Input: What are the genetic changes related to surfactant dysfunction ?

Output: Surfactant dysfunction is caused by mutations in one of several genes, including SFTPB, SFTPC, and ABCA3. Each of these genes is involved in the production of surfactant. The production and release of surfactant is a complex process. The phospholipids and proteins that make up surfactant are packaged in cellular structures known as lamellar bodies. These structures are also important for some processing of surfactant proteins, which is necessary for the proteins to mature and become functional. Surfactant is released from the lung cells and spreads across the tissue that surrounds alveoli. This substance lowers surface tension, which keeps the alveoli from collapsing after exhalation and makes breathing easy.  The SFTPB and SFTPC genes provide instructions for making surfactant protein-B (SP-B) and surfactant protein-C (SP-C), respectively, two of the four proteins in surfactant. These two proteins help spread the surfactant across the surface of the lung tissue, aiding in the surface tension-lowering property of surfactant. In addition, SP-B plays a role in the formation of lamellar bodies.  Mutations in the SFTPB gene cause a type of surfactant dysfunction sometimes referred to as SP-B deficiency. These mutations lead to a reduction in or absence of mature SP-B. In addition, SFTPB gene mutations cause abnormal processing of SP-C, resulting in a lack of mature SP-C and a buildup of unprocessed forms of SP-C. These changes lead to abnormal surfactant composition and decreased surfactant function. The loss of functional surfactant raises surface tension in the alveoli, causing severe breathing problems. The combination of SP-B and SP-C dysfunction may explain why the signs and symptoms of SP-B deficiency are so severe.  Mutations in the SFTPC gene are involved in a type of surfactant dysfunction sometimes called SP-C dysfunction. These mutations result in a reduction or absence of mature SP-C and the buildup of abnormal forms of SP-C. It is unclear which of these outcomes causes the signs and symptoms of SP-C dysfunction. Lack of mature SP-C can lead to abnormal composition of surfactant and decreased surfactant function. Alternatively, research suggests that abnormally processed SP-C proteins form the wrong three-dimensional shape and accumulate inside the lung cells. These misfolded proteins may trigger a cellular response that results in cell damage and death. This damage may disrupt surfactant production and release.  The ABCA3 gene provides instructions for making a protein that is found in the membrane that surrounds lamellar bodies. The ABCA3 protein transports phospholipids into lamellar bodies where they form surfactant. The ABCA3 protein also appears to be involved in the formation of lamellar bodies.  ABCA3 gene mutations, which cause a type of surfactant dysfunction sometimes referred to as ABCA3 deficiency, lead to reduction or absence of the protein's function. Without ABCA3 protein function, the transport of surfactant phospholipids is decreased. In addition, lamellar body formation is impaired, which causes abnormal processing of SP-B and SP-C. ABCA3 gene mutations result in abnormal surfactant composition and function. It has been suggested that mutations that eliminate ABCA3 protein function cause severe forms of surfactant dysfunction, and mutations that leave some residual ABCA3 activity cause milder forms of the condition. </s>


Input: Is surfactant dysfunction inherited ?

Output: Surfactant dysfunction can have different inheritance patterns depending on its genetic cause.  When caused by mutations in the SFTPB or ABCA3 gene, 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.  When caused by mutations in the SFTPC gene, this condition has an autosomal dominant inheritance pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In about half of cases caused by changes in the SFTPC gene, an affected person inherits the mutation from one affected parent. The remainder result from new mutations in the gene and occur in people with no history of the disorder in their family. </s>


Input: What are the treatments for surfactant dysfunction ?

Output: These resources address the diagnosis or management of surfactant dysfunction:  - Children's Interstitial and Diffuse Lung Disease (chILD) Foundation: Surfactant Deficiency  - Genetic Testing Registry: Surfactant metabolism dysfunction, pulmonary, 1  - Genetic Testing Registry: Surfactant metabolism dysfunction, pulmonary, 2  - Genetic Testing Registry: Surfactant metabolism dysfunction, pulmonary, 4  - Genetic Testing Registry: Surfactant metabolism dysfunction, pulmonary, 5  - National Heart Lung and Blood Institute: How is Respiratory Distress Syndrome Diagnosed?  - National Heart Lung and Blood Institute: How is Respiratory Distress Syndrome Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) pyridoxal 5'-phosphate-dependent epilepsy ?

Output: Pyridoxal 5'-phosphate-dependent epilepsy is a condition that involves seizures beginning soon after birth or, in some cases, before birth. The seizures typically involve irregular involuntary muscle contractions (myoclonus), abnormal eye movements, and convulsions. Most babies with this condition are born prematurely and may have a temporary, potentially toxic, increase in lactic acid in the blood (lactic acidosis). Additionally, some infants have a slow heart rate and a lack of oxygen during delivery (fetal distress).  Anticonvulsant drugs, which are usually given to control seizures, are ineffective in people with pyridoxal 5'-phosphate-dependent epilepsy. Instead, individuals with this type of epilepsy are medically treated with large daily doses of pyridoxal 5'-phosphate (a form of vitamin B6). If left untreated, people with this condition can develop severe brain dysfunction (encephalopathy), which can lead to death. Even though seizures can be controlled with pyridoxal 5'-phosphate, neurological problems such as developmental delay and learning disorders may still occur. </s>


Input: How many people are affected by pyridoxal 5'-phosphate-dependent epilepsy ?

Output: Pyridoxal 5'-phosphate-dependent epilepsy is a rare condition; approximately 14 cases have been described in the scientific literature. </s>


Input: What are the genetic changes related to pyridoxal 5'-phosphate-dependent epilepsy ?

Output: Mutations in the PNPO gene cause pyridoxal 5'-phosphate-dependent epilepsy. The PNPO gene provides instructions for producing an enzyme called pyridoxine 5'-phosphate oxidase. This enzyme is involved in the conversion (metabolism) of vitamin B6 derived from food (in the form of pyridoxine and pyridoxamine) to the active form of vitamin B6 called pyridoxal 5'-phosphate (PLP). PLP is necessary for many processes in the body including protein metabolism and the production of chemicals that transmit signals in the brain (neurotransmitters).  PNPO gene mutations result in a pyridoxine 5'-phosphate oxidase enzyme that is unable to metabolize pyridoxine and pyridoxamine, leading to a deficiency of PLP. A shortage of PLP can disrupt the function of many other proteins and enzymes that need PLP in order to be effective. It is not clear how the lack of PLP affects the brain and leads to the seizures that are characteristic of pyridoxal 5'-phosphate-dependent epilepsy. </s>


Input: Is pyridoxal 5'-phosphate-dependent epilepsy 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 pyridoxal 5'-phosphate-dependent epilepsy ?

Output: These resources address the diagnosis or management of pyridoxal 5'-phosphate-dependent epilepsy:  - Genetic Testing Registry: Pyridoxal 5'-phosphate-dependent epilepsy  - MedlinePlus Encyclopedia: Lactic acidosis   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) Andersen-Tawil syndrome ?

Output: Anderson-Tawil syndrome is a disorder that causes episodes of muscle weakness (periodic paralysis), changes in heart rhythm (arrhythmia), and developmental abnormalities. The most common changes affecting the heart are ventricular arrhythmia, which is a disruption in the rhythm of the heart's lower chambers, and long QT syndrome. Long QT syndrome is a heart condition that causes the heart (cardiac) muscle to take longer than usual to recharge between beats. If untreated, the irregular heartbeats can lead to discomfort, fainting (syncope), or cardiac arrest.  Physical abnormalities associated with Andersen-Tawil syndrome typically affect the head, face, and limbs. These features often include a very small lower jaw (micrognathia), dental abnormalities, low-set ears, widely spaced eyes, and unusual curving of the fingers or toes (clinodactyly). Some affected people also have short stature and an abnormal curvature of the spine (scoliosis).  Two types of Andersen-Tawil syndrome are distinguished by their genetic causes. Type 1, which accounts for about 60 percent of all cases of the disorder, is caused by mutations in the KCNJ2 gene. The remaining 40 percent of cases are designated as type 2; the cause of these cases is unknown. </s>


Input: How many people are affected by Andersen-Tawil syndrome ?

Output: Andersen-Tawil syndrome is a rare genetic disorder; its incidence is unknown. About 100 people with this condition have been reported worldwide. </s>


Input: What are the genetic changes related to Andersen-Tawil syndrome ?

Output: Mutations in the KCNJ2 gene cause Andersen-Tawil syndrome.  The KCNJ2 gene provides instructions for making a protein that forms a channel across cell membranes. This channel transports positively charged atoms (ions) of potassium into muscle cells. The movement of potassium ions through these channels is critical for maintaining the normal functions of muscles used for movement (skeletal muscles) and cardiac muscle. Mutations in the KCNJ2 gene alter the usual structure and function of potassium channels or prevent the channels from being inserted correctly into the cell membrane. Many mutations prevent a molecule called PIP2 from binding to the channels and effectively regulating their activity. These changes disrupt the flow of potassium ions in skeletal and cardiac muscle, leading to the periodic paralysis and irregular heart rhythm characteristic of Andersen-Tawil syndrome.  Researchers have not determined the role of the KCNJ2 gene in bone development, and it is not known how mutations in the gene lead to the developmental abnormalities often found in Andersen-Tawil syndrome. </s>


Input: Is Andersen-Tawil syndrome inherited ?

