Input: What is (are) Duchenne and Becker muscular dystrophy ?

Output: Muscular dystrophies are a group of genetic conditions characterized by progressive muscle weakness and wasting (atrophy). The Duchenne and Becker types of muscular dystrophy are two related conditions that primarily affect skeletal muscles, which are used for movement, and heart (cardiac) muscle. These forms of muscular dystrophy occur almost exclusively in males.  Duchenne and Becker muscular dystrophies have similar signs and symptoms and are caused by different mutations in the same gene. The two conditions differ in their severity, age of onset, and rate of progression. In boys with Duchenne muscular dystrophy, muscle weakness tends to appear in early childhood and worsen rapidly. Affected children may have delayed motor skills, such as sitting, standing, and walking. They are usually wheelchair-dependent by adolescence. The signs and symptoms of Becker muscular dystrophy are usually milder and more varied. In most cases, muscle weakness becomes apparent later in childhood or in adolescence and worsens at a much slower rate.  Both the Duchenne and Becker forms of muscular dystrophy are associated with a heart condition called cardiomyopathy. This form of heart disease weakens the cardiac muscle, preventing the heart from pumping blood efficiently. In both Duchenne and Becker muscular dystrophy, cardiomyopathy typically begins in adolescence. Later, the heart muscle becomes enlarged, and the heart problems develop into a condition known as dilated cardiomyopathy. Signs and symptoms of dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath, extreme tiredness (fatigue), and swelling of the legs and feet. These heart problems worsen rapidly and become life-threatening in many cases. Males with Duchenne muscular dystrophy typically live into their twenties, while males with Becker muscular dystrophy can survive into their forties or beyond.  A related condition called DMD-associated dilated cardiomyopathy is a form of heart disease caused by mutations in the same gene as Duchenne and Becker muscular dystrophy, and it is sometimes classified as subclinical Becker muscular dystrophy. People with DMD-associated dilated cardiomyopathy typically do not have any skeletal muscle weakness or wasting, although they may have subtle changes in their skeletal muscle cells that are detectable through laboratory testing. </s>


Input: How many people are affected by Duchenne and Becker muscular dystrophy ?

Output: Duchenne and Becker muscular dystrophies together affect 1 in 3,500 to 5,000 newborn males worldwide. Between 400 and 600 boys in the United States are born with these conditions each year. </s>


Input: What are the genetic changes related to Duchenne and Becker muscular dystrophy ?

Output: Mutations in the DMD gene cause the Duchenne and Becker forms of muscular dystrophy. The DMD gene provides instructions for making a protein called dystrophin. This protein is located primarily in skeletal and cardiac muscle, where it helps stabilize and protect muscle fibers. Dystrophin may also play a role in chemical signaling within cells.  Mutations in the DMD gene alter the structure or function of dystrophin or prevent any functional dystrophin from being produced. Muscle cells without enough of this protein become damaged as muscles repeatedly contract and relax with use. The damaged fibers weaken and die over time, leading to the muscle weakness and heart problems characteristic of Duchenne and Becker muscular dystrophies. Mutations that lead to an abnormal version of dystrophin that retains some function usually cause Becker muscular dystrophy, while mutations that prevent the production of any functional dystrophin tend to cause Duchenne muscular dystrophy.  Because Duchenne and Becker muscular dystrophies result from faulty or missing dystrophin, these conditions are classified as dystrophinopathies. </s>


Input: Is Duchenne and Becker muscular dystrophy inherited ?

Output: This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In about two-thirds of cases, an affected male inherits the mutation from his mother, who carries one altered copy of the DMD gene. The other one-third of cases probably result from new mutations in the gene in affected males and are not inherited.  In X-linked recessive inheritance, a female with one mutated copy of the gene in each cell is called a carrier. She can pass on the altered gene but usually does not experience signs and symptoms of the disorder. Occasionally, however, females who carry a DMD gene mutation may have muscle weakness and cramping. These symptoms are typically milder than the severe muscle weakness and atrophy seen in affected males. Females who carry a DMD gene mutation also have an increased risk of developing heart abnormalities including cardiomyopathy. </s>


Input: What are the treatments for Duchenne and Becker muscular dystrophy ?

