Input: What is (are) central core disease ?

Output: Central core disease is a disorder that affects muscles used for movement (skeletal muscles). This condition causes muscle weakness that ranges from almost unnoticeable to very severe.  Most people with central core disease experience persistent, mild muscle weakness that does not worsen with time. This weakness affects the muscles near the center of the body (proximal muscles), particularly muscles in the upper legs and hips. Muscle weakness causes affected infants to appear "floppy" and can delay the development of motor skills such as sitting, standing, and walking. In severe cases, affected infants experience profoundly weak muscle tone (hypotonia) and serious or life-threatening breathing problems. Central core disease is also associated with skeletal abnormalities such as abnormal curvature of the spine (scoliosis), hip dislocation, and joint deformities called contractures that restrict the movement of certain joints.  Many people with central core disease also have an increased risk of developing a severe reaction to certain drugs used during surgery and other invasive procedures. This reaction is called malignant hyperthermia. Malignant hyperthermia occurs in response to some anesthetic gases, which are used to block the sensation of pain, and with a particular type of muscle relaxant. If given these drugs, people at risk for malignant hyperthermia may experience muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), a high fever, increased acid levels in the blood and other tissues (acidosis), and a rapid heart rate. The complications of malignant hyperthermia can be life-threatening unless they are treated promptly.  Central core disease gets its name from disorganized areas called cores, which are found in the center of muscle fibers in many affected individuals. These abnormal regions can only be seen under a microscope. Although the presence of cores can help doctors diagnose central core disease, it is unclear how they are related to muscle weakness and the other features of this condition. </s>


Input: How many people are affected by central core disease ?

Output: Central core disease is probably an uncommon condition, although its incidence is unknown. </s>


Input: What are the genetic changes related to central core disease ?

Output: Mutations in the RYR1 gene cause central core disease.  The RYR1 gene provides instructions for making a protein called ryanodine receptor 1. This protein plays an essential role in skeletal muscles. For the body to move normally, these muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of charged atoms (ions) into muscle cells. The ryanodine receptor 1 protein forms a channel that releases calcium ions stored within muscle cells. The resulting increase in calcium ion concentration inside muscle cells stimulates muscle fibers to contract, allowing the body to move.  Mutations in the RYR1 gene change the structure of ryanodine receptor 1, allowing calcium ions to "leak" through the abnormal channel or impairing the channel's ability to release stored calcium ions at the correct time. This disruption in calcium ion transport prevents muscles from contracting normally, leading to the muscle weakness characteristic of central core disease. </s>


Input: Is central core disease inherited ?

Output: Central core disease is most often inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.  Less commonly, central core disease is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but typically do not show signs and symptoms of the condition. People who carry one mutated copy of the RYR1 gene, however, may be at increased risk for malignant hyperthermia. </s>


Input: What are the treatments for central core disease ?

Output: These resources address the diagnosis or management of central core disease:  - Gene Review: Gene Review: Central Core Disease  - Genetic Testing Registry: Central core disease  - MedlinePlus Encyclopedia: Hypotonia  - MedlinePlus Encyclopedia: Malignant Hyperthermia   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) Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis ?

Output: Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis (NFJS/DPR) represents a rare type of ectodermal dysplasia, a group of about 150 conditions characterized by abnormal development of ectodermal tissues including the skin, hair, nails, teeth, and sweat glands. NFJS and DPR were originally described as separate conditions; however, because they have similar features and are caused by mutations in the same gene, they are now often considered forms of the same disorder.  Among the most common signs of NFJS/DPR is a net-like pattern of dark brown or gray skin coloring, known as reticulate hyperpigmentation. This darker pigmentation is seen most often on the neck, chest, and abdomen, although it can also occur in and around the eyes and mouth. Reticulate hyperpigmentation appears in infancy or early childhood. It may fade with age or persist throughout life.  NFJS/DPR also affects the skin on the hands and feet. The skin on the palms of the hands and soles of the feet often becomes thick, hard, and callused, a condition known as palmoplantar keratoderma. Some affected individuals also have blistering on their palms and soles. Their fingernails and toenails may be malformed, brittle, and either thicker or thinner than usual. Most affected individuals are missing the patterned ridges on the skin of the hands and feet, called dermatoglyphs, that are the basis for each person's unique fingerprints.  Additional features of NFJS/DPR can include a reduced ability to sweat (hypohidrosis) or excess sweating (hyperhidrosis) and dental abnormalities. Some affected individuals also have hair loss (alopecia) on the scalp, eyebrows, and underarms. The alopecia is described as noncicatricial because it does not leave scars (cicatrices). </s>


Input: How many people are affected by Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis ?

Output: NFJS/DPR is a rare condition; its prevalence is unknown. Only a few affected families have been reported in the medical literature. </s>


Input: What are the genetic changes related to Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis ?

Output: NFJS/DPR results from mutations in the KRT14 gene. This gene provides instructions for making a protein called keratin 14. Keratins are tough, fibrous proteins that provide strength and resiliency to the outer layer of the skin (the epidermis). Researchers believe that keratin 14 may also play a role in the formation of sweat glands and the development of dermatoglyphs.  The KRT14 gene mutations that cause NFJS/DPR most likely reduce the amount of functional keratin 14 that is produced in cells. A shortage of this protein makes cells in the epidermis more likely to self-destruct (undergo apoptosis). The resulting loss of these cells alters the normal development and structure of ectodermal tissues, which likely underlies most of the skin and nail problems characteristic of NFJS/DPR. However, it is unclear how a shortage of keratin 14 is related to changes in skin pigmentation. </s>


Input: Is Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis 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. </s>


Input: What are the treatments for Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis ?

Output: These resources address the diagnosis or management of NFJS/DPR:  - Foundation for Ichthyosis and Related Skin Types (FIRST): Palmoplantar Keratodermas  - Genetic Testing Registry: Dermatopathia pigmentosa reticularis  - Genetic Testing Registry: Naegeli-Franceschetti-Jadassohn syndrome  - MedlinePlus Encyclopedia: Ectodermal Dysplasia  - MedlinePlus Encyclopedia: Nail Abnormalities   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) Fanconi anemia ?

Output: Fanconi anemia is a condition that affects many parts of the body. People with this condition may have bone marrow failure, physical abnormalities, organ defects, and an increased risk of certain cancers.  The major function of bone marrow is to produce new blood cells. These include red blood cells, which carry oxygen to the body's tissues; white blood cells, which fight infections; and platelets, which are necessary for normal blood clotting. Approximately 90 percent of people with Fanconi anemia have impaired bone marrow function that leads to a decrease in the production of all blood cells (aplastic anemia). Affected individuals experience extreme tiredness (fatigue) due to low numbers of red blood cells (anemia), frequent infections due to low numbers of white blood cells (neutropenia), and clotting problems due to low numbers of platelets (thrombocytopenia). People with Fanconi anemia may also develop myelodysplastic syndrome, a condition in which immature blood cells fail to develop normally.  More than half of people with Fanconi anemia have physical abnormalities. These abnormalities can involve irregular skin coloring such as unusually light-colored skin (hypopigmentation) or caf-au-lait spots, which are flat patches on the skin that are darker than the surrounding area. Other possible symptoms of Fanconi anemia include malformed thumbs or forearms and other skeletal problems including short stature; malformed or absent kidneys and other defects of the urinary tract; gastrointestinal abnormalities; heart defects; eye abnormalities such as small or abnormally shaped eyes; and malformed ears and hearing loss. People with this condition may have abnormal genitalia or malformations of the reproductive system. As a result, most affected males and about half of affected females cannot have biological children (are infertile). Additional signs and symptoms can include abnormalities of the brain and spinal cord (central nervous system), including increased fluid in the center of the brain (hydrocephalus) or an unusually small head size (microcephaly).  Individuals with Fanconi anemia have an increased risk of developing a cancer of blood-forming cells in the bone marrow called acute myeloid leukemia (AML) or tumors of the head, neck, skin, gastrointestinal system, or genital tract. The likelihood of developing one of these cancers in people with Fanconi anemia is between 10 and 30 percent. </s>


Input: How many people are affected by Fanconi anemia ?

Output: Fanconi anemia occurs in 1 in 160,000 individuals worldwide. This condition is more common among people of Ashkenazi Jewish descent, the Roma population of Spain, and black South Africans. </s>


Input: What are the genetic changes related to Fanconi anemia ?

Output: Mutations in at least 15 genes can cause Fanconi anemia. Proteins produced from these genes are involved in a cell process known as the FA pathway. The FA pathway is turned on (activated) when the process of making new copies of DNA, called DNA replication, is blocked due to DNA damage. The FA pathway sends certain proteins to the area of damage, which trigger DNA repair so DNA replication can continue.  The FA pathway is particularly responsive to a certain type of DNA damage known as interstrand cross-links (ICLs). ICLs occur when two DNA building blocks (nucleotides) on opposite strands of DNA are abnormally attached or linked together, which stops the process of DNA replication. ICLs can be caused by a buildup of toxic substances produced in the body or by treatment with certain cancer therapy drugs.  Eight proteins associated with Fanconi anemia group together to form a complex known as the FA core complex. The FA core complex activates two proteins, called FANCD2 and FANCI. The activation of these two proteins brings DNA repair proteins to the area of the ICL so the cross-link can be removed and DNA replication can continue.  Eighty to 90 percent of cases of Fanconi anemia are due to mutations in one of three genes, FANCA, FANCC, and FANCG. These genes provide instructions for producing components of the FA core complex. Mutations in any of the many genes associated with the FA core complex will cause the complex to be nonfunctional and disrupt the entire FA pathway. As a result, DNA damage is not repaired efficiently and ICLs build up over time. The ICLs stall DNA replication, ultimately resulting in either abnormal cell death due to an inability make new DNA molecules or uncontrolled cell growth due to a lack of DNA repair processes. Cells that divide quickly, such as bone marrow cells and cells of the developing fetus, are particularly affected. The death of these cells results in the decrease in blood cells and the physical abnormalities characteristic of Fanconi anemia. When the buildup of errors in DNA leads to uncontrolled cell growth, affected individuals can develop acute myeloid leukemia or other cancers. </s>


Input: Is Fanconi anemia inherited ?