Output: This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, a person with Andersen-Tawil syndrome inherits the mutation from one affected parent. Other cases result from new mutations in the KCNJ2 gene. These cases occur in people with no history of the disorder in their family. </s>


Input: What are the treatments for Andersen-Tawil syndrome ?

Output: These resources address the diagnosis or management of Andersen-Tawil syndrome:  - Gene Review: Gene Review: Andersen-Tawil Syndrome  - Genetic Testing Registry: Andersen Tawil 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) Manitoba oculotrichoanal syndrome ?

Output: Manitoba oculotrichoanal syndrome is a condition involving several characteristic physical features, particularly affecting the eyes (oculo-), hair (tricho-), and anus (-anal).  People with Manitoba oculotrichoanal syndrome have widely spaced eyes (hypertelorism). They may also have other eye abnormalities including small eyes (microphthalmia), a notched or partially absent upper eyelid (upper eyelid coloboma), eyelids that are attached to the front surface of the eye (corneopalpebral synechiae), or eyes that are completely covered by skin and usually malformed (cryptophthalmos). These abnormalities may affect one or both eyes.  Individuals with Manitoba oculotrichoanal syndrome usually have abnormalities of the front hairline, such as hair growth extending from the temple to the eye on one or both sides of the face. One or both eyebrows may be completely or partially missing. Most people with this disorder also have a wide nose with a notched tip; in some cases this notch extends up from the tip so that the nose appears to be divided into two halves (bifid nose).  About 20 percent of people with Manitoba oculotrichoanal syndrome have defects in the abdominal wall, such as a soft out-pouching around the belly-button (an umbilical hernia) or an opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the navel. Another characteristic feature of Manitoba oculotrichoanal syndrome is a narrow anus (anal stenosis) or an anal opening farther forward than usual. Umbilical wall defects or anal malformations may require surgical correction. Some affected individuals also have malformations of the kidneys.  The severity of the features of Manitoba oculotrichoanal syndrome may vary even within the same family. With appropriate treatment, affected individuals generally have normal growth and development, intelligence, and life expectancy. </s>


Input: How many people are affected by Manitoba oculotrichoanal syndrome ?

Output: Manitoba oculotrichoanal syndrome is estimated to occur in 2 to 6 in 1,000 people in a small isolated Ojibway-Cree community in northern Manitoba, Canada. Although this region has the highest incidence of the condition, it has also been diagnosed in a few people from other parts of the world. </s>


Input: What are the genetic changes related to Manitoba oculotrichoanal syndrome ?

Output: Manitoba oculotrichoanal syndrome is caused by mutations in the FREM1 gene. The FREM1 gene provides instructions for making a protein that is involved in the formation and organization of basement membranes, which are thin, sheet-like structures that separate and support cells in many tissues.  The FREM1 protein is one of a group of proteins, including proteins called FRAS1 and FREM2, that interact during embryonic development as components of basement membranes. Basement membranes help anchor layers of cells lining the surfaces and cavities of the body (epithelial cells) to other embryonic tissues, including those that give rise to connective tissues such as skin and cartilage.  The FREM1 gene mutations that have been identified in people with Manitoba oculotrichoanal syndrome delete genetic material from the FREM1 gene or result in a premature stop signal that leads to an abnormally short FREM1 protein. These mutations most likely result in a nonfunctional protein.  Absence of functional FREM1 protein interferes with its role in embryonic basement membrane development and may also affect the location, stability, or function of the FRAS1 and FREM2 proteins. The features of Manitoba oculotrichoanal syndrome may result from the failure of neighboring embryonic tissues to fuse properly due to impairment of the basement membranes' anchoring function. </s>


Input: Is Manitoba oculotrichoanal 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 Manitoba oculotrichoanal syndrome ?

Output: These resources address the diagnosis or management of Manitoba oculotrichoanal syndrome:  - Gene Review: Gene Review: Manitoba Oculotrichoanal Syndrome  - Genetic Testing Registry: Marles Greenberg Persaud syndrome  - MedlinePlus Encyclopedia: Omphalocele Repair   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) isolated ectopia lentis ?

Output: Isolated ectopia lentis is a condition that affects the eyes, specifically the positioning of the lens. The lens is a clear structure at the front of the eye that helps focus light. In people with isolated ectopia lentis, the lens in one or both eyes is not centrally positioned as it should be but is off-center (displaced). Isolated ectopia lentis usually becomes apparent in childhood. The lens may drift further off-center over time.  Vision problems are common in isolated ectopia lentis. Affected individuals often have nearsightedness (myopia) and can have an irregular curvature of the lens or a structure that covers the front of the eye (the cornea), which causes blurred vision (astigmatism). They may also develop clouding of the lenses (cataracts) or increased pressure in the eyes (glaucoma) at an earlier age than other adults. In a small number of people with isolated ectopia lentis, tearing of the back lining of the eye (retinal detachment) occurs, which can lead to further vision problems and possible blindness.  In individuals with isolated ectopia lentis, each eye can be affected differently. In addition, the eye problems vary among affected individuals, even those within the same family.  Ectopia lentis is classified as isolated when it occurs alone without signs and symptoms affecting other body systems. Ectopia lentis can also be classified as syndromic, when it is part of a syndrome that affects multiple parts of the body. Ectopia lentis is a common feature of genetic syndromes such as Marfan syndrome and Weill-Marchesani syndrome. </s>


Input: How many people are affected by isolated ectopia lentis ?

Output: The prevalence of isolated ectopia lentis is unknown. In Denmark, an estimated 6.4 per 100,000 individuals have ectopia lentis, but a large proportion of these cases (about 75 percent) are syndromic. </s>


Input: What are the genetic changes related to isolated ectopia lentis ?

Output: Mutations in the FBN1 or ADAMTSL4 gene cause isolated ectopia lentis. These genes provide instructions for making proteins that are necessary for the formation of threadlike filaments called microfibrils. Microfibrils provide support to many tissues, including the lenses of the eyes, which are held in position by these filaments.  Mutations in the FBN1 or ADAMTSL4 gene impair protein function and lead to a decrease in microfibril formation or result in the formation of impaired microfibrils. Without functional microfibrils to anchor the lens in its central position at the front of the eye, the lens becomes displaced. The displaced lens cannot focus light correctly, contributing to the vision problems that are common in people with isolated ectopia lentis. </s>


Input: Is isolated ectopia lentis inherited ?

Output: When isolated ectopia lentis is caused by mutations in the FBN1 gene, it 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 some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  When isolated ectopia lentis is caused by mutations in the ADAMTSL4 gene, it 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 isolated ectopia lentis ?

Output: These resources address the diagnosis or management of isolated ectopia lentis:  - Gene Review: Gene Review: ADAMTSL4-Related Eye Disorders  - Genetic Testing Registry: Ectopia lentis, isolated autosomal recessive  - Genetic Testing Registry: Ectopia lentis, isolated, autosomal dominant   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) tuberous sclerosis complex ?

Output: Tuberous sclerosis complex is a genetic disorder characterized by the growth of numerous noncancerous (benign) tumors in many parts of the body. These tumors can occur in the skin, brain, kidneys, and other organs, in some cases leading to significant health problems. Tuberous sclerosis complex also causes developmental problems, and the signs and symptoms of the condition vary from person to person.  Virtually all affected people have skin abnormalities, including patches of unusually light-colored skin, areas of raised and thickened skin, and growths under the nails. Tumors on the face called facial angiofibromas are also common beginning in childhood.  Tuberous sclerosis complex often affects the brain, causing seizures, behavioral problems such as hyperactivity and aggression, and intellectual disability or learning problems. Some affected children have the characteristic features of autism, a developmental disorder that affects communication and social interaction. Benign brain tumors can also develop in people with tuberous sclerosis complex; these tumors can cause serious or life-threatening complications.  Kidney tumors are common in people with tuberous sclerosis complex; these growths can cause severe problems with kidney function and may be life-threatening in some cases. Additionally, tumors can develop in the heart, lungs, and the light-sensitive tissue at the back of the eye (the retina). </s>


Input: How many people are affected by tuberous sclerosis complex ?

Output: Tuberous sclerosis complex affects about 1 in 6,000 people. </s>


Input: What are the genetic changes related to tuberous sclerosis complex ?

Output: Mutations in the TSC1 or TSC2 gene can cause tuberous sclerosis complex. The TSC1 and TSC2 genes provide instructions for making the proteins hamartin and tuberin, respectively. Within cells, these two proteins likely work together to help regulate cell growth and size. The proteins act as tumor suppressors, which normally prevent cells from growing and dividing too fast or in an uncontrolled way.  People with tuberous sclerosis complex are born with one mutated copy of the TSC1 or TSC2 gene in each cell. This mutation prevents the cell from making functional hamartin or tuberin from the altered copy of the gene. However, enough protein is usually produced from the other, normal copy of the gene to regulate cell growth effectively. For some types of tumors to develop, a second mutation involving the other copy of the TSC1 or TSC2 gene must occur in certain cells during a person's lifetime.  When both copies of the TSC1 gene are mutated in a particular cell, that cell cannot produce any functional hamartin; cells with two altered copies of the TSC2 gene are unable to produce any functional tuberin. The loss of these proteins allows the cell to grow and divide in an uncontrolled way to form a tumor. In people with tuberous sclerosis complex, a second TSC1 or TSC2 mutation typically occurs in multiple cells over an affected person's lifetime. The loss of hamartin or tuberin in different types of cells leads to the growth of tumors in many different organs and tissues. </s>


Input: Is tuberous sclerosis complex inherited ?

