Input: What are the genetic changes related to ulcerative colitis ?

Output: A variety of genetic and environmental factors are likely involved in the development of ulcerative colitis. Recent studies have identified variations in dozens of genes that may be linked to ulcerative colitis; however, the role of these variations is not completely understood. Researchers speculate that this condition may result from changes in the intestinal lining's protective function or an abnormal immune response to the normal bacteria in the digestive tract, both of which may be influenced by genetic variations.  Several of the genes that may be associated with ulcerative colitis are involved in the protective function of the intestines. The inner surface of the intestines provides a barrier that protects the body's tissues from the bacteria that live in the intestines and from toxins that pass through the digestive tract. Researchers speculate that a breakdown of this barrier allows contact between the intestinal tissue and the bacteria and toxins, which can trigger an immune reaction. This immune response may lead to chronic inflammation and the digestive problems characteristic of ulcerative colitis.  Other possible disease-associated genes are involved in the immune system, particularly in the maturation and function of immune cells called T cells. T cells identify foreign substances and defend the body against infection. Certain genetic variations may make some individuals more prone to an overactive immune response to the bacteria and other microbes in the intestines, which may cause the chronic inflammation that occurs in ulcerative colitis. Another possible explanation is that ulcerative colitis occurs when the immune system malfunctions and attacks the cells of the intestines, causing inflammation. </s>


Input: Is ulcerative colitis inherited ?

Output: The inheritance pattern of ulcerative colitis is unknown because many genetic and environmental factors are likely to be involved. Even though the inheritance pattern of this condition is unclear, having a family member with ulcerative colitis increases the risk of developing the condition. </s>


Input: What are the treatments for ulcerative colitis ?

Output: These resources address the diagnosis or management of ulcerative colitis:  - American Society of Colon and Rectal Surgeons  - Cedars-Sinai  - Crohn's & Colitis Foundation of America: Colitis Diagnosis and Testing  - Crohn's & Colitis Foundation of America: Colitis Treatment Options  - Genetic Testing Registry: Inflammatory bowel disease 1  - MedlinePlus Encyclopedia: Ulcerative Colitis   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 pancreatitis ?

Output: Hereditary pancreatitis is a genetic condition characterized by recurrent episodes of inflammation of the pancreas (pancreatitis). The pancreas produces enzymes that help digest food, and it also produces insulin, a hormone that controls blood sugar levels in the body. Episodes of pancreatitis can lead to permanent tissue damage and loss of pancreatic function.  Signs and symptoms of this condition usually begin in late childhood with an episode of acute pancreatitis. A sudden (acute) attack can cause abdominal pain, fever, nausea, or vomiting. An episode typically lasts from one to three days, although some people may experience severe episodes that last longer. Hereditary pancreatitis progresses to recurrent acute pancreatitis with multiple episodes of acute pancreatitis that recur over a period of at least a year; the number of episodes a person experiences varies. Recurrent acute pancreatitis leads to chronic pancreatitis, which occurs when the pancreas is persistently inflamed. Chronic pancreatitis usually develops by early adulthood in affected individuals. Signs and symptoms of chronic pancreatitis include occasional or frequent abdominal pain of varying severity, flatulence, and bloating. Many individuals with hereditary pancreatitis also develop abnormal calcium deposits in the pancreas (pancreatic calcifications) by early adulthood.  Years of inflammation damage the pancreas, causing the formation of scar tissue (fibrosis) in place of functioning pancreatic tissue. Pancreatic fibrosis leads to the loss of pancreatic function in many affected individuals. This loss of function can impair the production of digestive enzymes and disrupt normal digestion, leading to fatty stool (steatorrhea), weight loss, and protein and vitamin deficiencies. Because of a decrease in insulin production due to a loss of pancreatic function, about a quarter of individuals with hereditary pancreatitis will develop type 1 diabetes mellitus by mid-adulthood; the risk of developing diabetes increases with age.  Chronic pancreatic inflammation and damage to the pancreas increase the risk of developing pancreatic cancer. The risk is particularly high in people with hereditary pancreatitis who also smoke, use alcohol, have type 1 diabetes mellitus, or have a family history of cancer. In affected individuals who develop pancreatic cancer, it is typically diagnosed in mid-adulthood.  Complications from pancreatic cancer and type 1 diabetes mellitus are the most common causes of death in individuals with hereditary pancreatitis, although individuals with this condition are thought to have a normal life expectancy. </s>


Input: How many people are affected by hereditary pancreatitis ?

Output: Hereditary pancreatitis is thought to be a rare condition. In Europe, its prevalence is estimated to be 3 to 6 per million individuals. </s>


Input: What are the genetic changes related to hereditary pancreatitis ?

Output: Mutations in the PRSS1 gene cause most cases of hereditary pancreatitis. The PRSS1 gene provides instructions for making an enzyme called cationic trypsinogen. This enzyme is produced in the pancreas and helps with the digestion of food. When cationic trypsinogen is needed, it is released (secreted) from the pancreas and transported to the small intestine, where it is cut (cleaved) into its working or active form called trypsin. When digestion is complete and trypsin is no longer needed, the enzyme is broken down.  Some PRSS1 gene mutations that cause hereditary pancreatitis result in the production of a cationic trypsinogen enzyme that is prematurely converted to trypsin while it is still in the pancreas. Other mutations prevent trypsin from being broken down. These changes result in elevated levels of trypsin in the pancreas. Trypsin activity in the pancreas can damage pancreatic tissue and can also trigger an immune response, causing inflammation in the pancreas.  It is estimated that 65 to 80 percent of people with hereditary pancreatitis have mutations in the PRSS1 gene. The remaining cases are caused by mutations in other genes, some of which have not been identified. </s>


Input: Is hereditary pancreatitis inherited ?

Output: When hereditary pancreatitis is caused by mutations in the PRSS1 gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the PRSS1 gene mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  It is estimated that 20 percent of people who have the altered PRSS1 gene never have an episode of pancreatitis. (This situation is known as reduced penetrance.) It is unclear why some people with a mutated gene never develop signs and symptoms of the disease. </s>


Input: What are the treatments for hereditary pancreatitis ?

Output: These resources address the diagnosis or management of hereditary pancreatitis:  - Encyclopedia: Chronic Pancreatitis  - Gene Review: Gene Review: PRSS1-Related Hereditary Pancreatitis  - Gene Review: Gene Review: Pancreatitis Overview  - Genetic Testing Registry: Hereditary pancreatitis  - Johns Hopkins Medicine: Treatment Options for Pancreatitis  - MD Anderson Cancer Center: Pancreatic Cancer Diagnosis  - MedlinePlus Encyclopedia: Acute Pancreatitis  - MedlinePlus Encyclopedia: Chronic Pancreatitis   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) alpha-1 antitrypsin deficiency ?

Output: Alpha-1 antitrypsin deficiency is an inherited disorder that may cause lung disease and liver disease. The signs and symptoms of the condition and the age at which they appear vary among individuals.  People with alpha-1 antitrypsin deficiency usually develop the first signs and symptoms of lung disease between ages 20 and 50. The earliest symptoms are shortness of breath following mild activity, reduced ability to exercise, and wheezing. Other signs and symptoms can include unintentional weight loss, recurring respiratory infections, fatigue, and rapid heartbeat upon standing. Affected individuals often develop emphysema, which is a lung disease caused by damage to the small air sacs in the lungs (alveoli). Characteristic features of emphysema include difficulty breathing, a hacking cough, and a barrel-shaped chest. Smoking or exposure to tobacco smoke accelerates the appearance of emphysema symptoms and damage to the lungs.  About 10 percent of infants with alpha-1 antitrypsin deficiency develop liver disease, which often causes yellowing of the skin and whites of the eyes (jaundice). Approximately 15 percent of adults with alpha-1 antitrypsin deficiency develop liver damage (cirrhosis) due to the formation of scar tissue in the liver. Signs of cirrhosis include a swollen abdomen, swollen feet or legs, and jaundice. Individuals with alpha-1 antitrypsin deficiency are also at risk of developing a type of liver cancer called hepatocellular carcinoma.  In rare cases, people with alpha-1 antitrypsin deficiency develop a skin condition called panniculitis, which is characterized by hardened skin with painful lumps or patches. Panniculitis varies in severity and can occur at any age. </s>


Input: How many people are affected by alpha-1 antitrypsin deficiency ?

Output: Alpha-1 antitrypsin deficiency occurs worldwide, but its prevalence varies by population. This disorder affects about 1 in 1,500 to 3,500 individuals with European ancestry. It is uncommon in people of Asian descent. Many individuals with alpha-1 antitrypsin deficiency are likely undiagnosed, particularly people with a lung condition called chronic obstructive pulmonary disease (COPD). COPD can be caused by alpha-1 antitrypsin deficiency; however, the alpha-1 antitrypsin deficiency is often never diagnosed. Some people with alpha-1 antitrypsin deficiency are misdiagnosed with asthma. </s>


Input: What are the genetic changes related to alpha-1 antitrypsin deficiency ?