Output: Fanconi anemia is most often 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.  Very rarely, this condition is inherited in an X-linked recessive pattern. The gene associated with X-linked recessive Fanconi anemia is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently 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 Fanconi anemia ?

Output: These resources address the diagnosis or management of Fanconi anemia:  - Cincinnati Children's Hospital: Fanconi Anemia Comprehensive Care Center  - Fanconi Anemia Research Fund: Fanconi Anemia Guidelines for Diagnosis and Management  - Gene Review: Gene Review: Fanconi Anemia  - Genetic Testing Registry: Fanconi anemia  - Genetic Testing Registry: Fanconi anemia, complementation group A  - Genetic Testing Registry: Fanconi anemia, complementation group B  - Genetic Testing Registry: Fanconi anemia, complementation group C  - Genetic Testing Registry: Fanconi anemia, complementation group D1  - Genetic Testing Registry: Fanconi anemia, complementation group D2  - Genetic Testing Registry: Fanconi anemia, complementation group E  - Genetic Testing Registry: Fanconi anemia, complementation group F  - Genetic Testing Registry: Fanconi anemia, complementation group G  - Genetic Testing Registry: Fanconi anemia, complementation group I  - Genetic Testing Registry: Fanconi anemia, complementation group J  - Genetic Testing Registry: Fanconi anemia, complementation group L  - Genetic Testing Registry: Fanconi anemia, complementation group M  - Genetic Testing Registry: Fanconi anemia, complementation group N  - Genetic Testing Registry: Fanconi anemia, complementation group O  - Genetic Testing Registry: Fanconi anemia, complementation group P  - MedlinePlus Encyclopedia: Fanconi's Anemia  - National Cancer Institute: Adult Acute Myeloid Leukemia Treatment PDQ  - National Cancer Institute: Myelodysplastic Syndromes Treatment PDQ  - National Heart Lung and Blood Institute: How is Fanconi Anemia Treated?  - The Rockefeller University: International Fanconi Anemia Registry   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) 18q deletion syndrome ?

Output: 18q deletion syndrome is a chromosomal condition that results when a piece of chromosome 18 is missing. The condition can lead to a wide variety of signs and symptoms among affected individuals.  Most people with 18q deletion syndrome have intellectual disability and delayed development that can range from mild to severe, but some affected individuals have normal intelligence and development. Seizures, hyperactivity, aggression, and autistic behaviors that affect communication and social interaction may also occur. Some people with 18q deletion syndrome have a loss of tissue called white matter in the brain and spinal cord (leukodystrophy), structural abnormalities of the brain, or an abnormally small head size (microcephaly).  Other features that are common in 18q deletion syndrome include short stature, weak muscle tone (hypotonia), narrow auditory canals leading to hearing loss, and limb abnormalities such as foot deformities and thumbs that are positioned unusually close to the wrist. Some affected individuals have mild facial differences such as deep-set eyes, a flat or sunken appearance of the middle of the face (midface hypoplasia), a wide mouth, and prominent ears; these features are often not noticeable except in a detailed medical evaluation. Eye movement disorders and other vision problems, genital abnormalities, heart disease, and skin problems may also occur in this disorder. </s>


Input: How many people are affected by 18q deletion syndrome ?

Output: 18q deletion syndrome occurs in an estimated 1 in 40,000 newborns. This condition is found in people of all ethnic backgrounds. </s>


Input: What are the genetic changes related to 18q deletion syndrome ?

Output: 18q deletion syndrome is caused by a deletion of genetic material from the long (q) arm of chromosome 18. This chromosomal change is written as 18q-. The size of the deletion and its location on the chromosome vary among affected individuals.  The signs and symptoms of 18q deletion syndrome, including the leukodystrophy that likely contributes to the neurological problems, are probably related to the loss of multiple genes on the long arm of chromosome 18. 18q deletion syndrome is often categorized into two types: individuals with deletions near the end of the long arm of chromosome 18 are said to have distal 18q deletion syndrome, and those with deletions in the part of the long arm near the center of chromosome 18 are said to have proximal 18q deletion syndrome. The signs and symptoms of these two types of the condition are overlapping, with certain features being more common in one form of the disorder than in the other. For example, hearing loss and heart abnormalities are more common in people with distal 18q deletion syndrome, while seizures occur more often in people with proximal 18q deletion syndrome. Researchers are working to determine how the loss of specific genes in these regions contributes to the various features of 18q deletion syndrome. </s>


Input: Is 18q deletion syndrome inherited ?

Output: Most cases of 18q deletion syndrome are not inherited. The deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family.  In some cases, 18q deletion syndrome is inherited, usually from a mildly affected parent. The deletion can also be inherited from an unaffected parent who carries a chromosomal rearrangement called a balanced translocation, in which no genetic material is gained or lost. Individuals with a balanced translocation do not usually have any related health problems; however, the translocation can become unbalanced as it is passed to the next generation. Children who inherit an unbalanced translocation can have a chromosomal rearrangement with extra or missing genetic material. Individuals with 18q deletion syndrome who inherit an unbalanced translocation are missing genetic material from the long arm of chromosome 18, which results in the signs and symptoms of this disorder. </s>


Input: What are the treatments for 18q deletion syndrome ?

Output: These resources address the diagnosis or management of 18q deletion syndrome:  - Gene Review: Gene Review: Leukodystrophy Overview  - University of Texas Chromosome 18 Clinical Research Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) X-linked adrenoleukodystrophy ?

Output: X-linked adrenoleukodystrophy is a genetic disorder that occurs primarily in males. It mainly affects the nervous system and the adrenal glands, which are small glands located on top of each kidney. In this disorder, the fatty covering (myelin) that insulates nerves in the brain and spinal cord is prone to deterioration (demyelination), which reduces the ability of the nerves to relay information to the brain. In addition, damage to the outer layer of the adrenal glands (adrenal cortex) causes a shortage of certain hormones (adrenocortical insufficiency). Adrenocortical insufficiency may cause weakness, weight loss, skin changes, vomiting, and coma.  There are three distinct types of X-linked adrenoleukodystrophy: a childhood cerebral form, an adrenomyeloneuropathy type, and a form called Addison disease only.  Children with the cerebral form of X-linked adrenoleukodystrophy experience learning and behavioral problems that usually begin between the ages of 4 and 10. Over time the symptoms worsen, and these children may have difficulty reading, writing, understanding speech, and comprehending written material. Additional signs and symptoms of the cerebral form include aggressive behavior, vision problems, difficulty swallowing, poor coordination, and impaired adrenal gland function. The rate at which this disorder progresses is variable but can be extremely rapid, often leading to total disability within a few years. The life expectancy of individuals with this type depends on the severity of the signs and symptoms and how quickly the disorder progresses. Individuals with the cerebral form of X-linked adrenoleukodystrophy usually survive only a few years after symptoms begin but may survive longer with intensive medical support.  Signs and symptoms of the adrenomyeloneuropathy type appear between early adulthood and middle age. Affected individuals develop progressive stiffness and weakness in their legs (paraparesis), experience urinary and genital tract disorders, and often show changes in behavior and thinking ability. Most people with the adrenomyeloneuropathy type also have adrenocortical insufficiency. In some severely affected individuals, damage to the brain and nervous system can lead to early death.  People with X-linked adrenoleukodystrophy whose only symptom is adrenocortical insufficiency are said to have the Addison disease only form. In these individuals, adrenocortical insufficiency can begin anytime between childhood and adulthood. However, most affected individuals develop the additional features of the adrenomyeloneuropathy type by the time they reach middle age. The life expectancy of individuals with this form depends on the severity of the signs and symptoms, but typically this is the mildest of the three types.  Rarely, individuals with X-linked adrenoleukodystrophy develop multiple features of the disorder in adolescence or early adulthood. In addition to adrenocortical insufficiency, these individuals usually have psychiatric disorders and a loss of intellectual function (dementia). It is unclear whether these individuals have a distinct form of the condition or a variation of one of the previously described types.  For reasons that are unclear, different forms of X-linked adrenoleukodystrophy can be seen in affected individuals within the same family. </s>


Input: How many people are affected by X-linked adrenoleukodystrophy ?

Output: The prevalence of X-linked adrenoleukodystrophy is 1 in 20,000 to 50,000 individuals worldwide. This condition occurs with a similar frequency in all populations. </s>


Input: What are the genetic changes related to X-linked adrenoleukodystrophy ?

Output: Mutations in the ABCD1 gene cause X-linked adrenoleukodystrophy. The ABCD1 gene provides instructions for producing the adrenoleukodystrophy protein (ALDP), which is involved in transporting certain fat molecules called very long-chain fatty acids (VLCFAs) into peroxisomes. Peroxisomes are small sacs within cells that process many types of molecules, including VLCFAs.  ABCD1 gene mutations result in a shortage (deficiency) of ALDP. When this protein is lacking, the transport and subsequent breakdown of VLCFAs is disrupted, causing abnormally high levels of these fats in the body. The accumulation of VLCFAs may be toxic to the adrenal cortex and myelin. Research suggests that the accumulation of VLCFAs triggers an inflammatory response in the brain, which could lead to the breakdown of myelin. The destruction of these tissues leads to the signs and symptoms of X-linked adrenoleukodystrophy. </s>


Input: Is X-linked adrenoleukodystrophy inherited ?

