bowang0911/MedQuAD huggingface dataset:
These resources address the diagnosis or management of Lennox-Gastaut syndrome:  - Cleveland Clinic  - Genetic Testing Registry: Epileptic encephalopathy Lennox-Gastaut type  - National Institute of Neurological Disorders and Stroke: Diagnosis and Treatment of Epilepsy  - News Release: FDA Approves New Drug to Treat Severe Form of Epilepsy (U.S. Food and Drug Administration, November 20, 2008)   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care
Nonsyndromic aplasia cutis congenita is a condition in which babies are born with localized areas of missing skin (lesions). These areas resemble ulcers or open wounds, although they are sometimes already healed at birth. Lesions most commonly occur on the top of the head (skull vertex), although they can be found on the torso or limbs. In some cases, the bone and other tissues under the skin defect are also underdeveloped.  Most affected babies have a single lesion. The lesions vary in size and can be differently shaped: some are round or oval, others rectangular, and still others star-shaped. They usually leave a scar after they heal. When the scalp is involved, there may be an absence of hair growth (alopecia) in the affected area.  When the underlying bone and other tissues are involved, affected individuals are at higher risk of infections. If these severe defects occur on the head, the membrane that covers the brain (the dura mater) may be exposed, and life-threatening bleeding may occur from nearby vessels.  Skin lesions are typically the only feature of nonsyndromic aplasia cutis congenita, although other skin problems and abnormalities of the bones and other tissues occur rarely. However, the characteristic skin lesions can occur as one of many symptoms in other conditions, including Johanson-Blizzard syndrome and Adams-Oliver syndrome. These instances are described as syndromic aplasia cutis congenita.
Nonsyndromic aplasia cutis congenita can have different causes, and often the cause is unknown. Because the condition is sometimes found in multiple members of a family, it is thought to have a genetic component; however, the genetic factors are not fully understood. Researchers suggest that genes important for skin growth may be involved. It is thought that impairments of skin growth more commonly affect the skin at the top of the head because that region needs to be able to grow quickly to cover the fast-growing skull of a developing baby.  In some cases, nonsyndromic aplasia cutis congenita is caused by exposure to a drug called methimazole before birth. This medication is given to treat an overactive thyroid gland. Babies whose mothers take this medication during pregnancy are at increased risk of having the condition. In addition, certain viral infections in a pregnant mother can cause the baby to be born with the skin lesions characteristic of nonsyndromic aplasia cutis congenita. Other cases are thought to be caused by injury to the baby during development.
Most cases of nonsyndromic aplasia cutis congenita are sporadic, which means they occur in people with no history of the disorder in their family. When the condition runs in families, inheritance usually follows an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. Rarely, the condition appears to follow an autosomal recessive pattern of inheritance, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
DOORS syndrome is a disorder involving multiple abnormalities that are present from birth (congenital). "DOORS" is an abbreviation for the major features of the disorder including deafness; short or absent nails (onychodystrophy); short fingers and toes (osteodystrophy); developmental delay and intellectual disability (previously called mental retardation); and seizures. Some people with DOORS syndrome do not have all of these features.  Most people with DOORS syndrome have profound hearing loss caused by changes in the inner ears (sensorineural deafness). Developmental delay and intellectual disability are also often severe in this disorder.  The nail abnormalities affect both the hands and the feet in DOORS syndrome. Impaired growth of the bones at the tips of the fingers and toes (hypoplastic terminal phalanges) account for the short fingers and toes characteristic of this disorder. Some affected individuals also have an extra bone and joint in their thumbs, causing the thumbs to look more like the other fingers (triphalangeal thumbs).  The seizures that occur in people with DOORS syndrome usually start in infancy. The most common seizures in people with this condition are generalized tonic-clonic seizures (also known as grand mal seizures), which cause muscle rigidity, convulsions, and loss of consciousness. Affected individuals may also have other types of seizures, including partial seizures, which affect only one area of the brain and do not cause a loss of consciousness; absence seizures, which cause loss of consciousness for a short period that appears as a staring spell; or myoclonic seizures, which cause rapid, uncontrolled muscle jerks. In some affected individuals the seizures increase in frequency and become more severe and difficult to control, and a potentially life-threatening prolonged seizure (status epilepticus) can occur.  Other features that can occur in people with DOORS syndrome include an unusually small head size (microcephaly) and facial differences, most commonly a wide, bulbous nose. A narrow or high arched roof of the mouth (palate), broadening of the ridges in the upper and lower jaw that contain the sockets of the teeth (alveolar ridges), or shortening of the membrane between the floor of the mouth and the tongue (frenulum) have also been observed in some affected individuals. People with DOORS syndrome may also have dental abnormalities, structural abnormalities of the heart or urinary tract, and abnormally low levels of thyroid hormones (hypothyroidism). Most affected individuals also have higher-than-normal levels of a substance called 2-oxoglutaric acid in their urine; these levels can fluctuate between normal and elevated.
