Input: What is (are) Warsaw breakage syndrome ?

Output: Warsaw breakage syndrome is a condition that can cause multiple abnormalities. People with Warsaw breakage syndrome have intellectual disability that varies from mild to severe. They also have impaired growth from birth leading to short stature and a small head size (microcephaly). Affected individuals have distinctive facial features that may include a small forehead, a short nose, a small lower jaw, a flat area between the nose and mouth (philtrum), and prominent cheeks. Other common features include hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss) and heart malformations. </s>


Input: How many people are affected by Warsaw breakage syndrome ?

Output: Warsaw breakage syndrome is a rare condition; at least four cases have been described in the medical literature. </s>


Input: What are the genetic changes related to Warsaw breakage syndrome ?

Output: Mutations in the DDX11 gene cause Warsaw breakage syndrome. The DDX11 gene provides instructions for making an enzyme called ChlR1. This enzyme functions as a helicase. Helicases are enzymes that attach (bind) to DNA and temporarily unwind the two spiral strands (double helix) of the DNA molecule. This unwinding is necessary for copying (replicating) DNA in preparation for cell division, and for repairing damaged DNA and any mistakes that are made when DNA is copied. In addition, after DNA is copied, ChlR1 plays a role in ensuring proper separation of each chromosome during cell division. By helping repair mistakes in DNA and ensuring proper DNA replication, the ChlR1 enzyme is involved in maintaining the stability of a cell's genetic information.  DDX11 gene mutations severely reduce or completely eliminate ChlR1 enzyme activity. As a result, the enzyme cannot bind to DNA and cannot unwind the DNA strands to help with DNA replication and repair. A lack of functional ChlR1 impairs cell division and leads to an accumulation of DNA damage. This DNA damage can appear as breaks in the DNA, giving the condition its name. It is unclear how these problems in DNA maintenance lead to the specific abnormalities characteristic of Warsaw breakage syndrome. </s>


Input: Is Warsaw breakage 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 Warsaw breakage syndrome ?

Output: These resources address the diagnosis or management of Warsaw breakage syndrome:  - Centers for Disease Control and Prevention: Hearing Loss in Children  - Genetic Testing Registry: Warsaw breakage syndrome  - MedlinePlus Encyclopedia: Hearing Loss--Infants   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) Carpenter syndrome ?

Output: Carpenter syndrome is a condition characterized by the premature fusion of certain skull bones (craniosynostosis), abnormalities of the fingers and toes, and other developmental problems.  Craniosynostosis prevents the skull from growing normally, frequently giving the head a pointed appearance (acrocephaly). In severely affected individuals, the abnormal fusion of the skull bones results in a deformity called a cloverleaf skull. Craniosynostosis can cause differences between the two sides of the head and face (craniofacial asymmetry). Early fusion of the skull bones can affect the development of the brain and lead to increased pressure within the skull (intracranial pressure). Premature fusion of the skull bones can cause several characteristic facial features in people with Carpenter syndrome. Distinctive facial features may include a flat nasal bridge, outside corners of the eyes that point downward (down-slanting palpebral fissures), low-set and abnormally shaped ears, underdeveloped upper and lower jaws, and abnormal eye shape. Some affected individuals also have dental abnormalities including small primary (baby) teeth. Vision problems also frequently occur.  Abnormalities of the fingers and toes include fusion of the skin between two or more fingers or toes (cutaneous syndactyly), unusually short fingers or toes (brachydactyly), or extra fingers or toes (polydactyly). In Carpenter syndrome, cutaneous syndactyly is most common between the third (middle) and fourth (ring) fingers, and polydactyly frequently occurs next to the big or second toe or the fifth (pinky) finger.  People with Carpenter syndrome often have intellectual disability, which can range from mild to profound. However, some individuals with this condition have normal intelligence. The cause of intellectual disability is unknown, as the severity of craniosynostosis does not appear to be related to the severity of intellectual disability.  Other features of Carpenter syndrome include obesity that begins in childhood, a soft out-pouching around the belly-button (umbilical hernia), hearing loss, and heart defects. Additional skeletal abnormalities such as deformed hips, a rounded upper back that also curves to the side (kyphoscoliosis), and knees that are angled inward (genu valgum) frequently occur. Nearly all affected males have genital abnormalities, most frequently undescended testes (cryptorchidism).  A few people with Carpenter syndrome have organs or tissues within their chest and abdomen that are in mirror-image reversed positions. This abnormal placement may affect several internal organs (situs inversus); just the heart (dextrocardia), placing the heart on the right side of the body instead of on the left; or only the major (great) arteries of the heart, altering blood flow.  The signs and symptoms of this disorder vary considerably, even within the same family. The life expectancy for individuals with Carpenter syndrome is shortened but extremely variable.  The signs and symptoms of Carpenter syndrome are similar to another genetic condition called Greig cephalopolysyndactyly syndrome. The overlapping features, which include craniosynostosis, polydactyly, and heart abnormalities, can cause these two conditions to be misdiagnosed; genetic testing is often required for an accurate diagnosis. </s>


Input: How many people are affected by Carpenter syndrome ?

Output: Carpenter syndrome is thought to be a rare condition; approximately 70 cases have been described in the scientific literature. </s>


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

Output: Mutations in the RAB23 or MEGF8 gene cause Carpenter syndrome.  The RAB23 gene provides instructions for making a protein that is involved in a process called vesicle trafficking, which moves proteins and other molecules within cells in sac-like structures called vesicles. The Rab23 protein transports vesicles from the cell membrane to their proper location inside the cell. Vesicle trafficking is important for the transport of materials that are needed to trigger signaling during development. For example, the Rab23 protein regulates a developmental pathway called the hedgehog signaling pathway that is critical in cell growth (proliferation), cell specialization, and the normal shaping (patterning) of many parts of the body.  The MEGF8 gene provides instructions for making a protein whose function is unclear. Based on its structure, the Megf8 protein may be involved in cell processes such as sticking cells together (cell adhesion) and helping proteins interact with each other. Researchers also suspect that the Megf8 protein plays a role in normal body patterning.  Mutations in the RAB23 or MEGF8 gene lead to the production of proteins with little or no function. It is unclear how disruptions in protein function lead to the features of Carpenter syndrome, but it is likely that interference with normal body patterning plays a role. For reasons that are unknown, people with MEGF8 gene mutations are more likely to have dextrocardia and other organ positioning abnormalities and less severe craniosynostosis than individuals with RAB23 gene mutations. </s>


Input: Is Carpenter 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 Carpenter syndrome ?

Output: These resources address the diagnosis or management of Carpenter syndrome:  - Genetic Testing Registry: Carpenter syndrome 1  - Genetic Testing Registry: Carpenter syndrome 2  - Great Ormond Street Hospital for Children (UK): Craniosynostosis Information  - Johns Hopkins Medicine: Craniosynostosis Treatment Options  - MedlinePlus Encyclopedia: Craniosynostosis Repair  - MedlinePlus Encyclopedia: Dextrocardia   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) Potocki-Shaffer syndrome ?

Output: Potocki-Shaffer syndrome is a disorder that affects development of the bones, nerve cells in the brain, and other tissues. Most people with this condition have multiple noncancerous (benign) bone tumors called osteochondromas. In rare instances, these tumors become cancerous. People with Potocki-Shaffer syndrome also have enlarged openings in the two bones that make up much of the top and sides of the skull (enlarged parietal foramina). These abnormal openings form extra "soft spots" on the head, in addition to the two that newborns normally have. Unlike the usual newborn soft spots, the enlarged parietal foramina remain open throughout life.  The signs and symptoms of Potocki-Shaffer syndrome vary widely. In addition to multiple osteochondromas and enlarged parietal foramina, affected individuals often have intellectual disability and delayed development of speech, motor skills (such as sitting and walking), and social skills. Many people with this condition have distinctive facial features, which can include a wide, short skull (brachycephaly); a prominent forehead; a narrow bridge of the nose; a shortened distance between the nose and upper lip (a short philtrum); and a downturned mouth. Less commonly, Potocki-Shaffer syndrome causes vision problems, additional skeletal abnormalities, and defects in the heart, kidneys, and urinary tract. </s>


Input: How many people are affected by Potocki-Shaffer syndrome ?

Output: Potocki-Shaffer syndrome is a rare condition, although its prevalence is unknown. Fewer than 100 cases have been reported in the scientific literature. </s>


Input: What are the genetic changes related to Potocki-Shaffer syndrome ?

Output: Potocki-Shaffer syndrome (also known as proximal 11p deletion syndrome) is caused by a deletion of genetic material from the short (p) arm of chromosome 11 at a position designated 11p11.2. The size of the deletion varies among affected individuals. Studies suggest that the full spectrum of features is caused by a deletion of at least 2.1 million DNA building blocks (base pairs), also written as 2.1 megabases (Mb). The loss of multiple genes within the deleted region causes the varied signs and symptoms of Potocki-Shaffer syndrome.  In particular, deletion of the EXT2, ALX4, and PHF21A genes are associated with several of the characteristic features of Potocki-Shaffer syndrome. Research shows that loss of the EXT2 gene is associated with the development of multiple osteochondromas in affected individuals. Deletion of another gene, ALX4, causes the enlarged parietal foramina found in people with this condition. In addition, loss of the PHF21A gene is the cause of intellectual disability and distinctive facial features in many people with the condition. The loss of additional genes in the deleted region likely contributes to the other features of Potocki-Shaffer syndrome. </s>


Input: Is Potocki-Shaffer syndrome inherited ?

