantile-spasm-syndrome,C0037769,T047,Disorders
Is X-linked infantile spasm syndrome inherited ?,0001055-4,inheritance,"X-linked infantile spasm syndrome can have different inheritance patterns depending on the genetic cause.  When caused by mutations in the ARX gene, this condition is inherited in an X-linked recessive pattern. The ARX gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. Usually in females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. However, in some instances, one altered copy of the ARX gene is sufficient because the X chromosome with the normal copy of the ARX gene is turned off through a process called X-inactivation. Early in embryonic development in females, one of the two X chromosomes is permanently inactivated in somatic cells (cells other than egg and sperm cells). X-inactivation ensures that females, like males, have only one active copy of the X chromosome in each body cell. Usually X-inactivation occurs randomly, such that each X chromosome is active in about half of the body cells. Sometimes X-inactivation is not random, and one X chromosome is active in more than half of cells. When X-inactivation does not occur randomly, it is called skewed X-inactivation. Some ARX gene mutations may be associated with skewed X-inactivation, which results in the inactivation of the X chromosome with the normal copy of the ARX gene in most cells of the body. This skewed X-inactivation causes the chromosome with the mutated ARX gene to be expressed in more than half of cells, causing X-linked infantile spasm syndrome.  When caused by mutations in the CDKL5 gene, this condition is thought to have an X-linked dominant inheritance pattern. The CDKL5 gene is also located on the X chromosome, making this condition X-linked. The inheritance is dominant because one copy of the altered gene in each cell is sufficient to cause the condition in both males and females.  X-linked infantile spasm syndrome caused by CDKL5 gene mutations usually occurs in individuals with no history of the disorder in their family. These mutations likely occur in early embryonic development (called de novo mutations). Because males have only one X chromosome, X-linked dominant disorders are often more severe in males than in females. Male fetuses with CDKL5-related X-linked infantile spasm syndrome may not survive to birth, so more females are diagnosed with the condition. In females, the distribution of active and inactive X chromosomes due to X-inactivation may affect whether a woman develops the condition or the severity of the signs and symptoms. Generally, the larger the proportion of active X chromosomes that contain the mutated CDKL5 gene, the more severe the signs and symptoms of the condition are.  A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",X-linked infantile spasm syndrome,0001055,GHR,https://ghr.nlm.nih.gov/condition/x-linked-infantile-spasm-syndrome,C0037769,T047,Disorders
What are the treatments for X-linked infantile spasm syndrome ?,0001055-5,treatment,These resources address the diagnosis or management of X-linked infantile spasm syndrome:  - Child Neurology Foundation  - Genetic Testing Registry: Early infantile epileptic encephalopathy 2  - Genetic Testing Registry: West syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,X-linked infantile spasm syndrome,0001055,GHR,https://ghr.nlm.nih.gov/condition/x-linked-infantile-spasm-syndrome,C0037769,T047,Disorders
"What is (are) X-linked intellectual disability, Siderius type ?",0001056-1,information,"X-linked intellectual disability, Siderius type is a condition characterized by mild to moderate intellectual disability that affects only males. Affected boys often have delayed development of motor skills such as walking, and their speech may be delayed.  Individuals with X-linked intellectual disability, Siderius type frequently also have an opening in the lip (cleft lip) with an opening in the roof of the mouth (cleft palate). A cleft can occur on one or both sides of the upper lip.  Some boys and men with this condition have distinctive facial features, including a long face, a sloping forehead, a broad nasal bridge, a prominent bone in the lower forehead (supraorbital ridge), and outside corners of the eyes that point upward (upslanting palpebral fissures). Affected individuals may also have low-set ears and large hands.","X-linked intellectual disability, Siderius type",0001056,GHR,https://ghr.nlm.nih.gov/condition/x-linked-intellectual-disability-siderius-type,C3714756,T048,Disorders
"How many people are affected by X-linked intellectual disability, Siderius type ?",0001056-2,frequency,"While X-linked intellectual disability of all types and causes is relatively common, with a prevalence of 1 in 600 to 1,000 males, the prevalence of the Siderius type is unknown. Only a few affected families have been described in the scientific literature.","X-linked intellectual disability, Siderius type",0001056,GHR,https://ghr.nlm.nih.gov/condition/x-linked-intellectual-disability-siderius-type,C3714756,T048,Disorders
"What are the genetic changes related to X-linked intellectual disability, Siderius type ?",0001056-3,genetic changes,"X-linked intellectual disability, Siderius type is caused by mutations in the PHF8 gene. This gene provides instructions for making a protein that is found in the nucleus of cells, particularly in brain cells before and just after birth. The PHF8 protein attaches (binds) to complexes called chromatin to regulate the activity (expression) of other genes. Chromatin is the network of DNA and protein that packages DNA into chromosomes. Binding with the PHF8 protein is part of the process that changes the structure of chromatin (chromatin remodeling) to alter how tightly regions of DNA are packaged. Chromatin remodeling is one way gene expression is regulated; when DNA is tightly packed, gene expression is often lower than when DNA is loosely packed.  Most PHF8 gene mutations lead to an abnormally short protein that gets transported out of the cell's nucleus. Outside of the nucleus, the PHF8 protein cannot interact with chromatin to regulate gene expression. While the exact disease mechanism is unknown, it is likely that a lack of PHF8 protein in the nucleus of brain cells before birth prevents chromatin remodeling, altering the normal expression of genes involved in intellectual function and formation of structures along the midline of the skull. This altered gene expression leads to intellectual disability, cleft lip and palate, and the other features of X-linked intellectual disability, Siderius type.","X-linked intellectual disability, Siderius type",0001056,GHR,https://ghr.nlm.nih.gov/condition/x-linked-intellectual-disability-siderius-type,C3714756,T048,Disorders
"Is X-linked intellectual disability, Siderius type inherited ?",0001056-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.","X-linked intellectual disability, Siderius type",0001056,GHR,https://ghr.nlm.nih.gov/condition/x-linked-intellectual-disability-siderius-type,C3714756,T048,Disorders
"What are the treatments for X-linked intellectual disability, Siderius type ?",0001056-5,treatment,"These resources address the diagnosis or management of X-linked intellectual disability, Siderius type:  - Cincinnati Children's Hospital: Cleft Lip / Cleft Palate Bottle Feeding  - Cleveland Clinic: Cleft Lip & Palate Surgery  - Genetic Testing Registry: Siderius X-linked mental retardation syndrome  - Nemours Children's Health System: Cleft Lip and Palate   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","X-linked intellectual disability, Siderius type",0001056,GHR,https://ghr.nlm.nih.gov/condition/x-linked-intellectual-disability-siderius-type,C3714756,T048,Disorders
What is (are) X-linked juvenile retinoschisis ?,0001057-1,information,"X-linked juvenile retinoschisis is a condition characterized by impaired vision that begins in childhood and occurs almost exclusively in males. This disorder affects the retina, which is a specialized light-sensitive tissue that lines the back of the eye. Damage to the retina impairs the sharpness of vision (visual acuity) in both eyes. Typically, X-linked juvenile retinoschisis affects cells in the central area of the retina called the macula. The macula is responsible for sharp central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. X-linked juvenile retinoschisis is one type of a broader disorder called macular degeneration, which disrupts the normal functioning of the macula. Occasionally, side (peripheral) vision is affected in people with X-linked juvenile retinoschisis.  X-linked juvenile retinoschisis is usually diagnosed when affected boys start school and poor vision and difficulty with reading become apparent. In more severe cases, eye squinting and involuntary movement of the eyes (nystagmus) begin in infancy. Other early features of X-linked juvenile retinoschisis include eyes that do not look in the same direction (strabismus) and farsightedness (hyperopia). Visual acuity often declines in childhood and adolescence but then stabilizes throughout adulthood until a significant decline in visual acuity typically occurs in a man's fifties or sixties. Sometimes, severe complications develop, such as separation of the retinal layers (retinal detachment) or leakage of blood vessels in the retina (vitreous hemorrhage). These eye abnormalities can further impair vision or cause blindness.",X-linked juvenile retinoschisis,0001057,GHR,https://ghr.nlm.nih.gov/condition/x-linked-juvenile-retinoschisis,C0271091,T047,Disorders
How many people are affected by X-linked juvenile retinoschisis ?,0001057-2,frequency,"The prevalence of X-linked juvenile retinoschisis is estimated to be 1 in 5,000 to 25,000 men worldwide.",X-linked juvenile retinoschisis,0001057,GHR,https://ghr.nlm.nih.gov/condition/x-linked-juvenile-retinoschisis,C0271091,T047,Disorders
What are the genetic changes related to X-linked juvenile retinoschisis ?,0001057-3,genetic changes,"Mutations in the RS1 gene cause most cases of X-linked juvenile retinoschisis. The RS1 gene provides instructions for making a protein called retinoschisin, which is found in the retina. Studies suggest that retinoschisin plays a role in the development and maintenance of the retina. The protein is probably involved in the organization of cells in the retina by attaching cells together (cell adhesion).  RS1 gene mutations result in a decrease in or complete loss of functional retinoschisin, which disrupts the maintenance and organization of cells in the retina. As a result, tiny splits (schisis) or tears form in the retina. This damage often forms a ""spoke-wheel"" pattern in the macula, which can be seen during an eye examination. In half of affected individuals, these abnormalities can occur in the area of the macula, affecting visual acuity, in the other half of cases the schisis occurs in the sides of the retina, resulting in impaired peripheral vision.  Some individuals with X-linked juvenile retinoschisis do not have a mutation in the RS1 gene. In these individuals, the cause of the disorder is unknown.",X-linked juvenile retinoschisis,0001057,GHR,https://ghr.nlm.nih.gov/condition/x-linked-juvenile-retinoschisis,C0271091,T047,Disorders
Is X-linked juvenile retinoschisis inherited ?,0001057-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",X-linked juvenile retinoschisis,0001057,GHR,https://ghr.nlm.nih.gov/condition/x-linked-juvenile-retinoschisis,C0271091,T047,Disorders
What are the treatments for X-linked juvenile retinoschisis ?,0001057-5,treatment,These resources address the diagnosis or management of X-linked juvenile retinoschisis:  - Gene Review: Gene Review: X-Linked Juvenile Retinoschisis  - Genetic Testing Registry: Juvenile retinoschisis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,X-linked juvenile retinoschisis,0001057,GHR,https://ghr.nlm.nih.gov/condition/x-linked-juvenile-retinoschisis,C0271091,T047,Disorders
What is (are) X-linked lissencephaly with abnormal genitalia ?,0001058-1,information,"X-linked lissencephaly with abnormal genitalia (XLAG) is a condition that affects the development of the brain and genitalia. It occurs most often in males.  XLAG is characterized by abnormal brain development that results in the brain having a smooth appearance (lissencephaly) instead of its normal folds and grooves. Individuals without any folds in the brain (agyria) typically have more severe symptoms than people with reduced folds and grooves (pachygyria). Individuals with XLAG may also have a lack of development (agenesis) of the tissue connecting the left and right halves of the brain (corpus callosum). The brain abnormalities can cause severe intellectual disability and developmental delay, abnormal muscle stiffness (spasticity), weak muscle tone (hypotonia), and feeding difficulties. Starting soon after birth, babies with XLAG have frequent and recurrent seizures (epilepsy). Most children with XLAG do not survive past early childhood.  Another key feature of XLAG in males is abnormal genitalia that can include an unusually small penis (micropenis), undescended testes (cryptorchidism), or external genitalia that do not look clearly male or clearly female (ambiguous genitalia).  Additional signs and symptoms of XLAG include chronic diarrhea, periods of increased blood sugar (transient hyperglycemia), and problems with body temperature regulation.",X-linked lissencephaly with abnormal genitalia,0001058,GHR,https://ghr.nlm.nih.gov/condition/x-linked-lissencephaly-with-abnormal-genitalia,C0266463,T019,Disorders
How many people are affected by X-linked lissencephaly with abnormal genitalia ?,0001058-2,frequency,The incidence of XLAG is unknown; approximately 30 affected families have been described in the medical literature.,X-linked lissencephaly with abnormal genitalia,0001058,GHR,https://ghr.nlm.nih.gov/condition/x-linked-lissencephaly-with-abnormal-genitalia,C0266463,T019,Disorders
What are the genetic changes related to X-linked lissencephaly with abnormal genitalia ?,0001058-3,genetic changes,"Mutations in the ARX gene cause XLAG. The ARX gene provides instructions for producing a protein that is involved in the development of several organs, including the brain, testes, and pancreas. In the developing brain, the ARX protein is involved with movement and communication in nerve cells (neurons). The ARX protein regulates genes that play a role in the migration of specialized neurons (interneurons) to their proper location. Interneurons relay signals between neurons. In the pancreas and testes, the ARX protein helps to regulate the process by which cells mature to carry out specific functions (differentiation).  ARX gene mutations lead to the production of a nonfunctional ARX protein or to the complete absence of ARX protein. As a result, the ARX protein cannot perform its role regulating the activity of genes important for interneuron migration. In addition to impairing normal brain development, a lack of functional ARX protein disrupts cell differentiation during the formation of the testes, leading to abnormal genitalia. It is thought that the disruption of ARX protein function in the pancreas plays a role in the chronic diarrhea and hyperglycemia experienced by individuals with XLAG.",X-linked lissencephaly with abnormal genitalia,0001058,GHR,https://ghr.nlm.nih.gov/condition/x-linked-lissencephaly-with-abnormal-genitalia,C0266463,T019,Disorders
Is X-linked lissencephaly with abnormal genitalia inherited ?,0001058-4,inheritance,"This condition is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females, who have two copies of the X chromosome, one altered copy of the gene in each cell can lead to less severe brain malformations or may cause no symptoms at all. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",X-linked lissencephaly with abnormal genitalia,0001058,GHR,https://ghr.nlm.nih.gov/condition/x-linked-lissencephaly-with-abnormal-genitalia,C0266463,T019,Disorders
What are the treatments for X-linked lissencephaly with abnormal genitalia ?,0001058-5,treatment,"These resources address the diagnosis or management of X-linked lissencephaly with abnormal genitalia:  - Genetic Testing Registry: Lissencephaly 2, X-linked   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",X-linked lissencephaly with abnormal genitalia,0001058,GHR,https://ghr.nlm.nih.gov/condition/x-linked-lissencephaly-with-abnormal-genitalia,C0266463,T019,Disorders
What is (are) X-linked lymphoproliferative disease ?,0001059-1,information,"X-linked lymphoproliferative disease (XLP) is a disorder of the immune system and blood-forming cells that is found almost exclusively in males. More than half of individuals with this disorder experience an exaggerated immune response to the Epstein-Barr virus (EBV). EBV is a very common virus that eventually infects most humans. In some people it causes infectious mononucleosis (commonly known as ""mono""). Normally, after initial infection, EBV remains in certain immune system cells (lymphocytes) called B cells. However, the virus is generally inactive (latent) because it is controlled by other lymphocytes called T cells that specifically target EBV-infected B cells.  People with XLP may respond to EBV infection by producing abnormally large numbers of T cells, B cells, and other lymphocytes called macrophages. This proliferation of immune cells often causes a life-threatening reaction called hemophagocytic lymphohistiocytosis. Hemophagocytic lymphohistiocytosis causes fever, destroys blood-producing cells in the bone marrow, and damages the liver. The spleen, heart, kidneys, and other organs and tissues may also be affected. In some individuals with XLP, hemophagocytic lymphohistiocytosis or related symptoms may occur without EBV infection.  About one-third of people with XLP experience dysgammaglobulinemia, which means they have abnormal levels of some types of antibodies. Antibodies (also known as immunoglobulins) are proteins that attach to specific foreign particles and germs, marking them for destruction. Individuals with dysgammaglobulinemia are prone to recurrent infections.  Cancers of immune system cells (lymphomas) occur in about one-third of people with XLP.  Without treatment, most people with XLP survive only into childhood. Death usually results from hemophagocytic lymphohistiocytosis.  XLP can be divided into two types based on its genetic cause and pattern of signs and symptoms: XLP1 (also known as classic XLP) and XLP2. People with XLP2 have not been known to develop lymphoma, are more likely to develop hemophagocytic lymphohistiocytosis without EBV infection, usually have an enlarged spleen (splenomegaly), and may also have inflammation of the large intestine (colitis). Some researchers believe that these individuals should actually be considered to have a similar but separate disorder rather than a type of XLP.",X-linked lymphoproliferative disease,0001059,GHR,https://ghr.nlm.nih.gov/condition/x-linked-lymphoproliferative-disease,C0549463,T191,Disorders
How many people are affected by X-linked lymphoproliferative disease ?,0001059-2,frequency,"XLP1 is estimated to occur in about 1 per million males worldwide. XLP2 is less common, occurring in about 1 per 5 million males.",X-linked lymphoproliferative disease,0001059,GHR,https://ghr.nlm.nih.gov/condition/x-linked-lymphoproliferative-disease,C0549463,T191,Disorders
What are the genetic changes related to X-linked lymphoproliferative disease ?,0001059-3,genetic changes,"Mutations in the SH2D1A and XIAP genes cause XLP. SH2D1A gene mutations cause XLP1, and XIAP gene mutations cause XLP2.  The SH2D1A gene provides instructions for making a protein called signaling lymphocyte activation molecule (SLAM) associated protein (SAP). This protein is involved in the functioning of lymphocytes that destroy other cells (cytotoxic lymphocytes) and is necessary for the development of specialized T cells called natural killer T cells. The SAP protein also helps control immune reactions by triggering self-destruction (apoptosis) of cytotoxic lymphocytes when they are no longer needed.  Some SH2D1A gene mutations impair SAP function. Others result in an abnormally short protein that is unstable or nonfunctional, or prevent any SAP from being produced. The loss of functional SAP disrupts proper signaling in the immune system and may prevent the body from controlling the immune reaction to EBV infection. In addition, lymphomas may develop when defective lymphocytes are not properly destroyed by apoptosis.  The XIAP gene provides instructions for making a protein that helps protect cells from undergoing apoptosis in response to certain signals. XIAP gene mutations can lead to an absence of XIAP protein or decrease the amount of XIAP protein that is produced. It is unknown how a lack of XIAP protein results in the signs and symptoms of XLP, or why features of this disorder differ somewhat between people with XIAP and SH2D1A gene mutations.",X-linked lymphoproliferative disease,0001059,GHR,https://ghr.nlm.nih.gov/condition/x-linked-lymphoproliferative-disease,C0549463,T191,Disorders
Is X-linked lymphoproliferative disease inherited ?,0001059-4,inheritance,"This condition is generally inherited in an X-linked recessive pattern. The genes associated with this condition are located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of an associated gene in each cell is sufficient to cause the condition. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In females (who have two X chromosomes), a mutation usually has to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of an associated gene, males are affected by X-linked recessive disorders much more frequently than females. However, in rare cases a female carrying one altered copy of the SH2D1A or XIAP gene in each cell may develop signs and symptoms of this condition.",X-linked lymphoproliferative disease,0001059,GHR,https://ghr.nlm.nih.gov/condition/x-linked-lymphoproliferative-disease,C0549463,T191,Disorders
What are the treatments for X-linked lymphoproliferative disease ?,0001059-5,treatment,"These resources address the diagnosis or management of XLP:  - Children's Hospital of Philadelphia  - Gene Review: Gene Review: Lymphoproliferative Disease, X-Linked  - Genetic Testing Registry: Lymphoproliferative syndrome 1, X-linked  - Genetic Testing Registry: Lymphoproliferative syndrome 2, X-linked  - MedlinePlus Encyclopedia: Epstein-Barr Virus Test  - Merck Manual for Healthcare Professionals  - XLP Research Trust: Immunoglobulin Replacement  - XLP Research Trust: Preparing for Bone Marrow Transplant   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",X-linked lymphoproliferative disease,0001059,GHR,https://ghr.nlm.nih.gov/condition/x-linked-lymphoproliferative-disease,C0549463,T191,Disorders
What is (are) X-linked myotubular myopathy ?,0001060-1,information,"X-linked myotubular myopathy is a condition that primarily affects muscles used for movement (skeletal muscles) and occurs almost exclusively in males. People with this condition have muscle weakness (myopathy) and decreased muscle tone (hypotonia) that are usually evident at birth.  The muscle problems in X-linked myotubular myopathy impair the development of motor skills such as sitting, standing, and walking. Affected infants may also have difficulties with feeding due to muscle weakness. Individuals with this condition often do not have the muscle strength to breathe on their own and must be supported with a machine to help them breathe (mechanical ventilation). Some affected individuals need breathing assistance only periodically, typically during sleep, while others require it continuously. People with X-linked myotubular myopathy may also have weakness in the muscles that control eye movement (ophthalmoplegia), weakness in other muscles of the face, and absent reflexes (areflexia).  In X-linked myotubular myopathy, muscle weakness often disrupts normal bone development and can lead to fragile bones, an abnormal curvature of the spine (scoliosis), and joint deformities (contractures) of the hips and knees. People with X-linked myotubular myopathy may have a large head with a narrow and elongated face and a high, arched roof of the mouth (palate). They may also have liver disease, recurrent ear and respiratory infections, or seizures.  Because of their severe breathing problems, individuals with X-linked myotubular myopathy usually survive only into early childhood; however, some people with this condition have lived into adulthood.  X-linked myotubular myopathy is a member of a group of disorders called centronuclear myopathies. In centronuclear myopathies, the nucleus is found at the center of many rod-shaped muscle cells instead of at either end, where it is normally located.",X-linked myotubular myopathy,0001060,GHR,https://ghr.nlm.nih.gov/condition/x-linked-myotubular-myopathy,C0410203,T019,Disorders
How many people are affected by X-linked myotubular myopathy ?,0001060-2,frequency,"The incidence of X-linked myotubular myopathy is estimated to be 1 in 50,000 newborn males worldwide.",X-linked myotubular myopathy,0001060,GHR,https://ghr.nlm.nih.gov/condition/x-linked-myotubular-myopathy,C0410203,T019,Disorders
What are the genetic changes related to X-linked myotubular myopathy ?,0001060-3,genetic changes,"Mutations in the MTM1 gene cause X-linked myotubular myopathy. The MTM1 gene provides instructions for producing an enzyme called myotubularin. Myotubularin is thought to be involved in the development and maintenance of muscle cells.  MTM1 gene mutations probably disrupt myotubularin's role in muscle cell development and maintenance, causing muscle weakness and other signs and symptoms of X-linked myotubular myopathy.",X-linked myotubular myopathy,0001060,GHR,https://ghr.nlm.nih.gov/condition/x-linked-myotubular-myopathy,C0410203,T019,Disorders
Is X-linked myotubular myopathy inherited ?,0001060-4,inheritance,"X-linked myotubular myopathy is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In X-linked myotubular myopathy, the affected male inherits one altered copy from his mother in 80 to 90 percent of cases. In the remaining 10 to 20 percent of cases, the disorder results from a new mutation in the gene that occurs during the formation of a parent's reproductive cells (eggs or sperm) or in early embryonic development. Females with one altered copy of the MTM1 gene generally do not experience signs and symptoms of the disorder. In rare cases, however, females who have one altered copy of the MTM1 gene experience some mild muscle weakness.",X-linked myotubular myopathy,0001060,GHR,https://ghr.nlm.nih.gov/condition/x-linked-myotubular-myopathy,C0410203,T019,Disorders
What are the treatments for X-linked myotubular myopathy ?,0001060-5,treatment,These resources address the diagnosis or management of X-linked myotubular myopathy:  - Gene Review: Gene Review: X-Linked Centronuclear Myopathy  - Genetic Testing Registry: Severe X-linked myotubular myopathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,X-linked myotubular myopathy,0001060,GHR,https://ghr.nlm.nih.gov/condition/x-linked-myotubular-myopathy,C0410203,T019,Disorders
What is (are) X-linked severe combined immunodeficiency ?,0001061-1,information,"X-linked severe combined immunodeficiency (SCID) is an inherited disorder of the immune system that occurs almost exclusively in males. Boys with X-linked SCID are prone to recurrent and persistent infections because they lack the necessary immune cells to fight off certain bacteria, viruses, and fungi. Many infants with X-linked SCID develop chronic diarrhea, a fungal infection called thrush, and skin rashes. Affected individuals also grow more slowly than other children. Without treatment, males with X-linked SCID usually do not live beyond infancy.",X-linked severe combined immunodeficiency,0001061,GHR,https://ghr.nlm.nih.gov/condition/x-linked-severe-combined-immunodeficiency,C0085110,T047,Disorders