DOORS syndrome can be caused by mutations in the TBC1D24 gene. This gene provides instructions for making a protein whose specific function in the cell is unclear. Studies suggest the protein may have several roles in cells. The TBC1D24 protein belongs to a group of proteins that are involved in the movement (transport) of vesicles, which are small sac-like structures that transport proteins and other materials within cells. Research suggests that the TBC1D24 protein may also help cells respond to oxidative stress. Oxidative stress occurs when unstable molecules called free radicals accumulate to levels that can damage or kill cells. Studies indicate that the TBC1D24 protein is active in a variety of organs and tissues; it is particularly active in the brain and likely plays an important role in normal brain development. The TBC1D24 protein is also active in specialized structures called stereocilia. In the inner ear, stereocilia project from certain cells called hair cells. The stereocilia bend in response to sound waves, which is critical for converting sound waves to nerve impulses.  TBC1D24 gene mutations that cause DOORS syndrome are thought to reduce or eliminate the function of the TBC1D24 protein, but the specific mechanism by which loss of TBC1D24 function leads to the signs and symptoms of DOORS syndrome is not well understood.  In about half of affected individuals, no TBC1D24 gene mutation has been identified. The cause of DOORS syndrome in these individuals is unknown.
Arts syndrome is a disorder that causes serious neurological problems in males. Females can also be affected by this condition, but they typically have much milder symptoms.  Boys with Arts syndrome have profound sensorineural hearing loss, which is a complete or almost complete loss of hearing caused by abnormalities in the inner ear. Other features of the disorder include weak muscle tone (hypotonia), impaired muscle coordination (ataxia), developmental delay, and intellectual disability. In early childhood, affected boys develop vision loss caused by degeneration of nerves that carry information from the eyes to the brain (optic nerve atrophy). They also experience loss of sensation and weakness in the limbs (peripheral neuropathy).  Boys with Arts syndrome also usually have recurrent infections, especially involving the respiratory system. Because of these infections and their complications, affected boys often do not survive past early childhood.  In females with Arts syndrome, hearing loss that begins in adulthood may be the only symptom.
Mutations in the PRPS1 gene cause Arts syndrome. The PRPS1 gene provides instructions for making an enzyme called phosphoribosyl pyrophosphate synthetase 1, or PRPP synthetase 1. This enzyme is involved in producing purines and pyrimidines, which are building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in the cell.  The PRPS1 gene mutations that cause Arts syndrome replace single protein building blocks (amino acids) in the PRPP synthetase 1 enzyme. The resulting enzyme is probably unstable, reducing or eliminating its ability to perform its function. The disruption of purine and pyrimidine production may impair energy storage and transport in cells. Impairment of these processes may have a particularly severe effect on tissues that require a large amount of energy, such as the nervous system, resulting in the neurological problems characteristic of Arts syndrome. The reason for the increased risk of respiratory infections in Arts syndrome is unclear.
This condition is inherited in an X-linked pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell sometimes causes features of the disorder; in other cases, these females do not experience any symptoms.  In the small number of Arts syndrome cases that have been identified, affected individuals have inherited the mutation from a mother who carries an altered copy of the PRPS1 gene.