Output: Potocki-Shaffer syndrome follows an autosomal dominant inheritance pattern, which means a deletion of genetic material from one copy of chromosome 11 is sufficient to cause the disorder. In some cases, an affected person inherits the chromosome with a deleted segment from an affected parent. More commonly, the condition results from a deletion that occurs during the formation of reproductive cells (eggs and sperm) in a parent or in early fetal development. These cases occur in people with no history of the disorder in their family. </s>


Input: What are the treatments for Potocki-Shaffer syndrome ?

Output: These resources address the diagnosis or management of Potocki-Shaffer syndrome:  - Genetic Testing Registry: Potocki-Shaffer 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) osteogenesis imperfecta ?

Output: Osteogenesis imperfecta (OI) is a group of genetic disorders that mainly affect the bones. The term "osteogenesis imperfecta" means imperfect bone formation. People with this condition have bones that break easily, often from mild trauma or with no apparent cause. Multiple fractures are common, and in severe cases, can occur even before birth. Milder cases may involve only a few fractures over a person's lifetime.  There are at least eight recognized forms of osteogenesis imperfecta, designated type I through type VIII. The types can be distinguished by their signs and symptoms, although their characteristic features overlap. Type I is the mildest form of osteogenesis imperfecta and type II is the most severe; other types of this condition have signs and symptoms that fall somewhere between these two extremes. Increasingly, genetic factors are used to define the different forms of osteogenesis imperfecta.  The milder forms of osteogenesis imperfecta, including type I, are characterized by bone fractures during childhood and adolescence that often result from minor trauma. Fractures occur less frequently in adulthood. People with mild forms of the condition typically have a blue or grey tint to the part of the eye that is usually white (the sclera), and may develop hearing loss in adulthood. Affected individuals are usually of normal or near normal height.  Other types of osteogenesis imperfecta are more severe, causing frequent bone fractures that may begin before birth and result from little or no trauma. Additional features of these conditions can include blue sclerae, short stature, hearing loss, respiratory problems, and a disorder of tooth development called dentinogenesis imperfecta. The most severe forms of osteogenesis imperfecta, particularly type II, can include an abnormally small, fragile rib cage and underdeveloped lungs. Infants with these abnormalities have life-threatening problems with breathing and often die shortly after birth. </s>


Input: How many people are affected by osteogenesis imperfecta ?

Output: This condition affects an estimated 6 to 7 per 100,000 people worldwide. Types I and IV are the most common forms of osteogenesis imperfecta, affecting 4 to 5 per 100,000 people. </s>


Input: What are the genetic changes related to osteogenesis imperfecta ?

Output: Mutations in the COL1A1, COL1A2, CRTAP, and P3H1 genes cause osteogenesis imperfecta.  Mutations in the COL1A1 and COL1A2 genes are responsible for more than 90 percent of all cases of osteogenesis imperfecta. These genes provide instructions for making proteins that are used to assemble type I collagen. This type of collagen is the most abundant protein in bone, skin, and other connective tissues that provide structure and strength to the body.  Most of the mutations that cause osteogenesis imperfecta type I occur in the COL1A1 gene. These genetic changes reduce the amount of type I collagen produced in the body, which causes bones to be brittle and to fracture easily. The mutations responsible for most cases of osteogenesis imperfecta types II, III, and IV occur in either the COL1A1 or COL1A2 gene. These mutations typically alter the structure of type I collagen molecules. A defect in the structure of type I collagen weakens connective tissues, particularly bone, resulting in the characteristic features of osteogenesis imperfecta.  Mutations in the CRTAP and P3H1 genes are responsible for rare, often severe cases of osteogenesis imperfecta. Cases caused by CRTAP mutations are usually classified as type VII; when P3H1 mutations underlie the condition, it is classified as type VIII. The proteins produced from these genes work together to process collagen into its mature form. Mutations in either gene disrupt the normal folding, assembly, and secretion of collagen molecules. These defects weaken connective tissues, leading to severe bone abnormalities and problems with growth.  In cases of osteogenesis imperfecta without identified mutations in one of the genes described above, the cause of the disorder is unknown. These cases include osteogenesis imperfecta types V and VI. Researchers are working to identify additional genes that may be responsible for these conditions. </s>


Input: Is osteogenesis imperfecta inherited ?

Output: Most cases of osteogenesis imperfecta have an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the condition. Many people with type I or type IV osteogenesis imperfecta inherit a mutation from a parent who has the disorder. Most infants with more severe forms of osteogenesis imperfecta (such as type II and type III) have no history of the condition in their family. In these infants, the condition is caused by new (sporadic) mutations in the COL1A1 or COL1A2 gene.  Less commonly, osteogenesis imperfecta has an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means two copies of the gene in each cell are altered. The parents of a child with an autosomal recessive disorder typically are not affected, but each carry one copy of the altered gene. Some cases of osteogenesis imperfecta type III are autosomal recessive; these cases usually result from mutations in genes other than COL1A1 and COL1A2. When osteogenesis imperfecta is caused by mutations in the CRTAP or P3H1 gene, the condition also has an autosomal recessive pattern of inheritance. </s>


Input: What are the treatments for osteogenesis imperfecta ?

Output: These resources address the diagnosis or management of osteogenesis imperfecta:  - Gene Review: Gene Review: COL1A1/2-Related Osteogenesis Imperfecta  - Genetic Testing Registry: Osteogenesis imperfecta  - Genetic Testing Registry: Osteogenesis imperfecta type 5  - Genetic Testing Registry: Osteogenesis imperfecta type 6  - Genetic Testing Registry: Osteogenesis imperfecta type 7  - Genetic Testing Registry: Osteogenesis imperfecta type 8  - Genetic Testing Registry: Osteogenesis imperfecta type I  - Genetic Testing Registry: Osteogenesis imperfecta type III  - Genetic Testing Registry: Osteogenesis imperfecta with normal sclerae, dominant form  - Genetic Testing Registry: Osteogenesis imperfecta, recessive perinatal lethal  - MedlinePlus Encyclopedia: Osteogenesis Imperfecta   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) lung cancer ?

Output: Lung cancer is a disease in which certain cells in the lungs become abnormal and multiply uncontrollably to form a tumor. Lung cancer may or may not cause signs or symptoms in its early stages. Some people with lung cancer have chest pain, frequent coughing, breathing problems, trouble swallowing or speaking, blood in the mucus, loss of appetite and weight loss, fatigue, or swelling in the face or neck. Lung cancer occurs most often in adults in their sixties or seventies. Most people who develop lung cancer have a history of long-term tobacco smoking; however, the condition can occur in people who have never smoked.  Lung cancer is generally divided into two types, small cell lung cancer and non-small cell lung cancer, based on the size of the affected cells when viewed under a microscope. Non-small cell lung cancer accounts for 85 percent of lung cancer, while small cell lung cancer accounts for the remaining 15 percent.  Small cell lung cancer grows quickly and often spreads to other tissues (metastasizes), most commonly to the adrenal glands (small hormone-producing glands located on top of each kidney), liver, brain, and bones. In more than half of cases, the small cell lung cancer has spread beyond the lung at the time of diagnosis. After diagnosis, most people with small cell lung cancer survive for about one year; less than seven percent survive 5 years.  Non-small cell lung cancer is divided into three main subtypes: adenocarcinoma, squamous cell carcinoma, and large cell lung carcinoma. Adenocarcinoma arises from the cells that line the small air sacs (alveoli) located throughout the lungs. Squamous cell carcinoma arises from the squamous cells that line the passages leading from the windpipe to the lungs (bronchi). Large cell carcinoma describes non-small cell lung cancers that do not appear to be adenocarcinomas or squamous cell carcinomas. As the name suggests, the tumor cells are large when viewed under a microscope. The 5-year survival rate for people with non-small cell lung cancer is usually between 11 and 17 percent; it can be lower or higher depending on the subtype and stage of the cancer. </s>


Input: How many people are affected by lung cancer ?

Output: In the United States, it is estimated that more than 221,000 people develop lung cancer each year. An estimated 72 to 80 percent of lung cancer cases occur in tobacco smokers.  Approximately 6.6 percent of individuals will develop lung cancer during their lifetime. It is the leading cause of cancer deaths, accounting for an estimated 27 percent of all cancer deaths in the United States. </s>


Input: What are the genetic changes related to lung cancer ?