Output: Tuberous sclerosis complex has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing tumors and other problems with development. In about one-third of cases, an affected person inherits an altered TSC1 or TSC2 gene from a parent who has the disorder. The remaining two-thirds of people with tuberous sclerosis complex are born with new mutations in the TSC1 or TSC2 gene. These cases, which are described as sporadic, occur in people with no history of tuberous sclerosis complex in their family. TSC1 mutations appear to be more common in familial cases of tuberous sclerosis complex, while mutations in the TSC2 gene occur more frequently in sporadic cases. </s>


Input: What are the treatments for tuberous sclerosis complex ?

Output: These resources address the diagnosis or management of tuberous sclerosis complex:  - Gene Review: Gene Review: Tuberous Sclerosis Complex  - Genetic Testing Registry: Tuberous sclerosis syndrome  - MedlinePlus Encyclopedia: Tuberous Sclerosis  - Tuberous Sclerosis Alliance: TSC Clinics   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) factor V Leiden thrombophilia ?

Output: Factor V Leiden thrombophilia is an inherited disorder of blood clotting. Factor V Leiden is the name of a specific gene mutation that results in thrombophilia, which is an increased tendency to form abnormal blood clots that can block blood vessels.  People with factor V Leiden thrombophilia have a higher than average risk of developing a type of blood clot called a deep venous thrombosis (DVT). DVTs occur most often in the legs, although they can also occur in other parts of the body, including the brain, eyes, liver, and kidneys. Factor V Leiden thrombophilia also increases the risk that clots will break away from their original site and travel through the bloodstream. These clots can lodge in the lungs, where they are known as pulmonary emboli. Although factor V Leiden thrombophilia increases the risk of blood clots, only about 10 percent of individuals with the factor V Leiden mutation ever develop abnormal clots.  The factor V Leiden mutation is associated with a slightly increased risk of pregnancy loss (miscarriage). Women with this mutation are two to three times more likely to have multiple (recurrent) miscarriages or a pregnancy loss during the second or third trimester. Some research suggests that the factor V Leiden mutation may also increase the risk of other complications during pregnancy, including pregnancy-induced high blood pressure (preeclampsia), slow fetal growth, and early separation of the placenta from the uterine wall (placental abruption). However, the association between the factor V Leiden mutation and these complications has not been confirmed. Most women with factor V Leiden thrombophilia have normal pregnancies. </s>


Input: How many people are affected by factor V Leiden thrombophilia ?

Output: Factor V Leiden is the most common inherited form of thrombophilia. Between 3 and 8 percent of people with European ancestry carry one copy of the factor V Leiden mutation in each cell, and about 1 in 5,000 people have two copies of the mutation. The mutation is less common in other populations. </s>


Input: What are the genetic changes related to factor V Leiden thrombophilia ?

Output: A particular mutation in the F5 gene causes factor V Leiden thrombophilia. The F5 gene provides instructions for making a protein called coagulation factor V. This protein plays a critical role in the coagulation system, which is a series of chemical reactions that forms blood clots in response to injury.  The coagulation system is controlled by several proteins, including a protein called activated protein C (APC). APC normally inactivates coagulation factor V, which slows down the clotting process and prevents clots from growing too large. However, in people with factor V Leiden thrombophilia, coagulation factor V cannot be inactivated normally by APC. As a result, the clotting process remains active longer than usual, increasing the chance of developing abnormal blood clots.  Other factors also increase the risk of developing blood clots in people with factor V Leiden thrombophilia. These factors include increasing age, obesity, injury, surgery, smoking, pregnancy, and the use of oral contraceptives (birth control pills) or hormone replacement therapy. The risk of abnormal clots is also much higher in people who have a combination of the factor V Leiden mutation and another mutation in the F5 gene. Additionally, the risk is increased in people who have the factor V Leiden mutation together with a mutation in another gene involved in the coagulation system. </s>


Input: Is factor V Leiden thrombophilia inherited ?

Output: The chance of developing an abnormal blood clot depends on whether a person has one or two copies of the factor V Leiden mutation in each cell. People who inherit two copies of the mutation, one from each parent, have a higher risk of developing a clot than people who inherit one copy of the mutation. Considering that about 1 in 1,000 people per year in the general population will develop an abnormal blood clot, the presence of one copy of the factor V Leiden mutation increases that risk to 3 to 8 in 1,000, and having two copies of the mutation may raise the risk to as high as 80 in 1,000. </s>


Input: What are the treatments for factor V Leiden thrombophilia ?

Output: These resources address the diagnosis or management of factor V Leiden thrombophilia:  - American College of Medical Genetics Consensus Statement on Factor V Leiden Mutation Testing  - Gene Review: Gene Review: Factor V Leiden Thrombophilia  - GeneFacts: Factor V Leiden-Associated Thrombosis: Diagnosis  - GeneFacts: Factor V Leiden-Associated Thrombosis: Management  - Genetic Testing Registry: Thrombophilia due to activated protein C resistance  - Genetic Testing Registry: Thrombophilia due to factor V Leiden  - MedlinePlus Encyclopedia: Deep Venous Thrombosis  - MedlinePlus Encyclopedia: Pulmonary Embolus   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) chronic granulomatous disease ?

Output: Chronic granulomatous disease is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. Immunodeficiencies are conditions in which the immune system is not able to protect the body from foreign invaders such as bacteria and fungi. Individuals with chronic granulomatous disease may have recurrent bacterial and fungal infections. People with this condition may also have areas of inflammation (granulomas) in various tissues that can result in damage to those tissues. The features of chronic granulomatous disease usually first appear in childhood, although some individuals do not show symptoms until later in life.  People with chronic granulomatous disease typically have at least one serious bacterial or fungal infection every 3 to 4 years. The lungs are the most frequent area of infection; pneumonia is a common feature of this condition. Individuals with chronic granulomatous disease may develop a type of fungal pneumonia, called mulch pneumonitis, which causes fever and shortness of breath after exposure to decaying organic materials such as mulch, hay, or dead leaves. Exposure to these organic materials and the numerous fungi involved in their decomposition causes people with chronic granulomatous disease to develop fungal infections in their lungs. Other common areas of infection in people with chronic granulomatous disease include the skin, liver, and lymph nodes.  Inflammation can occur in many different areas of the body in people with chronic granulomatous disease. Most commonly, granulomas occur in the gastrointestinal tract and the genitourinary tract. In many cases the intestinal wall is inflamed, causing a form of inflammatory bowel disease that varies in severity but can lead to stomach pain, diarrhea, bloody stool, nausea, and vomiting. Other common areas of inflammation in people with chronic granulomatous disease include the stomach, colon, and rectum, as well as the mouth, throat, and skin. Additionally, granulomas within the gastrointestinal tract can lead to tissue breakdown and pus production (abscesses). Inflammation in the stomach can prevent food from passing through to the intestines (gastric outlet obstruction), leading to an inability to digest food. These digestive problems cause vomiting after eating and weight loss. In the genitourinary tract, inflammation can occur in the kidneys and bladder. Inflammation of the lymph nodes (lymphadenitis) and bone marrow (osteomyelitis), which both produce immune cells, can lead to further impairment of the immune system.  Rarely, people with chronic granulomatous disease develop autoimmune disorders, which occur when the immune system malfunctions and attacks the body's own tissues and organs.  Repeated episodes of infection and inflammation reduce the life expectancy of individuals with chronic granulomatous disease; however, with treatment, most affected individuals live into mid- to late adulthood. </s>


Input: How many people are affected by chronic granulomatous disease ?

Output: Chronic granulomatous disease is estimated to occur in 1 in 200,000 to 250,000 people worldwide. </s>


Input: What are the genetic changes related to chronic granulomatous disease ?

Output: Mutations in the CYBA, CYBB, NCF1, NCF2, or NCF4 gene can cause chronic granulomatous disease. There are five types of this condition that are distinguished by the gene that is involved. The proteins produced from the affected genes are parts (subunits) of an enzyme complex called NADPH oxidase, which plays an essential role in the immune system. Specifically, NADPH oxidase is primarily active in immune system cells called phagocytes. These cells catch and destroy foreign invaders such as bacteria and fungi. Within phagocytes, NADPH oxidase is involved in the production of a toxic molecule called superoxide. Superoxide is used to generate other toxic substances, which play a role in killing foreign invaders and preventing them from reproducing in the body and causing illness. NADPH oxidase is also thought to regulate the activity of immune cells called neutrophils. These cells play a role in adjusting the inflammatory response to optimize healing and reduce injury to the body.  Mutations in the CYBA, CYBB, NCF1, NCF2, and NCF4 genes result in the production of proteins with little or no function or the production of no protein at all. Mutations in the genes that cause chronic granulomatous disease that prevent the production of any functional protein are designated "0". For example, mutations in the CYBB gene that lead to no functional beta chain are designated CYBB0. Mutations that lead to a reduction of the amount of protein produced are designated "-", for example, CYBB-.  Without any one of its subunit proteins, NADPH oxidase cannot assemble or function properly. As a result, phagocytes are unable to kill foreign invaders and neutrophil activity is not regulated. A lack of NADPH oxidase leaves affected individuals vulnerable to many types of infection and excessive inflammation.  Some people with chronic granulomatous disease do not have an identified mutation in any of these genes. The cause of the condition in these individuals is unknown. </s>


Input: Is chronic granulomatous disease inherited ?