Output: These resources address the diagnosis or management of Duchenne and Becker muscular dystrophy:  - Gene Review: Gene Review: Dilated Cardiomyopathy Overview  - Gene Review: Gene Review: Dystrophinopathies  - Genetic Testing Registry: Becker muscular dystrophy  - Genetic Testing Registry: Duchenne muscular dystrophy  - Genomics Education Programme (UK)  - MedlinePlus Encyclopedia: Becker Muscular Dystrophy  - MedlinePlus Encyclopedia: Dilated Cardiomyopathy  - MedlinePlus Encyclopedia: Duchenne Muscular Dystrophy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) combined pituitary hormone deficiency ?

Output: Combined pituitary hormone deficiency is a condition that causes a shortage (deficiency) of several hormones produced by the pituitary gland, which is located at the base of the brain. A lack of these hormones may affect the development of many parts of the body. The first signs of this condition include a failure to grow at the expected rate and short stature that usually becomes apparent in early childhood.  People with combined pituitary hormone deficiency may have hypothyroidism, which is underactivity of the butterfly-shaped thyroid gland in the lower neck. Hypothyroidism can cause many symptoms, including weight gain and fatigue. Other features of combined pituitary hormone deficiency include delayed or absent puberty and lack the ability to have biological children (infertility). The condition can also be associated with a deficiency of the hormone cortisol. Cortisol deficiency can impair the body's immune system, causing individuals to be more susceptible to infection.  Rarely, people with combined pituitary hormone deficiency have intellectual disability; a short, stiff neck; or underdeveloped optic nerves, which carry visual information from the eyes to the brain. </s>


Input: How many people are affected by combined pituitary hormone deficiency ?

Output: The prevalence of combined pituitary hormone deficiency is estimated to be 1 in 8,000 individuals worldwide. </s>


Input: What are the genetic changes related to combined pituitary hormone deficiency ?

Output: Mutations in at least eight genes have been found to cause combined pituitary hormone deficiency. Mutations in the PROP1 gene are the most common known cause of this disorder, accounting for an estimated 12 to 55 percent of cases. Mutations in other genes have each been identified in a smaller number of affected individuals.  The genes associated with combined pituitary hormone deficiency provide instructions for making proteins called transcription factors, which help control the activity of many other genes. The proteins are involved in the development of the pituitary gland and the specialization (differentiation) of its cell types. The cells of the pituitary gland are responsible for triggering the release of several hormones that direct the development of many parts of the body. Some of the transcription factors are found only in the pituitary gland, and some are also active in other parts of the body.  Mutations in the genes associated with combined pituitary hormone deficiency can result in abnormal differentiation of pituitary gland cells and may prevent the production of several hormones. These hormones can include growth hormone (GH), which is needed for normal growth; follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which both play a role in sexual development and the ability to have children (fertility); thyroid-stimulating hormone (TSH), which helps with thyroid gland function; prolactin, which stimulates the production of breast milk; and adrenocorticotropic hormone (ACTH), which influences energy production in the body and maintains normal blood sugar and blood pressure levels. The degree to which these hormones are deficient is variable, with prolactin and ACTH showing the most variability. In many affected individuals, ACTH deficiency does not occur until late adulthood.  Most people with combined pituitary hormone deficiency do not have identified mutations in any of the genes known to be associated with this condition. The cause of the disorder in these individuals is unknown. </s>


Input: Is combined pituitary hormone deficiency inherited ?

Output: Most cases of combined pituitary hormone deficiency are sporadic, which means they occur in people with no history of the disorder in their family. Less commonly, this condition has been found to run in families. When the disorder is familial, it can have an autosomal dominant or an autosomal recessive pattern of inheritance.  Autosomal dominant inheritance means one copy of an altered gene in each cell is sufficient to cause the disorder.  Autosomal recessive inheritance means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of a mutated gene, but they typically do not show signs and symptoms of the condition. Most cases of familial combined pituitary hormone deficiency are inherited in an autosomal recessive pattern. </s>


Input: What are the treatments for combined pituitary hormone deficiency ?