Output: Cancers occur when genetic mutations build up in critical genes, specifically those that control cell growth and division or the repair of damaged DNA. These changes allow cells to grow and divide uncontrollably to form a tumor. In nearly all cases of lung cancer, these genetic changes are acquired during a person's lifetime and are present only in certain cells in the lung. These changes, which are called somatic mutations, are not inherited. Somatic mutations in many different genes have been found in lung cancer cells.  Mutations in the EGFR and KRAS genes are estimated to be present in up to half of all lung cancer cases. These genes each provide instructions for making a protein that is embedded within the cell membrane. When these proteins are turned on (activated) by binding to other molecules, signaling pathways are triggered within cells that promote cell growth and division (proliferation).  Mutations in either the EGFR or KRAS gene lead to the production of a protein that is constantly turned on (constitutively activated). As a result, cells are signaled to constantly proliferate, leading to tumor formation. When these gene changes occur in cells in the lungs, lung cancer develops.  Mutations in many other genes have each been found in a small proportion of cases.  In addition to genetic changes, researchers have identified many personal and environmental factors that expose individuals to cancer-causing compounds (carcinogens) and increase the rate at which somatic mutations occur, contributing to a person's risk of developing lung cancer. The greatest risk factor is long-term tobacco smoking, which increases a person's risk of developing lung cancer 20-fold. Other risk factors include exposure to air pollution, radon, asbestos, or secondhand smoke; long-term use of hormone replacement therapy for menopause; and a history of lung disease such as tuberculosis, emphysema, or chronic bronchitis. A history of lung cancer in closely related family members is also an important risk factor; however, because relatives with lung cancer were likely smokers, it is unclear whether the increased risk of lung cancer is the result of genetic factors or exposure to secondhand smoke. </s>


Input: Is lung cancer inherited ?

Output: Most cases of lung cancer are not related to inherited gene changes. These cancers are associated with somatic mutations that occur only in certain cells in the lung.  When lung cancer is related to inherited gene changes, the cancer risk is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase a person's chance of developing cancer. It is important to note that people inherit an increased risk of cancer, not the disease itself. Not all people who inherit mutations in these genes will develop lung cancer. </s>


Input: What are the treatments for lung cancer ?

Output: These resources address the diagnosis or management of lung cancer:  - Genetic Testing Registry: Lung cancer  - Genetic Testing Registry: Non-small cell lung cancer  - Lung Cancer Mutation Consortium: About Mutation Testing  - MedlinePlus Encyclopedia: Lung Cancer--Non-Small Cell  - MedlinePlus Encyclopedia: Lung Cancer--Small Cell  - National Cancer Institute: Drugs Approved for Lung Cancer  - National Cancer Institute: Non-Small Cell Lung Cancer Treatment  - National Cancer Institute: Small Cell Lung Cancer 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) cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy ?

Output: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, commonly known as CARASIL, is an inherited condition that causes stroke and other impairments.  Abnormalities affecting the brain and other parts of the nervous system become apparent in an affected person's twenties or thirties. Often, muscle stiffness (spasticity) in the legs and problems with walking are the first signs of the disorder. About half of affected individuals have a stroke or similar episode before age 40. As the disease progresses, most people with CARASIL also develop mood and personality changes, a decline in thinking ability (dementia), memory loss, and worsening problems with movement.  Other characteristic features of CARASIL include premature hair loss (alopecia) and attacks of low back pain. The hair loss often begins during adolescence and is limited to the scalp. Back pain, which develops in early to mid-adulthood, results from the breakdown (degeneration) of the discs that separate the bones of the spine (vertebrae) from one another.  The signs and symptoms of CARASIL worsen slowly with time. Over the course of several years, affected individuals become less able to control their emotions and communicate with others. They increasingly require help with personal care and other activities of daily living; after a few years, they become unable to care for themselves. Most affected individuals die within a decade after signs and symptoms first appear, although few people with the disease have survived for 20 to 30 years. </s>


Input: How many people are affected by cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy ?

Output: CARASIL appears to be a rare condition. It has been identified in about 50 people, primarily in Japan and China. </s>


Input: What are the genetic changes related to cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy ?

Output: CARASIL is caused by mutations in the HTRA1 gene. This gene provides instructions for making an enzyme that is found in many of the body's organs and tissues. One of the major functions of the HTRA1 enzyme is to regulate signaling by proteins in the transforming growth factor-beta (TGF-) family. TGF- signaling is essential for many critical cell functions. It also plays an important role in the formation of new blood vessels (angiogenesis).  In people with CARASIL, mutations in the HTRA1 gene prevent the effective regulation of TGF- signaling. Researchers suspect that abnormally increased TGF- signaling alters the structure of small blood vessels, particularly in the brain. These blood vessel abnormalities (described as arteriopathy) greatly increase the risk of stroke and lead to the death of nerve cells (neurons) in many areas of the brain. Dysregulation of TGF- signaling may also underlie the hair loss and back pain seen in people with CARASIL, although the relationship between abnormal TGF- signaling and these features is less clear. </s>


Input: Is cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy inherited ?

Output: As its name suggests, this condition is inherited in an autosomal recessive pattern. 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. </s>


Input: What are the treatments for cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy ?

Output: These resources address the diagnosis or management of CARASIL:  - Gene Review: Gene Review: CARASIL  - Genetic Testing Registry: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy   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) galactosialidosis ?

Output: Galactosialidosis is a condition that affects many areas of the body. The three forms of galactosialidosis are distinguished by the age at which symptoms develop and the pattern of features.  The early infantile form of galactosialidosis is associated with extensive swelling caused by fluid accumulation before birth (hydrops fetalis), a soft out-pouching in the lower abdomen (an inguinal hernia), and an enlarged liver and spleen (hepatosplenomegaly). Additional features of this form include abnormal bone development (dysostosis multiplex) and distinctive facial features that are often described as "coarse." Some infants have an enlarged heart (cardiomegaly); an eye abnormality called a cherry-red spot, which can be identified with an eye examination; and kidney disease that can progress to kidney failure. Infants with this form usually are diagnosed between birth and 3 months; they typically live into late infancy.  The late infantile form of galactosialidosis shares some features with the early infantile form, although the signs and symptoms are somewhat less severe and begin later in infancy. This form is characterized by short stature, dysostosis multiplex, heart valve problems, hepatosplenomegaly, and "coarse" facial features. Other symptoms seen in some individuals with this type include intellectual disability, hearing loss, and a cherry-red spot. Children with this condition typically develop symptoms within the first year of life. The life expectancy of individuals with this type varies depending on the severity of symptoms.  The juvenile/adult form of galactosialidosis has signs and symptoms that are somewhat different than those of the other two types. This form is distinguished by difficulty coordinating movements (ataxia), muscle twitches (myoclonus), seizures, and progressive intellectual disability. People with this form typically also have dark red spots on the skin (angiokeratomas), abnormalities in the bones of the spine, "coarse" facial features, a cherry-red spot, vision loss, and hearing loss. The age at which symptoms begin to develop varies widely among affected individuals, but the average age is 16. This form is typically associated with a normal life expectancy. </s>


Input: How many people are affected by galactosialidosis ?

Output: The prevalence of galactosialidosis is unknown; more than 100 cases have been reported. Approximately 60 percent of people with galactosialidosis have the juvenile/adult form. Most people with this type of the condition are of Japanese descent. </s>


Input: What are the genetic changes related to galactosialidosis ?

Output: Mutations in the CTSA gene cause all forms of galactosialidosis. The CTSA gene provides instructions for making a protein called cathepsin A, which is active in cellular compartments called lysosomes. These compartments contain enzymes that digest and recycle materials when they are no longer needed. Cathepsin A works together with two enzymes, neuraminidase 1 and beta-galactosidase, to form a protein complex. This complex breaks down sugar molecules (oligosaccharides) attached to certain proteins (glycoproteins) or fats (glycolipids). Cathepsin A is also found on the cell surface, where it forms a complex with neuraminidase 1 and a protein called elastin binding protein. Elastin binding protein plays a role in the formation of elastic fibers, a component of the connective tissues that form the body's supportive framework.  CTSA mutations interfere with the normal function of cathepsin A. Most mutations disrupt the protein structure of cathepsin A, impairing its ability to form complexes with neuraminidase 1, beta-galactosidase, and elastin binding protein. As a result, these other enzymes are not functional, or they break down prematurely.  Galactosialidosis belongs to a large family of lysosomal storage disorders, each caused by the deficiency of a specific lysosomal enzyme or protein. In galactosialidosis, impaired functioning of cathepsin A and other enzymes causes certain substances to accumulate in the lysosomes. </s>


Input: Is galactosialidosis 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 galactosialidosis ?

Output: These resources address the diagnosis or management of galactosialidosis:  - Genetic Testing Registry: Combined deficiency of sialidase AND beta galactosidase  - MedlinePlus Encyclopedia: Hepatosplenomegaly (image)  - MedlinePlus Encyclopedia: Hydrops fetalis   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 IE ?

