Input: What are the treatments for mucolipidosis III gamma ?

Output: These resources address the diagnosis or management of mucolipidosis III gamma:  - Gene Review: Gene Review: Mucolipidosis III Gamma  - Genetic Testing Registry: Mucolipidosis III Gamma  - MedlinePlus Encyclopedia: Cloudy Cornea  - MedlinePlus Encyclopedia: Heart Valves   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) neonatal onset multisystem inflammatory disease ?

Output: Neonatal onset multisystem inflammatory disease (NOMID) is a disorder that causes persistent inflammation and tissue damage primarily affecting the nervous system, skin, and joints. Recurrent episodes of mild fever may also occur in this disorder.  People with NOMID have a skin rash that is usually present from birth. The rash persists throughout life, although it changes in size and location.  Affected individuals often have headaches, seizures, and vomiting resulting from chronic meningitis, which is inflammation of the tissue that covers and protects the brain and spinal cord (meninges). Intellectual disability may occur in some people with this disorder. Hearing and vision problems may result from nerve damage and inflammation in various tissues of the eyes.  People with NOMID experience joint inflammation, swelling, and cartilage overgrowth, causing characteristic prominent knees and other skeletal abnormalities that worsen over time. Joint deformities called contractures may restrict the movement of certain joints.  Other features of this disorder include short stature with shortening of the lower legs and forearms, and characteristic facial features such as a prominent forehead and protruding eyes. Abnormal deposits of a protein called amyloid (amyloidosis) may cause progressive kidney damage. </s>


Input: How many people are affected by neonatal onset multisystem inflammatory disease ?

Output: NOMID is a very rare disorder; approximately 100 affected individuals have been reported worldwide. </s>


Input: What are the genetic changes related to neonatal onset multisystem inflammatory disease ?

Output: Mutations in the NLRP3 gene (also known as CIAS1) cause NOMID. The NLRP3 gene provides instructions for making a protein called cryopyrin.  Cryopyrin belongs to a family of proteins called nucleotide-binding domain and leucine-rich repeat containing (NLR) proteins. These proteins are involved in the immune system, helping to regulate the process of inflammation. Inflammation occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight microbial invaders and facilitate tissue repair. When this has been accomplished, the body stops (inhibits) the inflammatory response to prevent damage to its own cells and tissues.  Cryopyrin is involved in the assembly of a molecular complex called an inflammasome, which helps trigger the inflammatory process. Researchers believe that NLRP3 mutations that cause NOMID result in a hyperactive cryopyrin protein and an inappropriate inflammatory response. Impairment of the body's mechanisms for controlling inflammation results in the episodes of fever and widespread inflammatory damage to the body's cells and tissues seen in NOMID.  In about 50 percent of individuals diagnosed with NOMID, no mutations in the NLRP3 gene have been identified. The cause of NOMID in these individuals is unknown. </s>


Input: Is neonatal onset multisystem inflammatory disease 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 almost all cases, NOMID results from new mutations. These cases occur in people with no history of the disorder in their family. A few cases have been reported in which an affected person has inherited the mutation from one affected parent. </s>


Input: What are the treatments for neonatal onset multisystem inflammatory disease ?

Output: These resources address the diagnosis or management of NOMID:  - Genetic Testing Registry: Chronic infantile neurological, cutaneous and articular 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) Ewing sarcoma ?

Output: Ewing sarcoma is a cancerous tumor that occurs in bones or soft tissues, such as cartilage or nerves. There are several types of Ewing sarcoma, including Ewing sarcoma of bone, extraosseous Ewing sarcoma, peripheral primitive neuroectodermal tumor (pPNET), and Askin tumor. These tumors are considered to be related because they have similar genetic causes. These types of Ewing sarcoma can be distinguished from one another by the tissue in which the tumor develops. Approximately 87 percent of Ewing sarcomas are Ewing sarcoma of bone, which is a bone tumor that usually occurs in the thigh bones (femurs), pelvis, ribs, or shoulder blades. Extraosseous (or extraskeletal) Ewing sarcoma describes tumors in the soft tissues around bones, such as cartilage. pPNETs occur in nerve tissue and can be found in many parts of the body. A type of pPNET found in the chest is called Askin tumor.  Ewing sarcomas most often occur in children and young adults. Affected individuals usually feel stiffness, pain, swelling, or tenderness of the bone or surrounding tissue. Sometimes, there is a lump near the surface of the skin that feels warm and soft to the touch. Often, children have a fever that does not go away. Ewing sarcoma of bone can cause weakening of the involved bone, and affected individuals may have a broken bone with no obvious cause.  It is common for Ewing sarcoma to spread to other parts of the body (metastasize), usually to the lungs, to other bones, or to the bone marrow. </s>


Input: How many people are affected by Ewing sarcoma ?

Output: Approximately 3 per 1 million children each year are diagnosed with a Ewing sarcoma. It is estimated that, in the United States, 250 children are diagnosed with one of these types of tumor each year. Ewing sarcoma accounts for about 1.5 percent of all childhood cancers, and it is the second most common type of bone tumor in children (the most common type of bone cancer is called osteosarcoma). </s>


Input: What are the genetic changes related to Ewing sarcoma ?

Output: The most common mutation that causes Ewing sarcoma involves two genes, the EWSR1 gene on chromosome 22 and the FLI1 gene on chromosome 11. A rearrangement (translocation) of genetic material between chromosomes 22 and 11, written as t(11;22), fuses part of the EWSR1 gene with part of the FLI1 gene, creating the EWSR1/FLI1 fusion gene. This mutation is acquired during a person's lifetime and is present only in tumor cells. This type of genetic change, called a somatic mutation, is not inherited.  The protein produced from the EWSR1/FLI1 fusion gene, called EWS/FLI, has functions of the protein products of both genes. The FLI protein, produced from the FLI1 gene, attaches (binds) to DNA and regulates an activity called transcription, which is the first step in the production of proteins from genes. The FLI protein controls the growth and development of some cell types by regulating the transcription of certain genes. The EWS protein, produced from the EWSR1 gene, also regulates transcription. The EWS/FLI protein has the DNA-binding function of the FLI protein as well as the transcription regulation function of the EWS protein. It is thought that the EWS/FLI protein turns the transcription of a variety of genes on and off abnormally. This dysregulation of transcription leads to uncontrolled growth and division (proliferation) and abnormal maturation and survival of cells, causing tumor development.  The EWSR1/FLI1 fusion gene occurs in approximately 85 percent of Ewing sarcomas. Translocations that fuse the EWSR1 gene with other genes that are related to the FLI1 gene can also cause these types of tumors, although these alternative translocations are relatively uncommon. The fusion proteins produced from the less common gene translocations have the same function as the EWS/FLI protein. </s>


Input: Is Ewing sarcoma inherited ?

Output: This condition is generally not inherited but arises from a mutation in the body's cells that occurs after conception. This alteration is called a somatic mutation. </s>


Input: What are the treatments for Ewing sarcoma ?

Output: These resources address the diagnosis or management of Ewing sarcoma:  - Cancer.Net: Ewing Family of Tumors - Childhood: Diagnosis  - Cancer.Net: Ewing Family of Tumors - Childhood: Treatment  - Genetic Testing Registry: Ewing's sarcoma  - MedlinePlus Encyclopedia: Ewing Sarcoma   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) otopalatodigital syndrome type 1 ?

Output: Otopalatodigital syndrome type 1 is a disorder primarily involving abnormalities in skeletal development. It is a member of a group of related conditions called otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 2, frontometaphyseal dysplasia, and Melnick-Needles syndrome. In general, these disorders involve hearing loss caused by malformations in the tiny bones in the ears (ossicles), problems in the development of the roof of the mouth (palate), and skeletal abnormalities involving the fingers and/or toes (digits).  Otopalatodigital syndrome type 1 is usually the mildest of the otopalatodigital spectrum disorders. People with this condition usually have characteristic facial features including wide-set and downward-slanting eyes; prominent brow ridges; and a small, flat nose. Affected individuals also have hearing loss and chest deformities. They have abnormalities of the fingers and toes, such as blunt, square-shaped (spatulate) fingertips; shortened thumbs and big toes; and unusually long second toes.  Affected individuals may be born with an opening in the roof of the mouth (a cleft palate). They may have mildly bowed limbs, and limited range of motion in some joints. People with otopalatodigital syndrome type 1 may be somewhat shorter than other members of their family. Males with this disorder often have more severe signs and symptoms than do females, who may show only the characteristic facial features. </s>


Input: How many people are affected by otopalatodigital syndrome type 1 ?

Output: Otopalatodigital syndrome type 1 is a rare disorder, affecting fewer than 1 in every 100,000 individuals. Its specific incidence is unknown. </s>


Input: What are the genetic changes related to otopalatodigital syndrome type 1 ?

