bowang0911/MedQuAD huggingface dataset:
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).
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.
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
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 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.
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
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.
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.
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
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.
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.
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.
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.
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
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 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.
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.