Output: Hereditary sensory and autonomic neuropathy type IE (HSAN IE) is a disorder that affects the nervous system. Affected individuals have a gradual loss of intellectual function (dementia), typically beginning in their thirties. In some people with this disorder, changes in personality become apparent before problems with thinking skills.  People with HSAN IE also develop hearing loss that is caused by abnormalities in the inner ear (sensorineural hearing loss). The hearing loss gets worse over time and usually progresses to moderate or severe deafness between the ages of 20 and 35.  HSAN IE is characterized by impaired function of nerve cells called sensory neurons, which transmit information about sensations such as pain, temperature, and touch. Sensations in the feet and legs are particularly affected in people with HSAN IE. Gradual loss of sensation in the feet (peripheral neuropathy), which usually begins in adolescence or early adulthood, can lead to difficulty walking. Affected individuals may not be aware of injuries to their feet, which can lead to open sores and infections. If these complications are severe, amputation of the affected areas may be required.  HSAN IE is also characterized by a loss of the ability to sweat (sudomotor function), especially on the hands and feet. Sweating is a function of the autonomic nervous system, which also controls involuntary body functions such as heart rate, digestion, and breathing. These other autonomic functions are unaffected in people with HSAN IE.  The severity of the signs and symptoms of HSAN IE and their age of onset are variable, even within the same family. </s>


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

Output: HSAN IE is a rare disorder; its prevalence is unknown. Small numbers of affected families have been identified in populations around the world. </s>


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

Output: HSAN IE is caused by mutations in the DNMT1 gene. This gene provides instructions for making an enzyme called DNA (cytosine-5)-methyltransferase 1. This enzyme is involved in DNA methylation, which is the addition of methyl groups, consisting of one carbon atom and three hydrogen atoms, to DNA molecules. In particular, the enzyme helps add methyl groups to DNA building blocks (nucleotides) called cytosines.  DNA methylation is important in many cellular functions. These include determining whether the instructions in a particular segment of DNA are carried out or suppressed (gene silencing), regulating reactions involving proteins and fats (lipids), and controlling the processing of chemicals that relay signals in the nervous system (neurotransmitters). DNA (cytosine-5)-methyltransferase 1 is active in the adult nervous system. Although its specific function is not well understood, the enzyme may help regulate nerve cell (neuron) maturation and specialization (differentiation), the ability of neurons to migrate where needed and connect with each other, and neuron survival.  DNMT1 gene mutations that cause HSAN IE reduce or eliminate the enzyme's methylation function, resulting in abnormalities in the maintenance of the neurons that make up the nervous system. However, it is not known how the mutations cause the specific signs and symptoms of HSAN IE. </s>


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

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


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

Output: These resources address the diagnosis or management of hereditary sensory and autonomic neuropathy type IE:  - Gene Review: Gene Review: DNMT1-Related Dementia, Deafness, and Sensory Neuropathy  - University of Chicago: Center for Peripheral Neuropathy   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) CAV3-related distal myopathy ?

Output: CAV3-related distal myopathy is one form of distal myopathy, a group of disorders characterized by weakness and loss of function affecting the muscles farthest from the center of the body (distal muscles), such as those of the hands and feet. People with CAV3-related distal myopathy experience wasting (atrophy) and weakness of the small muscles in the hands and feet that generally become noticeable in adulthood. A bump or other sudden impact on the muscles, especially those in the forearms, may cause them to exhibit repetitive tensing (percussion-induced rapid contraction). The rapid contractions can continue for up to 30 seconds and may be painful. Overgrowth (hypertrophy) of the calf muscles can also occur in CAV3-related distal myopathy. The muscles closer to the center of the body (proximal muscles) such as the thighs and upper arms are normal in this condition. </s>


Input: How many people are affected by CAV3-related distal myopathy ?

Output: The prevalence of CAV3-related distal myopathy is unknown. Only a few affected individuals have been described in the medical literature. </s>


Input: What are the genetic changes related to CAV3-related distal myopathy ?

Output: CAV3-related distal myopathy is part of a group of conditions called caveolinopathies, which are muscle disorders caused by mutations in the CAV3 gene. The CAV3 gene provides instructions for making a protein called caveolin-3, which is found in the membrane surrounding muscle cells. This protein is the main component of caveolae, which are small pouches in the muscle cell membrane. Within the caveolae, the caveolin-3 protein acts as a scaffold to organize other molecules that are important for cell signaling and maintenance of the cell structure.  CAV3 gene mutations result in a shortage of caveolin-3 protein in the muscle cell membrane and a reduction in the number of caveolae. Researchers suggest that a shortage of caveolae impairs the structural integrity of muscle cells, interferes with cell signaling, and causes the self-destruction of cells (apoptosis). The resulting degeneration of muscle tissue leads to the signs and symptoms of CAV3-related distal myopathy.  In addition to CAV3-related distal myopathy, CAV3 gene mutations can cause other caveolinopathies including limb-girdle muscular dystrophy, rippling muscle disease, isolated hyperCKemia, and a heart disorder called hypertrophic cardiomyopathy. Several CAV3 gene mutations have been found to cause different caveolinopathies in different individuals. It is unclear why a single CAV3 gene mutation may cause different patterns of signs and symptoms, even within the same family. </s>


Input: Is CAV3-related distal myopathy inherited ?

Output: This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with CAV3-related distal myopathy or another caveolinopathy. Rare cases result from new mutations in the gene and occur in people with no history of caveolinopathies in their family. </s>


Input: What are the treatments for CAV3-related distal myopathy ?

Output: These resources address the diagnosis or management of CAV3-related distal myopathy:  - Gene Review: Gene Review: Caveolinopathies  - Genetic Testing Registry: CAV3-Related Distal Myopathy  - Genetic Testing Registry: Distal myopathy, Tateyama type  - MedlinePlus Encyclopedia: Electromyography  - MedlinePlus Encyclopedia: Muscle Biopsy   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) galactosemia ?

Output: Galactosemia is a disorder that affects how the body processes a simple sugar called galactose. A small amount of galactose is present in many foods. It is primarily part of a larger sugar called lactose, which is found in all dairy products and many baby formulas. The signs and symptoms of galactosemia result from an inability to use galactose to produce energy.  Researchers have identified several types of galactosemia. These conditions are each caused by mutations in a particular gene and affect different enzymes involved in breaking down galactose.  Classic galactosemia, also known as type I, is the most common and most severe form of the condition. If infants with classic galactosemia are not treated promptly with a low-galactose diet, life-threatening complications appear within a few days after birth. Affected infants typically develop feeding difficulties, a lack of energy (lethargy), a failure to gain weight and grow as expected (failure to thrive), yellowing of the skin and whites of the eyes (jaundice), liver damage, and abnormal bleeding. Other serious complications of this condition can include overwhelming bacterial infections (sepsis) and shock. Affected children are also at increased risk of delayed development, clouding of the lens of the eye (cataract), speech difficulties, and intellectual disability. Females with classic galactosemia may develop reproductive problems caused by an early loss of function of the ovaries (premature ovarian insufficiency).  Galactosemia type II (also called galactokinase deficiency) and type III (also called galactose epimerase deficiency) cause different patterns of signs and symptoms. Galactosemia type II causes fewer medical problems than the classic type. Affected infants develop cataracts but otherwise experience few long-term complications. The signs and symptoms of galactosemia type III vary from mild to severe and can include cataracts, delayed growth and development, intellectual disability, liver disease, and kidney problems. </s>


Input: How many people are affected by galactosemia ?

Output: Classic galactosemia occurs in 1 in 30,000 to 60,000 newborns. Galactosemia type II and type III are less common; type II probably affects fewer than 1 in 100,000 newborns and type III appears to be very rare. </s>


Input: What are the genetic changes related to galactosemia ?

Output: Mutations in the GALT, GALK1, and GALE genes cause galactosemia. These genes provide instructions for making enzymes that are essential for processing galactose obtained from the diet. These enzymes break down galactose into another simple sugar, glucose, and other molecules that the body can store or use for energy.  Mutations in the GALT gene cause classic galactosemia (type I). Most of these genetic changes almost completely eliminate the activity of the enzyme produced from the GALT gene, preventing the normal processing of galactose and resulting in the life-threatening signs and symptoms of this disorder. Another GALT gene mutation, known as the Duarte variant, reduces but does not eliminate the activity of the enzyme. People with the Duarte variant tend to have much milder features of galactosemia.  Galactosemia type II results from mutations in the GALK1 gene, while mutations in the GALE gene underlie galactosemia type III. Like the enzyme produced from the GALT gene, the enzymes made from the GALK1 and GALE genes play important roles in processing galactose. A shortage of any of these critical enzymes allows galactose and related compounds to build up to toxic levels in the body. The accumulation of these substances damages tissues and organs, leading to the characteristic features of galactosemia. </s>


Input: Is galactosemia 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 galactosemia ?

Output: These resources address the diagnosis or management of galactosemia:  - Baby's First Test: Classic Galactosemia  - Baby's First Test: Galactoepimerase Deficiency  - Baby's First Test: Galactokinase Deficiency  - Gene Review: Gene Review: Classic Galactosemia and Clinical Variant Galactosemia  - Gene Review: Gene Review: Duarte Variant Galactosemia  - Gene Review: Gene Review: Epimerase Deficiency Galactosemia  - Genetic Testing Registry: Galactosemia  - MedlinePlus Encyclopedia: Galactose-1-phosphate uridyltransferase  - MedlinePlus Encyclopedia: Galactosemia   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) Erdheim-Chester disease ?