Output: Mutations in the FLNA gene cause otopalatodigital syndrome type 1.  The FLNA gene provides instructions for producing the protein filamin A, which helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. Filamin A binds to another protein called actin, and helps the actin to form the branching network of filaments that make up the cytoskeleton. Filamin A also links actin to many other proteins to perform various functions within the cell.  A small number of mutations in the FLNA gene have been identified in people with otopalatodigital syndrome type 1. The mutations all result in changes to the filamin A protein in the region that binds to actin. The mutations responsible for otopalatodigital syndrome type 1 are described as "gain-of-function" because they appear to enhance the activity of the filamin A protein or give the protein a new, atypical function. Researchers believe that the mutations may change the way the filamin A protein helps regulate processes involved in skeletal development, but it is not known how changes in the protein relate to the specific signs and symptoms of otopalatodigital syndrome type 1. </s>


Input: Is otopalatodigital syndrome type 1 inherited ?

Output: This condition is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In most cases, males experience more severe symptoms of the disorder than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. </s>


Input: What are the treatments for otopalatodigital syndrome type 1 ?

Output: These resources address the diagnosis or management of otopalatodigital syndrome type 1:  - Gene Review: Gene Review: Otopalatodigital Spectrum Disorders  - Genetic Testing Registry: Oto-palato-digital syndrome, type I   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) autoimmune Addison disease ?

Output: Autoimmune Addison disease affects the function of the adrenal glands, which are small hormone-producing glands located on top of each kidney. It is classified as an autoimmune disorder because it results from a malfunctioning immune system that attacks the adrenal glands. As a result, the production of several hormones is disrupted, which affects many body systems.  The signs and symptoms of autoimmune Addison disease can begin at any time, although they most commonly begin between ages 30 and 50. Common features of this condition include extreme tiredness (fatigue), nausea, decreased appetite, and weight loss. In addition, many affected individuals have low blood pressure (hypotension), which can lead to dizziness when standing up quickly; muscle cramps; and a craving for salty foods. A characteristic feature of autoimmune Addison disease is abnormally dark areas of skin (hyperpigmentation), especially in regions that experience a lot of friction, such as the armpits, elbows, knuckles, and palm creases. The lips and the inside lining of the mouth can also be unusually dark. Because of an imbalance of hormones involved in development of sexual characteristics, women with this condition may lose their underarm and pubic hair.  Other signs and symptoms of autoimmune Addison disease include low levels of sugar (hypoglycemia) and sodium (hyponatremia) and high levels of potassium (hyperkalemia) in the blood. Affected individuals may also have a shortage of red blood cells (anemia) and an increase in the number of white blood cells (lymphocytosis), particularly those known as eosinophils (eosinophilia).  Autoimmune Addison disease can lead to a life-threatening adrenal crisis, characterized by vomiting, abdominal pain, back or leg cramps, and severe hypotension leading to shock. The adrenal crisis is often triggered by a stressor, such as surgery, trauma, or infection.  Individuals with autoimmune Addison disease or their family members often have another autoimmune disorder, most commonly autoimmune thyroid disease or type 1 diabetes. </s>


Input: How many people are affected by autoimmune Addison disease ?

Output: Addison disease affects approximately 11 to 14 in 100,000 people of European descent. The autoimmune form of the disorder is the most common form in developed countries, accounting for up to 90 percent of cases. </s>


Input: What are the genetic changes related to autoimmune Addison disease ?

Output: The cause of autoimmune Addison disease is complex and not completely understood. A combination of environmental and genetic factors plays a role in the disorder, and changes in multiple genes are thought to affect the risk of developing the condition.  The genes that have been associated with autoimmune Addison disease participate in the body's immune response. The most commonly associated genes belong to a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Each HLA gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. The most well-known risk factor for autoimmune Addison disease is a variant of the HLA-DRB1 gene called HLA-DRB1*04:04. This and other disease-associated HLA gene variants likely contribute to an inappropriate immune response that leads to autoimmune Addison disease, although the mechanism is unknown.  Normally, the immune system responds only to proteins made by foreign invaders, not to the body's own proteins. In autoimmune Addison disease, however, an immune response is triggered by a normal adrenal gland protein, typically a protein called 21-hydroxylase. This protein plays a key role in producing certain hormones in the adrenal glands. The prolonged immune attack triggered by 21-hydroxylase damages the adrenal glands (specifically the outer layers of the glands known, collectively, as the adrenal cortex), preventing hormone production. A shortage of adrenal hormones (adrenal insufficiency) disrupts several normal functions in the body, leading to hypoglycemia, hyponatremia, hypotension, muscle cramps, skin hyperpigmentation and other features of autoimmune Addison disease.  Rarely, Addison disease is not caused by an autoimmune reaction. Other causes include infections that damage the adrenal glands, such as tuberculosis, or tumors in the adrenal glands. Addison disease can also be one of several features of other genetic conditions, including X-linked adrenoleukodystrophy and autoimmune polyglandular syndrome, type 1, which are caused by mutations in other genes. </s>


Input: Is autoimmune Addison disease inherited ?

Output: A predisposition to develop autoimmune Addison disease is passed through generations in families, but the inheritance pattern is unknown. </s>


Input: What are the treatments for autoimmune Addison disease ?

Output: These resources address the diagnosis or management of autoimmune Addison disease:  - Genetic Testing Registry: Addison's disease  - MedlinePlus Encyclopedia: Addison's 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) Gorlin syndrome ?

Output: Gorlin syndrome, also known as nevoid basal cell carcinoma syndrome, is a condition that affects many areas of the body and increases the risk of developing various cancerous and noncancerous tumors.  In people with Gorlin syndrome, the type of cancer diagnosed most often is basal cell carcinoma, which is the most common form of skin cancer. Individuals with Gorlin syndrome typically begin to develop basal cell carcinomas during adolescence or early adulthood. These cancers occur most often on the face, chest, and back. The number of basal cell carcinomas that develop during a person's lifetime varies among affected individuals. Some people with Gorlin syndrome never develop any basal cell carcinomas, while others may develop thousands of these cancers. Individuals with lighter skin are more likely to develop basal cell carcinomas than are people with darker skin.  Most people with Gorlin syndrome also develop noncancerous (benign) tumors of the jaw, called keratocystic odontogenic tumors. These tumors usually first appear during adolescence, and new tumors form until about age 30. Keratocystic odontogenic tumors rarely develop later in adulthood. If untreated, these tumors may cause painful facial swelling and tooth displacement.  Individuals with Gorlin syndrome have a higher risk than the general population of developing other tumors. A small proportion of affected individuals develop a brain tumor called medulloblastoma during childhood. A type of benign tumor called a fibroma can occur in the heart or in a woman's ovaries. Heart (cardiac) fibromas often do not cause any symptoms, but they may obstruct blood flow or cause irregular heartbeats (arrhythmia). Ovarian fibromas are not thought to affect a woman's ability to have children (fertility).  Other features of Gorlin syndrome include small depressions (pits) in the skin of the palms of the hands and soles of the feet; an unusually large head size (macrocephaly) with a prominent forehead; and skeletal abnormalities involving the spine, ribs, or skull. These signs and symptoms are typically apparent from birth or become evident in early childhood. </s>


Input: How many people are affected by Gorlin syndrome ?

Output: Gorlin syndrome affects an estimated 1 in 31,000 people. While more than 1 million new cases of basal cell carcinoma are diagnosed each year in the United States, fewer than 1 percent of these skin cancers are related to Gorlin syndrome. </s>


Input: What are the genetic changes related to Gorlin syndrome ?

Output: Mutations in the PTCH1 gene cause Gorlin syndrome. This gene provides instructions for making a protein called patched-1, which functions as a receptor. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. Together, ligands and their receptors trigger signals that affect cell development and function. A protein called Sonic Hedgehog is the ligand for the patched-1 receptor. Patched-1 blocks cell growth and division (proliferation) until Sonic Hedgehog is attached.  The PTCH1 gene is a tumor suppressor gene, which means it stops cells from proliferating too rapidly or in an uncontrolled way. Mutations in this gene prevent the production of patched-1 or lead to the production of an abnormal version of the receptor. An altered or missing patched-1 receptor cannot effectively suppress cell growth and division. As a result, cells proliferate uncontrollably to form the tumors that are characteristic of Gorlin syndrome. It is less clear how PTCH1 gene mutations cause the other signs and symptoms related to this condition.  The characteristic features of Gorlin syndrome can also be associated with a chromosomal change called a 9q22.3 microdeletion, in which a small piece of chromosome 9 is deleted in each cell. This deletion includes the segment of chromosome 9 that contains the PTCH1 gene, and as a result, people with a 9q22.3 microdeletion are missing one copy of this gene. Loss of this gene underlies the signs and symptoms of Gorlin syndrome in people with 9q22.3 microdeletions. Affected individuals also have features that are not typically associated with Gorlin syndrome, including delayed development, intellectual disability, overgrowth of the body (macrosomia), and other physical abnormalities. Researchers believe that these other signs and symptoms may result from the loss of additional genes in the deleted region of chromosome 9. </s>


Input: Is Gorlin syndrome inherited ?

Output: Gorlin syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the condition. In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the PTCH1 gene and occur in people with no history of the disorder in their family.  Having one mutated copy of the PTCH1 gene in each cell is enough to cause the features of Gorlin syndrome that are present early in life, including macrocephaly and skeletal abnormalities. For basal cell carcinomas and other tumors to develop, a mutation in the second copy of the PTCH1 gene must also occur in certain cells during the person's lifetime. Most people who are born with one PTCH1 gene mutation eventually acquire a second mutation in some cells and consequently develop various types of tumors. </s>


Input: What are the treatments for Gorlin syndrome ?

