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