Output: When chronic granulomatous disease is caused by mutations in the CYBB gene, the condition is inherited in an X-linked recessive pattern. The CYBB gene 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. Rarely, females with one altered copy of the CYBB gene have mild symptoms of chronic granulomatous disease, such as an increased frequency of bacterial or fungal infections.  When chronic granulomatous disease is caused by CYBA, NCF1, NCF2, or NCF4 gene mutations, the 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. Men and women are affected by autosomal recessive conditions equally. </s>


Input: What are the treatments for chronic granulomatous disease ?

Output: These resources address the diagnosis or management of chronic granulomatous disease:  - American Academy of Allergy, Asthma, and Immunology  - Gene Review: Gene Review: Chronic Granulomatous Disease  - Genetic Testing Registry: Chronic granulomatous disease, X-linked  - Genetic Testing Registry: Chronic granulomatous disease, autosomal recessive cytochrome b-positive, type 1  - Genetic Testing Registry: Chronic granulomatous disease, autosomal recessive cytochrome b-positive, type 2  - Genetic Testing Registry: Chronic granulomatous disease, autosomal recessive cytochrome b-positive, type 3  - Genetic Testing Registry: Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative  - MedlinePlus Encyclopedia: Chronic Granulomatous Disease  - Primary Immune Deficiency Treatment Consortium   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) osteoporosis-pseudoglioma syndrome ?

Output: Osteoporosis-pseudoglioma syndrome is a rare condition characterized by severe thinning of the bones (osteoporosis) and eye abnormalities that lead to vision loss. In people with this condition, osteoporosis is usually recognized in early childhood. It is caused by a shortage of minerals, such as calcium, in bones (decreased bone mineral density), which makes the bones brittle and prone to fracture. Affected individuals often have multiple bone fractures, including in the bones that form the spine (vertebrae). Multiple fractures can cause collapse of the affected vertebrae (compressed vertebrae), abnormal side-to-side curvature of the spine (scoliosis), short stature, and limb deformities. Decreased bone mineral density can also cause softening or thinning of the skull (craniotabes).  Most affected individuals have impaired vision at birth or by early infancy and are blind by young adulthood. Vision problems are usually caused by one of several eye conditions, grouped together as pseudoglioma, that affect the light-sensitive tissue at the back of the eye (the retina), although other eye conditions have been identified in affected individuals. Pseudogliomas are so named because, on examination, the conditions resemble an eye tumor known as a retinal glioma.  Rarely, people with osteoporosis-pseudoglioma syndrome have additional signs or symptoms such as mild intellectual disability, weak muscle tone (hypotonia), abnormally flexible joints, or seizures. </s>


Input: How many people are affected by osteoporosis-pseudoglioma syndrome ?

Output: Osteoporosis-pseudoglioma syndrome is a rare disorder that occurs in approximately 1 in 2 million people. </s>


Input: What are the genetic changes related to osteoporosis-pseudoglioma syndrome ?

Output: Osteoporosis-pseudoglioma syndrome is caused by mutations in the LRP5 gene. This gene provides instructions for making a protein that participates in a chemical signaling pathway that affects the way cells and tissues develop. In particular, the LRP5 protein helps regulate bone mineral density and plays a critical role in development of the retina.  LRP5 gene mutations that cause osteoporosis-pseudoglioma syndrome prevent cells from making any LRP5 protein or lead to a protein that cannot function. Loss of this protein's function disrupts the chemical signaling pathways that are needed for the formation of bone and for normal retinal development, leading to the bone and eye abnormalities characteristic of osteoporosis-pseudoglioma syndrome. </s>


Input: Is osteoporosis-pseudoglioma syndrome inherited ?

Output: Osteoporosis-pseudoglioma syndrome is inherited in an autosomal recessive pattern, which means both copies of the LRP5 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. However, some carriers may have decreased bone mineral density. </s>


Input: What are the treatments for osteoporosis-pseudoglioma syndrome ?

Output: These resources address the diagnosis or management of osteoporosis-pseudoglioma syndrome:  - Genetic Testing Registry: Osteoporosis with pseudoglioma  - Lucile Packard Children's Hospital at Stanford: Juvenile Osteoporosis  - MedlinePlus Encyclopedia: Bone Mineral Density Test  - Merck Manual Home Health Edition: Osteoporosis   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) 15q24 microdeletion ?

Output: 15q24 microdeletion is a chromosomal change in which a small piece of chromosome 15 is deleted in each cell. The deletion occurs on the long (q) arm of the chromosome at a position designated q24.  15q24 microdeletion is associated with mild to moderate intellectual disability and delayed speech development. Other common signs and symptoms include short stature, weak muscle tone (hypotonia), and skeletal abnormalities including loose (lax) joints. Affected males may have genital abnormalities, which can include an unusually small penis (micropenis) and the opening of the urethra on the underside of the penis (hypospadias). Affected individuals also have distinctive facial features such as a high front hairline, broad eyebrows, widely set eyes (hypertelorism), outside corners of the eyes that point downward (downslanting palpebral fissures), a broad nasal bridge, a full lower lip, and a long, smooth space between the upper lip and nose (philtrum). </s>


Input: How many people are affected by 15q24 microdeletion ?

Output: This condition is very rare; only a few dozen affected individuals have been identified. </s>


Input: What are the genetic changes related to 15q24 microdeletion ?

Output: People with a 15q24 microdeletion are missing between 1.7 million and 6.1 million DNA building blocks (base pairs), also written as 1.7-6.1 megabases (Mb), at position q24 on chromosome 15. The exact size of the deletion varies, but all individuals are missing the same 1.2 Mb region. This region contains several genes that are thought to be important for normal development.  The signs and symptoms that result from a 15q24 microdeletion are probably related to the loss of one or more genes in the deleted region. However, it is unclear which missing genes contribute to the specific features of the disorder. </s>


Input: Is 15q24 microdeletion inherited ?

Output: The identified cases of 15q24 microdeletion have occurred in people with no history of the condition in their family. The chromosomal change likely occurs as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. </s>


Input: What are the treatments for 15q24 microdeletion ?

Output: These resources address the diagnosis or management of 15q24 microdeletion:  - Gene Review: Gene Review: 15q24 Microdeletion  - Genetic Testing Registry: 15q24 deletion 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) branchio-oculo-facial syndrome ?

Output: Branchio-oculo-facial syndrome is a condition that affects development before birth, particularly of structures in the face and neck. Its characteristic features include skin anomalies on the neck, malformations of the eyes and ears, and distinctive facial features.  "Branchio-" refers to the branchial arches, which are structures in the developing embryo that give rise to tissues in the face and neck. In people with branchio-oculo-facial syndrome, the first and second branchial arches do not develop properly, leading to abnormal patches of skin, typically on the neck or near the ears. These patches can be unusually thin, hairy, or red and densely packed with blood vessels (hemangiomatous). In a small number of individuals, tissue from a gland called the thymus is abnormally located on the skin of the neck (dermal thymus). Problems with branchial arch development underlie many of the other features of branchio-oculo-facial syndrome.  "Oculo-" refers to the eyes. Many people with branchio-oculo-facial syndrome have malformations of the eyes that can lead to vision impairment. These abnormalities include unusually small eyeballs (microphthalmia), no eyeballs (anophthalmia), a gap or split in structures that make up the eyes (coloboma), or blockage of the tear ducts (nasolacrimal duct stenosis).  Problems with development of the face lead to distinctive facial features in people with branchio-oculo-facial syndrome. Many affected individuals have a split in the upper lip (cleft lip) or a pointed upper lip that resembles a poorly repaired cleft lip (often called a pseudocleft lip) with or without an opening in the roof of the mouth (cleft palate). Other facial characteristics include widely spaced eyes (hypertelorism), an increased distance between the inner corners of the eyes (telecanthus), outside corners of the eyes that point upward (upslanting palpebral fissures), a broad nose with a flattened tip, and weakness of the muscles in the lower face. The ears are also commonly affected, resulting in malformed or prominent ears. Abnormalities of the inner ear or of the tiny bones in the ears (ossicles) can cause hearing loss in people with this condition.  Branchio-oculo-facial syndrome can affect other structures and tissues as well. Some affected individuals have kidney abnormalities, such as malformed kidneys or multiple kidney cysts. Nail and teeth abnormalities also occur, and some people with this condition have prematurely graying hair. </s>


Input: How many people are affected by branchio-oculo-facial syndrome ?

Output: Branchio-oculo-facial syndrome is a rare condition, although the prevalence is unknown. </s>


Input: What are the genetic changes related to branchio-oculo-facial syndrome ?