Output: These resources address the diagnosis or management of Gorlin syndrome:  - Gene Review: Gene Review: Nevoid Basal Cell Carcinoma Syndrome  - Genetic Testing Registry: Gorlin syndrome  - MedlinePlus Encyclopedia: Basal Cell Nevus 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) familial hemiplegic migraine ?

Output: Familial hemiplegic migraine is a form of migraine headache that runs in families. Migraines usually cause intense, throbbing pain in one area of the head, often accompanied by nausea, vomiting, and extreme sensitivity to light and sound. These recurrent headaches typically begin in childhood or adolescence and can be triggered by certain foods, emotional stress, and minor head trauma. Each headache may last from a few hours to a few days.  In some types of migraine, including familial hemiplegic migraine, a pattern of neurological symptoms called an aura precedes the headache. The most common symptoms associated with an aura are temporary visual changes such as blind spots (scotomas), flashing lights, zig-zagging lines, and double vision. In people with familial hemiplegic migraine, auras are also characterized by temporary numbness or weakness, often affecting one side of the body (hemiparesis). Additional features of an aura can include difficulty with speech, confusion, and drowsiness. An aura typically develops gradually over a few minutes and lasts about an hour.  Unusually severe migraine episodes have been reported in some people with familial hemiplegic migraine. These episodes have included fever, seizures, prolonged weakness, coma, and, rarely, death. Although most people with familial hemiplegic migraine recover completely between episodes, neurological symptoms such as memory loss and problems with attention can last for weeks or months. About 20 percent of people with this condition develop mild but permanent difficulty coordinating movements (ataxia), which may worsen with time, and rapid, involuntary eye movements called nystagmus. </s>


Input: How many people are affected by familial hemiplegic migraine ?

Output: The worldwide prevalence of familial hemiplegic migraine is unknown. Studies suggest that in Denmark about 1 in 10,000 people have hemiplegic migraine and that the condition occurs equally in families with multiple affected individuals (familial hemiplegic migraine) and in individuals with no family history of the condition (sporadic hemiplegic migraine). Like other forms of migraine, familial hemiplegic migraine affects females more often than males. </s>


Input: What are the genetic changes related to familial hemiplegic migraine ?

Output: Mutations in the CACNA1A, ATP1A2, SCN1A, and PRRT2 genes have been found to cause familial hemiplegic migraine. The first three genes provide instructions for making proteins that are involved in the transport of charged atoms (ions) across cell membranes. The movement of these ions is critical for normal signaling between nerve cells (neurons) in the brain and other parts of the nervous system. The function of the protein produced from the PRRT2 gene is unknown, although studies suggest it interacts with a protein that helps control signaling between neurons.  Communication between neurons depends on chemicals called neurotransmitters, which are released from one neuron and taken up by neighboring neurons. Researchers believe that mutations in the CACNA1A, ATP1A2, and SCN1A genes can upset the balance of ions in neurons, which disrupts the normal release and uptake of certain neurotransmitters in the brain. Although the mechanism is unknown, researchers speculate that mutations in the PRRT2 gene, which reduce the amount of PRRT2 protein, also disrupt normal control of neurotransmitter release. The resulting changes in signaling between neurons lead people with familial hemiplegic migraine to develop these severe headaches.  There is little evidence that mutations in the CACNA1A, ATP1A2, SCN1A, and PRRT2 genes play a role in common migraines, which affect millions of people each year. Researchers are searching for additional genetic changes that may underlie rare types of migraine, such as familial hemiplegic migraine, as well as the more common forms of migraine. </s>


Input: Is familial hemiplegic migraine 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, affected individuals have one affected parent. However, some people who inherit an altered gene never develop features of familial hemiplegic migraine. (This situation is known as reduced penetrance.) A related condition, sporadic hemiplegic migraine, has identical signs and symptoms but occurs in individuals with no history of the disorder in their family. </s>


Input: What are the treatments for familial hemiplegic migraine ?

Output: These resources address the diagnosis or management of familial hemiplegic migraine:  - Gene Review: Gene Review: Familial Hemiplegic Migraine  - Genetic Testing Registry: Familial hemiplegic migraine  - Genetic Testing Registry: Familial hemiplegic migraine type 1  - Genetic Testing Registry: Familial hemiplegic migraine type 2  - Genetic Testing Registry: Familial hemiplegic migraine type 3   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) protein S deficiency ?

Output: Protein S deficiency is a disorder of blood clotting. People with this condition have an increased risk of developing abnormal blood clots.  Individuals with mild protein S deficiency are at risk of a type of clot called a deep vein thrombosis (DVT) that occurs in the deep veins of the arms or legs. If a DVT travels through the bloodstream and lodges in the lungs, it can cause a life-threatening clot known as a pulmonary embolism (PE). Other factors can raise the risk of abnormal blood clots in people with mild protein S deficiency. These factors include increasing age, surgery, immobility, or pregnancy. The combination of protein S deficiency and other inherited disorders of blood clotting can also influence risk. Many people with mild protein S deficiency never develop an abnormal blood clot, however.  In severe cases of protein S deficiency, infants develop a life-threatening blood clotting disorder called purpura fulminans soon after birth. Purpura fulminans is characterized by the formation of blood clots within small blood vessels throughout the body. These blood clots disrupt normal blood flow and can lead to death of body tissue (necrosis). Widespread blood clotting uses up all available blood clotting proteins. As a result, abnormal bleeding occurs in various parts of the body and is often noticeable as large, purple skin lesions. Individuals who survive the newborn period may experience recurrent episodes of purpura fulminans. </s>


Input: How many people are affected by protein S deficiency ?

Output: Mild protein S deficiency is estimated to occur in approximately 1 in 500 individuals. Severe protein S deficiency is rare; however, its exact prevalence is unknown. </s>


Input: What are the genetic changes related to protein S deficiency ?

Output: Protein S deficiency is caused by mutations in the PROS1 gene. This gene provides instructions for making protein S, which is found in the bloodstream and is important for controlling blood clotting. Protein S helps block the activity of (inactivate) certain proteins that promote the formation of blood clots.  Most mutations that cause protein S deficiency change single protein building blocks (amino acids) in protein S, which disrupts its ability to control blood clotting. Individuals with this condition do not have enough functional protein S to inactivate clotting proteins, which results in the increased risk of developing abnormal blood clots. Protein S deficiency can be divided into types I, II and III based on how mutations in the PROS1 gene affect protein S. </s>


Input: Is protein S deficiency inherited ?

Output: Protein S deficiency is inherited in an autosomal dominant pattern, which means one altered copy of the PROS1 gene in each cell is sufficient to cause mild protein S deficiency. Individuals who inherit two altered copies of this gene in each cell have severe protein S deficiency. </s>


Input: What are the treatments for protein S deficiency ?

Output: These resources address the diagnosis or management of protein S deficiency:  - Genetic Testing Registry: Protein S deficiency  - MedlinePlus Encyclopedia: Congenital Protein C or S Deficiency  - MedlinePlus Encyclopedia: Necrosis  - MedlinePlus Encyclopedia: Protein S  - MedlinePlus Encyclopedia: Purpura   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) narcolepsy ?

Output: Narcolepsy is a chronic sleep disorder that disrupts the normal sleep-wake cycle. Although this condition can appear at any age, it most often begins in adolescence.  Narcolepsy is characterized by excessive daytime sleepiness. Affected individuals feel tired during the day, and several times a day they may experience an overwhelming urge to sleep. "Sleep attacks" can occur at unusual times, such as during a meal or in the middle of a conversation. They last from a few seconds to a few minutes and often lead to a longer nap, after which affected individuals wake up feeling refreshed.  Another common feature of narcolepsy is cataplexy, which is a sudden loss of muscle tone in response to strong emotion (such as laughing, surprise, or anger). These episodes of muscle weakness can cause an affected person to slump over or fall, which occasionally leads to injury. Episodes of cataplexy usually last just a few seconds, and they may occur from several times a day to a few times a year. Most people diagnosed with narcolepsy also have cataplexy. However, some do not, which has led researchers to distinguish two major forms of the condition: narcolepsy with cataplexy and narcolepsy without cataplexy.  Narcolepsy also affects nighttime sleep. Most affected individuals have trouble sleeping for more than a few hours at night. They often experience vivid hallucinations while falling asleep (hypnogogic hallucinations) or while waking up (hypnopompic hallucinations). Affected individuals often have realistic and distressing dreams, and they may act out their dreams by moving excessively or talking in their sleep. Many people with narcolepsy also experience sleep paralysis, which is an inability to move or speak for a short period while falling asleep or awakening. The combination of hallucinations, vivid dreams, and sleep paralysis is often frightening and unpleasant for affected individuals.  Some people with narcolepsy have all of the major features of the disorder, while others have only one or two. Most of the signs and symptoms persist throughout life, although episodes of cataplexy may become less frequent with age and treatment. </s>


Input: How many people are affected by narcolepsy ?

Output: Narcolepsy affects about 1 in 2,000 people in the United States and Western Europe. However, the disorder is likely underdiagnosed, particularly in people with mild symptoms. Worldwide, narcolepsy appears to be most common in Japan, where it affects an estimated 1 in 600 people. </s>


Input: What are the genetic changes related to narcolepsy ?

