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