Input: What is (are) adolescent idiopathic scoliosis ?

Output: Adolescent idiopathic scoliosis is an abnormal curvature of the spine that appears in late childhood or adolescence. Instead of growing straight, the spine develops a side-to-side curvature, usually in an elongated "S" or "C" shape; the bones of the spine are also slightly twisted or rotated.  Adolescent idiopathic scoliosis appears during the adolescent growth spurt, a time when children are growing rapidly. In many cases the abnormal spinal curve is stable, although in some children the curve is progressive (meaning it becomes more severe over time). For unknown reasons, severe and progressive curves occur more frequently in girls than in boys. However, mild spinal curvature is equally common in girls and boys.  Mild scoliosis generally does not cause pain, problems with movement, or difficulty breathing. It may only be diagnosed if it is noticed during a regular physical examination or a scoliosis screening at school. The most common signs of the condition include a tilt or unevenness (asymmetry) in the shoulders, hips, or waist, or having one leg that appears longer than the other. A small percentage of affected children develop more severe, pronounced spinal curvature.  Scoliosis can occur as a feature of other conditions, including a variety of genetic syndromes. However, adolescent idiopathic scoliosis typically occurs by itself, without signs and symptoms affecting other parts of the body. </s>


Input: How many people are affected by adolescent idiopathic scoliosis ?

Output: Adolescent idiopathic scoliosis is the most common spinal abnormality in children. It affects an estimated 2 to 3 percent of children in the U.S. </s>


Input: What are the genetic changes related to adolescent idiopathic scoliosis ?

Output: The term "idiopathic" means that the cause of this condition is unknown. Adolescent idiopathic scoliosis probably results from a combination of genetic and environmental factors. Studies suggest that the abnormal spinal curvature may be related to hormonal problems, abnormal bone or muscle growth, nervous system abnormalities, or other factors that have not been identified.  Researchers suspect that many genes are involved in adolescent idiopathic scoliosis. Some of these genes likely contribute to causing the disorder, while others play a role in determining the severity of spinal curvature and whether the curve is stable or progressive. Although many genes have been studied, few clear and consistent genetic associations with adolescent idiopathic scoliosis have been identified. </s>


Input: Is adolescent idiopathic scoliosis inherited ?

Output: Adolescent idiopathic scoliosis can be sporadic, which means it occurs in people without a family history of the condition, or it can cluster in families. The inheritance pattern of adolescent idiopathic scoliosis is unclear because many genetic and environmental factors appear to be involved. However, having a close relative (such as a parent or sibling) with adolescent idiopathic scoliosis increases a child's risk of developing the condition. </s>


Input: What are the treatments for adolescent idiopathic scoliosis ?

Output: These resources address the diagnosis or management of adolescent idiopathic scoliosis:  - Genetic Testing Registry: Scoliosis, idiopathic 1  - Genetic Testing Registry: Scoliosis, idiopathic 2  - Genetic Testing Registry: Scoliosis, idiopathic 3  - National Scoliosis Foundation: FAQs  - Scoliosis Research Society: Find A Specialist  - Scoliosis Research Society: For Adolescents   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 </s>


Input: What is (are) polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy ?

Output: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, commonly known as PLOSL, is a progressive disorder that affects the bones and brain. "Polycystic lipomembranous osteodysplasia" refers to cyst-like bone changes that can be seen on x-rays. "Sclerosing leukoencephalopathy" describes specific changes in the brain that are found in people with this disorder.  The bone abnormalities associated with PLOSL usually become apparent in a person's twenties. In most affected individuals, pain and tenderness in the ankles and feet are the first symptoms of the disease. Several years later, broken bones (fractures) begin to occur frequently, particularly in bones of the ankles, feet, wrists, and hands. Bone pain and fractures are caused by thinning of the bones (osteoporosis) and cyst-like changes. These abnormalities weaken bones and make them more likely to break.  The brain abnormalities characteristic of PLOSL typically appear in a person's thirties. Personality changes are among the first noticeable problems, followed by a loss of judgment, feelings of intense happiness (euphoria), a loss of inhibition, and poor concentration. These neurologic changes cause significant problems in an affected person's social and family life. As the disease progresses, it causes a severe decline in thinking and reasoning abilities (dementia). Affected people ultimately become unable to walk, speak, or care for themselves. People with this disease usually live only into their thirties or forties. </s>


Input: How many people are affected by polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy ?

Output: PLOSL is a very rare condition. It was first reported in the Finnish population, where it has an estimated prevalence of 1 to 2 per million people. This condition has also been diagnosed in more than 100 people in the Japanese population. Although affected individuals have been reported worldwide, PLOSL appears to be less common in other countries. </s>


Input: What are the genetic changes related to polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy ?

Output: Mutations in the TREM2 gene or the TYROBP gene (also called DAP12) can cause PLOSL. The proteins produced from these two genes work together to activate certain kinds of cells. These proteins appear to be particularly important in osteoclasts, which are specialized cells that break down and remove (resorb) bone tissue that is no longer needed. These cells are involved in bone remodeling, which is a normal process that replaces old bone tissue with new bone. The TREM2 and TYROBP proteins are also critical for the normal function of microglia, which are a type of immune cell in the brain and spinal cord (central nervous system). Although these proteins play essential roles in osteoclasts and microglia, their exact function in these cells is unclear.  Mutations in the TREM2 or TYROBP gene disrupt normal bone growth and lead to progressive brain abnormalities in people with PLOSL. Researchers believe that the bone changes seen with this disorder are related to malfunctioning osteoclasts, which are less able to resorb bone tissue during bone remodeling. In the central nervous system, TREM2 or TYROBP mutations cause widespread abnormalities of microglia. Researchers are working to determine how these abnormalities lead to the progressive neurological problems associated with PLOSL. </s>


Input: Is polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy inherited ?

Output: This condition is 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. </s>


Input: What are the treatments for polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy ?

Output: These resources address the diagnosis or management of PLOSL:  - Gene Review: Gene Review: Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL)  - Genetic Testing Registry: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy  - MedlinePlus Encyclopedia: Dementia   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 </s>


Input: What is (are) aromatase excess syndrome ?

Output: Aromatase excess syndrome is a condition characterized by elevated levels of the female sex hormone estrogen in both males and females. Males with aromatase excess syndrome experience breast enlargement (gynecomastia) in late childhood or adolescence. The bones of affected males grow and develop more quickly and stop growing sooner than usual (advanced bone age). As a result males have an early growth spurt, typically during late childhood, with short stature as an adult. Affected females rarely show signs and symptoms of the condition, but they may have increased breast growth (macromastia), irregular menstrual periods, and short stature. The ability to have children (fertility) is usually normal in both males and females with aromatase excess syndrome. </s>


Input: How many people are affected by aromatase excess syndrome ?

Output: The prevalence of aromatase excess syndrome is unknown; more than 20 cases have been described in the medical literature. </s>


Input: What are the genetic changes related to aromatase excess syndrome ?

Output: Rearrangements of genetic material involving the CYP19A1 gene cause aromatase excess syndrome. The CYP19A1 gene provides instructions for making an enzyme called aromatase. This enzyme converts a class of hormones called androgens, which are involved in male sexual development, to different forms of estrogen. In females, estrogen guides female sexual development before birth and during puberty. In both males and females, estrogen plays a role in regulating bone growth.  The condition can result from several types of genetic rearrangements involving the CYP19A1 gene. These rearrangements alter the activity of the gene and lead to an increase in aromatase production. In affected males, the increased aromatase and subsequent conversion of androgens to estrogen are responsible for the gynecomastia and limited bone growth characteristic of aromatase excess syndrome. Increased estrogen in females can cause symptoms such as irregular menstrual periods and short stature. </s>


Input: Is aromatase excess syndrome inherited ?

Output: This condition is inherited in an autosomal dominant pattern, which means a genetic rearrangement involving one copy of the CYP19A1 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 genetic changes and occur in people with no history of the disorder in their family. </s>


Input: What are the treatments for aromatase excess syndrome ?

Output: These resources address the diagnosis or management of aromatase excess syndrome:  - Genetic Testing Registry: Familial gynecomastia, due to increased aromatase activity   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 </s>


Input: What is (are) juvenile primary lateral sclerosis ?

Output: Juvenile primary lateral sclerosis is a rare disorder characterized by progressive weakness and tightness (spasticity) of muscles in the arms, legs, and face. The features of this disorder are caused by damage to motor neurons, which are specialized nerve cells in the brain and spinal cord that control muscle movement.  Symptoms of juvenile primary lateral sclerosis begin in early childhood and progress slowly over many years. Early symptoms include clumsiness, muscle weakness and spasticity in the legs, and difficulty with balance. As symptoms progress, the spasticity spreads to the arms and hands and individuals develop slurred speech, drooling, difficulty swallowing, and an inability to walk. </s>


Input: How many people are affected by juvenile primary lateral sclerosis ?

Output: Juvenile primary lateral sclerosis is a rare disorder, with few reported cases. </s>


Input: What are the genetic changes related to juvenile primary lateral sclerosis ?