Output: X-linked adrenoleukodystrophy is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), one altered copy of the ABCD1 gene in each cell is sufficient to cause X-linked adrenoleukodystrophy. Because females have two copies of the X chromosome, one altered copy of the ABCD1 gene in each cell usually does not cause any features of X-linked adrenoleukodystrophy; however, some females with one altered copy of the gene have health problems associated with this disorder. The signs and symptoms of X-linked adrenoleukodystrophy tend to appear at a later age in females than in males. Affected women usually develop features of the adrenomyeloneuropathy type. </s>


Input: What are the treatments for X-linked adrenoleukodystrophy ?

Output: These resources address the diagnosis or management of X-linked adrenoleukodystrophy:  - Gene Review: Gene Review: X-Linked Adrenoleukodystrophy  - Genetic Testing Registry: Adrenoleukodystrophy  - Genomics Education Programme (UK)  - MedlinePlus Encyclopedia: Adrenoleukodystrophy  - National Marrow Donor Program  - X-linked Adrenoleukodystrophy Database: Diagnosis of X-ALD   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 restrictive cardiomyopathy ?

Output: Familial restrictive cardiomyopathy is a genetic form of heart disease. For the heart to beat normally, the heart (cardiac) muscle must contract and relax in a coordinated way. Oxygen-rich blood from the lungs travels first through the upper chambers of the heart (the atria), and then to the lower chambers of the heart (the ventricles).  In people with familial restrictive cardiomyopathy, the heart muscle is stiff and cannot fully relax after each contraction. Impaired muscle relaxation causes blood to back up in the atria and lungs, which reduces the amount of blood in the ventricles.  Familial restrictive cardiomyopathy can appear anytime from childhood to adulthood. The first signs and symptoms of this condition in children are failure to gain weight and grow at the expected rate (failure to thrive), extreme tiredness (fatigue), and fainting. Children who are severely affected may also have abnormal swelling or puffiness (edema), increased blood pressure, an enlarged liver, an abnormal buildup of fluid in the abdominal cavity (ascites), and lung congestion. Some children with familial restrictive cardiomyopathy do not have any obvious signs or symptoms, but they may die suddenly due to heart failure. Without treatment, the majority of affected children survive only a few years after they are diagnosed.  Adults with familial restrictive cardiomyopathy typically first develop shortness of breath, fatigue, and a reduced ability to exercise. Some individuals have an irregular heart beat (arrhythmia) and may also experience a sensation of fluttering or pounding in the chest (palpitations) and dizziness. Abnormal blood clots are commonly seen in adults with this condition. Without treatment, approximately one-third of adults with familial restrictive cardiomyopathy do not survive more than five years after diagnosis. </s>


Input: How many people are affected by familial restrictive cardiomyopathy ?

Output: The prevalence of familial restrictive cardiomyopathy is unknown. Although cardiomyopathy is a relatively common condition, restrictive cardiomyopathy, in which relaxation of the heart muscle is impaired, is the least common type. Some other forms of cardiomyopathy involve a weak or enlarged heart muscle with impaired contraction. In the United States and in Europe, restrictive cardiomyopathy accounts for less than five percent of all cardiomyopathies. The proportion of restrictive cardiomyopathy that runs in families is not known. </s>


Input: What are the genetic changes related to familial restrictive cardiomyopathy ?

Output: Mutations in several genes have been found to cause familial restrictive cardiomyopathy. Mutations in the TNNI3 gene are one of the major causes of this condition. The TNNI3 gene provides instructions for making a protein called cardiac troponin I, which is found solely in the heart. Cardiac troponin I is one of three proteins that make up the troponin protein complex, which helps regulate tensing (contraction) and relaxation of the heart muscle.  TNNI3 gene mutations associated with familial restrictive cardiomyopathy result in the production of a defective cardiac troponin I protein. The altered protein disrupts the function of the troponin protein complex and does not allow the heart muscle to fully relax. As a result, not enough blood enters the ventricles, leading to a buildup in the atria and lungs. The abnormal heart relaxation and blood flow is responsible for many of the signs and symptoms of familial restrictive cardiomyopathy.  Mutations in other genes associated with familial restrictive cardiomyopathy each account for a small percentage of cases of this condition. Some people with familial restrictive cardiomyopathy do not have an identified mutation in any of the known associated genes. The cause of the disorder in these individuals is unknown. </s>


Input: Is familial restrictive cardiomyopathy 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. </s>


Input: What are the treatments for familial restrictive cardiomyopathy ?

Output: These resources address the diagnosis or management of familial restrictive cardiomyopathy:  - Genetic Testing Registry: Familial restrictive cardiomyopathy  - Genetic Testing Registry: Familial restrictive cardiomyopathy 1  - Genetic Testing Registry: Familial restrictive cardiomyopathy 2  - Genetic Testing Registry: Familial restrictive cardiomyopathy 3  - Johns Hopkins Medicine: Cardiomyopathy/Heart Failure  - MedlinePlus Encyclopedia: Restrictive Cardiomyopathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) nail-patella syndrome ?

Output: Nail-patella syndrome is characterized by abnormalities of the nails, knees, elbows, and pelvis. The features of nail-patella syndrome vary in severity between affected individuals, even among members of the same family.  Nail abnormalities are seen in almost all individuals with nail-patella syndrome. The nails may be absent or underdeveloped and discolored, split, ridged, or pitted. The fingernails are more likely to be affected than the toenails, and the thumbnails are usually the most severely affected. In many people with this condition, the areas at the base of the nails (lunulae) are triangular instead of the usual crescent shape.  Individuals with nail-patella syndrome also commonly have skeletal abnormalities involving the knees, elbows, and hips. The kneecaps (patellae) are small, irregularly shaped, or absent, and dislocation of the patella is common. Some people with this condition may not be able to fully extend their arms or turn their palms up while keeping their elbows straight. The elbows may also be angled outward (cubitus valgus) or have abnormal webbing. Many individuals with nail-patella syndrome have horn-like outgrowths of the iliac bones of the pelvis (iliac horns). These abnormal projections may be felt through the skin, but they do not cause any symptoms and are usually detected on a pelvic x-ray. Iliac horns are very common in people with nail-patella syndrome and are rarely, if ever, seen in people without this condition.  Other areas of the body may also be affected in nail-patella syndrome, particularly the eyes and kidneys. Individuals with this condition are at risk of developing increased pressure within the eyes (glaucoma) at an early age. Some people develop kidney disease, which can progress to kidney failure. </s>


Input: How many people are affected by nail-patella syndrome ?

Output: The prevalence of nail-patella syndrome is estimated to be 1 in 50,000 individuals. </s>


Input: What are the genetic changes related to nail-patella syndrome ?

Output: Mutations in the LMX1B gene cause nail-patella syndrome. The LMX1B gene provides instructions for producing a protein that attaches (binds) to specific regions of DNA and regulates the activity of other genes. On the basis of this role, the LMX1B protein is called a transcription factor. The LMX1B protein appears to be particularly important during early embryonic development of the limbs, kidneys, and eyes. Mutations in the LMX1B gene lead to the production of an abnormally short, nonfunctional protein or affect the protein's ability to bind to DNA. It is unclear how mutations in the LMX1B gene lead to the signs and symptoms of nail-patella syndrome. </s>


Input: Is nail-patella syndrome inherited ?

Output: Nail-patella syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the LMX1B gene. These cases occur in people with no history of the disorder in their family. </s>


Input: What are the treatments for nail-patella syndrome ?

Output: These resources address the diagnosis or management of nail-patella syndrome:  - Gene Review: Gene Review: Nail-Patella Syndrome  - Genetic Testing Registry: Nail-patella 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) Fraser syndrome ?

Output: Fraser syndrome is a rare disorder that affects development starting before birth. Characteristic features of this condition include eyes that are completely covered by skin and usually malformed (cryptophthalmos), fusion of the skin between the fingers and toes (cutaneous syndactyly), and abnormalities of the genitalia and the urinary tract (genitourinary anomalies). Other tissues and organs can also be affected. Depending on the severity of the signs and symptoms, Fraser syndrome can be fatal before or shortly after birth; less severely affected individuals can live into childhood or adulthood.  Cryptophthalmos is the most common abnormality in people with Fraser syndrome. Both eyes are usually completely covered by skin, but in some cases, only one eye is covered or one or both eyes are partially covered. In cryptophthalmos, the eyes can also be malformed; for example, the eyeballs may be fused to the skin covering them, or they may be small (microphthalmia) or missing (anophthalmia). Eye abnormalities typically lead to impairment or loss of vision in people with Fraser syndrome. Affected individuals can have other problems related to abnormal eye development, including missing eyebrows or eyelashes or a patch of hair extending from the side hairline to the eyebrow.  Cutaneous syndactyly typically occurs in both the hands and the feet in Fraser syndrome. In most people with this feature, the skin between the middle three fingers and toes are fused, but the other digits can also be involved. Other abnormalities of the hands and feet can occur in people with Fraser syndrome.  Individuals with Fraser syndrome can have abnormalities of the genitalia, such as an enlarged clitoris in females or undescended testes (cryptorchidism) in males. Some affected individuals have external genitalia that do not appear clearly female or male (ambiguous genitalia).  The most common urinary tract abnormality in Fraser syndrome is the absence of one or both kidneys (renal agenesis). Affected individuals can have other kidney problems or abnormalities of the bladder and other parts of the urinary tract.  A variety of other signs and symptoms can be involved in Fraser syndrome, including heart malformations or abnormalities of the voicebox (larynx) or other parts of the respiratory tract. Some affected individuals have facial abnormalities, including ear or nose abnormalities or an opening in the upper lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate). </s>


Input: How many people are affected by Fraser syndrome ?