Output: Mutations in the SERPINA1 gene cause alpha-1 antitrypsin deficiency. This gene provides instructions for making a protein called alpha-1 antitrypsin, which protects the body from a powerful enzyme called neutrophil elastase. Neutrophil elastase is released from white blood cells to fight infection, but it can attack normal tissues (especially the lungs) if not tightly controlled by alpha-1 antitrypsin.  Mutations in the SERPINA1 gene can lead to a shortage (deficiency) of alpha-1 antitrypsin or an abnormal form of the protein that cannot control neutrophil elastase. Without enough functional alpha-1 antitrypsin, neutrophil elastase destroys alveoli and causes lung disease. Abnormal alpha-1 antitrypsin can also accumulate in the liver and damage this organ.  Environmental factors, such as exposure to tobacco smoke, chemicals, and dust, likely impact the severity of alpha-1 antitrypsin deficiency. </s>


Input: Is alpha-1 antitrypsin deficiency inherited ?

Output: This condition is inherited in an autosomal codominant pattern. Codominance means that two different versions of the gene may be active (expressed), and both versions contribute to the genetic trait.  The most common version (allele) of the SERPINA1 gene, called M, produces normal levels of alpha-1 antitrypsin. Most people in the general population have two copies of the M allele (MM) in each cell. Other versions of the SERPINA1 gene lead to reduced levels of alpha-1 antitrypsin. For example, the S allele produces moderately low levels of this protein, and the Z allele produces very little alpha-1 antitrypsin. Individuals with two copies of the Z allele (ZZ) in each cell are likely to have alpha-1 antitrypsin deficiency. Those with the SZ combination have an increased risk of developing lung diseases (such as emphysema), particularly if they smoke.  Worldwide, it is estimated that 161 million people have one copy of the S or Z allele and one copy of the M allele in each cell (MS or MZ). Individuals with an MS (or SS) combination usually produce enough alpha-1 antitrypsin to protect the lungs. People with MZ alleles, however, have a slightly increased risk of impaired lung or liver function. </s>


Input: What are the treatments for alpha-1 antitrypsin deficiency ?

Output: These resources address the diagnosis or management of alpha-1 antitrypsin deficiency:  - Alpha-1 Foundation: Testing for Alpha-1  - Cleveland Clinic Respiratory Institute  - Gene Review: Gene Review: Alpha-1 Antitrypsin Deficiency  - GeneFacts: Alpha-1 Antitrypsin Deficiency: Diagnosis  - GeneFacts: Alpha-1 Antitrypsin Deficiency: Management  - Genetic Testing Registry: Alpha-1-antitrypsin deficiency  - MedlinePlus Encyclopedia: Alpha-1 antitrypsin deficiency  - MedlinePlus Encyclopedia: Pulmonary function tests  - MedlinePlus Encyclopedia: Wheezing   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) spastic paraplegia type 4 ?

Output: Spastic paraplegia type 4 is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve only the lower limbs, whereas the complex types also involve the upper limbs (to a lesser degree) and the nervous system. Spastic paraplegia type 4 is a pure hereditary spastic paraplegia.  Like all hereditary spastic paraplegias, spastic paraplegia type 4 involves spasticity of the leg muscles and muscle weakness. People with this condition can also experience exaggerated reflexes (hyperreflexia), ankle spasms, high-arched feet (pes cavus), and reduced bladder control. Spastic paraplegia type 4 generally affects nerve and muscle function in the lower half of the body only. </s>


Input: How many people are affected by spastic paraplegia type 4 ?

Output: The prevalence of spastic paraplegia type 4 is estimated to be 2 to 6 in 100,000 people worldwide. </s>


Input: What are the genetic changes related to spastic paraplegia type 4 ?

Output: Mutations in the SPAST gene cause spastic paraplegia type 4. The SPAST gene provides instructions for producing a protein called spastin. Spastin is found throughout the body, particularly in certain nerve cells (neurons). The spastin protein plays a role in the function of microtubules, which are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). Microtubules are also involved in transporting cell components and facilitating cell division. Spastin likely helps restrict microtubule length and disassemble microtubule structures when they are no longer needed. Mutations in spastin impair the microtubules' ability to transport cell components, especially in nerve cells; researchers believe this contributes to the major signs and symptoms of spastic paraplegia type 4. </s>


Input: Is spastic paraplegia type 4 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. The remaining cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family. </s>


Input: What are the treatments for spastic paraplegia type 4 ?

Output: These resources address the diagnosis or management of spastic paraplegia type 4:  - Gene Review: Gene Review: Hereditary Spastic Paraplegia Overview  - Gene Review: Gene Review: Spastic Paraplegia 4  - Genetic Testing Registry: Spastic paraplegia 4, autosomal dominant  - Spastic Paraplegia Foundation, Inc.: Treatments and Therapies   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) Marinesco-Sjgren syndrome ?

Output: Marinesco-Sjgren syndrome is a condition that has a variety of signs and symptoms affecting many tissues. People with Marinesco-Sjgren syndrome have clouding of the lens of the eyes (cataracts) that usually develops soon after birth or in early childhood. Affected individuals also have muscle weakness (myopathy) and difficulty coordinating movements (ataxia), which may impair their ability to walk. People with Marinesco-Sjgren syndrome may experience further decline in muscle function later in life.  Most people with Marinesco-Sjgren syndrome have mild to moderate intellectual disability. They also have skeletal abnormalities including short stature and a spine that curves to the side (scoliosis). Other features of Marinesco-Sjgren syndrome include eyes that do not look in the same direction (strabismus), involuntary eye movements (nystagmus), and impaired speech (dysarthria).  Affected individuals may have hypergonadotropic hypogonadism, which affects the production of hormones that direct sexual development. As a result, puberty is either delayed or absent. </s>


Input: How many people are affected by Marinesco-Sjgren syndrome ?

Output: Marinesco-Sjgren syndrome appears to be a rare condition. More than 100 cases have been reported worldwide. </s>


Input: What are the genetic changes related to Marinesco-Sjgren syndrome ?

Output: Mutations in the SIL1 gene cause Marinesco-Sjgren syndrome. The SIL1 gene provides instructions for producing a protein located in a cell structure called the endoplasmic reticulum. Among its many functions, the endoplasmic reticulum folds and modifies newly formed proteins so they have the correct 3-dimensional shape. The SIL1 protein plays a role in the process of protein folding.  SIL1 gene mutations result in the production of a protein that has little or no activity. A lack of SIL1 protein is thought to impair protein folding, which could disrupt protein transport and cause proteins to accumulate in the endoplasmic reticulum. This accumulation likely damages and destroys cells in many different tissues, leading to ataxia, myopathy, and the other features of Marinesco-Sjgren syndrome.  Approximately one-third of people with Marinesco-Sjgren syndrome do not have identified mutations in the SIL1 gene. In these cases, the cause of the condition is unknown. </s>


Input: Is Marinesco-Sjgren 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 Marinesco-Sjgren syndrome ?

Output: These resources address the diagnosis or management of Marinesco-Sjgren syndrome:  - Gene Review: Gene Review: Marinesco-Sjogren Syndrome  - Genetic Testing Registry: Marinesco-Sjgren syndrome  - MedlinePlus Encyclopedia: Congenital Cataract  - MedlinePlus Encyclopedia: Hypogonadism  - MedlinePlus Encyclopedia: Muscle Atrophy   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 adrenal hypoplasia congenita ?

Output: X-linked adrenal hypoplasia congenita is a disorder that mainly affects males. It involves many hormone-producing (endocrine) tissues in the body, particularly a pair of small glands on top of each kidney called the adrenal glands. These glands produce a variety of hormones that regulate many essential functions in the body.  One of the main signs of this disorder is adrenal insufficiency, which occurs when the adrenal glands do not produce enough hormones. Adrenal insufficiency typically begins in infancy or childhood and can cause vomiting, difficulty with feeding, dehydration, extremely low blood sugar (hypoglycemia), and shock. If untreated, these complications are often life-threatening.  Affected males may also have a shortage of male sex hormones, which leads to underdeveloped reproductive tissues, undescended testicles (cryptorchidism), delayed puberty, and an inability to father children (infertility). Together, these characteristics are known as hypogonadotropic hypogonadism.  The onset and severity of these signs and symptoms can vary, even among affected members of the same family. </s>


Input: How many people are affected by X-linked adrenal hypoplasia congenita ?

Output: X-linked adrenal hypoplasia congenita is estimated to affect 1 in 12,500 newborns. </s>


Input: What are the genetic changes related to X-linked adrenal hypoplasia congenita ?

Output: Mutations in the NR0B1 gene cause X-linked adrenal hypoplasia congenita. The NR0B1 gene provides instructions to make a protein called DAX1. This protein plays an important role in the development and function of several hormone-producing (endocrine) tissues including the adrenal glands, two hormone-secreting glands in the brain (the hypothalamus and pituitary), and the gonads (ovaries in females and testes in males). The hormones produced by these glands control many important body functions.  Some NR0B1 mutations result in the production of an inactive version of the DAX1 protein, while other mutations delete the entire gene. The resulting shortage of DAX1 disrupts the normal development and function of hormone-producing tissues in the body. The signs and symptoms of adrenal insufficiency and hypogonadotropic hypogonadism occur when endocrine glands do not produce the right amounts of certain hormones. </s>


Input: Is X-linked adrenal hypoplasia congenita inherited ?

