Input: What is (are) congenital central hypoventilation syndrome ?

Output: Congenital central hypoventilation syndrome (CCHS) is a disorder that affects breathing. People with this disorder take shallow breaths (hypoventilate), especially during sleep, resulting in a shortage of oxygen and a buildup of carbon dioxide in the blood. Ordinarily, the part of the nervous system that controls involuntary body processes (autonomic nervous system) would react to such an imbalance by stimulating the individual to breathe more deeply or wake up. This reaction is impaired in people with CCHS, and they must be supported with a machine to help them breathe (mechanical ventilation) or a device that stimulates a normal breathing pattern (diaphragm pacemaker). Some affected individuals need this support 24 hours a day, while others need it only at night.  Symptoms of CCHS usually become apparent shortly after birth. Affected infants hypoventilate upon falling asleep and exhibit a bluish appearance of the skin or lips (cyanosis). Cyanosis is caused by lack of oxygen in the blood. In some milder cases, CCHS may be diagnosed later in life. In addition to the breathing problem, people with this disorder may have difficulty regulating their heart rate and blood pressure, for example in response to exercise or changes in body position. They may have abnormalities in the nerves that control the digestive tract (Hirschsprung disease), resulting in severe constipation, intestinal blockage, and enlargement of the colon. They are also at increased risk of developing certain tumors of the nervous system called neuroblastomas, ganglioneuromas, and ganglioneuroblastomas. Some affected individuals develop learning difficulties or other neurological problems, which may be worsened by oxygen deprivation if treatment to support their breathing is not completely effective.  Individuals with CCHS usually have eye abnormalities, including a decreased response of the pupils to light. They also have decreased perception of pain, low body temperature, and occasional episodes of profuse sweating.  People with CCHS, especially children, may have a characteristic appearance with a short, wide, somewhat flattened face often described as "box-shaped." Life expectancy and the extent of any cognitive disabilities depend on the severity of the disorder, timing of the diagnosis, and the success of treatment. </s>


Input: How many people are affected by congenital central hypoventilation syndrome ?

Output: CCHS is a relatively rare disorder. Approximately 1,000 individuals with this condition have been identified. Researchers believe that some cases of sudden infant death syndrome (SIDS) or sudden unexplained death in children may be caused by undiagnosed CCHS. </s>


Input: What are the genetic changes related to congenital central hypoventilation syndrome ?

Output: Mutations in the PHOX2B gene cause CCHS. The PHOX2B gene provides instructions for making a protein that acts early in development to help promote the formation of nerve cells (neurons) and regulate the process by which the neurons mature to carry out specific functions (differentiation). The protein is active in the neural crest, which is a group of cells in the early embryo that give rise to many tissues and organs. Neural crest cells migrate to form parts of the autonomic nervous system, many tissues in the face and skull, and other tissue and cell types.  Mutations are believed to interfere with the PHOX2B protein's role in promoting neuron formation and differentiation, especially in the autonomic nervous system, resulting in the problems regulating breathing and other body functions that occur in CCHS. </s>


Input: Is congenital central hypoventilation syndrome inherited ?

Output: This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  More than 90 percent of cases of CCHS result from new mutations in the PHOX2B gene. These cases occur in people with no history of the disorder in their family. Occasionally an affected person inherits the mutation from one affected parent. The number of such cases has been increasing as better treatment has allowed more affected individuals to live into adulthood.  About 5 to 10 percent of affected individuals inherit the mutation from a seemingly unaffected parent with somatic mosaicism. Somatic mosaicism means that some of the body's cells have a PHOX2B gene mutation, and others do not. A parent with mosaicism for a PHOX2B gene mutation may not show any signs or symptoms of CCHS. </s>


Input: What are the treatments for congenital central hypoventilation syndrome ?

Output: These resources address the diagnosis or management of CCHS:  - Gene Review: Gene Review: Congenital Central Hypoventilation Syndrome  - Genetic Testing Registry: Congenital central hypoventilation  - MedlinePlus Encyclopedia: Hirschsprung's 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) Aicardi syndrome ?

Output: Aicardi syndrome is a disorder that occurs almost exclusively in females. It is characterized by three main features that occur together in most affected individuals. People with Aicardi syndrome have absent or underdeveloped tissue connecting the left and right halves of the brain (agenesis or dysgenesis of the corpus callosum). They have seizures beginning in infancy (infantile spasms), which tend to progress to recurrent seizures (epilepsy) that can be difficult to treat. Affected individuals also have chorioretinal lacunae, which are defects in the light-sensitive tissue at the back of the eye (retina).  People with Aicardi syndrome often have additional brain abnormalities, including asymmetry between the two sides of the brain, brain folds and grooves that are small in size or reduced in number, cysts, and enlargement of the fluid-filled cavities (ventricles) near the center of the brain. Some have an unusually small head (microcephaly). Most affected individuals have moderate to severe developmental delay and intellectual disability, although some people with this disorder have milder disability.  In addition to chorioretinal lacunae, people with Aicardi syndrome may have other eye abnormalities such as small or poorly developed eyes (microphthalmia) or a gap or hole (coloboma) in the optic nerve, a structure that carries information from the eye to the brain. These eye abnormalities may cause blindness in affected individuals.  Some people with Aicardi syndrome have unusual facial features including a short area between the upper lip and the nose (philtrum), a flat nose with an upturned tip, large ears, and sparse eyebrows. Other features of this condition include small hands, hand malformations, and spinal and rib abnormalities leading to progressive abnormal curvature of the spine (scoliosis). They often have gastrointestinal problems such as constipation or diarrhea, gastroesophageal reflux, and difficulty feeding.  The severity of Aicardi syndrome varies. Some people with this disorder have very severe epilepsy and may not survive past childhood. Less severely affected individuals may live into adulthood with milder signs and symptoms. </s>


Input: How many people are affected by Aicardi syndrome ?

Output: Aicardi syndrome is a very rare disorder. It occurs in about 1 in 105,000 to 167,000 newborns in the United States. Researchers estimate that there are approximately 4,000 affected individuals worldwide. </s>


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

Output: The cause of Aicardi syndrome is unknown. Because it occurs almost exclusively in females, researchers believe that it is probably the result of a mutation in a gene on the X chromosome. People normally have 46 chromosomes in each cell. Two of the 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male or female sex characteristics. Genes on these chromosomes are also involved in other functions in the body. Females typically have two X chromosomes (46,XX), and males have one X chromosome and one Y chromosome (46,XY).  Early in embryonic development in females, one of the two X chromosomes is permanently inactivated in somatic cells (cells other than egg and sperm cells). X-inactivation ensures that females, like males, have only one active copy of the X chromosome in each body cell. Usually X-inactivation occurs randomly, so that each X chromosome is active in about half the body's cells. Sometimes X-inactivation is not random, and one X chromosome is active in more than half of cells. When X-inactivation does not occur randomly, it is called skewed X-inactivation.  Skewed X-inactivation sometimes occurs when there is a severe gene mutation in one of the X chromosomes in each cell. Because the cells where this chromosome is active will not be able to survive as well, X-inactivation will appear to be skewed. Skewed X-inactivation has been identified in girls with Aicardi syndrome, further supporting the idea that the disorder is caused by a mutation in a gene on the X chromosome. However, this gene has not been identified, and it is unknown how the genetic change that causes Aicardi syndrome results in the various signs and symptoms of this disorder. </s>


Input: Is Aicardi syndrome inherited ?

Output: Nearly all known cases of Aicardi syndrome are sporadic, which means that they are not passed down through generations and occur in people with no history of the disorder in their family. The disorder is believed to result from new gene mutations.  Aicardi syndrome is classified as an X-linked dominant condition. While the gene associated with this disorder is not known, it is believed to be located on the X chromosome. 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 is nearly always lethal very early in development, so almost all babies with Aicardi syndrome are female. However, a few affected males with an extra copy of the X chromosome in each cell (47,XXY) have been identified. Males with a 47,XXY chromosome pattern also have a condition called Klinefelter syndrome. </s>


Input: What are the treatments for Aicardi syndrome ?

Output: These resources address the diagnosis or management of Aicardi syndrome:  - Baylor College of Medicine  - Gene Review: Gene Review: Aicardi Syndrome  - Genetic Testing Registry: Aicardi's 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) medium-chain acyl-CoA dehydrogenase deficiency ?

Output: Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a condition that prevents the body from converting certain fats to energy, particularly during periods without food (fasting).  Signs and symptoms of MCAD deficiency typically appear during infancy or early childhood and can include vomiting, lack of energy (lethargy), and low blood sugar (hypoglycemia). In rare cases, symptoms of this disorder are not recognized early in life, and the condition is not diagnosed until adulthood. People with MCAD deficiency are at risk of serious complications such as seizures, breathing difficulties, liver problems, brain damage, coma, and sudden death.  Problems related to MCAD deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections. </s>


Input: How many people are affected by medium-chain acyl-CoA dehydrogenase deficiency ?

Output: In the United States, the estimated incidence of MCAD deficiency is 1 in 17,000 people. The condition is more common in people of northern European ancestry than in other ethnic groups. </s>


Input: What are the genetic changes related to medium-chain acyl-CoA dehydrogenase deficiency ?