Output: Fraser syndrome affects an estimated 1 in 200,000 newborns. The condition occurs in approximately 1 in 10,000 fetuses that do not survive to birth. </s>


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

Output: Mutations in the FRAS1, FREM2, or GRIP1 gene can cause Fraser syndrome. FRAS1 gene mutations are the most common cause, accounting for about half of cases of Fraser syndrome. FREM2 and GRIP1 gene mutations are each found in a small percentage of cases.  The FRAS1 and FREM2 proteins (produced from the FRAS1 and FREM2 genes, respectively) are part of a group of proteins called the FRAS/FREM complex. The GRIP1 protein (produced from the GRIP1 gene) ensures that FRAS1 and FREM2 get to the correct location of the cell to form the FRAS/FREM complex.  The FRAS/FREM complex is found in basement membranes, which are thin, sheet-like structures that separate and support cells in many tissues. This complex is particularly important during development before birth. One of the complex's roles is to anchor the top layer of skin by connecting its basement membrane to the layer of skin below. The FRAS/FREM complex is also involved in the proper development of other organs and tissues, including the kidneys, although the mechanism is unclear.  Mutations in any of these genes prevent formation of the FRAS/FREM complex. Lack of this complex in the basement membrane of the skin leads to detachment of the top layer of skin, causing blisters to form during development. These blisters likely impair the proper formation of certain structures before birth, leading to cryptophthalmos and cutaneous syndactyly. It is unknown how lack of the FRAS/FREM complex leads to kidney and genital abnormalities and other problems in Fraser syndrome. </s>


Input: Is Fraser 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 Fraser syndrome ?

Output: These resources address the diagnosis or management of Fraser syndrome:  - Genetic Testing Registry: Cryptophthalmos syndrome  - University of Arizona College of Medicine: Cryptophthalmos   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) Mayer-Rokitansky-Kster-Hauser syndrome ?

Output: Mayer-Rokitansky-Kster-Hauser (MRKH) syndrome is a disorder that occurs in females and mainly affects the reproductive system. This condition causes the vagina and uterus to be underdeveloped or absent. Affected women usually do not have menstrual periods due to the absent uterus. Often, the first noticeable sign of MRKH syndrome is that menstruation does not begin by age 16 (primary amenorrhea). Women with MRKH syndrome have a female chromosome pattern (46,XX) and normally functioning ovaries. They also have normal female external genitalia and normal breast and pubic hair development. Although women with this condition are usually unable to carry a pregnancy, they may be able to have children through assisted reproduction.  Women with MRKH syndrome may also have abnormalities in other parts of the body. The kidneys may be abnormally formed or positioned, or one kidney may fail to develop (unilateral renal agenesis). Affected individuals commonly develop skeletal abnormalities, particularly of the spinal bones (vertebrae). Females with MRKH syndrome may also have hearing loss or heart defects. </s>


Input: How many people are affected by Mayer-Rokitansky-Kster-Hauser syndrome ?

Output: MRKH syndrome affects approximately 1 in 4,500 newborn girls. </s>


Input: What are the genetic changes related to Mayer-Rokitansky-Kster-Hauser syndrome ?

Output: The cause of MRKH syndrome is unknown, although it probably results from a combination of genetic and environmental factors. Researchers have not identified any genes associated with MRKH syndrome.  The reproductive abnormalities of MRKH syndrome are due to incomplete development of the Mllerian duct. This structure in the embryo develops into the uterus, fallopian tubes, cervix, and the upper part of the vagina. The cause of the abnormal development of the Mllerian duct in affected individuals is unknown. Originally, researchers believed that MRKH syndrome was caused by something the fetus was exposed to during pregnancy, such as a medication or maternal illness. However, studies have not identified an association with maternal drug use, illness, or other factors. It is also unclear why some affected individuals have abnormalities in parts of the body other than the reproductive system. </s>


Input: Is Mayer-Rokitansky-Kster-Hauser syndrome inherited ?

Output: Most cases of MRKH syndrome occur in people with no history of the disorder in their family.  Less often, MRKH syndrome is passed through generations in families. Its inheritance pattern is usually unclear because the signs and symptoms of the condition frequently vary among affected individuals in the same family. However, in some families, the condition appears to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of the altered gene in each cell is typically sufficient to cause the disorder, although no genes have been associated with MRKH syndrome. </s>


Input: What are the treatments for Mayer-Rokitansky-Kster-Hauser syndrome ?

Output: These resources address the diagnosis or management of Mayer-Rokitansky-Kster-Hauser syndrome:  - American Urological Association Foundation: Vaginal Agenesis  - Children's Hospital Boston: Center for Young Women's Health  - Genetic Testing Registry: Rokitansky Kuster Hauser 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) Axenfeld-Rieger syndrome ?

Output: Axenfeld-Rieger syndrome is primarily an eye disorder, although it can also affect other parts of the body. This condition is characterized by abnormalities of the front part of the eye, an area known as the anterior segment. For example, the colored part of the eye (the iris), may be thin or poorly developed. The iris normally has a single central hole, called the pupil, through which light enters the eye. People with Axenfeld-Rieger syndrome often have a pupil that is off-center (corectopia) or extra holes in the iris that can look like multiple pupils (polycoria). This condition can also cause abnormalities of the cornea, which is the clear front covering of the eye.  About half of affected individuals develop glaucoma, a serious condition that increases pressure inside the eye. When glaucoma occurs with Axenfeld-Rieger syndrome, it most often develops in late childhood or adolescence, although it can occur as early as infancy. Glaucoma can cause vision loss or blindness.  The signs and symptoms of Axenfeld-Rieger syndrome can also affect other parts of the body. Many affected individuals have distinctive facial features such as widely spaced eyes (hypertelorism); a flattened mid-face with a broad, flat nasal bridge; and a prominent forehead. The condition is also associated with dental abnormalities including unusually small teeth (microdontia) or fewer than normal teeth (oligodontia). Some people with Axenfeld-Rieger syndrome have extra folds of skin around their belly button (redundant periumbilical skin). Other, less common features can include heart defects, the opening of the urethra on the underside of the penis (hypospadias), narrowing of the anus (anal stenosis), and abnormalities of the pituitary gland that can result in slow growth.  Researchers have described at least three types of Axenfeld-Rieger syndrome. The types, which are numbered 1 through 3, are distinguished by their genetic cause. </s>


Input: How many people are affected by Axenfeld-Rieger syndrome ?

Output: Axenfeld-Rieger syndrome has an estimated prevalence of 1 in 200,000 people. </s>


Input: What are the genetic changes related to Axenfeld-Rieger syndrome ?

Output: Axenfeld-Rieger syndrome results from mutations in at least two known genes, PITX2 and FOXC1. PITX2 gene mutations cause type 1, and FOXC1 gene mutations cause type 3. The gene associated with type 2 is likely located on chromosome 13, but it has not been identified. The proteins produced from the PITX2 and FOXC1 genes are transcription factors, which means they attach (bind) to DNA and help control the activity of other genes. These transcription factors are active before birth in the developing eye and in other parts of the body. They appear to play important roles in embryonic development, particularly in the formation of structures in the anterior segment of the eye.  Mutations in either the PITX2 or FOXC1 gene disrupt the activity of other genes that are needed for normal development. Impaired regulation of these genes leads to problems in the formation of the anterior segment of the eye and other parts of the body. These developmental abnormalities underlie the characteristic features of Axenfeld-Rieger syndrome. Affected individuals with PITX2 gene mutations are more likely than those with FOXC1 gene mutations to have abnormalities affecting parts of the body other than the eye.  Some people with Axenfeld-Rieger syndrome do not have identified mutations in the PITX2 or FOXC1 genes. In these individuals, the cause of the condition is unknown. Other as-yet-unidentified genes may also cause Axenfeld-Rieger syndrome. </s>


Input: Is Axenfeld-Rieger 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. </s>


Input: What are the treatments for Axenfeld-Rieger syndrome ?

Output: These resources address the diagnosis or management of Axenfeld-Rieger syndrome:  - Genetic Testing Registry: Axenfeld-Rieger syndrome type 1  - Genetic Testing Registry: Axenfeld-Rieger syndrome type 2  - Genetic Testing Registry: Axenfeld-Rieger syndrome type 3  - Genetic Testing Registry: Rieger syndrome  - Glaucoma Research Foundation: Care and 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) spondylocarpotarsal synostosis syndrome ?