Output: This condition is inherited in an X-linked recessive 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 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 must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In X-linked recessive inheritance, a female with one mutated copy of the gene in each cell is called a carrier. She can pass on the altered gene, but usually does not experience signs and symptoms of the disorder. In rare cases, however, females who carry a NR0B1 mutation may experience adrenal insufficiency or signs of hypogonadotropic hypogonadism such as underdeveloped reproductive tissues, delayed puberty, and an absence of menstruation. </s>


Input: What are the treatments for X-linked adrenal hypoplasia congenita ?

Output: These resources address the diagnosis or management of X-linked adrenal hypoplasia congenita:  - Gene Review: Gene Review: X-Linked Adrenal Hypoplasia Congenita  - Genetic Testing Registry: Congenital adrenal hypoplasia, X-linked  - MedlinePlus Encyclopedia: Adrenal Glands  - MedlinePlus Encyclopedia: Hypogonadotropic Hypogonadism   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) prothrombin deficiency ?

Output: Prothrombin deficiency is a bleeding disorder that slows the blood clotting process. People with this condition often experience prolonged bleeding following an injury, surgery, or having a tooth pulled. In severe cases of prothrombin deficiency, heavy bleeding occurs after minor trauma or even in the absence of injury (spontaneous bleeding). Women with prothrombin deficiency can have prolonged and sometimes abnormally heavy menstrual bleeding. Serious complications can result from bleeding into the joints, muscles, brain, or other internal organs. Milder forms of prothrombin deficiency do not involve spontaneous bleeding, and the condition may only become apparent following surgery or a serious injury. </s>


Input: How many people are affected by prothrombin deficiency ?

Output: Prothrombin deficiency is very rare; it is estimated to affect 1 in 2 million people in the general population. </s>


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

Output: Mutations in the F2 gene cause prothrombin deficiency. The F2 gene provides instructions for making the prothrombin protein (also called coagulation factor II), which plays a critical role in the formation of blood clots in response to injury. Prothrombin is the precursor to thrombin, a protein that initiates a series of chemical reactions to form a blood clot. After an injury, clots protect the body by sealing off damaged blood vessels and preventing further blood loss.  F2 gene mutations reduce the production of prothrombin in cells, which prevents clots from forming properly in response to injury. Problems with blood clotting can lead to excessive bleeding. Some mutations drastically reduce the activity of prothrombin and can lead to severe bleeding episodes. Other F2 gene mutations allow for a moderate amount of prothrombin activity, typically resulting in mild bleeding episodes. </s>


Input: Is prothrombin 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 prothrombin deficiency ?

Output: These resources address the diagnosis or management of prothrombin deficiency:  - Genetic Testing Registry: Prothrombin deficiency, congenital  - MedlinePlus Encyclopedia: Factor II 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) mucopolysaccharidosis type IV ?

Output: Mucopolysaccharidosis type IV (MPS IV), also known as Morquio syndrome, is a progressive condition that mainly affects the skeleton. The rate at which symptoms worsen varies among affected individuals.  The first signs and symptoms of MPS IV usually become apparent during early childhood. Affected individuals develop various skeletal abnormalities, including short stature, knock knees, and abnormalities of the ribs, chest, spine, hips, and wrists. People with MPS IV often have joints that are loose and very flexible (hypermobile), but they may also have restricted movement in certain joints. A characteristic feature of this condition is underdevelopment (hypoplasia) of a peg-like bone in the neck called the odontoid process. The odontoid process helps stabilize the spinal bones in the neck (cervical vertebrae). Odontoid hypoplasia can lead to misalignment of the cervical vertebrae, which may compress and damage the spinal cord, resulting in paralysis or death.  In people with MPS IV, the clear covering of the eye (cornea) typically becomes cloudy, which can cause vision loss. Some affected individuals have recurrent ear infections and hearing loss. The airway may become narrow in some people with MPS IV, leading to frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea). Other common features of this condition include mildly "coarse" facial features, thin tooth enamel, multiple cavities, heart valve abnormalities, a mildly enlarged liver (hepatomegaly), and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). Unlike some other types of mucopolysaccharidosis, MPS IV does not affect intelligence.  The life expectancy of individuals with MPS IV depends on the severity of symptoms. Severely affected individuals may survive only until late childhood or adolescence. Those with milder forms of the disorder usually live into adulthood, although their life expectancy may be reduced. Spinal cord compression and airway obstruction are major causes of death in people with MPS IV. </s>


Input: How many people are affected by mucopolysaccharidosis type IV ?

Output: The exact prevalence of MPS IV is unknown, although it is estimated to occur in 1 in 200,000 to 300,000 individuals. </s>


Input: What are the genetic changes related to mucopolysaccharidosis type IV ?

Output: Mutations in the GALNS and GLB1 genes cause MPS IV. These genes provide instructions for producing enzymes involved in the breakdown of large sugar molecules called glycosaminoglycans (GAGs). GAGs were originally called mucopolysaccharides, which is where this condition gets its name. When MPS IV is caused by mutations in the GALNS gene it is called MPS IV type A (MPS IVA), and when it is caused by mutations in the GLB1 gene it is called MPS IV type B (MPS IVB). In general, the two types of MPS IV cannot be distinguished by their signs and symptoms.  Mutations in the GALNS and GLB1 genes reduce or completely eliminate the activity of the enzymes produced from these genes. Without these enzymes, GAGs accumulate within cells, specifically inside the lysosomes. Lysosomes are compartments in the cell that break down and recycle different types of molecules. Conditions such as MPS IV that cause molecules to build up inside the lysosomes are called lysosomal storage disorders. In MPS IV, GAGs accumulate to toxic levels in many tissues and organs, particularly in the bones. The accumulation of GAGs causes the bone deformities in this disorder. Researchers believe that the buildup of GAGs may also cause the features of MPS IV by interfering with the functions of other proteins inside lysosomes and disrupting the movement of molecules inside the cell. </s>


Input: Is mucopolysaccharidosis type IV 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 mucopolysaccharidosis type IV ?

Output: These resources address the diagnosis or management of mucopolysaccharidosis type IV:  - Genetic Testing Registry: Morquio syndrome  - Genetic Testing Registry: Mucopolysaccharidosis, MPS-IV-A  - Genetic Testing Registry: Mucopolysaccharidosis, MPS-IV-B  - MedlinePlus Encyclopedia: Morquio 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) otopalatodigital syndrome type 2 ?

Output: Otopalatodigital syndrome type 2 is a disorder involving abnormalities in skeletal development and other health problems. It is a member of a group of related conditions called otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 1, frontometaphyseal dysplasia, and Melnick-Needles syndrome. In general, these disorders involve hearing loss caused by malformations in the tiny bones in the ears (ossicles), problems in the development of the roof of the mouth (palate), and skeletal abnormalities involving the fingers and/or toes (digits). Otopalatodigital syndrome type 2 also tends to cause problems in other areas of the body, such as the brain and heart.  People with otopalatodigital syndrome type 2 have characteristic facial features including wide-set and downward-slanting eyes; prominent brow ridges; a broad, flat nose; and a very small lower jaw and chin (micrognathia). The base of the skull may be thickened. Some people with this disorder have hearing loss. Affected individuals are usually of short stature and may have abnormalities of the fingers and toes, such as unusual curvature of the fingers (camptodactyly) and shortened or absent thumbs and big toes. They may have bowed limbs; underdeveloped, irregular ribs that may cause problems with breathing; and other abnormal or absent bones. Some may be born with an opening in the roof of the mouth (a cleft palate).  In addition to skeletal abnormalities, individuals with otopalatodigital syndrome type 2 may have developmental delay, increased fluid in the center of the brain (hydrocephalus), protrusion of the abdominal organs through the navel (omphalocele), heart defects, chest abnormalities, obstruction of the ducts between the kidneys and bladder (ureters), and, in males, opening of the urethra on the underside of the penis (hypospadias).  Males with otopalatodigital syndrome type 2 generally have much more severe signs and symptoms than do females. Males with the disorder usually do not live beyond their first year, because their underdeveloped rib cage does not allow sufficient lung expansion for breathing. </s>


Input: How many people are affected by otopalatodigital syndrome type 2 ?

Output: Otopalatodigital syndrome type 2 is a rare disorder, affecting fewer than 1 in every 100,000 individuals. Its specific incidence is unknown. </s>


Input: What are the genetic changes related to otopalatodigital syndrome type 2 ?

Output: Mutations in the FLNA gene cause otopalatodigital syndrome type 2.  The FLNA gene provides instructions for producing the protein filamin A, which helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. Filamin A binds to another protein called actin, and helps the actin to form the branching network of filaments that make up the cytoskeleton. Filamin A also links actin to many other proteins to perform various functions within the cell.  A small number of mutations in the FLNA gene have been identified in people with otopalatodigital syndrome type 2. The mutations all result in changes to the filamin A protein in the region that binds to actin. The mutations responsible for otopalatodigital syndrome type 2 are described as "gain-of-function" because they appear to enhance the activity of the filamin A protein or give the protein a new, atypical function. Researchers believe that the mutations may change the way the filamin A protein helps regulate processes involved in skeletal development, but it is not known how changes in the protein relate to the specific signs and symptoms of otopalatodigital syndrome type 2. </s>


Input: Is otopalatodigital syndrome type 2 inherited ?