Output: These resources address the diagnosis or management of combined pituitary hormone deficiency:  - Gene Review: Gene Review: PROP1-Related Combined Pituitary Hormone Deficiency  - Genetic Testing Registry: Pituitary hormone deficiency, combined  - Genetic Testing Registry: Pituitary hormone deficiency, combined 1  - Genetic Testing Registry: Pituitary hormone deficiency, combined 2  - Genetic Testing Registry: Pituitary hormone deficiency, combined 3  - Genetic Testing Registry: Pituitary hormone deficiency, combined 4  - Genetic Testing Registry: Pituitary hormone deficiency, combined 5  - Genetic Testing Registry: Pituitary hormone deficiency, combined 6  - Great Ormond Street Hospital for Children (UK): Growth Hormone Deficiency  - MedlinePlus Encyclopedia: ACTH  - MedlinePlus Encyclopedia: FSH  - MedlinePlus Encyclopedia: Growth Hormone Deficiency  - MedlinePlus Encyclopedia: Prolactin  - MedlinePlus Encyclopedia: TSH Test   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) multiple mitochondrial dysfunctions syndrome ?

Output: Multiple mitochondrial dysfunctions syndrome is characterized by impairment of cellular structures called mitochondria, which are the energy-producing centers of cells. While certain mitochondrial disorders are caused by impairment of a single stage of energy production, individuals with multiple mitochondrial dysfunctions syndrome have reduced function of more than one stage. The signs and symptoms of this severe condition begin early in life, and affected individuals usually do not live past infancy.  Affected infants typically have severe brain dysfunction (encephalopathy), which can contribute to weak muscle tone (hypotonia), seizures, and delayed development of mental and movement abilities (psychomotor delay). These infants often have difficulty growing and gaining weight at the expected rate (failure to thrive). Most affected babies have a buildup of a chemical called lactic acid in the body (lactic acidosis), which can be life-threatening. They may also have high levels of a molecule called glycine (hyperglycinemia) or elevated levels of sugar (hyperglycemia) in the blood. Some babies with multiple mitochondrial dysfunctions syndrome have high blood pressure in the blood vessels that connect to the lungs (pulmonary hypertension) or weakening of the heart muscle (cardiomyopathy). </s>


Input: How many people are affected by multiple mitochondrial dysfunctions syndrome ?

Output: Multiple mitochondrial dysfunctions syndrome is a rare condition; its prevalence is unknown. It is one of several conditions classified as mitochondrial disorders, which affect an estimated 1 in 5,000 people worldwide. </s>


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

Output: Multiple mitochondrial dysfunctions syndrome can be caused by mutations in the NFU1 or BOLA3 gene. The proteins produced from each of these genes appear to be involved in the formation of molecules called iron-sulfur (Fe-S) clusters or in the attachment of these clusters to other proteins. Certain proteins require attachment of Fe-S clusters to function properly.  The NFU-1 and BOLA3 proteins play an important role in mitochondria. In these structures, several proteins carry out a series of chemical steps to convert the energy in food into a form that cells can use. Many of the proteins involved in these steps require Fe-S clusters to function, including protein complexes called complex I, complex II, and complex III.  Fe-S clusters are also required for another mitochondrial protein to function; this protein is involved in the modification of additional proteins that aid in energy production in mitochondria, including the pyruvate dehydrogenase complex and the alpha-ketoglutarate dehydrogenase complex (also known as the oxoglutarate dehydrogenase complex). This modification is also critical to the function of the glycine cleavage system, a set of proteins that breaks down a protein building block (amino acid) called glycine when levels become too high.  Mutations in the NFU1 or BOLA3 gene reduce or eliminate production of the respective protein, which impairs Fe-S cluster formation. Consequently, proteins affected by the presence of Fe-S clusters, including those involved in energy production and glycine breakdown, cannot function normally. Reduced activity of complex I, II, or III, pyruvate dehydrogenase, or alpha-ketoglutarate dehydrogenase leads to potentially fatal lactic acidosis, encephalopathy, and other signs and symptoms of multiple mitochondrial dysfunctions syndrome. In some affected individuals, impairment of the glycine cleavage system leads to a buildup of glycine. </s>


Input: Is multiple mitochondrial dysfunctions syndrome inherited ?