Output: Narcolepsy probably results from a combination of genetic and environmental factors, some of which have been identified, but many of which remain unknown.  In most cases of narcolepsy with cataplexy, and in some cases without cataplexy, sleep abnormalities result from a loss of particular brain cells (neurons) in a part of the brain called the hypothalamus. These cells normally produce chemicals called hypocretins (also known as orexins), which have many important functions in the body. In particular, hypocretins regulate the daily sleep-wake cycle. It is unclear what triggers the death of hypocretin-producing neurons in people with narcolepsy, although evidence increasingly points to an abnormality of the immune system.  Researchers have identified changes in several genes that influence the risk of developing narcolepsy. The most well-studied of these genes is HLA-DQB1, which provides instructions for making part of a protein that plays an important role in the immune system. The HLA-DQB1 gene is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). The HLA-DQB1 gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. A variation of the HLA-DQB1 gene called HLA-DQB1*06:02 has been strongly associated with narcolepsy, particularly in people who also have cataplexy and a loss of hypocretins. Most people with narcolepsy have the HLA-DQB1*06:02 variation, and many also have specific versions of other, closely related HLA genes. It is unclear how these genetic changes influence the risk of developing the condition.  Variations in several additional genes have also been associated with narcolepsy. Many of these genes are thought to play roles in immune system function. However, variations in these genes probably make only a small contribution to the overall risk of developing narcolepsy. Other genetic and environmental factors are also likely to influence a person's chances of developing this disorder. For example, studies suggest that bacterial or viral infections such as strep throat (streptococcus), colds, and influenza may be involved in triggering narcolepsy in people who are at risk. </s>


Input: Is narcolepsy inherited ?

Output: Most cases of narcolepsy are sporadic, which means they occur in people with no history of the disorder in their family. A small percentage of all cases have been reported to run in families; however, the condition does not have a clear pattern of inheritance. First-degree relatives (parents, siblings, and children) of people with narcolepsy with cataplexy have a 40 times greater risk of developing the condition compared with people in the general population. </s>


Input: What are the treatments for narcolepsy ?

Output: These resources address the diagnosis or management of narcolepsy:  - Genetic Testing Registry: Narcolepsy 1  - Genetic Testing Registry: Narcolepsy 2, susceptibility to  - Genetic Testing Registry: Narcolepsy 3  - Genetic Testing Registry: Narcolepsy 4, susceptibility to  - Genetic Testing Registry: Narcolepsy 5, susceptibility to  - Narcolepsy Network: Treatment   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) Troyer syndrome ?

Output: Troyer syndrome is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve the lower limbs. The complex types involve the lower limbs and can also affect the upper limbs to a lesser degree; the structure or functioning of the brain; and the nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound (the peripheral nervous system). Troyer syndrome is a complex hereditary spastic paraplegia.  People with Troyer syndrome can experience a variety of signs and symptoms. The most common characteristics of Troyer syndrome are spasticity of the leg muscles, progressive muscle weakness, paraplegia, muscle wasting in the hands and feet (distal amyotrophy), small stature, developmental delay, learning disorders, speech difficulties (dysarthria), and mood swings. Other characteristics can include exaggerated reflexes (hyperreflexia) in the lower limbs, uncontrollable movements of the limbs (choreoathetosis), skeletal abnormalities, and a bending outward (valgus) of the knees.  Troyer syndrome causes the degeneration and death of muscle cells and motor neurons (specialized nerve cells that control muscle movement) throughout a person's lifetime, leading to a slow progressive decline in muscle and nerve function. The severity of impairment related to Troyer syndrome increases as a person ages. Most affected individuals require a wheelchair by the time they are in their fifties or sixties. </s>


Input: How many people are affected by Troyer syndrome ?

Output: About 20 cases of Troyer syndrome have been reported in the Old Order Amish population of Ohio. It has not been found outside this population. </s>


Input: What are the genetic changes related to Troyer syndrome ?

Output: Troyer syndrome is caused by a mutation in the SPG20 gene. The SPG20 gene provides instructions for producing a protein called spartin, whose function is not entirely understood. Researchers believe that spartin may be involved in a variety of cell functions, from breaking down proteins to transporting materials from the cell surface into the cell (endocytosis). Spartin is found in a wide range of body tissues, including the nervous system. </s>


Input: Is Troyer syndrome 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 Troyer syndrome ?

Output: These resources address the diagnosis or management of Troyer syndrome:  - Gene Review: Gene Review: Hereditary Spastic Paraplegia Overview  - Gene Review: Gene Review: Troyer Syndrome  - Genetic Testing Registry: Troyer syndrome  - Spastic Paraplegia Foundation, Inc.: Treatments and Therapies   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) microcephalic osteodysplastic primordial dwarfism type II ?

Output: Microcephalic osteodysplastic primordial dwarfism type II (MOPDII) is a condition characterized by short stature (dwarfism) with other skeletal abnormalities (osteodysplasia) and an unusually small head size (microcephaly). The growth problems in MOPDII are primordial, meaning they begin before birth, with affected individuals showing slow prenatal growth (intrauterine growth retardation). After birth, affected individuals continue to grow at a very slow rate. The final adult height of people with this condition ranges from 20 inches to 40 inches. Other skeletal abnormalities in MOPDII include abnormal development of the hip joints (hip dysplasia), thinning of the bones in the arms and legs, an abnormal side-to-side curvature of the spine (scoliosis), and shortened wrist bones. In people with MOPDII head growth slows over time; affected individuals have an adult brain size comparable to that of a 3-month-old infant. However, intellectual development is typically normal.  People with this condition typically have a high-pitched, nasal voice that results from a narrowing of the voicebox (subglottic stenosis). Facial features characteristic of MOPDII include a prominent nose, full cheeks, a long midface, and a small jaw. Other signs and symptoms seen in some people with MOPDII include small teeth (microdontia) and farsightedness. Over time, affected individuals may develop areas of abnormally light or dark skin coloring (pigmentation).  Many individuals with MOPDII have blood vessel abnormalities. For example, some affected individuals develop a bulge in one of the blood vessels at the center of the brain (intracranial aneurysm). These aneurysms are dangerous because they can burst, causing bleeding within the brain. Some affected individuals have Moyamoya disease, in which arteries at the base of the brain are narrowed, leading to restricted blood flow. These vascular abnormalities are often treatable, though they increase the risk of stroke and reduce the life expectancy of affected individuals. </s>


Input: How many people are affected by microcephalic osteodysplastic primordial dwarfism type II ?

Output: MOPDII appears to be a rare condition, although its prevalence is unknown. </s>


Input: What are the genetic changes related to microcephalic osteodysplastic primordial dwarfism type II ?

Output: Mutations in the PCNT gene cause MOPDII. The PCNT gene provides instructions for making a protein called pericentrin. Within cells, this protein is located in structures called centrosomes. Centrosomes play a role in cell division and the assembly of microtubules. Microtubules are fibers that help cells maintain their shape, assist in the process of cell division, and are essential for the transport of materials within cells. Pericentrin acts as an anchoring protein, securing other proteins to the centrosome. Through its interactions with these proteins, pericentrin plays a role in regulation of the cell cycle, which is the cell's way of replicating itself in an organized, step-by-step fashion.  PCNT gene mutations lead to the production of a nonfunctional pericentrin protein that cannot anchor other proteins to the centrosome. As a result, centrosomes cannot properly assemble microtubules, leading to disruption of the cell cycle and cell division. Impaired cell division causes a reduction in cell production, while disruption of the cell cycle can lead to cell death. This overall reduction in the number of cells leads to short bones, microcephaly, and the other signs and symptoms of MOPDII. </s>


Input: Is microcephalic osteodysplastic primordial dwarfism type II 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 microcephalic osteodysplastic primordial dwarfism type II ?

Output: These resources address the diagnosis or management of MOPDII:  - Genetic Testing Registry: Microcephalic osteodysplastic primordial dwarfism type 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) genitopatellar syndrome ?

Output: Genitopatellar syndrome is a rare condition characterized by genital abnormalities, missing or underdeveloped kneecaps (patellae), intellectual disability, and abnormalities affecting other parts of the body.  The genital abnormalities in affected males typically include undescended testes (cryptorchidism) and underdevelopment of the scrotum. Affected females can have an enlarged clitoris (clitoromegaly) and small labia.  Missing or underdeveloped patellae is the most common skeletal abnormality associated with genitopatellar syndrome. Affected individuals may have additional skeletal problems, including joint deformities (contractures) involving the hips and knees or an inward- and upward-turning foot called a clubfoot. Bone abnormalities of the spine, ribs, collarbone (clavicle), and pelvis have also been reported.  Genitopatellar syndrome is also associated with delayed development and intellectual disability, which are often severe. Affected individuals may have an usually small head (microcephaly) and structural brain abnormalities, including underdeveloped or absent tissue connecting the left and right halves of the brain (agenesis of the corpus callosum).  People with genitopatellar syndrome may have distinctive facial features such as prominent cheeks and eyes, a nose with a rounded tip or a broad bridge, an unusually small chin (micrognathia) or a chin that protrudes (prognathism), and a narrowing of the head at the temples. Many affected infants have weak muscle tone (hypotonia) that leads to breathing and feeding difficulties. The condition can also be associated with abnormalities of the heart, kidneys, and teeth. </s>


Input: How many people are affected by genitopatellar syndrome ?