Output: Mutations in the ALS2 gene cause most cases of juvenile primary lateral sclerosis. This gene provides instructions for making a protein called alsin. Alsin is abundant in motor neurons, but its function is not fully understood. Mutations in the ALS2 gene alter the instructions for producing alsin. As a result, alsin is unstable and is quickly broken down, or it cannot function properly. It is unclear how the loss of functional alsin protein damages motor neurons and causes juvenile primary lateral sclerosis. </s>


Input: Is juvenile primary lateral sclerosis inherited ?

Output: When caused by mutations in the ALS2 gene, juvenile primary lateral sclerosis is 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. </s>


Input: What are the treatments for juvenile primary lateral sclerosis ?

Output: These resources address the diagnosis or management of juvenile primary lateral sclerosis:  - Gene Review: Gene Review: ALS2-Related Disorders  - Genetic Testing Registry: Juvenile primary lateral sclerosis   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 </s>


Input: What is (are) myasthenia gravis ?

Output: Myasthenia gravis is a disorder that causes weakness of the skeletal muscles, which are muscles that the body uses for movement. The weakness most often starts in the muscles around the eyes, causing drooping of the eyelids (ptosis) and difficulty coordinating eye movements, which results in blurred or double vision. In a form of the disorder called ocular myasthenia, the weakness remains confined to the eye muscles. In most people with myasthenia gravis, however, additional muscles in the face and neck are affected. Affected individuals may have unusual facial expressions, difficulty holding up the head, speech impairment (dysarthria), and chewing and swallowing problems (dysphagia) that may lead to choking, gagging, or drooling.  Other muscles in the body are also affected in some people with myasthenia gravis. The muscles of the arms and legs may be involved, causing affected individuals to have changes in their gait or trouble with lifting objects, rising from a seated position, or climbing stairs. The muscle weakness tends to fluctuate over time; it typically worsens with activity and improves with rest.  Weakness of the muscles in the chest wall and the muscle that separates the abdomen from the chest cavity (the diaphragm) can cause breathing problems in some people with myasthenia gravis. About 10 percent of people with this disorder experience a potentially life-threatening complication in which these respiratory muscles weaken to the point that breathing is dangerously impaired, and the affected individual requires ventilation assistance. This respiratory failure, called a myasthenic crisis, may be triggered by stresses such as infections or reactions to medications.  People can develop myasthenia gravis at any age. For reasons that are unknown, it is most commonly diagnosed in women younger than age 40 and men older than age 60. It is uncommon in children, but some infants born to women with myasthenia gravis show signs and symptoms of the disorder for the first few days or weeks of life. This temporary occurrence of symptoms is called transient neonatal myasthenia gravis. </s>


Input: How many people are affected by myasthenia gravis ?

Output: Myasthenia gravis affects about 20 per 100,000 people worldwide. The prevalence has been increasing in recent decades, which likely results from earlier diagnosis and better treatments leading to longer lifespans for affected individuals. </s>


Input: What are the genetic changes related to myasthenia gravis ?

Output: Researchers believe that variations in particular genes may increase the risk of myasthenia gravis, but the identity of these genes is unknown. Many factors likely contribute to the risk of developing this complex disorder.  Myasthenia gravis is an autoimmune disorder, which occurs when the immune system malfunctions and attacks the body's own tissues and organs. In myasthenia gravis, the immune system disrupts the transmission of nerve impulses to muscles by producing a protein called an antibody that attaches (binds) to proteins important for nerve signal transmission. Antibodies normally bind to specific foreign particles and germs, marking them for destruction, but the antibody in myasthenia gravis attacks a normal human protein. In most affected individuals, the antibody targets a protein called acetylcholine receptor (AChR); in others, the antibodies attack a related protein called muscle-specific kinase (MuSK). In both cases, the abnormal antibodies lead to a reduction of available AChR.  The AChR protein is critical for signaling between nerve and muscle cells, which is necessary for movement. In myasthenia gravis, because of the abnormal immune response, less AChR is present, which reduces signaling between nerve and muscle cells. These signaling abnormalities lead to decreased muscle movement and the muscle weakness characteristic of this condition.  It is unclear why the immune system malfunctions in people with myasthenia gravis. About 75 percent of affected individuals have an abnormally large and overactive thymus, which is a gland located behind the breastbone that plays an important role in the immune system. The thymus sometimes develops tumors (thymomas) that are usually noncancerous (benign). However, the relationship between the thymus problems and the specific immune system malfunction that occurs in myasthenia gravis is not well understood.  People with myasthenia gravis are at increased risk of developing other autoimmune disorders, including autoimmune thyroid disease and systemic lupus erythematosus. Gene variations that affect immune system function likely affect the risk of developing myasthenia gravis and other autoimmune disorders.  Some families are affected by an inherited disorder with symptoms similar to those of myasthenia gravis, but in which antibodies to the AChR or MuSK proteins are not present. This condition, which is not an autoimmune disorder, is called congenital myasthenic syndrome. </s>


Input: Is myasthenia gravis inherited ?

Output: In most cases, myasthenia gravis is not inherited and occurs in people with no history of the disorder in their family. About 3 to 5 percent of affected individuals have other family members with myasthenia gravis or other autoimmune disorders, but the inheritance pattern is unknown. </s>


Input: What are the treatments for myasthenia gravis ?

Output: These resources address the diagnosis or management of myasthenia gravis:  - Cleveland Clinic  - Genetic Testing Registry: Myasthenia gravis  - Genetic Testing Registry: Myasthenia gravis with thymus hyperplasia  - MedlinePlus Encyclopedia: Acetylcholine Receptor Antibody  - MedlinePlus Encyclopedia: Tensilon Test   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 </s>


Input: What is (are) familial isolated pituitary adenoma ?

Output: Familial isolated pituitary adenoma (FIPA) is an inherited condition characterized by development of a noncancerous tumor in the pituitary gland (called a pituitary adenoma). The pituitary gland, which is found at the base of the brain, produces hormones that control many important body functions.  Tumors that form in the pituitary gland can release excess levels of one or more hormones, although some tumors do not produce hormones (nonfunctioning pituitary adenomas). Those that do are typically distinguished by the particular hormones they produce. Prolactinomas are the most common tumors in FIPA. These tumors release prolactin, a hormone that stimulates breast milk production in females. Both women and men can develop prolactinomas, although they are more common in women. In women, these tumors may lead to changes in the menstrual cycle or difficulty becoming pregnant. Some affected women may produce breast milk, even though they are not pregnant or nursing. In men, prolactinomas may cause erectile dysfunction or decreased interest in sex. Rarely, affected men produce breast milk. Large prolactinomas can press on nearby tissues such as the nerves that carry information from the eyes to the brain (the optic nerves), causing problems with vision.  Another type of tumor called somatotropinoma is also common in FIPA. These tumors release growth hormone (also called somatotropin), which promotes growth of the body. Somatotropinomas in children or adolescents can lead to increased height (gigantism), because the long bones of their arms and legs are still growing. In adults, growth of the long bones has stopped, but the tumors can cause overgrowth of the hands, feet, and face (acromegaly) as well as other tissues.  Less common tumor types in FIPA include somatolactotropinomas, nonfunctioning pituitary adenomas, adrenocorticotropic hormone-secreting tumors (which cause a condition known as Cushing disease), thyrotropinomas, and gonadotropinomas. In a family with the condition, affected members can develop the same type of tumor (homogenous FIPA) or different types (heterogenous FIPA).  In FIPA, pituitary tumors usually occur at a younger age than sporadic pituitary adenomas, which are not inherited. In general, FIPA tumors are also larger than sporadic pituitary tumors. Often, people with FIPA have macroadenomas, which are tumors larger than 10 millimeters.  Familial pituitary adenomas can occur as one of many features in other inherited conditions such as multiple endocrine neoplasia type 1 and Carney complex; however, in FIPA, the pituitary adenomas are described as isolated because only the pituitary gland is affected. </s>


Input: How many people are affected by familial isolated pituitary adenoma ?

Output: Pituitary adenomas, including sporadic tumors, are relatively common; they are identified in an estimated 1 in 1,000 people. FIPA, though, is quite rare, accounting for approximately 2 percent of pituitary adenomas. More than 200 families with FIPA have been described in the medical literature. </s>


Input: What are the genetic changes related to familial isolated pituitary adenoma ?

Output: FIPA can be caused by mutations in the AIP gene. The function of the protein produced from this gene is not well understood, but it is thought to act as a tumor suppressor, which means it helps prevent cells from growing and dividing in an uncontrolled way. Mutations in the AIP gene alter the protein or reduce the production of functional protein. These changes likely impair the ability of the AIP protein to control the growth and division of cells, allowing pituitary cells to grow and divide unchecked and form a tumor. It is not known why the pituitary gland is specifically affected or why certain types of pituitary adenomas develop.  AIP gene mutations account for approximately 15 to 25 percent of cases of FIPA. Somatotropinomas are the most common type of tumor in these individuals. The tumors usually occur at a younger age, often in childhood, and are larger than FIPA tumors not caused by AIP gene mutations. The other genetic causes of FIPA are unknown. </s>


Input: Is familial isolated pituitary adenoma inherited ?