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


Input: What are the treatments for multiple mitochondrial dysfunctions syndrome ?

Output: These resources address the diagnosis or management of multiple mitochondrial dysfunctions syndrome:  - Gene Review: Gene Review: Mitochondrial Disorders Overview  - Genetic Testing Registry: Multiple mitochondrial dysfunctions syndrome 1  - Genetic Testing Registry: Multiple mitochondrial dysfunctions syndrome 2  - Genetic Testing Registry: Multiple mitochondrial dysfunctions syndrome 3   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) Charcot-Marie-Tooth disease ?

Output: Charcot-Marie-Tooth disease is a group of progressive disorders that affect the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound. Damage to the peripheral nerves can result in loss of sensation and wasting (atrophy) of muscles in the feet, legs, and hands.  Charcot-Marie-Tooth disease usually becomes apparent in adolescence or early adulthood, but onset may occur anytime from early childhood through late adulthood. Symptoms of Charcot-Marie-Tooth disease vary in severity, even among members of the same family. Some people never realize they have the disorder, but most have a moderate amount of physical disability. A small percentage of people experience severe weakness or other problems which, in rare cases, can be life-threatening. In most affected individuals, however, Charcot-Marie-Tooth disease does not affect life expectancy.  Typically, the earliest symptoms of Charcot-Marie-Tooth disease involve balance difficulties, clumsiness, and muscle weakness in the feet. Affected individuals may have foot abnormalities such as high arches (pes cavus), flat feet (pes planus), or curled toes (hammer toes). They often have difficulty flexing the foot or walking on the heel of the foot. These difficulties may cause a higher than normal step (or gait) and increase the risk of ankle injuries and tripping.  As the disease progresses, muscles in the lower legs usually weaken, but leg and foot problems rarely require the use of a wheelchair. Affected individuals may also develop weakness in the hands, causing difficulty with daily activities such as writing, fastening buttons, and turning doorknobs. People with this disorder typically experience a decreased sensitivity to touch, heat, and cold in the feet and lower legs, but occasionally feel aching or burning sensations. In some cases, affected individuals experience gradual hearing loss, deafness, or loss of vision.  There are several types of Charcot-Marie-Tooth disease. Type 1 Charcot-Marie-Tooth disease (CMT1) is characterized by abnormalities in myelin, the fatty substance that covers nerve cells, protecting them and helping to conduct nerve impulses. These abnormalities slow the transmission of nerve impulses. Type 2 Charcot-Marie-Tooth disease (CMT2) is characterized by abnormalities in the fiber, or axon, that extends from a nerve cell body and transmits nerve impulses. These abnormalities reduce the strength of the nerve impulse. Type 4 Charcot-Marie-Tooth disease (CMT4) affects either the axon or myelin and is distinguished from the other types by its pattern of inheritance. In intermediate forms of Charcot-Marie-Tooth disease, the nerve impulses are both slowed and reduced in strength, probably due to abnormalities in both axons and myelin. Type X Charcot-Marie-Tooth disease (CMTX) is caused by mutations in a gene on the X chromosome, one of the two sex chromosomes. Within the various types of Charcot-Marie-Tooth disease, subtypes (such as CMT1A, CMT1B, CMT2A, CMT4A, and CMTX1) are distinguished by the specific gene that is altered.  Sometimes other, more historical names are used to describe this disorder. For example, Roussy-Levy syndrome is a form of Charcot-Marie-Tooth disease defined by the additional feature of rhythmic shaking (tremors). Dejerine-Sottas syndrome is a term sometimes used to describe a severe, early childhood form of Charcot-Marie-Tooth disease; it is also sometimes called Charcot-Marie-Tooth disease type 3 (CMT3). Depending on the specific gene that is altered, this severe, early onset form of the disorder may also be classified as CMT1 or CMT4. CMTX5 is also known as Rosenberg-Chutorian syndrome. Some researchers believe that this condition is not actually a form of Charcot-Marie-Tooth disease. Instead, they classify it as a separate disorder characterized by peripheral nerve problems, deafness, and vision loss. </s>


Input: How many people are affected by Charcot-Marie-Tooth disease ?