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


Input: What are the treatments for otopalatodigital syndrome type 2 ?

Output: These resources address the diagnosis or management of otopalatodigital syndrome type 2:  - Gene Review: Gene Review: Otopalatodigital Spectrum Disorders  - Genetic Testing Registry: Oto-palato-digital syndrome, type II   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) sialic acid storage disease ?

Output: Sialic acid storage disease is an inherited disorder that primarily affects the nervous system. People with sialic acid storage disease have signs and symptoms that may vary widely in severity. This disorder is generally classified into one of three forms: infantile free sialic acid storage disease, Salla disease, and intermediate severe Salla disease.  Infantile free sialic acid storage disease (ISSD) is the most severe form of this disorder. Babies with this condition have severe developmental delay, weak muscle tone (hypotonia), and failure to gain weight and grow at the expected rate (failure to thrive). They may have unusual facial features that are often described as "coarse," seizures, bone malformations, an enlarged liver and spleen (hepatosplenomegaly), and an enlarged heart (cardiomegaly). The abdomen may be swollen due to the enlarged organs and an abnormal buildup of fluid in the abdominal cavity (ascites). Affected infants may have a condition called hydrops fetalis in which excess fluid accumulates in the body before birth. Children with this severe form of the condition usually live only into early childhood.  Salla disease is a less severe form of sialic acid storage disease. Babies with Salla disease usually begin exhibiting hypotonia during the first year of life and go on to experience progressive neurological problems. Signs and symptoms of Salla disease include intellectual disability and developmental delay, seizures, problems with movement and balance (ataxia), abnormal tensing of the muscles (spasticity), and involuntary slow, sinuous movements of the limbs (athetosis). Individuals with Salla disease usually survive into adulthood.  People with intermediate severe Salla disease have signs and symptoms that fall between those of ISSD and Salla disease in severity. </s>


Input: How many people are affected by sialic acid storage disease ?

Output: Sialic acid storage disease is a very rare disorder. ISSD has been identified in only a few dozen infants worldwide. Salla disease occurs mainly in Finland and Sweden and has been reported in approximately 150 people. A few individuals have been identified as having intermediate severe Salla disease. </s>


Input: What are the genetic changes related to sialic acid storage disease ?

Output: Mutations in the SLC17A5 gene cause all forms of sialic acid storage disease. This gene provides instructions for producing a protein called sialin that is located mainly on the membranes of lysosomes, compartments in the cell that digest and recycle materials. Sialin moves a molecule called free sialic acid, which is produced when certain proteins and fats are broken down, out of the lysosomes to other parts of the cell. Free sialic acid means that the sialic acid is not attached (bound) to other molecules. Researchers believe that sialin may also have other functions in brain cells, in addition to those associated with the lysosomes, but these additional functions are not well understood.  Approximately 20 mutations that cause sialic acid storage disease have been identified in the SLC17A5 gene. Some of these mutations result in sialin that does not function normally; others prevent sialin from being produced. In a few cases, sialin is produced but not routed properly to the lysosomal membrane.  SLC17A5 gene mutations that reduce or eliminate sialin activity result in a buildup of free sialic acid in the lysosomes. It is not known how this buildup, or the disruption of other possible functions of sialin in the brain, causes the specific signs and symptoms of sialic acid storage disease. </s>


Input: Is sialic acid storage disease 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 sialic acid storage disease ?

Output: These resources address the diagnosis or management of sialic acid storage disease:  - Gene Review: Gene Review: Free Sialic Acid Storage Disorders  - Genetic Testing Registry: Salla disease  - Genetic Testing Registry: Sialic acid storage disease, severe infantile type   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) familial dilated cardiomyopathy ?

Output: Familial dilated cardiomyopathy is a genetic form of heart disease. It occurs when heart (cardiac) muscle becomes stretched out in at least one chamber of the heart, causing the open area of the chamber to become enlarged (dilated). As a result, the heart is unable to pump blood as efficiently as usual. Eventually, all four chambers of the heart become dilated as the cardiac muscle tries to increase the amount of blood being pumped through the heart. However, as the cardiac muscle becomes increasingly thin and weakened, it is less able to pump blood. Over time, this condition results in heart failure.  It usually takes many years for symptoms of familial dilated cardiomyopathy to appear. They typically begin in mid-adulthood, but can occur at any time from infancy to late adulthood. Signs and symptoms of familial dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath (dyspnea), extreme tiredness (fatigue), fainting episodes (syncope), and swelling of the legs and feet. In some cases, the first sign of the disorder is sudden cardiac death. The severity of the condition varies among affected individuals, even in members of the same family. </s>


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

Output: It is estimated that 750,000 people in the United States have dilated cardiomyopathy; roughly half of these cases are familial. </s>


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

Output: Mutations in more than 30 genes have been found to cause familial dilated cardiomyopathy. These genes provide instructions for making proteins that are found in cardiac muscle cells called cardiomyocytes.  Many of these proteins play important roles in the contraction of the cardiac muscle through their association with cell structures called sarcomeres. Sarcomeres are the basic units of muscle contraction; they are made of proteins that generate the mechanical force needed for muscles to contract. Many other proteins associated with familial dilated cardiomyopathy make up the structural framework (the cytoskeleton) of cardiomyocytes. The remaining proteins play various roles within cardiomyocytes to ensure their proper functioning.  Mutations in one gene, TTN, account for approximately 20 percent of cases of familial dilated cardiomyopathy. The TTN gene provides instructions for making a protein called titin, which is found in the sarcomeres of many types of muscle cells, including cardiomyocytes. Titin has several functions within sarcomeres. One of its most important jobs is to provide structure, flexibility, and stability to these cell structures. Titin also plays a role in chemical signaling and in assembling new sarcomeres. The TTN gene mutations that cause familial dilated cardiomyopathy result in the production of an abnormally short titin protein. It is unclear how the altered protein causes familial dilated cardiomyopathy, but it is likely that it impairs sarcomere function and disrupts chemical signaling.  It is unclear how mutations in the other genes cause familial dilated cardiomyopathy. It is likely that the changes impair cardiomyocyte function and reduce the ability of these cells to contract, weakening and thinning cardiac muscle.  People with familial dilated cardiomyopathy often do not have an identified mutation in any of the known associated genes. The cause of the condition in these individuals is unknown.  Familial dilated cardiomyopathy is described as nonsyndromic or isolated because it typically affects only the heart. However, dilated cardiomyopathy can also occur as part of syndromes that affect other organs and tissues in the body. These forms of the condition are described as syndromic and are caused by mutations in other genes. Additionally, there are many nongenetic causes of dilated cardiomyopathy, including viral infection and chronic alcohol abuse. </s>


Input: Is familial dilated cardiomyopathy inherited ?

Output: Familial dilated cardiomyopathy has different inheritance patterns depending on the gene involved.  In 80 to 90 percent of cases, familial dilated cardiomyopathy 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. However, some people who inherit the altered gene never develop features of familial dilated cardiomyopathy. (This situation is known as reduced penetrance.) Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  In rare instances, 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.  In other rare cases, this condition is inherited in an X-linked pattern. In these cases, the gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell increases the risk of developing heart disease, but females with such a mutation may not develop familial dilated cardiomyopathy. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes familial dilated cardiomyopathy. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. </s>


Input: What are the treatments for familial dilated cardiomyopathy ?

Output: These resources address the diagnosis or management of familial dilated cardiomyopathy:  - Cincinnati Children's Hospital  - Gene Review: Gene Review: Dilated Cardiomyopathy Overview  - Gene Review: Gene Review: Dystrophinopathies  - Gene Review: Gene Review: LMNA-Related Dilated Cardiomyopathy  - MedlinePlus Encyclopedia: Dilated Cardiomyopathy  - National Heart, Lung, and Blood Institute: How Is Cardiomyopathy Treated?  - Seattle Children's Hospital: Cardiomyopathy Treatment Options  - The Sarcomeric Human Cardiomyopathies Registry (ShaRe)   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) retinal arterial macroaneurysm with supravalvular pulmonic stenosis ?

Output: Retinal arterial macroaneurysm with supravalvular pulmonic stenosis (RAMSVPS) is a disorder that affects blood vessels in the eyes and heart. The condition generally becomes apparent in infancy or childhood.  RAMSVPS damages the arteries in the light-sensitive tissue at the back of the eye (the retina). These arteries gradually develop multiple small bulges called beading. Eventually, larger bulges in the blood vessel walls (macroaneurysms) occur. These macroaneurysms can tear (rupture), leading to bleeding that can spread into other areas of the eye and cause vision loss.  People with RAMSVPS also have a heart condition called supravalvular pulmonic stenosis. Pulmonic stenosis is a narrowing that affects the pulmonic valve between the heart and the lungs. The term "supravalvular" means that the narrowing occurs just above the valve, in a blood vessel called the pulmonary artery. Supravalvular pulmonic stenosis impairs blood flow into the lungs, where blood normally picks up oxygen for distribution to cells and tissues throughout the body. As a result, less oxygen is carried through the bloodstream, leading to signs and symptoms that include shortness of breath; a rapid heartbeat; fatigue; and swelling in the face, feet, or abdomen. </s>


Input: How many people are affected by retinal arterial macroaneurysm with supravalvular pulmonic stenosis ?