Output: FIPA is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. However, only 20 to 30 percent of individuals with an AIP gene mutation develop a pituitary adenoma. This phenomenon, in which some individuals with a mutation do not develop the features of a particular disorder, is called incomplete penetrance. </s>


Input: What are the treatments for familial isolated pituitary adenoma ?

Output: These resources address the diagnosis or management of familial isolated pituitary adenoma:  - American Cancer Society: How are Pituitary Tumors Diagnosed?  - Gene Review: Gene Review: AIP-Related Familial Isolated Pituitary Adenomas  - Genetic Testing Registry: AIP-Related Familial Isolated Pituitary Adenomas  - MedlinePlus Encyclopedia: Prolactinoma  - MedlinePlus Health Topic: Pituitary Tumors   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 </s>


Input: What is (are) dopamine beta-hydroxylase deficiency ?

Output: Dopamine beta ()-hydroxylase deficiency is a condition that affects the autonomic nervous system, which controls involuntary body processes such as the regulation of blood pressure and body temperature. Problems related to this disorder can first appear during infancy. Early signs and symptoms may include episodes of vomiting, dehydration, decreased blood pressure (hypotension), difficulty maintaining body temperature, and low blood sugar (hypoglycemia).  Individuals with dopamine -hydroxylase deficiency typically experience a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting. This sudden drop in blood pressure is usually more severe when getting out of bed in the morning, during hot weather, and as a person gets older. People with dopamine -hydroxylase deficiency experience extreme fatigue during exercise (exercise intolerance) due to their problems maintaining a normal blood pressure.  Other features of dopamine -hydroxylase deficiency include droopy eyelids (ptosis), nasal congestion, and an inability to stand for a prolonged period of time. Affected males may also experience retrograde ejaculation, a discharge of semen backwards into the bladder. Less common features include an unusually large range of joint movement (hypermobility) and muscle weakness. </s>


Input: How many people are affected by dopamine beta-hydroxylase deficiency ?

Output: Dopamine -hydroxylase deficiency is a very rare disorder. Fewer than 20 affected individuals, all of Western European descent, have been described in the scientific literature. </s>


Input: What are the genetic changes related to dopamine beta-hydroxylase deficiency ?

Output: Mutations in the DBH gene cause dopamine -hydroxylase deficiency. The DBH gene provides instructions for producing the enzyme dopamine -hydroxylase. This enzyme converts dopamine to norepinephrine, both of which are chemical messengers (neurotransmitters) that transmit signals between nerve cells.  DBH gene mutations result in the production of a nonfunctional dopamine -hydroxylase enzyme. People who lack functional dopamine -hydroxylase cannot convert dopamine to norepinephrine, which leads to a shortage of norepinephrine in the body. The lack of norepinephrine causes difficulty with regulating blood pressure and other autonomic nervous system problems seen in dopamine -hydroxylase deficiency. </s>


Input: Is dopamine beta-hydroxylase deficiency inherited ?

Output: This condition is 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. </s>


Input: What are the treatments for dopamine beta-hydroxylase deficiency ?

Output: These resources address the diagnosis or management of dopamine beta-hydroxylase deficiency:  - Gene Review: Gene Review: Dopamine Beta-Hydroxylase Deficiency  - Genetic Testing Registry: Dopamine beta hydroxylase deficiency  - Vanderbilt Autonomic Dysfunction Center   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 </s>


Input: What is (are) holocarboxylase synthetase deficiency ?

Output: Holocarboxylase synthetase deficiency is an inherited disorder in which the body is unable to use the vitamin biotin effectively. This disorder is classified as a multiple carboxylase deficiency, a group of disorders characterized by impaired activity of certain enzymes that depend on biotin.  The signs and symptoms of holocarboxylase synthetase deficiency typically appear within the first few months of life, but the age of onset varies. Affected infants often have difficulty feeding, breathing problems, a skin rash, hair loss (alopecia), and a lack of energy (lethargy). Immediate treatment and lifelong management with biotin supplements may prevent many of these complications. If left untreated, the disorder can lead to delayed development, seizures, and coma. These medical problems may be life-threatening in some cases. </s>


Input: How many people are affected by holocarboxylase synthetase deficiency ?

Output: The exact incidence of this condition is unknown, but it is estimated to affect 1 in 87,000 people. </s>


Input: What are the genetic changes related to holocarboxylase synthetase deficiency ?

Output: Mutations in the HLCS gene cause holocarboxylase synthetase deficiency.  The HLCS gene provides instructions for making an enzyme called holocarboxylase synthetase. This enzyme is important for the effective use of biotin, a B vitamin found in foods such as liver, egg yolks, and milk. Holocarboxylase synthetase attaches biotin to certain enzymes that are essential for the normal production and breakdown of proteins, fats, and carbohydrates in the body. Mutations in the HLCS gene reduce the enzyme's ability to attach biotin to these enzymes, preventing them from processing nutrients properly and disrupting many cellular functions. These defects lead to the serious medical problems associated with holocarboxylase synthetase deficiency. </s>


Input: Is holocarboxylase synthetase deficiency inherited ?

Output: This condition is 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. </s>


Input: What are the treatments for holocarboxylase synthetase deficiency ?

Output: These resources address the diagnosis or management of holocarboxylase synthetase deficiency:  - Baby's First Test  - Genetic Testing Registry: Holocarboxylase synthetase deficiency  - MedlinePlus Encyclopedia: Pantothenic Acid and Biotin   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 </s>


Input: What is (are) multiple familial trichoepithelioma ?

Output: Multiple familial trichoepithelioma is a condition involving multiple skin tumors that develop from structures associated with the skin (skin appendages), such as hair follicles and sweat glands. People with multiple familial trichoepithelioma typically develop large numbers of smooth, round tumors called trichoepitheliomas, which arise from hair follicles. Trichoepitheliomas are generally noncancerous (benign) but occasionally develop into a type of skin cancer called basal cell carcinoma.  Individuals with multiple familial trichoepithelioma occasionally also develop other types of tumors, including growths called spiradenomas and cylindromas. Spiradenomas develop in sweat glands. The origin of cylindromas has been unclear; while previously thought to derive from sweat glands, they are now generally believed to begin in hair follicles. Affected individuals are also at increased risk of developing tumors in tissues other than skin appendages, particularly benign or malignant tumors of the salivary glands.  People with multiple familial trichoepithelioma typically begin developing tumors during childhood or adolescence. The tumors mostly appear on the face, especially in the folds in the skin between the nose and lips (nasolabial folds, sometimes called smile lines), but may also occur on the neck, scalp, or trunk. They may grow larger and increase in number over time.  In severe cases, the tumors may get in the way of the eyes, ears, nose, or mouth and affect vision, hearing, or other functions. The growths can be disfiguring and may contribute to depression or other psychological problems. For reasons that are unclear, females with multiple familial trichoepithelioma are often more severely affected than males. </s>


Input: How many people are affected by multiple familial trichoepithelioma ?

Output: Multiple familial trichoepithelioma is a rare disorder; its prevalence is unknown. </s>


Input: What are the genetic changes related to multiple familial trichoepithelioma ?

Output: Multiple familial trichoepithelioma can be caused by mutations in the CYLD gene. This gene provides instructions for making a protein that helps regulate nuclear factor-kappa-B. Nuclear factor-kappa-B is a group of related proteins that help protect cells from self-destruction (apoptosis) in response to certain signals. In regulating the action of nuclear factor-kappa-B, the CYLD protein allows cells to respond properly to signals to self-destruct when appropriate, such as when the cells become abnormal. By this mechanism, the CYLD protein acts as a tumor suppressor, which means that it helps prevent cells from growing and dividing too fast or in an uncontrolled way.  People with CYLD-related multiple familial trichoepithelioma are born with a mutation in one of the two copies of the CYLD gene in each cell. This mutation prevents the cell from making functional CYLD protein from the altered copy of the gene. However, enough protein is usually produced from the other, normal copy of the gene to regulate cell growth effectively. For tumors to develop, a second mutation or deletion of genetic material involving the other copy of the CYLD gene must occur in certain cells during a person's lifetime.  When both copies of the CYLD gene are mutated in a particular cell, that cell cannot produce any functional CYLD protein. The loss of this protein allows the cell to grow and divide in an uncontrolled way to form a tumor. In people with multiple familial trichoepithelioma, a second CYLD mutation typically occurs in multiple cells over an affected person's lifetime. The loss of CYLD protein in these cells leads to the growth of skin appendage tumors.  Some researchers consider multiple familial trichoepithelioma and two related conditions called familial cylindromatosis and Brooke-Spiegler syndrome, which are also caused by CYLD gene mutations, to be different forms of the same disorder. It is unclear why mutations in the CYLD gene cause different patterns of skin appendage tumors in each of these conditions, or why the tumors are generally confined to the skin in these disorders.  Some people with multiple familial trichoepithelioma do not have mutations in the CYLD gene. Scientists are working to identify the genetic cause of the disorder in these individuals. </s>


Input: Is multiple familial trichoepithelioma inherited ?

Output: Susceptibility to multiple familial trichoepithelioma has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell increases the risk of developing this condition. However, a second, non-inherited mutation is required for development of skin appendage tumors in this disorder. </s>


Input: What are the treatments for multiple familial trichoepithelioma ?