How many people are affected by X-linked severe combined immunodeficiency ?,0001061-2,frequency,"X-linked SCID is the most common form of severe combined immunodeficiency. Its exact incidence is unknown, but the condition probably affects at least 1 in 50,000 to 100,000 newborns.",X-linked severe combined immunodeficiency,0001061,GHR,https://ghr.nlm.nih.gov/condition/x-linked-severe-combined-immunodeficiency,C0085110,T047,Disorders
What are the genetic changes related to X-linked severe combined immunodeficiency ?,0001061-3,genetic changes,"Mutations in the IL2RG gene cause X-linked SCID. The IL2RG gene provides instructions for making a protein that is critical for normal immune system function. This protein is necessary for the growth and maturation of developing immune system cells called lymphocytes. Lymphocytes defend the body against potentially harmful invaders, make antibodies, and help regulate the entire immune system. Mutations in the IL2RG gene prevent these cells from developing and functioning normally. Without functional lymphocytes, the body is unable to fight off infections.",X-linked severe combined immunodeficiency,0001061,GHR,https://ghr.nlm.nih.gov/condition/x-linked-severe-combined-immunodeficiency,C0085110,T047,Disorders
Is X-linked severe combined immunodeficiency inherited ?,0001061-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",X-linked severe combined immunodeficiency,0001061,GHR,https://ghr.nlm.nih.gov/condition/x-linked-severe-combined-immunodeficiency,C0085110,T047,Disorders
What are the treatments for X-linked severe combined immunodeficiency ?,0001061-5,treatment,These resources address the diagnosis or management of X-linked SCID:  - Baby's First Test: Severe Combined Immunodeficiency  - Gene Review: Gene Review: X-Linked Severe Combined Immunodeficiency  - Genetic Testing Registry: X-linked severe combined immunodeficiency  - MedlinePlus Encyclopedia: Immunodeficiency Disorders  - National Marrow Donor Program: Severe Combined Immunodeficiency and Transplant   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,X-linked severe combined immunodeficiency,0001061,GHR,https://ghr.nlm.nih.gov/condition/x-linked-severe-combined-immunodeficiency,C0085110,T047,Disorders
What is (are) X-linked sideroblastic anemia ?,0001062-1,information,"X-linked sideroblastic anemia is an inherited disorder that prevents developing red blood cells (erythroblasts) from making enough hemoglobin, which is the protein that carries oxygen in the blood. People with X-linked sideroblastic anemia have mature red blood cells that are smaller than normal (microcytic) and appear pale (hypochromic) because of the shortage of hemoglobin. This disorder also leads to an abnormal accumulation of iron in red blood cells. The iron-loaded erythroblasts, which are present in bone marrow, are called ring sideroblasts. These abnormal cells give the condition its name.  The signs and symptoms of X-linked sideroblastic anemia result from a combination of reduced hemoglobin and an overload of iron. They range from mild to severe and most often appear in young adulthood. Common features include fatigue, dizziness, a rapid heartbeat, pale skin, and an enlarged liver and spleen (hepatosplenomegaly). Over time, severe medical problems such as heart disease and liver damage (cirrhosis) can result from the buildup of excess iron in these organs.",X-linked sideroblastic anemia,0001062,GHR,https://ghr.nlm.nih.gov/condition/x-linked-sideroblastic-anemia,C0221018,T047,Disorders
How many people are affected by X-linked sideroblastic anemia ?,0001062-2,frequency,"This form of anemia is uncommon. However, researchers believe that it may not be as rare as they once thought. Increased awareness of the disease has led to more frequent diagnoses.",X-linked sideroblastic anemia,0001062,GHR,https://ghr.nlm.nih.gov/condition/x-linked-sideroblastic-anemia,C0221018,T047,Disorders
What are the genetic changes related to X-linked sideroblastic anemia ?,0001062-3,genetic changes,"Mutations in the ALAS2 gene cause X-linked sideroblastic anemia. The ALAS2 gene provides instructions for making an enzyme called erythroid ALA-synthase, which plays a critical role in the production of heme (a component of the hemoglobin protein) in bone marrow.  ALAS2 mutations impair the activity of erythroid ALA-synthase, which disrupts normal heme production and prevents erythroblasts from making enough hemoglobin. Because almost all of the iron transported into erythroblasts is normally incorporated into heme, the reduced production of heme leads to a buildup of excess iron in these cells. Additionally, the body attempts to compensate for the hemoglobin shortage by absorbing more iron from the diet. This buildup of excess iron damages the body's organs. Low hemoglobin levels and the resulting accumulation of iron in the body's organs lead to the characteristic features of X-linked sideroblastic anemia.  People who have a mutation in another gene, HFE, along with a mutation in the ALAS2 gene may experience a more severe form of X-linked sideroblastic anemia. In this uncommon situation, the combined effect of these two mutations can lead to a more serious iron overload. Mutations in the HFE gene alone can increase the absorption of iron from the diet and result in hemochromatosis, which is another type of iron overload disorder.",X-linked sideroblastic anemia,0001062,GHR,https://ghr.nlm.nih.gov/condition/x-linked-sideroblastic-anemia,C0221018,T047,Disorders
Is X-linked sideroblastic anemia inherited ?,0001062-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In X-linked recessive inheritance, a female with one altered copy of the gene in each cell is called a carrier. Carriers of an ALAS2 mutation can pass on the mutated gene, but most do not develop any symptoms associated with X-linked sideroblastic anemia. However, carriers may have abnormally small, pale red blood cells and related changes that can be detected with a blood test.",X-linked sideroblastic anemia,0001062,GHR,https://ghr.nlm.nih.gov/condition/x-linked-sideroblastic-anemia,C0221018,T047,Disorders
What are the treatments for X-linked sideroblastic anemia ?,0001062-5,treatment,These resources address the diagnosis or management of X-linked sideroblastic anemia:  - Genetic Testing Registry: Hereditary sideroblastic anemia  - MedlinePlus Encyclopedia: Anemia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,X-linked sideroblastic anemia,0001062,GHR,https://ghr.nlm.nih.gov/condition/x-linked-sideroblastic-anemia,C0221018,T047,Disorders
What is (are) X-linked sideroblastic anemia and ataxia ?,0001063-1,information,"X-linked sideroblastic anemia and ataxia is a rare condition characterized by a blood disorder called sideroblastic anemia and movement problems known as ataxia. This condition occurs only in males.  Sideroblastic anemia results when developing red blood cells called erythroblasts do not make enough hemoglobin, which is the protein that carries oxygen in the blood. People with X-linked sideroblastic anemia and ataxia have mature red blood cells that are smaller than normal (microcytic) and appear pale (hypochromic) because of the shortage of hemoglobin. This disorder also leads to an abnormal accumulation of iron in red blood cells. The iron-loaded erythroblasts, which are present in bone marrow, are called ring sideroblasts. These abnormal cells give the condition its name. Unlike other forms of sideroblastic anemia, X-linked sideroblastic anemia and ataxia does not cause a potentially dangerous buildup of iron in the body. The anemia is typically mild and usually does not cause any symptoms.  X-linked sideroblastic anemia and ataxia causes problems with balance and coordination that appear early in life. The ataxia primarily affects the trunk, making it difficult to sit, stand, and walk unassisted. In addition to ataxia, people with this condition often have trouble coordinating movements that involve judging distance or scale (dysmetria) and find it difficult to make rapid, alternating movements (dysdiadochokinesis). Mild speech difficulties (dysarthria), tremor, and abnormal eye movements have also been reported in some affected individuals.",X-linked sideroblastic anemia and ataxia,0001063,GHR,https://ghr.nlm.nih.gov/condition/x-linked-sideroblastic-anemia-and-ataxia,C0002896,T047,Disorders
How many people are affected by X-linked sideroblastic anemia and ataxia ?,0001063-2,frequency,X-linked sideroblastic anemia and ataxia is a rare disorder; only a few affected families have been reported.,X-linked sideroblastic anemia and ataxia,0001063,GHR,https://ghr.nlm.nih.gov/condition/x-linked-sideroblastic-anemia-and-ataxia,C0002896,T047,Disorders
What are the genetic changes related to X-linked sideroblastic anemia and ataxia ?,0001063-3,genetic changes,"Mutations in the ABCB7 gene cause X-linked sideroblastic anemia and ataxia. The ABCB7 gene provides instructions for making a protein that is critical for heme production. Heme is a component of the hemoglobin protein, which is vital for supplying oxygen to the entire body. The ABCB7 protein also plays a role in the formation of certain proteins containing clusters of iron and sulfur atoms. Overall, researchers believe that the ABCB7 protein helps maintain an appropriate balance of iron (iron homeostasis) in developing red blood cells.  ABCB7 mutations slightly alter the structure of the ABCB7 protein, disrupting its usual role in heme production and iron homeostasis. Anemia results when heme cannot be produced normally, and therefore not enough hemoglobin is made. It is unclear how changes in the ABCB7 gene lead to ataxia and other problems with movement.",X-linked sideroblastic anemia and ataxia,0001063,GHR,https://ghr.nlm.nih.gov/condition/x-linked-sideroblastic-anemia-and-ataxia,C0002896,T047,Disorders
Is X-linked sideroblastic anemia and ataxia inherited ?,0001063-4,inheritance,"This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In X-linked recessive inheritance, a female with one altered copy of the gene in each cell is called a carrier. Carriers of an ABCB7 mutation can pass on the mutated gene but do not develop ataxia or other health problems associated with X-linked sideroblastic anemia and ataxia. However, carriers may have abnormally small, pale red blood cells and related changes that can be detected with a blood test.",X-linked sideroblastic anemia and ataxia,0001063,GHR,https://ghr.nlm.nih.gov/condition/x-linked-sideroblastic-anemia-and-ataxia,C0002896,T047,Disorders
What are the treatments for X-linked sideroblastic anemia and ataxia ?,0001063-5,treatment,These resources address the diagnosis or management of X-linked sideroblastic anemia and ataxia:  - Gene Review: Gene Review: X-Linked Sideroblastic Anemia and Ataxia  - Genetic Testing Registry: Anemia sideroblastic and spinocerebellar ataxia  - MedlinePlus Encyclopedia: Anemia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,X-linked sideroblastic anemia and ataxia,0001063,GHR,https://ghr.nlm.nih.gov/condition/x-linked-sideroblastic-anemia-and-ataxia,C0002896,T047,Disorders
What is (are) X-linked spondyloepiphyseal dysplasia tarda ?,0001064-1,information,"X-linked spondyloepiphyseal dysplasia tarda is a condition that impairs bone growth and occurs almost exclusively in males. The name of the condition indicates that it affects the bones of the spine (spondylo-) and the ends (epiphyses) of long bones in the arms and legs. ""Tarda"" indicates that signs and symptoms of this condition are not present at birth, but appear later in childhood, typically between ages 6 and 10.  Males with X-linked spondyloepiphyseal dysplasia tarda have skeletal abnormalities and short stature. Affected boys grow steadily until late childhood, when their growth slows. Male adult height ranges from 4 feet 10 inches to 5 feet 6 inches. Individuals with X-linked spondyloepiphyseal dysplasia tarda have a short trunk and neck, and their arms appear disproportionately long. Impaired growth of the spinal bones (vertebrae) causes the short stature seen in this disorder. The spinal abnormalities include flattened vertebrae (platyspondyly) with hump-shaped bulges, progressive thinning of the discs between vertebrae, and an abnormal curvature of the spine (scoliosis or kyphosis). Other skeletal features of X-linked spondyloepiphyseal dysplasia tarda include an abnormality of the hip joint that causes the upper leg bones to turn inward (coxa vara); a broad, barrel-shaped chest; and decreased mobility of the elbow and hip joints. Arthritis often develops in early adulthood, typically affecting the hip joints and spine.",X-linked spondyloepiphyseal dysplasia tarda,0001064,GHR,https://ghr.nlm.nih.gov/condition/x-linked-spondyloepiphyseal-dysplasia-tarda,C0334044,T019,Disorders
How many people are affected by X-linked spondyloepiphyseal dysplasia tarda ?,0001064-2,frequency,"The prevalence of X-linked spondyloepiphyseal dysplasia tarda is estimated to be 1 in 150,000 to 200,000 people worldwide.",X-linked spondyloepiphyseal dysplasia tarda,0001064,GHR,https://ghr.nlm.nih.gov/condition/x-linked-spondyloepiphyseal-dysplasia-tarda,C0334044,T019,Disorders
What are the genetic changes related to X-linked spondyloepiphyseal dysplasia tarda ?,0001064-3,genetic changes,"Mutations in the TRAPPC2 gene (often called the SEDL gene) cause X-linked spondyloepiphyseal dysplasia tarda. The TRAPPC2 gene provides instructions for producing the protein sedlin. The function of sedlin is unclear. Researchers believe that sedlin is part of a large molecule called the trafficking protein particle (TRAPP) complex, which plays a role in the transport of proteins between various cell compartments (organelles). Because sedlin is active (expressed) in cells throughout the body; it is unclear why mutations in the TRAPPC2 gene affect only bone growth.",X-linked spondyloepiphyseal dysplasia tarda,0001064,GHR,https://ghr.nlm.nih.gov/condition/x-linked-spondyloepiphyseal-dysplasia-tarda,C0334044,T019,Disorders
Is X-linked spondyloepiphyseal dysplasia tarda inherited ?,0001064-4,inheritance,"X-linked spondyloepiphyseal dysplasia tarda is inherited in an X-linked recessive pattern. The TRAPPC2 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In X-linked recessive inheritance, a female with one mutated copy of the gene in each cell is called a carrier. She can pass on the altered gene, but usually does not experience signs and symptoms of the disorder. In rare cases, however, females who carry a TRAPPC2 mutation may develop arthritis in early adulthood.",X-linked spondyloepiphyseal dysplasia tarda,0001064,GHR,https://ghr.nlm.nih.gov/condition/x-linked-spondyloepiphyseal-dysplasia-tarda,C0334044,T019,Disorders
What are the treatments for X-linked spondyloepiphyseal dysplasia tarda ?,0001064-5,treatment,These resources address the diagnosis or management of X-linked spondyloepiphyseal dysplasia tarda:  - Gene Review: Gene Review: X-Linked Spondyloepiphyseal Dysplasia Tarda  - Genetic Testing Registry: Spondyloepiphyseal dysplasia tarda   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,X-linked spondyloepiphyseal dysplasia tarda,0001064,GHR,https://ghr.nlm.nih.gov/condition/x-linked-spondyloepiphyseal-dysplasia-tarda,C0334044,T019,Disorders
What is (are) X-linked thrombocytopenia ?,0001065-1,information,"X-linked thrombocytopenia is a bleeding disorder that primarily affects males. This condition is characterized by a blood cell abnormality called thrombocytopenia, which is a shortage in the number of cells involved in clotting (platelets). Affected individuals often have abnormally small platelets as well, a condition called microthrombocytopenia. X-linked thrombocytopenia can cause individuals to bruise easily or have episodes of prolonged bleeding following minor trauma or even in the absence of injury (spontaneous bleeding). Some people with this condition experience spontaneous bleeding in the brain (cerebral hemorrhage), which can cause brain damage that can be life-threatening.  Some people with X-linked thrombocytopenia also have patches of red, irritated skin (eczema) or an increased susceptibility to infections. In severe cases, additional features can develop, such as cancer or autoimmune disorders, which occur when the immune system malfunctions and attacks the body's own tissues and organs. It is unclear, however, if people with these features have X-linked thrombocytopenia or a more severe disorder with similar signs and symptoms called Wiskott-Aldrich syndrome.  Some people have a mild form of the disorder called intermittent thrombocytopenia. These individuals have normal platelet production at times with episodes of thrombocytopenia.",X-linked thrombocytopenia,0001065,GHR,https://ghr.nlm.nih.gov/condition/x-linked-thrombocytopenia,C1839163,T047,Disorders
How many people are affected by X-linked thrombocytopenia ?,0001065-2,frequency,The estimated incidence of X-linked thrombocytopenia is between 1 and 10 per million males worldwide; this condition is rarer among females.,X-linked thrombocytopenia,0001065,GHR,https://ghr.nlm.nih.gov/condition/x-linked-thrombocytopenia,C1839163,T047,Disorders
What are the genetic changes related to X-linked thrombocytopenia ?,0001065-3,genetic changes,"Mutations in the WAS gene cause X-linked thrombocytopenia. The WAS gene provides instructions for making a protein called WASP. This protein is found in all blood cells. WASP is involved in relaying signals from the surface of blood cells to the actin cytoskeleton, which is a network of fibers that make up the cell's structural framework. WASP signaling activates the cell when it is needed and triggers its movement and attachment to other cells and tissues (adhesion). In white blood cells, which protect the body from infection, this signaling allows the actin cytoskeleton to establish the interaction between cells and the foreign invaders that they target (immune synapse).  WAS gene mutations that cause X-linked thrombocytopenia typically lead to the production of an altered protein. The altered WASP has reduced function and cannot efficiently relay signals from the cell membrane to the actin cytoskeleton. In people with X-linked thrombocytopenia, these signaling problems primarily affect platelets, impairing their development. In some cases, white blood cells are affected. When WASP function is impaired in white blood cells, they are less able to respond to foreign invaders and immune problems such as infections, eczema, and autoimmune disorders can occur.",X-linked thrombocytopenia,0001065,GHR,https://ghr.nlm.nih.gov/condition/x-linked-thrombocytopenia,C1839163,T047,Disorders
Is X-linked thrombocytopenia inherited ?,0001065-4,inheritance,"This condition is inherited in an X-linked pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell may or may not cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In most cases of X-linked inheritance, males experience more severe symptoms of the disorder than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.",X-linked thrombocytopenia,0001065,GHR,https://ghr.nlm.nih.gov/condition/x-linked-thrombocytopenia,C1839163,T047,Disorders
What are the treatments for X-linked thrombocytopenia ?,0001065-5,treatment,"These resources address the diagnosis or management of X-linked thrombocytopenia:  - Gene Review: Gene Review: WAS-Related Disorders  - Genetic Testing Registry: Thrombocytopenia, X-linked  - National Heart Lung and Blood Institute: How is Thrombocytopenia Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",X-linked thrombocytopenia,0001065,GHR,https://ghr.nlm.nih.gov/condition/x-linked-thrombocytopenia,C1839163,T047,Disorders
What is (are) xeroderma pigmentosum ?,0001066-1,information,"Xeroderma pigmentosum, which is commonly known as XP, is an inherited condition characterized by an extreme sensitivity to ultraviolet (UV) rays from sunlight. This condition mostly affects the eyes and areas of skin exposed to the sun. Some affected individuals also have problems involving the nervous system.  The signs of xeroderma pigmentosum usually appear in infancy or early childhood. Many affected children develop a severe sunburn after spending just a few minutes in the sun. The sunburn causes redness and blistering that can last for weeks. Other affected children do not get sunburned with minimal sun exposure, but instead tan normally. By age 2, almost all children with xeroderma pigmentosum develop freckling of the skin in sun-exposed areas (such as the face, arms, and lips); this type of freckling rarely occurs in young children without the disorder. In affected individuals, exposure to sunlight often causes dry skin (xeroderma) and changes in skin coloring (pigmentation). This combination of features gives the condition its name, xeroderma pigmentosum.  People with xeroderma pigmentosum have a greatly increased risk of developing skin cancer. Without sun protection, about half of children with this condition develop their first skin cancer by age 10. Most people with xeroderma pigmentosum develop multiple skin cancers during their lifetime. These cancers occur most often on the face, lips, and eyelids. Cancer can also develop on the scalp, in the eyes, and on the tip of the tongue. Studies suggest that people with xeroderma pigmentosum may also have an increased risk of other types of cancer, including brain tumors. Additionally, affected individuals who smoke cigarettes have a significantly increased risk of lung cancer.  The eyes of people with xeroderma pigmentosum may be painfully sensitive to UV rays from the sun. If the eyes are not protected from the sun, they may become bloodshot and irritated, and the clear front covering of the eyes (the cornea) may become cloudy. In some people, the eyelashes fall out and the eyelids may be thin and turn abnormally inward or outward. In addition to an increased risk of eye cancer, xeroderma pigmentosum is associated with noncancerous growths on the eye. Many of these eye abnormalities can impair vision.  About 30 percent of people with xeroderma pigmentosum develop progressive neurological abnormalities in addition to problems involving the skin and eyes. These abnormalities can include hearing loss, poor coordination, difficulty walking, movement problems, loss of intellectual function, difficulty swallowing and talking, and seizures. When these neurological problems occur, they tend to worsen with time.  Researchers have identified at least eight inherited forms of xeroderma pigmentosum: complementation group A (XP-A) through complementation group G (XP-G) plus a variant type (XP-V). The types are distinguished by their genetic cause. All of the types increase skin cancer risk, although some are more likely than others to be associated with neurological abnormalities.",xeroderma pigmentosum,0001066,GHR,https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum,C0043346,T019,Disorders
How many people are affected by xeroderma pigmentosum ?,0001066-2,frequency,"Xeroderma pigmentosum is a rare disorder; it is estimated to affect about 1 in 1 million people in the United States and Europe. The condition is more common in Japan, North Africa, and the Middle East.",xeroderma pigmentosum,0001066,GHR,https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum,C0043346,T019,Disorders
What are the genetic changes related to xeroderma pigmentosum ?,0001066-3,genetic changes,"Xeroderma pigmentosum is caused by mutations in genes that are involved in repairing damaged DNA. DNA can be damaged by UV rays from the sun and by toxic chemicals such as those found in cigarette smoke. Normal cells are usually able to fix DNA damage before it causes problems. However, in people with xeroderma pigmentosum, DNA damage is not repaired normally. As more abnormalities form in DNA, cells malfunction and eventually become cancerous or die.  Many of the genes related to xeroderma pigmentosum are part of a DNA-repair process known as nucleotide excision repair (NER). The proteins produced from these genes play a variety of roles in this process. They recognize DNA damage, unwind regions of DNA where the damage has occurred, snip out (excise) the abnormal sections, and replace the damaged areas with the correct DNA. Inherited abnormalities in the NER-related genes prevent cells from carrying out one or more of these steps. The POLH gene also plays a role in protecting cells from UV-induced DNA damage, although it is not involved in NER; mutations in this gene cause the variant type of xeroderma pigmentosum.  The major features of xeroderma pigmentosum result from a buildup of unrepaired DNA damage. When UV rays damage genes that control cell growth and division, cells can either die or grow too fast and in an uncontrolled way. Unregulated cell growth can lead to the development of cancerous tumors. Neurological abnormalities are also thought to result from an accumulation of DNA damage, although the brain is not exposed to UV rays. Researchers suspect that other factors damage DNA in nerve cells. It is unclear why some people with xeroderma pigmentosum develop neurological abnormalities and others do not.  Inherited mutations in at least eight genes have been found to cause xeroderma pigmentosum. More than half of all cases in the United States result from mutations in the XPC, ERCC2, or POLH genes. Mutations in the other genes generally account for a smaller percentage of cases.",xeroderma pigmentosum,0001066,GHR,https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum,C0043346,T019,Disorders
Is xeroderma pigmentosum inherited ?,0001066-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",xeroderma pigmentosum,0001066,GHR,https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum,C0043346,T019,Disorders
What are the treatments for xeroderma pigmentosum ?,0001066-5,treatment,"These resources address the diagnosis or management of xeroderma pigmentosum:  - American Cancer Society: How are Squamous and Basal Cell Skin Cancer Diagnosed?  - American Cancer Society: How is Melanoma Diagnosed?  - Gene Review: Gene Review: Xeroderma Pigmentosum  - Genetic Testing Registry: Xeroderma pigmentosum  - Genetic Testing Registry: Xeroderma pigmentosum, complementation group b  - Genetic Testing Registry: Xeroderma pigmentosum, group C  - Genetic Testing Registry: Xeroderma pigmentosum, group D  - Genetic Testing Registry: Xeroderma pigmentosum, group E  - Genetic Testing Registry: Xeroderma pigmentosum, group F  - Genetic Testing Registry: Xeroderma pigmentosum, group G  - Genetic Testing Registry: Xeroderma pigmentosum, type 1  - Genetic Testing Registry: Xeroderma pigmentosum, variant type  - MedlinePlus Encyclopedia: Xeroderma Pigmentosum  - National Cancer Institute: Melanoma Treatment  - National Cancer Institute: Skin Cancer Treatment  - Xeroderma Pigmentosum Society, Inc.: Beta Carotene  - Xeroderma Pigmentosum Society, Inc.: Ultraviolet Radiation and Protection   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",xeroderma pigmentosum,0001066,GHR,https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum,C0043346,T019,Disorders
What is (are) Y chromosome infertility ?,0001067-1,information,"Y chromosome infertility is a condition that affects the production of sperm, making it difficult or impossible for affected men to father children. An affected man's body may produce no sperm cells (azoospermia), a smaller than usual number of sperm cells (oligospermia), or sperm cells that are abnormally shaped or that do not move properly.  Some men with Y chromosome infertility who have mild to moderate oligospermia may eventually father a child naturally. Assisted reproductive technologies may help other affected men; most men with Y chromosome infertility have some sperm cells in the testes that can be extracted for this purpose. The most severely affected men do not have any mature sperm cells in the testes. This form of Y chromosome infertility is called Sertoli cell-only syndrome.  Men with Y chromosome infertility usually do not have any other signs or symptoms. Occasionally they may have unusually small testes or undescended testes (cryptorchidism).",Y chromosome infertility,0001067,GHR,https://ghr.nlm.nih.gov/condition/y-chromosome-infertility,C3711648,T047,Disorders