Output: Genitopatellar syndrome is estimated to occur in fewer than 1 per million people. At least 18 cases have been reported in the medical literature. </s>


Input: What are the genetic changes related to genitopatellar syndrome ?

Output: Genitopatellar syndrome is caused by mutations in the KAT6B gene. This gene provides instructions for making a type of enzyme called a histone acetyltransferase. These enzymes modify histones, which are structural proteins that attach (bind) to DNA and give chromosomes their shape. By adding a small molecule called an acetyl group to histones, histone acetyltransferases control the activity of certain genes. Little is known about the function of the histone acetyltransferase produced from the KAT6B gene. It appears to regulate genes that are important for early development, including development of the skeleton and nervous system.  The mutations that cause genitopatellar syndrome occur near the end of the KAT6B gene and lead to the production of a shortened histone acetyltransferase enzyme. Researchers suspect that the shortened enzyme may function differently than the full-length version, altering the regulation of various genes during early development. However, it is unclear how these changes lead to the specific features of genitopatellar syndrome. </s>


Input: Is genitopatellar syndrome inherited ?

Output: This condition has an autosomal dominant inheritance pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. All reported cases have resulted from new mutations in the gene and have occurred in people with no history of the disorder in their family. </s>


Input: What are the treatments for genitopatellar syndrome ?

Output: These resources address the diagnosis or management of genitopatellar syndrome:  - Gene Review: Gene Review: KAT6B-Related Disorders  - Genetic Testing Registry: Genitopatellar 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) amyotrophic lateral sclerosis ?

Output: Amyotrophic lateral sclerosis (ALS) is a progressive disease that affects motor neurons, which are specialized nerve cells that control muscle movement. These nerve cells are found in the spinal cord and the brain. In ALS, motor neurons die (atrophy) over time, leading to muscle weakness, a loss of muscle mass, and an inability to control movement.  There are many different types of ALS; these types are distinguished by their signs and symptoms and their genetic cause or lack of clear genetic association. Most people with ALS have a form of the condition that is described as sporadic, which means it occurs in people with no apparent history of the disorder in their family. People with sporadic ALS usually first develop features of the condition in their late fifties or early sixties. A small proportion of people with ALS, estimated at 5 to 10 percent, have a family history of ALS or a related condition called frontotemporal dementia (FTD), which is a progressive brain disorder that affects personality, behavior, and language. The signs and symptoms of familial ALS typically first appear in one's late forties or early fifties. Rarely, people with familial ALS develop symptoms in childhood or their teenage years. These individuals have a rare form of the disorder known as juvenile ALS.  The first signs and symptoms of ALS may be so subtle that they are overlooked. The earliest symptoms include muscle twitching, cramping, stiffness, or weakness. Affected individuals may develop slurred speech (dysarthria) and, later, difficulty chewing or swallowing (dysphagia). Many people with ALS experience malnutrition because of reduced food intake due to dysphagia and an increase in their body's energy demands (metabolism) due to prolonged illness. Muscles become weaker as the disease progresses, and arms and legs begin to look thinner as muscle tissue atrophies. Individuals with ALS eventually lose muscle strength and the ability to walk. Affected individuals eventually become wheelchair-dependent and increasingly require help with personal care and other activities of daily living. Over time, muscle weakness causes affected individuals to lose the use of their hands and arms. Breathing becomes difficult because the muscles of the respiratory system weaken. Most people with ALS die from respiratory failure within 2 to 10 years after the signs and symptoms of ALS first appear; however, disease progression varies widely among affected individuals.  Approximately 20 percent of individuals with ALS also develop FTD. Changes in personality and behavior may make it difficult for affected individuals to interact with others in a socially appropriate manner. Communication skills worsen as the disease progresses. It is unclear how the development of ALS and FTD are related. Individuals who develop both conditions are diagnosed as having ALS-FTD.  A rare form of ALS that often runs in families is known as ALS-parkinsonism-dementia complex (ALS-PDC). This disorder is characterized by the signs and symptoms of ALS, in addition to a pattern of movement abnormalities known as parkinsonism, and a progressive loss of intellectual function (dementia). Signs of parkinsonism include unusually slow movements (bradykinesia), stiffness, and tremors. Affected members of the same family can have different combinations of signs and symptoms. </s>


Input: How many people are affected by amyotrophic lateral sclerosis ?

Output: About 5,000 people in the United States are diagnosed with ALS each year. Worldwide, this disorder occurs in 2 to 5 per 100,000 individuals. Only a small percentage of cases have a known genetic cause.  Among the Chamorro people of Guam and people from the Kii Peninsula of Japan, ALS-PDC can be 100 times more frequent than ALS is in other populations. ALS-PDC has not been reported outside of these populations. </s>


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

Output: Mutations in several genes can cause familial ALS and contribute to the development of sporadic ALS. Mutations in the C9orf72 gene account for 30 to 40 percent of familial ALS in the United States and Europe. Worldwide, SOD1 gene mutations cause 15 to 20 percent of familial ALS, and TARDBP and FUS gene mutations each account for about 5 percent of cases. The other genes that have been associated with familial ALS each account for a small proportion of cases. It is estimated that 60 percent of individuals with familial ALS have an identified genetic mutation. The cause of the condition in the remaining individuals is unknown.  The C9orf72, SOD1, TARDBP, and FUS genes are key to the normal functioning of motor neurons and other cells. It is unclear how mutations in these genes contribute to the death of motor neurons, but it is thought that motor neurons are more sensitive to disruptions in function because of their large size. Most motor neurons affected by ALS have a buildup of protein clumps (aggregates); however, it is unknown whether these aggregates are involved in causing ALS or are a byproduct of the dying cell.  In some cases of familial ALS due to mutations in other genes, studies have identified the mechanisms that lead to ALS. Some gene mutations lead to a disruption in the development of axons, the specialized extensions of nerve cells (such as motor neurons) that transmit nerve impulses. The altered axons may impair transmission of impulses from nerves to muscles, leading to muscle weakness and atrophy. Other mutations lead to a slowing in the transport of materials needed for the proper function of axons in motor neurons, eventually causing the motor neurons to die. Additional gene mutations prevent the breakdown of toxic substances, leading to their buildup in nerve cells. The accumulation of toxic substances can damage motor neurons and eventually cause cell death. In some cases of ALS, it is unknown how the gene mutation causes the condition.  The cause of sporadic ALS is largely unknown but probably involves a combination of genetic and environmental factors. Variations in many genes, including the previously mentioned genes involved in transmission of nerve impulses and transportation of materials within neurons, increase the risk of developing ALS. Gene mutations that are risk factors for ALS may add, delete, or change DNA building blocks (nucleotides), resulting in the production of a protein with an altered or reduced function. While genetic variations have been associated with sporadic ALS, not all genetic factors have been identified and it is unclear how most genetic changes influence the development of the disease. People with a gene variation that increases their risk of ALS likely require additional genetic and environmental triggers to develop the disorder. </s>


Input: Is amyotrophic lateral sclerosis inherited ?

Output: About 90 to 95 percent of ALS cases are sporadic, which means they are not inherited.  An estimated 5 to 10 percent of ALS is familial and caused by mutations in one of several genes. The pattern of inheritance varies depending on the gene involved. Most cases are 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. Some people who inherit a familial genetic mutation known to cause ALS never develop features of the condition. (This situation is known as reduced penetrance.) It is unclear why some people with a mutated gene develop the disease and other people with a mutated gene do not.  Less frequently, ALS 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. Because an affected person's parents are not affected, autosomal recessive ALS is often mistaken for sporadic ALS even though it is caused by a familial genetic mutation.  Very rarely, ALS is inherited in an X-linked dominant pattern. X-linked conditions occur when the gene associated with the condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In most cases, males tend to develop the disease earlier and have a decreased life expectancy compared with females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. </s>


Input: What are the treatments for amyotrophic lateral sclerosis ?

Output: These resources address the diagnosis or management of amyotrophic lateral sclerosis:  - Gene Review: Gene Review: ALS2-Related Disorders  - Gene Review: Gene Review: Amyotrophic Lateral Sclerosis Overview  - Gene Review: Gene Review: C9orf72-Related Amyotrophic Lateral Sclerosis and Frontotemporal Dementia  - Gene Review: Gene Review: TARDBP-Related Amyotrophic Lateral Sclerosis  - Genetic Testing Registry: Amyotrophic lateral sclerosis  - Genetic Testing Registry: Amyotrophic lateral sclerosis type 1  - Massachusetts General Hospital: How is ALS Diagnosed?  - MedlinePlus Encyclopedia: Amyotrophic 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) giant congenital melanocytic nevus ?