Output: These resources address the diagnosis or management of multiple familial trichoepithelioma:  - Genetic Testing Registry: Familial multiple trichoepitheliomata  - Genetic Testing Registry: Trichoepithelioma multiple familial 2   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 </s>


Input: What is (are) myoclonic epilepsy myopathy sensory ataxia ?

Output: Myoclonic epilepsy myopathy sensory ataxia, commonly called MEMSA, is part of a group of conditions called the POLG-related disorders. The conditions in this group feature a range of similar signs and symptoms involving muscle-, nerve-, and brain-related functions. The signs and symptoms of MEMSA typically appear during young adulthood. This condition had previously been known as spinocerebellar ataxia with epilepsy (SCAE).  The first symptom of MEMSA is usually cerebellar ataxia, which refers to problems with coordination and balance due to defects in the part of the brain that is involved in coordinating movement (cerebellum). Recurrent seizures (epilepsy) usually develop later, often in combination with uncontrollable muscle jerks (myoclonus). The seizures usually begin in the right arm and spread to become generalized throughout the body. Additionally, affected individuals may have severe brain dysfunction (encephalopathy) or muscle weakness (myopathy). The myopathy can affect muscles close to the center of the body (proximal), such as the muscles of the hips, thighs, upper arms, or neck, or muscles farther away from the center of the body (distal), such as the muscles of the hands or feet. The myopathy may be especially noticeable during exercise (exercise intolerance). </s>


Input: How many people are affected by myoclonic epilepsy myopathy sensory ataxia ?

Output: The prevalence of myoclonic epilepsy myopathy sensory ataxia is unknown. </s>


Input: What are the genetic changes related to myoclonic epilepsy myopathy sensory ataxia ?

Output: MEMSA is caused by mutations in the POLG gene. This gene provides instructions for making one part, the alpha subunit, of a protein called polymerase gamma (pol ). Pol  functions in mitochondria, which are structures within cells that use oxygen to convert the energy from food into a form cells can use. Mitochondria each contain a small amount of DNA, known as mitochondrial DNA (mtDNA), which is essential for the normal function of these structures. Pol  "reads" sequences of mtDNA and uses them as templates to produce new copies of mtDNA in a process called DNA replication.  Most POLG gene mutations change single protein building blocks (amino acids) in the alpha subunit of pol . These changes result in a mutated pol  that has a reduced ability to replicate DNA. Although the mechanism is unknown, mutations in the POLG gene often result in fewer copies of mtDNA (mtDNA depletion), particularly in muscle, brain, or liver cells. MtDNA depletion causes a decrease in cellular energy, which could account for the signs and symptoms of MEMSA. </s>


Input: Is myoclonic epilepsy myopathy sensory ataxia inherited ?

Output: This condition is 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. </s>


Input: What are the treatments for myoclonic epilepsy myopathy sensory ataxia ?

Output: These resources address the diagnosis or management of MEMSA:  - Gene Review: Gene Review: POLG-Related Disorders  - Genetic Testing Registry: Myoclonic epilepsy myopathy sensory ataxia  - United Mitochondrial Disease Foundation: Diagnosis of Mitochondrial Disease   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 </s>


Input: What is (are) Salih myopathy ?

Output: Salih myopathy is an inherited muscle disease that affects the skeletal muscles, which are used for movement, and the heart (cardiac) muscle. This condition is characterized by skeletal muscle weakness that becomes apparent in early infancy. Affected individuals have delayed development of motor skills, such as sitting, standing, and walking. Beginning later in childhood, people with Salih myopathy may also develop joint deformities called contractures that restrict the movement of the neck and back. Scoliosis, which is an abnormal side-to-side curvature of the spine, also develops in late childhood.  A form of heart disease called dilated cardiomyopathy is another feature of Salih myopathy. Dilated cardiomyopathy enlarges and weakens the cardiac muscle, preventing the heart from pumping blood efficiently. Signs and symptoms of this condition can include an irregular heartbeat (arrhythmia), shortness of breath, extreme tiredness (fatigue), and swelling of the legs and feet. The heart abnormalities associated with Salih myopathy usually become apparent in childhood, after the skeletal muscle abnormalities. The heart disease worsens quickly, and it often causes heart failure and sudden death in adolescence or early adulthood. </s>


Input: How many people are affected by Salih myopathy ?

Output: Salih myopathy appears to be a rare disorder, although its prevalence is unknown. It has been reported in a small number of families of Moroccan and Sudanese descent. </s>


Input: What are the genetic changes related to Salih myopathy ?

Output: Salih myopathy is caused by mutations in the TTN gene. This gene provides instructions for making a protein called titin, which plays an important role in skeletal and cardiac muscle function.  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 this protein's 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.  The TTN gene mutations responsible for Salih myopathy lead to the production of an abnormally short version of titin. The defective protein disrupts the function of sarcomeres, which prevents skeletal and cardiac muscle from contracting normally. These muscle abnormalities underlie the features of Salih myopathy, including skeletal muscle weakness and dilated cardiomyopathy. </s>


Input: Is Salih myopathy inherited ?

Output: This condition is 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. </s>


Input: What are the treatments for Salih myopathy ?

Output: These resources address the diagnosis or management of Salih myopathy:  - Gene Review: Gene Review: Salih Myopathy  - Genetic Testing Registry: Myopathy, early-onset, with fatal cardiomyopathy   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 </s>


Input: What is (are) keratoderma with woolly hair ?

Output: Keratoderma with woolly hair is a group of related conditions that affect the skin and hair and in many cases increase the risk of potentially life-threatening heart problems. People with these conditions have hair that is unusually coarse, dry, fine, and tightly curled. In some cases, the hair is also sparse. The woolly hair texture typically affects only scalp hair and is present from birth. Starting early in life, affected individuals also develop palmoplantar keratoderma, a condition that causes skin on the palms of the hands and the soles of the feet to become thick, scaly, and calloused.  Cardiomyopathy, which is a disease of the heart muscle, is a life-threatening health problem that can develop in people with keratoderma with woolly hair. Unlike the other features of this condition, signs and symptoms of cardiomyopathy may not appear until adolescence or later. Complications of cardiomyopathy can include an abnormal heartbeat (arrhythmia), heart failure, and sudden death.  Keratoderma with woolly hair comprises several related conditions with overlapping signs and symptoms. Researchers have recently proposed classifying keratoderma with woolly hair into four types, based on the underlying genetic cause. Type I, also known as Naxos disease, is characterized by palmoplantar keratoderma, woolly hair, and a form of cardiomyopathy called arrhythmogenic right ventricular cardiomyopathy (ARVC). Type II, also known as Carvajal syndrome, has hair and skin abnormalities similar to type I but features a different form of cardiomyopathy, called dilated left ventricular cardiomyopathy. Type III also has signs and symptoms similar to those of type I, including ARVC, although the hair and skin abnormalities are often milder. Type IV is characterized by palmoplantar keratoderma and woolly and sparse hair, as well as abnormal fingernails and toenails. Type IV does not appear to cause cardiomyopathy. </s>


Input: How many people are affected by keratoderma with woolly hair ?

Output: Keratoderma with woolly hair is rare; its prevalence worldwide is unknown.  Type I (Naxos disease) was first described in families from the Greek island of Naxos. Since then, affected families have been found in other Greek islands, Turkey, and the Middle East. This form of the condition may affect up to 1 in 1,000 people from the Greek islands.  Type II (Carvajal syndrome), type III, and type IV have each been identified in only a small number of families worldwide. </s>


Input: What are the genetic changes related to keratoderma with woolly hair ?

Output: Mutations in the JUP, DSP, DSC2, and KANK2 genes cause keratoderma with woolly hair types I through IV, respectively. The JUP, DSP, and DSC2 genes provide instructions for making components of specialized cell structures called desmosomes. Desmosomes are located in the membrane surrounding certain cells, including skin and heart muscle cells. Desmosomes help attach cells to one another, which provides strength and stability to tissues. They also play a role in signaling between cells.  Mutations in the JUP, DSP, or DSC2 gene alter the structure and impair the function of desmosomes. Abnormal or missing desmosomes prevent cells from sticking to one another effectively, which likely makes the hair, skin, and heart muscle more fragile. Over time, as these tissues are exposed to mechanical stress (for example, friction on the surface of the skin or the constant contraction and relaxation of the heart muscle), they become damaged and can no longer function normally. This mechanism probably underlies the skin, hair, and heart problems that occur in keratoderma with woolly hair. Some studies suggest that abnormal cell signaling may also contribute to cardiomyopathy in people with this group of conditions.  Unlike the other genes associated with keratoderma with woolly hair, the KANK2 gene provides instructions for making a protein that is not part of desmosomes. Instead, it regulates other proteins called steroid receptor coactivators (SRCs), whose function is to help turn on (activate) certain genes. SRCs play important roles in tissues throughout the body, including the skin. Studies suggest that mutations in the KANK2 gene disrupt the regulation of SRCs, which leads to abnormal gene activity. However, it is unclear how these changes underlie the skin and hair abnormalities in keratoderma with woolly hair type IV. </s>


Input: Is keratoderma with woolly hair inherited ?