Output: Branchio-oculo-facial syndrome is caused by mutations in the TFAP2A gene. This gene provides instructions for making a protein called transcription factor AP-2 alpha (AP-2). As its name suggests, this protein is a transcription factor, which means it attaches (binds) to specific regions of DNA and helps control the activity of particular genes. Transcription factor AP-2 regulates genes that are involved in several cellular processes, such as cell division and the self-destruction of cells that are no longer needed (apoptosis). This protein is critical during development before birth, particularly of the branchial arches, which form the structures of the face and neck.  Most TFAP2A gene mutations that cause branchio-oculo-facial syndrome change single protein building blocks (amino acids) in the transcription factor AP-2 protein. These changes tend to occur in a region of the protein that allows it to bind to DNA. Without this function, transcription factor AP-2 cannot control the activity of genes during development, which disrupts the development of the eyes, ears, and face and causes the features of branchio-oculo-facial syndrome. </s>


Input: Is branchio-oculo-facial syndrome inherited ?

Output: Branchio-oculo-facial 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 about half of cases, an affected person inherits the mutation from one affected parent. The remaining cases occur in people whose parents do not have a mutation in the TFAP2A gene. In these situations, the mutation likely occurs as a random event during the formation of reproductive cells (eggs and sperm) in a parent or in early fetal development of the affected individual. </s>


Input: What are the treatments for branchio-oculo-facial syndrome ?

Output: These resources address the diagnosis or management of branchio-oculo-facial syndrome:  - Gene Review: Gene Review: Branchiooculofacial Syndrome  - Genetic Testing Registry: Branchiooculofacial syndrome  - MedlinePlus Encyclopedia: Cleft Lip and Palate   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) Pallister-Hall syndrome ?

Output: Pallister-Hall syndrome is a disorder that affects the development of many parts of the body. Most people with this condition have extra fingers and/or toes (polydactyly), and the skin between some fingers or toes may be fused (cutaneous syndactyly). An abnormal growth in the brain called a hypothalamic hamartoma is characteristic of this disorder. In many cases, these growths do not cause any medical problems; however, some hypothalamic hamartomas lead to seizures or hormone abnormalities that can be life-threatening in infancy. Other features of Pallister-Hall syndrome include a malformation of the airway called a bifid epiglottis, an obstruction of the anal opening (imperforate anus), and kidney abnormalities. Although the signs and symptoms of this disorder vary from mild to severe, only a small percentage of affected people have serious complications. </s>


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

Output: This condition is very rare; its prevalence is unknown. </s>


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

Output: Mutations in the GLI3 gene cause Pallister-Hall syndrome.  The GLI3 gene provides instructions for making a protein that controls gene expression, which is a process that regulates whether genes are turned on or off in particular cells. By interacting with certain genes at specific times during development, the GLI3 protein plays a role in the normal shaping (patterning) of many organs and tissues before birth.  Mutations that cause Pallister-Hall syndrome typically lead to the production of an abnormally short version of the GLI3 protein. Unlike the normal GLI3 protein, which can turn target genes on or off, the short protein can only turn off (repress) target genes. Researchers are working to determine how this change in the protein's function affects early development. It remains uncertain how GLI3 mutations can cause polydactyly, hypothalamic hamartoma, and the other features of Pallister-Hall syndrome. </s>


Input: Is Pallister-Hall syndrome inherited ?

Output: This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits a mutation in the GLI3 gene from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family. </s>


Input: What are the treatments for Pallister-Hall syndrome ?

Output: These resources address the diagnosis or management of Pallister-Hall syndrome:  - Gene Review: Gene Review: Pallister-Hall Syndrome  - Genetic Testing Registry: Pallister-Hall syndrome  - MedlinePlus Encyclopedia: Epiglottis (Image)  - MedlinePlus Encyclopedia: Imperforate Anus  - MedlinePlus Encyclopedia: Polydactyly   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) congenital fibrosis of the extraocular muscles ?

Output: Congenital fibrosis of the extraocular muscles is a disorder that affects the muscles that surround the eyes. These muscles control eye movement and the position of the eyes (for example, looking straight ahead). Congenital fibrosis of the extraocular muscles prevents the normal development and function of these muscles. As a result, affected individuals are unable to move their eyes normally. Most people with this condition have difficulty looking upward, and their side-to-side eye movement may also be limited. The eyes may be misaligned such that they look in different directions (strabismus). Instead of moving their eyes, affected individuals may need to turn their head to track moving objects. Additionally, many people with congenital fibrosis of the extraocular muscles have droopy eyelids (ptosis), which further limits their vision.  Researchers have identified at least four forms of congenital fibrosis of the extraocular muscles, designated CFEOM1, CFEOM2, CFEOM3, and Tukel syndrome. The specific problems with eye movement vary among the types. Tukel syndrome is characterized by missing fingers (oligodactyly) and other hand abnormalities in addition to problems with eye movement. </s>


Input: How many people are affected by congenital fibrosis of the extraocular muscles ?

Output: CFEOM1 is the most common form of congenital fibrosis of the extraocular muscles, affecting at least 1 in 230,000 people. CFEOM1 and CFEOM3 have been reported worldwide, whereas CFEOM2 has been seen in only a few families of Turkish, Saudi Arabian, and Iranian descent. Tukel syndrome appears to be very rare; it has been diagnosed in only one large Turkish family. </s>


Input: What are the genetic changes related to congenital fibrosis of the extraocular muscles ?

Output: CFEOM1 and rare cases of CFEOM3 result from mutations in the KIF21A gene. This gene provides instructions for making a protein called a kinesin, which is essential for the transport of materials within cells. Researchers believe that this protein plays an important role in the normal development and function of nerves in the head and face. In particular, this protein plays a critical role in the development of a particular branch of cranial nerve III, which emerges from the brain and controls muscles that raise the eyes and eyelids. Mutations in the KIF21A gene likely alter the protein's ability to transport materials within nerve cells, preventing the normal development of these cranial nerves and the extraocular muscles they control. Abnormal function of the extraocular muscles leads to restricted eye movement and related problems with vision.  Mutations in the PHOX2A gene cause CFEOM2. This gene provides instructions for making a protein that is found in the developing nervous system. Studies suggest that the PHOX2A protein plays a critical role in the development of cranial nerves III and IV, which are necessary for normal eye movement. Mutations likely eliminate the function of the PHOX2A protein, which prevents the normal development of these cranial nerves and the extraocular muscles they control.  In most cases of CFEOM3, the genetic cause of the condition is unknown. Studies suggest that a gene associated with CFEOM3 may be located near one end of chromosome 16. The gene associated with Tukel syndrome has not been identified either, although researchers think that it may be located near one end of chromosome 21. </s>


Input: Is congenital fibrosis of the extraocular muscles inherited ?

Output: The different types of congenital fibrosis of the extraocular muscles have different patterns of inheritance. CFEOM1 and CFEOM3 are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  CFEOM2 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. Tukel syndrome also appears to have an autosomal recessive pattern of inheritance, although the genetic change responsible for this disorder is unknown. </s>


Input: What are the treatments for congenital fibrosis of the extraocular muscles ?

Output: These resources address the diagnosis or management of congenital fibrosis of the extraocular muscles:  - Gene Review: Gene Review: Congenital Fibrosis of the Extraocular Muscles  - Genetic Testing Registry: Fibrosis of extraocular muscles, congenital, 1  - Genetic Testing Registry: Fibrosis of extraocular muscles, congenital, 2  - Genetic Testing Registry: Fibrosis of extraocular muscles, congenital, 3a, with or without extraocular involvement  - Genetic Testing Registry: Tukel syndrome  - MedlinePlus Encyclopedia: Extraocular Muscle Function Testing  - MedlinePlus Encyclopedia: Strabismus   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 dystonia-parkinsonism ?

