Input: What are the genetic changes related to pseudocholinesterase deficiency ?

Output: Pseudocholinesterase deficiency can be caused by mutations in the BCHE gene. This gene provides instructions for making the pseudocholinesterase enzyme, also known as butyrylcholinesterase, which is produced by the liver and circulates in the blood. The pseudocholinesterase enzyme is involved in the breakdown of choline ester drugs. It is likely that the enzyme has other functions in the body, but these functions are not well understood. Studies suggest that the enzyme may be involved in the transmission of nerve signals.  Some BCHE gene mutations that cause pseudocholinesterase deficiency result in an abnormal pseudocholinesterase enzyme that does not function properly. Other mutations prevent the production of the pseudocholinesterase enzyme. A lack of functional pseudocholinesterase enzyme impairs the body's ability to break down choline ester drugs efficiently, leading to abnormally prolonged drug effects.  Pseudocholinesterase deficiency can also have nongenetic causes. In these cases, the condition is called acquired pseudocholinesterase deficiency; it is not inherited and cannot be passed to the next generation. Activity of the pseudocholinesterase enzyme can be impaired by kidney or liver disease, malnutrition, major burns, cancer, or certain drugs. </s>


Input: Is pseudocholinesterase deficiency inherited ?

Output: When due to genetic causes, this condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive disorder have one copy of the altered gene in each cell and are called carriers. They can pass on the gene mutation to their children, but they do not usually experience signs and symptoms of the disorder. In some cases, carriers of BCHE gene mutations take longer than usual to clear choline ester drugs from the body, but not as long as those with two copies of the altered gene in each cell. </s>


Input: What are the treatments for pseudocholinesterase deficiency ?

Output: These resources address the diagnosis or management of pseudocholinesterase deficiency:  - MedlinePlus Encyclopedia: Cholinesterase (blood test)   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) Tourette syndrome ?

Output: Tourette syndrome is a complex disorder characterized by repetitive, sudden, and involuntary movements or noises called tics. Tics usually appear in childhood, and their severity varies over time. In most cases, tics become milder and less frequent in late adolescence and adulthood.  Tourette syndrome involves both motor tics, which are uncontrolled body movements, and vocal or phonic tics, which are outbursts of sound. Some motor tics are simple and involve only one muscle group. Simple motor tics, such as rapid eye blinking, shoulder shrugging, or nose twitching, are usually the first signs of Tourette syndrome. Motor tics also can be complex (involving multiple muscle groups), such as jumping, kicking, hopping, or spinning.  Vocal tics, which generally appear later than motor tics, also can be simple or complex. Simple vocal tics include grunting, sniffing, and throat-clearing. More complex vocalizations include repeating the words of others (echolalia) or repeating one's own words (palilalia). The involuntary use of inappropriate or obscene language (coprolalia) is possible, but uncommon, among people with Tourette syndrome.  In addition to frequent tics, people with Tourette syndrome are at risk for associated problems including attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, depression, and problems with sleep. </s>


Input: How many people are affected by Tourette syndrome ?

Output: Although the exact incidence of Tourette syndrome is uncertain, it is estimated to affect 1 to 10 in 1,000 children. This disorder occurs in populations and ethnic groups worldwide, and it is more common in males than in females. </s>


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

Output: A variety of genetic and environmental factors likely play a role in causing Tourette syndrome. Most of these factors are unknown, and researchers are studying risk factors before and after birth that may contribute to this complex disorder. Scientists believe that tics may result from changes in brain chemicals (neurotransmitters) that are responsible for producing and controlling voluntary movements.  Mutations involving the SLITRK1 gene have been identified in a small number of people with Tourette syndrome. This gene provides instructions for making a protein that is active in the brain. The SLITRK1 protein probably plays a role in the development of nerve cells, including the growth of specialized extensions (axons and dendrites) that allow each nerve cell to communicate with nearby cells. It is unclear how mutations in the SLITRK1 gene can lead to this disorder.  Most people with Tourette syndrome do not have a mutation in the SLITRK1 gene. Because mutations have been reported in so few people with this condition, the association of the SLITRK1 gene with this disorder has not been confirmed. Researchers suspect that changes in other genes, which have not been identified, are also associated with Tourette syndrome. </s>


Input: Is Tourette syndrome inherited ?

Output: The inheritance pattern of Tourette syndrome is unclear. Although the features of this condition can cluster in families, many genetic and environmental factors are likely to be involved. Among family members of an affected person, it is difficult to predict who else may be at risk of developing the condition.  Tourette syndrome was previously thought to have an autosomal dominant pattern of inheritance, which suggests that one mutated copy of a gene in each cell would be sufficient to cause the condition. Several decades of research have shown that this is not the case. Almost all cases of Tourette syndrome probably result from a variety of genetic and environmental factors, not changes in a single gene. </s>


Input: What are the treatments for Tourette syndrome ?

Output: These resources address the diagnosis or management of Tourette syndrome:  - Gene Review: Gene Review: Tourette Disorder Overview  - Genetic Testing Registry: Tourette Syndrome  - MedlinePlus Encyclopedia: Gilles de la Tourette 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) fibrodysplasia ossificans progressiva ?

Output: Fibrodysplasia ossificans progressiva (FOP) is a disorder in which muscle tissue and connective tissue such as tendons and ligaments are gradually replaced by bone (ossified), forming bone outside the skeleton (extra-skeletal or heterotopic bone) that constrains movement. This process generally becomes noticeable in early childhood, starting with the neck and shoulders and proceeding down the body and into the limbs.  Extra-skeletal bone formation causes progressive loss of mobility as the joints become affected. Inability to fully open the mouth may cause difficulty in speaking and eating. Over time, people with this disorder may experience malnutrition due to their eating problems. They may also have breathing difficulties as a result of extra bone formation around the rib cage that restricts expansion of the lungs.  Any trauma to the muscles of an individual with fibrodysplasia ossificans progressiva, such as a fall or invasive medical procedures, may trigger episodes of muscle swelling and inflammation (myositis) followed by more rapid ossification in the injured area. Flare-ups may also be caused by viral illnesses such as influenza.  People with fibrodysplasia ossificans progressiva are generally born with malformed big toes. This abnormality of the big toes is a characteristic feature that helps to distinguish this disorder from other bone and muscle problems. Affected individuals may also have short thumbs and other skeletal abnormalities. </s>


Input: How many people are affected by fibrodysplasia ossificans progressiva ?

Output: Fibrodysplasia ossificans progressiva is a very rare disorder, believed to occur in approximately 1 in 2 million people worldwide. Several hundred cases have been reported. </s>


Input: What are the genetic changes related to fibrodysplasia ossificans progressiva ?

Output: Mutations in the ACVR1 gene cause fibrodysplasia ossificans progressiva.  The ACVR1 gene provides instructions for producing a member of a protein family called bone morphogenetic protein (BMP) type I receptors. The ACVR1 protein is found in many tissues of the body including skeletal muscle and cartilage. It helps to control the growth and development of the bones and muscles, including the gradual replacement of cartilage by bone (ossification) that occurs in normal skeletal maturation from birth to young adulthood.  Researchers believe that a mutation in the ACVR1 gene may change the shape of the receptor under certain conditions and disrupt mechanisms that control the receptor's activity. As a result, the receptor may be constantly turned on (constitutive activation). Constitutive activation of the receptor causes overgrowth of bone and cartilage and fusion of joints, resulting in the signs and symptoms of fibrodysplasia ossificans progressiva. </s>


Input: Is fibrodysplasia ossificans progressiva 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.  Most cases of fibrodysplasia ossificans progressiva result from new mutations in the gene. These cases occur in people with no history of the disorder in their family. In a small number of cases, an affected person has inherited the mutation from one affected parent. </s>


Input: What are the treatments for fibrodysplasia ossificans progressiva ?

Output: These resources address the diagnosis or management of fibrodysplasia ossificans progressiva:  - Genetic Testing Registry: Progressive myositis ossificans   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) adenosine monophosphate deaminase deficiency ?

Output: Adenosine monophosphate (AMP) deaminase deficiency is a condition that can affect the muscles used for movement (skeletal muscles). People with this condition do not make enough of an enzyme called AMP deaminase. In most people, AMP deaminase deficiency does not cause any symptoms. People who do experience symptoms typically have muscle pain (myalgia) or weakness after exercise or prolonged physical activity. They often get tired more quickly and stay tired longer than would normally be expected. Some affected individuals have more severe symptoms, but it is unclear whether these symptoms are due solely to a lack of AMP deaminase or additional factors. Muscle weakness is typically apparent beginning in childhood or early adulthood.  Researchers have proposed three types of AMP deaminase deficiency, which are distinguished by their symptoms and genetic cause. </s>


Input: How many people are affected by adenosine monophosphate deaminase deficiency ?

Output: AMP deaminase deficiency is one of the most common inherited muscle disorders in white populations, affecting 1 in 50 to 100 people. The prevalence is lower in African Americans, affecting an estimated 1 in 40,000 people, and the condition is even less common in the Japanese population. </s>


Input: What are the genetic changes related to adenosine monophosphate deaminase deficiency ?