Output: Erdheim-Chester disease is a rare disorder characterized by histiocytosis, a condition in which the immune system produces excess quantities of cells called histiocytes. Histiocytes normally function to destroy foreign substances and protect the body from infection. Erdheim-Chester disease is classified as a form of non-Langerhans cell histiocytosis to distinguish it from Langerhans cell histiocytosis, which involves accumulation of a specific type of histiocyte called Langerhans cells. In Erdheim-Chester disease, histiocytosis leads to inflammation that can damage organs and tissues throughout the body, causing them to become thickened, dense, and scarred (fibrotic); this tissue damage may lead to organ failure.  People with Erdheim-Chester disease often have bone pain, especially in the lower legs and upper arms, due to an abnormal increase in bone density (osteosclerosis). Damage to the pituitary gland (a structure at the base of the brain that produces several hormones, including a hormone that controls the amount of water released in the urine) may result in hormonal problems such as a condition called diabetes insipidus that leads to excessive urination. Abnormally high pressure of the cerebrospinal fluid within the skull (intracranial hypertension) caused by accumulation of histiocytes in the brain may result in headaches, seizures, cognitive impairment, or problems with movement or sensation. People with this condition can also have shortness of breath, heart or kidney disease, protruding eyes (exophthalmos), skin growths, or inability to conceive a child (infertility). Affected individuals may also experience fever, night sweats, fatigue, weakness, and weight loss.  The signs and symptoms of Erdheim-Chester disease usually appear between the ages of 40 and 60, although the disorder can occur at any age. The severity of the condition varies widely; some affected individuals have few or no associated health problems, while others have severe complications that can be life-threatening. </s>


Input: How many people are affected by Erdheim-Chester disease ?

Output: Erdheim-Chester disease is a rare disorder; its exact prevalence is unknown. More than 500 affected individuals worldwide have been described in the medical literature. For unknown reasons, men are slightly more likely to develop the disease, accounting for about 60 percent of cases. </s>


Input: What are the genetic changes related to Erdheim-Chester disease ?

Output: More than half of people with Erdheim-Chester disease have a specific mutation in the BRAF gene. Mutations in other genes are also thought to be involved in this disorder.  The BRAF gene provides instructions for making a protein that helps transmit chemical signals from outside the cell to the cell's nucleus. This protein is part of a signaling pathway known as the RAS/MAPK pathway, which controls several important cell functions. Specifically, the RAS/MAPK pathway regulates the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement (migration), and the self-destruction of cells (apoptosis).  The BRAF gene mutation that causes Erdheim-Chester disease is somatic, which means that it occurs during a person's lifetime and is present only in certain cells. The mutation occurs in histiocytes or in immature precursor cells that will develop into histiocytes. This mutation leads to production of a BRAF protein that is abnormally active, which disrupts regulation of cell growth and division. The unregulated overproduction of histiocytes results in their accumulation in the body's tissues and organs, leading to the signs and symptoms of Erdheim-Chester disease.  The BRAF gene belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous. Researchers disagree on whether Erdheim-Chester disease should be considered a form of cancer because of the unregulated accumulation of histiocytes. </s>


Input: Is Erdheim-Chester disease inherited ?

Output: This condition is not inherited. It arises from a somatic mutation in histiocytes or their precursor cells during an individual's lifetime. </s>


Input: What are the treatments for Erdheim-Chester disease ?

Output: These resources address the diagnosis or management of Erdheim-Chester disease:  - Histiocytosis Association: Erdheim-Chester Disease Diagnosis and Treatment   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) Ohdo syndrome, Maat-Kievit-Brunner type ?

Output: The Maat-Kievit-Brunner type of Ohdo syndrome is a rare condition characterized by intellectual disability and distinctive facial features. It has only been reported in males.  The intellectual disability associated with this condition varies from mild to severe, and the development of motor skills (such as sitting, standing, and walking) is delayed. Some affected individuals also have behavioral problems.  Distinctive facial features often seen in this condition include a narrowing of the eye opening (blepharophimosis), droopy eyelids (ptosis), prominent cheeks, a broad nasal bridge, a nose with a rounded tip, a large space between the nose and upper lip (a long philtrum), and a narrow mouth. Some affected individuals also have widely set eyes (hypertelorism), an unusually small chin (micrognathia), and small and low-set ears. As people with the condition get older, these facial characteristics become more pronounced and the face becomes more triangular.  Other possible signs of this condition include dental problems, weak muscle tone (hypotonia), and hearing loss. </s>


Input: How many people are affected by Ohdo syndrome, Maat-Kievit-Brunner type ?

Output: The Maat-Kievit-Brunner type of Ohdo syndrome is a very rare condition, with only a few affected individuals reported in the medical literature. </s>


Input: What are the genetic changes related to Ohdo syndrome, Maat-Kievit-Brunner type ?

Output: The Maat-Kievit-Brunner type of Ohdo syndrome results from mutations in the MED12 gene. This gene provides instructions for making a protein that helps regulate gene activity; it is thought to play an essential role in development both before and after birth. The MED12 gene mutations that cause this condition alter the structure of the MED12 protein, impairing its ability to control gene activity. It is unclear how these changes lead to the particular cognitive and physical features of the Maat-Kievit-Brunner type of Ohdo syndrome. </s>


Input: Is Ohdo syndrome, Maat-Kievit-Brunner type inherited ?

Output: This condition is inherited in an X-linked recessive pattern. The MED12 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder.  Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. Females with only one altered copy of the gene in each cell are called carriers. They do not usually experience health problems related to the condition, but they can pass the mutation to their children. Sons who inherit the altered gene will have the condition, while daughters who inherit the altered gene will be carriers.  A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. </s>


Input: What are the treatments for Ohdo syndrome, Maat-Kievit-Brunner type ?

Output: These resources address the diagnosis or management of Ohdo syndrome, Maat-Kievit-Brunner type:  - Genetic Testing Registry: Ohdo syndrome, X-linked   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) Huntington disease-like syndrome ?

Output: As its name suggests, a Huntington disease-like (HDL) syndrome is a condition that resembles Huntington disease. Researchers have described four HDL syndromes, designated Huntington disease-like 1 (HDL1) through Huntington disease-like 4 (HDL4). These progressive brain disorders are characterized by uncontrolled movements, emotional problems, and loss of thinking ability. HDL syndromes occur in people with the characteristic features of Huntington disease who do not have a mutation in HD, the gene typically associated with that disorder.  HDL1, HDL2, and HDL4 usually appear in early to mid-adulthood, although they can begin earlier in life. The first signs and symptoms of these conditions often include irritability, emotional problems, small involuntary movements, poor coordination, and trouble learning new information or making decisions. Many affected people develop involuntary jerking or twitching movements known as chorea. As the disease progresses, these abnormal movements become more pronounced. Affected individuals may develop problems with walking, speaking, and swallowing. People with these disorders also experience changes in personality and a decline in thinking and reasoning abilities. Individuals with an HDL syndrome can live for a few years to more than a decade after signs and symptoms begin.  HDL3 begins much earlier in life than most of the other HDL syndromes (usually around age 3 or 4). Affected children experience a decline in thinking ability, difficulties with movement and speech, and seizures. Because HDL3 has a somewhat different pattern of signs and symptoms and a different pattern of inheritance, researchers are unsure whether it belongs in the same category as the other HDL syndromes. </s>


Input: How many people are affected by Huntington disease-like syndrome ?

Output: Overall, HDL syndromes are rare. They are much less common than Huntington disease, which affects an estimated 3 to 7 per 100,000 people of European ancestry.  Of the four described HDL syndromes, HDL4 appears to be the most common. HDL2 is the second most common and occurs almost exclusively in people of African heritage (especially black South Africans). HDL1 has been reported in only one family. HDL3 has been found in two families, both of which were from Saudi Arabia. </s>


Input: What are the genetic changes related to Huntington disease-like syndrome ?

Output: In about one percent of people with the characteristic features of Huntington disease, no mutation in the HD gene has been identified. Mutations in the PRNP, JPH3, and TBP genes have been found to cause the signs and symptoms in some of these individuals. HDL1 is caused by mutations in the PRNP gene, while HDL2 results from mutations in JPH3. Mutations in the TBP gene are responsible for HDL4 (also known as spinocerebellar ataxia type 17). The genetic cause of HDL3 is unknown.  The PRNP, JPH3, and TBP genes provide instructions for making proteins that are important for normal brain function. The features of HDL syndromes result from a particular type of mutation in any one of these genes. This mutation increases the length of a repeated segment of DNA within the gene, which leads to the production of an abnormal PRNP, JPH3, or TBP protein. The abnormal protein can build up in nerve cells (neurons) and disrupt the normal functions of these cells. The dysfunction and eventual death of neurons in certain areas of the brain underlie the signs and symptoms of HDL syndromes.  Other medical conditions and gene mutations may also cause signs and symptoms resembling Huntington disease. In some affected people, the cause of the disorder is never identified. </s>


Input: Is Huntington disease-like syndrome inherited ?

Output: HDL1, HDL2, and HDL4 are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent.  As the mutation responsible for HDL2 or HDL4 is passed down from one generation to the next, the length of the repeated DNA segment may increase. A longer repeat segment is often associated with more severe signs and symptoms that appear earlier in life. This phenomenon is known as anticipation.  HDL3 is probably 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 do not show signs and symptoms of the condition. </s>


Input: What are the treatments for Huntington disease-like syndrome ?

Output: These resources address the diagnosis or management of Huntington disease-like syndrome:  - Gene Review: Gene Review: Huntington Disease-Like 2  - Gene Review: Gene Review: Spinocerebellar Ataxia Type 17  - Genetic Testing Registry: Huntington disease-like 1  - Genetic Testing Registry: Huntington disease-like 2  - Genetic Testing Registry: Huntington disease-like 3  - Genetic Testing Registry: Spinocerebellar ataxia 17   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) lymphangioleiomyomatosis ?