Output: Mutations in the ACADM gene cause MCAD deficiency. This gene provides instructions for making an enzyme called medium-chain acyl-CoA dehydrogenase, which is required to break down (metabolize) a group of fats called medium-chain fatty acids. These fatty acids are found in foods and the body's fat tissues. Fatty acids are a major source of energy for the heart and muscles. During periods of fasting, fatty acids are also an important energy source for the liver and other tissues.  Mutations in the ACADM gene lead to a shortage (deficiency) of the MCAD enzyme within cells. Without sufficient amounts of this enzyme, medium-chain fatty acids are not metabolized properly. As a result, these fats are not converted to energy, which can lead to the characteristic signs and symptoms of this disorder such as lethargy and hypoglycemia. Medium-chain fatty acids or partially metabolized fatty acids may also build up in tissues and damage the liver and brain. This abnormal buildup causes the other signs and symptoms of MCAD deficiency. </s>


Input: Is medium-chain acyl-CoA dehydrogenase 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 medium-chain acyl-CoA dehydrogenase deficiency ?

Output: These resources address the diagnosis or management of MCAD deficiency:  - Baby's First Test  - Gene Review: Gene Review: Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency  - Genetic Testing Registry: Medium-chain acyl-coenzyme A dehydrogenase deficiency  - MedlinePlus Encyclopedia: Newborn Screening Tests   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 hemochromatosis ?

Output: Hereditary hemochromatosis is a disorder that causes the body to absorb too much iron from the diet. The excess iron is stored in the body's tissues and organs, particularly the skin, heart, liver, pancreas, and joints. Because humans cannot increase the excretion of iron, excess iron can overload and eventually damage tissues and organs. For this reason, hereditary hemochromatosis is also called an iron overload disorder.  Early symptoms of hereditary hemochromatosis are nonspecific and may include fatigue, joint pain, abdominal pain, and loss of sex drive. Later signs and symptoms can include arthritis, liver disease, diabetes, heart abnormalities, and skin discoloration. The appearance and progression of symptoms can be affected by environmental and lifestyle factors such as the amount of iron in the diet, alcohol use, and infections.  Hereditary hemochromatosis is classified by type depending on the age of onset and other factors such as genetic cause and mode of inheritance. Type 1, the most common form of the disorder, and type 4 (also called ferroportin disease) begin in adulthood. Men with type 1 or type 4 hemochromatosis typically develop symptoms between the ages of 40 and 60, and women usually develop symptoms after menopause.  Type 2 hemochromatosis is a juvenile-onset disorder. Iron accumulation begins early in life, and symptoms may appear in childhood. By age 20, decreased or absent secretion of sex hormones is evident. Females usually begin menstruation in a normal manner, but menses stop after a few years. Males may experience delayed puberty or symptoms related to a shortage of sex hormones. If the disorder is untreated, heart disease becomes evident by age 30.  The onset of type 3 hemochromatosis is usually intermediate between types 1 and 2. Symptoms of type 3 hemochromatosis generally begin before age 30. </s>


Input: How many people are affected by hereditary hemochromatosis ?

Output: Type 1 hemochromatosis is one of the most common genetic disorders in the United States, affecting about 1 million people. It most often affects people of Northern European descent. The other types of hemochromatosis are considered rare and have been studied in only a small number of families worldwide. </s>


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

Output: Mutations in the HAMP, HFE, HFE2, SLC40A1, and TFR2 genes cause hereditary hemochromatosis. Type 1 hemochromatosis results from mutations in the HFE gene, and type 2 hemochromatosis results from mutations in either the HFE2 or HAMP gene. Mutations in the TFR2 gene cause type 3 hemochromatosis, and mutations in the SLC40A1 gene cause type 4 hemochromatosis.  The proteins produced from these genes play important roles in regulating the absorption, transport, and storage of iron. Mutations in any of these genes impair the control of iron absorption during digestion and alter the distribution of iron to other parts of the body. As a result, iron accumulates in tissues and organs, which can disrupt their normal functions. </s>


Input: Is hereditary hemochromatosis inherited ?

Output: Types 1, 2, and 3 hemochromatosis are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene but do not show signs and symptoms of the condition.  Type 4 hemochromatosis is distinguished by its autosomal dominant inheritance pattern. With this type of inheritance, one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition. </s>


Input: What are the treatments for hereditary hemochromatosis ?

Output: These resources address the diagnosis or management of hereditary hemochromatosis:  - Gene Review: Gene Review: HFE-Associated Hereditary Hemochromatosis  - Gene Review: Gene Review: Juvenile Hereditary Hemochromatosis  - Gene Review: Gene Review: TFR2-Related Hereditary Hemochromatosis  - GeneFacts: Hereditary Hemochromatosis: Diagnosis  - GeneFacts: Hereditary Hemochromatosis: Management  - Genetic Testing Registry: Hemochromatosis type 1  - Genetic Testing Registry: Hemochromatosis type 2A  - Genetic Testing Registry: Hemochromatosis type 3  - Genetic Testing Registry: Hemochromatosis type 4  - MedlinePlus Encyclopedia: Hemochromatosis   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) incontinentia pigmenti ?

Output: Incontinentia pigmenti is a condition that can affect many body systems, particularly the skin. This condition occurs much more often in females than in males.  Incontinentia pigmenti is characterized by skin abnormalities that evolve throughout childhood and young adulthood. Many affected infants have a blistering rash at birth and in early infancy, which heals and is followed by the development of wart-like skin growths. In early childhood, the skin develops grey or brown patches (hyperpigmentation) that occur in a swirled pattern. These patches fade with time, and adults with incontinentia pigmenti usually have lines of unusually light-colored skin (hypopigmentation) on their arms and legs.  Other signs and symptoms of incontinentia pigmenti can include hair loss (alopecia) affecting the scalp and other parts of the body, dental abnormalities (such as small teeth or few teeth), eye abnormalities that can lead to vision loss, and lined or pitted fingernails and toenails. Most people with incontinentia pigmenti have normal intelligence; however, this condition may affect the brain. Associated problems can include delayed development or intellectual disability, seizures, and other neurological problems. </s>


Input: How many people are affected by incontinentia pigmenti ?

Output: Incontinentia pigmenti is an uncommon disorder. Between 900 and 1,200 affected individuals have been reported in the scientific literature. Most of these individuals are female, but several dozen males with incontinentia pigmenti have also been identified. </s>


Input: What are the genetic changes related to incontinentia pigmenti ?

Output: Mutations in the IKBKG gene cause incontinentia pigmenti. The IKBKG gene provides instructions for making a protein that helps regulate nuclear factor-kappa-B. Nuclear factor-kappa-B is a group of related proteins that helps protect cells from self-destructing (undergoing apoptosis) in response to certain signals.  About 80 percent of affected individuals have a mutation that deletes some genetic material from the IKBKG gene. This deletion probably leads to the production of an abnormally small, nonfunctional version of the IKBKG protein. Other people with incontinentia pigmenti have mutations that prevent the production of any IKBKG protein. Without this protein, nuclear factor-kappa-B is not regulated properly, and cells are more sensitive to signals that trigger them to self-destruct. Researchers believe that this abnormal cell death leads to the signs and symptoms of incontinentia pigmenti. </s>


Input: Is incontinentia pigmenti 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. Some cells produce a normal amount of IKBKG protein and other cells produce none. The resulting imbalance in cells producing this protein leads to the signs and symptoms of incontinentia pigmenti.  In males (who have only one X chromosome), most IKBKG mutations result in a total loss of the IKBKG protein. A lack of this protein appears to be lethal early in development, so few males are born with incontinentia pigmenti. Affected males who survive may have an IKBKG mutation with relatively mild effects, an IKBKG mutation in only some of the body's cells (mosaicism), or an extra copy of the X chromosome in each cell.  Some people with incontinentia pigmenti inherit an IKBKG 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. </s>


Input: What are the treatments for incontinentia pigmenti ?

Output: These resources address the diagnosis or management of incontinentia pigmenti:  - Gene Review: Gene Review: Incontinentia Pigmenti  - Genetic Testing Registry: Incontinentia pigmenti syndrome  - MedlinePlus Encyclopedia: Incontinentia Pigmenti 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) Stve-Wiedemann syndrome ?

Output: Stve-Wiedemann syndrome is a severe condition characterized by bone abnormalities and dysfunction of the autonomic nervous system, which controls involuntary body processes such as the regulation of breathing rate and body temperature. The condition is apparent from birth, and its key features include abnormal curvature (bowing) of the long bones in the legs, difficulty feeding and swallowing, and episodes of dangerously high body temperature (hyperthermia).  In addition to bowed legs, affected infants can have bowed arms, permanently bent fingers and toes (camptodactyly), and joint deformities (contractures) in the elbows and knees that restrict their movement. Other features include abnormalities of the pelvic bones (the ilia) and reduced bone mineral density (osteopenia).  In infants with Stve-Wiedemann syndrome, dysfunction of the autonomic nervous system typically leads to difficulty feeding and swallowing, breathing problems, and episodes of hyperthermia. Affected infants may also sweat excessively, even when the body temperature is not elevated, or have a reduced ability to feel pain. Many babies with this condition do not survive past infancy because of the problems regulating breathing and body temperature; however, some people with Stve-Wiedemann syndrome live into adolescence or later.  Problems with breathing and swallowing usually improve in affected children who survive infancy; however, they still have difficulty regulating body temperature. In addition, the leg bowing worsens, and children with Stve-Wiedemann syndrome may develop prominent joints, an abnormal curvature of the spine (scoliosis), and spontaneous bone fractures. Some affected individuals have a smooth tongue that lacks the bumps that house taste buds (fungiform papillae). Affected children may also lose certain reflexes, particularly the reflex to blink when something touches the eye (corneal reflex) and the knee-jerk reflex (patellar reflex).  Another condition once known as Schwartz-Jampel syndrome type 2 is now considered to be part of Stve-Wiedemann syndrome. Researchers have recommended that the designation Schwartz-Jampel syndrome type 2 no longer be used. </s>


Input: How many people are affected by Stve-Wiedemann syndrome ?