Output: X-linked dystonia-parkinsonism is a movement disorder that has been found only in people of Filipino descent. This condition affects men much more often than women.  Parkinsonism is usually the first sign of X-linked dystonia-parkinsonism. Parkinsonism is a group of movement abnormalities including tremors, unusually slow movement (bradykinesia), rigidity, an inability to hold the body upright and balanced (postural instability), and a shuffling gait that can cause recurrent falls.  Later in life, many affected individuals also develop a pattern of involuntary, sustained muscle contractions known as dystonia. The dystonia associated with X-linked dystonia-parkinsonism typically starts in one area, most often the eyes, jaw, or neck, and later spreads to other parts of the body. The continuous muscle cramping and spasms can be disabling. Depending on which muscles are affected, widespread (generalized) dystonia can cause difficulty with speaking, swallowing, coordination, and walking.  The signs and symptoms of X-linked dystonia-parkinsonism vary widely. In the mildest cases, affected individuals have slowly progressive parkinsonism with little or no dystonia. More severe cases involve dystonia that rapidly becomes generalized. These individuals become dependent on others for care within a few years after signs and symptoms appear, and they may die prematurely from breathing difficulties, infections (such as aspiration pneumonia), or other complications. </s>


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

Output: X-linked dystonia-parkinsonism has been reported in more than 500 people of Filipino descent, although it is likely that many more Filipinos are affected. Most people with this condition can trace their mother's ancestry to the island of Panay in the Philippines. The prevalence of the disorder is 5.24 per 100,000 people on the island of Panay. </s>


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

Output: Mutations in and near the TAF1 gene can cause X-linked dystonia-parkinsonism. The TAF1 gene provides instructions for making part of a protein called transcription factor IID (TFIID). This protein is active in cells and tissues throughout the body, where it plays an essential role in regulating the activity of most genes.  The TAF1 gene is part of a complex region of DNA known as the TAF1/DYT3 multiple transcript system. This region consists of short stretches of DNA from the TAF1 gene plus some extra segments of genetic material near the gene. These stretches of DNA can be combined in different ways to create various sets of instructions for making proteins. Researchers believe that some of these variations are critical for the normal function of nerve cells (neurons) in the brain.  Several changes in the TAF1/DYT3 multiple transcript system have been identified in people with X-linked dystonia-parkinsonism. Scientists are uncertain how these changes are related to the movement abnormalities characteristic of this disease. However, they suspect that the changes disrupt the regulation of critical genes in neurons. This defect leads to the eventual death of these cells, particularly in areas of the brain called the caudate nucleus and putamen. These regions are critical for normal movement, learning, and memory. It is unclear why the effects of changes in the TAF1/DYT3 multiple transcript system appear to be limited to dystonia and parkinsonism. </s>


Input: Is X-linked dystonia-parkinsonism inherited ?

Output: This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation typically must 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.  In X-linked recessive inheritance, females with one altered copy of the gene in each cell are called carriers. They can pass on the gene to their children, but they usually do not experience signs and symptoms of the disorder. However, a few females carrying one altered copy of the TAF1 gene have developed movement abnormalities associated with X-linked dystonia-parkinsonism. These movement problems tend to be milder than those seen in affected men, and they are usually not progressive or disabling. </s>


Input: What are the treatments for X-linked dystonia-parkinsonism ?

Output: These resources address the diagnosis or management of X-linked dystonia-parkinsonism:  - Gene Review: Gene Review: X-Linked Dystonia-Parkinsonism Syndrome  - Genetic Testing Registry: Dystonia 3, torsion, X-linked   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) osteopetrosis ?

Output: Osteopetrosis is a bone disease that makes bones abnormally dense and prone to breakage (fracture). Researchers have described several major types of osteopetrosis, which are usually distinguished by their pattern of inheritance: autosomal dominant, autosomal recessive, or X-linked. The different types of the disorder can also be distinguished by the severity of their signs and symptoms.  Autosomal dominant osteopetrosis (ADO), which is also called Albers-Schnberg disease, is typically the mildest type of the disorder. Some affected individuals have no symptoms. In these people, the unusually dense bones may be discovered by accident when an x-ray is done for another reason. In affected individuals who develop signs and symptoms, the major features of the condition include multiple bone fractures, abnormal side-to-side curvature of the spine (scoliosis) or other spinal abnormalities, arthritis in the hips, and a bone infection called osteomyelitis. These problems usually become apparent in late childhood or adolescence.  Autosomal recessive osteopetrosis (ARO) is a more severe form of the disorder that becomes apparent in early infancy. Affected individuals have a high risk of bone fracture resulting from seemingly minor bumps and falls. Their abnormally dense skull bones pinch nerves in the head and face (cranial nerves), often resulting in vision loss, hearing loss, and paralysis of facial muscles. Dense bones can also impair the function of bone marrow, preventing it from producing new blood cells and immune system cells. As a result, people with severe osteopetrosis are at risk of abnormal bleeding, a shortage of red blood cells (anemia), and recurrent infections. In the most severe cases, these bone marrow abnormalities can be life-threatening in infancy or early childhood.  Other features of autosomal recessive osteopetrosis can include slow growth and short stature, dental abnormalities, and an enlarged liver and spleen (hepatosplenomegaly). Depending on the genetic changes involved, people with severe osteopetrosis can also have brain abnormalities, intellectual disability, or recurrent seizures (epilepsy).  A few individuals have been diagnosed with intermediate autosomal osteopetrosis (IAO), a form of the disorder that can have either an autosomal dominant or an autosomal recessive pattern of inheritance. The signs and symptoms of this condition become noticeable in childhood and include an increased risk of bone fracture and anemia. People with this form of the disorder typically do not have life-threatening bone marrow abnormalities. However, some affected individuals have had abnormal calcium deposits (calcifications) in the brain, intellectual disability, and a form of kidney disease called renal tubular acidosis.  Rarely, osteopetrosis can have an X-linked pattern of inheritance. In addition to abnormally dense bones, the X-linked form of the disorder is characterized by abnormal swelling caused by a buildup of fluid (lymphedema) and a condition called anhydrotic ectodermal dysplasia that affects the skin, hair, teeth, and sweat glands. Affected individuals also have a malfunctioning immune system (immunodeficiency), which allows severe, recurrent infections to develop. Researchers often refer to this condition as OL-EDA-ID, an acronym derived from each of the major features of the disorder. </s>


Input: How many people are affected by osteopetrosis ?

Output: Autosomal dominant osteopetrosis is the most common form of the disorder, affecting about 1 in 20,000 people. Autosomal recessive osteopetrosis is rarer, occurring in an estimated 1 in 250,000 people.  Other forms of osteopetrosis are very rare. Only a few cases of intermediate autosomal osteopetrosis and OL-EDA-ID have been reported in the medical literature. </s>


Input: What are the genetic changes related to osteopetrosis ?

Output: Mutations in at least nine genes cause the various types of osteopetrosis. Mutations in the CLCN7 gene are responsible for about 75 percent of cases of autosomal dominant osteopetrosis, 10 to 15 percent of cases of autosomal recessive osteopetrosis, and all known cases of intermediate autosomal osteopetrosis. TCIRG1 gene mutations cause about 50 percent of cases of autosomal recessive osteopetrosis. Mutations in other genes are less common causes of autosomal dominant and autosomal recessive forms of the disorder. The X-linked type of osteopetrosis, OL-EDA-ID, results from mutations in the IKBKG gene. In about 30 percent of all cases of osteopetrosis, the cause of the condition is unknown.  The genes associated with osteopetrosis are involved in the formation, development, and function of specialized cells called osteoclasts. These cells break down bone tissue during bone remodeling, a normal process in which old bone is removed and new bone is created to replace it. Bones are constantly being remodeled, and the process is carefully controlled to ensure that bones stay strong and healthy.  Mutations in any of the genes associated with osteopetrosis lead to abnormal or missing osteoclasts. Without functional osteoclasts, old bone is not broken down as new bone is formed. As a result, bones throughout the skeleton become unusually dense. The bones are also structurally abnormal, making them prone to fracture. These problems with bone remodeling underlie all of the major features of osteopetrosis. </s>


Input: Is osteopetrosis inherited ?

Output: Osteopetrosis can have several different patterns of inheritance. Most commonly, the disorder has an autosomal dominant inheritance pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. Most people with autosomal dominant osteopetrosis inherit the condition from an affected parent.  Osteopetrosis can also be inherited in an autosomal recessive pattern, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  OL-EDA-ID is inherited in an X-linked recessive pattern. The IKBKG gene 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 osteopetrosis ?

Output: These resources address the diagnosis or management of osteopetrosis:  - Gene Review: Gene Review: CLCN7-Related Osteopetrosis  - Genetic Testing Registry: Ectodermal dysplasia, anhidrotic, with immunodeficiency, osteopetrosis, and lymphedema  - Genetic Testing Registry: OSTEOPETROSIS, AUTOSOMAL RECESSIVE 5  - Genetic Testing Registry: Osteopetrosis and infantile neuroaxonal dystrophy  - Genetic Testing Registry: Osteopetrosis autosomal dominant type 2  - Genetic Testing Registry: Osteopetrosis autosomal recessive 1  - Genetic Testing Registry: Osteopetrosis autosomal recessive 2  - Genetic Testing Registry: Osteopetrosis autosomal recessive 4  - Genetic Testing Registry: Osteopetrosis autosomal recessive 6  - Genetic Testing Registry: Osteopetrosis autosomal recessive 7  - Genetic Testing Registry: Osteopetrosis with renal tubular acidosis   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) 21-hydroxylase deficiency ?

Output: 21-hydroxylase deficiency is an inherited disorder that affects the adrenal glands. The adrenal glands are located on top of the kidneys and produce a variety of hormones that regulate many essential functions in the body. In people with 21-hydroxylase deficiency, the adrenal glands produce excess androgens, which are male sex hormones.  There are three types of 21-hydroxylase deficiency. Two types are classic forms, known as the salt-wasting and simple virilizing types. The third type is called the non-classic type. The salt-wasting type is the most severe, the simple virilizing type is less severe, and the non-classic type is the least severe form.  Males and females with either classic form of 21-hydroxylase deficiency tend to have an early growth spurt, but their final adult height is usually shorter than others in their family. Additionally, affected individuals may have a reduced ability to have biological children (decreased fertility). Females may also develop excessive body hair growth (hirsutism), male pattern baldness, and irregular menstruation.  Approximately 75 percent of individuals with classic 21-hydroxylase deficiency have the salt-wasting type. Hormone production is extremely low in this form of the disorder. Affected individuals lose large amounts of sodium in their urine, which can be life-threatening in early infancy. Babies with the salt-wasting type can experience poor feeding, weight loss, dehydration, and vomiting. Individuals with the simple virilizing form do not experience salt loss.  In both the salt-wasting and simple virilizing forms of this disorder, females typically have external genitalia that do not look clearly male or female (ambiguous genitalia). Males usually have normal genitalia, but the testes may be small.  Females with the non-classic type of 21-hydroxylase deficiency have normal female genitalia. As affected females get older, they may experience hirsutism, male pattern baldness, irregular menstruation, and decreased fertility. Males with the non-classic type may have early beard growth and small testes. Some individuals with this type of 21-hydroxylase deficiency have no symptoms of the disorder. </s>


Input: How many people are affected by 21-hydroxylase deficiency ?