Output: Lymphangioleiomyomatosis (LAM) is a condition that affects the lungs, the kidneys, and the lymphatic system. The lymphatic system consists of a network of vessels that transport lymph fluid and immune cells throughout the body.  LAM is found almost exclusively in women. It usually occurs as a feature of an inherited syndrome called tuberous sclerosis complex. When LAM occurs alone it is called isolated or sporadic LAM.  Signs and symptoms of LAM most often appear during a woman's thirties. Affected women have an overgrowth of abnormal smooth muscle-like cells (LAM cells) in the lungs, resulting in the formation of lung cysts and the destruction of normal lung tissue. They may also have an accumulation of fluid in the cavity around the lungs (chylothorax).  The lung abnormalities resulting from LAM may cause difficulty breathing (dyspnea), chest pain, and coughing, which may bring up blood (hemoptysis). Many women with this disorder have recurrent episodes of collapsed lung (spontaneous pneumothorax). The lung problems may be progressive and, without lung transplantation, may eventually lead to limitations in activities of daily living, the need for oxygen therapy, and respiratory failure. Although LAM cells are not considered cancerous, they may spread between tissues (metastasize). As a result, the condition may recur even after lung transplantation.  Women with LAM may develop cysts in the lymphatic vessels of the chest and abdomen. These cysts are called lymphangioleiomyomas. Affected women may also develop tumors called angiomyolipomas made up of LAM cells, fat cells, and blood vessels. Angiomyolipomas usually develop in the kidneys. Internal bleeding is a common complication of angiomyolipomas. </s>


Input: How many people are affected by lymphangioleiomyomatosis ?

Output: Sporadic LAM is estimated to occur in 2 to 5 per million women worldwide. This condition may be underdiagnosed because its symptoms are similar to those of other lung disorders such as asthma, bronchitis, and chronic obstructive pulmonary disease. </s>


Input: What are the genetic changes related to lymphangioleiomyomatosis ?

Output: Mutations in the TSC1 gene or, more commonly, the TSC2 gene, cause LAM. The TSC1 and TSC2 genes provide instructions for making the proteins hamartin and tuberin, respectively. Within cells, these two proteins likely help regulate cell growth and size. The proteins act as tumor suppressors, which normally prevent cells from growing and dividing too fast or in an uncontrolled way.  When both copies of the TSC1 gene are mutated in a particular cell, that cell cannot produce any functional hamartin; cells with two altered copies of the TSC2 gene are unable to produce any functional tuberin. The loss of these proteins allows the cell to grow and divide in an uncontrolled way, resulting in the tumors and cysts associated with LAM.  It is not well understood why LAM occurs predominantly in women. Researchers believe that the female sex hormone estrogen may be involved in the development of the disorder. </s>


Input: Is lymphangioleiomyomatosis inherited ?

Output: Sporadic LAM is not inherited. Instead, researchers suggest that it is caused by a random mutation in the TSC1 or TSC2 gene that occurs very early in development. As a result, some of the body's cells have a normal version of the gene, while others have the mutated version. This situation is called mosaicism. When a mutation occurs in the other copy of the TSC1 or TSC2 gene in certain cells during a woman's lifetime (a somatic mutation), she may develop LAM. These women typically have no history of this disorder in their family. </s>


Input: What are the treatments for lymphangioleiomyomatosis ?

Output: These resources address the diagnosis or management of LAM:  - Canadian Lung Association  - Genetic Testing Registry: Lymphangiomyomatosis  - Merck Manual for Healthcare Professionals  - National Heart, Lung, and Blood Institute: How is LAM Diagnosed?  - National Heart, Lung, and Blood Institute: How is LAM Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) VACTERL association ?

Output: VACTERL association is a disorder that affects many body systems. VACTERL stands for vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. People diagnosed with VACTERL association typically have at least three of these characteristic features. Affected individuals may have additional abnormalities that are not among the characteristic features of VACTERL association.  Defects in the bones of the spine (vertebrae) are present in 60 to 80 percent of people with VACTERL association. These defects may include misshapen vertebrae, fused vertebrae, and missing or extra vertebrae. In some people, spinal problems require surgery or cause health problems, such as back pain of varying severity, throughout life. Sixty to 90 percent of individuals with VACTERL association have narrowing or blockage of the anus (anal atresia). Anal atresia may be accompanied by abnormalities of the genitalia and urinary tract (genitourinary anomalies). Heart (cardiac) defects occur in 40 to 80 percent of individuals with VACTERL association. Cardiac defects can range in severity from a life-threatening problem to a subtle defect that does not cause health problems. Fifty to 80 percent of people with VACTERL association have a tracheo-esophageal fistula, which is an abnormal connection (fistula) between the esophagus and the windpipe (trachea). Tracheo-esophageal fistula can cause problems with breathing and feeding early in life and typically requires surgical correction in infancy. Kidney (renal) anomalies occur in 50 to 80 percent of individuals with VACTERL association. Affected individuals may be missing one or both kidneys or have abnormally developed or misshapen kidneys, which can affect kidney function. Limb abnormalities are seen in 40 to 50 percent of people with VACTERL association. These abnormalities most commonly include poorly developed or missing thumbs or underdeveloped forearms and hands.  Some of the features of VACTERL association can be subtle and are not identified until late in childhood or adulthood, making diagnosis of this condition difficult. </s>


Input: How many people are affected by VACTERL association ?

Output: VACTERL association occurs in 1 in 10,000 to 40,000 newborns. </s>


Input: What are the genetic changes related to VACTERL association ?

Output: VACTERL association is a complex condition that may have different causes in different people. In some people, the condition is likely caused by the interaction of multiple genetic and environmental factors. Some possible genetic and environmental influences have been identified and are being studied.  The developmental abnormalities characteristic of VACTERL association develop before birth. The disruption to fetal development that causes VACTERL association likely occurs early in development, resulting in birth defects that affect multiple body systems. It is unclear why the features characteristic of VACTERL association group together in affected individuals. </s>


Input: Is VACTERL association inherited ?

Output: Most cases of VACTERL association are sporadic, which means they occur in people with no history of the condition in their family. Rarely, families have multiple people affected with VACTERL association. A few affected individuals have family members with one or two features, but not enough signs to be diagnosed with the condition. In these families, the features of VACTERL association often do not have a clear pattern of inheritance. Multiple genetic and environmental factors likely play a part in determining the risk of developing this condition and how severe the condition will be in an individual. </s>


Input: What are the treatments for VACTERL association ?

Output: These resources address the diagnosis or management of VACTERL association:  - MedlinePlus Encyclopedia: Tracheoesophageal Fistula and Esophageal Atresia Repair   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) age-related macular degeneration ?

Output: Age-related macular degeneration is an eye disease that is a leading cause of vision loss in older people in developed countries. The vision loss usually becomes noticeable in a person's sixties or seventies and tends to worsen over time.  Age-related macular degeneration mainly affects central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. The vision loss in this condition results from a gradual deterioration of light-sensing cells in the tissue at the back of the eye that detects light and color (the retina). Specifically, age-related macular degeneration affects a small area near the center of the retina, called the macula, which is responsible for central vision. Side (peripheral) vision and night vision are generally not affected.  Researchers have described two major types of age-related macular degeneration, known as the dry form and the wet form. The dry form is much more common, accounting for 85 to 90 percent of all cases of age-related macular degeneration. It is characterized by a buildup of yellowish deposits called drusen beneath the retina and slowly progressive vision loss. The condition typically affects vision in both eyes, although vision loss often occurs in one eye before the other.  The wet form of age-related macular degeneration is associated with severe vision loss that can worsen rapidly. This form of the condition is characterized by the growth of abnormal, fragile blood vessels underneath the macula. These vessels leak blood and fluid, which damages the macula and makes central vision appear blurry and distorted. </s>


Input: How many people are affected by age-related macular degeneration ?

Output: Age-related macular degeneration has an estimated prevalence of 1 in 2,000 people in the United States and other developed countries. The condition currently affects several million Americans, and the prevalence is expected to increase over the coming decades as the proportion of older people in the population increases.  For reasons that are unclear, age-related macular degeneration affects individuals of European descent more frequently than African Americans in the United States. </s>


Input: What are the genetic changes related to age-related macular degeneration ?

Output: Age-related macular degeneration results from a combination of genetic and environmental factors. Many of these factors have been identified, but some remain unknown.  Researchers have considered changes in many genes as possible risk factors for age-related macular degeneration. The best-studied of these genes are involved in a part of the body's immune response known as the complement system. This system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. Genetic changes in and around several complement system genes, including the CFH gene, contribute to a person's risk of developing age-related macular degeneration. It is unclear how these genetic changes are related to the retinal damage and vision loss characteristic of this condition.  Changes on the long (q) arm of chromosome 10 in a region known as 10q26 are also associated with an increased risk of age-related macular degeneration. The 10q26 region contains two genes of interest, ARMS2 and HTRA1. Changes in both genes have been studied as possible risk factors for the disease. However, because the two genes are so close together, it is difficult to tell which gene is associated with age-related macular degeneration risk, or whether increased risk results from variations in both genes.  Other genes that are associated with age-related macular degeneration include genes involved in transporting and processing high-density lipoprotein (HDL, also known as "good" cholesterol) and genes that have been associated with other forms of macular disease.  Researchers have also examined nongenetic factors that contribute to the risk of age-related macular degeneration. Age appears to be the most important risk factor; the chance of developing the condition increases significantly as a person gets older. Smoking is another established risk factor for age-related macular degeneration. Other factors that may increase the risk of this condition include high blood pressure, heart disease, a high-fat diet or one that is low in certain nutrients (such as antioxidants and zinc), obesity, and exposure to ultraviolet (UV) rays from sunlight. However, studies of these factors in age-related macular degeneration have had conflicting results </s>


Input: Is age-related macular degeneration inherited ?