Output: Giant congenital melanocytic nevus is a skin condition characterized by an abnormally dark, noncancerous skin patch (nevus) that is composed of pigment-producing cells called melanocytes. It is present from birth (congenital) or is noticeable soon after birth. The nevus may be small in infants, but it will usually grow at the same rate the body grows and will eventually be at least 40 cm (15.75 inches) across. The nevus can appear anywhere on the body, but it is more often found on the trunk or limbs. The color ranges from tan to black and can become darker or lighter over time. The surface of a nevus can be flat, rough, raised, thickened, or bumpy; the surface can vary in different regions of the nevus, and it can change over time. The skin of the nevus is often dry and prone to irritation and itching (dermatitis). Excessive hair growth (hypertrichosis) can occur within the nevus. There is often less fat tissue under the skin of the nevus; the skin may appear thinner there than over other areas of the body.  People with giant congenital melanocytic nevus may have more than one nevus (plural: nevi). The other nevi are often smaller than the giant nevus. Affected individuals may have one or two additional nevi or multiple small nevi that are scattered over the skin; these are known as satellite or disseminated nevi.  Affected individuals may feel anxiety or emotional stress due to the impact the nevus may have on their appearance and their health. Children with giant congenital melanocytic nevus can develop emotional or behavior problems.  Some people with giant congenital melanocytic nevus develop a condition called neurocutaneous melanosis, which is the presence of pigment-producing skin cells (melanocytes) in the tissue that covers the brain and spinal cord. These melanocytes may be spread out or grouped together in clusters. Their growth can cause increased pressure in the brain, leading to headache, vomiting, irritability, seizures, and movement problems. Tumors in the brain may also develop.  Individuals with giant congenital melanocytic nevus have an increased risk of developing an aggressive form of cancer called melanoma, which arises from melanocytes. Estimates vary, but it is generally thought that people with giant congenital melanocytic nevus have a 5 to 10 percent lifetime risk of developing melanoma. Melanoma commonly begins in the nevus, but it can develop when melanocytes that invade other tissues, such as those in the brain and spinal cord, become cancerous. When melanoma occurs in people with giant congenital melanocytic nevus, the survival rate is low.  Other types of tumors can also develop in individuals with giant congenital melanocytic nevus, including soft tissue tumors (sarcomas), fatty tumors (lipomas), and tumors of the nerve cells (schwannomas). </s>


Input: How many people are affected by giant congenital melanocytic nevus ?

Output: Giant congenital melanocytic nevus occurs in approximately 1 in 20,000 newborns worldwide. </s>


Input: What are the genetic changes related to giant congenital melanocytic nevus ?

Output: NRAS gene mutations cause most cases of giant congenital melanocytic nevus. Rarely, mutations in the BRAF gene are responsible for this condition.  The proteins produced from these genes are involved in a process known as signal transduction by which signals are relayed from outside the cell to the cell's nucleus. Signals relayed by the N-Ras and BRAF proteins instruct the cell to grow and divide (proliferate) or to mature and take on specialized functions (differentiate). To transmit signals, these proteins must be turned on; when the proteins are turned off, they do not relay signals to the cell's nucleus.  The NRAS or BRAF gene mutations responsible for giant congenital melanocytic nevus are somatic, meaning that they are acquired during a person's lifetime and are present only in certain cells. These mutations occur early in embryonic development during the growth and division (proliferation) of cells that develop into melanocytes. Somatic NRAS or BRAF gene mutations cause the altered protein in affected cells to be constantly turned on (constitutively active) and relaying signals. The overactive protein may contribute to the development of giant congenital melanocytic nevus by allowing cells that develop into melanocytes to grow and divide uncontrollably, starting before birth. </s>


Input: Is giant congenital melanocytic nevus inherited ?

Output: This condition is generally not inherited but arises from a mutation in the body's cells that occurs after conception. This alteration is called a somatic mutation. A somatic mutation in one copy of the NRAS or BRAF gene is sufficient to cause this disorder. </s>


Input: What are the treatments for giant congenital melanocytic nevus ?

Output: These resources address the diagnosis or management of giant congenital melanocytic nevus:  - Cleveland Clinic: The Facts About Melanoma  - Genetic Testing Registry: Giant pigmented hairy nevus  - MedlinePlus Encyclopedia: Giant Congenital Nevus  - Nevus Outreach: Treatment Options  - Primary Care Dermatology Society   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) cartilage-hair hypoplasia ?

Output: Cartilage-hair hypoplasia is a disorder of bone growth characterized by short stature (dwarfism) with other skeletal abnormalities; fine, sparse hair (hypotrichosis); and abnormal immune system function (immune deficiency) that can lead to recurrent infections.  People with cartilage-hair hypoplasia have unusually short limbs and short stature from birth. They typically have malformations in the cartilage near the ends of the long bones in the arms and legs (metaphyseal chondrodysplasia), which then affects development of the bone itself. Most people with cartilage-hair hypoplasia are unusually flexible in some joints, but they may have difficulty extending their elbows fully.  Affected individuals have hair that is lighter in color than that of other family members because the core of each hair, which contains some of the pigment that contributes the hair's color, is missing. The missing core also makes each strand of hair thinner, causing the hair to have a sparse appearance overall. Unusually light-colored skin (hypopigmentation), malformed nails, and dental abnormalities may also be seen in this disorder.  The extent of the immune deficiency in cartilage-hair hypoplasia varies from mild to severe. Affected individuals with the most severe immune problems are considered to have severe combined immunodeficiency (SCID). People with SCID lack virtually all immune protection from bacteria, viruses, and fungi and are prone to repeated and persistent infections that can be very serious or life-threatening. These infections are often caused by "opportunistic" organisms that ordinarily do not cause illness in people with a normal immune system. Most people with cartilage-hair hypoplasia, even those who have milder immune deficiency, experience infections of the respiratory system, ears, and sinuses. In particular, the chicken pox virus (varicella) often causes dangerous infections in people with this disorder. Autoimmune disorders, which occur when the immune system malfunctions and attacks the body's tissues and organs, occur in some people with cartilage-hair hypoplasia. Affected individuals are also at an increased risk of developing cancer, particularly certain skin cancers (basal cell carcinomas), cancer of blood-forming cells (leukemia), and cancer of immune system cells (lymphoma).  Some people with cartilage-hair hypoplasia experience gastrointestinal problems. These problems may include an inability to properly absorb nutrients or intolerance of a protein called gluten found in wheat and other grains (celiac disease). Affected individuals may have Hirschsprung disease, an intestinal disorder that causes severe constipation, intestinal blockage, and enlargement of the colon. Narrowing of the anus (anal stenosis) or blockage of the esophagus (esophageal atresia) may also occur. </s>


Input: How many people are affected by cartilage-hair hypoplasia ?

Output: Cartilage-hair hypoplasia occurs most often in the Old Order Amish population, where it affects about 1 in 1,300 newborns. In people of Finnish descent, its incidence is approximately 1 in 20,000. Outside of these populations, the condition is rare, and its specific incidence is not known. It has been reported in individuals of European and Japanese descent. </s>


Input: What are the genetic changes related to cartilage-hair hypoplasia ?

Output: Cartilage-hair hypoplasia is caused by mutations in the RMRP gene. Unlike many genes, the RMRP gene does not contain instructions for making a protein. Instead, a molecule called a noncoding RNA, a chemical cousin of DNA, is produced from the RMRP gene. This RNA attaches (binds) to several proteins, forming an enzyme complex called mitochondrial RNA-processing endoribonuclease, or RNase MRP.  The RNase MRP enzyme is thought to be involved in several important processes in the cell. For example, it likely helps copy (replicate) the DNA found in the energy-producing centers of cells (mitochondria). The RNase MRP enzyme probably also processes ribosomal RNA, which is required for assembling protein building blocks (amino acids) into functioning proteins. In addition, this enzyme helps control the cell cycle, which is the cell's way of replicating itself in an organized, step-by-step fashion.  Mutations in the RMRP gene likely result in the production of a noncoding RNA that is unstable. This unstable molecule cannot bind to some of the proteins needed to make the RNase MRP enzyme complex. These changes are believed to affect the activity of the enzyme, which interferes with its important functions within cells. Disruption of the RNase MRP enzyme complex causes the signs and symptoms of cartilage-hair hypoplasia. </s>


Input: Is cartilage-hair hypoplasia 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 cartilage-hair hypoplasia ?

Output: These resources address the diagnosis or management of cartilage-hair hypoplasia:  - Gene Review: Gene Review: Cartilage-Hair Hypoplasia - Anauxetic Dysplasia Spectrum Disorders  - Genetic Testing Registry: Metaphyseal chondrodysplasia, McKusick type   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) Buschke-Ollendorff syndrome ?

Output: Buschke-Ollendorff syndrome is a hereditary disorder of connective tissues, which are tissues that provide strength and flexibility to structures throughout the body. Specifically, the condition is characterized by skin growths called connective tissue nevi and a bone abnormality known as osteopoikilosis.  Connective tissue nevi are small, noncancerous lumps on the skin. They tend to appear in childhood and are widespread in people with Buschke-Ollendorff syndrome. The most common form of these nevi are elastomas, which are made up of a type of stretchy connective tissue called elastic fibers. Less commonly, affected individuals have nevi called collagenomas, which are made up of another type of connective tissue called collagen.  Osteopoikilosis, which is from the Greek words for "spotted bones," is a skeletal abnormality characterized by small, round areas of increased bone density that appear as brighter spots on x-rays. Osteopoikilosis usually occurs near the ends of the long bones of the arms and legs, and in the bones of the hands, feet, and pelvis. The areas of increased bone density appear during childhood. They do not cause pain or other health problems. </s>


Input: How many people are affected by Buschke-Ollendorff syndrome ?