Output: Mutations in the AMPD1 gene cause AMP deaminase deficiency. The AMPD1 gene provides instructions for producing an enzyme called AMP deaminase. This enzyme is found in skeletal muscle, where it plays a role in producing energy within muscle cells. Mutations in the AMPD1 gene disrupt the function of AMP deaminase and impair the muscle cells' ability to produce energy. This lack of energy can lead to myalgia or other muscle problems associated with AMP deaminase deficiency.  The three types of AMP deaminase deficiency are known as the inherited type, acquired type, and coincidental inherited type.  Individuals with the inherited type have a mutation in both copies of the AMPD1 gene in each cell. Most people are asymptomatic, meaning they have no symptoms. Some people with AMP deaminase deficiency experience muscle weakness or pain following exercise.  The acquired type occurs in people who have decreased levels of AMP deaminase due to the presence of a muscle or joint condition.  People with the coincidental inherited type have a mutation in both copies of the AMPD1 gene. Additionally, they have a separate joint or muscle disorder. Some individuals experience more severe joint or muscle symptoms related to their disorder if they have AMP deaminase deficiency than do people without this enzyme deficiency. Most, however, do not have any symptoms associated with AMP deaminase deficiency.  It is not known why most people with this condition do not experience symptoms. Researchers speculate that additional mutations in other genes may be involved. </s>


Input: Is adenosine monophosphate deaminase 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 adenosine monophosphate deaminase deficiency ?

Output: These resources address the diagnosis or management of adenosine monophosphate deaminase deficiency:  - MedlinePlus Encyclopedia: Muscle aches  - MedlinePlus Encyclopedia: Weakness   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) Snyder-Robinson syndrome ?

Output: Snyder-Robinson syndrome is a condition characterized by intellectual disability, muscle and bone abnormalities, and other problems with development. It occurs exclusively in males.  Males with Snyder-Robinson syndrome have delayed development and intellectual disability beginning in early childhood. The intellectual disability can range from mild to profound. Speech often develops late, and speech difficulties are common. Some affected individuals never develop any speech.  Most affected males are thin and have low muscle mass, a body type described as an asthenic habitus. Weakness or "floppiness" (hypotonia) typically becomes apparent in infancy, and the loss of muscle tissue continues with age. People with this condition often have difficulty walking; most have an unsteady gait.  Snyder-Robinson syndrome causes skeletal problems, particularly thinning of the bones (osteoporosis) that starts in early childhood. Osteoporosis causes the bones to be brittle and to break easily, often during normal activities. In people with Snyder-Robinson syndrome, broken bones occur most often in the arms and legs. Most affected individuals also develop an abnormal side-to-side and back-to-front curvature of the spine (scoliosis and kyphosis, often called kyphoscoliosis when they occur together). Affected individuals tend to be shorter than their peers and others in their family.  Snyder-Robinson syndrome is associated with distinctive facial features, including a prominent lower lip; a high, narrow roof of the mouth or an opening in the roof of the mouth (a cleft palate); and differences in the size and shape of the right and left sides of the face (facial asymmetry). Other signs and symptoms that have been reported include seizures that begin in childhood and abnormalities of the genitalia and kidneys. </s>


Input: How many people are affected by Snyder-Robinson syndrome ?

Output: Snyder-Robinson syndrome is a rare condition; its prevalence is unknown. About 10 affected families have been identified worldwide. </s>


Input: What are the genetic changes related to Snyder-Robinson syndrome ?

Output: Snyder-Robinson syndrome results from mutations in the SMS gene. This gene provides instructions for making an enzyme called spermine synthase. This enzyme is involved in the production of spermine, which is a type of small molecule called a polyamine. Polyamines have many critical functions within cells. Studies suggest that these molecules play roles in cell growth and division, the production of new proteins, the repair of damaged tissues, the function of molecules called ion channels, and the controlled self-destruction of cells (apoptosis). Polyamines appear to be necessary for normal development and function of the brain and other parts of the body.  Mutations in the SMS gene greatly reduce or eliminate the activity of spermine synthase, which decreases the amount of spermine in cells. A shortage of this polyamine clearly impacts normal development, including the development of the brain, muscles, and bones, but it is unknown how it leads to the specific signs and symptoms of Snyder-Robinson syndrome. </s>


Input: Is Snyder-Robinson syndrome 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 would have to occur in both copies of the gene to cause the disorder. No cases of Snyder-Robinson syndrome in females have been reported. </s>


Input: What are the treatments for Snyder-Robinson syndrome ?

Output: These resources address the diagnosis or management of Snyder-Robinson syndrome:  - Gene Review: Gene Review: Snyder-Robinson Syndrome  - Genetic Testing Registry: Snyder Robinson 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) thrombotic thrombocytopenic purpura ?

Output: Thrombotic thrombocytopenic purpura is a rare disorder that causes blood clots (thrombi) to form in small blood vessels throughout the body. These clots can cause serious medical problems if they block vessels and restrict blood flow to organs such as the brain, kidneys, and heart. Resulting complications can include neurological problems (such as personality changes, headaches, confusion, and slurred speech), fever, abnormal kidney function, abdominal pain, and heart problems.  Blood clots normally form to prevent excess blood loss at the site of an injury. In people with thrombotic thrombocytopenic purpura, clots develop in blood vessels even in the absence of injury. Blood clots are formed from clumps of cell fragments called platelets, which circulate in the blood and assist with clotting. Because a large number of platelets are used to make clots in people with thrombotic thrombocytopenic purpura, fewer platelets are available in the bloodstream. A reduced level of circulating platelets is known as thrombocytopenia. Thrombocytopenia can lead to small areas of bleeding just under the surface of the skin, resulting in purplish spots called purpura.  This disorder also causes red blood cells to break down (undergo hemolysis) prematurely. As blood squeezes past clots within blood vessels, red blood cells can break apart. A condition called hemolytic anemia occurs when red blood cells are destroyed faster than the body can replace them. This type of anemia leads to paleness, yellowing of the eyes and skin (jaundice), fatigue, shortness of breath, and a rapid heart rate.  There are two major forms of thrombotic thrombocytopenic purpura, an acquired (noninherited) form and a familial form. The acquired form usually appears in late childhood or adulthood. Affected individuals may have a single episode of signs and symptoms, or they may recur over time. The familial form of this disorder is much rarer and typically appears in infancy or early childhood. In people with the familial form, signs and symptoms often recur on a regular basis. </s>


Input: How many people are affected by thrombotic thrombocytopenic purpura ?

Output: The precise incidence of thrombotic thrombocytopenic purpura is unknown. Researchers estimate that, depending on geographic location, the condition affects 1.7 to 11 per million people each year in the United States. For unknown reasons, the disorder occurs more frequently in women than in men. The acquired form of thrombotic thrombocytopenic purpura is much more common than the familial form. </s>


Input: What are the genetic changes related to thrombotic thrombocytopenic purpura ?

Output: Mutations in the ADAMTS13 gene cause the familial form of thrombotic thrombocytopenic purpura. The ADAMTS13 gene provides instructions for making an enzyme that is involved in the normal process of blood clotting. Mutations in this gene lead to a severe reduction in the activity of this enzyme. The acquired form of thrombotic thrombocytopenic purpura also results from a reduction in ADAMTS13 enzyme activity; however, people with the acquired form do not have mutations in the ADAMTS13 gene. Instead, their immune systems often produce specific proteins called autoantibodies that block the activity of the enzyme.  A lack of ADAMTS13 enzyme activity disrupts the usual balance between bleeding and clotting. Normally, blood clots form at the site of an injury to seal off damaged blood vessels and prevent excess blood loss. In people with thrombotic thrombocytopenic purpura, clots form throughout the body as platelets bind together abnormally and stick to the walls of blood vessels. These clots can block small blood vessels, causing organ damage and the other features of thrombotic thrombocytopenic purpura.  Researchers believe that other genetic or environmental factors may contribute to the signs and symptoms of thrombotic thrombocytopenic purpura. In people with reduced ADAMTS13 enzyme activity, factors such as pregnancy, surgery, and infection may trigger abnormal blood clotting and its associated complications. </s>


Input: Is thrombotic thrombocytopenic purpura inherited ?

Output: The familial form of thrombotic thrombocytopenic purpura 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.  The acquired form of thrombotic thrombocytopenic purpura is not inherited. </s>


Input: What are the treatments for thrombotic thrombocytopenic purpura ?

Output: These resources address the diagnosis or management of thrombotic thrombocytopenic purpura:  - Genetic Testing Registry: Upshaw-Schulman syndrome  - MedlinePlus Encyclopedia: Blood Clots  - MedlinePlus Encyclopedia: Hemolytic anemia  - MedlinePlus Encyclopedia: Purpura  - MedlinePlus Encyclopedia: Thrombocytopenia  - MedlinePlus Encyclopedia: Thrombotic thrombocytopenic purpura   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) autosomal dominant hypocalcemia ?