Output: Spondylocarpotarsal synostosis syndrome is a disorder that affects the development of bones throughout the body. Newborns with this disorder are of approximately normal length, but impaired growth of the trunk results in short stature over time. The bones of the spine (vertebrae) are misshapen and abnormally joined together (fused). The vertebral abnormalities may result in an abnormally curved lower back (lordosis) and a spine that curves to the side (scoliosis).  Affected individuals also have abnormalities of the wrist (carpal) and ankle (tarsal) bones and inward- and upward-turning feet (clubfeet). Characteristic facial features include a round face, a large forehead (frontal bossing), and nostrils that open to the front rather than downward (anteverted nares).  Some people with spondylocarpotarsal synostosis syndrome have an opening in the roof of the mouth (a cleft palate), hearing loss, thin tooth enamel, flat feet, or an unusually large range of joint movement (hypermobility). Individuals with this disorder can survive into adulthood. Intelligence is generally unaffected, although mild developmental delay has been reported in some affected individuals. </s>


Input: How many people are affected by spondylocarpotarsal synostosis syndrome ?

Output: Spondylocarpotarsal synostosis syndrome is a rare disorder; its prevalence is unknown. At least 25 affected individuals have been identified. </s>


Input: What are the genetic changes related to spondylocarpotarsal synostosis syndrome ?

Output: Mutations in the FLNB gene cause spondylocarpotarsal synostosis syndrome. The FLNB gene provides instructions for making a protein called filamin B. This protein helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. Filamin B attaches (binds) to another protein called actin and helps the actin to form the branching network of filaments that makes up the cytoskeleton. It also links actin to many other proteins to perform various functions within the cell, including the cell signaling that helps determine how the cytoskeleton will change as tissues grow and take shape during development.  Filamin B is especially important in the development of the skeleton before birth. It is active (expressed) in the cell membranes of cartilage-forming cells (chondrocytes). Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone (a process called ossification), except for the cartilage that continues to cover and protect the ends of bones and is present in the nose, airways (trachea and bronchi), and external ears. Filamin B appears to be important for normal cell growth and division (proliferation) and maturation (differentiation) of chondrocytes and for the ossification of cartilage.  FLNB gene mutations that cause spondylocarpotarsal synostosis syndrome result in the production of an abnormally short filamin B protein that is unstable and breaks down rapidly. Loss of the filamin B protein appears to result in out-of-place (ectopic) ossification, resulting in fusion of the bones in the spine, wrists, and ankles and other signs and symptoms of spondylocarpotarsal synostosis syndrome.  A few individuals who have been diagnosed with spondylocarpotarsal synostosis syndrome do not have mutations in the FLNB gene. In these cases, the genetic cause of the disorder is unknown. </s>


Input: Is spondylocarpotarsal synostosis syndrome inherited ?

Output: Spondylocarpotarsal synostosis syndrome caused by FLNB gene mutations 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.  In a few individuals with signs and symptoms similar to those of spondylocarpotarsal synostosis syndrome but without FLNB gene mutations, the condition appears to have been inherited in an autosomal dominant pattern. Autosomal dominant means one copy of the altered gene in each cell is sufficient to cause the disorder. </s>


Input: What are the treatments for spondylocarpotarsal synostosis syndrome ?

Output: These resources address the diagnosis or management of spondylocarpotarsal synostosis syndrome:  - Gene Review: Gene Review: FLNB-Related Disorders  - Genetic Testing Registry: Spondylocarpotarsal synostosis 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) nonsyndromic paraganglioma ?

Output: Paraganglioma is a type of noncancerous (benign) tumor that occurs in structures called paraganglia. Paraganglia are groups of cells that are found near nerve cell bunches called ganglia. Paragangliomas are usually found in the head, neck, or torso. However, a type of paraganglioma known as pheochromocytoma develops in the adrenal glands. Adrenal glands are located on top of each kidney and produce hormones in response to stress. Most people with paraganglioma develop only one tumor in their lifetime.  Some people develop a paraganglioma or pheochromocytoma as part of a hereditary syndrome that may affect other organs and tissues in the body. However, the tumors often are not associated with any syndromes, in which case the condition is called nonsyndromic paraganglioma or pheochromocytoma.  Pheochromocytomas and some other paragangliomas are associated with ganglia of the sympathetic nervous system. The sympathetic nervous system controls the "fight-or-flight" response, a series of changes in the body due to hormones released in response to stress. Although most sympathetic paragangliomas are pheochromocytomas, some are found outside the adrenal glands, usually in the abdomen, and are called extra-adrenal paragangliomas. Most sympathetic paragangliomas, including pheochromocytomas, produce hormones called catecholamines, such as epinephrine (adrenaline) or norepinephrine. These excess catecholamines can cause signs and symptoms such as high blood pressure (hypertension), episodes of rapid heartbeat (palpitations), headaches, or sweating.  Most paragangliomas are associated with ganglia of the parasympathetic nervous system, which controls involuntary body functions such as digestion and saliva formation. Parasympathetic paragangliomas, typically found in the head and neck, usually do not produce hormones. However, large tumors may cause signs and symptoms such as coughing, hearing loss in one ear, or difficulty swallowing.  Although most paragangliomas and pheochromocytomas are noncancerous, some can become cancerous (malignant) and spread to other parts of the body (metastasize). Extra-adrenal paragangliomas become malignant more often than other types of paraganglioma or pheochromocytoma. </s>


Input: How many people are affected by nonsyndromic paraganglioma ?

Output: It is estimated that the prevalence of pheochromocytoma is 1 in 500,000 people, and the prevalence of other paragangliomas is 1 in 1 million people. These statistics include syndromic and nonsyndromic paraganglioma and pheochromocytoma. </s>


Input: What are the genetic changes related to nonsyndromic paraganglioma ?

Output: The VHL, RET, SDHB, and SDHD genes can be mutated in both syndromic and nonsyndromic forms of paraganglioma and pheochromocytoma. Mutations in at least three additional genes, TMEM127, SDHA, and KIF1B, have been identified in people with the nonsyndromic form of these conditions. Gene mutations increase the risk of developing paraganglioma or pheochromocytoma by affecting control of cell growth and division.  Mutations in the VHL, SDHA, SDHB, and SDHD genes increase the risk of developing nonsyndromic paraganglioma or pheochromocytoma. The protein produced from the VHL gene helps break down other, unneeded proteins, including a protein called HIF that stimulates cell division and blood vessel formation under certain cellular conditions. The proteins produced from the SDHA, SHDB, and SDHD genes are each pieces (subunits) of an enzyme that is important for energy production in the cell. This enzyme also plays a role in the breakdown of the HIF protein. Mutations in the VHL, SDHA, SDHB, and SDHD genes stabilize the HIF protein, causing it to build up in cells. Excess HIF protein stimulates cells to divide and triggers the production of blood vessels when they are not needed. Rapid and uncontrolled cell division, along with the formation of new blood vessels, can lead to the development of tumors.  Mutations in the RET gene have been found in nonsyndromic pheochromocytoma in addition to a pheochromocytoma-predisposing syndrome. The protein produced from the RET gene is involved in signaling within cells that can stimulate cell division or maturation. Mutations in the RET gene overactivate the protein's signaling function, which can trigger cell growth and division in the absence of signals from outside the cell. This unchecked cell division can lead to the formation of tumors in the adrenal glands.  Mutations in the TMEM127 gene have been identified most commonly in people with nonsyndromic pheochromocytoma and are rarely seen in people with other paraganglioma. The TMEM127 protein normally controls a signaling pathway that induces cell growth and survival. Studies suggest that mutations in the TMEM127 gene lead to abnormal activation of cell growth, which may cause tumor formation.  Mutations in the KIF1B gene have been reported in nonsyndromic pheochromocytoma. Studies suggest that these mutations impair the function of the KIF1B protein, which normally triggers cells to self-destruct in a process called apoptosis. When apoptosis is impaired, cells grow and divide too quickly or in an uncontrolled way, potentially leading to tumor formation.  Many people with nonsyndromic paraganglioma or pheochromocytoma do not have a mutation in any of the genes associated with the conditions. It is likely that other, unidentified genes also predispose to development of paraganglioma or pheochromocytoma. </s>


Input: Is nonsyndromic paraganglioma inherited ?

Output: Nonsyndromic paraganglioma can be inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing a paraganglioma or pheochromocytoma. People with mutations in the gene inherit an increased risk of this condition, not the condition itself. Not all people with this condition have a mutation in the gene, and not all people with a gene mutation will develop the disorder.  Most cases of nonsyndromic paraganglioma and pheochromocytoma are considered sporadic, which means the tumors occur in people with no history of the disorder in their family. </s>


Input: What are the treatments for nonsyndromic paraganglioma ?

Output: These resources address the diagnosis or management of nonsyndromic paraganglioma:  - Genetic Testing Registry: Pheochromocytoma   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) hypomagnesemia with secondary hypocalcemia ?

Output: Hypomagnesemia with secondary hypocalcemia is an inherited condition caused by the body's inability to absorb and retain magnesium that is taken in through the diet. As a result, magnesium levels in the blood are severely low (hypomagnesemia).  Hypomagnesemia impairs the function of the parathyroid glands, which are small hormone-producing glands located in the neck. Normally, the parathyroid glands release a hormone that increases blood calcium levels when they are low. Magnesium is required for the production and release of parathyroid hormone, so when magnesium is too low, insufficient parathyroid hormone is produced and blood calcium levels are also reduced (hypocalcemia). The hypocalcemia is described as "secondary" because it occurs as a consequence of hypomagnesemia.  Shortages of magnesium and calcium can cause neurological problems that begin in infancy, including painful muscle spasms (tetany) and seizures. If left untreated, hypomagnesemia with secondary hypocalcemia can lead to developmental delay, intellectual disability, a failure to gain weight and grow at the expected rate (failure to thrive), and heart failure. </s>


Input: How many people are affected by hypomagnesemia with secondary hypocalcemia ?