Output: Most cases of keratoderma with woolly hair have an autosomal recessive pattern of inheritance, 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 usually do not show signs and symptoms of the condition. </s>


Input: What are the treatments for keratoderma with woolly hair ?

Output: These resources address the diagnosis or management of keratoderma with woolly hair:  - Gene Review: Gene Review: Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy  - Gene Review: Gene Review: Dilated Cardiomyopathy Overview  - Genetic Testing Registry: Arrhythmogenic right ventricular cardiomyopathy, type 11  - Genetic Testing Registry: Cardiomyopathy, dilated, with woolly hair, keratoderma, and tooth agenesis  - Genetic Testing Registry: Naxos disease  - Genetic Testing Registry: Palmoplantar keratoderma and woolly hair  - National Heart, Lung, and Blood Institute: How is Cardiomyopathy Diagnosed?  - National Heart, Lung, and Blood Institute: How is Cardiomyopathy 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 </s>


Input: What is (are) progressive osseous heteroplasia ?

Output: Progressive osseous heteroplasia is a disorder in which bone forms within skin and muscle tissue. Bone that forms outside the skeleton is called heterotopic or ectopic bone. In progressive osseous heteroplasia, ectopic bone formation begins in the deep layers of the skin (dermis and subcutaneous fat) and gradually moves into other tissues such as skeletal muscle and tendons. The bony lesions within the skin may be painful and may develop into open sores (ulcers). Over time, joints can become involved, resulting in impaired mobility.  Signs and symptoms of progressive osseous heteroplasia usually become noticeable during infancy. In some affected individuals, however, this may not occur until later in childhood or in early adulthood. </s>


Input: How many people are affected by progressive osseous heteroplasia ?

Output: Progressive osseous heteroplasia is a rare condition. Its exact incidence is unknown. </s>


Input: What are the genetic changes related to progressive osseous heteroplasia ?

Output: Progressive osseous heteroplasia is caused by a mutation in the GNAS gene. The GNAS gene provides instructions for making one part of a protein complex called a guanine nucleotide-binding protein, or a G protein.  In a process called signal transduction, G proteins trigger a complex network of signaling pathways that ultimately influence many cell functions. The protein produced from the GNAS gene is believed to play a key role in signaling pathways that help regulate the development of bone (osteogenesis), preventing bony tissue from being produced outside the skeleton.  The GNAS gene mutations that cause progressive osseous heteroplasia disrupt the function of the G protein and impair its ability to regulate osteogenesis. As a result, bony tissue grows outside the skeleton and causes the complications associated with this disorder. </s>


Input: Is progressive osseous heteroplasia inherited ?

Output: 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.  People normally inherit one copy of each gene from their mother and one copy from their father. For most genes, both copies are active, or "turned on," in all cells. For a small subset of genes, however, only one of the two copies is active. For some of these genes, only the copy inherited from a person's father (the paternal copy) is active, while for other genes, only the copy inherited from a person's mother (the maternal copy) is active. These differences in gene activation based on the gene's parent of origin are caused by a phenomenon called genomic imprinting.  The GNAS gene has a complex genomic imprinting pattern. In some cells of the body the maternal copy of the gene is active, while in others the paternal copy is active. Progressive osseous heteroplasia occurs when mutations affect the paternal copy of the gene. </s>


Input: What are the treatments for progressive osseous heteroplasia ?

Output: These resources address the diagnosis or management of progressive osseous heteroplasia:  - Genetic Testing Registry: Progressive osseous heteroplasia   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 </s>


Input: What is (are) Miller-Dieker syndrome ?

Output: Miller-Dieker syndrome is a condition characterized by a pattern of abnormal brain development known as lissencephaly. Normally the exterior of the brain (cerebral cortex) is multi-layered with folds and grooves. People with lissencephaly have an abnormally smooth brain with fewer folds and grooves. These brain malformations cause severe intellectual disability, developmental delay, seizures, abnormal muscle stiffness (spasticity), weak muscle tone (hypotonia), and feeding difficulties. Seizures usually begin before six months of age, and some occur from birth. Typically, the smoother the surface of the brain is, the more severe the associated symptoms are.  In addition to lissencephaly, people with Miller-Dieker syndrome tend to have distinctive facial features that include a prominent forehead; a sunken appearance in the middle of the face (midface hypoplasia); a small, upturned nose; low-set and abnormally shaped ears; a small jaw; and a thick upper lip. Some individuals with this condition also grow more slowly than other children. Rarely, affected individuals will have heart or kidney malformations or an opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the navel. People with Miller-Dieker syndrome may also have life-threatening breathing problems. Most individuals with this condition do not survive beyond childhood. </s>


Input: How many people are affected by Miller-Dieker syndrome ?

Output: Miller-Dieker syndrome appears to be a rare disorder, although its prevalence is unknown. </s>


Input: What are the genetic changes related to Miller-Dieker syndrome ?

Output: Miller-Dieker syndrome is caused by a deletion of genetic material near the end of the short (p) arm of chromosome 17. The signs and symptoms of Miller-Dieker syndrome are probably related to the loss of multiple genes in this region. The size of the deletion varies among affected individuals.  Researchers are working to identify all of the genes that contribute to the features of Miller-Dieker syndrome. They have determined that the loss of a particular gene on chromosome 17, PAFAH1B1, is responsible for the syndrome's characteristic sign of lissencephaly. The loss of another gene, YWHAE, in the same region of chromosome 17 increases the severity of the lissencephaly in people with Miller-Dieker syndrome. Additional genes in the deleted region probably contribute to the varied features of Miller-Dieker syndrome. </s>


Input: Is Miller-Dieker syndrome inherited ?

Output: Most cases of Miller-Dieker syndrome are not inherited. The deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family.  When Miller-Dieker syndrome is inherited, its inheritance pattern is considered autosomal dominant because a deletion in one copy of chromosome 17 in each cell is sufficient to cause the condition. About 12 percent of people with Miller-Dieker syndrome inherit a chromosome abnormality from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which no genetic material is gained or lost. Balanced translocations usually do not cause any health problems; however, they can become unbalanced as they are passed to the next generation. Children who inherit an unbalanced translocation can have a chromosomal rearrangement with extra or missing genetic material. Individuals with Miller-Dieker syndrome who inherit an unbalanced translocation are missing genetic material from the short arm of chromosome 17, which results in the health problems characteristic of this disorder. </s>


Input: What are the treatments for Miller-Dieker syndrome ?

Output: These resources address the diagnosis or management of Miller-Dieker syndrome:  - Gene Review: Gene Review: LIS1-Associated Lissencephaly/Subcortical Band Heterotopia  - Genetic Testing Registry: Miller Dieker 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 </s>


Input: What is (are) congenital insensitivity to pain with anhidrosis ?

Output: Congenital insensitivity to pain with anhidrosis (CIPA) has two characteristic features: the inability to feel pain and temperature, and decreased or absent sweating (anhidrosis). This condition is also known as hereditary sensory and autonomic neuropathy type IV. The signs and symptoms of CIPA appear early, usually at birth or during infancy, but with careful medical attention, affected individuals can live into adulthood.  An inability to feel pain and temperature often leads to repeated severe injuries. Unintentional self-injury is common in people with CIPA, typically by biting the tongue, lips, or fingers, which may lead to spontaneous amputation of the affected area. In addition, people with CIPA heal slowly from skin and bone injuries. Repeated trauma can lead to chronic bone infections (osteomyelitis) or a condition called Charcot joints, in which the bones and tissue surrounding joints are destroyed.  Normally, sweating helps cool the body temperature. However, in people with CIPA, anhidrosis often causes recurrent, extremely high fevers (hyperpyrexia) and seizures brought on by high temperature (febrile seizures).  In addition to the characteristic features, there are other signs and symptoms of CIPA. Many affected individuals have thick, leathery skin (lichenification) on the palms of their hands or misshapen fingernails or toenails. They can also have patches on their scalp where hair does not grow (hypotrichosis). About half of people with CIPA show signs of hyperactivity or emotional instability, and many affected individuals have intellectual disability. Some people with CIPA have weak muscle tone (hypotonia) when they are young, but muscle strength and tone become more normal as they get older. </s>


Input: How many people are affected by congenital insensitivity to pain with anhidrosis ?

Output: CIPA is a rare condition; however, the prevalence is unknown. </s>


Input: What are the genetic changes related to congenital insensitivity to pain with anhidrosis ?

Output: Mutations in the NTRK1 gene cause CIPA. The NTRK1 gene provides instructions for making a receptor protein that attaches (binds) to another protein called NGF. The NTRK1 receptor is important for the survival of nerve cells (neurons).  The NTRK1 receptor is found on the surface of cells, particularly neurons that transmit pain, temperature, and touch sensations (sensory neurons). When the NGF protein binds to the NTRK1 receptor, signals are transmitted inside the cell that tell the cell to grow and divide, and that help it survive. Mutations in the NTRK1 gene lead to a protein that cannot transmit signals. Without the proper signaling, neurons die by a process of self-destruction called apoptosis. Loss of sensory neurons leads to the inability to feel pain in people with CIPA. In addition, people with CIPA lose the nerves leading to their sweat glands, which causes the anhidrosis seen in affected individuals. </s>


Input: Is congenital insensitivity to pain with anhidrosis inherited ?