Output: Autosomal dominant hypocalcemia is characterized by low levels of calcium in the blood (hypocalcemia). Affected individuals can have an imbalance of other molecules in the blood as well, including too much phosphate (hyperphosphatemia) or too little magnesium (hypomagnesemia). Some people with autosomal dominant hypocalcemia also have low levels of a hormone called parathyroid hormone (hypoparathyroidism). This hormone is involved in the regulation of calcium levels in the blood. Abnormal levels of calcium and other molecules in the body can lead to a variety of signs and symptoms, although about half of affected individuals have no associated health problems.  The most common features of autosomal dominant hypocalcemia include muscle spasms in the hands and feet (carpopedal spasms) and muscle cramping, prickling or tingling sensations (paresthesias), or twitching of the nerves and muscles (neuromuscular irritability) in various parts of the body. More severely affected individuals develop seizures, usually in infancy or childhood. Sometimes, these symptoms occur only during episodes of illness or fever.  Some people with autosomal dominant hypocalcemia have high levels of calcium in their urine (hypercalciuria), which can lead to deposits of calcium in the kidneys (nephrocalcinosis) or the formation of kidney stones (nephrolithiasis). These conditions can damage the kidneys and impair their function. Sometimes, abnormal deposits of calcium form in the brain, typically in structures called basal ganglia, which help control movement.  A small percentage of severely affected individuals have features of a kidney disorder called Bartter syndrome in addition to hypocalcemia. These features can include a shortage of potassium (hypokalemia) and magnesium and a buildup of the hormone aldosterone (hyperaldosteronism) in the blood. The abnormal balance of molecules can raise the pH of the blood, which is known as metabolic alkalosis. The combination of features of these two conditions is sometimes referred to as autosomal dominant hypocalcemia with Bartter syndrome or Bartter syndrome type V.  There are two types of autosomal dominant hypocalcemia distinguished by their genetic cause. The signs and symptoms of the two types are generally the same. </s>


Input: How many people are affected by autosomal dominant hypocalcemia ?

Output: The prevalence of autosomal dominant hypocalcemia is unknown. The condition is likely underdiagnosed because it often causes no signs or symptoms. </s>


Input: What are the genetic changes related to autosomal dominant hypocalcemia ?

Output: Autosomal dominant hypocalcemia is primarily caused by mutations in the CASR gene; these cases are known as type 1. A small percentage of cases, known as type 2, are caused by mutations in the GNA11 gene. The proteins produced from these genes work together to regulate the amount of calcium in the blood.  The CASR gene provides instructions for making a protein called the calcium-sensing receptor (CaSR). Calcium molecules attach (bind) to the CaSR protein, which allows this protein to monitor and regulate the amount of calcium in the blood. G11, which is produced from the GNA11 gene, is one component of a signaling protein that works in conjunction with CaSR. When a certain concentration of calcium is reached, CaSR stimulates G11 to send signals to block processes that increase the amount of calcium in the blood.  Mutations in the CASR or GNA11 gene lead to overactivity of the respective protein. The altered CaSR protein is more sensitive to calcium, meaning even low levels of calcium can trigger it to stimulate G11 signaling. Similarly, the altered G11 protein continues to send signals to prevent calcium increases, even when levels in the blood are very low. As a result, calcium levels in the blood remain low, causing hypocalcemia. Calcium plays an important role in the control of muscle movement, and a shortage of this molecule can lead to cramping or twitching of the muscles. Impairment of the processes that increase calcium can also disrupt the normal regulation of other molecules, such as phosphate and magnesium, leading to other signs of autosomal dominant hypocalcemia. Studies show that the lower the amount of calcium in the blood, the more severe the symptoms of the condition are. </s>


Input: Is autosomal dominant hypocalcemia inherited ?

Output: This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In most cases, an affected person inherits the mutation from one affected parent. A small number of 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 autosomal dominant hypocalcemia ?

Output: These resources address the diagnosis or management of autosomal dominant hypocalcemia:  - Genetic Testing Registry: Autosomal dominant hypocalcemia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) progressive supranuclear palsy ?

Output: Progressive supranuclear palsy is a brain disorder that affects movement, vision, speech, and thinking ability (cognition). The signs and symptoms of this disorder usually become apparent in mid- to late adulthood, most often in a person's 60s. Most people with progressive supranuclear palsy survive 5 to 9 years after the disease first appears, although a few affected individuals have lived for more than a decade.  Loss of balance and frequent falls are the most common early signs of progressive supranuclear palsy. Affected individuals have problems with walking, including poor coordination and an unsteady, lurching gait. Other movement abnormalities develop as the disease progresses, including unusually slow movements (bradykinesia), clumsiness, and stiffness of the trunk muscles. These problems worsen with time, and most affected people ultimately require wheelchair assistance.  Progressive supranuclear palsy is also characterized by abnormal eye movements, which typically develop several years after the other movement problems first appear. Restricted up-and-down eye movement (vertical gaze palsy) is a hallmark of this disease. Other eye movement problems include difficulty opening and closing the eyelids, infrequent blinking, and pulling back (retraction) of the eyelids. These abnormalities can lead to blurred vision, an increased sensitivity to light (photophobia), and a staring gaze.  Additional features of progressive supranuclear palsy include slow and slurred speech (dysarthria) and trouble swallowing (dysphagia). Most affected individuals also experience changes in personality and behavior, such as a general loss of interest and enthusiasm (apathy). They develop problems with cognition, including difficulties with attention, planning, and problem solving. As the cognitive and behavioral problems worsen, affected individuals increasingly require help with personal care and other activities of daily living. </s>


Input: How many people are affected by progressive supranuclear palsy ?

Output: The exact prevalence of progressive supranuclear palsy is unknown. It may affect about 6 in 100,000 people worldwide. </s>


Input: What are the genetic changes related to progressive supranuclear palsy ?

Output: In most cases, the genetic cause of progressive supranuclear palsy is unknown. Rarely, the disease results from mutations in the MAPT gene. Certain normal variations (polymorphisms) in the MAPT gene have also been associated with an increased risk of developing progressive supranuclear palsy.  The MAPT gene provides instructions for making a protein called tau. This protein is found throughout the nervous system, including in nerve cells (neurons) in the brain. It is involved in assembling and stabilizing microtubules, which are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). Microtubules help cells maintain their shape, assist in the process of cell division, and are essential for the transport of materials within cells.  The signs and symptoms of progressive supranuclear palsy appear to be related to abnormalities in the tau protein. In people with MAPT gene mutations, genetic changes disrupt the protein's normal structure and function. However, abnormal tau is also found in affected individuals without MAPT gene mutations. The defective tau protein assembles into abnormal clumps within neurons and other brain cells, although it is unclear what effect these clumps have on cell function and survival. Progressive supranuclear palsy is characterized by the gradual death of brain cells, particularly in structures deep within the brain that are essential for coordinating movement. This loss of brain cells underlies the movement abnormalities and other features of progressive supranuclear palsy.  This condition is one of several related diseases known as tauopathies, which are characterized by an abnormal buildup of tau in the brain.  Researchers suspect that other genetic and environmental factors also contribute to progressive supranuclear palsy. For example, the disease has been linked to genetic changes on chromosome 1 and chromosome 11. However, the specific genes involved have not been identified. </s>


Input: Is progressive supranuclear palsy inherited ?

Output: Most cases of progressive supranuclear palsy are sporadic, which means they occur in people with no history of the disorder in their family. However, some people with this disorder have had family members with related conditions, such as parkinsonism and a loss of intellectual functions (dementia).  When progressive supranuclear palsy runs in families, it can have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of an altered gene in each cell is sufficient to cause the disorder. </s>


Input: What are the treatments for progressive supranuclear palsy ?

Output: These resources address the diagnosis or management of progressive supranuclear palsy:  - Gene Review: Gene Review: MAPT-Related Disorders  - Genetic Testing Registry: Progressive supranuclear ophthalmoplegia  - NHS Choices (UK): Diagnosis of Progressive Supranuclear Palsy  - NHS Choices (UK): Treatment of Progressive Supranuclear Palsy  - Partners in Parkinson's: Movement Disorder Specialist Finder  - University of California, San Francisco (UCSF) Memory and Aging Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) X-linked infantile nystagmus ?

Output: X-linked infantile nystagmus is a condition characterized by abnormal eye movements. Nystagmus is a term that refers to involuntary side-to-side movements of the eyes. In people with this condition, nystagmus is present at birth or develops within the first six months of life. The abnormal eye movements may worsen when an affected person is feeling anxious or tries to stare directly at an object. The severity of nystagmus varies, even among affected individuals within the same family. Sometimes, affected individuals will turn or tilt their head to compensate for the irregular eye movements. </s>


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

Output: The incidence of all forms of infantile nystagmus is estimated to be 1 in 5,000 newborns; however, the precise incidence of X-linked infantile nystagmus is unknown. </s>


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

Output: Mutations in the FRMD7 gene cause X-linked infantile nystagmus. The FRMD7 gene provides instructions for making a protein whose exact function is unknown. This protein is found mostly in areas of the brain that control eye movement and in the light-sensitive tissue at the back of the eye (retina). Research suggests that FRMD7 gene mutations cause nystagmus by disrupting the development of certain nerve cells in the brain and retina.  In some people with X-linked infantile nystagmus, no mutation in the FRMD7 gene has been found. The genetic cause of the disorder is unknown in these individuals. Researchers believe that mutations in at least one other gene, which has not been identified, can cause this disorder. </s>


Input: Is X-linked infantile nystagmus inherited ?