Output: RAMSVPS is a rare disorder. Only a small number of affected individuals and families, all from Saudi Arabia, have been described in the medical literature. </s>


Input: What are the genetic changes related to retinal arterial macroaneurysm with supravalvular pulmonic stenosis ?

Output: RAMSVPS is caused by a mutation in the IGFBP7 gene. This gene provides instructions for making a protein called insulin-like growth factor-binding protein 7 (IGFBP7). The IGFBP7 protein is active in the lining of blood vessels (the vascular endothelium). It is thought to help stop a pathway called BRAF signaling, which is involved in directing cell growth.  The IGFBP7 gene mutation that causes RAMSVPS results in an abnormally short IGFBP7 protein that does not function properly. Without normally functioning IGFBP7 protein to control BRAF signaling, this signaling is increased. It is unknown how this increase is related to the specific blood vessel abnormalities that occur in RAMSVPS, or why these abnormalities are confined to the eyes and the pulmonary artery. Researchers suggest that differences in normal levels of IGFBP7 protein in various parts of the body or the presence of other proteins with a similar function in different tissues may account for the specific signs and symptoms of this disorder. </s>


Input: Is retinal arterial macroaneurysm with supravalvular pulmonic stenosis 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 retinal arterial macroaneurysm with supravalvular pulmonic stenosis ?

Output: These resources address the diagnosis or management of RAMSVPS:  - Calgary Retina Consultants: Retinal Arterial Macroaneurysm  - Genetic Testing Registry: Retinal arterial macroaneurysm with supravalvular pulmonic stenosis  - MedlinePlus Encyclopedia: Fluorescein Angiography  - University of Rochester Medical Center: Pulmonary Stenosis   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) oral-facial-digital syndrome ?

Output: Oral-facial-digital syndrome is actually a group of related conditions that affect the development of the oral cavity (the mouth and teeth), facial features, and digits (fingers and toes).  Researchers have identified at least 13 potential forms of oral-facial-digital syndrome. The different types are classified by their patterns of signs and symptoms. However, the features of the various types overlap significantly, and some types are not well defined. The classification system for oral-facial-digital syndrome continues to evolve as researchers find more affected individuals and learn more about this disorder.  The signs and symptoms of oral-facial-digital syndrome vary widely. However, most forms of this disorder involve problems with development of the oral cavity, facial features, and digits. Most forms are also associated with brain abnormalities and some degree of intellectual disability.  Abnormalities of the oral cavity that occur in many types of oral-facial-digital syndrome include a split (cleft) in the tongue, a tongue with an unusual lobed shape, and the growth of noncancerous tumors or nodules on the tongue. Affected individuals may also have extra, missing, or defective teeth. Another common feature is an opening in the roof of the mouth (a cleft palate). Some people with oral-facial-digital syndrome have bands of extra tissue (called hyperplastic frenula) that abnormally attach the lip to the gums.  Distinctive facial features often associated with oral-facial-digital syndrome include a split in the lip (a cleft lip); a wide nose with a broad, flat nasal bridge; and widely spaced eyes (hypertelorism).  Abnormalities of the digits can affect both the fingers and the toes in people with oral-facial-digital syndrome. These abnormalities include fusion of certain fingers or toes (syndactyly), digits that are shorter than usual (brachydactyly), or digits that are unusually curved (clinodactyly). The presence of extra digits (polydactyly) is also seen in most forms of oral-facial-digital syndrome.  Other features occur in only one or a few types of oral-facial digital syndrome. These features help distinguish the different forms of the disorder. For example, the most common form of oral-facial-digital syndrome, type I, is associated with polycystic kidney disease. This kidney disease is characterized by the growth of fluid-filled sacs (cysts) that interfere with the kidneys' ability to filter waste products from the blood. Other forms of oral-facial-digital syndrome are characterized by neurological problems, particular changes in the structure of the brain, bone abnormalities, vision loss, and heart defects. </s>


Input: How many people are affected by oral-facial-digital syndrome ?

Output: Oral-facial-digital syndrome has an estimated incidence of 1 in 50,000 to 250,000 newborns. Type I accounts for the majority of cases of this disorder. The other forms of oral-facial-digital syndrome are very rare; most have been identified in only one or a few families. </s>


Input: What are the genetic changes related to oral-facial-digital syndrome ?

Output: Only one gene, OFD1, has been associated with oral-facial-digital syndrome. Mutations in this gene cause oral-facial-digital syndrome type I. OFD1 gene mutations were also found in an affected family whose disorder was classified as type VII; however, researchers now believe that type VII is the same as type I.  The OFD1 gene provides instructions for making a protein whose function is not fully understood. It appears to play an important role in the early development of many parts of the body, including the brain, face, limbs, and kidneys. Mutations in the OFD1 gene prevent cells from making enough functional OFD1 protein, which disrupts the normal development of these structures. It is unclear how a shortage of this protein causes the specific features of oral-facial-digital syndrome type I.  Researchers are actively searching for the genetic changes responsible for the other forms of oral-facial-digital syndrome. </s>


Input: Is oral-facial-digital syndrome inherited ?

Output: Oral-facial-digital syndrome type I is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. Some cells produce a normal amount of OFD1 protein and other cells produce none. The resulting overall reduction in the amount of this protein leads to the signs and symptoms of oral-facial-digital syndrome type I.  In males (who have only one X chromosome), mutations result in a total loss of the OFD1 protein. A lack of this protein is usually lethal very early in development, so very few males are born with oral-facial-digital syndrome type I. Affected males usually die before birth, although a few have lived into early infancy.  Most of the other forms of oral-facial-digital syndrome are inherited in an autosomal recessive pattern, which suggests that both copies of a causative 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 oral-facial-digital syndrome ?

Output: These resources address the diagnosis or management of oral-facial-digital syndrome:  - Gene Review: Gene Review: Oral-Facial-Digital Syndrome Type I  - Genetic Testing Registry: Mohr syndrome  - Genetic Testing Registry: Oral-facial-digital syndrome  - Genetic Testing Registry: Orofacial-digital syndrome III  - Genetic Testing Registry: Orofacial-digital syndrome IV  - Genetic Testing Registry: Orofaciodigital syndrome 10  - Genetic Testing Registry: Orofaciodigital syndrome 11  - Genetic Testing Registry: Orofaciodigital syndrome 5  - Genetic Testing Registry: Orofaciodigital syndrome 6  - Genetic Testing Registry: Orofaciodigital syndrome 7  - Genetic Testing Registry: Orofaciodigital syndrome 8  - Genetic Testing Registry: Orofaciodigital syndrome 9  - Genetic Testing Registry: Orofaciodigital syndromes  - MedlinePlus Encyclopedia: Cleft Lip and Palate  - MedlinePlus Encyclopedia: Polycystic Kidney Disease  - MedlinePlus Encyclopedia: Polydactyly   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) congenital hemidysplasia with ichthyosiform erythroderma and limb defects ?

Output: Congenital hemidysplasia with ichthyosiform erythroderma and limb defects, more commonly known by the acronym CHILD syndrome, is a condition that affects the development of several parts of the body. The signs and symptoms of this disorder are typically limited to either the right side or the left side of the body. ("Hemi-" means "half," and "dysplasia" refers to abnormal growth.) The right side is affected about twice as often as the left side.  People with CHILD syndrome have a skin condition characterized by large patches of skin that are red and inflamed (erythroderma) and covered with flaky scales (ichthyosis). This condition is most likely to occur in skin folds and creases and usually does not affect the face. The skin abnormalities are present at birth and persist throughout life.  CHILD syndrome also disrupts the formation of the arms and legs during early development. Children with this disorder may be born with one or more limbs that are shortened or missing. The limb abnormalities occur on the same side of the body as the skin abnormalities.  Additionally, CHILD syndrome may affect the development of the brain, heart, lungs, and kidneys. </s>


Input: How many people are affected by congenital hemidysplasia with ichthyosiform erythroderma and limb defects ?

Output: CHILD syndrome is a rare disorder; it has been reported in about 60 people worldwide. This condition occurs almost exclusively in females. </s>


Input: What are the genetic changes related to congenital hemidysplasia with ichthyosiform erythroderma and limb defects ?

Output: Mutations in the NSDHL gene cause CHILD syndrome. This gene provides instructions for making an enzyme that is involved in the production of cholesterol. Cholesterol is a type of fat that is produced in the body and obtained from foods that come from animals, particularly egg yolks, meat, fish, and dairy products. Although high cholesterol levels are a well-known risk factor for heart disease, the body needs some cholesterol to develop and function normally both before and after birth. Cholesterol is an important component of cell membranes and the protective substance covering nerve cells (myelin). Additionally, cholesterol plays a role in the production of certain hormones and digestive acids.  The mutations that underlie CHILD syndrome eliminate the activity of the NSDHL enzyme, which disrupts the normal production of cholesterol within cells. A shortage of this enzyme may also allow potentially toxic byproducts of cholesterol production to build up in the body's tissues. Researchers suspect that low cholesterol levels and/or an accumulation of other substances disrupt the growth and development of many parts of the body. It is not known, however, how a disturbance in cholesterol production leads to the specific features of CHILD syndrome. </s>


Input: Is congenital hemidysplasia with ichthyosiform erythroderma and limb defects inherited ?