Output: The classic forms of 21-hydroxylase deficiency occur in 1 in 15,000 newborns. The prevalence of the non-classic form of 21-hydroxylase deficiency is estimated to be 1 in 1,000 individuals. The prevalence of both classic and non-classic forms varies among different ethnic populations.  21-hydroxylase deficiency is one of a group of disorders known as congenital adrenal hyperplasias that impair hormone production and disrupt sexual development. 21-hydroxylase deficiency is responsible for about 95 percent of all cases of congenital adrenal hyperplasia. </s>


Input: What are the genetic changes related to 21-hydroxylase deficiency ?

Output: Mutations in the CYP21A2 gene cause 21-hydroxylase deficiency. The CYP21A2 gene provides instructions for making an enzyme called 21-hydroxylase. This enzyme is found in the adrenal glands, where it plays a role in producing hormones called cortisol and aldosterone. Cortisol has numerous functions, such as maintaining blood sugar levels, protecting the body from stress, and suppressing inflammation. Aldosterone is sometimes called the salt-retaining hormone because it regulates the amount of salt retained by the kidneys. The retention of salt affects fluid levels in the body and blood pressure.  21-hydroxylase deficiency is caused by a shortage (deficiency) of the 21-hydroxylase enzyme. When 21-hydroxylase is lacking, substances that are usually used to form cortisol and aldosterone instead build up in the adrenal glands and are converted to androgens. The excess production of androgens leads to abnormalities of sexual development in people with 21-hydroxylase deficiency. A lack of aldosterone production contributes to the salt loss in people with the salt-wasting form of this condition.  The amount of functional 21-hydroxylase enzyme determines the severity of the disorder. Individuals with the salt-wasting type have CYP21A2 mutations that result in a completely nonfunctional enzyme. People with the simple virilizing type of this condition have CYP21A2 gene mutations that allow the production of low levels of functional enzyme. Individuals with the non-classic type of this disorder have CYP21A2 mutations that result in the production of reduced amounts of the enzyme, but more enzyme than either of the other types. </s>


Input: Is 21-hydroxylase deficiency inherited ?

Output: This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. </s>


Input: What are the treatments for 21-hydroxylase deficiency ?

Output: These resources address the diagnosis or management of 21-hydroxylase deficiency:  - Baby's First Test  - CARES Foundation: Treatment  - Gene Review: Gene Review: 21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia  - Genetic Testing Registry: 21-hydroxylase deficiency  - MedlinePlus Encyclopedia: Congenital Adrenal Hyperplasia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) multiple system atrophy ?

Output: Multiple system atrophy is a progressive brain disorder that affects movement and balance and disrupts the function of the autonomic nervous system. The autonomic nervous system controls body functions that are mostly involuntary, such as regulation of blood pressure.  Researchers have described two major types of multiple system atrophy, which are distinguished by their major signs and symptoms at the time of diagnosis. In one type, known as MSA-P, a group of movement abnormalities called parkinsonism are predominant. These abnormalities include unusually slow movement (bradykinesia), muscle rigidity, tremors, and an inability to hold the body upright and balanced (postural instability). The other type of multiple system atrophy, known as MSA-C, is characterized by cerebellar ataxia, which causes problems with coordination and balance. This form of the condition can also include speech difficulties (dysarthria) and problems controlling eye movement.  Both forms of multiple system atrophy are associated with abnormalities of the autonomic nervous system. The most frequent autonomic symptoms associated with multiple system atrophy are a sudden drop in blood pressure upon standing (orthostatic hypotension), urinary difficulties, and erectile dysfunction in men.  Multiple system atrophy usually occurs in older adults; on average, signs and symptoms appear around age 55. The signs and symptoms of the condition worsen with time, and affected individuals survive an average of 9 years after their diagnosis. </s>


Input: How many people are affected by multiple system atrophy ?

Output: Multiple system atrophy has a prevalence of about 2 to 5 per 100,000 people. </s>


Input: What are the genetic changes related to multiple system atrophy ?

Output: Multiple system atrophy is a complex condition that is likely caused by the interaction of multiple genetic and environmental factors. Some of these factors have been identified, but many remain unknown.  Changes in several genes have been studied as possible risk factors for multiple system atrophy. The only confirmed genetic risk factors are variants in the SNCA gene. This gene provides instructions for making a protein called alpha-synuclein, which is abundant in normal brain cells but whose function is unknown. Studies suggest that several common variations in the SNCA gene are associated with an increased risk of multiple system atrophy in people of European descent. However, it is unclear how having one of these SNCA gene variants increases the risk of developing this condition.  Researchers have also examined environmental factors that could contribute to the risk of multiple system atrophy. Initial studies suggested that exposure to solvents, certain types of plastic or metal, and other potential toxins might be associated with the condition. However, these associations have not been confirmed.  Multiple system atrophy is characterized by clumps of abnormal alpha-synuclein protein that build up in cells in many parts of the brain and spinal cord. Over time, these clumps (which are known as inclusions) damage cells in parts of the nervous system that control movement, balance and coordination, and autonomic functioning. The progressive loss of cells in these regions underlies the major features of multiple system atrophy. </s>


Input: Is multiple system atrophy inherited ?

Output: Most cases of multiple system atrophy are sporadic, which means they occur in people with no history of the disorder in their family. Rarely, the condition has been reported to run in families; however, it does not have a clear pattern of inheritance. </s>


Input: What are the treatments for multiple system atrophy ?

Output: These resources address the diagnosis or management of multiple system atrophy:  - Genetic Testing Registry: Shy-Drager syndrome  - Vanderbilt Autonomic Dysfunction Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) complement component 2 deficiency ?

Output: Complement component 2 deficiency is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. Immunodeficiencies are conditions in which the immune system is not able to protect the body effectively from foreign invaders such as bacteria and viruses. People with complement component 2 deficiency have a significantly increased risk of recurrent bacterial infections, specifically of the lungs (pneumonia), the membrane covering the brain and spinal cord (meningitis), and the blood (sepsis), which may be life-threatening. These infections most commonly occur in infancy and childhood and become less frequent in adolescence and adulthood.  Complement component 2 deficiency is also associated with an increased risk of developing autoimmune disorders such as systemic lupus erythematosus (SLE) or vasculitis. Autoimmune disorders occur when the immune system malfunctions and attacks the body's tissues and organs. Between 10 and 20 percent of individuals with complement component 2 deficiency develop SLE. Females with complement component 2 deficiency are more likely to have SLE than affected males, but this is also true of SLE in the general population.  The severity of complement component 2 deficiency varies widely. While some affected individuals experience recurrent infections and other immune system difficulties, others do not have any health problems related to the disorder. </s>


Input: How many people are affected by complement component 2 deficiency ?

Output: In Western countries, complement component 2 deficiency is estimated to affect 1 in 20,000 individuals; its prevalence in other areas of the world is unknown. </s>


Input: What are the genetic changes related to complement component 2 deficiency ?

Output: Complement component 2 deficiency is caused by mutations in the C2 gene. This gene provides instructions for making the complement component 2 protein, which helps regulate a part of the body's immune response known as the complement system. The complement system is a group of proteins that work together to destroy foreign invaders, trigger inflammation, and remove debris from cells and tissues. The complement component 2 protein is involved in the pathway that turns on (activates) the complement system when foreign invaders, such as bacteria, are detected.  The most common C2 gene mutation, which is found in more than 90 percent of people with complement component 2 deficiency, prevents the production of complement component 2 protein. A lack of this protein impairs activation of the complement pathway. As a result, the complement system's ability to fight infections is diminished. It is unclear how complement component 2 deficiency leads to an increase in autoimmune disorders. Researchers speculate that the dysfunctional complement system is unable to distinguish what it should attack, and it sometimes attacks normal tissues, leading to autoimmunity. Alternatively, the dysfunctional complement system may perform partial attacks on invading molecules, which leaves behind foreign fragments that are difficult to distinguish from the body's tissues, so the complement system sometimes attacks the body's own cells. It is likely that other factors, both genetic and environmental, play a role in the variability of the signs and symptoms of complement component 2 deficiency. </s>


Input: Is complement component 2 deficiency inherited ?

Output: This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. </s>


Input: What are the treatments for complement component 2 deficiency ?