How many people are affected by Y chromosome infertility ?,0001067-2,frequency,"Y chromosome infertility occurs in approximately 1 in 2,000 to 1 in 3,000 males of all ethnic groups. This condition accounts for between 5 percent and 10 percent of cases of azoospermia or severe oligospermia.",Y chromosome infertility,0001067,GHR,https://ghr.nlm.nih.gov/condition/y-chromosome-infertility,C3711648,T047,Disorders
What are the genetic changes related to Y chromosome infertility ?,0001067-3,genetic changes,"As its name suggests, this form of infertility is caused by changes in the Y chromosome. People normally have 46 chromosomes in each cell. Two of the 46 chromosomes are sex chromosomes, called X and Y. Females have two X chromosomes (46,XX), and males have one X chromosome and one Y chromosome (46,XY). Because only males have the Y chromosome, the genes on this chromosome tend to be involved in male sex determination and development.  Y chromosome infertility is usually caused by deletions of genetic material in regions of the Y chromosome called azoospermia factor (AZF) A, B, or C. Genes in these regions are believed to provide instructions for making proteins involved in sperm cell development, although the specific functions of these proteins are not well understood.  Deletions in the AZF regions may affect several genes. The missing genetic material likely prevents production of a number of proteins needed for normal sperm cell development, resulting in Y chromosome infertility.  In rare cases, changes to a single gene called USP9Y, which is located in the AZFA region of the Y chromosome, can cause Y chromosome infertility. The USP9Y gene provides instructions for making a protein called ubiquitin-specific protease 9. A small number of individuals with Y chromosome infertility have deletions of all or part of the USP9Y gene, while other genes in the AZF regions are unaffected. Deletions in the USP9Y gene prevent the production of ubiquitin-specific protease 9 or result in the production of an abnormally short, nonfunctional protein. The absence of functional ubiquitin-specific protease 9 impairs the production of sperm cells, resulting in Y chromosome infertility.",Y chromosome infertility,0001067,GHR,https://ghr.nlm.nih.gov/condition/y-chromosome-infertility,C3711648,T047,Disorders
Is Y chromosome infertility inherited ?,0001067-4,inheritance,"Because Y chromosome infertility impedes the ability to father children, this condition is usually caused by new deletions on the Y chromosome and occurs in men with no history of the disorder in their family. When men with Y chromosome infertility do father children, either naturally or with the aid of assisted reproductive technologies, they pass on the genetic changes on the Y chromosome to all their sons. As a result, the sons will also have Y chromosome infertility. This form of inheritance is called Y-linked. Daughters, who do not inherit the Y chromosome, are not affected.",Y chromosome infertility,0001067,GHR,https://ghr.nlm.nih.gov/condition/y-chromosome-infertility,C3711648,T047,Disorders
What are the treatments for Y chromosome infertility ?,0001067-5,treatment,"These resources address the diagnosis or management of Y chromosome infertility:  - Gene Review: Gene Review: Y Chromosome Infertility  - Genetic Testing Registry: Spermatogenic failure, Y-linked 2  - Genetic Testing Registry: Spermatogenic failure, Y-linked, 1  - MedlinePlus Encyclopedia: Semen Analysis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Y chromosome infertility,0001067,GHR,https://ghr.nlm.nih.gov/condition/y-chromosome-infertility,C3711648,T047,Disorders
What is (are) ZAP70-related severe combined immunodeficiency ?,0001068-1,information,"ZAP70-related severe combined immunodeficiency (SCID) is an inherited disorder that damages the immune system. ZAP70-related SCID is one of several forms of severe combined immunodeficiency, a group of disorders with several genetic causes. Children with SCID lack virtually all immune protection from bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. Often the organisms that cause infection in people with this disorder are described as opportunistic because they ordinarily do not cause illness in healthy people. Infants with SCID typically experience pneumonia, chronic diarrhea, and widespread skin rashes. They also grow much more slowly than healthy children. If not treated in a way that restores immune function, children with SCID usually live only a year or two.  Most individuals with ZAP70-related SCID are diagnosed in the first 6 months of life. At least one individual first showed signs of the condition later in childhood and had less severe symptoms, primarily recurrent respiratory and skin infections.",ZAP70-related severe combined immunodeficiency,0001068,GHR,https://ghr.nlm.nih.gov/condition/zap70-related-severe-combined-immunodeficiency,C0085110,T047,Disorders
How many people are affected by ZAP70-related severe combined immunodeficiency ?,0001068-2,frequency,"ZAP70-related SCID is a rare disorder. Only about 20 affected individuals have been identified. The prevalence of SCID from all genetic causes combined is approximately 1 in 50,000.",ZAP70-related severe combined immunodeficiency,0001068,GHR,https://ghr.nlm.nih.gov/condition/zap70-related-severe-combined-immunodeficiency,C0085110,T047,Disorders
What are the genetic changes related to ZAP70-related severe combined immunodeficiency ?,0001068-3,genetic changes,"As the name indicates, this condition is caused by mutations in the ZAP70 gene. The ZAP70 gene provides instructions for making a protein called zeta-chain-associated protein kinase. This protein is part of a signaling pathway that directs the development of and turns on (activates) immune system cells called T cells. T cells identify foreign substances and defend the body against infection.  The ZAP70 gene is important for the development and function of several types of T cells. These include cytotoxic T cells (CD8+ T cells), whose functions include destroying cells infected by viruses. The ZAP70 gene is also involved in the activation of helper T cells (CD4+ T cells). These cells direct and assist the functions of the immune system by influencing the activities of other immune system cells.  Mutations in the ZAP70 gene prevent the production of zeta-chain-associated protein kinase or result in a protein that is unstable and cannot perform its function. A loss of functional zeta-chain-associated protein kinase leads to the absence of CD8+ T cells and an excess of inactive CD4+ T cells. The resulting shortage of active T cells causes people with ZAP70-related SCID to be more susceptible to infection.",ZAP70-related severe combined immunodeficiency,0001068,GHR,https://ghr.nlm.nih.gov/condition/zap70-related-severe-combined-immunodeficiency,C0085110,T047,Disorders
Is ZAP70-related severe combined immunodeficiency inherited ?,0001068-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",ZAP70-related severe combined immunodeficiency,0001068,GHR,https://ghr.nlm.nih.gov/condition/zap70-related-severe-combined-immunodeficiency,C0085110,T047,Disorders
What are the treatments for ZAP70-related severe combined immunodeficiency ?,0001068-5,treatment,"These resources address the diagnosis or management of ZAP70-related severe combined immunodeficiency:  - Baby's First Test: Severe Combined Immunodeficiency  - Gene Review: Gene Review: ZAP70-Related Severe Combined Immunodeficiency  - Genetic Testing Registry: Severe combined immunodeficiency, atypical   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",ZAP70-related severe combined immunodeficiency,0001068,GHR,https://ghr.nlm.nih.gov/condition/zap70-related-severe-combined-immunodeficiency,C0085110,T047,Disorders
What is (are) Zellweger spectrum disorder ?,0001069-1,information,"Zellweger spectrum disorder is a group of conditions that have overlapping signs and symptoms and affect many parts of the body. This group of conditions includes Zellweger syndrome, neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease. These conditions were once thought to be distinct disorders but are now considered to be part of the same condition spectrum. Zellweger syndrome is the most severe form of the Zellweger spectrum disorder, NALD is intermediate in severity, and infantile Refsum disease is the least severe form. Because these three conditions are now considered one disorder, some researchers prefer not to use the separate condition names but to instead refer to cases as severe, intermediate, or mild.  Individuals with Zellweger syndrome, at the severe end of the spectrum, develop signs and symptoms of the condition during the newborn period. These infants experience weak muscle tone (hypotonia), feeding problems, hearing and vision loss, and seizures. These problems are caused by the breakdown of myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. The part of the brain and spinal cord that contains myelin is called white matter. Destruction of myelin (demyelination) leads to loss of white matter (leukodystrophy). Children with Zellweger syndrome also develop life-threatening problems in other organs and tissues, such as the liver, heart, and kidneys. They may have skeletal abnormalities, including a large space between the bones of the skull (fontanels) and characteristic bone spots known as chondrodysplasia punctata that can be seen on x-ray. Affected individuals have distinctive facial features, including a flattened face, broad nasal bridge, and high forehead. Children with Zellweger syndrome typically do not survive beyond the first year of life.  People with NALD or infantile Refsum disease, which are at the less-severe end of the spectrum, have more variable features than those with Zellweger syndrome and usually do not develop signs and symptoms of the disease until late infancy or early childhood. They may have many of the features of Zellweger syndrome; however, their condition typically progresses more slowly. Children with these less-severe conditions often have hypotonia, vision problems, hearing loss, liver dysfunction, developmental delay, and some degree of intellectual disability. Most people with NALD survive into childhood, and those with infantile Refsum disease may reach adulthood. In rare cases, individuals at the mildest end of the condition spectrum have developmental delay in childhood and hearing loss or vision problems beginning in adulthood and do not develop the other features of this disorder.",Zellweger spectrum disorder,0001069,GHR,https://ghr.nlm.nih.gov/condition/zellweger-spectrum-disorder,C3658299,T047,Disorders
How many people are affected by Zellweger spectrum disorder ?,0001069-2,frequency,"Zellweger spectrum disorder is estimated to occur in 1 in 50,000 individuals.",Zellweger spectrum disorder,0001069,GHR,https://ghr.nlm.nih.gov/condition/zellweger-spectrum-disorder,C3658299,T047,Disorders
What are the genetic changes related to Zellweger spectrum disorder ?,0001069-3,genetic changes,"Mutations in at least 12 genes have been found to cause Zellweger spectrum disorder. These genes provide instructions for making a group of proteins known as peroxins, which are essential for the formation and normal functioning of cell structures called peroxisomes. Peroxisomes are sac-like compartments that contain enzymes needed to break down many different substances, including fatty acids and certain toxic compounds. They are also important for the production of fats (lipids) used in digestion and in the nervous system. Peroxins assist in the formation (biogenesis) of peroxisomes by producing the membrane that separates the peroxisome from the rest of the cell and by importing enzymes into the peroxisome.  Mutations in the genes that cause Zellweger spectrum disorder prevent peroxisomes from forming normally. Diseases that disrupt the formation of peroxisomes, including Zellweger spectrum disorder, are called peroxisome biogenesis disorders. If the production of peroxisomes is altered, these structures cannot perform their usual functions. The signs and symptoms of Zellweger syndrome are due to the absence of functional peroxisomes within cells. NALD and infantile Refsum disease are caused by mutations that allow some peroxisomes to form.  Mutations in the PEX1 gene are the most common cause of Zellweger spectrum disorder and are found in nearly 70 percent of affected individuals. The other genes associated with Zellweger spectrum disorder each account for a smaller percentage of cases of this condition.",Zellweger spectrum disorder,0001069,GHR,https://ghr.nlm.nih.gov/condition/zellweger-spectrum-disorder,C3658299,T047,Disorders
Is Zellweger spectrum disorder inherited ?,0001069-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",Zellweger spectrum disorder,0001069,GHR,https://ghr.nlm.nih.gov/condition/zellweger-spectrum-disorder,C3658299,T047,Disorders
What are the treatments for Zellweger spectrum disorder ?,0001069-5,treatment,"These resources address the diagnosis or management of Zellweger spectrum disorder:  - Gene Review: Gene Review: Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum  - Genetic Testing Registry: Infantile Refsum's disease  - Genetic Testing Registry: Neonatal adrenoleucodystrophy  - Genetic Testing Registry: Peroxisome biogenesis disorders, Zellweger syndrome spectrum  - Genetic Testing Registry: Zellweger syndrome  - MedlinePlus Encyclopedia: Seizures   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",Zellweger spectrum disorder,0001069,GHR,https://ghr.nlm.nih.gov/condition/zellweger-spectrum-disorder,C3658299,T047,Disorders
What is (are) 15q13.3 microdeletion ?,0001070-1,information,"15q13.3 microdeletion is a chromosomal change in which a small piece of chromosome 15 is deleted in each cell. The deletion occurs on the long (q) arm of the chromosome at a position designated q13.3. This chromosomal change increases the risk of intellectual disability, seizures, behavioral problems, and psychiatric disorders. However, some people with a 15q13.3 microdeletion do not appear to have any associated features.  About half of all people with a 15q13.3 microdeletion have learning difficulties or intellectual disability, which is usually mild or moderate. Many of these individuals have delayed speech and language skills. 15q13.3 microdeletion also appears to be a major risk factor for recurrent seizures (epilepsy); about one-third of people with this chromosomal change have epilepsy.  15q13.3 microdeletion has also been associated with behavioral problems, including a short attention span, aggression, impulsive behavior, and hyperactivity. Some people with a 15q13.3 microdeletion have been diagnosed with developmental disorders that affect communication and social interaction (autism spectrum disorders). This chromosomal change may also be associated with an increased risk of psychiatric disorders, particularly schizophrenia. Other signs and symptoms of 15q13.3 microdeletion can include heart defects, minor abnormalities involving the hands and arms, and subtle differences in facial features.  Some people with a 15q13.3 microdeletion do not have any of the intellectual, behavioral, or physical features described above. In these individuals, the microdeletion is often detected when they undergo genetic testing because they have an affected relative. It is unknown why a 15q13.3 microdeletion causes cognitive and behavioral problems in some individuals but few or no health problems in others.",15q13.3 microdeletion,0001070,GHR,https://ghr.nlm.nih.gov/condition/15q133-microdeletion,C2677613,T019,Disorders
How many people are affected by 15q13.3 microdeletion ?,0001070-2,frequency,"15q13.3 microdeletion likely occurs in about 1 in 40,000 people in the general population. It appears to be more common in people with intellectual disability, epilepsy, schizophrenia, or autism spectrum disorders.",15q13.3 microdeletion,0001070,GHR,https://ghr.nlm.nih.gov/condition/15q133-microdeletion,C2677613,T019,Disorders
What are the genetic changes related to 15q13.3 microdeletion ?,0001070-3,genetic changes,"Most people with a 15q13.3 microdeletion are missing a sequence of about 2 million DNA building blocks (base pairs), also written as 2 megabases (Mb), at position q13.3 on chromosome 15. The exact size of the deleted region varies, but it typically contains at least six genes. This deletion usually affects one of the two copies of chromosome 15 in each cell.  The signs and symptoms that can result from a 15q13.3 microdeletion are probably related to the loss of one or more genes in this region. However, it is unclear which missing genes contribute to the specific features of the disorder. Because some people with a 15q13.3 microdeletion have no obvious signs or symptoms, researchers believe that other genetic or environmental factors may also be involved.",15q13.3 microdeletion,0001070,GHR,https://ghr.nlm.nih.gov/condition/15q133-microdeletion,C2677613,T019,Disorders
Is 15q13.3 microdeletion inherited ?,0001070-4,inheritance,"15q13.3 microdeletion is inherited in an autosomal dominant pattern, which means one copy of the deleted region on chromosome 15 in each cell is sufficient to increase the risk of intellectual disability and other characteristic features.  In about 75 percent of cases, individuals with 15q13.3 microdeletion inherit the chromosomal change from a parent. In the remaining cases, 15q13.3 microdeletion occurs in people whose parents do not carry the chromosomal change. In these individuals, the deletion occurs most often as a random event during the formation of reproductive cells (eggs and sperm) or in early fetal development.",15q13.3 microdeletion,0001070,GHR,https://ghr.nlm.nih.gov/condition/15q133-microdeletion,C2677613,T019,Disorders
What are the treatments for 15q13.3 microdeletion ?,0001070-5,treatment,These resources address the diagnosis or management of 15q13.3 microdeletion:  - Gene Review: Gene Review: 15q13.3 Microdeletion  - Genetic Testing Registry: 15q13.3 microdeletion syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,15q13.3 microdeletion,0001070,GHR,https://ghr.nlm.nih.gov/condition/15q133-microdeletion,C2677613,T019,Disorders
What is (are) 15q24 microdeletion ?,0001071-1,information,"15q24 microdeletion is a chromosomal change in which a small piece of chromosome 15 is deleted in each cell. The deletion occurs on the long (q) arm of the chromosome at a position designated q24.  15q24 microdeletion is associated with mild to moderate intellectual disability and delayed speech development. Other common signs and symptoms include short stature, weak muscle tone (hypotonia), and skeletal abnormalities including loose (lax) joints. Affected males may have genital abnormalities, which can include an unusually small penis (micropenis) and the opening of the urethra on the underside of the penis (hypospadias). Affected individuals also have distinctive facial features such as a high front hairline, broad eyebrows, widely set eyes (hypertelorism), outside corners of the eyes that point downward (downslanting palpebral fissures), a broad nasal bridge, a full lower lip, and a long, smooth space between the upper lip and nose (philtrum).",15q24 microdeletion,0001071,GHR,https://ghr.nlm.nih.gov/condition/15q24-microdeletion,C3697269,T019,Disorders
How many people are affected by 15q24 microdeletion ?,0001071-2,frequency,This condition is very rare; only a few dozen affected individuals have been identified.,15q24 microdeletion,0001071,GHR,https://ghr.nlm.nih.gov/condition/15q24-microdeletion,C3697269,T019,Disorders
What are the genetic changes related to 15q24 microdeletion ?,0001071-3,genetic changes,"People with a 15q24 microdeletion are missing between 1.7 million and 6.1 million DNA building blocks (base pairs), also written as 1.7-6.1 megabases (Mb), at position q24 on chromosome 15. The exact size of the deletion varies, but all individuals are missing the same 1.2 Mb region. This region contains several genes that are thought to be important for normal development.  The signs and symptoms that result from a 15q24 microdeletion are probably related to the loss of one or more genes in the deleted region. However, it is unclear which missing genes contribute to the specific features of the disorder.",15q24 microdeletion,0001071,GHR,https://ghr.nlm.nih.gov/condition/15q24-microdeletion,C3697269,T019,Disorders
Is 15q24 microdeletion inherited ?,0001071-4,inheritance,The identified cases of 15q24 microdeletion have occurred in people with no history of the condition in their family. The chromosomal change likely occurs as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development.,15q24 microdeletion,0001071,GHR,https://ghr.nlm.nih.gov/condition/15q24-microdeletion,C3697269,T019,Disorders
What are the treatments for 15q24 microdeletion ?,0001071-5,treatment,These resources address the diagnosis or management of 15q24 microdeletion:  - Gene Review: Gene Review: 15q24 Microdeletion  - Genetic Testing Registry: 15q24 deletion syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,15q24 microdeletion,0001071,GHR,https://ghr.nlm.nih.gov/condition/15q24-microdeletion,C3697269,T019,Disorders
What is (are) 16p11.2 deletion syndrome ?,0001072-1,information,"16p11.2 deletion syndrome is a disorder caused by a deletion of a small piece of chromosome 16. The deletion occurs near the middle of the chromosome at a location designated p11.2.  People with 16p11.2 deletion syndrome usually have developmental delay and intellectual disability. Most also have at least some features of autism spectrum disorders. These disorders are characterized by impaired communication and socialization skills, as well as delayed development of speech and language. In 16p11.2 deletion syndrome, expressive language skills (vocabulary and the production of speech) are generally more severely affected than receptive language skills (the ability to understand speech). Some people with this disorder have recurrent seizures (epilepsy).  Some affected individuals have minor physical abnormalities such as low-set ears or partially webbed toes (partial syndactyly). People with this disorder are also at increased risk of obesity compared with the general population. However, there is no particular pattern of physical abnormalities that characterizes 16p11.2 deletion syndrome. Signs and symptoms of the disorder vary even among affected members of the same family. Some people with the deletion have no identified physical, intellectual, or behavioral abnormalities.",16p11.2 deletion syndrome,0001072,GHR,https://ghr.nlm.nih.gov/condition/16p112-deletion-syndrome,C3697355,T019,Disorders
How many people are affected by 16p11.2 deletion syndrome ?,0001072-2,frequency,"Most people tested for the 16p11.2 deletion have come to medical attention as a result of developmental delay or autistic behaviors. Other individuals with the 16p11.2 deletion have no associated health or behavioral problems, and so the deletion may never be detected. For this reason, the prevalence of this deletion in the general population is difficult to determine but has been estimated at approximately 3 in 10,000.",16p11.2 deletion syndrome,0001072,GHR,https://ghr.nlm.nih.gov/condition/16p112-deletion-syndrome,C3697355,T019,Disorders
What are the genetic changes related to 16p11.2 deletion syndrome ?,0001072-3,genetic changes,"People with 16p11.2 deletion syndrome are missing a sequence of about 600,000 DNA building blocks (base pairs), also written as 600 kilobases (kb), at position p11.2 on chromosome 16. This deletion affects one of the two copies of chromosome 16 in each cell. The 600 kb region contains more than 25 genes, and in many cases little is known about their function. Researchers are working to determine how the missing genes contribute to the features of 16p11.2 deletion syndrome.",16p11.2 deletion syndrome,0001072,GHR,https://ghr.nlm.nih.gov/condition/16p112-deletion-syndrome,C3697355,T019,Disorders
Is 16p11.2 deletion syndrome inherited ?,0001072-4,inheritance,"16p11.2 deletion syndrome is considered to have an autosomal dominant inheritance pattern because a deletion in one copy of chromosome 16 in each cell is sufficient to cause the condition. However, most cases of 16p11.2 deletion syndrome are not inherited. The deletion occurs most often as a random event during the formation of reproductive cells (eggs and sperm) or in early fetal development. Affected people typically have no history of the disorder in their family, although they can pass the condition to their children. Several examples of inherited 16p11.2 deletion have been reported. In inherited cases, other family members may be affected as well.",16p11.2 deletion syndrome,0001072,GHR,https://ghr.nlm.nih.gov/condition/16p112-deletion-syndrome,C3697355,T019,Disorders
What are the treatments for 16p11.2 deletion syndrome ?,0001072-5,treatment,"These resources address the diagnosis or management of 16p11.2 deletion syndrome:  - Gene Review: Gene Review: 16p11.2 Recurrent Microdeletion  - Genetic Testing Registry: 16p11.2 deletion syndrome  - Genetic Testing Registry: Autism, susceptibility to, 14a   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",16p11.2 deletion syndrome,0001072,GHR,https://ghr.nlm.nih.gov/condition/16p112-deletion-syndrome,C3697355,T019,Disorders
"What is (are) 17 alpha-hydroxylase/17,20-lyase deficiency ?",0001074-1,information,"17 alpha()-hydroxylase/17,20-lyase deficiency is a condition that affects the function of certain hormone-producing glands called the gonads (ovaries in females and testes in males) and the adrenal glands. The gonads direct sexual development before birth and during puberty and are important for reproduction. The adrenal glands, which are located on top of the kidneys, regulate the production of certain hormones, including those that control salt levels in the body. People with 17-hydroxylase/17,20-lyase deficiency have an imbalance of many of the hormones that are made in these glands. 17-hydroxylase/17,20-lyase deficiency is one of a group of disorders, known as congenital adrenal hyperplasias, that impair hormone production and disrupt sexual development and maturation.  Hormone imbalances lead to the characteristic signs and symptoms of 17-hydroxylase/17,20-lyase deficiency, which include high blood pressure (hypertension), low levels of potassium in the blood (hypokalemia), and abnormal sexual development. The severity of the features varies. Two forms of the condition are recognized: complete 17-hydroxylase/17,20-lyase deficiency, which is more severe, and partial 17-hydroxylase/17,20-lyase deficiency, which is typically less so.  Males and females are affected by disruptions to sexual development differently. Females (who have two X chromosomes) with 17-hydroxylase/17,20-lyase deficiency are born with normal external female genitalia; however, the internal reproductive organs, including the uterus and ovaries, may be underdeveloped. Women with complete 17-hydroxylase/17,20-lyase deficiency do not develop secondary sex characteristics, such as breasts and pubic hair, and do not menstruate (amenorrhea). Women with partial 17-hydroxylase/17,20-lyase deficiency may develop some secondary sex characteristics; menstruation is typically irregular or absent. Either form of the disorder results in an inability to conceive a baby (infertility).  In affected individuals who are chromosomally male (having an X and a Y chromosome), problems with sexual development lead to abnormalities of the external genitalia. The most severely affected are born with characteristically female external genitalia and are generally raised as females. However, because they do not have female internal reproductive organs, these individuals have amenorrhea and do not develop female secondary sex characteristics. These individuals have testes, but they are abnormally located in the abdomen (undescended). Sometimes, complete 17-hydroxylase/17,20-lyase deficiency leads to external genitalia that do not look clearly male or clearly female (ambiguous genitalia). Males with partial 17-hydroxylase/17,20-lyase deficiency usually have abnormal male genitalia, such as a small penis (micropenis), the opening of the urethra on the underside of the penis (hypospadias), or a scrotum divided into two lobes (bifid scrotum). Males with either complete or partial 17-hydroxylase/17,20-lyase deficiency are also infertile.","17 alpha-hydroxylase/17,20-lyase deficiency",0001074,GHR,https://ghr.nlm.nih.gov/condition/17-alpha-hydroxylase-17-20-lyase-deficiency,C1291557,T047,Disorders