Output: Buschke-Ollendorff syndrome has an estimated incidence of 1 in 20,000 people worldwide. </s>


Input: What are the genetic changes related to Buschke-Ollendorff syndrome ?

Output: Buschke-Ollendorff syndrome results from mutations in the LEMD3 gene. This gene provides instructions for making a protein that helps control signaling through two chemical pathways known as the bone morphogenic protein (BMP) and transforming growth factor-beta (TGF-) pathways. These signaling pathways regulate various cellular processes and are involved in the growth of cells, including new bone cells.  Mutations in the LEMD3 gene reduce the amount of functional LEMD3 protein that is produced. A shortage of this protein prevents it from controlling BMP and TGF- signaling effectively, leading to increased signaling through both of these pathways. Studies suggest that the enhanced signaling increases the formation of bone tissue, resulting in areas of overly dense bone. It is unclear how it is related to the development of connective tissue nevi in people with Buschke-Ollendorff syndrome. </s>


Input: Is Buschke-Ollendorff syndrome 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 many cases, an affected person has a parent and other family members with the condition. While most people with Buschke-Ollendorff syndrome have both connective tissue nevi and osteopoikilosis, some affected families include individuals who have the skin abnormalities alone or the bone abnormalities alone. When osteopoikilosis occurs without connective tissue nevi, the condition is often called isolated osteopoikilosis. </s>


Input: What are the treatments for Buschke-Ollendorff syndrome ?

Output: These resources address the diagnosis or management of Buschke-Ollendorff syndrome:  - Genetic Testing Registry: Dermatofibrosis lenticularis disseminata   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) granulomatosis with polyangiitis ?

Output: Granulomatosis with polyangiitis (GPA) is a condition that causes inflammation that primarily affects the respiratory tract (including the lungs and airways) and the kidneys. This disorder is also commonly known as Wegener granulomatosis. A characteristic feature of GPA is inflammation of blood vessels (vasculitis), particularly the small- and medium-sized blood vessels in the lungs, nose, sinuses, windpipe, and kidneys, although vessels in any organ can be involved. Polyangiitis refers to the inflammation of multiple types of vessels, such as small arteries and veins. Vasculitis causes scarring and tissue death in the vessels and impedes blood flow to tissues and organs.  Another characteristic feature of GPA is the formation of granulomas, which are small areas of inflammation composed of immune cells that aid in the inflammatory reaction. The granulomas usually occur in the lungs or airways of people with this condition, although they can occur in the eyes or other organs. As granulomas grow, they can invade surrounding areas, causing tissue damage.  The signs and symptoms of GPA vary based on the tissues and organs affected by vasculitis. Many people with this condition experience a vague feeling of discomfort (malaise), fever, weight loss, or other general symptoms of the body's immune reaction. In most people with GPA, inflammation begins in the vessels of the respiratory tract, leading to nasal congestion, frequent nosebleeds, shortness of breath, or coughing. Severe inflammation in the nose can lead to a hole in the tissue that separates the two nostrils (nasal septum perforation) or a collapse of the septum, causing a sunken bridge of the nose (saddle nose).  The kidneys are commonly affected in people with GPA. Tissue damage caused by vasculitis in the kidneys can lead to decreased kidney function, which may cause increased blood pressure or blood in the urine, and life-threatening kidney failure. Inflammation can also occur in other regions of the body, including the eyes, middle and inner ear structures, skin, joints, nerves, heart, and brain. Depending on which systems are involved, additional symptoms can include skin rashes, inner ear pain, swollen and painful joints, and numbness or tingling in the limbs.  GPA is most common in middle-aged adults, although it can occur at any age. If untreated, the condition is usually fatal within 2 years of diagnosis. Even after treatment, vasculitis can return. </s>


Input: How many people are affected by granulomatosis with polyangiitis ?

Output: GPA is a rare disorder that affects an estimated 3 in 100,000 people in the United States. </s>


Input: What are the genetic changes related to granulomatosis with polyangiitis ?

Output: The genetic basis of GPA is not well understood. Having a particular version of the HLA-DPB1 gene is the strongest genetic risk factor for developing this condition, although several other genes, some of which have not been identified, may be involved. It is likely that a combination of genetic and environmental factors lead to GPA.  GPA is an autoimmune disorder. Such disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. Approximately 90 percent of people with GPA have an abnormal immune protein called an anti-neutrophil cytoplasmic antibody (ANCA) in their blood. Antibodies normally bind to specific foreign particles and germs, marking them for destruction, but ANCAs attack normal human proteins. Most people with GPA have an ANCA that attacks the human protein proteinase 3 (PR3). A few affected individuals have an ANCA that attacks a protein called myeloperoxidase (MPO). When these antibodies attach to the protein they recognize, they trigger inflammation, which contributes to the signs and symptoms of GPA.  The HLA-DPB1 gene belongs to a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Each HLA gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. A particular variant of the HLA-DPB1 gene called HLA-DPB1*0401 has been found more frequently in people with GPA, especially those with ANCAs, than in people without the condition.  Because the HLA-DPB1 gene is involved in the immune system, changes in it might be related to the autoimmune response and inflammation in the respiratory tract and kidneys characteristic of GPA. However, it is unclear what specific role the HLA-DPB1*0401 gene variant plays in development of this condition. </s>


Input: Is granulomatosis with polyangiitis inherited ?

Output: The inheritance pattern of GPA is unknown. Most instances are sporadic and occur in individuals with no history of the disorder in their family. Only rarely is more than one member of the same family affected by the disorder. </s>


Input: What are the treatments for granulomatosis with polyangiitis ?

Output: These resources address the diagnosis or management of granulomatosis with polyangiitis:  - Genetic Testing Registry: Wegener's granulomatosis  - Johns Hopkins Vasculitis Center: How is Wegener's Granulomatosis Diagnosed?  - MedlinePlus Encyclopedia: Wegener's Granulomatosis  - Merck Manual Home Health Edition   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) SLC4A1-associated distal renal tubular acidosis ?

Output: SLC4A1-associated distal renal tubular acidosis is a kidney (renal) disorder that sometimes includes blood cell abnormalities. The kidneys normally filter fluid and waste products from the body and remove them in urine; however, in people with distal renal tubular acidosis, the kidneys are unable to remove enough acid from the body, and the blood becomes too acidic. This chemical imbalance is called metabolic acidosis. The inability to remove acids from the body often results in slowed growth and may also lead to softening and weakening of the bones, called rickets in children and osteomalacia in adults. This bone disorder is characterized by bone pain, bowed legs, and difficulty walking. In addition, most children and adults with SLC4A1-associated distal renal tubular acidosis have excess calcium in the urine (hypercalciuria), calcium deposits in the kidneys (nephrocalcinosis), and kidney stones (nephrolithiasis). In rare cases, these kidney abnormalities lead to life-threatening kidney failure. Affected individuals may also have low levels of potassium in the blood (hypokalemia).  Individuals with the features described above have complete distal renal tubular acidosis, which usually becomes apparent in childhood. Some people do not develop metabolic acidosis even though their kidneys have trouble removing acids; these individuals are said to have incomplete distal renal tubular acidosis. Additionally, these individuals may have other features of distal renal tubular acidosis, such as bone problems and kidney stones. Often, people who initially have incomplete distal renal tubular acidosis develop metabolic acidosis later in life.  Some people with SLC4A1-associated distal renal tubular acidosis also have blood cell abnormalities. These can vary in severity from no symptoms to a condition called hemolytic anemia, in which red blood cells prematurely break down (undergo hemolysis), causing a shortage of red blood cells (anemia). Hemolytic anemia can lead to unusually pale skin (pallor), extreme tiredness (fatigue), shortness of breath (dyspnea), and an enlarged spleen (splenomegaly).  There are two forms of SLC4A1-associated distal renal tubular acidosis; they are distinguished by their inheritance pattern (described below). The autosomal dominant form is more common and is usually less severe than the autosomal recessive form. The autosomal dominant form can be associated with incomplete or complete distal renal tubular acidosis and is rarely associated with blood cell abnormalities. The autosomal recessive form is always associated with complete distal renal tubular acidosis and is more commonly associated with blood cell abnormalities, although not everyone with this form has abnormal blood cells. </s>


Input: How many people are affected by SLC4A1-associated distal renal tubular acidosis ?

Output: The prevalence of SLC4A1-associated distal renal tubular acidosis is unknown. The condition is most common in Southeast Asia, especially Thailand. </s>


Input: What are the genetic changes related to SLC4A1-associated distal renal tubular acidosis ?