Output: Hypomagnesemia with secondary hypocalcemia is thought to be a rare condition, but its prevalence is unknown. </s>


Input: What are the genetic changes related to hypomagnesemia with secondary hypocalcemia ?

Output: Hypomagnesemia with secondary hypocalcemia is caused by mutations in the TRPM6 gene. This gene provides instructions for making a protein that acts as a channel, which allows charged atoms (ions) of magnesium (Mg2+) to flow into cells; the channel may also allow small amounts of calcium ions (Ca2+) to pass into cells. Magnesium is involved in many cell processes, including production of cellular energy, maintenance of DNA building blocks (nucleotides), protein production, and cell growth and death. Magnesium and calcium are also required for the normal functioning of nerve cells that control muscle movement (motor neurons).  The TRPM6 channel is embedded in the membrane of epithelial cells that line the large intestine, structures in the kidneys known as distal convoluted tubules, the lungs, and the testes in males. When the body needs additional Mg2+, the TRPM6 channel allows it to be absorbed in the intestine and filtered from the fluids that pass through the kidneys by the distal convoluted tubules. When the body has sufficient or too much Mg2+, the TRPM6 channel does not filter out the Mg2+ from fluids but allows the ion to be released from the kidney cells into the urine. The channel also helps to regulate Ca2+, but to a lesser degree.  Most TRPM6 gene mutations that cause hypomagnesemia with secondary hypocalcemia result in a lack of functional protein. A loss of functional TRPM6 channels prevent Mg2+ absorption in the intestine and cause excessive amounts of Mg2+ to be excreted by the kidneys and released in the urine. A lack of Mg2+ in the body impairs the production of parathyroid hormone, which likely reduces blood Ca2+ levels. Additionally, hypomagnesemia and hypocalcemia can disrupt many cell processes and impair the function of motor neurons, leading to neurological problems and movement disorders. If the condition is not effectively treated and low Mg2+ levels persist, signs and symptoms can worsen over time and may lead to early death. </s>


Input: Is hypomagnesemia with secondary hypocalcemia 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 hypomagnesemia with secondary hypocalcemia ?

Output: These resources address the diagnosis or management of hypomagnesemia with secondary hypocalcemia:  - Genetic Testing Registry: Hypomagnesemia 1, intestinal  - MedlinePlus Encyclopedia: Hypomagnesemia   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) tetrasomy 18p ?

Output: Tetrasomy 18p is a chromosomal condition that affects many parts of the body. This condition usually causes feeding difficulties in infancy, delayed development, intellectual disability that is often mild to moderate but can be severe, changes in muscle tone, distinctive facial features, and other birth defects. However, the signs and symptoms vary among affected individuals.  Babies with tetrasomy 18p often have trouble feeding and may vomit frequently, which makes it difficult for them to gain weight. Some affected infants also have breathing problems and jaundice, which is a yellowing of the skin and the whites of the eyes.  Changes in muscle tone are commonly seen with tetrasomy 18p. Some affected children have weak muscle tone (hypotonia), while others have increased muscle tone (hypertonia) and stiffness (spasticity). These changes contribute to delayed development of motor skills, including sitting, crawling, and walking.  Tetrasomy 18p is associated with a distinctive facial appearance that can include unusually shaped and low-set ears, a small mouth, a flat area between the upper lip and the nose (philtrum), and a thin upper lip. Many affected individuals also have a high, arched roof of the mouth (palate), and a few have had a split in the roof of the mouth (cleft palate).  Additional features of tetrasomy 18p can include seizures, vision problems, recurrent ear infections, mild to moderate hearing loss, constipation and other gastrointestinal problems, abnormal curvature of the spine (scoliosis or kyphosis), a shortage of growth hormone, and birth defects affecting the heart and other organs. Males with tetrasomy 18p may be born with undescended testes (cryptorchidism) or the opening of the urethra on the underside of the penis (hypospadias). Psychiatric conditions, such as attention deficit hyperactivity disorder (ADHD) and anxiety, as well as social and behavioral challenges have also been reported in some people with tetrasomy 18p. </s>


Input: How many people are affected by tetrasomy 18p ?

Output: Tetrasomy 18p is a rare disorder. It is known to affect about 250 families worldwide. </s>


Input: What are the genetic changes related to tetrasomy 18p ?

Output: Tetrasomy 18p results from the presence of an abnormal extra chromosome, called an isochromosome 18p, in each cell. An isochromosome is a chromosome with two identical arms. Normal chromosomes have one long (q) arm and one short (p) arm, but isochromosomes have either two q arms or two p arms. Isochromosome 18p is a version of chromosome 18 made up of two p arms.  Cells normally have two copies of each chromosome, one inherited from each parent. In people with tetrasomy 18p, cells have the usual two copies of chromosome 18 plus an isochromosome 18p. As a result, each cell has four copies of the short arm of chromosome 18. (The word "tetrasomy" is derived from "tetra," the Greek word for "four.") The extra genetic material from the isochromosome disrupts the normal course of development, causing the characteristic features of this disorder. </s>


Input: Is tetrasomy 18p inherited ?

Output: Tetrasomy 18p is usually not inherited. The chromosomal change responsible for the disorder typically occurs as a random event during the formation of reproductive cells (eggs or sperm) in a parent of the affected individual, usually the mother. Most affected individuals have no history of the disorder in their family. However, rare inherited cases of tetrasomy 18p have been reported. </s>


Input: What are the treatments for tetrasomy 18p ?

Output: These resources address the diagnosis or management of tetrasomy 18p:  - Chromosome 18 Clinical Research Center, University of Texas Health Science Center at San Antonio  - Genetic Testing Registry: Chromosome 18, tetrasomy 18p   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) spinocerebellar ataxia type 3 ?

Output: Spinocerebellar ataxia type 3 (SCA3) is a condition characterized by progressive problems with movement. People with this condition initially experience problems with coordination and balance (ataxia). Other early signs and symptoms of SCA3 include speech difficulties, uncontrolled muscle tensing (dystonia), muscle stiffness (spasticity), rigidity, tremors, bulging eyes, and double vision. People with this condition may experience sleep disorders such as restless leg syndrome or REM sleep behavior disorder. Restless leg syndrome is a condition characterized by numbness or tingling in the legs accompanied by an urge to move the legs to stop the sensations. REM sleep behavior disorder is a condition in which the muscles are active during the dream (REM) stage of sleep, so an affected person often acts out his or her dreams. These sleep disorders tend to leave affected individuals feeling tired during the day.  Over time, individuals with SCA3 may develop loss of sensation and weakness in the limbs (peripheral neuropathy), muscle cramps, muscle twitches (fasciculations), and swallowing difficulties. Individuals with SCA3 may have problems with memory, planning, and problem solving.  Signs and symptoms of the disorder typically begin in mid-adulthood but can appear anytime from childhood to late adulthood. People with SCA3 eventually require wheelchair assistance. They usually survive 10 to 20 years after symptoms first appear. </s>


Input: How many people are affected by spinocerebellar ataxia type 3 ?

Output: The prevalence of SCA3 is unknown. This condition is thought to be the most common type of spinocerebellar ataxia; however, all types of spinocerebellar ataxia are relatively rare. </s>


Input: What are the genetic changes related to spinocerebellar ataxia type 3 ?

Output: Mutations in the ATXN3 gene cause SCA3. The ATXN3 gene provides instructions for making an enzyme called ataxin-3, which is found in cells throughout the body. Ataxin-3 is involved in a mechanism called the ubiquitin-proteasome system that destroys and gets rid of excess or damaged proteins. The molecule ubiquitin is attached (bound) to unneeded proteins, which tags them to be broken down (degraded) within cells. Ataxin-3 removes the ubiquitin from these unwanted proteins just before they are degraded so that the ubiquitin can be used again. Researchers believe that ataxin-3 also may be involved in regulating the first stage of protein production (transcription).  The ATXN3 gene mutations that cause SCA3 involve a DNA segment known as a CAG trinucleotide repeat. This segment is made up of a series of three DNA building blocks (cytosine, adenine, and guanine) that appear multiple times in a row. Normally, the CAG segment is repeated 12 to 43 times within the gene. Most people have fewer than 31 CAG repeats. In people with SCA3, the CAG segment is repeated more than 50 times. People who have 44 to 52 CAG repeats are described as having an "intermediate repeat." These individuals may or may not develop SCA3. People with 75 or fewer repeats tend to first experience signs and symptoms of SCA3 in mid-adulthood, while people with around 80 repeats usually have signs and symptoms by their teens.  An increase in the length of the CAG segment leads to the production of an abnormally long version of the ataxin-3 enzyme that folds into the wrong 3-dimensional shape. This nonfunctional ataxin-3 enzyme cannot remove ubiquitin from proteins that are no longer needed. As a result, these unwanted proteins, along with ubiquitin and ataxin-3, cluster together to form clumps (aggregates) within the nucleus of the cells. It is unclear how these aggregates affect cell function, because they are found in healthy cells as well as those that die.  Nerve cells (neurons) and other types of brain cells are most affected by mutations in the ATXN3 gene. SCA3 is associated with cell death in the part of the brain that is connected to the spinal cord (the brainstem), the part of the brain involved in coordinating movements (the cerebellum), and other areas of the brain. This condition is also associated with the death of neurons in the spinal cord. Over time, the loss of cells in the brain and spinal cord cause the signs and symptoms characteristic of SCA3. </s>


Input: Is spinocerebellar ataxia type 3 inherited ?