"How many people are affected by 17 alpha-hydroxylase/17,20-lyase deficiency ?",0001074-2,frequency,"17-hydroxylase/17,20-lyase deficiency accounts for about 1 percent of congenital adrenal hyperplasia cases. It is estimated to occur in 1 in 1 million people worldwide.","17 alpha-hydroxylase/17,20-lyase deficiency",0001074,GHR,https://ghr.nlm.nih.gov/condition/17-alpha-hydroxylase-17-20-lyase-deficiency,C1291557,T047,Disorders
"What are the genetic changes related to 17 alpha-hydroxylase/17,20-lyase deficiency ?",0001074-3,genetic changes,"17-hydroxylase/17,20-lyase deficiency is caused by mutations in the CYP17A1 gene. The protein produced from this gene is involved in the formation of steroid hormones. This group of hormones includes sex hormones such as testosterone and estrogen, which are needed for normal sexual development and reproduction; mineralocorticoids, which help regulate the body's salt and water balance; and glucocorticoids, which are involved in maintaining blood sugar levels and regulating the body's response to stress.  Steroid hormones are produced through a series of chemical reactions. The CYP17A1 enzyme performs two important reactions in this process. The enzyme has 17 alpha()-hydroxylase activity, which is important for production of glucocorticoids and sex hormones. CYP17A1 also has 17,20-lyase activity, which is integral to the production of sex hormones.  17-hydroxylase/17,20-lyase deficiency results from a shortage (deficiency) of both enzyme activities. The amount of remaining enzyme activity determines whether a person will have the complete or partial form of the disorder. Individuals with the complete form have CYP17A1 gene mutations that result in the production of an enzyme with very little or no 17-hydroxylase and 17,20-lyase activity. People with the partial form of this condition have CYP17A1 gene mutations that allow some enzyme activity, although at reduced levels.  With little or no 17-hydroxylase activity, production of glucocorticoids is impaired, and instead, mineralocorticoids are produced. An excess of these salt-regulating hormones leads to hypertension and hypokalemia.  Loss of 17,20-lyase activity impairs sex hormone production. Shortage of these hormones disrupts development of the reproductive system and impairs the onset of puberty in males and females with 17-hydroxylase/17,20-lyase deficiency.","17 alpha-hydroxylase/17,20-lyase deficiency",0001074,GHR,https://ghr.nlm.nih.gov/condition/17-alpha-hydroxylase-17-20-lyase-deficiency,C1291557,T047,Disorders
"Is 17 alpha-hydroxylase/17,20-lyase deficiency inherited ?",0001074-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.","17 alpha-hydroxylase/17,20-lyase deficiency",0001074,GHR,https://ghr.nlm.nih.gov/condition/17-alpha-hydroxylase-17-20-lyase-deficiency,C1291557,T047,Disorders
"What are the treatments for 17 alpha-hydroxylase/17,20-lyase deficiency ?",0001074-5,treatment,"These resources address the diagnosis or management of 17 alpha-hydroxylase/17,20-lyase deficiency:  - Genetic Testing Registry: Deficiency of steroid 17-alpha-monooxygenase   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","17 alpha-hydroxylase/17,20-lyase deficiency",0001074,GHR,https://ghr.nlm.nih.gov/condition/17-alpha-hydroxylase-17-20-lyase-deficiency,C1291557,T047,Disorders
What is (are) 17-beta hydroxysteroid dehydrogenase 3 deficiency ?,0001075-1,information,"17-beta hydroxysteroid dehydrogenase 3 deficiency is a condition that affects male sexual development. People with this condition are genetically male, with one X and one Y chromosome in each cell, and they have male gonads (testes). Their bodies, however, do not produce enough of the male sex hormone testosterone. Testosterone has a critical role in male sexual development, and a shortage of this hormone disrupts the formation of the external sex organs before birth.  Most people with 17-beta hydroxysteroid dehydrogenase 3 deficiency are born with external genitalia that appear female. In some cases, the external genitalia do not look clearly male or clearly female (sometimes called ambiguous genitalia). Still other affected infants have genitalia that appear predominantly male, often with an unusually small penis (micropenis) or the urethra opening on the underside of the penis (hypospadias).  During puberty, people with this condition develop some secondary sex characteristics, such as increased muscle mass, deepening of the voice, and development of male pattern body hair. The penis and scrotum (the sac of skin that holds the testes) grow larger during this period. In addition to these changes typical of adolescent boys, some affected males may also experience breast enlargement (gynecomastia). Men with this disorder are generally unable to father children (infertile).  Children with 17-beta hydroxysteroid dehydrogenase 3 deficiency are often raised as girls. About half of these individuals adopt a male gender role in adolescence or early adulthood.",17-beta hydroxysteroid dehydrogenase 3 deficiency,0001075,GHR,https://ghr.nlm.nih.gov/condition/17-beta-hydroxysteroid-dehydrogenase-3-deficiency,C0268296,T047,Disorders
How many people are affected by 17-beta hydroxysteroid dehydrogenase 3 deficiency ?,0001075-2,frequency,"17-beta hydroxysteroid dehydrogenase 3 deficiency is a rare disorder. Researchers have estimated that this condition occurs in approximately 1 in 147,000 newborns. It is more common in the Arab population of Gaza, where it affects 1 in 200 to 300 people.",17-beta hydroxysteroid dehydrogenase 3 deficiency,0001075,GHR,https://ghr.nlm.nih.gov/condition/17-beta-hydroxysteroid-dehydrogenase-3-deficiency,C0268296,T047,Disorders
What are the genetic changes related to 17-beta hydroxysteroid dehydrogenase 3 deficiency ?,0001075-3,genetic changes,"Mutations in the HSD17B3 gene cause 17-beta hydroxysteroid dehydrogenase 3 deficiency. The HSD17B3 gene provides instructions for making an enzyme called 17-beta hydroxysteroid dehydrogenase 3. This enzyme is active in the testes, where it helps to produce testosterone from a precursor hormone called androstenedione.  Mutations in the HSD17B3 gene result in a 17-beta hydroxysteroid dehydrogenase 3 enzyme with little or no activity, reducing testosterone production. A shortage of testosterone affects the development of the reproductive tract in the male fetus, resulting in the abnormalities in the external sex organs that occur in 17-beta hydroxysteroid dehydrogenase 3 deficiency.  At puberty, conversion of androstenedione to testosterone increases in various tissues of the body through processes involving other enzymes. The additional testosterone results in the development of male secondary sex characteristics in adolescents, including those with 17-beta dehydrogenase 3 deficiency.  A portion of the androstenedione is also converted to the female sex hormone estrogen. Since impairment of the conversion to testosterone in this disorder results in excess androstenedione in the body, a corresponding excess of estrogen may be produced, leading to breast enlargement in some affected individuals.",17-beta hydroxysteroid dehydrogenase 3 deficiency,0001075,GHR,https://ghr.nlm.nih.gov/condition/17-beta-hydroxysteroid-dehydrogenase-3-deficiency,C0268296,T047,Disorders
Is 17-beta hydroxysteroid dehydrogenase 3 deficiency inherited ?,0001075-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Individuals who are genetically male and have two copies of a mutated gene in each cell are affected by 17-beta hydroxysteroid dehydrogenase 3 deficiency. People with two mutations who are genetically female do not usually experience any signs and symptoms of this disorder.",17-beta hydroxysteroid dehydrogenase 3 deficiency,0001075,GHR,https://ghr.nlm.nih.gov/condition/17-beta-hydroxysteroid-dehydrogenase-3-deficiency,C0268296,T047,Disorders
What are the treatments for 17-beta hydroxysteroid dehydrogenase 3 deficiency ?,0001075-5,treatment,These resources address the diagnosis or management of 17-beta hydroxysteroid dehydrogenase 3 deficiency:  - Genetic Testing Registry: Testosterone 17-beta-dehydrogenase deficiency  - MedlinePlus Encyclopedia: Ambiguous Genitalia  - MedlinePlus Encyclopedia: Intersex   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,17-beta hydroxysteroid dehydrogenase 3 deficiency,0001075,GHR,https://ghr.nlm.nih.gov/condition/17-beta-hydroxysteroid-dehydrogenase-3-deficiency,C0268296,T047,Disorders
What is (are) 18q deletion syndrome ?,0001077-1,information,"18q deletion syndrome is a chromosomal condition that results when a piece of chromosome 18 is missing. The condition can lead to a wide variety of signs and symptoms among affected individuals.  Most people with 18q deletion syndrome have intellectual disability and delayed development that can range from mild to severe, but some affected individuals have normal intelligence and development. Seizures, hyperactivity, aggression, and autistic behaviors that affect communication and social interaction may also occur. Some people with 18q deletion syndrome have a loss of tissue called white matter in the brain and spinal cord (leukodystrophy), structural abnormalities of the brain, or an abnormally small head size (microcephaly).  Other features that are common in 18q deletion syndrome include short stature, weak muscle tone (hypotonia), narrow auditory canals leading to hearing loss, and limb abnormalities such as foot deformities and thumbs that are positioned unusually close to the wrist. Some affected individuals have mild facial differences such as deep-set eyes, a flat or sunken appearance of the middle of the face (midface hypoplasia), a wide mouth, and prominent ears; these features are often not noticeable except in a detailed medical evaluation. Eye movement disorders and other vision problems, genital abnormalities, heart disease, and skin problems may also occur in this disorder.",18q deletion syndrome,0001077,GHR,https://ghr.nlm.nih.gov/condition/18q-deletion-syndrome,C0432443,T049,Disorders
How many people are affected by 18q deletion syndrome ?,0001077-2,frequency,"18q deletion syndrome occurs in an estimated 1 in 40,000 newborns. This condition is found in people of all ethnic backgrounds.",18q deletion syndrome,0001077,GHR,https://ghr.nlm.nih.gov/condition/18q-deletion-syndrome,C0432443,T049,Disorders
What are the genetic changes related to 18q deletion syndrome ?,0001077-3,genetic changes,"18q deletion syndrome is caused by a deletion of genetic material from the long (q) arm of chromosome 18. This chromosomal change is written as 18q-. The size of the deletion and its location on the chromosome vary among affected individuals.  The signs and symptoms of 18q deletion syndrome, including the leukodystrophy that likely contributes to the neurological problems, are probably related to the loss of multiple genes on the long arm of chromosome 18. 18q deletion syndrome is often categorized into two types: individuals with deletions near the end of the long arm of chromosome 18 are said to have distal 18q deletion syndrome, and those with deletions in the part of the long arm near the center of chromosome 18 are said to have proximal 18q deletion syndrome. The signs and symptoms of these two types of the condition are overlapping, with certain features being more common in one form of the disorder than in the other. For example, hearing loss and heart abnormalities are more common in people with distal 18q deletion syndrome, while seizures occur more often in people with proximal 18q deletion syndrome. Researchers are working to determine how the loss of specific genes in these regions contributes to the various features of 18q deletion syndrome.",18q deletion syndrome,0001077,GHR,https://ghr.nlm.nih.gov/condition/18q-deletion-syndrome,C0432443,T049,Disorders
Is 18q deletion syndrome inherited ?,0001077-4,inheritance,"Most cases of 18q deletion syndrome are not inherited. The deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family.  In some cases, 18q deletion syndrome is inherited, usually from a mildly affected parent. The deletion can also be inherited from an unaffected parent who carries a chromosomal rearrangement called a balanced translocation, in which no genetic material is gained or lost. Individuals with a balanced translocation do not usually have any related health problems; however, the translocation can become unbalanced as it is passed to the next generation. Children who inherit an unbalanced translocation can have a chromosomal rearrangement with extra or missing genetic material. Individuals with 18q deletion syndrome who inherit an unbalanced translocation are missing genetic material from the long arm of chromosome 18, which results in the signs and symptoms of this disorder.",18q deletion syndrome,0001077,GHR,https://ghr.nlm.nih.gov/condition/18q-deletion-syndrome,C0432443,T049,Disorders
What are the treatments for 18q deletion syndrome ?,0001077-5,treatment,These resources address the diagnosis or management of 18q deletion syndrome:  - Gene Review: Gene Review: Leukodystrophy Overview  - University of Texas Chromosome 18 Clinical Research Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,18q deletion syndrome,0001077,GHR,https://ghr.nlm.nih.gov/condition/18q-deletion-syndrome,C0432443,T049,Disorders
What is (are) 1p36 deletion syndrome ?,0001078-1,information,"1p36 deletion syndrome is a disorder that typically causes severe intellectual disability. Most affected individuals do not speak, or speak only a few words. They may have temper tantrums, bite themselves, or exhibit other behavior problems. Most have structural abnormalities of the brain, and seizures occur in more than half of individuals with this disorder. Affected individuals usually have weak muscle tone (hypotonia) and swallowing difficulties (dysphagia).  People with 1p36 deletion syndrome have a small head that is also unusually short and wide in proportion to its size (microbrachycephaly). Affected individuals also have distinctive facial features including deep-set eyes with straight eyebrows; a sunken appearance of the middle of the face (midface hypoplasia); a broad, flat nose; a long area between the nose and mouth (philtrum); a pointed chin; and ears that are low-set, rotated backwards, and abnormally shaped.  People with 1p36 deletion syndrome may have vision or hearing problems. Some have abnormalities of the skeleton, heart, gastrointestinal system, kidneys, or genitalia.",1p36 deletion syndrome,0001078,GHR,https://ghr.nlm.nih.gov/condition/1p36-deletion-syndrome,C1442161,T049,Disorders
How many people are affected by 1p36 deletion syndrome ?,0001078-2,frequency,"1p36 deletion syndrome is believed to affect between 1 in 5,000 and 1 in 10,000 newborns. However, this may be an underestimate because some affected individuals are likely never diagnosed.",1p36 deletion syndrome,0001078,GHR,https://ghr.nlm.nih.gov/condition/1p36-deletion-syndrome,C1442161,T049,Disorders
What are the genetic changes related to 1p36 deletion syndrome ?,0001078-3,genetic changes,1p36 deletion syndrome is caused by a deletion of genetic material from a specific region in the short (p) arm of chromosome 1. The signs and symptoms of 1p36 deletion syndrome are probably related to the loss of multiple genes in this region. The size of the deletion varies among affected individuals.,1p36 deletion syndrome,0001078,GHR,https://ghr.nlm.nih.gov/condition/1p36-deletion-syndrome,C1442161,T049,Disorders
Is 1p36 deletion syndrome inherited ?,0001078-4,inheritance,"Most cases of 1p36 deletion syndrome are not inherited. They result from a chromosomal deletion that occurs as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family.  About 20 percent of people with 1p36 deletion syndrome inherit the chromosome with a deleted segment from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which no genetic material is gained or lost. Balanced translocations usually do not cause any health problems; however, they can become unbalanced as they are passed to the next generation. Children who inherit an unbalanced translocation can have a chromosomal rearrangement with extra or missing genetic material. Individuals with 1p36 deletion syndrome who inherit an unbalanced translocation are missing genetic material from the short arm of chromosome 1, which results in birth defects and other health problems characteristic of this disorder.",1p36 deletion syndrome,0001078,GHR,https://ghr.nlm.nih.gov/condition/1p36-deletion-syndrome,C1442161,T049,Disorders
What are the treatments for 1p36 deletion syndrome ?,0001078-5,treatment,These resources address the diagnosis or management of 1p36 deletion syndrome:  - Gene Review: Gene Review: 1p36 Deletion Syndrome  - Genetic Testing Registry: Chromosome 1p36 deletion syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,1p36 deletion syndrome,0001078,GHR,https://ghr.nlm.nih.gov/condition/1p36-deletion-syndrome,C1442161,T049,Disorders
What is (are) 1q21.1 microdeletion ?,0001079-1,information,"1q21.1 microdeletion is a chromosomal change in which a small piece of chromosome 1 is deleted in each cell. The deletion occurs on the long (q) arm of the chromosome in a region designated q21.1. This chromosomal change increases the risk of delayed development, intellectual disability, physical abnormalities, and neurological and psychiatric problems. However, some people with a 1q21.1 microdeletion do not appear to have any associated features.  About 75 percent of all children with a 1q21.1 microdeletion have delayed development, particularly affecting the development of motor skills such as sitting, standing, and walking. The intellectual disability and learning problems associated with this genetic change are usually mild.  Distinctive facial features can also be associated with 1q21.1 microdeletions. The changes are usually subtle and can include a prominent forehead; a large, rounded nasal tip; a long space between the nose and upper lip (philtrum); and a high, arched roof of the mouth (palate). Other common signs and symptoms of 1q21.1 microdeletions include an unusually small head (microcephaly), short stature, and eye problems such as clouding of the lenses (cataracts). Less frequently, 1q21.1 microdeletions are associated with heart defects, abnormalities of the genitalia or urinary system, bone abnormalities (particularly in the hands and feet), and hearing loss.  Neurological problems that have been reported in people with a 1q21.1 microdeletion include seizures and weak muscle tone (hypotonia). Psychiatric or behavioral problems affect a small percentage of people with this genetic change. These include developmental conditions called autism spectrum disorders that affect communication and social interaction, attention deficit hyperactivity disorder (ADHD), and sleep disturbances. Studies suggest that deletions of genetic material from the 1q21.1 region may also be risk factors for schizophrenia.  Some people with a 1q21.1 microdeletion do not have any of the intellectual, physical, or psychiatric features described above. In these individuals, the microdeletion is often detected when they undergo genetic testing because they have a relative with the chromosomal change. It is unknown why 1q21.1 microdeletions cause cognitive and physical changes in some individuals but few or no health problems in others, even within the same family.",1q21.1 microdeletion,0001079,GHR,https://ghr.nlm.nih.gov/condition/1q211-microdeletion,C2675897,T019,Disorders
How many people are affected by 1q21.1 microdeletion ?,0001079-2,frequency,1q21.1 microdeletion is a rare chromosomal change; only a few dozen individuals with this deletion have been reported in the medical literature.,1q21.1 microdeletion,0001079,GHR,https://ghr.nlm.nih.gov/condition/1q211-microdeletion,C2675897,T019,Disorders
What are the genetic changes related to 1q21.1 microdeletion ?,0001079-3,genetic changes,"Most people with a 1q21.1 microdeletion are missing a sequence of about 1.35 million DNA building blocks (base pairs), also written as 1.35 megabases (Mb), in the q21.1 region of chromosome 1. However, the exact size of the deleted region varies. This deletion affects one of the two copies of chromosome 1 in each cell.  The signs and symptoms that can result from a 1q21.1 microdeletion are probably related to the loss of several genes in this region. Researchers are working to determine which missing genes contribute to the specific features associated with the deletion. Because some people with a 1q21.1 microdeletion have no obvious related features, additional genetic or environmental factors are thought to be involved in the development of signs and symptoms.  Researchers sometimes refer to 1q21.1 microdeletion as the recurrent distal 1.35-Mb deletion to distinguish it from the genetic change that causes thrombocytopenia-absent radius syndrome (TAR syndrome). TAR syndrome results from the deletion of a different, smaller DNA segment in the chromosome 1q21.1 region near the area where the 1.35-Mb deletion occurs. The chromosomal change related to TAR syndrome is often called the 200-kb deletion.",1q21.1 microdeletion,0001079,GHR,https://ghr.nlm.nih.gov/condition/1q211-microdeletion,C2675897,T019,Disorders
Is 1q21.1 microdeletion inherited ?,0001079-4,inheritance,"1q21.1 microdeletion is inherited in an autosomal dominant pattern, which means that missing genetic material from one of the two copies of chromosome 1 in each cell is sufficient to increase the risk of delayed development, intellectual disability, and other signs and symptoms.  In at least half of cases, individuals with a 1q21.1 microdeletion inherit the chromosomal change from a parent. In general, parents who carry a 1q21.1 microdeletion have milder signs and symptoms than their children who inherit the deletion, even though the deletion is the same size. About one-quarter of these parents have no associated features.  A 1q21.1 microdeletion can also occur in people whose parents do not carry the chromosomal change. In this situation, the deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) in a parent or in early embryonic development.",1q21.1 microdeletion,0001079,GHR,https://ghr.nlm.nih.gov/condition/1q211-microdeletion,C2675897,T019,Disorders
What are the treatments for 1q21.1 microdeletion ?,0001079-5,treatment,These resources address the diagnosis or management of 1q21.1 microdeletion:  - Gene Review: Gene Review: 1q21.1 Recurrent Microdeletion  - Genetic Testing Registry: 1q21.1 recurrent microdeletion   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,1q21.1 microdeletion,0001079,GHR,https://ghr.nlm.nih.gov/condition/1q211-microdeletion,C2675897,T019,Disorders
What is (are) 2-hydroxyglutaric aciduria ?,0001081-1,information,"2-hydroxyglutaric aciduria is a condition that causes progressive damage to the brain. The major types of this disorder are called D-2-hydroxyglutaric aciduria (D-2-HGA), L-2-hydroxyglutaric aciduria (L-2-HGA), and combined D,L-2-hydroxyglutaric aciduria (D,L-2-HGA).  The main features of D-2-HGA are delayed development, seizures, weak muscle tone (hypotonia), and abnormalities in the largest part of the brain (the cerebrum), which controls many important functions such as muscle movement, speech, vision, thinking, emotion, and memory. Researchers have described two subtypes of D-2-HGA, type I and type II. The two subtypes are distinguished by their genetic cause and pattern of inheritance, although they also have some differences in signs and symptoms. Type II tends to begin earlier and often causes more severe health problems than type I. Type II may also be associated with a weakened and enlarged heart (cardiomyopathy), a feature that is typically not found with type I.  L-2-HGA particularly affects a region of the brain called the cerebellum, which is involved in coordinating movements. As a result, many affected individuals have problems with balance and muscle coordination (ataxia). Additional features of L-2-HGA can include delayed development, seizures, speech difficulties, and an unusually large head (macrocephaly). Typically, signs and symptoms of this disorder begin during infancy or early childhood. The disorder worsens over time, usually leading to severe disability by early adulthood.  Combined D,L-2-HGA causes severe brain abnormalities that become apparent in early infancy. Affected infants have severe seizures, weak muscle tone (hypotonia), and breathing and feeding problems. They usually survive only into infancy or early childhood.",2-hydroxyglutaric aciduria,0001081,GHR,https://ghr.nlm.nih.gov/condition/2-hydroxyglutaric-aciduria,C2746066,T046,Disorders
How many people are affected by 2-hydroxyglutaric aciduria ?,0001081-2,frequency,"2-hydroxyglutaric aciduria is a rare disorder. D-2-HGA and L-2-HGA have each been reported to affect fewer than 150 individuals worldwide. Combined D,L-2-HGA appears to be even rarer, with only about a dozen reported cases.",2-hydroxyglutaric aciduria,0001081,GHR,https://ghr.nlm.nih.gov/condition/2-hydroxyglutaric-aciduria,C2746066,T046,Disorders
What are the genetic changes related to 2-hydroxyglutaric aciduria ?,0001081-3,genetic changes,"The different types of 2-hydroxyglutaric aciduria result from mutations in several genes. D-2-HGA type I is caused by mutations in the D2HGDH gene; type II is caused by mutations in the IDH2 gene. L-2-HGA results from mutations in the L2HGDH gene. Combined D,L-2-HGA is caused by mutations in the SLC25A1 gene.  The D2HGDH and L2HGDH genes provide instructions for making enzymes that are found in mitochondria, which are the energy-producing centers within cells. The enzymes break down compounds called D-2-hydroxyglutarate and L-2-hydroxyglutarate, respectively, as part of a series of reactions that produce energy for cell activities. Mutations in either of these genes lead to a shortage of functional enzyme, which allows D-2-hydroxyglutarate or L-2-hydroxyglutarate to build up in cells. At high levels, these compounds can damage cells and lead to cell death. Brain cells appear to be the most vulnerable to the toxic effects of these compounds, which may explain why the signs and symptoms of D-2-HGA type I and L-2-HGA primarily involve the brain.  The IDH2 gene provides instructions for making an enzyme in mitochondria that normally produces a different compound. When the enzyme is altered by mutations, it takes on a new, abnormal function: production of the potentially toxic compound D-2-hydroxyglutarate. The resulting excess of this compound damages brain cells, leading to the signs and symptoms of D-2-HGA type II. It is unclear why an accumulation of D-2-hydroxyglutarate may be associated with cardiomyopathy in some people with this form of the condition.  The SLC25A1 gene provides instructions for making a protein that transports certain molecules, such as citrate, in and out of mitochondria. Mutations in the SLC25A1 gene reduce the protein's function, which prevents it from carrying out this transport. Through processes that are not fully understood, a loss of this transport allows both D-2-hydroxyglutarate and L-2-hydroxyglutarate to build up, which damages brain cells. Researchers suspect that an imbalance of other molecules, particularly citrate, also contributes to the severe signs and symptoms of combined D,L-2-HGA.",2-hydroxyglutaric aciduria,0001081,GHR,https://ghr.nlm.nih.gov/condition/2-hydroxyglutaric-aciduria,C2746066,T046,Disorders