Output: Stve-Wiedemann syndrome is a rare condition that has been found worldwide. Its prevalence is unknown. </s>


Input: What are the genetic changes related to Stve-Wiedemann syndrome ?

Output: Stve-Wiedemann syndrome is usually caused by mutations in the LIFR gene. This gene provides instructions for making a protein called leukemia inhibitory factor receptor (LIFR). Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. Together, ligands and their receptors trigger signals that affect cell development and function.  The LIFR protein acts as a receptor for a ligand known as leukemia inhibitory factor (LIF). LIFR signaling can control several cellular processes, including growth and division (proliferation), maturation (differentiation), and survival. First found to be important in blocking (inhibiting) growth of blood cancer (leukemia) cells, this signaling is also involved in the formation of bone and the development of nerve cells. It appears to play an important role in normal development and functioning of the autonomic nervous system.  Most LIFR gene mutations that cause Stve-Wiedemann syndrome prevent production of any LIFR protein. Other mutations lead to production of an altered protein that likely cannot function. Without functional LIFR, signaling is impaired. The lack of LIFR signaling disrupts normal bone formation, leading to osteopenia, bowed legs, and other skeletal problems common in Stve-Wiedemann syndrome. In addition, development of nerve cells, particularly those involved in the autonomic nervous system, is abnormal, leading to the problems with breathing, feeding, and regulating body temperature characteristic of this condition.  A small number of people with Stve-Wiedemann syndrome do not have an identified mutation in the LIFR gene. Researchers suggest that other genes that have not been identified may be involved in this condition. </s>


Input: Is Stve-Wiedemann 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 Stve-Wiedemann syndrome ?

Output: These resources address the diagnosis or management of Stve-Wiedemann syndrome:  - Genetic Testing Registry: Stuve-Wiedemann 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) autoimmune lymphoproliferative syndrome ?

Output: Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder in which the body cannot properly regulate the number of immune system cells (lymphocytes). ALPS is characterized by the production of an abnormally large number of lymphocytes (lymphoproliferation). Accumulation of excess lymphocytes results in enlargement of the lymph nodes (lymphadenopathy), the liver (hepatomegaly), and the spleen (splenomegaly).  People with ALPS have an increased risk of developing cancer of the immune system cells (lymphoma) and may also be at increased risk of developing other cancers.  Autoimmune disorders are also common in ALPS. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. Most of the autoimmune disorders associated with ALPS target and damage blood cells. For example, the immune system may attack red blood cells (autoimmune hemolytic anemia), white blood cells (autoimmune neutropenia), or platelets (autoimmune thrombocytopenia). Less commonly, autoimmune disorders that affect other organs and tissues occur in people with ALPS. These disorders can damage the kidneys (glomerulonephritis), liver (autoimmune hepatitis), eyes (uveitis), nerves (Guillain-Barre syndrome), or the connective tissues (systemic lupus erythematosus) that provide strength and flexibility to structures throughout the body.  Skin problems, usually rashes or hives (urticaria), can occur in ALPS. Occasionally, affected individuals develop hardened skin with painful lumps or patches (panniculitis). Other rare signs and symptoms of ALPS include joint inflammation (arthritis), inflammation of blood vessels (vasculitis), mouth sores (oral ulcers), or an early loss of ovarian function (premature ovarian failure) may also occur in this disorder. Affected individuals can also develop neurological damage (organic brain syndrome) with symptoms that may include headaches, seizures, or a decline in intellectual functions (dementia).  ALPS can have different patterns of signs and symptoms, which are sometimes considered separate forms of the disorder. In the most common form, lymphoproliferation generally becomes apparent during childhood. Enlargement of the lymph nodes and spleen frequently occur in affected individuals. Autoimmune disorders typically develop several years later, most frequently as a combination of hemolytic anemia and thrombocytopenia, also called Evans syndrome. People with this classic form of ALPS have a greatly increased risk of developing lymphoma compared with the general population.  Other types of ALPS are very rare. In some affected individuals, severe lymphoproliferation begins around the time of birth, and autoimmune disorders and lymphoma develop at an early age. People with this pattern of signs and symptoms generally do not live beyond childhood. Another form of ALPS involves lymphoproliferation and the tendency to develop systemic lupus erythematosus. Individuals with this form of the disorder do not have an enlarged spleen.  Some people have signs and symptoms that resemble those of ALPS, but the specific pattern of these signs and symptoms or the genetic cause may be different than in other forms. Researchers disagree whether individuals with these non-classic forms should be considered to have ALPS or a separate condition. </s>


Input: How many people are affected by autoimmune lymphoproliferative syndrome ?

Output: ALPS is a rare disorder; its prevalence is unknown. More than 200 affected individuals have been identified worldwide. </s>


Input: What are the genetic changes related to autoimmune lymphoproliferative syndrome ?

Output: Mutations in the FAS gene cause ALPS in approximately 75 percent of affected individuals. The FAS gene provides instructions for making a protein involved in cell signaling that results in the self-destruction of cells (apoptosis).  When the immune system is turned on (activated) to fight an infection, large numbers of lymphocytes are produced. Normally, these lymphocytes undergo apoptosis when they are no longer required. FAS gene mutations result in an abnormal protein that interferes with apoptosis. Excess lymphocytes accumulate in the body's tissues and organs and often begin attacking them, leading to autoimmune disorders. Interference with apoptosis allows cells to multiply without control, leading to the lymphomas and other cancers that occur in people with this disorder.  ALPS may also be caused by mutations in additional genes, some of which have not been identified. </s>


Input: Is autoimmune lymphoproliferative syndrome inherited ?

Output: In most people with ALPS, including the majority of those with FAS gene mutations, this condition is inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. In these cases, an affected person usually inherits the mutation from one affected parent. Other cases with an autosomal dominant pattern result from new (de novo) gene mutations that occur early in embryonic development in people with no history of the disorder in their family.  In a small number of cases, including some cases caused by FAS gene mutations, ALPS is inherited in an autosomal recessive pattern, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  ALPS can also arise from a mutation in lymphocytes that is not inherited but instead occurs during an individual's lifetime. This alteration is called a somatic mutation. </s>


Input: What are the treatments for autoimmune lymphoproliferative syndrome ?

Output: These resources address the diagnosis or management of ALPS:  - Gene Review: Gene Review: Autoimmune Lymphoproliferative Syndrome  - Genetic Testing Registry: Autoimmune lymphoproliferative syndrome  - Genetic Testing Registry: Autoimmune lymphoproliferative syndrome type 1, autosomal recessive  - Genetic Testing Registry: Autoimmune lymphoproliferative syndrome, type 1a  - Genetic Testing Registry: Autoimmune lymphoproliferative syndrome, type 1b  - Genetic Testing Registry: Autoimmune lymphoproliferative syndrome, type 2  - Genetic Testing Registry: RAS-associated autoimmune leukoproliferative disorder  - National Institute of Allergy and Infectious Diseases (NIAID): ALPS Treatment   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) SOX2 anophthalmia syndrome ?

Output: SOX2 anophthalmia syndrome is a rare disorder characterized by abnormal development of the eyes and other parts of the body.  People with SOX2 anophthalmia syndrome are usually born without eyeballs (anophthalmia), although some individuals have small eyes (microphthalmia). The term anophthalmia is often used interchangeably with severe microphthalmia because individuals with no visible eyeballs typically have some remaining eye tissue. These eye problems can cause significant vision loss. While both eyes are usually affected in SOX2 anophthalmia syndrome, one eye may be more affected than the other.  Individuals with SOX2 anophthalmia syndrome may also have seizures, brain abnormalities, slow growth, delayed development of motor skills (such as walking), and mild to severe learning disabilities. Some people with this condition are born with a blocked esophagus (esophageal atresia), which is often accompanied by an abnormal connection between the esophagus and the trachea (tracheoesophageal fistula). Genital abnormalities have been described in affected individuals, especially males. Male genital abnormalities include undescended testes (cryptorchidism) and an unusually small penis (micropenis). </s>


Input: How many people are affected by SOX2 anophthalmia syndrome ?

Output: SOX2 anophthalmia syndrome is estimated to affect 1 in 250,000 individuals. About 10 percent to 15 percent of people with anophthalmia in both eyes have SOX2 anophthalmia syndrome. </s>


Input: What are the genetic changes related to SOX2 anophthalmia syndrome ?

Output: Mutations in the SOX2 gene cause SOX2 anophthalmia syndrome. This gene provides instructions for making a protein that plays a critical role in the formation of many different tissues and organs during embryonic development. The SOX2 protein regulates the activity of other genes, especially those that are important for normal development of the eyes.  Mutations in the SOX2 gene prevent the production of functional SOX2 protein. The absence of this protein disrupts the activity of genes that are essential for the development of the eyes and other parts of the body. Abnormal development of these structures causes the signs and symptoms of SOX2 anophthalmia syndrome. </s>


Input: Is SOX2 anophthalmia syndrome inherited ?