These resources address the diagnosis or management of Arts syndrome:  - Gene Review: Gene Review: Arts Syndrome  - Genetic Testing Registry: Arts syndrome  - MedlinePlus Encyclopedia: Hearing Loss  - MedlinePlus Encyclopedia: Movement, Uncoordinated  - MedlinePlus Encyclopedia: Optic Nerve Atrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care
Triple A syndrome is an inherited condition characterized by three specific features: achalasia, Addison disease, and alacrima. Achalasia is a disorder that affects the ability to move food through the esophagus, the tube that carries food from the throat to the stomach. It can lead to severe feeding difficulties and low blood sugar (hypoglycemia). Addison disease, also known as primary adrenal insufficiency, is caused by abnormal function of the small hormone-producing glands on top of each kidney (adrenal glands). The main features of Addison disease include fatigue, loss of appetite, weight loss, low blood pressure, and darkening of the skin. The third major feature of triple A syndrome is a reduced or absent ability to secrete tears (alacrima). Most people with triple A syndrome have all three of these features, although some have only two.  Many of the features of triple A syndrome are caused by dysfunction of the autonomic nervous system. This part of the nervous system controls involuntary body processes such as digestion, blood pressure, and body temperature. People with triple A syndrome often experience abnormal sweating, difficulty regulating blood pressure, unequal pupil size (anisocoria), and other signs and symptoms of autonomic nervous system dysfunction (dysautonomia).  People with this condition may have other neurological abnormalities, such as developmental delay, intellectual disability, speech problems (dysarthria), and a small head size (microcephaly). In addition, affected individuals commonly experience muscle weakness, movement problems, and nerve abnormalities in their extremities (peripheral neuropathy). Some develop optic atrophy, which is the degeneration (atrophy) of the nerves that carry information from the eyes to the brain. Many of the neurological symptoms of triple A syndrome worsen over time.  People with triple A syndrome frequently develop a thickening of the outer layer of skin (hyperkeratosis) on the palms of their hands and the soles of their feet. Other skin abnormalities may also be present in people with this condition.  Alacrima is usually the first noticeable sign of triple A syndrome, as it becomes apparent early in life that affected children produce little or no tears while crying. They develop Addison disease and achalasia during childhood or adolescence, and most of the neurologic features of triple A syndrome begin during adulthood. The signs and symptoms of this condition vary among affected individuals, even among members of the same family.
Mutations in the AAAS gene cause triple A syndrome. This gene provides instructions for making a protein called ALADIN whose function is not well understood. Within cells, ALADIN is found in the nuclear envelope, the structure that surrounds the nucleus and separates it from the rest of the cell. Based on its location, ALADIN is thought to be involved in the movement of molecules into and out of the nucleus.  Mutations in the AAAS gene change the structure of ALADIN in different ways; however, almost all mutations prevent this protein from reaching its proper location in the nuclear envelope. The absence of ALADIN in the nuclear envelope likely disrupts the movement of molecules across this membrane. Researchers suspect that DNA repair proteins may be unable to enter the nucleus if ALADIN is missing from the nuclear envelope. DNA damage that is not repaired can cause the cell to become unstable and lead to cell death. Although the nervous system is particularly vulnerable to DNA damage, it remains unknown exactly how mutations in the AAAS gene lead to the signs and symptoms of triple A syndrome.  Some individuals with triple A syndrome do not have an identified mutation in the AAAS gene. The genetic cause of the disorder is unknown in these individuals.
These resources address the diagnosis or management of triple A syndrome:  - Genetic Testing Registry: Glucocorticoid deficiency with achalasia  - MedlinePlus Encyclopedia: Achalasia  - MedlinePlus Encyclopedia: Anisocoria   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care
Ichthyosis with confetti is a disorder of the skin. Individuals with this condition are born with red, scaly skin all over the body, which can be itchy in some people. In childhood or adolescence, hundreds to thousands of small patches of normal skin appear, usually on the torso. The numerous pale spots surrounded by red skin look like confetti, giving the condition its name. The patches of normal skin increase in number and size over time.  In addition to red, scaly skin, people with ichthyosis with confetti typically have abnormally thick skin on the palms of the hands and soles of the feet (palmoplantar keratoderma). Many affected individuals have excess hair (hirsutism) on some parts of the body, particularly on the arms and legs. Because of their skin abnormalities, people with ichthyosis with confetti are at increased risk of developing skin infections.
Mutations in the KRT10 gene cause ichthyosis with confetti. This gene provides instructions for making a protein called keratin 10, which is found in cells called keratinocytes in the outer layer of the skin (the epidermis). In the fluid-filled space inside these cells (the cytoplasm), this tough, fibrous protein attaches to another keratin protein (produced from a different gene) to form fibers called intermediate filaments. These filaments assemble into strong networks that provide strength and resiliency to the skin.  KRT10 gene mutations associated with ichthyosis with confetti alter the keratin 10 protein. The altered protein is abnormally transported to the nucleus of cells, where it cannot form networks of intermediate filaments. Loss of these networks disrupts the epidermis, contributing to the red, scaly skin. However, in some abnormal cells, the mutated gene corrects itself through a complex process by which genetic material is exchanged between chromosomes. As a result, normal keratin 10 protein is produced and remains in the cytoplasm. The cell becomes normal and, as it continues to grow and divide, forms small patches of normal skin that give ichthyosis with confetti its name.