Output: Both the autosomal dominant and autosomal recessive forms of SLC4A1-associated distal renal tubular acidosis are caused by mutations in the SLC4A1 gene. This gene provides instructions for making the anion exchanger 1 (AE1) protein, which transports negatively charged atoms (anions) across cell membranes. Specifically, AE1 exchanges negatively charged atoms of chlorine (chloride ions) for negatively charged bicarbonate molecules (bicarbonate ions). The AE1 protein is found in the cell membrane of kidney cells and red blood cells. In kidney cells, the exchange of bicarbonate through AE1 allows acid to be released from the cell into the urine. In red blood cells, AE1 attaches to other proteins that make up the structural framework (the cytoskeleton) of the cells, helping to maintain their structure.  The SLC4A1 gene mutations involved in either form of SLC4A1-associated distal renal tubular acidosis lead to production of altered AE1 proteins that cannot get to the correct location in the cell membrane. In the autosomal dominant form of the condition, gene mutations affect only one copy of the SLC4A1 gene, and normal AE1 protein is produced from the other copy. However, the altered protein attaches to the normal protein and keeps it from getting to the correct location, leading to a severe reduction or absence of AE1 protein in the cell membrane. In autosomal recessive distal renal tubular acidosis, both copies of the SLC4A1 gene are mutated, so all of the protein produced from this gene is altered and not able to get to the correct location. Improper location or absence of AE1 in kidney cell membranes disrupts bicarbonate exchange, and as a result, acid cannot be released into the urine. Instead, the acid builds up in the blood in most affected individuals, leading to metabolic acidosis and the other features of complete distal renal tubular acidosis. It is not clear why some people develop metabolic acidosis and others do not. Researchers suggest that in individuals with incomplete distal renal tubular acidosis, another mechanism is able to help regulate blood acidity (pH) and keep metabolic acidosis from developing.  In red blood cells, interaction with a protein called glycophorin A can often help the altered AE1 protein get to the cell membrane where it can perform its function, which explains why most people with SLC4A1-associated distal renal tubular acidosis do not have blood cell abnormalities. However, some altered AE1 proteins cannot be helped by glycophorin A and are not found in the cell membrane. Without AE1, the red blood cells are unstable; breakdown of these abnormal red blood cells may lead to hemolytic anemia.  Some people have nonhereditary forms of distal renal tubular acidosis; these forms can be caused by immune system problems or other conditions that damage the kidneys. These individuals often have additional signs and symptoms related to the original condition. </s>


Input: Is SLC4A1-associated distal renal tubular acidosis inherited ?

Output: SLC4A1-associated distal renal tubular acidosis can have different patterns of inheritance. It is usually inherited in an autosomal dominant pattern, which means one copy of the altered SLC4A1 gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  Less commonly, SLC4A1-associated distal renal tubular acidosis has an autosomal recessive pattern of inheritance, which means a mutation must occur in both copies of the SLC4A1 gene for the condition to develop. This pattern occurs with certain types of SLC4A1 gene 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 SLC4A1-associated distal renal tubular acidosis ?

Output: These resources address the diagnosis or management of SLC4A1-associated distal renal tubular acidosis:  - Genetic Testing Registry: Renal tubular acidosis, distal, autosomal dominant  - Genetic Testing Registry: Renal tubular acidosis, distal, with hemolytic anemia   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) infantile-onset spinocerebellar ataxia ?

Output: Infantile-onset spinocerebellar ataxia (IOSCA) is a progressive disorder that affects the nervous system. Babies with IOSCA develop normally during the first year of life. During early childhood, however, they begin experiencing difficulty coordinating movements (ataxia); very weak muscle tone (hypotonia); involuntary writhing movements of the limbs (athetosis); and decreased reflexes. By their teenage years affected individuals require wheelchair assistance.  People with IOSCA often develop problems with the autonomic nervous system, which controls involuntary body functions. As a result, they may experience excessive sweating, difficulty controlling urination, and severe constipation.  IOSCA also leads to vision and hearing problems that begin by about age 7. Children with this disorder develop weakness in the muscles that control eye movement (ophthalmoplegia). In their teenage years they experience degeneration of the nerves that carry information from the eyes to the brain (optic atrophy), which can result in vision loss. Hearing loss caused by nerve damage (sensorineural hearing loss) typically occurs during childhood and progresses to profound deafness.  Individuals with IOSCA may have recurrent seizures (epilepsy). These seizures can lead to severe brain dysfunction (encephalopathy).  Most people with IOSCA survive into adulthood. However, a few individuals with IOSCA have an especially severe form of the disorder involving liver damage and encephalopathy that develops during early childhood. These children do not generally live past age 5. </s>


Input: How many people are affected by infantile-onset spinocerebellar ataxia ?

Output: More than 20 individuals with IOSCA have been identified in Finland. A few individuals with similar symptoms have been reported elsewhere in Europe. </s>


Input: What are the genetic changes related to infantile-onset spinocerebellar ataxia ?

Output: Mutations in the C10orf2 gene cause IOSCA. The C10orf2 gene provides instructions for making two very similar proteins called Twinkle and Twinky. These proteins are found in the mitochondria, which are structures within cells that convert the energy from food into a form that cells can use.  Mitochondria each contain a small amount of DNA, known as mitochondrial DNA or mtDNA, which is essential for the normal function of these structures. The Twinkle protein is involved in the production and maintenance of mtDNA. The function of the Twinky protein is unknown.  The C10orf2 gene mutations that cause IOSCA interfere with the function of the Twinkle protein and result in reduced quantities of mtDNA (mtDNA depletion). Impaired mitochondrial function in the nervous system, muscles, and other tissues that require a large amount of energy leads to neurological dysfunction and the other problems associated with IOSCA. </s>


Input: Is infantile-onset spinocerebellar 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 infantile-onset spinocerebellar ataxia ?

Output: These resources address the diagnosis or management of IOSCA:  - Gene Review: Gene Review: Infantile-Onset Spinocerebellar Ataxia  - Genetic Testing Registry: Mitochondrial DNA depletion syndrome 7 (hepatocerebral type)   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) androgenetic alopecia ?

Output: Androgenetic alopecia is a common form of hair loss in both men and women. In men, this condition is also known as male-pattern baldness. Hair is lost in a well-defined pattern, beginning above both temples. Over time, the hairline recedes to form a characteristic "M" shape. Hair also thins at the crown (near the top of the head), often progressing to partial or complete baldness.  The pattern of hair loss in women differs from male-pattern baldness. In women, the hair becomes thinner all over the head, and the hairline does not recede. Androgenetic alopecia in women rarely leads to total baldness.  Androgenetic alopecia in men has been associated with several other medical conditions including coronary heart disease and enlargement of the prostate. Additionally, prostate cancer, disorders of insulin resistance (such as diabetes and obesity), and high blood pressure (hypertension) have been related to androgenetic alopecia. In women, this form of hair loss is associated with an increased risk of polycystic ovary syndrome (PCOS). PCOS is characterized by a hormonal imbalance that can lead to irregular menstruation, acne, excess hair elsewhere on the body (hirsutism), and weight gain. </s>


Input: How many people are affected by androgenetic alopecia ?

Output: Androgenetic alopecia is a frequent cause of hair loss in both men and women. This form of hair loss affects an estimated 50 million men and 30 million women in the United States. Androgenetic alopecia can start as early as a person's teens and risk increases with age; more than 50 percent of men over age 50 have some degree of hair loss. In women, hair loss is most likely after menopause. </s>


Input: What are the genetic changes related to androgenetic alopecia ?

Output: A variety of genetic and environmental factors likely play a role in causing androgenetic alopecia. Although researchers are studying risk factors that may contribute to this condition, most of these factors remain unknown. Researchers have determined that this form of hair loss is related to hormones called androgens, particularly an androgen called dihydrotestosterone. Androgens are important for normal male sexual development before birth and during puberty. Androgens also have other important functions in both males and females, such as regulating hair growth and sex drive.  Hair growth begins under the skin in structures called follicles. Each strand of hair normally grows for 2 to 6 years, goes into a resting phase for several months, and then falls out. The cycle starts over when the follicle begins growing a new hair. Increased levels of androgens in hair follicles can lead to a shorter cycle of hair growth and the growth of shorter and thinner strands of hair. Additionally, there is a delay in the growth of new hair to replace strands that are shed.  Although researchers suspect that several genes play a role in androgenetic alopecia, variations in only one gene, AR, have been confirmed in scientific studies. The AR gene provides instructions for making a protein called an androgen receptor. Androgen receptors allow the body to respond appropriately to dihydrotestosterone and other androgens. Studies suggest that variations in the AR gene lead to increased activity of androgen receptors in hair follicles. It remains unclear, however, how these genetic changes increase the risk of hair loss in men and women with androgenetic alopecia.  Researchers continue to investigate the connection between androgenetic alopecia and other medical conditions, such as coronary heart disease and prostate cancer in men and polycystic ovary syndrome in women. They believe that some of these disorders may be associated with elevated androgen levels, which may help explain why they tend to occur with androgen-related hair loss. Other hormonal, environmental, and genetic factors that have not been identified also may be involved. </s>


Input: Is androgenetic alopecia inherited ?

Output: The inheritance pattern of androgenetic alopecia is unclear because many genetic and environmental factors are likely to be involved. This condition tends to cluster in families, however, and having a close relative with patterned hair loss appears to be a risk factor for developing the condition. </s>


Input: What are the treatments for androgenetic alopecia ?

Output: These resources address the diagnosis or management of androgenetic alopecia:  - Genetic Testing Registry: Baldness, male pattern  - MedlinePlus Encyclopedia: Female Pattern Baldness  - MedlinePlus Encyclopedia: Hair Loss  - MedlinePlus Encyclopedia: Male Pattern Baldness   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>