Output: This condition is 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. </s>


Input: What are the treatments for congenital insensitivity to pain with anhidrosis ?

Output: These resources address the diagnosis or management of CIPA:  - Gene Review: Gene Review: Congenital Insensitivity to Pain with Anhidrosis  - Genetic Testing Registry: Hereditary insensitivity to pain with anhidrosis   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 </s>


Input: What is (are) hypochondrogenesis ?

Output: Hypochondrogenesis is a rare, severe disorder of bone growth. This condition is characterized by a small body, short limbs, and abnormal bone formation (ossification) in the spine and pelvis.  Affected infants have short arms and legs, a small chest with short ribs, and underdeveloped lungs. Bones in the skull develop normally, but the bones of the spine (vertebrae) and pelvis do not harden (ossify) properly. The face appears flat and oval-shaped, with widely spaced eyes, a small chin, and, in some cases, an opening in the roof of the mouth called a cleft palate. Individuals with hypochondrogenesis have an enlarged abdomen and may have a condition called hydrops fetalis in which excess fluid builds up in the body before birth.  As a result of these serious health problems, some affected fetuses do not survive to term. Infants born with hypochondrogenesis usually die at birth or shortly thereafter from respiratory failure. Babies who live past the newborn period are usually reclassified as having spondyloepiphyseal dysplasia congenita, a related but milder disorder that similarly affects bone development. </s>


Input: How many people are affected by hypochondrogenesis ?

Output: Hypochondrogenesis and achondrogenesis, type 2 (a similar skeletal disorder) together affect 1 in 40,000 to 60,000 newborns. </s>


Input: What are the genetic changes related to hypochondrogenesis ?

Output: Hypochondrogenesis is one of the most severe conditions in a spectrum of disorders caused by mutations in the COL2A1 gene. This gene provides instructions for making a protein that forms type II collagen. This type of collagen is found mostly in the clear gel that fills the eyeball (the vitreous) and in cartilage. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Type II collagen is essential for the normal development of bones and other connective tissues that form the body's supportive framework. Mutations in the COL2A1 gene interfere with the assembly of type II collagen molecules, which prevents bones and other connective tissues from developing properly. </s>


Input: Is hypochondrogenesis inherited ?

Output: Hypochondrogenesis is considered an autosomal dominant disorder because one copy of the altered gene in each cell is sufficient to cause the condition. It is caused by new mutations in the COL2A1 gene and occurs in people with no history of the disorder in their family. This condition is not passed on to the next generation because affected individuals do not live long enough to have children. </s>


Input: What are the treatments for hypochondrogenesis ?

Output: These resources address the diagnosis or management of hypochondrogenesis:  - Genetic Testing Registry: Hypochondrogenesis  - MedlinePlus Encyclopedia: Achondrogenesis   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 </s>


Input: What is (are) Krabbe disease ?

Output: Krabbe disease (also called globoid cell leukodystrophy) is a degenerative disorder that affects the nervous system. It is caused by the shortage (deficiency) of an enzyme called galactosylceramidase. This enzyme deficiency impairs the growth and maintenance of myelin, the protective covering around certain nerve cells that ensures the rapid transmission of nerve impulses. Krabbe disease is part of a group of disorders known as leukodystrophies, which result from the loss of myelin (demyelination). This disorder is also characterized by the abnormal presence of globoid cells, which are globe-shaped cells that usually have more than one nucleus.  The symptoms of Krabbe disease usually begin before the age of 1 year (the infantile form). Initial signs and symptoms typically include irritability, muscle weakness, feeding difficulties, episodes of fever without any sign of infection, stiff posture, and slowed mental and physical development. As the disease progresses, muscles continue to weaken, affecting the infant's ability to move, chew, swallow, and breathe. Affected infants also experience vision loss and seizures.  Less commonly, onset of Krabbe disease can occur in childhood, adolescence, or adulthood (late-onset forms). Visual problems and walking difficulties are the most common initial symptoms in this form of the disorder, however, signs and symptoms vary considerably among affected individuals. </s>


Input: How many people are affected by Krabbe disease ?

Output: In the United States, Krabbe disease affects about 1 in 100,000 individuals. A higher incidence (6 cases per 1,000 people) has been reported in a few isolated communities in Israel. </s>


Input: What are the genetic changes related to Krabbe disease ?

Output: Mutations in the GALC gene cause Krabbe disease. These mutations cause a deficiency of the enzyme galactosylceramidase. This deficiency leads to a progressive loss of myelin that covers many nerves. Without myelin, nerves in the brain and other parts of the body cannot function properly, leading to the signs and symptoms of Krabbe disease. </s>


Input: Is Krabbe disease inherited ?

Output: This condition is 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. </s>


Input: What are the treatments for Krabbe disease ?

Output: These resources address the diagnosis or management of Krabbe disease:  - Baby's First Test  - Gene Review: Gene Review: Krabbe Disease  - Genetic Testing Registry: Galactosylceramide beta-galactosidase deficiency  - MedlinePlus Encyclopedia: Krabbe disease   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 </s>


Input: What is (are) septo-optic dysplasia ?

Output: Septo-optic dysplasia is a disorder of early brain development. Although its signs and symptoms vary, this condition is traditionally defined by three characteristic features: underdevelopment (hypoplasia) of the optic nerves, abnormal formation of structures along the midline of the brain, and pituitary hypoplasia.  The first major feature, optic nerve hypoplasia, is the underdevelopment of the optic nerves, which carry visual information from the eyes to the brain. In affected individuals, the optic nerves are abnormally small and make fewer connections than usual between the eyes and the brain. As a result, people with optic nerve hypoplasia have impaired vision in one or both eyes. Optic nerve hypoplasia can also be associated with unusual side-to-side eye movements (nystagmus) and other eye abnormalities.  The second characteristic feature of septo-optic dysplasia is the abnormal development of structures separating the right and left halves of the brain. These structures include the corpus callosum, which is a band of tissue that connects the two halves of the brain, and the septum pellucidum, which separates the fluid-filled spaces called ventricles in the brain. In the early stages of brain development, these structures may form abnormally or fail to develop at all. Depending on which structures are affected, abnormal brain development can lead to intellectual disability and other neurological problems.  The third major feature of this disorder is pituitary hypoplasia. The pituitary is a gland at the base of the brain that produces several hormones. These hormones help control growth, reproduction, and other critical body functions. Underdevelopment of the pituitary can lead to a shortage (deficiency) of many essential hormones. Most commonly, pituitary hypoplasia causes growth hormone deficiency, which results in slow growth and unusually short stature. Severe cases cause panhypopituitarism, a condition in which the pituitary produces no hormones. Panhypopituitarism is associated with slow growth, low blood sugar (hypoglycemia), genital abnormalities, and problems with sexual development.  The signs and symptoms of septo-optic dysplasia can vary significantly. Some researchers suggest that septo-optic dysplasia should actually be considered a group of related conditions rather than a single disorder. About one-third of people diagnosed with septo-optic dysplasia have all three major features; most affected individuals have two of the major features. In rare cases, septo-optic dysplasia is associated with additional signs and symptoms, including recurrent seizures (epilepsy), delayed development, and abnormal movements. </s>


Input: How many people are affected by septo-optic dysplasia ?

Output: Septo-optic dysplasia has a reported incidence of 1 in 10,000 newborns. </s>


Input: What are the genetic changes related to septo-optic dysplasia ?

Output: In most cases of septo-optic dysplasia, the cause of the disorder is unknown. Researchers suspect that a combination of genetic and environmental factors may play a role in causing this disorder. Proposed environmental risk factors include viral infections, specific medications, and a disruption in blood flow to certain areas of the brain during critical periods of development.  At least three genes have been associated with septo-optic dysplasia, although mutations in these genes appear to be rare causes of this disorder. The three genes, HESX1, OTX2, and SOX2, all play important roles in embryonic development. In particular, they are essential for the formation of the eyes, the pituitary gland, and structures at the front of the brain (the forebrain) such as the optic nerves. Mutations in any of these genes disrupt the early development of these structures, which leads to the major features of septo-optic dysplasia.  Researchers are looking for additional genetic changes that contribute to septo-optic dysplasia. </s>


Input: Is septo-optic dysplasia inherited ?

Output: Septo-optic dysplasia is usually sporadic, which means that the condition typically occurs in people with no history of the disorder in their family.  Less commonly, septo-optic dysplasia has been found to run in families. Most familial cases appear to have an autosomal recessive pattern of inheritance, which means that both copies of an associated 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. In a few affected families, the disorder has had an autosomal dominant pattern of inheritance, which means one copy of an altered gene in each cell is sufficient to cause the condition. </s>


Input: What are the treatments for septo-optic dysplasia ?

Output: These resources address the diagnosis or management of septo-optic dysplasia:  - Genetic Testing Registry: Septo-optic dysplasia sequence  - MedlinePlus Encyclopedia: Growth Hormone Deficiency  - MedlinePlus Encyclopedia: Hypopituitarism   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 </s>


Input: What is (are) spondylothoracic dysostosis ?

