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