Output: Charcot-Marie-Tooth disease is the most common inherited disorder that involves the peripheral nerves, affecting an estimated 150,000 people in the United States. It occurs in populations worldwide with a prevalence of about 1 in 2,500 individuals. </s>


Input: What are the genetic changes related to Charcot-Marie-Tooth disease ?

Output: Charcot-Marie-Tooth disease is caused by mutations in many different genes. These genes provide instructions for making proteins that are involved in the function of peripheral nerves in the feet, legs, and hands. The gene mutations that cause Charcot-Marie-Tooth disease affect the function of the proteins in ways that are not fully understood; however, they likely impair axons, which transmit nerve impulses, or affect the specialized cells that produce myelin. As a result, peripheral nerve cells slowly lose the ability to stimulate the muscles and to transmit sensory signals to the brain.  The list of genes associated with Charcot-Marie-Tooth disease continues to grow as researchers study this disorder. Different mutations within a particular gene may cause signs and symptoms of differing severities or lead to different types of Charcot-Marie-Tooth disease.  CMT1 is caused by mutations in the following genes: PMP22 (CMT1A and CMT1E), MPZ (CMT1B), LITAF (CMT1C), EGR2 (CMT1D), and NEFL (CMT1F).  CMT2 can result from alterations in many genes, including MFN2 and KIF1B (CMT2A); RAB7A (CMT2B); LMNA (CMT2B1); TRPV4 (CMT2C); BSCL2 and GARS (CMT2D); NEFL (CMT2E); HSPB1 (CMT2F); MPZ (CMT2I and CMT2J); GDAP1 (CMT2K); and HSPB8 (CMT2L). Certain DNM2 gene mutations also cause a form of CMT2.  CMT4 is caused by mutations in the following genes: GDAP1 (CMT4A), MTMR2 (CMT4B1), SBF2 (CMT4B2), SH3TC2 (CMT4C), NDRG1 (CMT4D), EGR2 (CMT4E), PRX (CMT4F), FGD4 (CMT4H), and FIG4 (CMT4J).  Intermediate forms of the disorder can be caused by alterations in genes including DNM2, MPZ, YARS, and GDAP1. CMTX is caused by mutations in genes including GJB1 (CMTX1) and PRPS1 (CMTX5). Mutations in additional genes, some of which have not been identified, also cause various forms of Charcot-Marie-Tooth disease. </s>


Input: Is Charcot-Marie-Tooth disease inherited ?

Output: The pattern of inheritance varies with the type of Charcot-Marie-Tooth disease. CMT1, most cases of CMT2, and most intermediate forms are inherited in an autosomal dominant pattern. This pattern of inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one affected parent.  CMT4, a few CMT2 subtypes, and some intermediate forms are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.  CMTX is inherited in an X-linked dominant pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome. The inheritance is dominant if one copy of the altered gene is sufficient to cause the condition. In most cases, affected males, who have the alteration on their only copy of the X chromosome, experience more severe symptoms of the disorder than females, who have two X chromosomes. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. All daughters of affected men will have one altered X chromosome, but they may only have mild symptoms of the disorder.  Some cases of Charcot-Marie-Tooth disease result from a new mutation and occur in people with no history of the disorder in their family. </s>


Input: What are the treatments for Charcot-Marie-Tooth disease ?