Output: Spondylothoracic dysostosis is a condition characterized by the malformation of the bones of the spine and ribs. The bones of the spine (vertebrae) do not develop properly, which causes them to be misshapen and abnormally joined together (fused). The ribs are also fused at the part nearest the spine (posteriorly), which gives the rib cage its characteristic fan-like or "crab" appearance in x-rays. Affected individuals have short, rigid necks and short midsections because of the bone malformations. As a result, people with spondylothoracic dysostosis have short bodies but normal length arms and legs, called short-trunk dwarfism.  The spine and rib abnormalities cause other signs and symptoms of spondylothoracic dysostosis. Infants with this condition are born with a small chest that cannot expand adequately, often leading to life-threatening breathing problems. As the lungs expand, the narrow chest forces the muscle that separates the abdomen from the chest cavity (the diaphragm) down and the abdomen is pushed out. The increased pressure in the abdomen can cause a soft out-pouching around the lower abdomen (inguinal hernia) or belly-button (umbilical hernia).  Spondylothoracic dysostosis is sometimes called spondylocostal dysostosis, a similar condition with abnormalities of the spine and ribs. The two conditions have been grouped in the past, and both are referred to as Jarcho-Levin syndrome; however, they are now considered distinct conditions. </s>


Input: How many people are affected by spondylothoracic dysostosis ?

Output: Spondylothoracic dysostosis affects about one in 200,000 people worldwide. However, it is much more common in people of Puerto Rican ancestry, affecting approximately one in 12,000 people. </s>


Input: What are the genetic changes related to spondylothoracic dysostosis ?

Output: The MESP2 gene provides instructions for a protein that plays a critical role in the development of vertebrae. Specifically, it is involved in separating vertebrae from one another during early development, a process called somite segmentation. Mutations in the MESP2 gene prevent the production of any protein or lead to the production of an abnormally short, nonfunctional protein. When the MESP2 protein is nonfunctional or absent, somite segmentation does not occur properly, which results in the malformation and fusion of the bones of the spine and ribs seen in spondylothoracic dysostosis. </s>


Input: Is spondylothoracic dysostosis inherited ?

Output: This condition is 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. </s>


Input: What are the treatments for spondylothoracic dysostosis ?

Output: These resources address the diagnosis or management of spondylothoracic dysostosis:  - Cleveland Clinic: Spine X-ray  - Gene Review: Gene Review: Spondylocostal Dysostosis, Autosomal Recessive   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 </s>


Input: What is (are) familial osteochondritis dissecans ?

Output: Familial osteochondritis dissecans is a condition that affects the joints and is associated with abnormal cartilage. Cartilage is a tough but flexible tissue that covers the ends of the bones at joints and is also part of the developing skeleton. A characteristic feature of familial osteochondritis dissecans is areas of bone damage (lesions) caused by detachment of cartilage and a piece of the underlying bone from the end of the bone at a joint. People with this condition develop multiple lesions that affect several joints, primarily the knees, elbows, hips, and ankles. The lesions cause stiffness, pain, and swelling in the joint. Often, the affected joint feels like it catches or locks during movement. Other characteristic features of familial osteochondritis dissecans include short stature and development of a joint disorder called osteoarthritis at an early age. Osteoarthritis is characterized by the breakdown of joint cartilage and the underlying bone. It causes pain and stiffness and restricts the movement of joints.  A similar condition called sporadic osteochondritis dissecans is associated with a single lesion in one joint, most often the knee. These cases may be caused by injury to or repetitive use of the joint (often sports-related). Some people with sporadic osteochondritis dissecans develop osteoarthritis in the affected joint, especially if the lesion occurs later in life after the bone has stopped growing. Short stature is not associated with this form of the condition. </s>


Input: How many people are affected by familial osteochondritis dissecans ?

Output: Familial osteochondritis dissecans is a rare condition, although the prevalence is unknown. Sporadic osteochondritis dissecans is more common; it is estimated to occur in the knee in 15 to 29 per 100,000 individuals. </s>


Input: What are the genetic changes related to familial osteochondritis dissecans ?

Output: Mutation of the ACAN gene can cause familial osteochondritis dissecans. The ACAN gene provides instructions for making the aggrecan protein, which is a component of cartilage. Aggrecan attaches to the other components of cartilage, organizing the network of molecules that gives cartilage its strength. In addition, aggrecan attracts water molecules and gives cartilage its gel-like structure. This feature enables the cartilage to resist compression, protecting bones and joints.  The ACAN gene mutation associated with familial osteochondritis dissecans results in an abnormal protein that is unable to attach to the other components of cartilage. As a result, the cartilage is disorganized and weak. It is unclear how the abnormal cartilage leads to the lesions and osteoarthritis characteristic of familial osteochondritis dissecans. Researchers suggest that a disorganized cartilage network in growing bones impairs their normal growth, leading to short stature.  Sporadic osteochondritis dissecans is not caused by genetic changes and is not inherited. </s>


Input: Is familial osteochondritis dissecans inherited ?

Output: 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 most cases, an affected person has one parent with the condition. </s>


Input: What are the treatments for familial osteochondritis dissecans ?

Output: These resources address the diagnosis or management of familial osteochondritis dissecans:  - Cedars-Sinai  - Genetic Testing Registry: Osteochondritis dissecans  - Seattle Children's: Osteochondritis Dissecans Symptoms and Diagnosis   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 </s>


Input: What is (are) sensorineural deafness and male infertility ?

Output: Sensorineural deafness and male infertility is a condition characterized by hearing loss and an inability to father children. Affected individuals have moderate to severe sensorineural hearing loss, which is caused by abnormalities in the inner ear. The hearing loss is typically diagnosed in early childhood and does not worsen over time. Males with this condition produce sperm that have decreased movement (motility), causing affected males to be infertile. </s>


Input: How many people are affected by sensorineural deafness and male infertility ?

Output: The prevalence of sensorineural deafness and male infertility is unknown. </s>


Input: What are the genetic changes related to sensorineural deafness and male infertility ?

Output: Sensorineural deafness and male infertility is caused by a deletion of genetic material on the long (q) arm of chromosome 15. The signs and symptoms of sensorineural deafness and male infertility are related to the loss of multiple genes in this region. The size of the deletion varies among affected individuals. Researchers have determined that the loss of a particular gene on chromosome 15, the STRC gene, is responsible for hearing loss in affected individuals. The loss of another gene, CATSPER2, in the same region of chromosome 15 is responsible for the sperm abnormalities and infertility in affected males. Researchers are working to determine how the loss of additional genes in the deleted region affects people with sensorineural deafness and male infertility. </s>


Input: Is sensorineural deafness and male infertility inherited ?

Output: Sensorineural deafness and male infertility is inherited in an autosomal recessive pattern, which means both copies of chromosome 15 in each cell have a deletion. The parents of an individual with sensorineural deafness and male infertility each carry one copy of the chromosome 15 deletion, but they do not show symptoms of the condition.  Males with two chromosome 15 deletions in each cell have sensorineural deafness and infertility. Females with two chromosome 15 deletions in each cell have sensorineural deafness as their only symptom because the CATSPER2 gene deletions affect sperm function, and women do not produce sperm. </s>


Input: What are the treatments for sensorineural deafness and male infertility ?

Output: These resources address the diagnosis or management of sensorineural deafness and male infertility:  - Cleveland Clinic: Male Infertility  - Gene Review: Gene Review: CATSPER-Related Male Infertility  - Genetic Testing Registry: Deafness, sensorineural, and male infertility  - MedlinePlus Health Topic: Assisted Reproductive Technology  - RESOLVE: The National Infertility Association: Semen Analysis   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 </s>


Input: What is (are) Unverricht-Lundborg disease ?

Output: Unverricht-Lundborg disease is a rare inherited form of epilepsy. Affected individuals usually begin showing signs and symptoms of the disorder between the ages of 6 and 15.  Unverricht-Lundborg disease is classified as a type of progressive myoclonus epilepsy. People with this disorder experience episodes of involuntary muscle jerking or twitching (myoclonus) that increase in frequency and severity over time. Episodes of myoclonus may be brought on by physical exertion, stress, light, or other stimuli. Within 5 to 10 years, the myoclonic episodes may become severe enough to interfere with walking and other everyday activities.  Affected individuals also usually have seizures involving loss of consciousness, muscle rigidity, and convulsions (tonic-clonic or grand mal seizures). Like the myoclonic episodes, these may increase in frequency over several years but may be controlled with treatment. After several years of progression, the frequency of seizures may stabilize or decrease.  Eventually people with Unverricht-Lundborg disease may develop problems with balance and coordination (ataxia), involuntary rhythmic shaking that worsens during movement (intentional tremor), difficulty speaking (dysarthria), depression, and a slow, mild decline in intellectual functioning.  People with Unverricht-Lundborg disease typically live into adulthood. Depending on the severity of the condition and a person's response to treatment, life expectancy may be normal. </s>


Input: How many people are affected by Unverricht-Lundborg disease ?

Output: Progressive myoclonus epilepsy is a rare condition. Unverricht-Lundborg disease is believed to be the most common cause of this type of epilepsy, but its worldwide prevalence is unknown. Unverricht-Lundborg disease occurs most frequently in Finland, where approximately 4 in 100,000 people are affected. </s>


Input: What are the genetic changes related to Unverricht-Lundborg disease ?