Output: This condition has an X-linked dominant pattern of inheritance. 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. The inheritance is dominant if one copy of the altered gene in each cell is sufficient to cause the condition.  Most cases of CHILD syndrome occur sporadically, which means only one member of a family is affected. Rarely, the condition can run in families and is passed from mother to daughter. Researchers believe that CHILD syndrome occurs almost exclusively in females because affected males die before birth. Only one male with CHILD syndrome has been reported. </s>


Input: What are the treatments for congenital hemidysplasia with ichthyosiform erythroderma and limb defects ?

Output: These resources address the diagnosis or management of CHILD syndrome:  - Gene Review: Gene Review: NSDHL-Related Disorders  - Genetic Testing Registry: Child 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) hereditary hemorrhagic telangiectasia ?

Output: Hereditary hemorrhagic telangiectasia is a disorder that results in the development of multiple abnormalities in the blood vessels.  In the circulatory system, blood carrying oxygen from the lungs is normally pumped by the heart into the arteries at high pressure. The pressure allows the blood to make its way through the arteries to the smaller vessels (arterioles and capillaries) that supply oxygen to the body's tissues. By the time blood reaches the capillaries, the pressure is much lower. The blood then proceeds from the capillaries into veins, through which it eventually returns to the heart.  In hereditary hemorrhagic telangiectasia, some arterial vessels flow directly into veins rather than into the capillaries. These abnormalities are called arteriovenous malformations. When they occur in vessels near the surface of the skin, where they are visible as red markings, they are known as telangiectases (the singular is telangiectasia).  Without the normal buffer of the capillaries, the blood moves from the arteries at high pressure into the thinner walled, less elastic veins. The extra pressure tends to strain and enlarge these blood vessels, and may result in compression or irritation of adjacent tissues and frequent episodes of severe bleeding (hemorrhage). Nosebleeds are very common in people with hereditary hemorrhagic telangiectasia, and more serious problems may arise from hemorrhages in the brain, liver, lungs, or other organs.  Forms of hereditary hemorrhagic telangiectasia include type 1, type 2, type 3, and juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome. People with type 1 tend to develop symptoms earlier than those with type 2, and are more likely to have blood vessel malformations in the lungs and brain. Type 2 and type 3 may be associated with a higher risk of liver involvement. Women are more likely than men to develop blood vessel malformations in the lungs with type 1, and are also at higher risk of liver involvement with both type 1 and type 2. Individuals with any form of hereditary hemorrhagic telangiectasia, however, can have any of these problems.  Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome is a condition that involves both arteriovenous malformations and a tendency to develop growths (polyps) in the gastrointestinal tract. Types 1, 2 and 3 do not appear to increase the likelihood of such polyps. </s>


Input: How many people are affected by hereditary hemorrhagic telangiectasia ?

Output: The incidence of hereditary hemorrhagic telangiectasia is difficult to determine because the severity of symptoms can vary widely and some symptoms, such as frequent nosebleeds, are common in the general population. In addition, arteriovenous malformations may be associated with other medical conditions. Hereditary hemorrhagic telangiectasia is widely distributed, occurring in many ethnic groups around the world. It is believed to affect between 1 in 5,000 and 1 in 10,000 people. </s>


Input: What are the genetic changes related to hereditary hemorrhagic telangiectasia ?

Output: Mutations in the ACVRL1, ENG, and SMAD4 genes cause hereditary hemorrhagic telangiectasia.  Hereditary hemorrhagic telangiectasia type 1 is caused by mutations in the gene ENG. Type 2 is caused by mutations in the gene ACVRL1. Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome is caused by mutations in the gene SMAD4. All these genes provide instructions for making proteins that are found in the lining of the blood vessels. These proteins interact with growth factors that control blood vessel development. The gene involved in hereditary hemorrhagic telangiectasia type 3 is not known, but is believed to be located on chromosome 5.  Mutations in these genes generally prevent the production of the associated protein, or result in the production of a defective protein that cannot fulfill its function. An individual with a mutated gene will therefore have a reduced amount of the functional protein available in the tissue lining the blood vessels. This deficiency is believed to result in the signs and symptoms of hereditary hemorrhagic telangiectasia. </s>


Input: Is hereditary hemorrhagic telangiectasia inherited ?

Output: This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. </s>


Input: What are the treatments for hereditary hemorrhagic telangiectasia ?

Output: These resources address the diagnosis or management of hereditary hemorrhagic telangiectasia:  - Gene Review: Gene Review: Hereditary Hemorrhagic Telangiectasia  - Genetic Testing Registry: Hereditary hemorrhagic telangiectasia type 2  - Genetic Testing Registry: Hereditary hemorrhagic telangiectasia type 3  - Genetic Testing Registry: Hereditary hemorrhagic telangiectasia type 4  - Genetic Testing Registry: Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome  - Genetic Testing Registry: Osler hemorrhagic telangiectasia syndrome  - MedlinePlus Encyclopedia: Osler-Weber-Rendu 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) mitochondrial membrane protein-associated neurodegeneration ?

Output: Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a disorder of the nervous system. The condition typically begins in childhood or early adulthood and worsens (progresses) over time.  MPAN commonly begins with difficulty walking. As the condition progresses, affected individuals usually develop other movement problems, including muscle stiffness (spasticity) and involuntary muscle cramping (dystonia). Many people with MPAN have a pattern of movement abnormalities known as parkinsonism. These abnormalities include unusually slow movement (bradykinesia), muscle rigidity, involuntary trembling (tremors), and an inability to hold the body upright and balanced (postural instability).  Other neurological problems that occur in individuals with MPAN include degeneration of the nerve cells that carry visual information from the eyes to the brain (optic atrophy), which can impair vision; problems with speech (dysarthria); difficulty swallowing (dysphagia); and, in later stages of the condition, an inability to control the bowels or the flow of urine (incontinence). Additionally, affected individuals may experience a loss of intellectual function (dementia) and psychiatric symptoms such as behavioral problems, mood swings, hyperactivity, and depression.  MPAN is characterized by an abnormal buildup of iron in certain regions of the brain. Because of these deposits, MPAN is considered part of a group of conditions known as neurodegeneration with brain iron accumulation (NBIA). </s>


Input: How many people are affected by mitochondrial membrane protein-associated neurodegeneration ?

Output: MPAN is a rare condition that is estimated to affect less than 1 in 1 million people. </s>


Input: What are the genetic changes related to mitochondrial membrane protein-associated neurodegeneration ?

Output: Mutations in the C19orf12 gene cause MPAN. The protein produced from this gene is found in the membrane of cellular structures called mitochondria, which are the energy-producing centers of the cell. Although its function is unknown, researchers suggest that the C19orf12 protein plays a role in the maintenance of fat (lipid) molecules, a process known as lipid homeostasis.  The gene mutations that cause this condition lead to an altered C19orf12 protein that likely has little or no function. It is unclear how these genetic changes lead to the neurological problems associated with MPAN. Researchers are working to determine whether there is a link between problems with lipid homeostasis and brain iron accumulation and how these abnormalities might contribute to the features of this disorder. </s>


Input: Is mitochondrial membrane protein-associated neurodegeneration 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 mitochondrial membrane protein-associated neurodegeneration ?

Output: These resources address the diagnosis or management of mitochondrial membrane protein-associated neurodegeneration:  - Gene Review: Gene Review: Mitochondrial Membrane Protein-Associated Neurodegeneration  - Gene Review: Gene Review: Neurodegeneration with Brain Iron Accumulation Disorders Overview  - Genetic Testing Registry: Neurodegeneration with brain iron accumulation 4  - Spastic Paraplegia Foundation: Treatments and Therapies   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) T-cell immunodeficiency, congenital alopecia, and nail dystrophy ?

Output: T-cell immunodeficiency, congenital alopecia, and nail dystrophy is a type of severe combined immunodeficiency (SCID), which is a group of disorders characterized by an almost total lack of immune protection from foreign invaders such as bacteria and viruses. People with this form of SCID are missing functional immune cells called T cells, which normally recognize and attack foreign invaders to prevent infection. Without functional T cells, affected individuals develop repeated and persistent infections starting early in life. The infections result in slow growth and can be life-threatening; without effective treatment, most affected individuals live only into infancy or early childhood.  T-cell immunodeficiency, congenital alopecia, and nail dystrophy also affects growth of the hair and nails. Congenital alopecia refers to an absence of hair that is apparent from birth. Affected individuals have no scalp hair, eyebrows, or eyelashes. Nail dystrophy is a general term that describes malformed fingernails and toenails; in this condition, the nails are often ridged, pitted, or abnormally curved.  Researchers have described abnormalities of the brain and spinal cord (central nervous system) in at least two cases of this condition. However, it is not yet known whether central nervous system abnormalities are a common feature of T-cell immunodeficiency, congenital alopecia, and nail dystrophy. </s>


Input: How many people are affected by T-cell immunodeficiency, congenital alopecia, and nail dystrophy ?

Output: T-cell immunodeficiency, congenital alopecia, and nail dystrophy is a rare disorder. It has been diagnosed in only a few individuals, almost all of whom are members of a large extended family from a community in southern Italy. </s>


Input: What are the genetic changes related to T-cell immunodeficiency, congenital alopecia, and nail dystrophy ?