Is 2-hydroxyglutaric aciduria inherited ?,0001081-4,inheritance,"D-2-HGA type I, L-2-HGA, and combined D,L-2-HGA all have an autosomal recessive pattern of inheritance, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  D-2-HGA type II is considered an autosomal dominant disorder because one copy of the altered gene in each cell is sufficient to cause the condition. The disorder typically results from a new mutation in the IDH2 gene and occurs in people with no history of the condition in their family.",2-hydroxyglutaric aciduria,0001081,GHR,https://ghr.nlm.nih.gov/condition/2-hydroxyglutaric-aciduria,C2746066,T046,Disorders
What are the treatments for 2-hydroxyglutaric aciduria ?,0001081-5,treatment,These resources address the diagnosis or management of 2-hydroxyglutaric aciduria:  - Genetic Testing Registry: Combined d-2- and l-2-hydroxyglutaric aciduria  - Genetic Testing Registry: D-2-hydroxyglutaric aciduria 1  - Genetic Testing Registry: D-2-hydroxyglutaric aciduria 2  - Genetic Testing Registry: L-2-hydroxyglutaric aciduria   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,2-hydroxyglutaric aciduria,0001081,GHR,https://ghr.nlm.nih.gov/condition/2-hydroxyglutaric-aciduria,C2746066,T046,Disorders
What is (are) 2-methylbutyryl-CoA dehydrogenase deficiency ?,0001082-1,information,"2-methylbutyryl-CoA dehydrogenase deficiency is a type of organic acid disorder in which the body is unable to process proteins properly. Organic acid disorders lead to an abnormal buildup of particular acids known as organic acids. Abnormal levels of organic acids in the blood (organic acidemia), urine (organic aciduria), and tissues can be toxic and can cause serious health problems.  Normally, the body breaks down proteins from food into smaller parts called amino acids. Amino acids can be further processed to provide energy for growth and development. People with 2-methylbutyryl-CoA dehydrogenase deficiency have inadequate levels of an enzyme that helps process a particular amino acid called isoleucine.  Health problems related to 2-methylbutyryl-CoA dehydrogenase deficiency vary widely from severe and life-threatening to mild or absent. Signs and symptoms of this disorder can begin a few days after birth or later in childhood. The initial symptoms often include poor feeding, lack of energy (lethargy), vomiting, and an irritable mood. These symptoms sometimes progress to serious medical problems such as difficulty breathing, seizures, and coma. Additional problems can include poor growth, vision problems, learning disabilities, muscle weakness, and delays in motor skills such as standing and walking.  Symptoms of 2-methylbutyryl-CoA dehydrogenase deficiency may be triggered by prolonged periods without food (fasting), infections, or eating an increased amount of protein-rich foods. Some people with this disorder never have any signs or symptoms (asymptomatic). For example, individuals of Hmong ancestry identified with 2-methylbutyryl-CoA dehydrogenase deficiency through newborn screening are usually asymptomatic.",2-methylbutyryl-CoA dehydrogenase deficiency,0001082,GHR,https://ghr.nlm.nih.gov/condition/2-methylbutyryl-coa-dehydrogenase-deficiency,C1864912,T047,Disorders
How many people are affected by 2-methylbutyryl-CoA dehydrogenase deficiency ?,0001082-2,frequency,"2-methylbutyryl-CoA dehydrogenase deficiency is a rare disorder; its actual incidence is unknown. This disorder is more common, however, among Hmong populations in southeast Asia and in Hmong Americans. 2-methylbutyryl-CoA dehydrogenase deficiency occurs in 1 in 250 to 1 in 500 people of Hmong ancestry.",2-methylbutyryl-CoA dehydrogenase deficiency,0001082,GHR,https://ghr.nlm.nih.gov/condition/2-methylbutyryl-coa-dehydrogenase-deficiency,C1864912,T047,Disorders
What are the genetic changes related to 2-methylbutyryl-CoA dehydrogenase deficiency ?,0001082-3,genetic changes,"Mutations in the ACADSB gene cause 2-methylbutyryl-CoA dehydrogenase deficiency.  The ACADSB gene provides instructions for making an enzyme called 2-methylbutyryl-CoA dehydrogenase that helps process the amino acid isoleucine. Mutations in the ACADSB gene reduce or eliminate the activity of this enzyme. With a shortage (deficiency) of 2-methylbutyryl-CoA dehydrogenase, the body is unable to break down isoleucine properly. As a result, isoleucine is not converted to energy, which can lead to characteristic features of this disorder, such as lethargy and muscle weakness. Also, an organic acid called 2-methylbutyrylglycine and related compounds may build up to harmful levels, causing serious health problems.",2-methylbutyryl-CoA dehydrogenase deficiency,0001082,GHR,https://ghr.nlm.nih.gov/condition/2-methylbutyryl-coa-dehydrogenase-deficiency,C1864912,T047,Disorders
Is 2-methylbutyryl-CoA dehydrogenase deficiency inherited ?,0001082-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",2-methylbutyryl-CoA dehydrogenase deficiency,0001082,GHR,https://ghr.nlm.nih.gov/condition/2-methylbutyryl-coa-dehydrogenase-deficiency,C1864912,T047,Disorders
What are the treatments for 2-methylbutyryl-CoA dehydrogenase deficiency ?,0001082-5,treatment,These resources address the diagnosis or management of 2-methylbutyryl-CoA dehydrogenase deficiency:  - Baby's First Test  - Genetic Testing Registry: Deficiency of 2-methylbutyryl-CoA dehydrogenase   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,2-methylbutyryl-CoA dehydrogenase deficiency,0001082,GHR,https://ghr.nlm.nih.gov/condition/2-methylbutyryl-coa-dehydrogenase-deficiency,C1864912,T047,Disorders
What is (are) 21-hydroxylase deficiency ?,0001083-1,information,"21-hydroxylase deficiency is an inherited disorder that affects the adrenal glands. The adrenal glands are located on top of the kidneys and produce a variety of hormones that regulate many essential functions in the body. In people with 21-hydroxylase deficiency, the adrenal glands produce excess androgens, which are male sex hormones.  There are three types of 21-hydroxylase deficiency. Two types are classic forms, known as the salt-wasting and simple virilizing types. The third type is called the non-classic type. The salt-wasting type is the most severe, the simple virilizing type is less severe, and the non-classic type is the least severe form.  Males and females with either classic form of 21-hydroxylase deficiency tend to have an early growth spurt, but their final adult height is usually shorter than others in their family. Additionally, affected individuals may have a reduced ability to have biological children (decreased fertility). Females may also develop excessive body hair growth (hirsutism), male pattern baldness, and irregular menstruation.  Approximately 75 percent of individuals with classic 21-hydroxylase deficiency have the salt-wasting type. Hormone production is extremely low in this form of the disorder. Affected individuals lose large amounts of sodium in their urine, which can be life-threatening in early infancy. Babies with the salt-wasting type can experience poor feeding, weight loss, dehydration, and vomiting. Individuals with the simple virilizing form do not experience salt loss.  In both the salt-wasting and simple virilizing forms of this disorder, females typically have external genitalia that do not look clearly male or female (ambiguous genitalia). Males usually have normal genitalia, but the testes may be small.  Females with the non-classic type of 21-hydroxylase deficiency have normal female genitalia. As affected females get older, they may experience hirsutism, male pattern baldness, irregular menstruation, and decreased fertility. Males with the non-classic type may have early beard growth and small testes. Some individuals with this type of 21-hydroxylase deficiency have no symptoms of the disorder.",21-hydroxylase deficiency,0001083,GHR,https://ghr.nlm.nih.gov/condition/21-hydroxylase-deficiency,C1291314,T019,Disorders
How many people are affected by 21-hydroxylase deficiency ?,0001083-2,frequency,"The classic forms of 21-hydroxylase deficiency occur in 1 in 15,000 newborns. The prevalence of the non-classic form of 21-hydroxylase deficiency is estimated to be 1 in 1,000 individuals. The prevalence of both classic and non-classic forms varies among different ethnic populations.  21-hydroxylase deficiency is one of a group of disorders known as congenital adrenal hyperplasias that impair hormone production and disrupt sexual development. 21-hydroxylase deficiency is responsible for about 95 percent of all cases of congenital adrenal hyperplasia.",21-hydroxylase deficiency,0001083,GHR,https://ghr.nlm.nih.gov/condition/21-hydroxylase-deficiency,C1291314,T019,Disorders
What are the genetic changes related to 21-hydroxylase deficiency ?,0001083-3,genetic changes,"Mutations in the CYP21A2 gene cause 21-hydroxylase deficiency. The CYP21A2 gene provides instructions for making an enzyme called 21-hydroxylase. This enzyme is found in the adrenal glands, where it plays a role in producing hormones called cortisol and aldosterone. Cortisol has numerous functions, such as maintaining blood sugar levels, protecting the body from stress, and suppressing inflammation. Aldosterone is sometimes called the salt-retaining hormone because it regulates the amount of salt retained by the kidneys. The retention of salt affects fluid levels in the body and blood pressure.  21-hydroxylase deficiency is caused by a shortage (deficiency) of the 21-hydroxylase enzyme. When 21-hydroxylase is lacking, substances that are usually used to form cortisol and aldosterone instead build up in the adrenal glands and are converted to androgens. The excess production of androgens leads to abnormalities of sexual development in people with 21-hydroxylase deficiency. A lack of aldosterone production contributes to the salt loss in people with the salt-wasting form of this condition.  The amount of functional 21-hydroxylase enzyme determines the severity of the disorder. Individuals with the salt-wasting type have CYP21A2 mutations that result in a completely nonfunctional enzyme. People with the simple virilizing type of this condition have CYP21A2 gene mutations that allow the production of low levels of functional enzyme. Individuals with the non-classic type of this disorder have CYP21A2 mutations that result in the production of reduced amounts of the enzyme, but more enzyme than either of the other types.",21-hydroxylase deficiency,0001083,GHR,https://ghr.nlm.nih.gov/condition/21-hydroxylase-deficiency,C1291314,T019,Disorders
Is 21-hydroxylase deficiency inherited ?,0001083-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",21-hydroxylase deficiency,0001083,GHR,https://ghr.nlm.nih.gov/condition/21-hydroxylase-deficiency,C1291314,T019,Disorders
What are the treatments for 21-hydroxylase deficiency ?,0001083-5,treatment,These resources address the diagnosis or management of 21-hydroxylase deficiency:  - Baby's First Test  - CARES Foundation: Treatment  - Gene Review: Gene Review: 21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia  - Genetic Testing Registry: 21-hydroxylase deficiency  - MedlinePlus Encyclopedia: Congenital Adrenal Hyperplasia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,21-hydroxylase deficiency,0001083,GHR,https://ghr.nlm.nih.gov/condition/21-hydroxylase-deficiency,C1291314,T019,Disorders
What is (are) 22q11.2 deletion syndrome ?,0001084-1,information,"22q11.2 deletion syndrome (which is also known by several other names, listed below) is a disorder caused by the deletion of a small piece of chromosome 22. The deletion occurs near the middle of the chromosome at a location designated q11.2.  22q11.2 deletion syndrome has many possible signs and symptoms that can affect almost any part of the body. The features of this syndrome vary widely, even among affected members of the same family. Common signs and symptoms include heart abnormalities that are often present from birth, an opening in the roof of the mouth (a cleft palate), and distinctive facial features. People with 22q11.2 deletion syndrome often experience recurrent infections caused by problems with the immune system, and some develop autoimmune disorders such as rheumatoid arthritis and Graves disease in which the immune system attacks the body's own tissues and organs. Affected individuals may also have breathing problems, kidney abnormalities, low levels of calcium in the blood (which can result in seizures), a decrease in blood platelets (thrombocytopenia), significant feeding difficulties, gastrointestinal problems, and hearing loss. Skeletal differences are possible, including mild short stature and, less frequently, abnormalities of the spinal bones.  Many children with 22q11.2 deletion syndrome have developmental delays, including delayed growth and speech development, and learning disabilities. Later in life, they are at an increased risk of developing mental illnesses such as schizophrenia, depression, anxiety, and bipolar disorder. Additionally, affected children are more likely than children without 22q11.2 deletion syndrome to have attention deficit hyperactivity disorder (ADHD) and developmental conditions such as autism spectrum disorders that affect communication and social interaction.  Because the signs and symptoms of 22q11.2 deletion syndrome are so varied, different groupings of features were once described as separate conditions. Doctors named these conditions DiGeorge syndrome, velocardiofacial syndrome (also called Shprintzen syndrome), and conotruncal anomaly face syndrome. In addition, some children with the 22q11.2 deletion were diagnosed with the autosomal dominant form of Opitz G/BBB syndrome and Cayler cardiofacial syndrome. Once the genetic basis for these disorders was identified, doctors determined that they were all part of a single syndrome with many possible signs and symptoms. To avoid confusion, this condition is usually called 22q11.2 deletion syndrome, a description based on its underlying genetic cause.",22q11.2 deletion syndrome,0001084,GHR,https://ghr.nlm.nih.gov/condition/22q112-deletion-syndrome,C1442161,T049,Disorders
How many people are affected by 22q11.2 deletion syndrome ?,0001084-2,frequency,"22q11.2 deletion syndrome affects an estimated 1 in 4,000 people. However, the condition may actually be more common than this estimate because doctors and researchers suspect it is underdiagnosed due to its variable features. The condition may not be identified in people with mild signs and symptoms, or it may be mistaken for other disorders with overlapping features.",22q11.2 deletion syndrome,0001084,GHR,https://ghr.nlm.nih.gov/condition/22q112-deletion-syndrome,C1442161,T049,Disorders
What are the genetic changes related to 22q11.2 deletion syndrome ?,0001084-3,genetic changes,"Most people with 22q11.2 deletion syndrome are missing a sequence of about 3 million DNA building blocks (base pairs) on one copy of chromosome 22 in each cell. This region contains 30 to 40 genes, many of which have not been well characterized. A small percentage of affected individuals have shorter deletions in the same region. This condition is described as a contiguous gene deletion syndrome because it results from the loss of many genes that are close together.  Researchers are working to identify all of the genes that contribute to the features of 22q11.2 deletion syndrome. They have determined that the loss of a particular gene on chromosome 22, TBX1, is probably responsible for many of the syndrome's characteristic signs (such as heart defects, a cleft palate, distinctive facial features, hearing loss, and low calcium levels). Some studies suggest that a deletion of this gene may contribute to behavioral problems as well. The loss of another gene, COMT, in the same region of chromosome 22 may also help explain the increased risk of behavioral problems and mental illness. The loss of additional genes in the deleted region likely contributes to the varied features of 22q11.2 deletion syndrome.",22q11.2 deletion syndrome,0001084,GHR,https://ghr.nlm.nih.gov/condition/22q112-deletion-syndrome,C1442161,T049,Disorders
Is 22q11.2 deletion syndrome inherited ?,0001084-4,inheritance,"The inheritance of 22q11.2 deletion syndrome is considered autosomal dominant because a deletion in one copy of chromosome 22 in each cell is sufficient to cause the condition. Most cases of 22q11.2 deletion syndrome are not inherited, however. The deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family, though they can pass the condition to their children. In about 10 percent of cases, a person with this condition inherits the deletion in chromosome 22 from a parent. In inherited cases, other family members may be affected as well.",22q11.2 deletion syndrome,0001084,GHR,https://ghr.nlm.nih.gov/condition/22q112-deletion-syndrome,C1442161,T049,Disorders
What are the treatments for 22q11.2 deletion syndrome ?,0001084-5,treatment,These resources address the diagnosis or management of 22q11.2 deletion syndrome:  - Gene Review: Gene Review: 22q11.2 Deletion Syndrome  - Genetic Testing Registry: Asymmetric crying face association  - Genetic Testing Registry: DiGeorge sequence  - Genetic Testing Registry: Opitz G/BBB syndrome  - Genetic Testing Registry: Shprintzen syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,22q11.2 deletion syndrome,0001084,GHR,https://ghr.nlm.nih.gov/condition/22q112-deletion-syndrome,C1442161,T049,Disorders
What is (are) 22q11.2 duplication ?,0001085-1,information,"22q11.2 duplication is a condition caused by an extra copy of a small piece of chromosome 22. The duplication occurs near the middle of the chromosome at a location designated q11.2.  The features of this condition vary widely, even among members of the same family. Affected individuals may have developmental delay, intellectual disability, slow growth leading to short stature, and weak muscle tone (hypotonia). Many people with the duplication have no apparent physical or intellectual disabilities.",22q11.2 duplication,0001085,GHR,https://ghr.nlm.nih.gov/condition/22q112-duplication,C1705960,T049,Disorders
How many people are affected by 22q11.2 duplication ?,0001085-2,frequency,"The prevalence of the 22q11.2 duplication in the general population is difficult to determine. Because many individuals with this duplication have no associated symptoms, their duplication may never be detected.  Most people tested for the 22q11.2 duplication have come to medical attention as a result of developmental delay or other problems affecting themselves or a family member. In one study, about 1 in 700 people tested for these reasons had the 22q11.2 duplication. Overall, more than 60 individuals with the duplication have been identified.",22q11.2 duplication,0001085,GHR,https://ghr.nlm.nih.gov/condition/22q112-duplication,C1705960,T049,Disorders
What are the genetic changes related to 22q11.2 duplication ?,0001085-3,genetic changes,"People with 22q11.2 duplication have an extra copy of some genetic material at position q11.2 on chromosome 22. In most cases, this extra genetic material consists of a sequence of about 3 million DNA building blocks (base pairs), also written as 3 megabases (Mb).  The 3 Mb duplicated region contains 30 to 40 genes. For many of these genes, little is known about their function. A small percentage of affected individuals have a shorter duplication in the same region. Researchers are working to determine which duplicated genes may contribute to the developmental delay and other problems that sometimes affect people with this condition.",22q11.2 duplication,0001085,GHR,https://ghr.nlm.nih.gov/condition/22q112-duplication,C1705960,T049,Disorders
Is 22q11.2 duplication inherited ?,0001085-4,inheritance,"The inheritance of 22q11.2 duplication is considered autosomal dominant because the duplication affects one of the two copies of chromosome 22 in each cell. About 70 percent of affected individuals inherit the duplication from a parent. In other cases, the duplication is not inherited and instead occurs as a random event during the formation of reproductive cells (eggs and sperm) or in early fetal development. These affected people typically have no history of the disorder in their family, although they can pass the duplication to their children.",22q11.2 duplication,0001085,GHR,https://ghr.nlm.nih.gov/condition/22q112-duplication,C1705960,T049,Disorders
What are the treatments for 22q11.2 duplication ?,0001085-5,treatment,These resources address the diagnosis or management of 22q11.2 duplication:  - Gene Review: Gene Review: 22q11.2 Duplication  - Genetic Testing Registry: 22q11.2 duplication syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,22q11.2 duplication,0001085,GHR,https://ghr.nlm.nih.gov/condition/22q112-duplication,C1705960,T049,Disorders
What is (are) 22q13.3 deletion syndrome ?,0001086-1,information,"22q13.3 deletion syndrome, which is also commonly known as Phelan-McDermid syndrome, is a disorder caused by the loss of a small piece of chromosome 22. The deletion occurs near the end of the chromosome at a location designated q13.3.  The features of 22q13.3 deletion syndrome vary widely and involve many parts of the body. Characteristic signs and symptoms include developmental delay, moderate to profound intellectual disability, decreased muscle tone (hypotonia), and absent or delayed speech. Some people with this condition have autism or autistic-like behavior that affects communication and social interaction, such as poor eye contact, sensitivity to touch, and aggressive behaviors. They may also chew on non-food items such as clothing. Less frequently, people with this condition have seizures.  Individuals with 22q13.3 deletion syndrome tend to have a decreased sensitivity to pain. Many also have a reduced ability to sweat, which can lead to a greater risk of overheating and dehydration. Some people with this condition have episodes of frequent vomiting and nausea (cyclic vomiting) and backflow of stomach acids into the esophagus (gastroesophageal reflux).  People with 22q13.3 deletion syndrome typically have distinctive facial features, including a long, narrow head; prominent ears; a pointed chin; droopy eyelids (ptosis); and deep-set eyes. Other physical features seen with this condition include large and fleshy hands and/or feet, a fusion of the second and third toes (syndactyly), and small or abnormal toenails. Some affected individuals have rapid (accelerated) growth.",22q13.3 deletion syndrome,0001086,GHR,https://ghr.nlm.nih.gov/condition/22q133-deletion-syndrome,C1853490,T049,Disorders
How many people are affected by 22q13.3 deletion syndrome ?,0001086-2,frequency,At least 500 cases of 22q13.3 deletion syndrome are known.,22q13.3 deletion syndrome,0001086,GHR,https://ghr.nlm.nih.gov/condition/22q133-deletion-syndrome,C1853490,T049,Disorders
What are the genetic changes related to 22q13.3 deletion syndrome ?,0001086-3,genetic changes,"22q13.3 deletion syndrome is caused by a deletion near the end of the long (q) arm of chromosome 22. The signs and symptoms of 22q13.3 deletion syndrome are probably related to the loss of multiple genes in this region. The size of the deletion varies among affected individuals.  A ring chromosome 22 can also cause 22q13.3 deletion syndrome. A ring chromosome is a circular structure that occurs when a chromosome breaks in two places, the tips of the chromosome are lost, and the broken ends fuse together. People with ring chromosome 22 have one copy of this abnormal chromosome in some or all of their cells. Researchers believe that several critical genes near the end of the long (q) arm of chromosome 22 are lost when the ring chromosome 22 forms. If one of the chromosome break points is at position 22q13.3, people with ring chromosome 22 have similar signs and symptoms as those with a simple deletion.  Researchers are working to identify all of the genes that contribute to the features of 22q13.3 deletion syndrome. They have determined that the loss of a particular gene on chromosome 22, SHANK3, is likely to be responsible for many of the syndrome's characteristic signs (such as developmental delay, intellectual disability, and impaired speech). Additional genes in the deleted region probably contribute to the varied features of 22q13.3 deletion syndrome.",22q13.3 deletion syndrome,0001086,GHR,https://ghr.nlm.nih.gov/condition/22q133-deletion-syndrome,C1853490,T049,Disorders
Is 22q13.3 deletion syndrome inherited ?,0001086-4,inheritance,"Most cases of 22q13.3 deletion syndrome are not inherited. The deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family, though they can pass the chromosome deletion to their children.  When 22q13.3 deletion syndrome is inherited, its inheritance pattern is considered autosomal dominant because a deletion in one copy of chromosome 22 in each cell is sufficient to cause the condition. About 15 to 20 percent of people with 22q13.3 deletion syndrome inherit a chromosome abnormality from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which a segment from one chromosome has traded places with a segment from another chromosome, but no genetic material is gained or lost. Balanced translocations usually do not cause any health problems; however, they can become unbalanced as they are passed to the next generation. Children who inherit an unbalanced translocation can have a chromosomal rearrangement with extra or missing genetic material. Individuals with 22q13.3 deletion syndrome who inherit an unbalanced translocation are missing genetic material from the long arm of chromosome 22, which results in the health problems characteristic of this disorder.",22q13.3 deletion syndrome,0001086,GHR,https://ghr.nlm.nih.gov/condition/22q133-deletion-syndrome,C1853490,T049,Disorders
What are the treatments for 22q13.3 deletion syndrome ?,0001086-5,treatment,These resources address the diagnosis or management of 22q13.3 deletion syndrome:  - Gene Review: Gene Review: Phelan-McDermid Syndrome  - Genetic Testing Registry: 22q13.3 deletion syndrome  - MedlinePlus Encyclopedia: Sweating--absent   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,22q13.3 deletion syndrome,0001086,GHR,https://ghr.nlm.nih.gov/condition/22q133-deletion-syndrome,C1853490,T049,Disorders
What is (are) 2q37 deletion syndrome ?,0001087-1,information,"2q37 deletion syndrome is a condition that can affect many parts of the body. This condition is characterized by weak muscle tone (hypotonia) in infancy, mild to severe intellectual disability and developmental delay, behavioral problems, characteristic facial features, and other physical abnormalities.  Most babies with 2q37 deletion syndrome are born with hypotonia, which usually improves with age. About 25 percent of people with this condition have autism, a developmental condition that affects communication and social interaction.  The characteristic facial features associated with 2q37 deletion syndrome include a prominent forehead, highly arched eyebrows, deep-set eyes, a flat nasal bridge, a thin upper lip, and minor ear abnormalities. Other features of this condition can include short stature, obesity, unusually short fingers and toes (brachymetaphalangy), sparse hair, heart defects, seizures, and an inflammatory skin disorder called eczema. A few people with 2q37 deletion syndrome have a rare form of kidney cancer called Wilms tumor. Some affected individuals have malformations of the brain, gastrointestinal system, kidneys, or genitalia.",2q37 deletion syndrome,0001087,GHR,https://ghr.nlm.nih.gov/condition/2q37-deletion-syndrome,C2931817,T019,Disorders
