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