Output: T-cell immunodeficiency, congenital alopecia, and nail dystrophy results from mutations in the FOXN1 gene. This gene provides instructions for making a protein that is important for development of the skin, hair, nails, and immune system. Studies suggest that this protein helps guide the formation of hair follicles and the growth of fingernails and toenails. The FOXN1 protein also plays a critical role in the formation of the thymus, which is a gland located behind the breastbone where T cells mature and become functional. Researchers suspect that the FOXN1 protein is also involved in the development of the central nervous system, although its role is unclear.  Mutations in the FOXN1 gene prevent cells from making any functional FOXN1 protein. Without this protein, hair and nails cannot grow normally. A lack of FOXN1 protein also prevents the formation of the thymus. When this gland is not present, the immune system cannot produce mature, functional T cells to fight infections. As a result, people with T-cell immunodeficiency, congenital alopecia, and nail dystrophy develop recurrent serious infections starting early in life. </s>


Input: Is T-cell immunodeficiency, congenital alopecia, and nail dystrophy 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. However, some people who carry one copy of a mutated FOXN1 gene have abnormal fingernails or toenails. </s>


Input: What are the treatments for T-cell immunodeficiency, congenital alopecia, and nail dystrophy ?

Output: These resources address the diagnosis or management of T-cell immunodeficiency, congenital alopecia, and nail dystrophy:  - Be The Match: What is a Bone Marrow Transplant?  - Genetic Testing Registry: T-cell immunodeficiency, congenital alopecia and nail dystrophy  - MedlinePlus Encyclopedia: 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) Alpers-Huttenlocher syndrome ?

Output: Alpers-Huttenlocher syndrome is one of the most severe of a group of conditions called the POLG-related disorders. The conditions in this group feature a range of similar signs and symptoms involving muscle-, nerve-, and brain-related functions. Alpers-Huttenlocher syndrome typically becomes apparent in children between ages 2 and 4. People with this condition usually have three characteristic features: recurrent seizures that do not improve with treatment (intractable epilepsy), loss of mental and movement abilities (psychomotor regression), and liver disease.  People with Alpers-Huttenlocher syndrome usually have additional signs and symptoms. Most have problems with coordination and balance (ataxia) and disturbances in nerve function (neuropathy). Neuropathy can lead to abnormal or absent reflexes (areflexia). In addition, affected individuals may develop weak muscle tone (hypotonia) that worsens until they lose the ability to control their muscles and movement. Some people with Alpers-Huttenlocher syndrome lose the ability to walk, sit, or feed themselves. Other movement-related symptoms in affected individuals can include involuntary muscle twitches (myoclonus), uncontrollable movements of the limbs (choreoathetosis), or a pattern of movement abnormalities known as parkinsonism.  Affected individuals may have other brain-related signs and symptoms. Migraine headaches, often with visual sensations or auras, are common. Additionally, people with this condition may have decreased brain function that is demonstrated as sleepiness, inability to concentrate, irritability, or loss of language skills or memory. Some people with the condition may lose their eyesight or hearing. People with Alpers-Huttenlocher syndrome can survive from a few months to more than 10 years after the condition first appears. </s>


Input: How many people are affected by Alpers-Huttenlocher syndrome ?

Output: The prevalence of Alpers-Huttenlocher syndrome is approximately 1 in 100,000 individuals. </s>


Input: What are the genetic changes related to Alpers-Huttenlocher syndrome ?

Output: Alpers-Huttenlocher syndrome is caused by mutations in the POLG gene. This gene provides instructions for making one part, the alpha subunit, of a protein called polymerase gamma (pol ). Pol  functions in mitochondria, which are structures within cells that use oxygen to convert the energy from food into a form cells can use. Mitochondria each contain a small amount of DNA, known as mitochondrial DNA (mtDNA), which is essential for the normal function of these structures. Pol  "reads" sequences of mtDNA and uses them as templates to produce new copies of mtDNA in a process called DNA replication.  Most POLG gene mutations change single protein building blocks (amino acids) in the alpha subunit of pol . These changes result in a mutated pol  that has a reduced ability to replicate DNA. Although the mechanism is unknown, mutations in the POLG gene often result in a reduced number of copies of mtDNA (mtDNA depletion), particularly in muscle, brain, and liver cells. MtDNA depletion causes a decrease in cellular energy, which could account for the signs and symptoms of Alpers-Huttenlocher syndrome.  A mutation in the POLG gene has not been identified in approximately 13 percent of people diagnosed with Alpers-Huttenlocher syndrome. Researchers are working to identify other genes that may be responsible for the condition. </s>


Input: Is Alpers-Huttenlocher 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 Alpers-Huttenlocher syndrome ?

Output: These resources address the diagnosis or management of Alpers-Huttenlocher syndrome:  - Gene Review: Gene Review: POLG-Related Disorders  - Genetic Testing Registry: Progressive sclerosing poliodystrophy  - United Mitochondrial Disease Foundation: Diagnosis of Mitochondrial Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) X-linked sideroblastic anemia and ataxia ?

Output: X-linked sideroblastic anemia and ataxia is a rare condition characterized by a blood disorder called sideroblastic anemia and movement problems known as ataxia. This condition occurs only in males.  Sideroblastic anemia results when developing red blood cells called erythroblasts do not make enough hemoglobin, which is the protein that carries oxygen in the blood. People with X-linked sideroblastic anemia and ataxia have mature red blood cells that are smaller than normal (microcytic) and appear pale (hypochromic) because of the shortage of hemoglobin. This disorder also leads to an abnormal accumulation of iron in red blood cells. The iron-loaded erythroblasts, which are present in bone marrow, are called ring sideroblasts. These abnormal cells give the condition its name. Unlike other forms of sideroblastic anemia, X-linked sideroblastic anemia and ataxia does not cause a potentially dangerous buildup of iron in the body. The anemia is typically mild and usually does not cause any symptoms.  X-linked sideroblastic anemia and ataxia causes problems with balance and coordination that appear early in life. The ataxia primarily affects the trunk, making it difficult to sit, stand, and walk unassisted. In addition to ataxia, people with this condition often have trouble coordinating movements that involve judging distance or scale (dysmetria) and find it difficult to make rapid, alternating movements (dysdiadochokinesis). Mild speech difficulties (dysarthria), tremor, and abnormal eye movements have also been reported in some affected individuals. </s>


Input: How many people are affected by X-linked sideroblastic anemia and ataxia ?

Output: X-linked sideroblastic anemia and ataxia is a rare disorder; only a few affected families have been reported. </s>


Input: What are the genetic changes related to X-linked sideroblastic anemia and ataxia ?

Output: Mutations in the ABCB7 gene cause X-linked sideroblastic anemia and ataxia. The ABCB7 gene provides instructions for making a protein that is critical for heme production. Heme is a component of the hemoglobin protein, which is vital for supplying oxygen to the entire body. The ABCB7 protein also plays a role in the formation of certain proteins containing clusters of iron and sulfur atoms. Overall, researchers believe that the ABCB7 protein helps maintain an appropriate balance of iron (iron homeostasis) in developing red blood cells.  ABCB7 mutations slightly alter the structure of the ABCB7 protein, disrupting its usual role in heme production and iron homeostasis. Anemia results when heme cannot be produced normally, and therefore not enough hemoglobin is made. It is unclear how changes in the ABCB7 gene lead to ataxia and other problems with movement. </s>


Input: Is X-linked sideroblastic anemia and ataxia 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. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In X-linked recessive inheritance, a female with one altered copy of the gene in each cell is called a carrier. Carriers of an ABCB7 mutation can pass on the mutated gene but do not develop ataxia or other health problems associated with X-linked sideroblastic anemia and ataxia. However, carriers may have abnormally small, pale red blood cells and related changes that can be detected with a blood test. </s>


Input: What are the treatments for X-linked sideroblastic anemia and ataxia ?

Output: These resources address the diagnosis or management of X-linked sideroblastic anemia and ataxia:  - Gene Review: Gene Review: X-Linked Sideroblastic Anemia and Ataxia  - Genetic Testing Registry: Anemia sideroblastic and spinocerebellar ataxia  - MedlinePlus Encyclopedia: Anemia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) pulmonary arterial hypertension ?

Output: Pulmonary arterial hypertension is a progressive disorder characterized by abnormally high blood pressure (hypertension) in the pulmonary artery, the blood vessel that carries blood from the heart to the lungs. Pulmonary arterial hypertension is one form of a broader condition known as pulmonary hypertension. Pulmonary hypertension occurs when most of the very small arteries throughout the lungs narrow in diameter, which increases the resistance to blood flow through the lungs. To overcome the increased resistance, blood pressure increases in the pulmonary artery and in the right ventricle of the heart, which is the chamber that pumps blood into the pulmonary artery. Ultimately, the increased blood pressure can damage the right ventricle of the heart.  Signs and symptoms of pulmonary arterial hypertension occur when increased blood pressure cannot fully overcome the elevated resistance. As a result, the flow of oxygenated blood from the lungs to the rest of the body is insufficient. Shortness of breath (dyspnea) during exertion and fainting spells are the most common symptoms of pulmonary arterial hypertension. People with this disorder may experience additional symptoms, particularly as the condition worsens. Other symptoms include dizziness, swelling (edema) of the ankles or legs, chest pain, and a rapid heart rate. </s>


Input: How many people are affected by pulmonary arterial hypertension ?