How many people are affected by 2q37 deletion syndrome ?,0001087-2,frequency,"2q37 deletion syndrome appears to be a rare condition, although its exact prevalence is unknown. Approximately 100 cases have been reported worldwide.",2q37 deletion syndrome,0001087,GHR,https://ghr.nlm.nih.gov/condition/2q37-deletion-syndrome,C2931817,T019,Disorders
What are the genetic changes related to 2q37 deletion syndrome ?,0001087-3,genetic changes,2q37 deletion syndrome is caused by a deletion of genetic material from a specific region in the long (q) arm of chromosome 2. The deletion occurs near the end of the chromosome at a location designated 2q37. The size of the deletion varies among affected individuals. The signs and symptoms of this disorder are probably related to the loss of multiple genes in this region.,2q37 deletion syndrome,0001087,GHR,https://ghr.nlm.nih.gov/condition/2q37-deletion-syndrome,C2931817,T019,Disorders
Is 2q37 deletion syndrome inherited ?,0001087-4,inheritance,"Most cases of 2q37 deletion syndrome are not inherited. They result from a chromosomal deletion that occurs as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family.  Rarely, affected individuals inherit a copy of chromosome 2 with a deleted segment from an unaffected parent. In these cases, one of the parents carries a chromosomal rearrangement between chromosome 2 and another chromosome. This rearrangement is called a balanced translocation. No genetic material is gained or lost in a balanced translocation, so these chromosomal changes usually do not cause any health problems. However, translocations can become unbalanced as they are passed to the next generation. Children who inherit an unbalanced translocation can have a chromosomal rearrangement with extra or missing genetic material. Some individuals with 2q37 deletion syndrome inherit an unbalanced translocation that deletes genetic material near the end of the long arm of chromosome 2, which results in birth defects and other health problems characteristic of this disorder.",2q37 deletion syndrome,0001087,GHR,https://ghr.nlm.nih.gov/condition/2q37-deletion-syndrome,C2931817,T019,Disorders
What are the treatments for 2q37 deletion syndrome ?,0001087-5,treatment,These resources address the diagnosis or management of 2q37 deletion syndrome:  - Gene Review: Gene Review: 2q37 Microdeletion Syndrome  - Genetic Testing Registry: Brachydactyly-Mental Retardation syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,2q37 deletion syndrome,0001087,GHR,https://ghr.nlm.nih.gov/condition/2q37-deletion-syndrome,C2931817,T019,Disorders
What is (are) 3-beta-hydroxysteroid dehydrogenase deficiency ?,0001088-1,information,"3-beta ()-hydroxysteroid dehydrogenase (HSD) deficiency is an inherited disorder that affects hormone-producing glands including the gonads (ovaries in females and testes in males) and the adrenal glands. The gonads direct sexual development before birth and during puberty. The adrenal glands, which are located on top of the kidneys, regulate the production of certain hormones and control salt levels in the body. People with 3-HSD deficiency lack many of the hormones that are made in these glands. 3-HSD deficiency is one of a group of disorders known as congenital adrenal hyperplasias that impair hormone production and disrupt sexual development and maturation.  There are three types of 3-HSD deficiency: the salt-wasting, non-salt-wasting, and non-classic types. In the salt-wasting type, hormone production is extremely low. Individuals with this type lose large amounts of sodium in their urine, which can be life-threatening. Individuals affected with the salt-wasting type are usually diagnosed soon after birth due to complications related to a lack of salt reabsorption, including dehydration, poor feeding, and vomiting. People with the non-salt-wasting type of 3-HSD deficiency produce enough hormone to allow sodium reabsorption in the kidneys. Individuals with the non-classic type have the mildest symptoms and do not experience salt wasting.  In males with any type of 3-HSD deficiency, problems with male sex hormones lead to abnormalities of the external genitalia. These abnormalities range from having the opening of the urethra on the underside of the penis (hypospadias) to having external genitalia that do not look clearly male or female (ambiguous genitalia). The severity of the genital abnormality does not consistently depend on the type of the condition. Because of the hormone dysfunction in the testes, males with 3-HSD deficiency are frequently unable to have biological children (infertile).  Females with 3-HSD deficiency may have slight abnormalities of the external genitalia at birth. Females affected with the non-salt-wasting or non-classic types are typically not diagnosed until mid-childhood or puberty, when they may experience irregular menstruation, premature pubic hair growth, and excessive body hair growth (hirsutism). Females with 3-HSD deficiency have difficulty conceiving a child (impaired fertility).",3-beta-hydroxysteroid dehydrogenase deficiency,0001088,GHR,https://ghr.nlm.nih.gov/condition/3-beta-hydroxysteroid-dehydrogenase-deficiency,C1291311,T047,Disorders
How many people are affected by 3-beta-hydroxysteroid dehydrogenase deficiency ?,0001088-2,frequency,The exact prevalence of 3-HSD deficiency is unknown. At least 60 affected individuals have been reported.,3-beta-hydroxysteroid dehydrogenase deficiency,0001088,GHR,https://ghr.nlm.nih.gov/condition/3-beta-hydroxysteroid-dehydrogenase-deficiency,C1291311,T047,Disorders
What are the genetic changes related to 3-beta-hydroxysteroid dehydrogenase deficiency ?,0001088-3,genetic changes,"Mutations in the HSD3B2 gene cause 3-HSD deficiency. The HSD3B2 gene provides instructions for making the 3-HSD enzyme. This enzyme is found in the gonads and adrenal glands. The 3-HSD enzyme is involved in the production of many hormones, including cortisol, aldosterone, androgens, and estrogen. Cortisol has numerous functions such as maintaining energy and blood sugar levels, protecting the body from stress, and suppressing inflammation. Aldosterone is sometimes called the salt-retaining hormone because it regulates the amount of salt retained by the kidney. The retention of salt affects fluid levels and blood pressure. Androgens and estrogen are essential for normal sexual development and reproduction.  3-HSD deficiency is caused by a deficiency (shortage) of the 3-HSD enzyme. The amount of functional 3-HSD enzyme determines whether a person will have the salt-wasting or non-salt-wasting type of the disorder. Individuals with the salt-wasting type have HSD3B2 gene mutations that result in the production of very little or no enzyme. People with the non-salt-wasting type of this condition have HSD3B2 gene mutations that allow the production of some functional enzyme, although in reduced amounts.",3-beta-hydroxysteroid dehydrogenase deficiency,0001088,GHR,https://ghr.nlm.nih.gov/condition/3-beta-hydroxysteroid-dehydrogenase-deficiency,C1291311,T047,Disorders
Is 3-beta-hydroxysteroid dehydrogenase deficiency inherited ?,0001088-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",3-beta-hydroxysteroid dehydrogenase deficiency,0001088,GHR,https://ghr.nlm.nih.gov/condition/3-beta-hydroxysteroid-dehydrogenase-deficiency,C1291311,T047,Disorders
What are the treatments for 3-beta-hydroxysteroid dehydrogenase deficiency ?,0001088-5,treatment,These resources address the diagnosis or management of 3-beta-hydroxysteroid dehydrogenase deficiency:  - Genetic Testing Registry: 3 beta-Hydroxysteroid dehydrogenase deficiency  - Great Ormond Street Hospital for Children: Cortisol Deficiency  - MedlinePlus Encyclopedia: Ambiguous Genitalia  - MedlinePlus Encyclopedia: Congenital Adrenal Hyperplasia  - MedlinePlus Health Topic: Assisted Reproductive Technology  - National Institutes of Health Clinical Center: Managing Adrenal Insufficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,3-beta-hydroxysteroid dehydrogenase deficiency,0001088,GHR,https://ghr.nlm.nih.gov/condition/3-beta-hydroxysteroid-dehydrogenase-deficiency,C1291311,T047,Disorders
What is (are) 3-hydroxy-3-methylglutaryl-CoA lyase deficiency ?,0001089-1,information,"3-hydroxy-3-methylglutaryl-CoA lyase deficiency (also known as HMG-CoA lyase deficiency) is an uncommon inherited disorder in which the body cannot process a particular protein building block (amino acid) called leucine. Additionally, the disorder prevents the body from making ketones, which are used for energy during periods without food (fasting).  The signs and symptoms of HMG-CoA lyase deficiency usually appear within the first year of life. The condition causes episodes of vomiting, diarrhea, dehydration, extreme tiredness (lethargy), and weak muscle tone (hypotonia). During an episode, blood sugar levels can become dangerously low (hypoglycemia), and a buildup of harmful compounds can cause the blood to become too acidic (metabolic acidosis). If untreated, the disorder can lead to breathing problems, convulsions, coma, and death. Episodes are often triggered by an infection, fasting, strenuous exercise, or other types of stress.  HMG-CoA lyase deficiency is sometimes mistaken for Reye syndrome, a severe disorder that develops in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.",3-hydroxy-3-methylglutaryl-CoA lyase deficiency,0001089,GHR,https://ghr.nlm.nih.gov/condition/3-hydroxy-3-methylglutaryl-coa-lyase-deficiency,C1291557,T047,Disorders
How many people are affected by 3-hydroxy-3-methylglutaryl-CoA lyase deficiency ?,0001089-2,frequency,"HMG-CoA lyase deficiency is a rare condition; it has been reported in fewer than 100 individuals worldwide. Most people diagnosed with this disorder have been from Saudi Arabia, Portugal, or Spain.",3-hydroxy-3-methylglutaryl-CoA lyase deficiency,0001089,GHR,https://ghr.nlm.nih.gov/condition/3-hydroxy-3-methylglutaryl-coa-lyase-deficiency,C1291557,T047,Disorders
What are the genetic changes related to 3-hydroxy-3-methylglutaryl-CoA lyase deficiency ?,0001089-3,genetic changes,"Mutations in the HMGCL gene cause HMG-CoA lyase deficiency. The HMGCL gene provides instructions for making an enzyme known as 3-hydroxymethyl-3-methylglutaryl-coenzyme A lyase (HMG-CoA lyase). This enzyme plays a critical role in breaking down dietary proteins and fats for energy. Specifically, it is responsible for processing leucine, an amino acid that is part of many proteins. HMG-CoA lyase also produces ketones during the breakdown of fats. Ketones are compounds that certain organs and tissues, particularly the brain, use for energy when the simple sugar glucose is not available. For example, ketones are important sources of energy during periods of fasting.  If a mutation in the HMGCL gene reduces or eliminates the activity of HMG-CoA lyase, the body is unable to process leucine or make ketones properly. When leucine is not processed normally, a buildup of chemical byproducts called organic acids can result in metabolic acidosis. A shortage of ketones often leads to hypoglycemia. Metabolic acidosis and hypoglycemia can damage cells, particularly in the brain, resulting in serious illness in children with HMG-CoA lyase deficiency.",3-hydroxy-3-methylglutaryl-CoA lyase deficiency,0001089,GHR,https://ghr.nlm.nih.gov/condition/3-hydroxy-3-methylglutaryl-coa-lyase-deficiency,C1291557,T047,Disorders
Is 3-hydroxy-3-methylglutaryl-CoA lyase deficiency inherited ?,0001089-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",3-hydroxy-3-methylglutaryl-CoA lyase deficiency,0001089,GHR,https://ghr.nlm.nih.gov/condition/3-hydroxy-3-methylglutaryl-coa-lyase-deficiency,C1291557,T047,Disorders
What are the treatments for 3-hydroxy-3-methylglutaryl-CoA lyase deficiency ?,0001089-5,treatment,These resources address the diagnosis or management of HMG-CoA lyase deficiency:  - Baby's First Test  - Genetic Testing Registry: Deficiency of hydroxymethylglutaryl-CoA lyase   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,3-hydroxy-3-methylglutaryl-CoA lyase deficiency,0001089,GHR,https://ghr.nlm.nih.gov/condition/3-hydroxy-3-methylglutaryl-coa-lyase-deficiency,C1291557,T047,Disorders
What is (are) 3-hydroxyacyl-CoA dehydrogenase deficiency ?,0001090-1,information,"3-hydroxyacyl-CoA dehydrogenase deficiency is an inherited condition that prevents the body from converting certain fats to energy, particularly during prolonged periods without food (fasting).  Initial signs and symptoms of this disorder typically occur during infancy or early childhood and can include poor appetite, vomiting, diarrhea, and lack of energy (lethargy). Affected individuals can also have muscle weakness (hypotonia), liver problems, low blood sugar (hypoglycemia), and abnormally high levels of insulin (hyperinsulinism). Insulin controls the amount of sugar that moves from the blood into cells for conversion to energy. Individuals with 3-hydroxyacyl-CoA dehydrogenase deficiency are also at risk for complications such as seizures, life-threatening heart and breathing problems, coma, and sudden death. This condition may explain some cases of sudden infant death syndrome (SIDS), which is defined as unexplained death in babies younger than 1 year.  Problems related to 3-hydroxyacyl-CoA dehydrogenase deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.",3-hydroxyacyl-CoA dehydrogenase deficiency,0001090,GHR,https://ghr.nlm.nih.gov/condition/3-hydroxyacyl-coa-dehydrogenase-deficiency,C2047396,T047,Disorders
How many people are affected by 3-hydroxyacyl-CoA dehydrogenase deficiency ?,0001090-2,frequency,The exact incidence of 3-hydroxyacyl-CoA dehydrogenase deficiency is unknown; it has been reported in only a small number of people worldwide.,3-hydroxyacyl-CoA dehydrogenase deficiency,0001090,GHR,https://ghr.nlm.nih.gov/condition/3-hydroxyacyl-coa-dehydrogenase-deficiency,C2047396,T047,Disorders
What are the genetic changes related to 3-hydroxyacyl-CoA dehydrogenase deficiency ?,0001090-3,genetic changes,"Mutations in the HADH gene cause 3-hydroxyacyl-CoA dehydrogenase deficiency. The HADH gene provides instructions for making an enzyme called 3-hydroxyacyl-CoA dehydrogenase.  Normally, through a process called fatty acid oxidation, several enzymes work in a step-wise fashion to break down (metabolize) fats and convert them to energy. The 3-hydroxyacyl-CoA dehydrogenase enzyme is required for a step that metabolizes groups of fats called medium-chain fatty acids and short-chain fatty acids.  Mutations in the HADH gene lead to a shortage of 3-hydroxyacyl-CoA dehydrogenase. Medium-chain and short-chain fatty acids cannot be metabolized properly without sufficient levels of this enzyme. As a result, these fatty acids are not converted to energy, which can lead to characteristic features of 3-hydroxyacyl-CoA dehydrogenase deficiency, such as lethargy and hypoglycemia. Medium-chain and short-chain fatty acids that are not broken down can build up in tissues and damage the liver, heart, and muscles, causing serious complications.  Conditions that disrupt the metabolism of fatty acids, including 3-hydroxyacyl-CoA dehydrogenase deficiency, are known as fatty acid oxidation disorders.",3-hydroxyacyl-CoA dehydrogenase deficiency,0001090,GHR,https://ghr.nlm.nih.gov/condition/3-hydroxyacyl-coa-dehydrogenase-deficiency,C2047396,T047,Disorders
Is 3-hydroxyacyl-CoA dehydrogenase deficiency inherited ?,0001090-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",3-hydroxyacyl-CoA dehydrogenase deficiency,0001090,GHR,https://ghr.nlm.nih.gov/condition/3-hydroxyacyl-coa-dehydrogenase-deficiency,C2047396,T047,Disorders
What are the treatments for 3-hydroxyacyl-CoA dehydrogenase deficiency ?,0001090-5,treatment,These resources address the diagnosis or management of 3-hydroxyacyl-CoA dehydrogenase deficiency:  - Baby's First Test  - Genetic Testing Registry: Deficiency of 3-hydroxyacyl-CoA dehydrogenase  - United Mitochondrial Disease Foundation: Treatments & Therapies   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,3-hydroxyacyl-CoA dehydrogenase deficiency,0001090,GHR,https://ghr.nlm.nih.gov/condition/3-hydroxyacyl-coa-dehydrogenase-deficiency,C2047396,T047,Disorders
What is (are) 3-M syndrome ?,0001091-1,information,"3-M syndrome is a disorder that causes short stature (dwarfism), unusual facial features, and skeletal abnormalities. The name of this condition comes from the initials of three researchers who first identified it: Miller, McKusick, and Malvaux.  Individuals with 3-M syndrome grow extremely slowly before birth, and this slow growth continues throughout childhood and adolescence. They have low birth weight and length and remain much smaller than others in their family, growing to an adult height of approximately 120 centimeters to 130 centimeters (4 feet to 4 feet 6 inches). Affected individuals have a normally sized head that looks disproportionately large in comparison with their body. The head may be unusually long and narrow in shape (dolichocephalic).  In addition to short stature, people with 3-M syndrome have a triangle-shaped face with a broad, prominent forehead (frontal bossing) and a pointed chin; the middle of the face is less prominent (hypoplastic midface). They may have large ears, full eyebrows, an upturned nose with a fleshy tip, a long area between the nose and mouth (philtrum), a prominent mouth, and full lips.  Affected individuals may have a short, broad neck and chest with prominent shoulder blades and square shoulders. They may have abnormal spinal curvature such as a rounded upper back that also curves to the side (kyphoscoliosis) or exaggerated curvature of the lower back (hyperlordosis). People with 3-M syndrome may also have unusual curving of the fingers (clinodactyly), short fifth (pinky) fingers, prominent heels, and loose joints. Other skeletal abnormalities, such as unusually slender long bones in the arms and legs, tall, narrow spinal bones (vertebrae), or slightly delayed bone age may be apparent in x-ray images.  3-M syndrome can also affect other body systems. Males with 3-M syndrome may produce reduced amounts of sex hormones (hypogonadism) and occasionally have the urethra opening on the underside of the penis (hypospadias). People with this condition may be at increased risk of developing bulges in blood vessel walls (aneurysms) in the brain. Intelligence is unaffected by 3-M syndrome, and life expectancy is generally normal.  A variant of 3-M syndrome called Yakut short stature syndrome has been identified in an isolated population in Siberia. In addition to having most of the physical features characteristic of 3-M syndrome, people with this form of the disorder are often born with respiratory problems that can be life-threatening in infancy.",3-M syndrome,0001091,GHR,https://ghr.nlm.nih.gov/condition/3-m-syndrome,C1848862,T047,Disorders
How many people are affected by 3-M syndrome ?,0001091-2,frequency,3-M syndrome is a rare disorder. About 50 individuals with this disorder have been identified worldwide.,3-M syndrome,0001091,GHR,https://ghr.nlm.nih.gov/condition/3-m-syndrome,C1848862,T047,Disorders
What are the genetic changes related to 3-M syndrome ?,0001091-3,genetic changes,"Mutations in the CUL7 gene cause 3-M syndrome. The CUL7 gene provides instructions for making a protein called cullin-7. This protein plays a role in the cell machinery that breaks down (degrades) unwanted proteins, called the ubiquitin-proteasome system.  Cullin-7 helps to assemble a complex known as an E3 ubiquitin ligase. This complex tags damaged and excess proteins with molecules called ubiquitin. Ubiquitin serves as a signal to specialized cell structures known as proteasomes, which attach (bind) to the tagged proteins and degrade them. The ubiquitin-proteasome system acts as the cell's quality control system by disposing of damaged, misshapen, and excess proteins. This system also regulates the level of proteins involved in several critical cell activities such as the timing of cell division and growth.  Mutations in the CUL7 gene that cause 3-M syndrome disrupt the ability of the cullin-7 protein to bring together the components of the E3 ubiquitin ligase complex, interfering with the process of tagging other proteins with ubiquitin (ubiquitination). It is not known how impaired ubiquitination results in the specific signs and symptoms of 3-M syndrome.",3-M syndrome,0001091,GHR,https://ghr.nlm.nih.gov/condition/3-m-syndrome,C1848862,T047,Disorders
Is 3-M syndrome inherited ?,0001091-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",3-M syndrome,0001091,GHR,https://ghr.nlm.nih.gov/condition/3-m-syndrome,C1848862,T047,Disorders
What are the treatments for 3-M syndrome ?,0001091-5,treatment,These resources address the diagnosis or management of 3-M syndrome:  - Gene Review: Gene Review: 3-M Syndrome  - Genetic Testing Registry: Three M syndrome 1   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,3-M syndrome,0001091,GHR,https://ghr.nlm.nih.gov/condition/3-m-syndrome,C1848862,T047,Disorders
What is (are) 3-methylcrotonyl-CoA carboxylase deficiency ?,0001092-1,information,"3-methylcrotonyl-CoA carboxylase deficiency (also known as 3-MCC deficiency) is an inherited disorder in which the body is unable to process certain proteins properly. People with this disorder have a shortage of an enzyme that helps break down proteins containing a particular building block (amino acid) called leucine.  Infants with 3-MCC deficiency appear normal at birth but usually develop signs and symptoms in infancy or early childhood. The characteristic features of this condition, which can range from mild to life-threatening, include feeding difficulties, recurrent episodes of vomiting and diarrhea, excessive tiredness (lethargy), and weak muscle tone (hypotonia). If untreated, this disorder can lead to delayed development, seizures, and coma. Many of these complications can be prevented with early detection and lifelong management with a low-protein diet and appropriate supplements. Some people with gene mutations that cause 3-MCC deficiency never experience any signs or symptoms of the condition.  The characteristic features of 3-MCC deficiency are similar to those of Reye syndrome, a severe disorder that develops in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.",3-methylcrotonyl-CoA carboxylase deficiency,0001092,GHR,https://ghr.nlm.nih.gov/condition/3-methylcrotonyl-coa-carboxylase-deficiency,C0268600,T047,Disorders
How many people are affected by 3-methylcrotonyl-CoA carboxylase deficiency ?,0001092-2,frequency,"This condition is detected in an estimated 1 in 36,000 newborns worldwide.",3-methylcrotonyl-CoA carboxylase deficiency,0001092,GHR,https://ghr.nlm.nih.gov/condition/3-methylcrotonyl-coa-carboxylase-deficiency,C0268600,T047,Disorders
What are the genetic changes related to 3-methylcrotonyl-CoA carboxylase deficiency ?,0001092-3,genetic changes,"Mutations in the MCCC1 or MCCC2 gene can cause 3-MCC deficiency. These two genes provide instructions for making different parts (subunits) of an enzyme called 3-methylcrotonyl-coenzyme A carboxylase (3-MCC). This enzyme plays a critical role in breaking down proteins obtained from the diet. Specifically, 3-MCC is responsible for the fourth step in processing leucine, an amino acid that is part of many proteins.  Mutations in the MCCC1 or MCCC2 gene reduce or eliminate the activity of 3-MCC, preventing the body from processing leucine properly. As a result, toxic byproducts of leucine processing build up to harmful levels, which can damage the brain. This damage underlies the signs and symptoms of 3-MCC deficiency.",3-methylcrotonyl-CoA carboxylase deficiency,0001092,GHR,https://ghr.nlm.nih.gov/condition/3-methylcrotonyl-coa-carboxylase-deficiency,C0268600,T047,Disorders
Is 3-methylcrotonyl-CoA carboxylase deficiency inherited ?,0001092-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",3-methylcrotonyl-CoA carboxylase deficiency,0001092,GHR,https://ghr.nlm.nih.gov/condition/3-methylcrotonyl-coa-carboxylase-deficiency,C0268600,T047,Disorders
What are the treatments for 3-methylcrotonyl-CoA carboxylase deficiency ?,0001092-5,treatment,These resources address the diagnosis or management of 3-MCC deficiency:  - Baby's First Test  - Genetic Testing Registry: 3 Methylcrotonyl-CoA carboxylase 1 deficiency  - Genetic Testing Registry: 3-methylcrotonyl CoA carboxylase 2 deficiency  - Genetic Testing Registry: Methylcrotonyl-CoA carboxylase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,3-methylcrotonyl-CoA carboxylase deficiency,0001092,GHR,https://ghr.nlm.nih.gov/condition/3-methylcrotonyl-coa-carboxylase-deficiency,C0268600,T047,Disorders
What is (are) 3-methylglutaconyl-CoA hydratase deficiency ?,0001093-1,information,"3-methylglutaconyl-CoA hydratase deficiency is an inherited condition that causes neurological problems. Beginning in infancy to early childhood, children with this condition often have delayed development of mental and motor skills (psychomotor delay), speech delay, involuntary muscle cramping (dystonia), and spasms and weakness of the arms and legs (spastic quadriparesis). Affected individuals can also have optic atrophy, which is the degeneration (atrophy) of nerve cells that carry visual information from the eyes to the brain.  In some cases, signs and symptoms of 3-methylglutaconyl-CoA hydratase deficiency begin in adulthood, often in a person's twenties or thirties. These individuals have damage to a type of brain tissue called white matter (leukoencephalopathy), which likely contributes to progressive problems with speech (dysarthria), difficulty coordinating movements (ataxia), stiffness (spasticity), optic atrophy, and a decline in intellectual function (dementia).  Affected individuals who show symptoms of 3-methylglutaconyl-CoA hydratase deficiency in childhood often go on to develop leukoencephalopathy and other neurological problems in adulthood.  All people with 3-methylglutaconyl-CoA hydratase deficiency accumulate large amounts of a substance called 3-methylglutaconic acid in their body fluids. As a result, they have elevated levels of acid in their blood (metabolic acidosis) and excrete large amounts of acid in their urine (aciduria). 3-methylglutaconyl-CoA hydratase deficiency is one of a group of metabolic disorders that can be diagnosed by the presence of increased levels 3-methylglutaconic acid in urine (3-methylglutaconic aciduria). People with 3-methylglutaconyl-CoA hydratase deficiency also have high urine levels of another acid called 3-methylglutaric acid.",3-methylglutaconyl-CoA hydratase deficiency,0001093,GHR,https://ghr.nlm.nih.gov/condition/3-methylglutaconyl-coa-hydratase-deficiency,C0342727,T047,Disorders
How many people are affected by 3-methylglutaconyl-CoA hydratase deficiency ?,0001093-2,frequency,3-methylglutaconyl-CoA hydratase deficiency is a rare disorder; at least 20 cases have been reported in the scientific literature.,3-methylglutaconyl-CoA hydratase deficiency,0001093,GHR,https://ghr.nlm.nih.gov/condition/3-methylglutaconyl-coa-hydratase-deficiency,C0342727,T047,Disorders