Output: SOX2 anophthalmia syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the SOX2 gene and occur in people with no history of the disorder in their family. In a small number of cases, people with SOX2 anophthalmia syndrome have inherited the altered gene from an unaffected parent who has a SOX2 mutation only in their sperm or egg cells. This phenomenon is called germline mosaicism. </s>


Input: What are the treatments for SOX2 anophthalmia syndrome ?

Output: These resources address the diagnosis or management of SOX2 anophthalmia syndrome:  - Gene Review: Gene Review: SOX2-Related Eye Disorders  - Genetic Testing Registry: Microphthalmia syndromic 3  - MedlinePlus Encyclopedia: Vision Problems   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 31 ?

Output: Spastic paraplegia type 31 is one 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) caused by degeneration of nerve cells (neurons) that trigger muscle movement. Hereditary spastic paraplegias are divided into two types: pure and complicated. The pure types involve only the lower limbs, while the complicated types also involve the upper limbs and other areas of the body, including the brain. Spastic paraplegia type 31 is usually a pure hereditary spastic paraplegia, although a few complicated cases have been reported.  The first signs and symptoms of spastic paraplegia type 31 usually appear before age 20 or after age 30. An early feature is difficulty walking due to spasticity and weakness, which typically affect both legs equally. People with spastic paraplegia type 31 can also experience progressive muscle wasting (amyotrophy) in the lower limbs, exaggerated reflexes (hyperreflexia), a decreased ability to feel vibrations, reduced bladder control, and high-arched feet (pes cavus). As the condition progresses, some individuals require walking support. </s>


Input: How many people are affected by spastic paraplegia type 31 ?

Output: Spastic paraplegia type 31 is one of a subgroup of hereditary spastic paraplegias known as autosomal dominant hereditary spastic paraplegia, which has an estimated prevalence of one to 12 per 100,000 individuals. Spastic paraplegia type 31 accounts for 3 to 9 percent of all autosomal dominant hereditary spastic paraplegia cases. </s>


Input: What are the genetic changes related to spastic paraplegia type 31 ?

Output: Spastic paraplegia type 31 is caused by mutations in the REEP1 gene. This gene provides instructions for making a protein called receptor expression-enhancing protein 1 (REEP1), which is found in neurons in the brain and spinal cord. The REEP1 protein is located within cell compartments called mitochondria, which are the energy-producing centers in cells, and the endoplasmic reticulum, which helps with protein processing and transport. The REEP1 protein plays a role in regulating the size of the endoplasmic reticulum and determining how many proteins it can process. The function of the REEP1 protein in the mitochondria is unknown.  REEP1 gene mutations that cause spastic paraplegia type 31 result in a short, nonfunctional protein that is usually broken down quickly. As a result, there is a reduction in functional REEP1 protein. It is unclear how REEP1 gene mutations lead to the signs and symptoms of spastic paraplegia type 31. Researchers have shown that mitochondria in cells of affected individuals are less able to produce energy, which may contribute to the death of neurons and lead to the progressive movement problems of spastic paraplegia type 31; however, the exact mechanism that causes this condition is unknown. </s>


Input: Is spastic paraplegia type 31 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 spastic paraplegia type 31 ?

Output: These resources address the diagnosis or management of spastic paraplegia type 31:  - Gene Review: Gene Review: Hereditary Spastic Paraplegia Overview  - Genetic Testing Registry: Spastic paraplegia 31, 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) microphthalmia with linear skin defects syndrome ?

Output: Microphthalmia with linear skin defects syndrome is a disorder that mainly affects females. In people with this condition, one or both eyes may be very small or poorly developed (microphthalmia). Affected individuals also typically have unusual linear skin markings on the head and neck. These markings follow the paths along which cells migrate as the skin develops before birth (lines of Blaschko). The skin defects generally improve over time and leave variable degrees of scarring.  The signs and symptoms of microphthalmia with linear skin defects syndrome vary widely, even among affected individuals within the same family. In addition to the characteristic eye problems and skin markings, this condition can cause abnormalities in the brain, heart, and genitourinary system. A hole in the muscle that separates the abdomen from the chest cavity (the diaphragm), which is called a diaphragmatic hernia, may occur in people with this disorder. Affected individuals may also have short stature and fingernails and toenails that do not grow normally (nail dystrophy). </s>


Input: How many people are affected by microphthalmia with linear skin defects syndrome ?

Output: The prevalence of microphthalmia with linear skin defects syndrome is unknown. More than 50 affected individuals have been identified. </s>


Input: What are the genetic changes related to microphthalmia with linear skin defects syndrome ?

Output: Mutations in the HCCS gene or a deletion of genetic material that includes the HCCS gene cause microphthalmia with linear skin defects syndrome. The HCCS gene carries instructions for producing an enzyme called holocytochrome c-type synthase. This enzyme is active in many tissues of the body and is found in the mitochondria, the energy-producing centers within cells.  Within the mitochondria, the holocytochrome c-type synthase enzyme helps produce a molecule called cytochrome c. Cytochrome c is involved in a process called oxidative phosphorylation, by which mitochondria generate adenosine triphosphate (ATP), the cell's main energy source. It also plays a role in the self-destruction of cells (apoptosis).  HCCS gene mutations result in a holocytochrome c-type synthase enzyme that cannot perform its function. A deletion of genetic material that includes the HCCS gene prevents the production of the enzyme. A lack of functional holocytochrome c-type synthase enzyme can damage cells by impairing their ability to generate energy. In addition, without the holocytochrome c-type synthase enzyme, the damaged cells may not be able to undergo apoptosis. These cells may instead die in a process called necrosis that causes inflammation and damages neighboring cells. During early development this spreading cell damage may lead to the eye abnormalities and other signs and symptoms of microphthalmia with linear skin defects syndrome. </s>


Input: Is microphthalmia with linear skin defects syndrome 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. Some cells produce a normal amount of the holocytochrome c-type synthase enzyme and other cells produce none. The resulting overall reduction in the amount of this enzyme leads to the signs and symptoms of microphthalmia with linear skin defects syndrome.  In males (who have only one X chromosome), mutations result in a total loss of the holocytochrome c-type synthase enzyme. A lack of this enzyme appears to be lethal very early in development, so almost no males are born with microphthalmia with linear skin defects syndrome. A few affected individuals with male appearance but who have two X chromosomes have been identified.  Most cases of microphthalmia with linear skin defects syndrome occur in people with no history of the disorder in their family. These cases usually result from the deletion of a segment of the X chromosome during the formation of reproductive cells (eggs and sperm) or in early fetal development. They may also result from a new mutation in the HCCS gene. </s>


Input: What are the treatments for microphthalmia with linear skin defects syndrome ?

Output: These resources address the diagnosis or management of microphthalmia with linear skin defects syndrome:  - Gene Review: Gene Review: Microphthalmia with Linear Skin Defects Syndrome  - Genetic Testing Registry: Microphthalmia, syndromic, 7   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) dystrophic epidermolysis bullosa ?

Output: Epidermolysis bullosa is a group of genetic conditions that cause the skin to be very fragile and to blister easily. Blisters and skin erosions form in response to minor injury or friction, such as rubbing or scratching. Dystrophic epidermolysis bullosa (DEB) is one of the major forms of epidermolysis bullosa. The signs and symptoms of this condition vary widely among affected individuals. In mild cases, blistering may primarily affect the hands, feet, knees, and elbows. Severe cases of this condition involve widespread blistering that can lead to vision loss, disfigurement, and other serious medical problems.  Researchers classify dystrophic epidermolysis bullosa into three major types. Although the types differ in severity, their features overlap significantly and they are caused by mutations in the same gene.  Autosomal recessive dystrophic epidermolysis bullosa, Hallopeau-Siemens type (RDEB-HS) is the most severe, classic form of the condition. Affected infants are typically born with widespread blistering and areas of missing skin, often caused by trauma during birth. Most often, blisters are present over the whole body and affect mucous membranes such as the moist lining of the mouth and digestive tract. As the blisters heal, they result in severe scarring. Scarring in the mouth and esophagus can make it difficult to chew and swallow food, leading to chronic malnutrition and slow growth. Additional complications of progressive scarring can include fusion of the fingers and toes, loss of fingernails and toenails, joint deformities (contractures) that restrict movement, and eye inflammation leading to vision loss. Additionally, young adults with the classic form of dystrophic epidermolysis bullosa have a very high risk of developing a form of skin cancer called squamous cell carcinoma, which tends to be unusually aggressive and is often life-threatening.  A second type of autosomal recessive dystrophic epidermolysis bullosa is known as the non-Hallopeau-Siemens type (non-HS RDEB). This form of the condition is somewhat less severe than the classic type and includes a range of subtypes. Blistering is limited to the hands, feet, knees, and elbows in mild cases, but may be widespread in more severe cases. Affected people often have malformed fingernails and toenails. Non-HS RDEB involves scarring in the areas where blisters occur, but this form of the condition does not cause the severe scarring characteristic of the classic type.  The third major type of dystrophic epidermolysis bullosa is known as the autosomal dominant type (DDEB). The signs and symptoms of this condition tend to be milder than those of the autosomal recessive forms, with blistering often limited to the hands, feet, knees, and elbows. The blisters heal with scarring, but it is less severe. Most affected people have malformed fingernails and toenails, and the nails may be lost over time. In the mildest cases, abnormal nails are the only sign of the condition. </s>


Input: How many people are affected by dystrophic epidermolysis bullosa ?