Output: This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.  As the altered ATXN3 gene is passed down from one generation to the next, the length of the CAG trinucleotide repeat often increases. A larger number of repeats is usually associated with an earlier onset of signs and symptoms. This phenomenon is called anticipation. Anticipation tends to be more prominent when the ATXN3 gene is inherited from a person's father (paternal inheritance) than when it is inherited from a person's mother (maternal inheritance).  In rare cases, individuals have been reported with expanded CAG repeats on both copies of the ATXN3 gene in each cell. These people have more severe signs and symptoms than people with only one mutation, and features of the condition appear in childhood. </s>


Input: What are the treatments for spinocerebellar ataxia type 3 ?

Output: These resources address the diagnosis or management of SCA3:  - Gene Review: Gene Review: Spinocerebellar Ataxia Type 3  - Genetic Testing Registry: Azorean 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) inherited thyroxine-binding globulin deficiency ?

Output: Inherited thyroxine-binding globulin deficiency is a genetic condition that typically does not cause any health problems.  Thyroxine-binding globulin is a protein that carries hormones made or used by the thyroid gland, which is a butterfly-shaped tissue in the lower neck. Thyroid hormones play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism). Most of the time, these hormones circulate in the bloodstream attached to thyroxine-binding globulin and similar proteins. If there is a shortage (deficiency) of thyroxine-binding globulin, the amount of circulating thyroid hormones is reduced.  Researchers have identified two forms of inherited thyroxine-binding globulin deficiency: the complete form (TBG-CD), which results in a total loss of thyroxine-binding globulin, and the partial form (TBG-PD), which reduces the amount of this protein or alters its structure. Neither of these conditions causes any problems with thyroid function. They are usually identified during routine blood tests that measure thyroid hormones.  Although inherited thyroxine-binding globulin deficiency does not cause any health problems, it can be mistaken for more serious thyroid disorders (such as hypothyroidism). Therefore, it is important to diagnose inherited thyroxine-binding globulin deficiency to avoid unnecessary treatments. </s>


Input: How many people are affected by inherited thyroxine-binding globulin deficiency ?

Output: The complete form of inherited thyroxine-binding globulin deficiency, TBG-CD, affects about 1 in 15,000 newborns worldwide. The partial form, TBG-PD, affects about 1 in 4,000 newborns. These conditions appear to be more common in the Australian Aborigine population and in the Bedouin population of southern Israel. </s>


Input: What are the genetic changes related to inherited thyroxine-binding globulin deficiency ?

Output: Inherited thyroxine-binding globulin deficiency results from mutations in the SERPINA7 gene. This gene provides instructions for making thyroxine-binding globulin. Some mutations in the SERPINA7 gene prevent the production of a functional protein, causing TBG-CD. Other mutations reduce the amount of this protein or alter its structure, resulting in TBG-PD.  Researchers have also described non-inherited forms of thyroxine-binding globulin deficiency, which are more common than the inherited form. Non-inherited thyroxine-binding globulin deficiency can occur with a variety of illnesses and is a side effect of some medications. </s>


Input: Is inherited thyroxine-binding globulin deficiency inherited ?

Output: Inherited thyroxine-binding globulin deficiency has an X-linked pattern of inheritance. The SERPINA7 gene is located on the X chromosome, which is one of the two sex chromosomes.  In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes partial or complete inherited thyroxine-binding globulin deficiency. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell reduces the amount of thyroxine-binding globulin. However, their levels of this protein are usually within the normal range.  A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. </s>


Input: What are the treatments for inherited thyroxine-binding globulin deficiency ?

Output: These resources address the diagnosis or management of inherited thyroxine-binding globulin deficiency:  - American Thyroid Association: Thyroid Function Tests  - MedlinePlus Encyclopedia: Serum TBG Level   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) lysinuric protein intolerance ?

Output: Lysinuric protein intolerance is a disorder caused by the body's inability to digest and use certain protein building blocks (amino acids), namely lysine, arginine, and ornithine. Because the body cannot effectively break down these amino acids, which are found in many protein-rich foods, nausea and vomiting are typically experienced after ingesting protein.  People with lysinuric protein intolerance have features associated with protein intolerance, including an enlarged liver and spleen (hepatosplenomegaly), short stature, muscle weakness, impaired immune function, and progressively brittle bones that are prone to fracture (osteoporosis). A lung disorder called pulmonary alveolar proteinosis may also develop. This disorder is characterized by protein deposits in the lungs, which interfere with lung function and can be life-threatening. An accumulation of amino acids in the kidneys can cause end-stage renal disease (ESRD) in which the kidneys become unable to filter fluids and waste products from the body effectively. A lack of certain amino acids can cause elevated levels of ammonia in the blood. If ammonia levels are too high for too long, they can cause coma and intellectual disability.  The signs and symptoms of lysinuric protein intolerance typically appear after infants are weaned and receive greater amounts of protein from solid foods. </s>


Input: How many people are affected by lysinuric protein intolerance ?

Output: Lysinuric protein intolerance is estimated to occur in 1 in 60,000 newborns in Finland and 1 in 57,000 newborns in Japan. Outside these populations this condition occurs less frequently, but the exact incidence is unknown. </s>


Input: What are the genetic changes related to lysinuric protein intolerance ?

Output: Mutations in the SLC7A7 gene cause lysinuric protein intolerance. The SLC7A7 gene provides instructions for producing a protein called y+L amino acid transporter 1 (y+LAT-1), which is involved in transporting lysine, arginine, and ornithine between cells in the body. The transportation of amino acids from the small intestines and kidneys to the rest of the body is necessary for the body to be able to use proteins. Mutations in the y+LAT-1 protein disrupt the transportation of amino acids, leading to a shortage of lysine, arginine, and ornithine in the body and an abnormally large amount of these amino acids in urine.  A shortage of lysine, arginine, and ornithine disrupts many vital functions. Arginine and ornithine are involved in a cellular process called the urea cycle, which processes excess nitrogen (in the form of ammonia) that is generated when protein is used by the body. The lack of arginine and ornithine in the urea cycle causes elevated levels of ammonia in the blood. Lysine is particularly abundant in collagen molecules that give structure and strength to connective tissues such as skin, tendons, and ligaments. A deficiency of lysine contributes to the short stature and osteoporosis seen in people with lysinuric protein intolerance. Other features of lysinuric protein intolerance are thought to result from abnormal protein transport (such as protein deposits in the lungs) or a lack of protein that can be used by the body (protein malnutrition). </s>


Input: Is lysinuric protein intolerance 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 lysinuric protein intolerance ?

Output: These resources address the diagnosis or management of lysinuric protein intolerance:  - Gene Review: Gene Review: Lysinuric Protein Intolerance  - Genetic Testing Registry: Lysinuric protein intolerance  - MedlinePlus Encyclopedia: Aminoaciduria  - MedlinePlus Encyclopedia: Malabsorption   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) Marfan syndrome ?

Output: Marfan syndrome is a disorder that affects the connective tissue in many parts of the body. Connective tissue provides strength and flexibility to structures such as bones, ligaments, muscles, blood vessels, and heart valves. The signs and symptoms of Marfan syndrome vary widely in severity, timing of onset, and rate of progression.  The two primary features of Marfan syndrome are vision problems caused by a dislocated lens (ectopia lentis) in one or both eyes and defects in the large blood vessel that distributes blood from the heart to the rest of the body (the aorta). The aorta can weaken and stretch, which may lead to a bulge in the blood vessel wall (an aneurysm). Stretching of the aorta may cause the aortic valve to leak, which can lead to a sudden tearing of the layers in the aorta wall (aortic dissection). Aortic aneurysm and dissection can be life threatening.  Many people with Marfan syndrome have additional heart problems including a leak in the valve that connects two of the four chambers of the heart (mitral valve prolapse) or the valve that regulates blood flow from the heart into the aorta (aortic valve regurgitation). Leaks in these valves can cause shortness of breath, fatigue, and an irregular heartbeat felt as skipped or extra beats (palpitations).  Individuals with Marfan syndrome are usually tall and slender, have elongated fingers and toes (arachnodactyly), and have an arm span that exceeds their body height. Other common features include a long and narrow face, crowded teeth, an abnormal curvature of the spine (scoliosis or kyphosis), and either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum). Some individuals develop an abnormal accumulation of air in the chest cavity that can result in the collapse of a lung (spontaneous pneumothorax). A membrane called the dura, which surrounds the brain and spinal cord, can be abnormally enlarged (dural ectasia) in people with Marfan syndrome. Dural ectasia can cause pain in the back, abdomen, legs, or head. Most individuals with Marfan syndrome have some degree of nearsightedness (myopia). Clouding of the lens (cataract) may occur in mid-adulthood, and increased pressure within the eye (glaucoma) occurs more frequently in people with Marfan syndrome than in those without the condition.  The features of Marfan syndrome can become apparent anytime between infancy and adulthood. Depending on the onset and severity of signs and symptoms, Marfan can be fatal early in life; however, the majority of affected individuals survive into mid- to late adulthood. </s>


Input: How many people are affected by Marfan syndrome ?

Output: The incidence of Marfan syndrome is approximately 1 in 5,000 worldwide. </s>


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

Output: Mutations in the FBN1 gene cause Marfan syndrome. The FBN1 gene provides instructions for making a protein called fibrillin-1. Fibrillin-1 attaches (binds) to other fibrillin-1 proteins and other molecules to form threadlike filaments called microfibrils. Microfibrils become part of the fibers that provide strength and flexibility to connective tissue. Additionally, microfibrils store molecules called growth factors and release them at various times to control the growth and repair of tissues and organs throughout the body. A mutation in the FBN1 gene can reduce the amount of functional fibrillin-1 that is available to form microfibrils, which leads to decreased microfibril formation. As a result, excess growth factors are released and elasticity in many tissues is decreased, leading to overgrowth and instability of tissues. </s>


Input: Is Marfan 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.  At least 25 percent of Marfan syndrome cases result from a new mutation in the FBN1 gene. These cases occur in people with no history of the disorder in their family. </s>


Input: What are the treatments for Marfan syndrome ?