Output: This condition is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two copies of the X chromosome), one altered copy of the gene in each cell can cause the condition, although affected females may experience less severe symptoms than affected males. Approximately half of the females with only one altered copy of the FRMD7 gene in each cell have no symptoms of this condition. </s>


Input: What are the treatments for X-linked infantile nystagmus ?

Output: These resources address the diagnosis or management of X-linked infantile nystagmus:  - Gene Review: Gene Review: FRMD7-Related Infantile Nystagmus  - Genetic Testing Registry: Infantile nystagmus, X-linked  - MedlinePlus Encyclopedia: Nystagmus   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) combined malonic and methylmalonic aciduria ?

Output: Combined malonic and methylmalonic aciduria (CMAMMA) is a condition characterized by high levels of certain chemicals, known as malonic acid and methylmalonic acid, in the body. A distinguishing feature of this condition is higher levels of methylmalonic acid than malonic acid in the urine, although both are elevated.  The signs and symptoms of CMAMMA can begin in childhood. In some children, the buildup of acids causes the blood to become too acidic (ketoacidosis), which can damage the body's tissues and organs. Other signs and symptoms may include involuntary muscle tensing (dystonia), weak muscle tone (hypotonia), developmental delay, an inability to grow and gain weight at the expected rate (failure to thrive), low blood sugar (hypoglycemia), and coma. Some affected children have an unusually small head size (microcephaly).  Other people with CMAMMA do not develop signs and symptoms until adulthood. These individuals usually have neurological problems, such as seizures, loss of memory, a decline in thinking ability, or psychiatric diseases. </s>


Input: How many people are affected by combined malonic and methylmalonic aciduria ?

Output: CMAMMA appears to be a rare disease. Approximately a dozen cases have been reported in the scientific literature. </s>


Input: What are the genetic changes related to combined malonic and methylmalonic aciduria ?

Output: Mutations in the ACSF3 gene cause CMAMMA. This gene provides instructions for making an enzyme that plays a role in the formation (synthesis) of fatty acids. Fatty acids are building blocks used to make fats (lipids). The ACSF3 enzyme performs a chemical reaction that converts malonic acid to malonyl-CoA, which is the first step of fatty acid synthesis in cellular structures called mitochondria. Based on this activity, the enzyme is classified as a malonyl-CoA synthetase. The ACSF3 enzyme also converts methylmalonic acid to methylmalonyl-CoA, making it a methylmalonyl-CoA synthetase as well.  The effects of ACSF3 gene mutations are unknown. Researchers suspect that the mutations lead to altered enzymes that have little or no function. Because the enzyme cannot convert malonic and methylmalonic acids, they build up in the body. Damage to organs and tissues caused by accumulation of these acids may be responsible for the signs and symptoms of CMAMMA, although the mechanisms are unclear. </s>


Input: Is combined malonic and methylmalonic aciduria 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 combined malonic and methylmalonic aciduria ?

Output: These resources address the diagnosis or management of CMAMMA:  - Genetic Testing Registry: Combined malonic and methylmalonic aciduria  - Organic Acidemia Association: What are Organic Acidemias?   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 fructose intolerance ?

Output: Hereditary fructose intolerance is a condition that affects a person's ability to digest the sugar fructose. Fructose is a simple sugar found primarily in fruits. Affected individuals develop signs and symptoms of the disorder in infancy when fruits, juices, or other foods containing fructose are introduced into the diet. After ingesting fructose, individuals with hereditary fructose intolerance may experience nausea, bloating, abdominal pain, diarrhea, vomiting, and low blood sugar (hypoglycemia). Affected infants may fail to grow and gain weight at the expected rate (failure to thrive).  Repeated ingestion of fructose-containing foods can lead to liver and kidney damage. The liver damage can result in a yellowing of the skin and whites of the eyes (jaundice), an enlarged liver (hepatomegaly), and chronic liver disease (cirrhosis). Continued exposure to fructose may result in seizures, coma, and ultimately death from liver and kidney failure. Due to the severity of symptoms experienced when fructose is ingested, most people with hereditary fructose intolerance develop a dislike for fruits, juices, and other foods containing fructose.  Hereditary fructose intolerance should not be confused with a condition called fructose malabsorption. In people with fructose malabsorption, the cells of the intestine cannot absorb fructose normally, leading to bloating, diarrhea or constipation, flatulence, and stomach pain. Fructose malabsorption is thought to affect approximately 40 percent of individuals in the Western hemisphere; its cause is unknown. </s>


Input: How many people are affected by hereditary fructose intolerance ?

Output: The incidence of hereditary fructose intolerance is estimated to be 1 in 20,000 to 30,000 individuals each year worldwide. </s>


Input: What are the genetic changes related to hereditary fructose intolerance ?

Output: Mutations in the ALDOB gene cause hereditary fructose intolerance. The ALDOB gene provides instructions for making the aldolase B enzyme. This enzyme is found primarily in the liver and is involved in the breakdown (metabolism) of fructose so this sugar can be used as energy. Aldolase B is responsible for the second step in the metabolism of fructose, which breaks down the molecule fructose-1-phosphate into other molecules called glyceraldehyde and dihydroxyacetone phosphate.  ALDOB gene mutations reduce the function of the enzyme, impairing its ability to metabolize fructose. A lack of functional aldolase B results in an accumulation of fructose-1-phosphate in liver cells. This buildup is toxic, resulting in the death of liver cells over time. Additionally, the breakdown products of fructose-1-phosphase are needed in the body to produce energy and to maintain blood sugar levels. The combination of decreased cellular energy, low blood sugar, and liver cell death leads to the features of hereditary fructose intolerance. </s>


Input: Is hereditary fructose intolerance inherited ?

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


Input: What are the treatments for hereditary fructose intolerance ?

Output: These resources address the diagnosis or management of hereditary fructose intolerance:  - Boston University: Specifics of Hereditary Fructose Intolerance and Its Diagnosis  - Gene Review: Gene Review: Hereditary Fructose Intolerance  - Genetic Testing Registry: Hereditary fructosuria  - MedlinePlus Encyclopedia: Hereditary Fructose Intolerance   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) Greig cephalopolysyndactyly syndrome ?

Output: Greig cephalopolysyndactyly syndrome is a disorder that affects development of the limbs, head, and face. The features of this syndrome are highly variable, ranging from very mild to severe. People with this condition typically have one or more extra fingers or toes (polydactyly) or an abnormally wide thumb or big toe (hallux). The skin between the fingers and toes may be fused (cutaneous syndactyly). This disorder is also characterized by widely spaced eyes (ocular hypertelorism), an abnormally large head size (macrocephaly), and a high, prominent forehead. Rarely, affected individuals may have more serious medical problems including seizures, developmental delay, and intellectual disability. </s>


Input: How many people are affected by Greig cephalopolysyndactyly syndrome ?

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


Input: What are the genetic changes related to Greig cephalopolysyndactyly syndrome ?

Output: Mutations in the GLI3 gene cause Greig cephalopolysyndactyly 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.  Different genetic changes involving the GLI3 gene can cause Greig cephalopolysyndactyly syndrome. In some cases, the condition results from a chromosomal abnormalitysuch as a large deletion or rearrangement of genetic materialin the region of chromosome 7 that contains the GLI3 gene. In other cases, a mutation in the GLI3 gene itself is responsible for the disorder. Each of these genetic changes prevents one copy of the gene in each cell from producing any functional protein. It remains unclear how a reduced amount of this protein disrupts early development and causes the characteristic features of Greig cephalopolysyndactyly syndrome. </s>


Input: Is Greig cephalopolysyndactyly syndrome inherited ?

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


Input: What are the treatments for Greig cephalopolysyndactyly syndrome ?

Output: These resources address the diagnosis or management of Greig cephalopolysyndactyly syndrome:  - Gene Review: Gene Review: Greig Cephalopolysyndactyly Syndrome  - Genetic Testing Registry: Greig cephalopolysyndactyly syndrome  - MedlinePlus Encyclopedia: Polydactyly  - MedlinePlus Encyclopedia: Syndactyly (image)   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) D-bifunctional protein deficiency ?

Output: D-bifunctional protein deficiency is a disorder that causes deterioration of nervous system functions (neurodegeneration) beginning in infancy. Newborns with D-bifunctional protein deficiency have weak muscle tone (hypotonia) and seizures. Most babies with this condition never acquire any developmental skills. Some may reach very early developmental milestones such as the ability to follow movement with their eyes or control their head movement, but they experience a gradual loss of these skills (developmental regression) within a few months. As the condition gets worse, affected children develop exaggerated reflexes (hyperreflexia), increased muscle tone (hypertonia), more severe and recurrent seizures (epilepsy), and loss of vision and hearing. Most children with D-bifunctional protein deficiency do not survive past the age of 2. A small number of individuals with this disorder are somewhat less severely affected. They may acquire additional basic skills, such as voluntary hand movements or unsupported sitting, before experiencing developmental regression, and they may survive longer into childhood than more severely affected individuals.  Individuals with D-bifunctional protein deficiency may have unusual facial features, including a high forehead, widely spaced eyes (hypertelorism), a lengthened area between the nose and mouth (philtrum), and a high arch of the hard palate at the roof of the mouth. Affected infants may also have an unusually large space between the bones of the skull (fontanel). An enlarged liver (hepatomegaly) occurs in about half of affected individuals. Because these features are similar to those of another disorder called Zellweger syndrome (part of a group of disorders called the Zellweger spectrum), D-bifunctional protein deficiency is sometimes called pseudo-Zellweger syndrome. </s>


Input: How many people are affected by D-bifunctional protein deficiency ?