Output: Considered together, the incidence of all types of dystrophic epidermolysis bullosa is estimated to be 6.5 per million newborns in the United States. The severe autosomal recessive forms of this disorder affect fewer than 1 per million newborns. </s>


Input: What are the genetic changes related to dystrophic epidermolysis bullosa ?

Output: Mutations in the COL7A1 gene cause all three major forms of dystrophic epidermolysis bullosa. This gene provides instructions for making a protein that is used to assemble type VII collagen. Collagens are molecules that give structure and strength to connective tissues, such as skin, tendons, and ligaments, throughout the body. Type VII collagen plays an important role in strengthening and stabilizing the skin. It is the main component of structures called anchoring fibrils, which anchor the top layer of skin, called the epidermis, to an underlying layer called the dermis.  COL7A1 mutations alter the structure or disrupt the production of type VII collagen, which impairs its ability to help connect the epidermis to the dermis. When type VII collagen is abnormal or missing, friction or other minor trauma can cause the two skin layers to separate. This separation leads to the formation of blisters, which can cause extensive scarring as they heal. Researchers are working to determine how abnormalities of type VII collagen also underlie the increased risk of skin cancer seen in the severe form of dystrophic epidermolysis bullosa. </s>


Input: Is dystrophic epidermolysis bullosa inherited ?

Output: The most severe types of dystrophic epidermolysis bullosa are inherited in an autosomal recessive pattern. Autosomal recessive inheritance means that both copies of the COL7A1 gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.  A milder form of dystrophic epidermolysis bullosa has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder. About 70 percent of all people with autosomal dominant dystrophic epidermolysis bullosa have inherited an altered COL7A1 gene from an affected parent. The remaining 30 percent of affected people have the condition as a result of a new mutation in the COL7A1 gene. These cases occur in people with no history of the disorder in their family. </s>


Input: What are the treatments for dystrophic epidermolysis bullosa ?

Output: These resources address the diagnosis or management of dystrophic epidermolysis bullosa:  - Gene Review: Gene Review: Dystrophic Epidermolysis Bullosa  - Genetic Testing Registry: Dystrophic epidermolysis bullosa  - Genetic Testing Registry: Generalized dominant dystrophic epidermolysis bullosa  - Genetic Testing Registry: Recessive dystrophic epidermolysis bullosa  - MedlinePlus Encyclopedia: Epidermolysis bullosa  - MedlinePlus Encyclopedia: Squamous Cell Skin Cancer   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) Leber congenital amaurosis ?

Output: Leber congenital amaurosis is an eye disorder that primarily affects the retina, which is the specialized tissue at the back of the eye that detects light and color. People with this disorder typically have severe visual impairment beginning in infancy. The visual impairment tends to be stable, although it may worsen very slowly over time.  Leber congenital amaurosis is also associated with other vision problems, including an increased sensitivity to light (photophobia), involuntary movements of the eyes (nystagmus), and extreme farsightedness (hyperopia). The pupils, which usually expand and contract in response to the amount of light entering the eye, do not react normally to light. Instead, they expand and contract more slowly than normal, or they may not respond to light at all. Additionally, the clear front covering of the eye (the cornea) may be cone-shaped and abnormally thin, a condition known as keratoconus.  A specific behavior called Franceschetti's oculo-digital sign is characteristic of Leber congenital amaurosis. This sign consists of poking, pressing, and rubbing the eyes with a knuckle or finger. Researchers suspect that this behavior may contribute to deep-set eyes and keratoconus in affected children.  In rare cases, delayed development and intellectual disability have been reported in people with the features of Leber congenital amaurosis. However, researchers are uncertain whether these individuals actually have Leber congenital amaurosis or another syndrome with similar signs and symptoms.  At least 13 types of Leber congenital amaurosis have been described. The types are distinguished by their genetic cause, patterns of vision loss, and related eye abnormalities. </s>


Input: How many people are affected by Leber congenital amaurosis ?

Output: Leber congenital amaurosis occurs in 2 to 3 per 100,000 newborns. It is one of the most common causes of blindness in children. </s>


Input: What are the genetic changes related to Leber congenital amaurosis ?

Output: Leber congenital amaurosis can result from mutations in at least 14 genes, all of which are necessary for normal vision. These genes play a variety of roles in the development and function of the retina. For example, some of the genes associated with this disorder are necessary for the normal development of light-detecting cells called photoreceptors. Other genes are involved in phototransduction, the process by which light entering the eye is converted into electrical signals that are transmitted to the brain. Still other genes play a role in the function of cilia, which are microscopic finger-like projections that stick out from the surface of many types of cells. Cilia are necessary for the perception of several types of sensory input, including vision.  Mutations in any of the genes associated with Leber congenital amaurosis disrupt the development and function of the retina, resulting in early vision loss. Mutations in the CEP290, CRB1, GUCY2D, and RPE65 genes are the most common causes of the disorder, while mutations in the other genes generally account for a smaller percentage of cases. In about 30 percent of all people with Leber congenital amaurosis, the cause of the disorder is unknown. </s>


Input: Is Leber congenital amaurosis inherited ?

Output: Leber congenital amaurosis usually has an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  When Leber congenital amaurosis is caused by mutations in the CRX or IMPDH1 genes, the disorder has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. In most of these cases, an affected person inherits a gene mutation from one affected parent. Other cases result from new mutations and occur in people with no history of the disorder in their family. </s>


Input: What are the treatments for Leber congenital amaurosis ?

Output: These resources address the diagnosis or management of Leber congenital amaurosis:  - Gene Review: Gene Review: Leber Congenital Amaurosis  - Genetic Testing Registry: Leber congenital amaurosis 1  - Genetic Testing Registry: Leber congenital amaurosis 10  - Genetic Testing Registry: Leber congenital amaurosis 12  - Genetic Testing Registry: Leber congenital amaurosis 13  - Genetic Testing Registry: Leber congenital amaurosis 14  - Genetic Testing Registry: Leber congenital amaurosis 2  - Genetic Testing Registry: Leber congenital amaurosis 3  - Genetic Testing Registry: Leber congenital amaurosis 4  - Genetic Testing Registry: Leber congenital amaurosis 5  - Genetic Testing Registry: Leber congenital amaurosis 9  - Genetic Testing Registry: Leber's amaurosis  - National Eye Institute: Gene Therapy for Leber Congenital Amaurosis   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) aniridia ?

Output: Aniridia is an eye disorder characterized by a complete or partial absence of the colored part of the eye (the iris). These iris abnormalities may cause the pupils to be abnormal or misshapen. Aniridia can cause reduction in the sharpness of vision (visual acuity) and increased sensitivity to light (photophobia).  People with aniridia can also have other eye problems. Increased pressure in the eye (glaucoma) typically appears in late childhood or early adolescence. Clouding of the lens of the eye (cataracts), occur in 50 percent to 85 percent of people with aniridia. In about 10 percent of affected people, the structures that carry information from the eyes to the brain (optic nerves) are underdeveloped. Individuals with aniridia may also have involuntary eye movements (nystagmus) or underdevelopment of the region at the back of the eye responsible for sharp central vision (foveal hypoplasia). Many of these eye problems contribute to progressive vision loss in affected individuals. The severity of symptoms is typically the same in both eyes.  Rarely, people with aniridia have behavioral problems, developmental delay, and problems detecting odors. </s>


Input: How many people are affected by aniridia ?

Output: Aniridia occurs in 1 in 50,000 to 100,000 newborns worldwide. </s>


Input: What are the genetic changes related to aniridia ?

Output: Aniridia is caused by mutations in the PAX6 gene. The PAX6 gene provides instructions for making a protein that is involved in the early development of the eyes, brain and spinal cord (central nervous system), and the pancreas. Within the brain, the PAX6 protein is involved in the development of a specialized group of brain cells that process smell (the olfactory bulb). The PAX6 protein attaches (binds) to specific regions of DNA and regulates the activity of other genes. On the basis of this role, the PAX6 protein is called a transcription factor. Following birth, the PAX6 protein regulates several genes that likely contribute to the maintenance of different eye structures.  Mutations in the PAX6 gene result in the production of a nonfunctional PAX6 protein that is unable to bind to DNA and regulate the activity of other genes. A lack of functional PAX6 protein disrupts the formation of the eyes during embryonic development. </s>


Input: Is aniridia inherited ?

Output: Aniridia 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 approximately two-thirds of cases, an affected person inherits the mutation from one affected parent. The remaining one-third of cases result from new mutations in the gene and occur in people with no history of the disorder in their family. </s>


Input: What are the treatments for aniridia ?

Output: These resources address the diagnosis or management of aniridia:  - Gene Review: Gene Review: Aniridia  - Genetic Testing Registry: Congenital aniridia   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) Pelizaeus-Merzbacher disease ?