Output: Age-related macular degeneration usually does not have a clear-cut pattern of inheritance, although the condition appears to run in families in some cases. An estimated 15 to 20 percent of people with age-related macular degeneration have at least one first-degree relative (such as a sibling) with the condition. </s>


Input: What are the treatments for age-related macular degeneration ?

Output: These resources address the diagnosis or management of age-related macular degeneration:  - BrightFocus Foundation: Macular Degeneration Treatment  - Genetic Testing Registry: Age-related macular degeneration  - Genetic Testing Registry: Age-related macular degeneration 1  - Genetic Testing Registry: Age-related macular degeneration 10  - Genetic Testing Registry: Age-related macular degeneration 11  - Genetic Testing Registry: Age-related macular degeneration 2  - Genetic Testing Registry: Age-related macular degeneration 3  - Genetic Testing Registry: Age-related macular degeneration 4  - Genetic Testing Registry: Age-related macular degeneration 7  - Genetic Testing Registry: Age-related macular degeneration 9  - Genetic Testing Registry: Susceptibility to age-related macular degeneration, wet type  - Genetic Testing Registry: Susceptibility to neovascular type of age-related macular degeneration  - Macular Degeneration Partnership: Low Vision Rehabilitation  - Prevent Blindness America: Age-Related Macular Degeneration (AMD) Test - Amsler Grid   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) propionic acidemia ?

Output: Propionic acidemia is an inherited disorder in which the body is unable to process certain parts of proteins and lipids (fats) properly. It is classified as an organic acid disorder, which is a condition that leads to an abnormal buildup of particular acids known as organic acids. Abnormal levels of organic acids in the blood (organic acidemia), urine (organic aciduria), and tissues can be toxic and can cause serious health problems.  In most cases, the features of propionic acidemia become apparent within a few days after birth. The initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These symptoms sometimes progress to more serious medical problems, including heart abnormalities, seizures, coma, and possibly death.  Less commonly, the signs and symptoms of propionic acidemia appear during childhood and may come and go over time. Some affected children experience intellectual disability or delayed development. In children with this later-onset form of the condition, episodes of more serious health problems can be triggered by prolonged periods without food (fasting), fever, or infections. </s>


Input: How many people are affected by propionic acidemia ?

Output: Propionic acidemia affects about 1 in 100,000 people in the United States. The condition appears to be more common in several populations worldwide, including the Inuit population of Greenland, some Amish communities, and Saudi Arabians. </s>


Input: What are the genetic changes related to propionic acidemia ?

Output: Mutations in the PCCA and PCCB genes cause propionic acidemia.  The PCCA and PCCB genes provide instructions for making two parts (subunits) of an enzyme called propionyl-CoA carboxylase. This enzyme plays a role in the normal breakdown of proteins. Specifically, it helps process several amino acids, which are the building blocks of proteins. Propionyl-CoA carboxylase also helps break down certain types of fat and cholesterol in the body. Mutations in the PCCA or PCCB gene disrupt the function of the enzyme and prevent the normal breakdown of these molecules. As a result, a substance called propionyl-CoA and other potentially harmful compounds can build up to toxic levels in the body. This buildup damages the brain and nervous system, causing the serious health problems associated with propionic acidemia. </s>


Input: Is propionic acidemia 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 propionic acidemia ?

Output: These resources address the diagnosis or management of propionic acidemia:  - Baby's First Test  - Gene Review: Gene Review: Propionic Acidemia  - Genetic Testing Registry: Propionic acidemia   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) early-onset primary dystonia ?

Output: Early-onset primary dystonia is a condition characterized by progressive problems with movement, typically beginning in childhood. Dystonia is a movement disorder that involves involuntary tensing of the muscles (muscle contractions), twisting of specific body parts such as an arm or a leg, rhythmic shaking (tremors), and other uncontrolled movements. A primary dystonia is one that occurs without other neurological symptoms, such as seizures or a loss of intellectual function (dementia). Early-onset primary dystonia does not affect a person's intelligence.  On average, the signs and symptoms of early-onset primary dystonia appear around age 12. Abnormal muscle spasms in an arm or a leg are usually the first sign. These unusual movements initially occur while a person is doing a specific action, such as writing or walking. In some affected people, dystonia later spreads to other parts of the body and may occur at rest. The abnormal movements persist throughout life, but they do not usually cause pain.  The signs and symptoms of early-onset primary dystonia vary from person to person, even among affected members of the same family. The mildest cases affect only a single part of the body, causing isolated problems such as a writer's cramp in the hand. Severe cases involve abnormal movements affecting many regions of the body. </s>


Input: How many people are affected by early-onset primary dystonia ?

Output: Early-onset primary dystonia is among the most common forms of childhood dystonia. This disorder occurs most frequently in people of Ashkenazi (central and eastern European) Jewish heritage, affecting 1 in 3,000 to 9,000 people in this population. The condition is less common among people with other backgrounds; it is estimated to affect 1 in 10,000 to 30,000 non-Jewish people worldwide. </s>


Input: What are the genetic changes related to early-onset primary dystonia ?

Output: A particular mutation in the TOR1A gene (also known as DYT1) is responsible for most cases of early-onset primary dystonia. The TOR1A gene provides instructions for making a protein called torsinA. Although little is known about its function, this protein may help process and transport other proteins within cells. It appears to be critical for the normal development and function of nerve cells in the brain.  A mutation in the TOR1A gene alters the structure of torsinA. The altered protein's effect on the function of nerve cells in the brain is unclear. People with early-onset primary dystonia do not have a loss of nerve cells or obvious changes in the structure of the brain that would explain the abnormal muscle contractions. Instead, the altered torsinA protein may have subtle effects on the connections between nerve cells and likely disrupts chemical signaling between nerve cells that control movement. Researchers are working to determine how a change in this protein leads to the characteristic features of this disorder. </s>


Input: Is early-onset primary dystonia inherited ?

Output: Mutations in the TOR1A gene are inherited in an autosomal dominant pattern, which means one of the two copies of the gene is altered in each cell. Many people who have a mutation in this gene are not affected by the disorder and may never know they have the mutation. Only 30 to 40 percent of people who inherit a TOR1A mutation will ever develop signs and symptoms of early-onset primary dystonia.  Everyone who has been diagnosed with early-onset primary dystonia has inherited a TOR1A mutation from one parent. The parent may or may not have signs and symptoms of the condition, and other family members may or may not be affected. </s>


Input: What are the treatments for early-onset primary dystonia ?

Output: These resources address the diagnosis or management of early-onset primary dystonia:  - Gene Review: Gene Review: DYT1 Early-Onset Primary Dystonia  - Genetic Testing Registry: Dystonia 1  - MedlinePlus Encyclopedia: Movement - uncontrolled or slow   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) epidermolysis bullosa simplex ?

Output: Epidermolysis bullosa simplex is one of a group of genetic conditions called epidermolysis bullosa that cause the skin to be very fragile and to blister easily. Blisters and areas of skin loss (erosions) occur in response to minor injury or friction, such as rubbing or scratching. Epidermolysis bullosa simplex is one of the major forms of epidermolysis bullosa. The signs and symptoms of this condition vary widely among affected individuals. Blistering primarily affects the hands and feet in mild cases, and the blisters usually heal without leaving scars. Severe cases of this condition involve widespread blistering that can lead to infections, dehydration, and other medical problems. Severe cases may be life-threatening in infancy.  Researchers have identified four major types of epidermolysis bullosa simplex. Although the types differ in severity, their features overlap significantly, and they are caused by mutations in the same genes. Most researchers now consider the major forms of this condition to be part of a single disorder with a range of signs and symptoms.  The mildest form of epidermolysis bullosa simplex, known as the localized type (formerly called the Weber-Cockayne type), is characterized by skin blistering that begins anytime between childhood and adulthood and is usually limited to the hands and feet. Later in life, skin on the palms of the hands and soles of the feet may thicken and harden (hyperkeratosis).  The Dowling-Meara type is the most severe form of epidermolysis bullosa simplex. Extensive, severe blistering can occur anywhere on the body, including the inside of the mouth, and blisters may appear in clusters. Blistering is present from birth and tends to improve with age. Affected individuals also experience abnormal nail growth and hyperkeratosis of the palms and soles.  Another form of epidermolysis bullosa simplex, known as the other generalized type (formerly called the Koebner type), is associated with widespread blisters that appear at birth or in early infancy. The blistering tends to be less severe than in the Dowling-Meara type.  Epidermolysis bullosa simplex with mottled pigmentation is characterized by patches of darker skin on the trunk, arms, and legs that fade in adulthood. This form of the disorder also involves skin blistering from early infancy, hyperkeratosis of the palms and soles, and abnormal nail growth.  In addition to the four major types described above, researchers have identified another skin condition related to epidermolysis bullosa simplex, which they call the Ogna type. It is caused by mutations in a gene that is not associated with the other types of epidermolysis bullosa simplex. It is unclear whether the Ogna type is a subtype of epidermolysis bullosa simplex or represents a separate form of epidermolysis bullosa.  Several other variants of epidermolysis bullosa simplex have been proposed, but they appear to be very rare. </s>