Output: D-bifunctional protein deficiency is estimated to affect 1 in 100,000 newborns. </s>


Input: What are the genetic changes related to D-bifunctional protein deficiency ?

Output: D-bifunctional protein deficiency is caused by mutations in the HSD17B4 gene. The protein produced from this gene (D-bifunctional protein) is an enzyme, which means that it helps specific biochemical reactions to take place. The D-bifunctional protein is found in sac-like cell structures (organelles) called peroxisomes, which contain a variety of enzymes that break down many different substances. The D-bifunctional protein is involved in the breakdown of certain molecules called fatty acids. The protein has two separate regions (domains) with enzyme activity, called the hydratase and dehydrogenase domains. These domains help carry out the second and third steps, respectively, of a process called the peroxisomal fatty acid beta-oxidation pathway. This process shortens the fatty acid molecules by two carbon atoms at a time until the fatty acids are converted to a molecule called acetyl-CoA, which is transported out of the peroxisomes for reuse by the cell.  HSD17B4 gene mutations that cause D-bifunctional protein deficiency can affect one or both of the protein's functions; however, this distinction does not seem to affect the severity or features of the disorder. Impairment of one or both of the protein's enzymatic activities prevents the D-bifunctional protein from breaking down fatty acids efficiently. As a result, these fatty acids accumulate in the body. It is unclear how fatty acid accumulation leads to the specific neurological and non-neurological features of D-bifunctional protein deficiency. However, the accumulation may result in abnormal development of the brain and the breakdown of myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. Destruction of myelin leads to a loss of myelin-containing tissue (white matter) in the brain and spinal cord; loss of white matter is described as leukodystrophy. Abnormal brain development and leukodystrophy likely underlie the neurological abnormalities that occur in D-bifunctional protein deficiency. </s>


Input: Is D-bifunctional protein 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 D-bifunctional protein deficiency ?

Output: These resources address the diagnosis or management of D-bifunctional protein deficiency:  - Gene Review: Gene Review: Leukodystrophy Overview  - Genetic Testing Registry: Bifunctional peroxisomal enzyme deficiency   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) ornithine translocase deficiency ?

Output: Ornithine translocase deficiency is an inherited disorder that causes ammonia to accumulate in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.  Ornithine translocase deficiency varies widely in its severity and age of onset. An infant with ornithine translocase deficiency may be lacking in energy (lethargic) or refuse to eat, or have poorly controlled breathing or body temperature. Some babies with this disorder may experience seizures or unusual body movements, or go into a coma. Episodes of illness may coincide with the introduction of high-protein formulas or solid foods into the diet.  In most affected individuals, signs and symptoms of ornithine translocase deficiency do not appear until later in life. Later-onset forms of ornithine translocase deficiency are usually less severe than the infantile form. Some people with later-onset ornithine translocase deficiency cannot tolerate high-protein foods, such as meat. Occasionally, high-protein meals or stress caused by illness or periods without food (fasting) may cause ammonia to accumulate more quickly in the blood. This rapid increase of ammonia may lead to episodes of vomiting, lack of energy (lethargy), problems with coordination (ataxia), confusion, or blurred vision. Complications of ornithine translocase deficiency may include developmental delay, learning disabilities, and stiffness caused by abnormal tensing of the muscles (spasticity). </s>


Input: How many people are affected by ornithine translocase deficiency ?

Output: Ornithine translocase deficiency is a very rare disorder. Fewer than 100 affected individuals have been reported worldwide. </s>


Input: What are the genetic changes related to ornithine translocase deficiency ?

Output: Mutations in the SLC25A15 gene cause ornithine translocase deficiency.  Ornithine translocase deficiency belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions that occurs in liver cells. This cycle processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys.  The SLC25A15 gene provides instructions for making a protein called a mitochondrial ornithine transporter. This protein is needed to move a molecule called ornithine within the mitochondria (the energy-producing centers in cells). Specifically, this protein transports ornithine across the inner membrane of mitochondria to the region called the mitochondrial matrix, where it participates in the urea cycle.  Mutations in the SLC25A15 gene result in a mitochondrial ornithine transporter that is unstable or the wrong shape, and which cannot bring ornithine to the mitochondrial matrix. This failure of ornithine transport causes an interruption of the urea cycle and the accumulation of ammonia, resulting in the signs and symptoms of ornithine translocase deficiency. </s>


Input: Is ornithine translocase 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 ornithine translocase deficiency ?

Output: These resources address the diagnosis or management of ornithine translocase deficiency:  - Baby's First Test  - Gene Review: Gene Review: Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome  - Gene Review: Gene Review: Urea Cycle Disorders Overview  - Genetic Testing Registry: Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome  - MedlinePlus Encyclopedia: Hereditary urea cycle abnormality   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 lymphoproliferative disease ?

Output: X-linked lymphoproliferative disease (XLP) is a disorder of the immune system and blood-forming cells that is found almost exclusively in males. More than half of individuals with this disorder experience an exaggerated immune response to the Epstein-Barr virus (EBV). EBV is a very common virus that eventually infects most humans. In some people it causes infectious mononucleosis (commonly known as "mono"). Normally, after initial infection, EBV remains in certain immune system cells (lymphocytes) called B cells. However, the virus is generally inactive (latent) because it is controlled by other lymphocytes called T cells that specifically target EBV-infected B cells.  People with XLP may respond to EBV infection by producing abnormally large numbers of T cells, B cells, and other lymphocytes called macrophages. This proliferation of immune cells often causes a life-threatening reaction called hemophagocytic lymphohistiocytosis. Hemophagocytic lymphohistiocytosis causes fever, destroys blood-producing cells in the bone marrow, and damages the liver. The spleen, heart, kidneys, and other organs and tissues may also be affected. In some individuals with XLP, hemophagocytic lymphohistiocytosis or related symptoms may occur without EBV infection.  About one-third of people with XLP experience dysgammaglobulinemia, which means they have abnormal levels of some types of antibodies. Antibodies (also known as immunoglobulins) are proteins that attach to specific foreign particles and germs, marking them for destruction. Individuals with dysgammaglobulinemia are prone to recurrent infections.  Cancers of immune system cells (lymphomas) occur in about one-third of people with XLP.  Without treatment, most people with XLP survive only into childhood. Death usually results from hemophagocytic lymphohistiocytosis.  XLP can be divided into two types based on its genetic cause and pattern of signs and symptoms: XLP1 (also known as classic XLP) and XLP2. People with XLP2 have not been known to develop lymphoma, are more likely to develop hemophagocytic lymphohistiocytosis without EBV infection, usually have an enlarged spleen (splenomegaly), and may also have inflammation of the large intestine (colitis). Some researchers believe that these individuals should actually be considered to have a similar but separate disorder rather than a type of XLP. </s>


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

Output: XLP1 is estimated to occur in about 1 per million males worldwide. XLP2 is less common, occurring in about 1 per 5 million males. </s>


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

Output: Mutations in the SH2D1A and XIAP genes cause XLP. SH2D1A gene mutations cause XLP1, and XIAP gene mutations cause XLP2.  The SH2D1A gene provides instructions for making a protein called signaling lymphocyte activation molecule (SLAM) associated protein (SAP). This protein is involved in the functioning of lymphocytes that destroy other cells (cytotoxic lymphocytes) and is necessary for the development of specialized T cells called natural killer T cells. The SAP protein also helps control immune reactions by triggering self-destruction (apoptosis) of cytotoxic lymphocytes when they are no longer needed.  Some SH2D1A gene mutations impair SAP function. Others result in an abnormally short protein that is unstable or nonfunctional, or prevent any SAP from being produced. The loss of functional SAP disrupts proper signaling in the immune system and may prevent the body from controlling the immune reaction to EBV infection. In addition, lymphomas may develop when defective lymphocytes are not properly destroyed by apoptosis.  The XIAP gene provides instructions for making a protein that helps protect cells from undergoing apoptosis in response to certain signals. XIAP gene mutations can lead to an absence of XIAP protein or decrease the amount of XIAP protein that is produced. It is unknown how a lack of XIAP protein results in the signs and symptoms of XLP, or why features of this disorder differ somewhat between people with XIAP and SH2D1A gene mutations. </s>


Input: Is X-linked lymphoproliferative disease inherited ?

Output: This condition is generally inherited in an X-linked recessive pattern. The genes associated with this condition are 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 an associated gene in each cell is sufficient to cause the condition. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In females (who have two X chromosomes), a mutation usually has to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of an associated gene, males are affected by X-linked recessive disorders much more frequently than females. However, in rare cases a female carrying one altered copy of the SH2D1A or XIAP gene in each cell may develop signs and symptoms of this condition. </s>


Input: What are the treatments for X-linked lymphoproliferative disease ?