Output: Mutations in the CSTB gene cause Unverricht-Lundborg disease. The CSTB gene provides instructions for making a protein called cystatin B. This protein reduces the activity of enzymes called cathepsins. Cathepsins help break down certain proteins in the lysosomes (compartments in the cell that digest and recycle materials). While the specific function of cystatin B is unclear, it may help protect the cells' proteins from cathepsins that leak out of the lysosomes.  In almost all affected individuals, Unverricht-Lundborg disease is caused by an increase in size of the CSTB gene. One region of the CSTB gene has a particular repeating sequence of 12 DNA building blocks (nucleotides). This sequence is normally repeated two or three times within the gene and is called a dodecamer repeat. Most people with this disorder have more than 30 repeats of the dodecamer sequence in both copies of the CSTB gene. A small number of people with Unverricht-Lundborg disease carry other mutations.  The increased number of dodecamer repeats in the CSTB gene seems to interfere with the production of the cystatin B protein. Levels of cystatin B in affected individuals are only 5 to 10 percent of normal, and cathepsin levels are significantly increased. These changes are believed to cause the signs and symptoms of Unverricht-Lundborg disease, but it is unclear how a reduction in the amount of cystatin B leads to the features of this disorder. </s>


Input: Is Unverricht-Lundborg disease inherited ?

Output: This condition is 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. </s>


Input: What are the treatments for Unverricht-Lundborg disease ?

Output: These resources address the diagnosis or management of Unverricht-Lundborg disease:  - Gene Review: Gene Review: Unverricht-Lundborg Disease  - Genetic Testing Registry: Unverricht-Lundborg 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 </s>


Input: What is (are) Bietti crystalline dystrophy ?

Output: Bietti crystalline dystrophy is a disorder in which numerous small, yellow or white crystal-like deposits of fatty (lipid) compounds accumulate in the light-sensitive tissue that lines the back of the eye (the retina). The deposits damage the retina, resulting in progressive vision loss.  People with Bietti crystalline dystrophy typically begin noticing vision problems in their teens or twenties. They experience a loss of sharp vision (reduction in visual acuity) and difficulty seeing in dim light (night blindness). They usually lose areas of vision (visual field loss), most often side (peripheral) vision. Color vision may also be impaired.  The vision problems may worsen at different rates in each eye, and the severity and progression of symptoms varies widely among affected individuals, even within the same family. However, most people with this condition become legally blind by their forties or fifties. Most affected individuals retain some degree of vision, usually in the center of the visual field, although it is typically blurry and cannot be corrected by glasses or contact lenses. Vision impairment that cannot be improved with corrective lenses is called low vision. </s>


Input: How many people are affected by Bietti crystalline dystrophy ?

Output: Bietti crystalline dystrophy has been estimated to occur in 1 in 67,000 people. It is more common in people of East Asian descent, especially those of Chinese and Japanese background. Researchers suggest that Bietti crystalline dystrophy may be underdiagnosed because its symptoms are similar to those of other eye disorders that progressively damage the retina. </s>


Input: What are the genetic changes related to Bietti crystalline dystrophy ?

Output: Bietti crystalline dystrophy is caused by mutations in the CYP4V2 gene. This gene provides instructions for making a member of the cytochrome P450 family of enzymes. These enzymes are involved in the formation and breakdown of various molecules and chemicals within cells. The CYP4V2 enzyme is involved in a multi-step process called fatty acid oxidation in which lipids are broken down and converted into energy, but the enzyme's specific function is not well understood. CYP4V2 gene mutations that cause Bietti crystalline dystrophy impair or eliminate the function of this enzyme and are believed to affect lipid breakdown. However, it is unknown how they lead to the specific signs and symptoms of Bietti crystalline dystrophy. For unknown reasons, the severity of the signs and symptoms differs significantly among individuals with the same CYP4V2 gene mutation. </s>


Input: Is Bietti crystalline dystrophy inherited ?

Output: This condition is 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. </s>


Input: What are the treatments for Bietti crystalline dystrophy ?

Output: These resources address the diagnosis or management of Bietti crystalline dystrophy:  - Gene Review: Gene Review: Bietti Crystalline Dystrophy  - Genetic Testing Registry: Bietti crystalline corneoretinal 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 </s>


Input: What is (are) Pallister-Killian mosaic syndrome ?

Output: Pallister-Killian mosaic syndrome is a developmental disorder that affects many parts of the body. This condition is characterized by extremely weak muscle tone (hypotonia) in infancy and early childhood, intellectual disability, distinctive facial features, sparse hair, areas of unusual skin coloring (pigmentation), and other birth defects.  Most babies with Pallister-Killian mosaic syndrome are born with significant hypotonia, which can cause difficulty breathing and problems with feeding. Hypotonia also interferes with the normal development of motor skills such as sitting, standing, and walking. About 30 percent of affected individuals are ultimately able to walk without assistance. Additional developmental delays result from intellectual disability, which is usually severe to profound. Speech is often limited or absent in people with this condition.  Pallister-Killian mosaic syndrome is associated with a distinctive facial appearance that is often described as "coarse." Characteristic facial features include a high, rounded forehead; a broad nasal bridge; a short nose; widely spaced eyes; low-set ears; rounded cheeks; and a wide mouth with a thin upper lip and a large tongue. Some affected children are born with an opening in the roof of the mouth (cleft palate) or a high arched palate.  Most children with Pallister-Killian mosaic syndrome have sparse hair on their heads, particularly around the temples. These areas may fill in as affected children get older. Many affected individuals also have streaks or patches of skin that are darker or lighter than the surrounding skin. These skin changes can occur anywhere on the body, and they may be apparent at birth or occur later in life.  Additional features of Pallister-Killian mosaic syndrome can include hearing loss, vision impairment, seizures, extra nipples, genital abnormalities, and heart defects. Affected individuals may also have skeletal abnormalities such as extra fingers and/or toes, large big toes (halluces), and unusually short arms and legs. About 40 percent of affected infants are born with a congenital diaphragmatic hernia, which is a hole in the muscle that separates the abdomen from the chest cavity (the diaphragm). This potentially serious birth defect allows the stomach and intestines to move into the chest, where they can crowd the developing heart and lungs.  The signs and symptoms of Pallister-Killian mosaic syndrome vary, although most people with this disorder have severe to profound intellectual disability and other serious health problems. The most severe cases involve birth defects that are life-threatening in early infancy. However, several affected people have had milder features, including mild intellectual disability and less noticeable physical abnormalities. </s>


Input: How many people are affected by Pallister-Killian mosaic syndrome ?

Output: Pallister-Killian mosaic syndrome appears to be a rare condition, although its exact prevalence is unknown. This disorder may be underdiagnosed because it can be difficult to detect in people with mild signs and symptoms. As a result, most diagnoses are made in children with more severe features of the disorder. More than 150 people with Pallister-Killian mosaic syndrome have been reported in the medical literature. </s>


Input: What are the genetic changes related to Pallister-Killian mosaic syndrome ?

Output: Pallister-Killian mosaic syndrome is usually caused by the presence of an abnormal extra chromosome called an isochromosome 12p or i(12p). An isochromosome is a chromosome with two identical arms. Normal chromosomes have one long (q) arm and one short (p) arm, but isochromosomes have either two q arms or two p arms. Isochromosome 12p is a version of chromosome 12 made up of two p arms.  Cells normally have two copies of each chromosome, one inherited from each parent. In people with Pallister-Killian mosaic syndrome, cells have the two usual copies of chromosome 12, but some cells also have the isochromosome 12p. These cells have a total of four copies of all the genes on the p arm of chromosome 12. The extra genetic material from the isochromosome disrupts the normal course of development, causing the characteristic features of this disorder.  Although Pallister-Killian mosaic syndrome is usually caused by the presence of an isochromosome 12p, other, more complex chromosomal changes involving chromosome 12 are responsible for the disorder in rare cases. </s>


Input: Is Pallister-Killian mosaic syndrome inherited ?

Output: Pallister-Killian mosaic syndrome is not inherited. The chromosomal change responsible for the disorder typically occurs as a random event during the formation of reproductive cells (eggs or sperm) in a parent of the affected individual, usually the mother. Affected individuals have no history of the disorder in their families.  An error in cell division called nondisjunction likely results in a reproductive cell containing an isochromosome 12p. If this atypical reproductive cell contributes to the genetic makeup of a child, the child will have two normal copies of chromosome 12 along with an isochromosome 12p.  As cells divide during early development, some cells lose the isochromosome 12p, while other cells retain the abnormal chromosome. This situation is called mosaicism. Almost all cases of Pallister-Killian mosaic syndrome are caused by mosaicism for an isochromosome 12p. If all of the body's cells contained the isochromosome, the resulting syndrome would probably not be compatible with life. </s>


Input: What are the treatments for Pallister-Killian mosaic syndrome ?

Output: These resources address the diagnosis or management of Pallister-Killian mosaic syndrome:  - Genetic Testing Registry: Pallister-Killian syndrome  - MedlinePlus Encyclopedia: Chromosome  - MedlinePlus Encyclopedia: Mosaicism   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 </s>