Output: In the United States, about 1,000 new cases of pulmonary arterial hypertension are diagnosed each year. This disorder is twice as common in females as in males. </s>


Input: What are the genetic changes related to pulmonary arterial hypertension ?

Output: Mutations in the BMPR2 gene are the most common genetic cause of pulmonary arterial hypertension. This gene plays a role in regulating the number of cells in certain tissues. Researchers suggest that a mutation in this gene promotes cell division or prevents cell death, resulting in an overgrowth of cells in small arteries throughout the lungs. As a result, these arteries narrow in diameter, which increases the resistance to blood flow. Blood pressure in the pulmonary artery and the right ventricle of the heart increases to overcome the increased resistance to blood flow.  Mutations in several additional genes have also been found to cause pulmonary arterial hypertension, but they are much less common causes of the disorder than are BMPR2 gene mutations. Variations in other genes may increase the risk of developing pulmonary arterial hypertension or modify the course of the disease (usually making it more severe). Changes in as-yet-unidentified genes may also be associated with this condition.  Although pulmonary arterial hypertension often occurs on its own, it can also be part of syndromes that affect many parts of the body. For example, this condition is occasionally found in people with systemic scleroderma, systemic lupus erythematosus, critical congenital heart disease, or Down syndrome.  Researchers have also identified nongenetic factors that increase the risk of developing pulmonary arterial hypertension. These include certain drugs used as appetite suppressants and several illegal drugs, such as cocaine and methamphetamine. Pulmonary arterial hypertension is also a rare complication of certain infectious diseases, including HIV and schistosomiasis. </s>


Input: Is pulmonary arterial hypertension inherited ?

Output: Pulmonary arterial hypertension is usually sporadic, which means it occurs in individuals with no known family history of the disorder. These non-familial cases are described as idiopathic pulmonary arterial hypertension. About 20 percent of these cases are caused by mutations in one of the genes known to be associated with the disease, but most of the time a causative gene mutation has not been identified.  Inherited cases of this disorder are known as familial pulmonary arterial hypertension. When the condition is inherited, it most often has an autosomal dominant pattern of inheritance, which means one copy of an altered gene in each cell is sufficient to cause the disorder. However, many people with an altered gene never develop pulmonary arterial hypertension; this phenomenon is called reduced penetrance. </s>


Input: What are the treatments for pulmonary arterial hypertension ?

Output: These resources address the diagnosis or management of pulmonary arterial hypertension:  - Gene Review: Gene Review: Heritable Pulmonary Arterial Hypertension  - Genetic Testing Registry: Primary pulmonary hypertension  - Genetic Testing Registry: Primary pulmonary hypertension 2  - Genetic Testing Registry: Primary pulmonary hypertension 3  - Genetic Testing Registry: Primary pulmonary hypertension 4  - MedlinePlus Encyclopedia: Pulmonary hypertension   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) systemic scleroderma ?

Output: Systemic scleroderma is an autoimmune disorder that affects the skin and internal organs. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. The word "scleroderma" means hard skin in Greek, and the condition is characterized by the buildup of scar tissue (fibrosis) in the skin and other organs. The condition is also called systemic sclerosis because the fibrosis can affect organs other than the skin. Fibrosis is due to the excess production of a tough protein called collagen, which normally strengthens and supports connective tissues throughout the body.  The signs and symptoms of systemic scleroderma usually begin with episodes of Raynaud phenomenon, which can occur weeks to years before fibrosis. In Raynaud phenomenon, the fingers and toes of affected individuals turn white or blue in response to cold temperature or other stresses. This effect occurs because of problems with the small vessels that carry blood to the extremities. Another early sign of systemic scleroderma is puffy or swollen hands before thickening and hardening of the skin due to fibrosis. Skin thickening usually occurs first in the fingers (called sclerodactyly) and may also involve the hands and face. In addition, people with systemic scleroderma often have open sores (ulcers) on their fingers, painful bumps under the skin (calcinosis), or small clusters of enlarged blood vessels just under the skin (telangiectasia).  Fibrosis can also affect internal organs and can lead to impairment or failure of the affected organs. The most commonly affected organs are the esophagus, heart, lungs, and kidneys. Internal organ involvement may be signaled by heartburn, difficulty swallowing (dysphagia), high blood pressure (hypertension), kidney problems, shortness of breath, diarrhea, or impairment of the muscle contractions that move food through the digestive tract (intestinal pseudo-obstruction).  There are three types of systemic scleroderma, defined by the tissues affected in the disorder. In one type of systemic scleroderma, known as limited cutaneous systemic scleroderma, fibrosis usually affects only the hands, arms, and face. Limited cutaneous systemic scleroderma used to be known as CREST syndrome, which is named for the common features of the condition: calcinosis, Raynaud phenomenon, esophageal motility dysfunction, sclerodactyly, and telangiectasia. In another type of systemic scleroderma, known as diffuse cutaneous systemic scleroderma, the fibrosis affects large areas of skin, including the torso and the upper arms and legs, and often involves internal organs. In diffuse cutaneous systemic scleroderma, the condition worsens quickly and organ damage occurs earlier than in other types of the condition. In the third type of systemic scleroderma, called systemic sclerosis sine scleroderma ("sine" means without in Latin), fibrosis affects one or more internal organs but not the skin.  Approximately 15 percent to 25 percent of people with features of systemic scleroderma also have signs and symptoms of another condition that affects connective tissue, such as polymyositis, dermatomyositis, rheumatoid arthritis, Sjgren syndrome, or systemic lupus erythematosus. The combination of systemic scleroderma with other connective tissue abnormalities is known as scleroderma overlap syndrome. </s>


Input: How many people are affected by systemic scleroderma ?

Output: The prevalence of systemic scleroderma is estimated to range from 50 to 300 cases per 1 million people. For reasons that are unknown, women are four times more likely to develop the condition than men. </s>


Input: What are the genetic changes related to systemic scleroderma ?

Output: Researchers have identified variations in several genes that may influence the risk of developing systemic scleroderma. The most commonly associated genes belong to a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Each HLA gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. Specific normal variations of several HLA genes seem to affect the risk of developing systemic scleroderma.  Normal variations in other genes related to the body's immune function, such as IRF5 and STAT4, are also associated with an increased risk of developing systemic scleroderma. Variations in the IRF5 gene are specifically associated with diffuse cutaneous systemic scleroderma, and a variation in the STAT4 gene is associated with limited cutaneous systemic scleroderma. The IRF5 and STAT4 genes both play a role in initiating an immune response when the body detects a foreign invader (pathogen) such as a virus.  It is not known how variations in the associated genes contribute to the increased risk of systemic scleroderma. Variations in multiple genes may work together to increase the risk of developing the condition, and researchers are working to identify and confirm other genes associated with increased risk. In addition, a combination of genetic and environmental factors seems to play a role in developing systemic scleroderma. </s>


Input: Is systemic scleroderma inherited ?

Output: Most cases of systemic scleroderma are sporadic, which means they occur in people with no history of the condition in their family. However, some people with systemic scleroderma have close relatives with other autoimmune disorders.  A small percentage of all cases of systemic scleroderma have been reported to run in families; however, the condition does not have a clear pattern of inheritance. Multiple genetic and environmental factors likely play a part in determining the risk of developing this condition. As a result, inheriting a genetic variation linked with systemic scleroderma does not mean that a person will develop the condition. </s>


Input: What are the treatments for systemic scleroderma ?

Output: These resources address the diagnosis or management of systemic scleroderma:  - Cedars-Sinai Medical Center  - Genetic Testing Registry: Scleroderma, familial progressive  - University of Maryland Medical 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) Denys-Drash syndrome ?

Output: Denys-Drash syndrome is a condition that affects the kidneys and genitalia.  Denys-Drash syndrome is characterized by kidney disease that begins within the first few months of life. Affected individuals have a condition called diffuse glomerulosclerosis, in which scar tissue forms throughout glomeruli, which are the tiny blood vessels in the kidneys that filter waste from blood. In people with Denys-Drash syndrome, this condition often leads to kidney failure in childhood. People with Denys-Drash syndrome have an estimated 90 percent chance of developing a rare form of kidney cancer known as Wilms tumor. Affected individuals may develop multiple tumors in one or both kidneys.  Although males with Denys-Drash syndrome have the typical male chromosome pattern (46,XY), they have gonadal dysgenesis, in which external genitalia do not look clearly male or clearly female (ambiguous genitalia) or the genitalia appear completely female. The testes of affected males are undescended, which means they are abnormally located in the pelvis, abdomen, or groin. As a result, males with Denys-Drash are typically unable to have biological children (infertile).  Affected females usually have normal genitalia and have only the kidney features of the condition. Because they do not have all the features of the condition, females are usually given the diagnosis of isolated nephrotic syndrome. </s>


Input: How many people are affected by Denys-Drash syndrome ?

Output: The prevalence of Denys-Drash syndrome is unknown; at least 150 affected individuals have been reported in the scientific literature. </s>