Output: These resources address the diagnosis or management of XLP:  - Children's Hospital of Philadelphia  - Gene Review: Gene Review: Lymphoproliferative Disease, X-Linked  - Genetic Testing Registry: Lymphoproliferative syndrome 1, X-linked  - Genetic Testing Registry: Lymphoproliferative syndrome 2, X-linked  - MedlinePlus Encyclopedia: Epstein-Barr Virus Test  - Merck Manual for Healthcare Professionals  - XLP Research Trust: Immunoglobulin Replacement  - XLP Research Trust: Preparing for Bone Marrow Transplant   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) metatropic dysplasia ?

Output: Metatropic dysplasia is a skeletal disorder characterized by short stature (dwarfism) with other skeletal abnormalities. The term "metatropic" is derived from the Greek word "metatropos," which means "changing patterns." This name reflects the fact that the skeletal abnormalities associated with the condition change over time.  Affected infants are born with a narrow chest and unusually short arms and legs with dumbbell-shaped long bones. Beginning in early childhood, people with this condition develop abnormal side-to-side and front-to-back curvature of the spine (scoliosis and kyphosis, often called kyphoscoliosis when they occur together). The curvature worsens with time and tends to be resistant to treatment. Because of the severe kyphoscoliosis, affected individuals may ultimately have a very short torso in relation to the length of their arms and legs.  Some people with metatropic dysplasia are born with an elongated tailbone known as a coccygeal tail; it is made of a tough but flexible tissue called cartilage. The coccygeal tail usually shrinks over time. Other skeletal problems associated with metatropic dysplasia include flattened bones of the spine (platyspondyly); excessive movement of spinal bones in the neck that can damage the spinal cord; either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum); and joint deformities called contractures that restrict the movement of joints in the shoulders, elbows, hips, and knees. Beginning early in life, affected individuals can also develop a degenerative form of arthritis that causes joint pain and further restricts movement.  The signs and symptoms of metatropic dysplasia can vary from relatively mild to life-threatening. In the most severe cases, the narrow chest and spinal abnormalities prevent the lungs from expanding fully, which restricts breathing. Researchers formerly recognized several distinct forms of metatropic dysplasia based on the severity of the condition's features. The forms included a mild type, a classic type, and a lethal type. However, all of these forms are now considered to be part of a single condition with a spectrum of overlapping signs and symptoms. </s>


Input: How many people are affected by metatropic dysplasia ?

Output: Metatropic dysplasia is a rare disease; its exact prevalence is unknown. More than 80 affected individuals have been reported in the scientific literature. </s>


Input: What are the genetic changes related to metatropic dysplasia ?

Output: Metatropic dysplasia is caused by mutations in the TRPV4 gene, which provides instructions for making a protein that acts as a calcium channel. The TRPV4 channel transports positively charged calcium atoms (calcium ions) across cell membranes and into cells. The channel is found in many types of cells, but little is known about its function. Studies suggest that it plays a role in the normal development of cartilage and bone. This role would help explain why TRPV4 gene mutations cause the skeletal abnormalities characteristic of metatropic dysplasia. Mutations in the TRPV4 gene appear to overactivate the channel, increasing the flow of calcium ions into cells. However, it remains unclear how changes in the activity of the calcium channel lead to the specific features of the condition. </s>


Input: Is metatropic dysplasia inherited ?

Output: Metatropic dysplasia is considered an autosomal dominant disorder because one mutated copy of the TRPV4 gene in each cell is sufficient to cause the condition. Most cases of metatropic dysplasia are caused by new mutations in the gene and occur in people with no history of the disorder in their family. In a few reported cases, an affected person has inherited the condition from an affected parent.  In the past, it was thought that the lethal type of metatropic dysplasia had an autosomal recessive pattern of inheritance, in which both copies of the gene in each cell have mutations. However, more recent research has confirmed that all metatropic dysplasia has an autosomal dominant pattern of inheritance. </s>


Input: What are the treatments for metatropic dysplasia ?

Output: These resources address the diagnosis or management of metatropic dysplasia:  - Gene Review: Gene Review: TRPV4-Associated Disorders  - Genetic Testing Registry: Metatrophic dysplasia   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) DOLK-congenital disorder of glycosylation ?

Output: DOLK-congenital disorder of glycosylation (DOLK-CDG, formerly known as congenital disorder of glycosylation type Im) is an inherited condition that often affects the heart but can also involve other body systems. The pattern and severity of this disorder's signs and symptoms vary among affected individuals.  Individuals with DOLK-CDG typically develop signs and symptoms of the condition during infancy or early childhood. Nearly all individuals with DOLK-CDG develop a weakened and enlarged heart (dilated cardiomyopathy). Other frequent signs and symptoms include recurrent seizures; developmental delay; poor muscle tone (hypotonia); and dry, scaly skin (ichthyosis). Less commonly, affected individuals can have distinctive facial features, kidney disease, hormonal abnormalities, or eye problems.  Individuals with DOLK-CDG typically do not survive into adulthood, often because of complications related to dilated cardiomyopathy, and some do not survive past infancy. </s>


Input: How many people are affected by DOLK-congenital disorder of glycosylation ?

Output: DOLK-CDG is likely a rare condition; at least 18 cases have been reported in the scientific literature. </s>


Input: What are the genetic changes related to DOLK-congenital disorder of glycosylation ?

Output: DOLK-CDG is caused by mutations in the DOLK gene. This gene provides instructions for making the enzyme dolichol kinase, which facilitates the final step of the production of a compound called dolichol phosphate. This compound is critical for a process called glycosylation, which attaches groups of sugar molecules (oligosaccharides) to proteins. Glycosylation changes proteins in ways that are important for their functions. During glycosylation, sugars are added to dolichol phosphate in order to build the oligosaccharide chain. Once the chain is formed, dolichol phosphate transports the oligosaccharide to the protein that needs to be glycosylated and attaches it to a specific site on the protein.  Mutations in the DOLK gene lead to the production of abnormal dolichol kinase with reduced or absent activity. Without properly functioning dolichol kinase, dolichol phosphate is not produced and glycosylation cannot proceed normally. In particular, a protein known to stabilize heart muscle fibers, called alpha-dystroglycan, has been shown to have reduced glycosylation in people with DOLK-CDG. Impaired glycosylation of alpha-dystroglycan disrupts its normal function, which damages heart muscle fibers as they repeatedly contract and relax. Over time, the fibers weaken and break down, leading to dilated cardiomyopathy. The other signs and symptoms of DOLK-CDG are likely due to the abnormal glycosylation of additional proteins in other organs and tissues. </s>


Input: Is DOLK-congenital disorder of glycosylation 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 DOLK-congenital disorder of glycosylation ?

Output: These resources address the diagnosis or management of DOLK-CDG:  - Gene Review: Gene Review: Congenital Disorders of N-Linked Glycosylation Pathway Overview  - Genetic Testing Registry: Congenital disorder of glycosylation type 1M  - MedlinePlus Encyclopedia: Dilated Cardiomyopathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) Li-Fraumeni syndrome ?

Output: Li-Fraumeni syndrome is a rare disorder that greatly increases the risk of developing several types of cancer, particularly in children and young adults.  The cancers most often associated with Li-Fraumeni syndrome include breast cancer, a form of bone cancer called osteosarcoma, and cancers of soft tissues (such as muscle) called soft tissue sarcomas. Other cancers commonly seen in this syndrome include brain tumors, cancers of blood-forming tissues (leukemias), and a cancer called adrenocortical carcinoma that affects the outer layer of the adrenal glands (small hormone-producing glands on top of each kidney). Several other types of cancer also occur more frequently in people with Li-Fraumeni syndrome.  A very similar condition called Li-Fraumeni-like syndrome shares many of the features of classic Li-Fraumeni syndrome. Both conditions significantly increase the chances of developing multiple cancers beginning in childhood; however, the pattern of specific cancers seen in affected family members is different. </s>


Input: How many people are affected by Li-Fraumeni syndrome ?

Output: The exact prevalence of Li-Fraumeni is unknown. One U.S. registry of Li-Fraumeni syndrome patients suggests that about 400 people from 64 families have this disorder. </s>


Input: What are the genetic changes related to Li-Fraumeni syndrome ?

Output: The CHEK2 and TP53 genes are associated with Li-Fraumeni syndrome.  More than half of all families with Li-Fraumeni syndrome have inherited mutations in the TP53 gene. TP53 is a tumor suppressor gene, which means that it normally helps control the growth and division of cells. Mutations in this gene can allow cells to divide in an uncontrolled way and form tumors. Other genetic and environmental factors are also likely to affect the risk of cancer in people with TP53 mutations.  A few families with cancers characteristic of Li-Fraumeni syndrome and Li-Fraumeni-like syndrome do not have TP53 mutations, but have mutations in the CHEK2 gene. Like the TP53 gene, CHEK2 is a tumor suppressor gene. Researchers are uncertain whether CHEK2 mutations actually cause these conditions or are merely associated with an increased risk of certain cancers (including breast cancer). </s>


Input: Is Li-Fraumeni syndrome inherited ?

Output: Li-Fraumeni syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing cancer. In most cases, an affected person has a parent and other family members with cancers characteristic of the condition. </s>


Input: What are the treatments for Li-Fraumeni syndrome ?