These resources address the diagnosis or management of ichthyosis with confetti:  - Foundation for Ichthyosis and Related Skin Types (FIRST): Skin Care Tips  - Foundation for Ichthyosis and Related Skin Types (FIRST): Treating Ichthyosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care
Congenital leptin deficiency is a condition that causes severe obesity beginning in the first few months of life. Affected individuals are of normal weight at birth, but they are constantly hungry and quickly gain weight. Without treatment, the extreme hunger continues and leads to chronic excessive eating (hyperphagia) and obesity. Beginning in early childhood, affected individuals develop abnormal eating behaviors such as fighting with other children over food, hoarding food, and eating in secret.  People with congenital leptin deficiency also have hypogonadotropic hypogonadism, which is a condition caused by reduced production of hormones that direct sexual development. Without treatment, affected individuals experience delayed puberty or do not go through puberty, and may be unable to conceive children (infertile).
Congenital leptin deficiency is caused by mutations in the LEP gene. This gene provides instructions for making a hormone called leptin, which is involved in the regulation of body weight. Normally, the body's fat cells release leptin in proportion to their size. As fat accumulates in cells, more leptin is produced. This rise in leptin indicates that fat stores are increasing.  Leptin attaches (binds) to and activates a protein called the leptin receptor, fitting into the receptor like a key into a lock. The leptin receptor protein is found on the surface of cells in many organs and tissues of the body including a part of the brain called the hypothalamus. The hypothalamus controls hunger and thirst as well as other functions such as sleep, moods, and body temperature. It also regulates the release of many hormones that have functions throughout the body. In the hypothalamus, the binding of leptin to its receptor triggers a series of chemical signals that affect hunger and help produce a feeling of fullness (satiety).  LEP gene mutations that cause congenital leptin deficiency lead to an absence of leptin. As a result, the signaling that triggers feelings of satiety does not occur, leading to the excessive hunger and weight gain associated with this disorder. Because hypogonadotropic hypogonadism occurs in congenital leptin deficiency, researchers suggest that leptin signaling is also involved in regulating the hormones that control sexual development. However, the specifics of this involvement and how it may be altered in congenital leptin deficiency are unknown.  Congenital leptin deficiency is a rare cause of obesity. Researchers are studying the factors involved in more common forms of obesity.
These resources address the diagnosis or management of congenital leptin deficiency:  - Eunice Kennedy Shriver National Institute of Child Health and Human Development: How Are Obesity and Overweight Diagnosed?  - Genetic Testing Registry: Obesity, severe, due to leptin deficiency  - Genetics of Obesity Study  - National Heart, Lung, and Blood Institute: How Are Overweight and Obesity Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care
Erythromelalgia is a condition characterized by episodes of pain, redness, and swelling in various parts of the body, particularly the hands and feet. These episodes are usually triggered by increased body temperature, which may be caused by exercise or entering a warm room. Ingesting alcohol or spicy foods may also trigger an episode. Wearing warm socks, tight shoes, or gloves can cause a pain episode so debilitating that it can impede everyday activities such as wearing shoes and walking. Pain episodes can prevent an affected person from going to school or work regularly.  The signs and symptoms of erythromelalgia typically begin in childhood, although mildly affected individuals may have their first pain episode later in life. As individuals with erythromelalgia get older and the disease progresses, the hands and feet may be constantly red, and the affected areas can extend from the hands to the arms, shoulders, and face, and from the feet to the entire legs.  Erythromelalgia is often considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and pain.
Mutations in the SCN9A gene can cause erythromelalgia. The SCN9A gene provides instructions for making one part (the alpha subunit) of a sodium channel called NaV1.7. Sodium channels transport positively charged sodium atoms (sodium ions) into cells and play a key role in a cell's ability to generate and transmit electrical signals. NaV1.7 sodium channels are found in nerve cells called nociceptors that transmit pain signals to the spinal cord and brain.  The SCN9A gene mutations that cause erythromelalgia result in NaV1.7 sodium channels that open more easily than usual and stays open longer than normal, increasing the flow of sodium ions into nociceptors. This increase in sodium ions enhances transmission of pain signals, leading to the signs and symptoms of erythromelalgia. It is unknown why the pain episodes associated with erythromelalgia mainly occur in the hands and feet.  An estimated 15 percent of cases of erythromelalgia are caused by mutations in the SCN9A gene. Other cases are thought to have a nongenetic cause or may be caused by mutations in one or more as-yet unidentified genes.