Output: Pelizaeus-Merzbacher disease is an inherited condition involving the brain and spinal cord (central nervous system). This disease is one of a group of genetic disorders called leukodystrophies. Leukodystrophies are characterized by degeneration of myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. Pelizaeus-Merzbacher disease is caused by an inability to form myelin (dysmyelination). As a result, individuals with this condition have impaired intellectual functions, such as language and memory, and delayed motor skills, such as coordination and walking. Typically, motor skills are more severely affected than intellectual function; motor skills development tends to occur more slowly and usually stops in a person's teens, followed by gradual deterioration.  Pelizaeus-Merzbacher disease is divided into classic and connatal types. Although these two types differ in severity, their features can overlap.  Classic Pelizaeus-Merzbacher disease is the more common type. Within the first year of life, those affected with classic Pelizaeus-Merzbacher disease typically experience weak muscle tone (hypotonia), involuntary movements of the eyes (nystagmus), and delayed development of motor skills such as crawling or walking. As the child gets older, nystagmus usually stops but other movement disorders develop, including muscle stiffness (spasticity), problems with movement and balance (ataxia), and involuntary jerking (choreiform movements).  Connatal Pelizaeus-Merzbacher disease is the more severe of the two types. Symptoms can begin in infancy and include problems feeding, a whistling sound when breathing, progressive spasticity leading to joint deformities (contractures) that restrict movement, speech difficulties (dysarthria), ataxia, and seizures. Those affected with connatal Pelizaeus-Merzbacher disease show little development of motor skills and intellectual function. </s>


Input: How many people are affected by Pelizaeus-Merzbacher disease ?

Output: The prevalence of Pelizaeus-Merzbacher disease is estimated to be 1 in 200,000 to 500,000 males in the United States. This condition rarely affects females. </s>


Input: What are the genetic changes related to Pelizaeus-Merzbacher disease ?

Output: Mutations in the PLP1 gene cause Pelizaeus-Merzbacher disease. The PLP1 gene provides instructions for producing proteolipid protein 1 and a modified version (isoform) of proteolipid protein 1, called DM20. Proteolipid protein 1 and DM20 are primarily located in the central nervous system and are the main proteins found in myelin, the fatty covering that insulates nerve fibers. A lack of proteolipid protein 1 and DM20 can cause dysmyelination, which can impair nervous system function, resulting in the signs and symptoms of Pelizaeus-Merzbacher disease.  It is estimated that 5 percent to 20 percent of people with Pelizaeus-Merzbacher disease do not have identified mutations in the PLP1 gene. In these cases, the cause of the condition is unknown. </s>


Input: Is Pelizaeus-Merzbacher disease 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. Because females have two copies of the X chromosome, one altered copy of the gene in each cell usually leads to less severe symptoms in females than in males, or may cause no symptoms at all. 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. She can pass on the gene, but generally does not experience signs and symptoms of the disorder. Some females who carry a PLP1 mutation, however, may experience muscle stiffness and a decrease in intellectual function. Females with one PLP1 mutation have an increased risk of experiencing progressive deterioration of cognitive functions (dementia) later in life. </s>


Input: What are the treatments for Pelizaeus-Merzbacher disease ?

Output: These resources address the diagnosis or management of Pelizaeus-Merzbacher disease:  - Gene Review: Gene Review: PLP1-Related Disorders  - Genetic Testing Registry: Pelizaeus-Merzbacher 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) mucolipidosis type IV ?

Output: Mucolipidosis type IV is an inherited disorder characterized by delayed development and vision impairment that worsens over time. The severe form of the disorder is called typical mucolipidosis type IV, and the mild form is called atypical mucolipidosis type IV.  Approximately 95 percent of individuals with this condition have the severe form. People with typical mucolipidosis type IV have delayed development of mental and motor skills (psychomotor delay). Motor skills include sitting, standing, walking, grasping objects, and writing. Psychomotor delay is moderate to severe and usually becomes apparent during the first year of life. Affected individuals have intellectual disability, limited or absent speech, difficulty chewing and swallowing, weak muscle tone (hypotonia) that gradually turns into abnormal muscle stiffness (spasticity), and problems controlling hand movements. Most people with typical mucolipidosis type IV are unable to walk independently. In about 15 percent of affected individuals, the psychomotor problems worsen over time.  Vision may be normal at birth in people with typical mucolipidosis type IV, but it becomes increasingly impaired during the first decade of life. Individuals with this condition develop clouding of the clear covering of the eye (cornea) and progressive breakdown of the light-sensitive layer at the back of the eye (retina). By their early teens, affected individuals have severe vision loss or blindness.  People with typical mucolipidosis type IV also have impaired production of stomach acid (achlorhydria). Achlorhydria does not cause any symptoms in these individuals, but it does result in unusually high levels of gastrin in the blood. Gastrin is a hormone that regulates the production of stomach acid. Individuals with mucolipidosis type IV may not have enough iron in their blood, which can lead to a shortage of red blood cells (anemia). People with the severe form of this disorder usually survive to adulthood; however, they may have a shortened lifespan.  About 5 percent of affected individuals have atypical mucolipidosis type IV. These individuals usually have mild psychomotor delay and may develop the ability to walk. People with atypical mucolipidosis type IV tend to have milder eye abnormalities than those with the severe form of the disorder. Achlorhydria also may be present in mildly affected individuals. </s>


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

Output: Mucolipidosis type IV is estimated to occur in 1 in 40,000 people. About 70 percent of affected individuals have Ashkenazi Jewish ancestry. </s>


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

Output: Mutations in the MCOLN1 gene cause mucolipidosis type IV. This gene provides instructions for making a protein called mucolipin-1. This protein is located in the membranes of lysosomes and endosomes, compartments within the cell that digest and recycle materials. While its function is not completely understood, mucolipin-1 plays a role in the transport (trafficking) of fats (lipids) and proteins between lysosomes and endosomes. Mucolipin-1 appears to be important for the development and maintenance of the brain and retina. In addition, this protein is likely critical for normal functioning of the cells in the stomach that produce digestive acids.  Most mutations in the MCOLN1 gene result in the production of a nonfunctional protein or prevent any protein from being produced. A lack of functional mucolipin-1 impairs transport of lipids and proteins, causing these substances to build up inside lysosomes. Conditions that cause molecules to accumulate inside the lysosomes, including mucolipidosis type IV, are called lysosomal storage disorders. Two mutations in the MCOLN1 gene account for almost all cases of mucolipidosis type IV in people with Ashkenazi Jewish ancestry. It remains unclear how mutations in this gene lead to the signs and symptoms of mucolipidosis type IV. </s>


Input: Is mucolipidosis 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 mucolipidosis type IV ?

Output: These resources address the diagnosis or management of mucolipidosis type IV:  - Gene Review: Gene Review: Mucolipidosis IV  - Genetic Testing Registry: Ganglioside sialidase deficiency  - MedlinePlus Encyclopedia: Gastrin   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) thrombocytopenia-absent radius syndrome ?

Output: Thrombocytopenia-absent radius (TAR) syndrome is characterized by the absence of a bone called the radius in each forearm. Affected individuals also have a shortage (deficiency) of blood cells involved in clotting (platelets). This platelet deficiency (thrombocytopenia) usually appears during infancy and becomes less severe over time; in some cases the platelet levels become normal.  Thrombocytopenia prevents normal blood clotting, resulting in easy bruising and frequent nosebleeds. Potentially life-threatening episodes of severe bleeding (hemorrhages) may occur in the brain and other organs, especially during the first year of life. Hemorrhages can damage the brain and lead to intellectual disability. Affected children who survive this period and do not have damaging hemorrhages in the brain usually have a normal life expectancy and normal intellectual development.  TAR syndrome is unusual among similar malformations in that affected individuals have thumbs, while people with other conditions involving an absent radius typically do not. TAR syndrome is also associated with short stature and additional skeletal abnormalities, including underdevelopment of other bones in the arms and legs. Affected individuals may also have malformations of the heart and kidneys. TAR syndrome is associated with unusual facial features including a small lower jaw (micrognathia), a prominent forehead, and low-set ears. About half of affected individuals have allergic reactions to cow's milk that may worsen the thrombocytopenia associated with this disorder. </s>


Input: How many people are affected by thrombocytopenia-absent radius syndrome ?

Output: TAR syndrome is a rare disorder, affecting fewer than 1 in 100,000 newborns. </s>


Input: What are the genetic changes related to thrombocytopenia-absent radius syndrome ?

Output: Mutations in the RBM8A gene cause TAR syndrome. The RBM8A gene provides instructions for making a protein called RNA-binding motif protein 8A. This protein is believed to be involved in several important cellular functions involving the production of other proteins.  Most people with TAR syndrome have a mutation in one copy of the RBM8A gene and a deletion of genetic material from chromosome 1 that includes the other copy of the RBM8A gene in each cell. A small number of affected individuals have mutations in both copies of the RBM8A gene in each cell and do not have a deletion on chromosome 1. RBM8A gene mutations that cause TAR syndrome reduce the amount of RNA-binding motif protein 8A in cells. The deletions involved in TAR syndrome eliminate at least 200,000 DNA building blocks (200 kilobases, or 200 kb) from the long (q) arm of chromosome 1 in a region called 1q21.1. The deletion eliminates one copy of the RBM8A gene in each cell and the RNA-binding motif protein 8A that would have been produced from it.  People with either an RBM8A gene mutation and a chromosome 1 deletion or with two gene mutations have a decreased amount of RNA-binding motif protein 8A. This reduction is thought to cause problems in the development of certain tissues, but it is unknown how it causes the specific signs and symptoms of TAR syndrome. No cases have been reported in which a deletion that includes the RBM8A gene occurs on both copies of chromosome 1; studies indicate that the complete loss of RNA-binding motif protein 8A is not compatible with life.  Researchers sometimes refer to the deletion in chromosome 1 associated with TAR syndrome as the 200-kb deletion to distinguish it from another chromosomal abnormality called a 1q21.1 microdeletion. People with a 1q21.1 microdeletion are missing a different, larger DNA segment in the chromosome 1q21.1 region near the area where the 200-kb deletion occurs. The chromosomal change related to 1q21.1 microdeletion is often called the recurrent distal 1.35-Mb deletion. </s>


Input: Is thrombocytopenia-absent radius syndrome inherited ?