Output: These resources address the diagnosis or management of Li-Fraumeni syndrome:  - Gene Review: Gene Review: Li-Fraumeni Syndrome  - Genetic Testing Registry: Li-Fraumeni syndrome  - Genetic Testing Registry: Li-Fraumeni syndrome 1  - Genetic Testing Registry: Li-Fraumeni syndrome 2  - MedlinePlus Encyclopedia: Cancer  - National Cancer Institute: Genetic Testing for Hereditary Cancer Syndromes   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) CASK-related intellectual disability ?

Output: CASK-related intellectual disability is a disorder of brain development that has two main forms: microcephaly with pontine and cerebellar hypoplasia (MICPCH), and X-linked intellectual disability (XL-ID) with or without nystagmus. Within each of these forms, males typically have more severe signs and symptoms than do females; the more severe MICPCH mostly affects females, likely because only a small number of males survive to birth.  People with MICPCH often have an unusually small head at birth, and the head does not grow at the same rate as the rest of the body, so it appears that the head is getting smaller as the body grows (progressive microcephaly). Individuals with this condition have underdevelopment (hypoplasia) of areas of the brain called the cerebellum and the pons. The cerebellum is the part of the brain that coordinates movement. The pons is located at the base of the brain in an area called the brainstem, where it transmits signals from the cerebellum to the rest of the brain.  Individuals with MICPCH have intellectual disability that is usually severe. They may have sleep disturbances and exhibit self-biting, hand flapping, or other abnormal repetitive behaviors. Seizures are also common in this form of the disorder.  People with MICPCH do not usually develop language skills, and most do not learn to walk. They have hearing loss caused by nerve problems in the inner ear (sensorineural hearing loss), and most also have abnormalities affecting the eyes. These abnormalities include underdevelopment of the nerves that carry information from the eyes to the brain (optic nerve hypoplasia), breakdown of the light-sensing tissue at the back of the eyes (retinopathy), and eyes that do not look in the same direction (strabismus). Characteristic facial features may include arched eyebrows; a short, broad nose; a lengthened area between the nose and mouth (philtrum); a protruding upper jaw (maxilla); a short chin; and large ears.  Individuals with MICPCH may have weak muscle tone (hypotonia) in the torso along with increased muscle tone (hypertonia) and stiffness (spasticity) in the limbs. Movement problems such as involuntary tensing of various muscles (dystonia) may also occur in this form of the disorder.  XL-ID with or without nystagmus (rapid, involuntary eye movements) is a milder form of CASK-related intellectual disability. The intellectual disability in this form of the disorder can range from mild to severe; some affected females have normal intelligence. About half of affected individuals have nystagmus. Seizures and rhythmic shaking (tremors) may also occur in this form. </s>


Input: How many people are affected by CASK-related intellectual disability ?

Output: The prevalence of CASK-related intellectual disability is unknown. More than 50 females with MICPCH have been described in the medical literature, while only a few affected males have been described.  By contrast, more than 20 males but only a few females have been diagnosed with the milder form of the disorder, XL-ID with or without nystagmus. This form of the disorder may go unrecognized in mildly affected females. </s>


Input: What are the genetic changes related to CASK-related intellectual disability ?

Output: CASK-related intellectual disability, as its name suggests, is caused by mutations in the CASK gene. This gene provides instructions for making a protein called calcium/calmodulin-dependent serine protein kinase (CASK). The CASK protein is primarily found in nerve cells (neurons) in the brain, where it helps control the activity (expression) of other genes that are involved in brain development. It also helps regulate the movement of chemicals called neurotransmitters and of charged atoms (ions), which are necessary for signaling between neurons. Research suggests that the CASK protein may also interact with the protein produced from another gene, FRMD7, to promote development of the nerves that control eye movement (the oculomotor neural network).  Mutations in the CASK gene affect the role of the CASK protein in brain development and function, resulting in the signs and symptoms of CASK-related intellectual disability. The severe form of this disorder, MICPCH, is caused by mutations that eliminate CASK function, while mutations that impair the function of this protein cause the milder form, XL-ID with or without nystagmus. Affected individuals with nystagmus may have CASK gene mutations that disrupt the interaction between the CASK protein and the protein produced from the FRMD7 gene, leading to problems with the development of the oculomotor neural network and resulting in abnormal eye movements. </s>


Input: Is CASK-related intellectual disability inherited ?

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


Input: What are the treatments for CASK-related intellectual disability ?

Output: These resources address the diagnosis or management of CASK-related intellectual disability:  - Gene Review: Gene Review: CASK-Related Disorders  - Genetic Testing Registry: Mental retardation and microcephaly with pontine and cerebellar hypoplasia   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) facioscapulohumeral muscular dystrophy ?

Output: Facioscapulohumeral muscular dystrophy is a disorder characterized by muscle weakness and wasting (atrophy). This condition gets its name from the muscles that are affected most often: those of the face (facio-), around the shoulder blades (scapulo-), and in the upper arms (humeral). The signs and symptoms of facioscapulohumeral muscular dystrophy usually appear in adolescence. However, the onset and severity of the condition varies widely. Milder cases may not become noticeable until later in life, whereas rare severe cases become apparent in infancy or early childhood.  Weakness involving the facial muscles or shoulders is usually the first symptom of this condition. Facial muscle weakness often makes it difficult to drink from a straw, whistle, or turn up the corners of the mouth when smiling. Weakness in muscles around the eyes can prevent the eyes from closing fully while a person is asleep, which can lead to dry eyes and other eye problems. For reasons that are unclear, weakness may be more severe in one side of the face than the other. Weak shoulder muscles tend to make the shoulder blades (scapulae) protrude from the back, a common sign known as scapular winging. Weakness in muscles of the shoulders and upper arms can make it difficult to raise the arms over the head or throw a ball.  The muscle weakness associated with facioscapulohumeral muscular dystrophy worsens slowly over decades and may spread to other parts of the body. Weakness in muscles of the lower legs can lead to a condition called foot drop, which affects walking and increases the risk of falls. Muscular weakness in the hips and pelvis can make it difficult to climb stairs or walk long distances. Additionally, affected individuals may have an exaggerated curvature of the lower back (lordosis) due to weak abdominal muscles. About 20 percent of affected individuals eventually require the use of a wheelchair.  Additional signs and symptoms of facioscapulohumeral muscular dystrophy can include mild high-tone hearing loss and abnormalities involving the light-sensitive tissue at the back of the eye (the retina). These signs are often not noticeable and may be discovered only during medical testing. Rarely, facioscapulohumeral muscular dystrophy affects the heart (cardiac) muscle or muscles needed for breathing.  Researchers have described two types of facioscapulohumeral muscular dystrophy: type 1 (FSHD1) and type 2 (FSHD2). The two types have the same signs and symptoms and are distinguished by their genetic cause. </s>


Input: How many people are affected by facioscapulohumeral muscular dystrophy ?

Output: Facioscapulohumeral muscular dystrophy has an estimated prevalence of 1 in 20,000 people. About 95 percent of all cases are FSHD1; the remaining 5 percent are FSHD2. </s>


Input: What are the genetic changes related to facioscapulohumeral muscular dystrophy ?

Output: Facioscapulohumeral muscular dystrophy is caused by genetic changes involving the long (q) arm of chromosome 4. Both types of the disease result from changes in a region of DNA near the end of the chromosome known as D4Z4. This region consists of 11 to more than 100 repeated segments, each of which is about 3,300 DNA base pairs (3.3 kb) long. The entire D4Z4 region is normally hypermethylated, which means that it has a large number of methyl groups (consisting of one carbon atom and three hydrogen atoms) attached to the DNA. The addition of methyl groups turns off (silences) genes, so hypermethylated regions of DNA tend to have fewer genes that are turned on (active). Facioscapulohumeral muscular dystrophy results when the D4Z4 region is hypomethylated, with a shortage of attached methyl groups. In FSHD1, hypomethylation occurs because the D4Z4 region is abnormally shortened (contracted), containing between 1 and 10 repeats instead of the usual 11 to 100 repeats. In FSHD2, hypomethylation most often results from mutations in a gene called SMCHD1, which provides instructions for making a protein that normally hypermethylates the D4Z4 region. However, about 20 percent of people with FSHD2 do not have an identified mutation in the SMCHD1 gene, and the cause of the hypomethylation is unknown.  Hypermethylation of the D4Z4 region normally keeps a gene called DUX4 silenced in most adult cells and tissues. The DUX4 gene is located in the segment of the D4Z4 region closest to the end of chromosome 4. In people with facioscapulohumeral muscular dystrophy, hypomethylation of the D4Z4 region prevents the DUX4 gene from being silenced in cells and tissues where it is usually turned off. Although little is known about the function of the DUX4 gene when it is active, researchers believe that it influences the activity of other genes, particularly in muscle cells. It is unknown how abnormal activity of the DUX4 gene damages or destroys these cells, leading to progressive muscle weakness and atrophy.  The DUX4 gene is located next to a regulatory region of DNA on chromosome 4 known as a pLAM sequence, which is necessary for the production of the DUX4 protein. Some copies of chromosome 4 have a functional pLAM sequence, while others do not. Copies of chromosome 4 with a functional pLAM sequence are described as 4qA or "permissive." Those without a functional pLAM sequence are described as 4qB or "non-permissive." Without a functional pLAM sequence, no DUX4 protein is made. Because there are two copies of chromosome 4 in each cell, individuals may have two "permissive" copies of chromosome 4, two "non-permissive" copies, or one of each. Facioscapulohumeral muscular dystrophy can only occur in people who have at least one "permissive" copy of chromosome 4. Whether an affected individual has a contracted D4Z4 region or a SMCHD1 gene mutation, the disease results only if a functional pLAM sequence is also present to allow DUX4 protein to be produced.  Studies suggest that mutations in the SMCHD1 gene, which cause FSHD2, can also increase the severity of the disease in people with FSHD1. Researchers suspect that the combination of a contracted D4Z4 region and a SMCHD1 gene mutation causes the D4Z4 region to have even fewer methyl groups attached, which allows the DUX4 gene to be highly active. In people with both genetic changes, the overactive gene leads to severe muscle weakness and atrophy. </s>


Input: Is facioscapulohumeral muscular dystrophy inherited ?