Output: These resources address the diagnosis or management of Marfan syndrome:  - Gene Review: Gene Review: Marfan Syndrome  - Genetic Testing Registry: Marfan syndrome  - MarfanDX  - MedlinePlus Encyclopedia: Aortic Dissection  - MedlinePlus Encyclopedia: Marfan Syndrome  - MedlinePlus Encyclopedia: Thoracic Aortic Aneurysm  - National Marfan Foundation: Diagnosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) idiopathic pulmonary fibrosis ?

Output: Idiopathic pulmonary fibrosis is a chronic, progressive lung disease. This condition causes scar tissue (fibrosis) to build up in the lungs, which makes the lungs unable to transport oxygen into the bloodstream effectively. The disease usually affects people between the ages of 50 and 70.  The most common signs and symptoms of idiopathic pulmonary fibrosis are shortness of breath and a persistent dry, hacking cough. Many affected individuals also experience a loss of appetite and gradual weight loss. Some people with idiopathic pulmonary fibrosis develop widened and rounded tips of the fingers and toes (clubbing) resulting from a shortage of oxygen. These features are relatively nonspecific; not everyone with these health problems has idiopathic pulmonary fibrosis. Other respiratory diseases, some of which are less serious, can cause similar signs and symptoms.  In people with idiopathic pulmonary fibrosis, scarring of the lungs increases over time until the lungs can no longer provide enough oxygen to the body's organs and tissues. Some people with idiopathic pulmonary fibrosis develop other serious lung conditions, including lung cancer, blood clots in the lungs (pulmonary emboli), pneumonia, or high blood pressure in the blood vessels that supply the lungs (pulmonary hypertension). Most affected individuals survive 3 to 5 years after their diagnosis. However, the course of the disease is highly variable; some affected people become seriously ill within a few months, while others may live with the disease for a decade or longer.  In most cases, idiopathic pulmonary fibrosis occurs in only one person in a family. These cases are described as sporadic. However, a small percentage of people with this disease have at least one other affected family member. When idiopathic pulmonary fibrosis occurs in multiple members of the same family, it is known as familial pulmonary fibrosis. </s>


Input: How many people are affected by idiopathic pulmonary fibrosis ?

Output: Idiopathic pulmonary fibrosis has an estimated prevalence of 13 to 20 per 100,000 people worldwide. About 100,000 people are affected in the United States, and 30,000 to 40,000 new cases are diagnosed each year.  Familial pulmonary fibrosis is less common than the sporadic form of the disease. Only a small percentage of cases of idiopathic pulmonary fibrosis appear to run in families. </s>


Input: What are the genetic changes related to idiopathic pulmonary fibrosis ?

Output: The cause of idiopathic pulmonary fibrosis is unknown, although the disease probably results from a combination of genetic and environmental factors. It is likely that genetic changes increase a person's risk of developing idiopathic pulmonary fibrosis, and then exposure to certain environmental factors triggers the disease.  Changes in several genes have been suggested as risk factors for idiopathic pulmonary fibrosis. Most of these genetic changes account for only a small proportion of cases. However, mutations in genes known as TERC and TERT have been found in about 15 percent of all cases of familial pulmonary fibrosis and a smaller percentage of cases of sporadic idiopathic pulmonary fibrosis. The TERC and TERT genes provide instructions for making components of an enzyme called telomerase, which maintains structures at the ends of chromosomes known as telomeres. It is not well understood how defects in telomerase are associated with the lung damage characteristic of idiopathic pulmonary fibrosis.  Researchers have also examined environmental risk factors that could contribute to idiopathic pulmonary fibrosis. These factors include exposure to wood or metal dust, viral infections, certain medications, and cigarette smoking. Some research suggests that gastroesophageal reflux disease (GERD) may also be a risk factor for idiopathic pulmonary fibrosis; affected individuals may breathe in (aspirate) stomach contents, which over time could damage the lungs. </s>


Input: Is idiopathic pulmonary fibrosis inherited ?

Output: Most cases of idiopathic pulmonary fibrosis are sporadic; they occur in people with no history of the disorder in their family.  Familial pulmonary fibrosis appears to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of an altered gene in each cell is sufficient to cause the disorder. However, some people who inherit the altered gene never develop features of familial pulmonary fibrosis. (This situation is known as reduced penetrance.) It is unclear why some people with a mutated gene develop the disease and other people with the mutated gene do not. </s>


Input: What are the treatments for idiopathic pulmonary fibrosis ?

Output: These resources address the diagnosis or management of idiopathic pulmonary fibrosis:  - Gene Review: Gene Review: Pulmonary Fibrosis, Familial  - Genetic Testing Registry: Idiopathic fibrosing alveolitis, chronic form   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) Blau syndrome ?

Output: Blau syndrome is an inflammatory disorder that primarily affects the skin, joints, and eyes. Signs and symptoms begin in childhood, usually before age 4.  A form of skin inflammation called granulomatous dermatitis is typically the earliest sign of Blau syndrome. This skin condition causes a persistent rash that can be scaly or involve hard lumps (nodules) that can be felt under the skin. The rash is usually found on the torso, arms, and legs.  Arthritis is another common feature of Blau syndrome. In affected individuals, arthritis is characterized by inflammation of the lining of joints (the synovium). This inflammation, known as synovitis, is associated with swelling and joint pain. Synovitis usually begins in the joints of the hands, feet, wrists, and ankles. As the condition worsens, it can restrict movement by decreasing the range of motion in many joints.  Most people with Blau syndrome also develop uveitis, which is swelling and inflammation of the middle layer of the eye (the uvea). The uvea includes the colored portion of the eye (the iris) and related tissues that underlie the white part of the eye (the sclera). Uveitis can cause eye irritation and pain, increased sensitivity to bright light (photophobia), and blurred vision. Other structures in the eye can also become inflamed, including the outermost protective layer of the eye (the conjunctiva), the tear glands, the specialized light-sensitive tissue that lines the back of the eye (the retina), and the nerve that carries information from the eye to the brain (the optic nerve). Inflammation of any of these structures can lead to severe vision impairment or blindness.  Less commonly, Blau syndrome can affect other parts of the body, including the liver, kidneys, brain, blood vessels, lungs, and heart. Inflammation involving these organs and tissues can cause life-threatening complications. </s>


Input: How many people are affected by Blau syndrome ?

Output: Although Blau syndrome appears to be uncommon, its prevalence is unknown. </s>


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

Output: Blau syndrome results from mutations in the NOD2 gene. The protein produced from this gene helps defend the body from foreign invaders, such as viruses and bacteria, by playing several essential roles in the immune response, including inflammatory reactions. An inflammatory reaction 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.  The NOD2 gene mutations that cause Blau syndrome result in a NOD2 protein that is overactive, which can trigger an abnormal inflammatory reaction. However, it is unclear how overactivation of the NOD2 protein causes the specific pattern of inflammation affecting the joints, eyes, and skin that is characteristic of Blau syndrome. </s>


Input: Is Blau syndrome inherited ?

Output: Blau syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most affected individuals have one parent with the condition.  In some cases, people with the characteristic features of Blau syndrome do not have a family history of the condition. Some researchers believe that these individuals have a non-inherited version of the disorder called early-onset sarcoidosis. </s>


Input: What are the treatments for Blau syndrome ?

Output: These resources address the diagnosis or management of Blau syndrome:  - Genetic Testing Registry: Blau syndrome  - Genetic Testing Registry: Sarcoidosis, early-onset  - Merck Manual Consumer Version: Overview of Dermatitis  - Merck Manual Consumer Version: Uveitis   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) McKusick-Kaufman syndrome ?

Output: McKusick-Kaufman syndrome is a condition that affects the development of the hands and feet, heart, and reproductive system. It is characterized by a combination of three features: extra fingers and/or toes (polydactyly), heart defects, and genital abnormalities.  Most females with McKusick-Kaufman syndrome are born with a genital abnormality called hydrometrocolpos, which is a large accumulation of fluid in the pelvis. Hydrometrocolpos results from a blockage of the vagina before birth, which can occur if part of the vagina fails to develop (vaginal agenesis) or if a membrane blocks the opening of the vagina. This blockage allows fluid to build up in the vagina and uterus, stretching these organs and leading to a fluid-filled mass. Genital abnormalities in males with McKusick-Kaufman syndrome can include placement of the urethral opening on the underside of the penis (hypospadias), a downward-curving penis (chordee), and undescended testes (cryptorchidism).  The signs and symptoms of McKusick-Kaufman syndrome overlap significantly with those of another genetic disorder, Bardet-Biedl syndrome. Bardet-Biedl syndrome has several features that are not seen in McKusick-Kaufman syndrome, however. These include vision loss, delayed development, obesity, and kidney (renal) failure. Because some of these features are not apparent at birth, the two conditions can be difficult to tell apart in infancy and early childhood. </s>


Input: How many people are affected by McKusick-Kaufman syndrome ?

Output: This condition was first described in the Old Order Amish population, where it affects an estimated 1 in 10,000 people. The incidence of McKusick-Kaufman syndrome in non-Amish populations is unknown. </s>