Output: TAR syndrome is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell are altered. In this disorder, either both copies of the RBM8A gene in each cell have mutations or, more commonly, one copy of the gene has a mutation and the other is lost as part of a deleted segment on chromosome 1. The affected individual usually inherits an RBM8A gene mutation from one parent. In about 75 percent of cases, the affected person inherits a copy of chromosome 1 with the 200-kb deletion from the other parent. In the remaining cases, the deletion occurs during the formation of reproductive cells (eggs and sperm) or in early fetal development. Although parents of an individual with TAR syndrome can carry an RBM8A gene mutation or a 200-kb deletion, they typically do not show signs and symptoms of the condition. </s>


Input: What are the treatments for thrombocytopenia-absent radius syndrome ?

Output: These resources address the diagnosis or management of TAR syndrome:  - Gene Review: Gene Review: Thrombocytopenia Absent Radius Syndrome  - Genetic Testing Registry: Radial aplasia-thrombocytopenia syndrome  - MedlinePlus Encyclopedia: Skeletal Limb Abnormalities   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) multiple pterygium syndrome ?

Output: Multiple pterygium syndrome is a condition that is evident before birth with webbing of the skin (pterygium) at the joints and a lack of muscle movement (akinesia) before birth. Akinesia frequently results in muscle weakness and joint deformities called contractures that restrict the movement of joints (arthrogryposis). As a result, multiple pterygium syndrome can lead to further problems with movement such as arms and legs that cannot fully extend.  The two forms of multiple pterygium syndrome are differentiated by the severity of their symptoms. Multiple pterygium syndrome, Escobar type (sometimes referred to as Escobar syndrome) is the milder of the two types. Lethal multiple pterygium syndrome is fatal before birth or very soon after birth.  In people with multiple pterygium syndrome, Escobar type, the webbing typically affects the skin of the neck, fingers, forearms, inner thighs, and backs of the knee. People with this type may also have arthrogryposis. A side-to-side curvature of the spine (scoliosis) is sometimes seen. Affected individuals may also have respiratory distress at birth due to underdeveloped lungs (lung hypoplasia). People with multiple pterygium syndrome, Escobar type usually have distinctive facial features including droopy eyelids (ptosis), outside corners of the eyes that point downward (downslanting palpebral fissures), skin folds covering the inner corner of the eyes (epicanthal folds), a small jaw, and low-set ears. Males with this condition can have undescended testes (cryptorchidism). This condition does not worsen after birth, and affected individuals typically do not have muscle weakness later in life.  Lethal multiple pterygium syndrome has many of the same signs and symptoms as the Escobar type. In addition, affected fetuses may develop a buildup of excess fluid in the body (hydrops fetalis) or a fluid-filled sac typically found on the back of the neck (cystic hygroma). Individuals with this type have severe arthrogryposis. Lethal multiple pterygium syndrome is associated with abnormalities such as underdevelopment (hypoplasia) of the heart, lung, or brain; twisting of the intestines (intestinal malrotation); kidney abnormalities; an opening in the roof of the mouth (a cleft palate); and an unusually small head size (microcephaly). Affected individuals may also develop a hole in the muscle that separates the abdomen from the chest cavity (the diaphragm), a condition called a congenital diaphragmatic hernia. Lethal multiple pterygium syndrome is typically fatal in the second or third trimester of pregnancy. </s>


Input: How many people are affected by multiple pterygium syndrome ?

Output: The prevalence of multiple pterygium syndrome is unknown. </s>


Input: What are the genetic changes related to multiple pterygium syndrome ?

Output: Mutations in the CHRNG gene cause most cases of multiple pterygium syndrome, Escobar type and a smaller percentage of cases of lethal multiple pterygium syndrome. The CHRNG gene provides instructions for making the gamma () protein component (subunit) of the acetylcholine receptor (AChR) protein. The AChR protein is found in the membrane of skeletal muscle cells and is critical for signaling between nerve and muscle cells. Signaling between these cells is necessary for movement. The AChR protein consists of five subunits. The  subunit is found only in the fetal AChR protein. At about the thirty-third week of pregnancy, the  subunit is replaced by another subunit to form adult AChR protein. The replacement of fetal AChR by adult AChR is the reason most people with multiple pterygium syndrome, Escobar type do not have problems with muscle movement after birth.  CHRNG gene mutations result in an impaired or missing  subunit. The severity of the CHRNG gene mutation influences the severity of the condition. Typically, mutations that prevent the production of any  subunit will result in the lethal type, while mutations that allow the production of some  subunit will lead to the Escobar type. Without a functional  subunit, the fetal AChR protein cannot be assembled or properly placed in the muscle cell membrane. As a result, the fetal AChR protein cannot function and the communication between nerve cells and muscle cells in the developing fetus is impaired. A lack of signaling between nerve and muscle cells leads to akinesia and pterygium before birth, and may result in many of the other signs and symptoms of multiple pterygium syndrome.  Mutations in other genes, most providing instructions for other AChR protein subunits, have been found to cause multiple pterygium syndrome. Changes in these genes can cause both the lethal and Escobar types of this condition, although they account for only a small number of cases. Some people with multiple pterygium syndrome do not have an identified mutation in any of the known genes associated with this condition. The cause of the disease in these individuals is unknown. </s>


Input: Is multiple pterygium 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 multiple pterygium syndrome ?

Output: These resources address the diagnosis or management of multiple pterygium syndrome:  - Genetic Testing Registry: Lethal multiple pterygium syndrome  - Genetic Testing Registry: Multiple pterygium syndrome Escobar 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) hereditary diffuse gastric cancer ?

Output: Hereditary diffuse gastric cancer (HDGC) is an inherited disorder that greatly increases the chance of developing a form of stomach (gastric) cancer. In this form, known as diffuse gastric cancer, there is no solid tumor. Instead cancerous (malignant) cells multiply underneath the stomach lining, making the lining thick and rigid. The invasive nature of this type of cancer makes it highly likely that these cancer cells will spread (metastasize) to other tissues, such as the liver or nearby bones.  Symptoms of diffuse gastric cancer occur late in the disease and can include stomach pain, nausea, vomiting, difficulty swallowing (dysphagia), decreased appetite, and weight loss. If the cancer metastasizes to other tissues, it may lead to an enlarged liver, yellowing of the eyes and skin (jaundice), an abnormal buildup of fluid in the abdominal cavity (ascites), firm lumps under the skin, or broken bones.  In HDGC, gastric cancer usually occurs in a person's late thirties or early forties, although it can develop anytime during adulthood. If diffuse gastric cancer is detected early, the survival rate is high; however, because this type of cancer is hidden underneath the stomach lining, it is usually not diagnosed until the cancer has become widely invasive. At that stage of the disease, the survival rate is approximately 20 percent.  Some people with HDGC have an increased risk of developing other types of cancer, such as a form of breast cancer in women that begins in the milk-producing glands (lobular breast cancer); prostate cancer; and cancers of the colon (large intestine) and rectum, which are collectively referred to as colorectal cancer. Most people with HDGC have family members who have had one of the types of cancer associated with HDGC. In some families, all the affected members have diffuse gastric cancer. In other families, some affected members have diffuse gastric cancer and others have another associated form of cancer, such as lobular breast cancer. Frequently, HDGC-related cancers develop in individuals before the age of 50. </s>


Input: How many people are affected by hereditary diffuse gastric cancer ?

Output: Gastric cancer is the fourth most common form of cancer worldwide, affecting 900,000 people per year. HDGC probably accounts for less than 1 percent of these cases. </s>


Input: What are the genetic changes related to hereditary diffuse gastric cancer ?

Output: It is likely that 30 to 40 percent of individuals with HDGC have a mutation in the CDH1 gene. The CDH1 gene provides instructions for making a protein called epithelial cadherin or E-cadherin. This protein is found within the membrane that surrounds epithelial cells, which are the cells that line the surfaces and cavities of the body. E-cadherin helps neighboring cells stick to one another (cell adhesion) to form organized tissues. E-cadherin has many other functions including acting as a tumor suppressor protein, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way.  People with HDGC caused by CDH1 gene mutations are born with one mutated copy of the gene in each cell. These mutations cause the production of an abnormally short, nonfunctional version of E-cadherin or alter the protein's structure. For diffuse gastric cancer to develop, a second mutation involving the other copy of the CDH1 gene must occur in the cells of the stomach lining during a person's lifetime. People who are born with one mutated copy of the CDH1 gene have a 80 percent chance of acquiring a second mutation in the other copy of the gene and developing gastric cancer in their lifetimes.  When both copies of the CDH1 gene are mutated in a particular cell, that cell cannot produce any functional E-cadherin. The loss of this protein prevents it from acting as a tumor suppressor, contributing to the uncontrollable growth and division of cells. A lack of E-cadherin also impairs cell adhesion, increasing the likelihood that cancer cells will not come together to form a tumor but will invade the stomach wall and metastasize as small clusters of cancer cells into nearby tissues.  These CDH1 gene mutations also lead to a 40 to 50 percent chance of lobular breast cancer in women, a slightly increased risk of prostate cancer in men, and a slightly increased risk of colorectal cancer. It is unclear why CDH1 gene mutations primarily occur in the stomach lining and these other tissues.  About 60 to 70 percent of individuals with HDGC do not have an identified mutation in the CDH1 gene. The cancer-causing mechanism in these individuals is unknown. </s>


Input: Is hereditary diffuse gastric cancer inherited ?