Output: These resources address the diagnosis or management of complement component 2 deficiency:  - Genetic Testing Registry: Complement component 2 deficiency  - MedlinePlus Encyclopedia: Complement  - MedlinePlus Encyclopedia: Immunodeficiency Disorders  - Primary Immune Deficiency Treatment Consortium   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) Darier disease ?

Output: Darier disease is a skin condition characterized by wart-like blemishes on the body. The blemishes are usually yellowish in color, hard to the touch, mildly greasy, and can emit a strong odor. The most common sites for blemishes are the scalp, forehead, upper arms, chest, back, knees, elbows, and behind the ear. The mucous membranes can also be affected, with blemishes on the roof of the mouth (palate), tongue, inside of the cheek, gums, and throat. Other features of Darier disease include nail abnormalities, such as red and white streaks in the nails with an irregular texture, and small pits in the palms of the hands and soles of the feet.  The wart-like blemishes characteristic of Darier disease usually appear in late childhood to early adulthood. The severity of the disease varies over time; affected people experience flare-ups alternating with periods when they have fewer blemishes. The appearance of the blemishes is influenced by environmental factors. Most people with Darier disease will develop more blemishes during the summertime when they are exposed to heat and humidity. UV light; minor injury or friction, such as rubbing or scratching; and ingestion of certain medications can also cause an increase in blemishes.  On occasion, people with Darier disease may have neurological disorders such as mild intellectual disability, epilepsy, and depression. Learning and behavior difficulties have also been reported in people with Darier disease. Researchers do not know if these conditions, which are common in the general population, are associated with the genetic changes that cause Darier disease, or if they are coincidental. Some researchers believe that behavioral problems might be linked to the social stigma experienced by people with numerous skin blemishes.  A form of Darier disease known as the linear or segmental form is characterized by blemishes on localized areas of the skin. The blemishes are not as widespread as they are in typical Darier disease. Some people with the linear form of this condition have the nail abnormalities that are seen in people with classic Darier disease, but these abnormalities occur only on one side of the body. </s>


Input: How many people are affected by Darier disease ?

Output: The worldwide prevalence of Darier disease is unknown. The prevalence of Darier disease is estimated to be 1 in 30,000 people in Scotland, 1 in 36,000 people in northern England, and 1 in 100,000 people in Denmark. </s>


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

Output: Mutations in the ATP2A2 gene cause Darier disease. The ATP2A2 gene provides instructions for producing an enzyme abbreviated as SERCA2. This enzyme acts as a pump that helps control the level of positively charged calcium atoms (calcium ions) inside cells, particularly in the endoplasmic reticulum and the sarcoplasmic reticulum. The endoplasmic reticulum is a structure inside the cell that is involved in protein processing and transport. The sarcoplasmic reticulum is a structure in muscle cells that assists with muscle contraction and relaxation by releasing and storing calcium ions. Calcium ions act as signals for a large number of activities that are important for the normal development and function of cells. SERCA2 allows calcium ions to pass into and out of the cell in response to cell signals.  Mutations in the ATP2A2 gene result in insufficient amounts of functional SERCA2 enzyme. A lack of SERCA2 enzyme reduces calcium levels in the endoplasmic reticulum, causing it to become dysfunctional. SERCA2 is expressed throughout the body; it is not clear why changes in this enzyme affect only the skin. Some researchers note that skin cells are the only cell types expressing SERCA2 that do not have a "back-up" enzyme for calcium transport. This dependence on the SERCA2 enzyme may make skin cells particularly vulnerable to changes in this enzyme.  The linear form of Darier disease is caused by ATP2A2 gene mutations that are acquired during a person's lifetime and are present only in certain cells. These changes are called somatic mutations and are not inherited. There have been no known cases of people with the linear form of Darier disease passing it on to their children. </s>


Input: Is Darier disease inherited ?

Output: This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In 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.  The linear form of Darier disease is generally not inherited but arises from mutations in the body's cells that occur after conception. These alterations are called somatic mutations. </s>


Input: What are the treatments for Darier disease ?

Output: These resources address the diagnosis or management of Darier disease:  - Genetic Testing Registry: Keratosis follicularis   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) hereditary myopathy with early respiratory failure ?

Output: Hereditary myopathy with early respiratory failure (HMERF) is an inherited muscle disease that predominantly affects muscles close to the center of the body (proximal muscles) and muscles that are needed for breathing.  The major signs and symptoms of HMERF usually appear in adulthood, on average around age 35. Among the earliest muscles affected in HMERF are the neck flexors, which are muscles at the front of the neck that help hold the head up. Other proximal muscles that become weak in people with HMERF include those of the hips, thighs, and upper arms. Some affected individuals have also reported weakness in muscles of the lower leg and foot called the dorsal foot extensors.  HMERF also causes severe weakness in muscles of the chest that are involved in breathing, particularly the diaphragm. This weakness leads to breathing problems and life-threatening respiratory failure. </s>


Input: How many people are affected by hereditary myopathy with early respiratory failure ?

Output: HMERF is a rare condition. It has been reported in several families of Swedish and French descent, and in at least one individual from Italy. </s>


Input: What are the genetic changes related to hereditary myopathy with early respiratory failure ?

Output: HMERF can be caused by a mutation in the TTN gene. This gene provides instructions for making a protein called titin. Titin plays an important role in muscles the body uses for movement (skeletal muscles) and in heart (cardiac) muscle.  Within muscle cells, titin is an essential component of structures called sarcomeres. Sarcomeres are the basic units of muscle contraction; they are made of proteins that generate the mechanical force needed for muscles to contract. Titin has several functions within sarcomeres. One of its most important jobs is to provide structure, flexibility, and stability to these cell structures. Titin also plays a role in chemical signaling and in assembling new sarcomeres.  The TTN gene mutation responsible for HMERF leads to the production of an altered version of the titin protein. Studies suggest that this change may disrupt titin's interactions with other proteins within sarcomeres and interfere with the protein's role in chemical signaling. Consequently, muscle fibers become damaged and weaken over time. It is unclear why these effects are usually limited to proximal muscles and muscles involved in breathing.  Some people with the characteristic features of HMERF do not have identified mutations in the TTN gene. In these cases, the genetic cause of the condition is unknown. </s>


Input: Is hereditary myopathy with early respiratory failure 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 hereditary myopathy with early respiratory failure ?

Output: These resources address the diagnosis or management of HMERF:  - Gene Review: Gene Review: Hereditary Myopathy with Early Respiratory Failure (HMERF)  - Genetic Testing Registry: Hereditary myopathy with early respiratory failure  - National Heart, Lung, and Blood Institute: How Is Respiratory Failure Diagnosed?  - National Heart, Lung, and Blood Institute: How Is Respiratory Failure Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) cyclic vomiting syndrome ?

Output: Cyclic vomiting syndrome is a disorder that causes recurrent episodes of nausea, vomiting, and tiredness (lethargy). This condition is diagnosed most often in young children, but it can affect people of any age.  The episodes of nausea, vomiting, and lethargy last anywhere from an hour to 10 days. An affected person may vomit several times per hour, potentially leading to a dangerous loss of fluids (dehydration). Additional symptoms can include unusually pale skin (pallor), abdominal pain, diarrhea, headache, fever, and an increased sensitivity to light (photophobia) or to sound (phonophobia). In most affected people, the signs and symptoms of each attack are quite similar. These attacks can be debilitating, making it difficult for an affected person to go to work or school.  Episodes of nausea, vomiting, and lethargy can occur regularly or apparently at random, or can be triggered by a variety of factors. The most common triggers are emotional excitement and infections. Other triggers can include periods without eating (fasting), temperature extremes, lack of sleep, overexertion, allergies, ingesting certain foods or alcohol, and menstruation.  If the condition is not treated, episodes usually occur four to 12 times per year. Between attacks, vomiting is absent, and nausea is either absent or much reduced. However, many affected people experience other symptoms during and between episodes, including pain, lethargy, digestive disorders such as gastroesophageal reflux and irritable bowel syndrome, and fainting spells (syncope). People with cyclic vomiting syndrome are also more likely than people without the disorder to experience depression, anxiety, and panic disorder. It is unclear whether these health conditions are directly related to nausea and vomiting.  Cyclic vomiting syndrome is often considered to be a variant of migraines, which are severe headaches often associated with pain, nausea, vomiting, and extreme sensitivity to light and sound. Cyclic vomiting syndrome is likely the same as or closely related to a condition called abdominal migraine, which is characterized by attacks of stomach pain and cramping. Attacks of nausea, vomiting, or abdominal pain in childhood may be replaced by migraine headaches as an affected person gets older. Many people with cyclic vomiting syndrome or abdominal migraine have a family history of migraines.  Most people with cyclic vomiting syndrome have normal intelligence, although some affected people have developmental delay or intellectual disability. Autism spectrum disorders, which affect communication and social interaction, have also been associated with cyclic vomiting syndrome. Additionally, muscle weakness (myopathy) and seizures are possible. People with any of these additional features are said to have cyclic vomiting syndrome plus. </s>


Input: How many people are affected by cyclic vomiting syndrome ?

Output: The exact prevalence of cyclic vomiting syndrome is unknown; estimates range from 4 to 2,000 per 100,000 children. The condition is diagnosed less frequently in adults, although recent studies suggest that the condition may begin in adulthood as commonly as it begins in childhood. </s>