What are the genetic changes related to 3-methylglutaconyl-CoA hydratase deficiency ?,0001093-3,genetic changes,"Mutations in the AUH gene cause 3-methylglutaconyl-CoA hydratase deficiency. This gene provides instructions for producing 3-methylglutaconyl-CoA hydratase, an enzyme that is involved in breaking down a protein building block (amino acid) called leucine to provide energy for cells. This amino acid is broken down in cell structures called mitochondria, which convert energy from food into a form that cells can use.  AUH gene mutations lead to an absence of enzyme activity. Without any functional 3-methylglutaconyl-CoA hydratase, leucine is not properly broken down, which leads to a buildup of related compounds, including multiple acids: 3-methylglutaconic acid, 3-methylglutaric acid, and 3-hydroxyisovaleric acid. Researchers speculate that an accumulation of these acids in the fluid that surrounds and protects the brain and spinal cord (the cerebrospinal fluid or CSF) can damage these structures and contribute to the neurological features of 3-methylglutaconyl-CoA hydratase deficiency.  Because the age at which the condition begins varies widely and because the signs and symptoms improve in some affected children, researchers speculate that other genes or environmental factors may play a role in the features of 3-methylglutaconyl-CoA hydratase deficiency.",3-methylglutaconyl-CoA hydratase deficiency,0001093,GHR,https://ghr.nlm.nih.gov/condition/3-methylglutaconyl-coa-hydratase-deficiency,C0342727,T047,Disorders
Is 3-methylglutaconyl-CoA hydratase deficiency inherited ?,0001093-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",3-methylglutaconyl-CoA hydratase deficiency,0001093,GHR,https://ghr.nlm.nih.gov/condition/3-methylglutaconyl-coa-hydratase-deficiency,C0342727,T047,Disorders
What are the treatments for 3-methylglutaconyl-CoA hydratase deficiency ?,0001093-5,treatment,These resources address the diagnosis or management of 3-methylglutaconyl-CoA hydratase deficiency:  - Baby's First Test  - Genetic Testing Registry: 3-Methylglutaconic aciduria  - MedlinePlus Encyclopedia: Metabolic Acidosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,3-methylglutaconyl-CoA hydratase deficiency,0001093,GHR,https://ghr.nlm.nih.gov/condition/3-methylglutaconyl-coa-hydratase-deficiency,C0342727,T047,Disorders
What is (are) 3MC syndrome ?,0001094-1,information,"3MC syndrome is a disorder characterized by unusual facial features and problems affecting other tissues and organs of the body.  The distinctive facial features of people with 3MC syndrome include widely spaced eyes (hypertelorism), a narrowing of the eye opening (blepharophimosis), droopy eyelids (ptosis), highly arched eyebrows, and an opening in the upper lip (cleft lip) with an opening in the roof of the mouth (cleft palate). Common features affecting other body systems include developmental delay, intellectual disability, hearing loss, and slow growth after birth resulting in short stature. Other features of 3MC syndrome can include abnormal fusion of certain bones in the skull (craniosynostosis) or forearm (radioulnar synostosis); an outgrowth of the tailbone (caudal appendage); a soft out-pouching around the belly-button (an umbilical hernia); and abnormalities of the kidneys, bladder, or genitals.  3MC syndrome encompasses four disorders that were formerly considered to be separate: Mingarelli, Malpeuch, Michels, and Carnevale syndromes. Researchers now generally consider these disorders to be part of the same condition, which is called 3MC based on the initials of the older condition names.",3MC syndrome,0001094,GHR,https://ghr.nlm.nih.gov/condition/3mc-syndrome,C0039082,T047,Disorders
How many people are affected by 3MC syndrome ?,0001094-2,frequency,3MC syndrome is a rare disorder; its exact prevalence is unknown.,3MC syndrome,0001094,GHR,https://ghr.nlm.nih.gov/condition/3mc-syndrome,C0039082,T047,Disorders
What are the genetic changes related to 3MC syndrome ?,0001094-3,genetic changes,"3MC syndrome is caused by mutations in the COLEC11 or MASP1 gene. These genes provide instructions for making proteins that are involved in a series of reactions called the lectin complement pathway. This pathway is thought to help direct the movement (migration) of cells during early development before birth to form the organs and systems of the body. It appears to be particularly important in directing the migration of neural crest cells, which give rise to various tissues including many tissues in the face and skull, the glands that produce hormones (endocrine glands), and portions of the nervous system.  The COLEC11 gene provides instructions for making a protein called CL-K1. Three different proteins, MASP-1, MASP-3, and MAp44 can be produced from the MASP1 gene, depending on how the gene's instructions are pieced together. The MASP1 gene mutations identified in people with 3MC syndrome affect the MASP-3 protein; some affect the MASP-1 protein in addition to MASP-3. COLEC11 and MASP1 gene mutations that cause 3MC syndrome impair or eliminate the function of the corresponding proteins, resulting in faulty control of cell migration in embryonic development and leading to the various abnormalities that occur in this disorder.  In some people with 3MC syndrome, no mutations in the COLEC11 or MASP1 gene have been identified. In these individuals, the cause of the disorder is unknown.",3MC syndrome,0001094,GHR,https://ghr.nlm.nih.gov/condition/3mc-syndrome,C0039082,T047,Disorders
Is 3MC syndrome inherited ?,0001094-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",3MC syndrome,0001094,GHR,https://ghr.nlm.nih.gov/condition/3mc-syndrome,C0039082,T047,Disorders
What are the treatments for 3MC syndrome ?,0001094-5,treatment,These resources address the diagnosis or management of 3MC syndrome:  - Genetic Testing Registry: Carnevale syndrome  - Genetic Testing Registry: Craniofacial-ulnar-renal syndrome  - Genetic Testing Registry: Malpuech facial clefting syndrome  - Genetic Testing Registry: Michels syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,3MC syndrome,0001094,GHR,https://ghr.nlm.nih.gov/condition/3mc-syndrome,C0039082,T047,Disorders
"What is (are) 46,XX testicular disorder of sex development ?",0001095-1,information,"46,XX testicular disorder of sex development is a condition in which individuals with two X chromosomes in each cell, the pattern normally found in females, have a male appearance. People with this disorder have male external genitalia. They generally have small testes and may also have abnormalities such as undescended testes (cryptorchidism) or the urethra opening on the underside of the penis (hypospadias). A small number of affected people have external genitalia that do not look clearly male or clearly female (ambiguous genitalia). Affected children are typically raised as males and have a male gender identity.  At puberty, most affected individuals require treatment with the male sex hormone testosterone to induce development of male secondary sex characteristics such as facial hair and deepening of the voice (masculinization). Hormone treatment can also help prevent breast enlargement (gynecomastia). Adults with this disorder are usually shorter than average for males and are unable to have children (infertile).","46,XX testicular disorder of sex development",0001095,GHR,https://ghr.nlm.nih.gov/condition/46xx-testicular-disorder-of-sex-development,C0036875,T019,Disorders
"How many people are affected by 46,XX testicular disorder of sex development ?",0001095-2,frequency,"Approximately 1 in 20,000 individuals with a male appearance have 46,XX testicular disorder.","46,XX testicular disorder of sex development",0001095,GHR,https://ghr.nlm.nih.gov/condition/46xx-testicular-disorder-of-sex-development,C0036875,T019,Disorders
"What are the genetic changes related to 46,XX testicular disorder of sex development ?",0001095-3,genetic changes,"People normally have 46 chromosomes in each cell. Two of the 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male or female sex characteristics. Females typically have two X chromosomes (46,XX), and males usually have one X chromosome and one Y chromosome (46,XY).  The SRY gene, normally located on the Y chromosome, provides instructions for making the sex-determining region Y protein. The sex-determining region Y protein causes a fetus to develop as a male.  In about 80 percent of individuals with 46,XX testicular disorder of sex development, the condition results from an abnormal exchange of genetic material between chromosomes (translocation). This exchange occurs as a random event during the formation of sperm cells in the affected person's father. The translocation causes the SRY gene to be misplaced, almost always onto an X chromosome. If a fetus is conceived from a sperm cell with an X chromosome bearing the SRY gene, it will develop as a male despite not having a Y chromosome. This form of the condition is called SRY-positive 46,XX testicular disorder of sex development.  About 20 percent of people with 46,XX testicular disorder of sex development do not have the SRY gene. This form of the condition is called SRY-negative 46,XX testicular disorder of sex development. The cause of the disorder in these individuals is unknown. They are more likely to have ambiguous genitalia than are people with the SRY-positive form.","46,XX testicular disorder of sex development",0001095,GHR,https://ghr.nlm.nih.gov/condition/46xx-testicular-disorder-of-sex-development,C0036875,T019,Disorders
"Is 46,XX testicular disorder of sex development inherited ?",0001095-4,inheritance,"SRY-positive 46,XX testicular disorder of sex development is almost never inherited. This condition results from the translocation of a Y chromosome segment containing the SRY gene during the formation of sperm (spermatogenesis). Affected people typically have no history of the disorder in their family and cannot pass on the disorder because they are infertile.  In rare cases, the SRY gene may be misplaced onto a chromosome other than the X chromosome. This translocation may be carried by an unaffected father and passed on to a child with two X chromosomes, resulting in 46,XX testicular disorder of sex development. In another very rare situation, a man may carry the SRY gene on both the X and Y chromosome; a child who inherits his X chromosome will develop male sex characteristics despite having no Y chromosome.  The inheritance pattern of SRY-negative 46,XX testicular disorder of sex development is unknown. A few families with unaffected parents have had more than one child with the condition, suggesting the possibility of autosomal recessive inheritance. Autosomal recessive means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.","46,XX testicular disorder of sex development",0001095,GHR,https://ghr.nlm.nih.gov/condition/46xx-testicular-disorder-of-sex-development,C0036875,T019,Disorders
"What are the treatments for 46,XX testicular disorder of sex development ?",0001095-5,treatment,"These resources address the diagnosis or management of 46,XX testicular disorder of sex development:  - Gene Review: Gene Review: Nonsyndromic 46,XX Testicular Disorders of Sex Development  - Genetic Testing Registry: 46,XX sex reversal, type 1  - Genetic Testing Registry: 46,XX testicular disorder of sex development  - MedlinePlus Encyclopedia: Ambiguous Genitalia  - MedlinePlus Encyclopedia: Intersex   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","46,XX testicular disorder of sex development",0001095,GHR,https://ghr.nlm.nih.gov/condition/46xx-testicular-disorder-of-sex-development,C0036875,T019,Disorders
"What is (are) 47,XYY syndrome ?",0001096-1,information,"47,XYY syndrome is characterized by an extra copy of the Y chromosome in each of a male's cells. Although males with this condition may be taller than average, this chromosomal change typically causes no unusual physical features. Most males with 47,XYY syndrome have normal sexual development and are able to father children.  47,XYY syndrome is associated with an increased risk of learning disabilities and delayed development of speech and language skills. Delayed development of motor skills (such as sitting and walking), weak muscle tone (hypotonia), hand tremors or other involuntary movements (motor tics), and behavioral and emotional difficulties are also possible. These characteristics vary widely among affected boys and men.  A small percentage of males with 47,XYY syndrome are diagnosed with autistic spectrum disorders, which are developmental conditions that affect communication and social interaction.","47,XYY syndrome",0001096,GHR,https://ghr.nlm.nih.gov/condition/47xyy-syndrome,C3266843,T019,Disorders
"How many people are affected by 47,XYY syndrome ?",0001096-2,frequency,"This condition occurs in about 1 in 1,000 newborn boys. Five to 10 boys with 47,XYY syndrome are born in the United States each day.","47,XYY syndrome",0001096,GHR,https://ghr.nlm.nih.gov/condition/47xyy-syndrome,C3266843,T019,Disorders
"What are the genetic changes related to 47,XYY syndrome ?",0001096-3,genetic changes,"People normally have 46 chromosomes in each cell. Two of the 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male or female sex characteristics. Females typically have two X chromosomes (46,XX), and males have one X chromosome and one Y chromosome (46,XY).  47,XYY syndrome is caused by the presence of an extra copy of the Y chromosome in each of a male's cells. As a result of the extra Y chromosome, each cell has a total of 47 chromosomes instead of the usual 46. It is unclear why an extra copy of the Y chromosome is associated with tall stature, learning problems, and other features in some boys and men.  Some males with 47,XYY syndrome have an extra Y chromosome in only some of their cells. This phenomenon is called 46,XY/47,XYY mosaicism.","47,XYY syndrome",0001096,GHR,https://ghr.nlm.nih.gov/condition/47xyy-syndrome,C3266843,T019,Disorders
"Is 47,XYY syndrome inherited ?",0001096-4,inheritance,"Most cases of 47,XYY syndrome are not inherited. The chromosomal change usually occurs as a random event during the formation of sperm cells. An error in cell division called nondisjunction can result in sperm cells with an extra copy of the Y chromosome. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have an extra Y chromosome in each of the body's cells.  46,XY/47,XYY mosaicism is also not inherited. It occurs as a random event during cell division in early embryonic development. As a result, some of an affected person's cells have one X chromosome and one Y chromosome (46,XY), and other cells have one X chromosome and two Y chromosomes (47,XYY).","47,XYY syndrome",0001096,GHR,https://ghr.nlm.nih.gov/condition/47xyy-syndrome,C3266843,T019,Disorders
"What are the treatments for 47,XYY syndrome ?",0001096-5,treatment,"These resources address the diagnosis or management of 47,XYY syndrome:  - Association for X and Y Chromosome Variations: Tell Me About 47,XYY  - Genetic Testing Registry: Double Y syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","47,XYY syndrome",0001096,GHR,https://ghr.nlm.nih.gov/condition/47xyy-syndrome,C3266843,T019,Disorders
"What is (are) 48,XXYY syndrome ?",0001097-1,information,"48,XXYY syndrome is a chromosomal condition that causes medical and behavioral problems in males.  48,XXYY disrupts male sexual development. Adolescent and adult males with this condition typically have small testes that do not produce enough testosterone, which is the hormone that directs male sexual development. A shortage of testosterone during puberty can lead to reduced facial and body hair, poor muscle development, low energy levels, and an increased risk for breast enlargement (gynecomastia). Because their testes do not function normally, males with 48, XXYY syndrome have an inability to father children (infertility).  48,XXYY syndrome can affect other parts of the body as well. Males with 48,XXYY syndrome are often taller than other males their age. They tend to develop a tremor that typically starts in adolescence and worsens with age. Dental problems are frequently seen with this condition; they include delayed appearance of the primary (baby) or secondary (adult) teeth, thin tooth enamel, crowded and/or misaligned teeth, and multiple cavities. As affected males get older, they may develop a narrowing of the blood vessels in the legs, called peripheral vascular disease. Peripheral vascular disease can cause skin ulcers to form. Affected males are also at risk for developing a type of clot called a deep vein thrombosis (DVT) that occurs in the deep veins of the legs. Additionally, males with 48,XXYY syndrome may have flat feet (pes planus), elbow abnormalities, allergies, asthma, type 2 diabetes, seizures, and congenital heart defects.  Most males with 48,XXYY syndrome have some degree of difficulty with speech and language development. Learning disabilities, especially reading problems, are very common in males with this disorder. Affected males seem to perform better at tasks focused on math, visual-spatial skills such as puzzles, and memorization of locations or directions. Some boys with 48,XXYY syndrome have delayed development of motor skills such as sitting, standing, and walking that can lead to poor coordination. Affected males have higher than average rates of behavioral disorders, such as attention deficit hyperactivity disorder (ADHD); mood disorders, including anxiety and bipolar disorder; and/or autism spectrum disorders, which affect communication and social interaction.","48,XXYY syndrome",0001097,GHR,https://ghr.nlm.nih.gov/condition/48xxyy-syndrome,C2936741,T019,Disorders
"How many people are affected by 48,XXYY syndrome ?",0001097-2,frequency,"48,XXYY syndrome is estimated to affect 1 in 18,000 to 50,000 males.","48,XXYY syndrome",0001097,GHR,https://ghr.nlm.nih.gov/condition/48xxyy-syndrome,C2936741,T019,Disorders
"What are the genetic changes related to 48,XXYY syndrome ?",0001097-3,genetic changes,"48,XXYY syndrome is a condition related to the X and Y chromosomes (the sex chromosomes). People normally have 46 chromosomes in each cell. Two of the 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male or female sex characteristics. Females typically have two X chromosomes (46,XX), and males have one X chromosome and one Y chromosome (46,XY). 48,XXYY syndrome results from the presence of an extra copy of both sex chromosomes in each of a male's cells (48,XXYY). Extra copies of genes on the X chromosome interfere with male sexual development, preventing the testes from functioning normally and reducing the levels of testosterone. Many genes are found only on the X or Y chromosome, but genes in areas known as the pseudoautosomal regions are present on both sex chromosomes. Extra copies of genes from the pseudoautosomal regions of the extra X and Y chromosome contribute to the signs and symptoms of 48,XXYY syndrome; however, the specific genes have not been identified.","48,XXYY syndrome",0001097,GHR,https://ghr.nlm.nih.gov/condition/48xxyy-syndrome,C2936741,T019,Disorders
"Is 48,XXYY syndrome inherited ?",0001097-4,inheritance,"This condition is not inherited; it usually occurs as a random event during the formation of reproductive cells (eggs and sperm). An error in cell division called nondisjunction results in a reproductive cell with an abnormal number of chromosomes. In 48,XXYY syndrome, the extra sex chromosomes almost always come from a sperm cell. Nondisjunction may cause a sperm cell to gain two extra sex chromosomes, resulting in a sperm cell with three sex chromosomes (one X and two Y chromosomes). If that sperm cell fertilizes a normal egg cell with one X chromosome, the resulting child will have two X chromosomes and two Y chromosomes in each of the body's cells.  In a small percentage of cases, 48,XXYY syndrome results from nondisjunction of the sex chromosomes in a 46,XY embryo very soon after fertilization has occurred. This means that an normal sperm cell with one Y chromosome fertilized a normal egg cell with one X chromosome, but right after fertilization nondisjunction of the sex chromosomes caused the embryo to gain two extra sex chromosomes, resulting in a 48,XXYY embryo.","48,XXYY syndrome",0001097,GHR,https://ghr.nlm.nih.gov/condition/48xxyy-syndrome,C2936741,T019,Disorders
"What are the treatments for 48,XXYY syndrome ?",0001097-5,treatment,"These resources address the diagnosis or management of 48,XXYY syndrome:  - Genetic Testing Registry: XXYY syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care","48,XXYY syndrome",0001097,GHR,https://ghr.nlm.nih.gov/condition/48xxyy-syndrome,C2936741,T019,Disorders
What is (are) 5-alpha reductase deficiency ?,0001098-1,information,"5-alpha reductase deficiency is a condition that affects male sexual development before birth and during puberty. People with this condition are genetically male, with one X and one Y chromosome in each cell, and they have male gonads (testes). Their bodies, however, do not produce enough of a hormone called dihydrotestosterone (DHT). DHT has a critical role in male sexual development, and a shortage of this hormone disrupts the formation of the external sex organs before birth.  Many people with 5-alpha reductase deficiency are born with external genitalia that appear female. In other cases, the external genitalia do not look clearly male or clearly female (sometimes called ambiguous genitalia). Still other affected infants have genitalia that appear predominantly male, often with an unusually small penis (micropenis) and the urethra opening on the underside of the penis (hypospadias).  During puberty, people with this condition develop some secondary sex characteristics, such as increased muscle mass, deepening of the voice, development of pubic hair, and a growth spurt. The penis and scrotum (the sac of skin that holds the testes) grow larger. Unlike many men, people with 5-alpha reductase deficiency do not develop much facial or body hair. Most affected males are unable to father a child (infertile).  Children with 5-alpha reductase deficiency are often raised as girls. About half of these individuals adopt a male gender role in adolescence or early adulthood.",5-alpha reductase deficiency,0001098,GHR,https://ghr.nlm.nih.gov/condition/5-alpha-reductase-deficiency,C1291316,T047,Disorders
How many people are affected by 5-alpha reductase deficiency ?,0001098-2,frequency,"5-alpha reductase deficiency is a rare condition; the exact incidence is unknown. Large families with affected members have been found in several countries, including the Dominican Republic, Papua New Guinea, Turkey, and Egypt.",5-alpha reductase deficiency,0001098,GHR,https://ghr.nlm.nih.gov/condition/5-alpha-reductase-deficiency,C1291316,T047,Disorders
What are the genetic changes related to 5-alpha reductase deficiency ?,0001098-3,genetic changes,"Mutations in the SRD5A2 gene cause 5-alpha reductase deficiency. The SRD5A2 gene provides instructions for making an enzyme called steroid 5-alpha reductase 2. This enzyme is involved in processing androgens, which are hormones that direct male sexual development. Specifically, the enzyme is responsible for a chemical reaction that converts the hormone testosterone to DHT. DHT is essential for the normal development of male sex characteristics before birth, particularly the formation of the external genitalia.  Mutations in the SRD5A2 gene prevent steroid 5-alpha reductase 2 from effectively converting testosterone to DHT in the developing reproductive tissues. These hormonal factors underlie the changes in sexual development seen in infants with 5-alpha reductase deficiency.  During puberty, the testes produce more testosterone. Researchers believe that people with 5-alpha reductase deficiency develop secondary male sex characteristics in response to higher levels of this hormone. Some affected people also retain a small amount of 5-alpha reductase 2 activity, which may produce DHT and contribute to the development of secondary sex characteristics during puberty.",5-alpha reductase deficiency,0001098,GHR,https://ghr.nlm.nih.gov/condition/5-alpha-reductase-deficiency,C1291316,T047,Disorders
Is 5-alpha reductase deficiency inherited ?,0001098-4,inheritance,"This condition is inherited in an autosomal recessive pattern, which means both copies of the SRD5A2 gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.  Although people who are genetically female (with two X chromosomes in each cell) may inherit mutations in both copies of the SRD5A2 gene, their sexual development is not affected. The development of female sex characteristics does not require DHT, so a lack of steroid 5-alpha reductase 2 activity does not cause physical changes in these individuals. Only people who have mutations in both copies of the SRD5A2 gene and are genetically male (with one X and one Y chromosome in each cell) have the characteristic signs of 5-alpha reductase deficiency.",5-alpha reductase deficiency,0001098,GHR,https://ghr.nlm.nih.gov/condition/5-alpha-reductase-deficiency,C1291316,T047,Disorders
What are the treatments for 5-alpha reductase deficiency ?,0001098-5,treatment,These resources address the diagnosis or management of 5-alpha reductase deficiency:  - Genetic Testing Registry: 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency  - MedlinePlus Encyclopedia: Ambiguous Genitalia  - MedlinePlus Encyclopedia: Intersex   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,5-alpha reductase deficiency,0001098,GHR,https://ghr.nlm.nih.gov/condition/5-alpha-reductase-deficiency,C1291316,T047,Disorders
What is (are) 5q minus syndrome ?,0001099-1,information,"5q minus (5q-) syndrome is a type of bone marrow disorder called myelodysplastic syndrome (MDS). MDS comprises a group of conditions in which immature blood cells fail to develop normally, resulting in too many immature cells and too few normal mature blood cells. In 5q- syndrome, development of red blood cells is particularly affected, leading to a shortage of these cells (anemia). In addition, the red blood cells that are present are unusually large (macrocytic). Although many people with 5q- syndrome have no symptoms related to anemia, especially in the early stages of the condition, some affected individuals develop extreme tiredness (fatigue), weakness, and an abnormally pale appearance (pallor) as the condition worsens. Individuals with 5q- syndrome also have abnormal development of bone marrow cells called megakaryocytes, which produce platelets, the cell fragments involved in blood clotting. A common finding in people with 5q- syndrome is abnormal cells described as hypolobated megakaryocytes. In addition, some individuals with 5q- syndrome have an excess of platelets, while others have normal numbers of platelets.  MDS is considered a slow-growing (chronic) blood cancer. It can progress to a fast-growing blood cancer called acute myeloid leukemia (AML). Progression to AML occurs less commonly in people with 5q- syndrome than in those with other forms of MDS.",5q minus syndrome,0001099,GHR,https://ghr.nlm.nih.gov/condition/5q-minus-syndrome,C1292779,T191,Disorders
How many people are affected by 5q minus syndrome ?,0001099-2,frequency,"MDS affects nearly 1 in 20,000 people in the United States. It is thought that 5q- syndrome accounts for 15 percent of MDS cases. Unlike other forms of MDS, which occur more frequently in men than women, 5q- syndrome is more than twice as common in women.",5q minus syndrome,0001099,GHR,https://ghr.nlm.nih.gov/condition/5q-minus-syndrome,C1292779,T191,Disorders