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

Output: The exact prevalence of epidermolysis bullosa simplex is unknown, but this condition is estimated to affect 1 in 30,000 to 50,000 people. The localized type is the most common form of the condition. </s>


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

Output: The four major types of epidermolysis bullosa simplex can result from mutations in either the KRT5 or KRT14 gene. These genes provide instructions for making proteins called keratin 5 and keratin 14. These tough, fibrous proteins work together to provide strength and resiliency to the outer layer of the skin (the epidermis). Mutations in either the KRT5 or KRT14 gene prevent the keratin proteins from assembling into strong networks, causing cells in the epidermis to become fragile and easily damaged. As a result, the skin is less resistant to friction and minor trauma and blisters easily. In rare cases, no KRT5 or KRT14 gene mutations are identified in people with one of the four major types of epidermolysis bullosa simplex.  Mutations in another gene, PLEC, have been associated with the rare Ogna type of epidermolysis bullosa simplex. The PLEC gene provides instructions for making a protein called plectin, which helps attach the epidermis to underlying layers of skin. Researchers are working to determine how PLEC gene mutations lead to the major features of the condition. </s>


Input: Is epidermolysis bullosa simplex inherited ?

Output: Epidermolysis bullosa simplex is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Some affected people inherit the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  In rare cases, epidermolysis bullosa simplex is inherited in an autosomal recessive pattern. Autosomal recessive inheritance means the condition results when two copies of the gene in each cell are altered. The parents of an individual with an autosomal recessive disorder typically each carry one copy of the altered gene, but do not show signs and symptoms of the disorder. </s>


Input: What are the treatments for epidermolysis bullosa simplex ?

Output: These resources address the diagnosis or management of epidermolysis bullosa simplex:  - Dystrophic Epidermolysis Bullosa Research Association (DebRA) of America: Wound Care  - Epidermolysis Bullosa Center, Cincinnati Children's Hospital Medical Center  - Gene Review: Gene Review: Epidermolysis Bullosa Simplex  - Genetic Testing Registry: Epidermolysis bullosa simplex  - Genetic Testing Registry: Epidermolysis bullosa simplex with mottled pigmentation  - Genetic Testing Registry: Epidermolysis bullosa simplex, Cockayne-Touraine type  - Genetic Testing Registry: Epidermolysis bullosa simplex, Koebner type  - Genetic Testing Registry: Epidermolysis bullosa simplex, Ogna type  - Genetic Testing Registry: Epidermolysis bullosa simplex, autosomal recessive  - MedlinePlus Encyclopedia: Epidermolysis Bullosa   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) fatty acid hydroxylase-associated neurodegeneration ?

Output: Fatty acid hydroxylase-associated neurodegeneration (FAHN) is a progressive disorder of the nervous system (neurodegeneration) characterized by problems with movement and vision that begin during childhood or adolescence.  Changes in the way a person walks (gait) and frequent falls are usually the first noticeable signs of FAHN. Affected individuals gradually develop extreme muscle stiffness (spasticity) and exaggerated reflexes. They typically have involuntary muscle cramping (dystonia), problems with coordination and balance (ataxia), or both. The movement problems worsen over time, and some people with this condition eventually require wheelchair assistance.  People with FAHN often develop vision problems, which occur due to deterioration (atrophy) of the nerves that carry information from the eyes to the brain (the optic nerves) and difficulties with the muscles that control eye movement. Affected individuals may have a loss of sharp vision (reduced visual acuity), decreased field of vision, impaired color perception, eyes that do not look in the same direction (strabismus), rapid involuntary eye movements (nystagmus), or difficulty moving the eyes intentionally (supranuclear gaze palsy).  Speech impairment (dysarthria) also occurs in FAHN, and severely affected individuals may lose the ability to speak. People with this disorder may also have difficulty chewing or swallowing (dysphagia). In severe cases, they may develop malnutrition and require a feeding tube. The swallowing difficulties can lead to a bacterial lung infection called aspiration pneumonia, which can be life-threatening. As the disorder progresses, some affected individuals experience seizures and a decline in intellectual function.  Magnetic resonance imaging (MRI) of the brain in people with FAHN shows signs of iron accumulation, especially in an area of the brain called the globus pallidus, which is involved in regulating movement. Similar patterns of iron accumulation are seen in certain other neurological disorders such as infantile neuroaxonal dystrophy and pantothenate kinase-associated neurodegeneration. All these conditions belong to a class of disorders called neurodegeneration with brain iron accumulation (NBIA). </s>


Input: How many people are affected by fatty acid hydroxylase-associated neurodegeneration ?

Output: FAHN is a rare disorder; only a few dozen cases have been reported. </s>


Input: What are the genetic changes related to fatty acid hydroxylase-associated neurodegeneration ?

Output: Mutations in the FA2H gene cause FAHN. The FA2H gene provides instructions for making an enzyme called fatty acid 2-hydroxylase. This enzyme modifies fatty acids, which are building blocks used to make fats (lipids). Specifically, fatty acid 2-hydroxylase adds a single oxygen atom to a hydrogen atom at a particular point on a fatty acid to create a 2-hydroxylated fatty acid. Certain 2-hydroxylated fatty acids are important in forming normal myelin; myelin is the protective covering that insulates nerves and ensures the rapid transmission of nerve impulses. The part of the brain and spinal cord that contains myelin is called white matter.  The FA2H gene mutations that cause FAHN reduce or eliminate the function of the fatty acid 2-hydroxylase enzyme. Reduction of this enzyme's function may result in abnormal myelin that is prone to deterioration (demyelination), leading to a loss of white matter (leukodystrophy). Leukodystrophy is likely involved in the development of the movement problems and other neurological abnormalities that occur in FAHN. Iron accumulation in the brain is probably also involved, although it is unclear how FA2H gene mutations lead to the buildup of iron.  People with FA2H gene mutations and some of the movement problems seen in FAHN were once classified as having a separate disorder called spastic paraplegia 35. People with mutations in this gene resulting in intellectual decline and optic nerve atrophy were said to have a disorder called FA2H-related leukodystrophy. However, these conditions are now generally considered to be forms of FAHN. </s>


Input: Is fatty acid hydroxylase-associated neurodegeneration inherited ?

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


Input: What are the treatments for fatty acid hydroxylase-associated neurodegeneration ?

Output: These resources address the diagnosis or management of fatty acid hydroxylase-associated neurodegeneration:  - Gene Review: Gene Review: Fatty Acid Hydroxylase-Associated Neurodegeneration  - Genetic Testing Registry: Spastic paraplegia 35   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) ulcerative colitis ?

Output: Ulcerative colitis is a chronic disorder that affects the digestive system. This condition is characterized by abnormal inflammation of the inner surface of the rectum and colon, which make up most of the length of the large intestine. The inflammation usually causes open sores (ulcers) to develop in the large intestine. Ulcerative colitis usually appears between ages 15 and 30, although it can develop at any age. The inflammation tends to flare up multiple times throughout life, which causes recurring signs and symptoms.  The most common symptoms of ulcerative colitis are abdominal pain and cramping and frequent diarrhea, often with blood, pus, or mucus in the stool. Other signs and symptoms include nausea, loss of appetite, fatigue, and fevers. Chronic bleeding from the inflamed and ulcerated intestinal tissue can cause a shortage of red blood cells (anemia) in some affected individuals. People with this disorder have difficulty absorbing enough fluids and nutrients from their diet and often experience weight loss. Affected children usually grow more slowly than normal. Less commonly, ulcerative colitis causes problems with the skin, joints, eyes, kidneys, or liver, which are most likely due to abnormal inflammation.  Toxic megacolon is a rare complication of ulcerative colitis that can be life-threatening. Toxic megacolon involves widening of the colon and an overwhelming bacterial infection (sepsis). Ulcerative colitis also increases the risk of developing colon cancer, especially in people whose entire colon is inflamed and in people who have had ulcerative colitis for 8 or more years.  Ulcerative colitis is one common form of inflammatory bowel disease (IBD). Another type of IBD, Crohn disease, also causes chronic inflammation of the intestines. Unlike ulcerative colitis, which affects only the inner surface of the large intestine, Crohn disease can cause inflammation in any part of the digestive system, and the inflammation extends deeper into the intestinal tissue. </s>


Input: How many people are affected by ulcerative colitis ?

Output: Ulcerative colitis is most common in North America and Western Europe; however the prevalence is increasing in other regions. In North America, ulcerative colitis affects approximately 40 to 240 in 100,000 people. It is estimated that more than 750,000 North Americans are affected by this disorder. Ulcerative colitis is more common in whites and people of eastern and central European (Ashkenazi) Jewish descent than among people of other ethnic backgrounds. </s>