Output: FSHD1 is inherited in an autosomal dominant pattern, which means one copy of the shortened D4Z4 region on a "permissive" chromosome 4 is sufficient to cause the disorder. In most cases, an affected person inherits the altered chromosome from one affected parent. Other people with FSHD1 have no history of the disorder in their family. These cases are described as sporadic and are caused by a new (de novo) D4Z4 contraction on one copy of a "permissive" chromosome 4.  FSHD2 is inherited in a digenic pattern, which means that two independent genetic changes are necessary to cause the disorder. To have FSHD2, an individual must inherit a mutation in the SMCHD1 gene (which is located on chromosome 18) and, separately, they must inherit one copy of a "permissive" chromosome 4. Affected individuals typically inherit the SMCHD1 gene mutation from one parent and the "permissive" chromosome 4 from the other parent. (Because neither parent has both genetic changes in most cases, they are typically unaffected.) </s>


Input: What are the treatments for facioscapulohumeral muscular dystrophy ?

Output: These resources address the diagnosis or management of facioscapulohumeral muscular dystrophy:  - Gene Review: Gene Review: Facioscapulohumeral Muscular Dystrophy  - Genetic Testing Registry: Facioscapulohumeral muscular dystrophy  - Genetic Testing Registry: Facioscapulohumeral muscular dystrophy 2  - MedlinePlus Encyclopedia: Facioscapulohumeral Muscular Dystrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) paramyotonia congenita ?

Output: Paramyotonia congenita is a disorder that affects muscles used for movement (skeletal muscles). Beginning in infancy or early childhood, people with this condition experience bouts of sustained muscle tensing (myotonia) that prevent muscles from relaxing normally. Myotonia causes muscle stiffness that typically appears after exercise and can be induced by muscle cooling. This stiffness chiefly affects muscles in the face, neck, arms, and hands, although it can also affect muscles used for breathing and muscles in the lower body. Unlike many other forms of myotonia, the muscle stiffness associated with paramyotonia congenita tends to worsen with repeated movements.  Most peopleeven those without muscle diseasefeel that their muscles do not work as well when they are cold. This effect is dramatic in people with paramyotonia congenita. Exposure to cold initially causes muscle stiffness in these individuals, and prolonged cold exposure leads to temporary episodes of mild to severe muscle weakness that may last for several hours at a time. Some older people with paramyotonia congenita develop permanent muscle weakness that can be disabling. </s>


Input: How many people are affected by paramyotonia congenita ?

Output: Paramyotonia congenita is an uncommon disorder; it is estimated to affect fewer than 1 in 100,000 people. </s>


Input: What are the genetic changes related to paramyotonia congenita ?

Output: Mutations in the SCN4A gene cause paramyotonia congenita. This gene provides instructions for making a protein that is critical for the normal function of skeletal muscle cells. For the body to move normally, skeletal muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of positively charged atoms (ions), including sodium, into skeletal muscle cells. The SCN4A protein forms channels that control the flow of sodium ions into these cells.  Mutations in the SCN4A gene alter the usual structure and function of sodium channels. The altered channels cannot effectively regulate the flow of sodium ions into skeletal muscle cells. The resulting increase in ion flow interferes with normal muscle contraction and relaxation, leading to episodes of muscle stiffness and weakness. </s>


Input: Is paramyotonia congenita inherited ?

Output: This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In many cases, an affected person has one parent with the condition. </s>


Input: What are the treatments for paramyotonia congenita ?

Output: These resources address the diagnosis or management of paramyotonia congenita:  - Genetic Testing Registry: Paramyotonia congenita of von Eulenburg  - Periodic Paralysis International: How is Periodic Paralysis Diagnosed?   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) Bowen-Conradi syndrome ?

Output: Bowen-Conradi syndrome is a disorder that affects many parts of the body and is usually fatal in infancy. Affected individuals have a low birth weight, experience feeding problems, and grow very slowly. Their head is unusually small overall (microcephaly), but is longer than expected compared with its width (dolichocephaly). Characteristic facial features include a prominent, high-bridged nose and an unusually small jaw (micrognathia) and chin. Affected individuals typically have pinky fingers that are curved toward or away from the ring finger (fifth finger clinodactyly) or permanently flexed (camptodactyly), feet with soles that are rounded outward (rocker-bottom feet), and restricted joint movement.  Other features that occur in some affected individuals include seizures; structural abnormalities of the kidneys, heart, brain, or other organs; and an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate). Affected males may have the opening of the urethra on the underside of the penis (hypospadias) or undescended testes (cryptorchidism).  Babies with Bowen-Conradi syndrome do not achieve developmental milestones such as smiling or sitting, and they usually do not survive more than 6 months. </s>


Input: How many people are affected by Bowen-Conradi syndrome ?

Output: Bowen-Conradi syndrome is common in the Hutterite population in Canada and the United States; it occurs in approximately 1 per 355 newborns in all three Hutterite sects (leuts). A few individuals from outside the Hutterite community with signs and symptoms similar to Bowen-Conradi syndrome have been described in the medical literature. Researchers differ as to whether these individuals have Bowen-Conradi syndrome or a similar but distinct disorder. </s>


Input: What are the genetic changes related to Bowen-Conradi syndrome ?

Output: Bowen-Conradi syndrome is caused by a mutation in the EMG1 gene. This gene provides instructions for making a protein that is involved in the production of cellular structures called ribosomes, which process the cell's genetic instructions to create new proteins. Ribosomes are assembled in a cell compartment called the nucleolus.  The particular EMG1 gene mutation known to cause Bowen-Conradi syndrome is thought to make the protein unstable, resulting in a decrease in the amount of EMG1 protein that is available in the nucleolus. A shortage of this protein in the nucleolus would impair ribosome production, which may reduce cell growth and division (proliferation); however, it is unknown how EMG1 gene mutations lead to the particular signs and symptoms of Bowen-Conradi syndrome. </s>


Input: Is Bowen-Conradi 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 Bowen-Conradi syndrome ?

Output: These resources address the diagnosis or management of Bowen-Conradi syndrome:  - Genetic Testing Registry: Bowen-Conradi syndrome  - MedlinePlus Encyclopedia: Feeding Tube--Infants   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) Paget disease of bone ?

Output: Paget disease of bone is a disorder that causes bones to grow larger and weaker than normal. Affected bones may be misshapen and easily broken (fractured).  The classic form of Paget disease of bone typically appears in middle age or later. It usually occurs in one or a few bones and does not spread from one bone to another. Any bones can be affected, although the disease most commonly affects bones in the spine, pelvis, skull, or legs.  Many people with classic Paget disease of bone do not experience any symptoms associated with their bone abnormalities. The disease is often diagnosed unexpectedly by x-rays or laboratory tests done for other reasons. People who develop symptoms are most likely to experience pain. The affected bones may themselves be painful, or pain may be caused by arthritis in nearby joints. Arthritis results when the distortion of bones, particularly weight-bearing bones in the legs, causes extra wear and tear on the joints. Arthritis most frequently affects the knees and hips in people with this disease.  Other complications of Paget disease of bone depend on which bones are affected. If the disease occurs in bones of the skull, it can cause an enlarged head, hearing loss, headaches, and dizziness. If the disease affects bones in the spine, it can lead to numbness and tingling (due to pinched nerves) and abnormal spinal curvature. In the leg bones, the disease can cause bowed legs and difficulty walking.  A rare type of bone cancer called osteosarcoma has been associated with Paget disease of bone. This type of cancer probably occurs in less than 1 in 1,000 people with this disease.  Early-onset Paget disease of bone is a less common form of the disease that appears in a person's teens or twenties. Its features are similar to those of the classic form of the disease, although it is more likely to affect the skull, spine, and ribs (the axial skeleton) and the small bones of the hands. The early-onset form of the disorder is also associated with hearing loss early in life. </s>


Input: How many people are affected by Paget disease of bone ?

Output: Classic Paget disease of bone occurs in approximately 1 percent of people older than 40 in the United States. Scientists estimate that about 1 million people in this country have the disease. It is most common in people of western European heritage.  Early-onset Paget disease of bone is much rarer. This form of the disorder has been reported in only a few families. </s>