What are the genetic changes related to 5q minus syndrome ?,0001099-3,genetic changes,"5q- syndrome is caused by deletion of a region of DNA from the long (q) arm of chromosome 5. Most people with 5q- syndrome are missing a sequence of about 1.5 million DNA building blocks (base pairs), also written as 1.5 megabases (Mb). However, the size of the deleted region varies. This deletion occurs in immature blood cells during a person's lifetime and affects one of the two copies of chromosome 5 in each cell.  The commonly deleted region of DNA contains 40 genes, many of which play a critical role in normal blood cell development. Research suggests that loss of multiple genes in this region contributes to the features of 5q- syndrome. Loss of the RPS14 gene leads to the problems with red blood cell development characteristic of 5q- syndrome, and loss of MIR145 or MIR146A contributes to the megakaryocyte and platelet abnormalities and may promote the overgrowth of immature cells. Scientists are still determining how the loss of other genes in the deleted region might be involved in the features of 5q- syndrome.",5q minus syndrome,0001099,GHR,https://ghr.nlm.nih.gov/condition/5q-minus-syndrome,C1292779,T191,Disorders
Is 5q minus syndrome inherited ?,0001099-4,inheritance,This condition is generally not inherited but arises from a mutation in the body's cells that occurs after conception. This alteration is called a somatic mutation. Affected people typically have no history of the disorder in their family.,5q minus syndrome,0001099,GHR,https://ghr.nlm.nih.gov/condition/5q-minus-syndrome,C1292779,T191,Disorders
What are the treatments for 5q minus syndrome ?,0001099-5,treatment,These resources address the diagnosis or management of 5q minus syndrome:  - American Cancer Society: How are Myelodysplastic Syndromes Diagnosed?  - Cancer.Net: MyelodysplasticSyndromes: Treatment Options  - Genetic Testing Registry: 5q- syndrome  - National Cancer Institute: FDA Approval for Lenalidomide   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,5q minus syndrome,0001099,GHR,https://ghr.nlm.nih.gov/condition/5q-minus-syndrome,C1292779,T191,Disorders
What is (are) 6q24-related transient neonatal diabetes mellitus ?,0001100-1,information,"6q24-related transient neonatal diabetes mellitus is a type of diabetes that occurs in infants. This form of diabetes is characterized by high blood sugar levels (hyperglycemia) resulting from a shortage of the hormone insulin. Insulin controls how much glucose (a type of sugar) is passed from the blood into cells for conversion to energy.  People with 6q24-related transient neonatal diabetes mellitus experience very slow growth before birth (severe intrauterine growth retardation). Affected infants have hyperglycemia and an excessive loss of fluids (dehydration), usually beginning in the first week of life. Signs and symptoms of this form of diabetes are transient, which means that they gradually lessen over time and generally disappear between the ages of 3 months and 18 months. Diabetes may recur, however, especially during childhood illnesses or pregnancy. Up to half of individuals with 6q24-related transient neonatal diabetes mellitus develop permanent diabetes mellitus later in life.  Other features of 6q24-related transient neonatal diabetes mellitus that occur in some affected individuals include an unusually large tongue (macroglossia); a soft out-pouching around the belly-button (an umbilical hernia); malformations of the brain, heart, or kidneys; weak muscle tone (hypotonia); deafness; and developmental delay.",6q24-related transient neonatal diabetes mellitus,0001100,GHR,https://ghr.nlm.nih.gov/condition/6q24-related-transient-neonatal-diabetes-mellitus,C3711391,T047,Disorders
How many people are affected by 6q24-related transient neonatal diabetes mellitus ?,0001100-2,frequency,"Between 1 in 215,000 and 1 in 400,000 babies are born with diabetes mellitus. In about half of these babies, the diabetes is transient. Researchers estimate that approximately 70 percent of transient diabetes in newborns is caused by 6q24-related transient neonatal diabetes mellitus.",6q24-related transient neonatal diabetes mellitus,0001100,GHR,https://ghr.nlm.nih.gov/condition/6q24-related-transient-neonatal-diabetes-mellitus,C3711391,T047,Disorders
What are the genetic changes related to 6q24-related transient neonatal diabetes mellitus ?,0001100-3,genetic changes,"6q24-related transient neonatal diabetes mellitus is caused by the overactivity (overexpression) of certain genes in a region of the long (q) arm of chromosome 6 called 6q24. People inherit two copies of their genes, one from their mother and one from their father. Usually both copies of each gene are active, or ""turned on,"" in cells. In some cases, however, only one of the two copies is normally turned on. Which copy is active depends on the parent of origin: some genes are normally active only when they are inherited from a person's father; others are active only when inherited from a person's mother. This phenomenon is known as genomic imprinting.  The 6q24 region includes paternally expressed imprinted genes, which means that normally only the copy of each gene that comes from the father is active. The copy of each gene that comes from the mother is inactivated (silenced) by a mechanism called methylation.  Overactivity of one of the paternally expressed imprinted genes in this region, PLAGL1, is believed to cause 6q24-related transient neonatal diabetes mellitus. Other paternally expressed imprinted genes in the region, some of which have not been identified, may also be involved in this disorder.  There are three ways that overexpression of imprinted genes in the 6q24 region can occur. About 40 percent of cases of 6q24-related transient neonatal diabetes mellitus are caused by a genetic change known as paternal uniparental disomy (UPD) of chromosome 6. In paternal UPD, people inherit both copies of the affected chromosome from their father instead of one copy from each parent. Paternal UPD causes people to have two active copies of paternally expressed imprinted genes, rather than one active copy from the father and one inactive copy from the mother.  Another 40 percent of cases of 6q24-related transient neonatal diabetes mellitus occur when the copy of chromosome 6 that comes from the father has a duplication of genetic material including the paternally expressed imprinted genes in the 6q24 region.  The third mechanism by which overexpression of genes in the 6q24 region can occur is by impaired silencing of the maternal copy of the genes (maternal hypomethylation). Approximately 20 percent of cases of 6q24-related transient neonatal diabetes mellitus are caused by maternal hypomethylation. Some people with this disorder have a genetic change in the maternal copy of the 6q24 region that prevents genes in that region from being silenced. Other affected individuals have a more generalized impairment of gene silencing involving many imprinted regions, called hypomethylation of imprinted loci (HIL).  About half the time, HIL is caused by mutations in the ZFP57 gene. Studies indicate that the protein produced from this gene is important in establishing and maintaining gene silencing. The other causes of HIL are unknown. Because HIL can cause overexpression of many genes, this mechanism may account for the additional health problems that occur in some people with 6q24-related transient neonatal diabetes mellitus.  It is not well understood how overexpression of PLAGL1 and other genes in the 6q24 region causes 6q24-related transient neonatal diabetes mellitus and why the condition improves after infancy. The protein produced from the PLAGL1 gene helps control another protein called the pituitary adenylate cyclase-activating polypeptide receptor (PACAP1), and one of the functions of this protein is to stimulate insulin secretion by beta cells in the pancreas. In addition, overexpression of the PLAGL1 protein has been shown to stop the cycle of cell division and lead to the self-destruction of cells (apoptosis). Researchers suggest that PLAGL1 gene overexpression may reduce the number of insulin-secreting beta cells or impair their function in affected individuals.  Lack of sufficient insulin results in the signs and symptoms of diabetes mellitus. In individuals with 6q24-related transient neonatal diabetes mellitus, these signs and symptoms are most likely to occur during times of physiologic stress, including the rapid growth of infancy, childhood illnesses, and pregnancy. Because insulin acts as a growth promoter during early development, a shortage of this hormone may account for the intrauterine growth retardation seen in 6q24-related transient neonatal diabetes mellitus.",6q24-related transient neonatal diabetes mellitus,0001100,GHR,https://ghr.nlm.nih.gov/condition/6q24-related-transient-neonatal-diabetes-mellitus,C3711391,T047,Disorders
Is 6q24-related transient neonatal diabetes mellitus inherited ?,0001100-4,inheritance,"Most cases of 6q24-related transient neonatal diabetes mellitus are not inherited, particularly those caused by paternal uniparental disomy. In these cases, genetic changes occur as random events during the formation of reproductive cells (eggs and sperm) or in early embryonic development. Affected people typically have no history of the disorder in their family.  Sometimes, the genetic change responsible for 6q24-related transient neonatal diabetes mellitus is inherited. For example, a duplication of genetic material on the paternal chromosome 6 can be passed from one generation to the next.  When 6q24-related transient neonatal diabetes mellitus is caused by ZFP57 gene mutations, it is inherited in an autosomal recessive pattern. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.",6q24-related transient neonatal diabetes mellitus,0001100,GHR,https://ghr.nlm.nih.gov/condition/6q24-related-transient-neonatal-diabetes-mellitus,C3711391,T047,Disorders
What are the treatments for 6q24-related transient neonatal diabetes mellitus ?,0001100-5,treatment,"These resources address the diagnosis or management of 6q24-related transient neonatal diabetes mellitus:  - Gene Review: Gene Review: Diabetes Mellitus, 6q24-Related Transient Neonatal  - Genetic Testing Registry: Transient neonatal diabetes mellitus 1  - The Merck Manual for Healthcare Professionals  - University of Chicago Kovler Diabetes Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care",6q24-related transient neonatal diabetes mellitus,0001100,GHR,https://ghr.nlm.nih.gov/condition/6q24-related-transient-neonatal-diabetes-mellitus,C3711391,T047,Disorders
What is (are) 7q11.23 duplication syndrome ?,0001101-1,information,"7q11.23 duplication syndrome is a condition that can cause a variety of neurological and behavioral problems as well as other abnormalities.  People with 7q11.23 duplication syndrome typically have delayed development of speech and delayed motor skills such as crawling and walking. Speech problems and abnormalities in the way affected individuals walk and stand may persist throughout life. Affected individuals may also have weak muscle tone (hypotonia) and abnormal movements, such as involuntary movements of one side of the body that mirror intentional movements of the other side.  Behavioral problems associated with this condition include anxiety disorders (such as social phobias and selective mutism, which is an inability to speak in certain circumstances), attention deficit hyperactivity disorder (ADHD), physical aggression, excessively defiant behavior (oppositional disorder), and autistic behaviors that affect communication and social interaction. While the majority of people with 7q11.23 duplication syndrome have low-average to average intelligence, intellectual development varies widely in this condition, from intellectual disability to, rarely, above-average intelligence. About one-fifth of people with 7q11.23 duplication syndrome experience seizures.  About half of individuals with 7q11.23 duplication syndrome have enlargement (dilatation) of the blood vessel that carries blood from the heart to the rest of the body (the aorta); this enlargement can get worse over time. Aortic dilatation can lead to life-threatening complications if the wall of the aorta separates into layers (aortic dissection) or breaks open (ruptures).  The characteristic appearance of people with 7q11.23 duplication syndrome can include a large head (macrocephaly) that is flattened in the back (brachycephaly), a broad forehead, straight eyebrows, and deep-set eyes with long eyelashes. The nose may be broad at the tip with the area separating the nostrils attaching lower than usual on the face (low insertion of the columella), resulting in a shortened area between the nose and the upper lip (philtrum). A high arch in the roof of the mouth (high-arched palate) and ear abnormalities may also occur in affected individuals.",7q11.23 duplication syndrome,0001101,GHR,https://ghr.nlm.nih.gov/condition/7q1123-duplication-syndrome,C0039082,T047,Disorders
How many people are affected by 7q11.23 duplication syndrome ?,0001101-2,frequency,"The prevalence of this disorder is estimated to be 1 in 7,500 to 20,000 people.",7q11.23 duplication syndrome,0001101,GHR,https://ghr.nlm.nih.gov/condition/7q1123-duplication-syndrome,C0039082,T047,Disorders
What are the genetic changes related to 7q11.23 duplication syndrome ?,0001101-3,genetic changes,"7q11.23 duplication syndrome results from an extra copy of a region on the long (q) arm of chromosome 7 in each cell. This region is called the Williams-Beuren syndrome critical region (WBSCR) because its deletion causes a different disorder called Williams syndrome, also known as Williams-Beuren syndrome. The region, which is 1.5 to 1.8 million DNA base pairs (Mb) in length, includes 26 to 28 genes.  Extra copies of several of the genes in the duplicated region, including the ELN and GTF2I genes, likely contribute to the characteristic features of 7q11.23 duplication syndrome. Researchers suggest that an extra copy of the ELN gene in each cell may be related to the increased risk for aortic dilatation in 7q11.23 duplication syndrome. Studies suggest that an extra copy of the GTF2I gene may be associated with some of the behavioral features of the disorder. However, the specific causes of these features are unclear.  Researchers are studying additional genes in the duplicated region, but none have been definitely linked to any of the specific signs or symptoms of 7q11.23 duplication syndrome.",7q11.23 duplication syndrome,0001101,GHR,https://ghr.nlm.nih.gov/condition/7q1123-duplication-syndrome,C0039082,T047,Disorders
Is 7q11.23 duplication syndrome inherited ?,0001101-4,inheritance,"7q11.23 duplication syndrome is considered to be an autosomal dominant condition, which means one copy of chromosome 7 with the duplication in each cell is sufficient to cause the disorder. Most cases result from a duplication that occurs during the formation of reproductive cells (eggs and sperm) or in early fetal development. These cases occur in people with no history of the disorder in their family. Less commonly, an affected person inherits the chromosome with a duplicated segment from a parent.",7q11.23 duplication syndrome,0001101,GHR,https://ghr.nlm.nih.gov/condition/7q1123-duplication-syndrome,C0039082,T047,Disorders
What are the treatments for 7q11.23 duplication syndrome ?,0001101-5,treatment,These resources address the diagnosis or management of 7q11.23 duplication syndrome:  - Cardiff University (United Kingdom): Copy Number Variant Research  - Gene Review: Gene Review: 7q11.23 Duplication Syndrome  - Genetic Testing Registry: Williams-Beuren region duplication syndrome  - University of Antwerp (Belgium): 7q11.23 Research Project  - University of Louisville: 7q11.23 Duplication Syndrome Research  - University of Toronto: 7q11.23 Duplication Syndrome Research   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,7q11.23 duplication syndrome,0001101,GHR,https://ghr.nlm.nih.gov/condition/7q1123-duplication-syndrome,C0039082,T047,Disorders
What is (are) 8p11 myeloproliferative syndrome ?,0001102-1,information,"8p11 myeloproliferative syndrome is a blood cancer that involves different types of blood cells. Blood cells are divided into several groups (lineages) based on the type of early cell from which they are descended. Two of these lineages are myeloid cells and lymphoid cells. Individuals with 8p11 myeloproliferative syndrome can develop both myeloid cell cancer and lymphoid cell cancer.  The condition can occur at any age. It usually begins as a myeloproliferative disorder, which is characterized by a high number of white blood cells (leukocytes). Most affected individuals also have an excess of myeloid cells known as eosinophils (eosinophilia).  In addition to a myeloproliferative disorder, many people with 8p11 myeloproliferative syndrome develop lymphoma, which is a form of blood cancer that involves lymphoid cells. The cancerous lymphoid cells grow and divide in lymph nodes, forming a tumor that enlarges the lymph nodes. In most cases of 8p11 myeloproliferative syndrome, the cancerous cells are lymphoid cells called T cells. Lymphoma can develop at the same time as the myeloproliferative disorder or later.  In most people with 8p11 myeloproliferative syndrome, the myeloproliferative disorder develops into a fast-growing blood cancer called acute myeloid leukemia.  The rapid myeloid and lymphoid cell production caused by these cancers results in enlargement of the spleen and liver (splenomegaly and hepatomegaly, respectively). Most people with 8p11 myeloproliferative syndrome have symptoms such as fatigue or night sweats. Some affected individuals have no symptoms, and the condition is discovered through routine blood tests.",8p11 myeloproliferative syndrome,0001102,GHR,https://ghr.nlm.nih.gov/condition/8p11-myeloproliferative-syndrome,C2827362,T191,Disorders
How many people are affected by 8p11 myeloproliferative syndrome ?,0001102-2,frequency,The prevalence of 8p11 myeloproliferative syndrome is unknown. It is thought to be a rare condition.,8p11 myeloproliferative syndrome,0001102,GHR,https://ghr.nlm.nih.gov/condition/8p11-myeloproliferative-syndrome,C2827362,T191,Disorders
What are the genetic changes related to 8p11 myeloproliferative syndrome ?,0001102-3,genetic changes,"8p11 myeloproliferative syndrome is caused by rearrangements of genetic material (translocations) between two chromosomes. All of the translocations that cause this condition involve the FGFR1 gene, which is found on the short (p) arm of chromosome 8 at a position described as p11. The translocations lead to fusion of part of the FGFR1 gene with part of another gene; the most common partner gene is ZMYM2 on chromosome 13. These genetic changes are found only in cancer cells.  The protein normally produced from the FGFR1 gene can trigger a cascade of chemical reactions that instruct the cell to undergo certain changes, such as growing and dividing. This signaling is turned on when the FGFR1 protein interacts with growth factors. In contrast, when the FGFR1 gene is fused with another gene, FGFR1 signaling is turned on without the need for stimulation by growth factors. The uncontrolled signaling promotes continuous cell growth and division, leading to cancer.  Researchers believe the mutations that cause this condition occur in a very early blood cell called a stem cell that has the ability to mature into either a myeloid cell or a lymphoid cell. For this reason, this condition is sometimes referred to as stem cell leukemia/lymphoma.",8p11 myeloproliferative syndrome,0001102,GHR,https://ghr.nlm.nih.gov/condition/8p11-myeloproliferative-syndrome,C2827362,T191,Disorders
Is 8p11 myeloproliferative syndrome inherited ?,0001102-4,inheritance,This condition is generally not inherited but arises from a mutation in the body's cells that occurs after conception. This alteration is called a somatic mutation.,8p11 myeloproliferative syndrome,0001102,GHR,https://ghr.nlm.nih.gov/condition/8p11-myeloproliferative-syndrome,C2827362,T191,Disorders
What are the treatments for 8p11 myeloproliferative syndrome ?,0001102-5,treatment,These resources address the diagnosis or management of 8p11 myeloproliferative syndrome:  - Cancer.Net from the American Society of Clinical Oncology: Acute Myeloid Leukemia Diagnosis  - Cancer.Net from the American Society of Clinical Oncology: Acute Myeloid Leukemia Treatment Options  - Cancer.Net from the American Society of Clinical Oncology: Non-Hodgkin Lymphoma Diagnosis  - Cancer.Net from the American Society of Clinical Oncology: Non-Hodgkin Lymphoma Treatment Options  - Genetic Testing Registry: Chromosome 8p11 myeloproliferative syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,8p11 myeloproliferative syndrome,0001102,GHR,https://ghr.nlm.nih.gov/condition/8p11-myeloproliferative-syndrome,C2827362,T191,Disorders
What is (are) 9q22.3 microdeletion ?,0001103-1,information,"9q22.3 microdeletion is a chromosomal change in which a small piece of chromosome 9 is deleted in each cell. The deletion occurs on the long (q) arm of the chromosome in a region designated q22.3. This chromosomal change is associated with delayed development, intellectual disability, certain physical abnormalities, and the characteristic features of a genetic condition called Gorlin syndrome.  Many individuals with a 9q22.3 microdeletion have delayed development, particularly affecting the development of motor skills such as sitting, standing, and walking. In some people, the delays are temporary and improve in childhood. More severely affected individuals have permanent developmental disabilities along with intellectual impairment and learning problems. Rarely, seizures have been reported in people with a 9q22.3 microdeletion.  About 20 percent of people with a 9q22.3 microdeletion experience overgrowth (macrosomia), which results in increased height and weight compared to unaffected peers. The macrosomia often begins before birth and continues into childhood. Other physical changes that can be associated with a 9q22.3 microdeletion include the premature fusion of certain bones in the skull (metopic craniosynostosis) and a buildup of fluid in the brain (hydrocephalus). Affected individuals can also have distinctive facial features such as a prominent forehead with vertical skin creases, upward- or downward-slanting eyes, a short nose, and a long space between the nose and upper lip (philtrum).  9q22.3 microdeletions also cause the characteristic features of Gorlin syndrome (also known as nevoid basal cell carcinoma syndrome). This genetic condition affects many areas of the body and increases the risk of developing various cancerous and noncancerous tumors. In people with Gorlin syndrome, the type of cancer diagnosed most often is basal cell carcinoma, which is the most common form of skin cancer. Most people with this condition also develop noncancerous (benign) tumors of the jaw, called keratocystic odontogenic tumors, which can cause facial swelling and tooth displacement. Other types of tumors that occur more often in people with Gorlin syndrome include a form of childhood brain cancer called a medulloblastoma and a type of benign tumor called a fibroma that occurs in the heart or in a woman's ovaries. Other features of Gorlin syndrome include small depressions (pits) in the skin of the palms of the hands and soles of the feet; an unusually large head size (macrocephaly) with a prominent forehead; and skeletal abnormalities involving the spine, ribs, or skull.",9q22.3 microdeletion,0001103,GHR,https://ghr.nlm.nih.gov/condition/9q223-microdeletion,C3711390,T047,Disorders
How many people are affected by 9q22.3 microdeletion ?,0001103-2,frequency,9q22.3 microdeletion appears to be a rare chromosomal change. About three dozen affected individuals have been reported in the medical literature.,9q22.3 microdeletion,0001103,GHR,https://ghr.nlm.nih.gov/condition/9q223-microdeletion,C3711390,T047,Disorders
What are the genetic changes related to 9q22.3 microdeletion ?,0001103-3,genetic changes,"People with a 9q22.3 microdeletion are missing a sequence of at least 352,000 DNA building blocks (base pairs), also written as 352 kilobases (kb), in the q22.3 region of chromosome 9. This 352-kb segment is known as the minimum critical region because it is the smallest deletion that has been found to cause the signs and symptoms described above. 9q22.3 microdeletions can also be much larger; the largest reported deletion includes 20.5 million base pairs (20.5 Mb). 9q22.3 microdeletion affects one of the two copies of chromosome 9 in each cell.  People with a 9q22.3 microdeletion are missing from two to more than 270 genes on chromosome 9. All known 9q22.3 microdeletions include the PTCH1 gene. The protein produced from this gene, patched-1, acts as a tumor suppressor, which means it keeps cells from growing and dividing (proliferating) too rapidly or in an uncontrolled way. Researchers believe that many of the features associated with 9q22.3 microdeletions, particularly the signs and symptoms of Gorlin syndrome, result from a loss of the PTCH1 gene. When this gene is missing, patched-1 is not available to suppress cell proliferation. As a result, cells divide uncontrollably to form the tumors that are characteristic of Gorlin syndrome.  Other signs and symptoms related to 9q22.3 microdeletions probably result from the loss of additional genes in the q22.3 region. Researchers are working to determine which missing genes contribute to the other features associated with the deletion.",9q22.3 microdeletion,0001103,GHR,https://ghr.nlm.nih.gov/condition/9q223-microdeletion,C3711390,T047,Disorders
Is 9q22.3 microdeletion inherited ?,0001103-4,inheritance,"9q22.3 microdeletions are inherited in an autosomal dominant pattern, which means that missing genetic material from one of the two copies of chromosome 9 in each cell is sufficient to cause delayed development, intellectual disability, and the features of Gorlin syndrome.  A 9q22.3 microdeletion most often occurs in people whose parents do not carry the chromosomal change. In these cases, the deletion occurs as a random (de novo) event during the formation of reproductive cells (eggs or sperm) in a parent or in early embryonic development. De novo chromosomal changes occur in people with no history of the disorder in their family.  Less commonly, individuals with a 9q22.3 microdeletion inherit the chromosomal change from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which a segment of chromosome 9 has traded places with a segment of another chromosome. No genetic material is gained or lost in a balanced translocation, so these chromosomal changes usually do not cause any health problems. However, translocations can become unbalanced as they are passed to the next generation. People who inherit a 9q22.3 microdeletion receive an unbalanced translocation that deletes genetic material from one copy of the q22.3 region of chromosome 9 in each cell.  Having one missing copy of the PTCH1 gene in each cell is enough to cause the features of Gorlin syndrome that are present early in life, including macrocephaly and skeletal abnormalities. For basal cell carcinomas and other tumors to develop, a mutation in the other copy of the PTCH1 gene must also occur in certain cells during the person's lifetime. Most people who are born with one missing copy of the PTCH1 gene eventually acquire a mutation in the other copy of the gene in some cells and consequently develop various types of tumors.",9q22.3 microdeletion,0001103,GHR,https://ghr.nlm.nih.gov/condition/9q223-microdeletion,C3711390,T047,Disorders
What are the treatments for 9q22.3 microdeletion ?,0001103-5,treatment,These resources address the diagnosis or management of 9q22.3 microdeletion:  - Gene Review: Gene Review: 9q22.3 Microdeletion  - Gene Review: Gene Review: Nevoid Basal Cell Carcinoma Syndrome  - Genetic Testing Registry: Gorlin syndrome  - MedlinePlus Encyclopedia: Basal Cell Nevus Syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care,9q22.3 microdeletion,0001103,GHR,https://ghr.nlm.nih.gov/condition/9q223-microdeletion,C3711390,T047,Disorders