Output: HDGC is inherited in an autosomal dominant pattern, which means one copy of the altered CDH1 gene in each cell is sufficient to increase the risk of developing cancer.  In most cases, an affected person has one parent with the condition. </s>


Input: What are the treatments for hereditary diffuse gastric cancer ?

Output: These resources address the diagnosis or management of hereditary diffuse gastric cancer:  - American Cancer Society: How is Stomach Cancer Diagnosed?  - Gene Review: Gene Review: Hereditary Diffuse Gastric Cancer  - Genetic Testing Registry: Hereditary diffuse gastric cancer  - MedlinePlus Encyclopedia: Gastric Cancer  - Memorial Sloan-Kettering Cancer Center: Early Onset and Familial Gastric Cancer Registry  - National Cancer Institute: Gastric Cancer Treatment Option Overview   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) chronic atrial and intestinal dysrhythmia ?

Output: Chronic atrial and intestinal dysrhythmia (CAID) is a disorder affecting the heart and the digestive system. CAID disrupts the normal rhythm of the heartbeat; affected individuals have a heart rhythm abnormality called sick sinus syndrome. The disorder also impairs the rhythmic muscle contractions that propel food through the intestines (peristalsis), causing a digestive condition called intestinal pseudo-obstruction. The heart and digestive issues develop at the same time, usually by age 20.  Sick sinus syndrome (also known as sinus node dysfunction) is an abnormality of the sinoatrial (SA) node, which is an area of specialized cells in the heart that functions as a natural pacemaker. The SA node generates electrical impulses that start each heartbeat. These signals travel from the SA node to the rest of the heart, signaling the heart (cardiac) muscle to contract and pump blood. In people with sick sinus syndrome, the SA node does not function normally, which usually causes the heartbeat to be too slow (bradycardia), although occasionally the heartbeat is too fast (tachycardia) or rapidly switches from being too fast to being too slow (tachycardia-bradycardia syndrome). Symptoms related to abnormal heartbeats can include dizziness, light-headedness, fainting (syncope), a sensation of fluttering or pounding in the chest (palpitations), and confusion or memory problems. During exercise, many affected individuals experience chest pain, difficulty breathing, or excessive tiredness (fatigue).  In intestinal pseudo-obstruction, impairment of peristalsis leads to a buildup of partially digested food in the intestines, abdominal swelling (distention) and pain, nausea, vomiting, and constipation or diarrhea. Affected individuals experience loss of appetite and impaired ability to absorb nutrients, which may lead to malnutrition. These symptoms resemble those caused by an intestinal blockage (obstruction) such as a tumor, but in intestinal pseudo-obstruction no such blockage is found. </s>


Input: How many people are affected by chronic atrial and intestinal dysrhythmia ?

Output: The prevalence of CAID is unknown. At least 17 affected individuals have been described in the medical literature. </s>


Input: What are the genetic changes related to chronic atrial and intestinal dysrhythmia ?

Output: CAID is caused by mutations in the SGO1 gene. This gene provides instructions for making part of a protein complex called cohesin. This protein complex helps control the placement of chromosomes during cell division. Before cells divide, they must copy all of their chromosomes. The copied DNA from each chromosome is arranged into two identical structures, called sister chromatids, which are attached to one another during the early stages of cell division. Cohesin holds the sister chromatids together, and in doing so helps maintain the stability of chromosomal structure during cell division.  Researchers suggest that SGO1 gene mutations may result in a cohesin complex that is less able to hold sister chromatids together, resulting in decreased chromosomal stability during cell division. This instability is thought to cause early aging (senescence) of cells in the intestinal muscle and in the SA node, resulting in problems maintaining proper rhythmic movements of the heart and intestines and leading to the signs and symptoms of CAID.  It is unclear why SGO1 gene mutations specifically affect the heart and intestines in CAID. Researchers suggest that the activity (expression) of the SGO1 gene in certain embryonic tissues or a particular function of the SGO1 protein in the SA node and in cells that help control peristalsis may account for the features of the disorder. </s>


Input: Is chronic atrial and intestinal dysrhythmia 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 chronic atrial and intestinal dysrhythmia ?

Output: These resources address the diagnosis or management of chronic atrial and intestinal dysrhythmia:  - Children's Hospital of Pittsburgh: Chronic Intestinal Pseudo-obstruction  - Genetic Testing Registry: Chronic atrial and intestinal dysrhythmia  - MedlinePlus Encyclopedia: Heart Pacemakers  - MedlinePlus Health Topic: Nutritional Support  - MedlinePlus Health Topic: Pacemakers and Implantable Defibrillators  - National Heart, Lung, and Blood Institute: What is a Pacemaker?   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 sensory and autonomic neuropathy type II ?

Output: Hereditary sensory and autonomic neuropathy type II (HSAN2) is a condition that primarily affects the sensory nerve cells (sensory neurons), which transmit information about sensations such as pain, temperature, and touch. These sensations are impaired in people with HSAN2. In some affected people, the condition may also cause mild abnormalities of the autonomic nervous system, which controls involuntary body functions such as heart rate, digestion, and breathing. The signs and symptoms of HSAN2 typically begin in infancy or early childhood.  The first sign of HSAN2 is usually numbness in the hands and feet. Soon after, affected individuals lose the ability to feel pain or sense hot and cold. People with HSAN2 often develop open sores (ulcers) on their hands and feet. Because affected individuals cannot feel the pain of these sores, they may not seek treatment right away. Without treatment, the ulcers can become infected and may lead to amputation of the affected area. Unintentional self-injury is common in people with HSAN2, typically by biting the tongue, lips, or fingers. These injuries may lead to spontaneous amputation of the affected areas. Affected individuals often have injuries and fractures in their hands, feet, limbs, and joints that go untreated because of the inability to feel pain. Repeated injury can lead to a condition called Charcot joints, in which the bones and tissue surrounding joints are destroyed.  The effects of HSAN2 on the autonomic nervous system are more variable. Some infants with HSAN2 have trouble sucking, which makes it difficult for them to eat. People with HSAN2 may experience episodes in which breathing slows or stops for short periods (apnea); digestive problems such as the backflow of stomach acids into the esophagus (gastroesophageal reflux); or slow eye blink or gag reflexes. Affected individuals may also have weak deep tendon reflexes, such as the reflex being tested when a doctor taps the knee with a hammer.  Some people with HSAN2 lose a type of taste bud on the tip of the tongue called lingual fungiform papillae and have a diminished sense of taste. </s>


Input: How many people are affected by hereditary sensory and autonomic neuropathy type II ?

Output: HSAN2 is a rare disease; however, the prevalence is unknown. </s>


Input: What are the genetic changes related to hereditary sensory and autonomic neuropathy type II ?

Output: There are two types of HSAN2, called HSAN2A and HSAN2B, each caused by mutations in a different gene. HSAN2A is caused by mutations in the WNK1 gene, and HSAN2B is caused by mutations in the FAM134B gene. Although two different genes are involved, the signs and symptoms of HSAN2A and HSAN2B are the same.  The WNK1 gene provides instructions for making multiple versions (isoforms) of the WNK1 protein. HSAN2A is caused by mutations that affect a particular isoform called the WNK1/HSN2 protein. This protein is found in the cells of the nervous system, including nerve cells that transmit the sensations of pain, temperature, and touch (sensory neurons). The mutations involved in HSAN2A result in an abnormally short WNK1/HSN2 protein. Although the function of this protein is unknown, it is likely that the abnormally short version cannot function properly. People with HSAN2A have a reduction in the number of sensory neurons; however, the role that WNK1/HSN2 mutations play in that loss is unclear.  HSAN2B is caused by mutations in the FAM134B gene. These mutations may lead to an abnormally short and nonfunctional protein. The FAM134B protein is found in sensory and autonomic neurons. It is involved in the survival of neurons, particularly those that transmit pain signals, which are called nociceptive neurons. When the FAM134B protein is nonfunctional, neurons die by a process of self-destruction called apoptosis.  The loss of neurons leads to the inability to feel pain, temperature, and touch sensations and to the impairment of the autonomic nervous system seen in people with HSAN2. </s>


Input: Is hereditary sensory and autonomic neuropathy type II inherited ?

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


Input: What are the treatments for hereditary sensory and autonomic neuropathy type II ?

Output: These resources address the diagnosis or management of HSAN2:  - Gene Review: Gene Review: Hereditary Sensory and Autonomic Neuropathy Type II  - Genetic Testing Registry: Hereditary sensory and autonomic neuropathy type IIA  - Genetic Testing Registry: Hereditary sensory and autonomic neuropathy type IIB   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>