Output: These resources address the diagnosis or management of Charcot-Marie-Tooth disease:  - Gene Review: Gene Review: Charcot-Marie-Tooth Hereditary Neuropathy Overview  - Gene Review: Gene Review: Charcot-Marie-Tooth Neuropathy Type 1  - Gene Review: Gene Review: Charcot-Marie-Tooth Neuropathy Type 2  - Gene Review: Gene Review: Charcot-Marie-Tooth Neuropathy Type 2A  - Gene Review: Gene Review: Charcot-Marie-Tooth Neuropathy Type 2E/1F  - Gene Review: Gene Review: Charcot-Marie-Tooth Neuropathy Type 4  - Gene Review: Gene Review: Charcot-Marie-Tooth Neuropathy Type 4A  - Gene Review: Gene Review: Charcot-Marie-Tooth Neuropathy Type 4C  - Gene Review: Gene Review: Charcot-Marie-Tooth Neuropathy X Type 1  - Gene Review: Gene Review: Charcot-Marie-Tooth Neuropathy X Type 5  - Gene Review: Gene Review: DNM2-Related Intermediate Charcot-Marie-Tooth Neuropathy  - Gene Review: Gene Review: GARS-Associated Axonal Neuropathy  - Gene Review: Gene Review: TRPV4-Associated Disorders  - Genetic Testing Registry: Charcot-Marie-Tooth disease  - Genetic Testing Registry: Charcot-Marie-Tooth disease dominant intermediate 3  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 1B  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 2B  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 2B1  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 2B2  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 2C  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 2D  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 2E  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 2F  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 2I  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 2J  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 2K  - Genetic Testing Registry: Charcot-Marie-Tooth disease type 2P  - Genetic Testing Registry: Charcot-Marie-Tooth disease, X-linked recessive, type 5  - Genetic Testing Registry: Charcot-Marie-Tooth disease, axonal, type 2O  - Genetic Testing Registry: Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, autosomal recessive  - Genetic Testing Registry: Charcot-Marie-Tooth disease, dominant intermediate C  - Genetic Testing Registry: Charcot-Marie-Tooth disease, dominant intermediate E  - Genetic Testing Registry: Charcot-Marie-Tooth disease, recessive intermediate A  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 1C  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 2A1  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 2A2  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 2L  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 2N  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 4A  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 4B1  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 4B2  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 4C  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 4D  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 4H  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type 4J  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type I  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type IA  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type ID  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type IE  - Genetic Testing Registry: Charcot-Marie-Tooth disease, type IF  - Genetic Testing Registry: Congenital hypomyelinating neuropathy  - Genetic Testing Registry: DNM2-related intermediate Charcot-Marie-Tooth neuropathy  - Genetic Testing Registry: Dejerine-Sottas disease  - Genetic Testing Registry: Roussy-Lvy syndrome  - Genetic Testing Registry: X-linked hereditary motor and sensory neuropathy  - MedlinePlus Encyclopedia: Charcot-Marie-Tooth Disease  - MedlinePlus Encyclopedia: Hammer Toe  - MedlinePlus Encyclopedia: High Arch   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) hypophosphatasia ?

Output: Hypophosphatasia is an inherited disorder that affects the development of bones and teeth. This condition disrupts a process called mineralization, in which minerals such as calcium and phosphorus are deposited in developing bones and teeth. Mineralization is critical for the formation of bones that are strong and rigid and teeth that can withstand chewing and grinding.  The signs and symptoms of hypophosphatasia vary widely and can appear anywhere from before birth to adulthood. The most severe forms of the disorder tend to occur before birth and in early infancy. Hypophosphatasia weakens and softens the bones, causing skeletal abnormalities similar to another childhood bone disorder called rickets. Affected infants are born with short limbs, an abnormally shaped chest, and soft skull bones. Additional complications in infancy include poor feeding and a failure to gain weight, respiratory problems, and high levels of calcium in the blood (hypercalcemia), which can lead to recurrent vomiting and kidney problems. These complications are life-threatening in some cases.  The forms of hypophosphatasia that appear in childhood or adulthood are typically less severe than those that appear in infancy. Early loss of primary (baby) teeth is one of the first signs of the condition in children. Affected children may have short stature with bowed legs or knock knees, enlarged wrist and ankle joints, and an abnormal skull shape. Adult forms of hypophosphatasia are characterized by a softening of the bones known as osteomalacia. In adults, recurrent fractures in the foot and thigh bones can lead to chronic pain. Affected adults may lose their secondary (adult) teeth prematurely and are at increased risk for joint pain and inflammation.  The mildest form of this condition, called odontohypophosphatasia, only affects the teeth. People with this disorder typically experience abnormal tooth development and premature tooth loss, but do not have the skeletal abnormalities seen in other forms of hypophosphatasia. </s>


Input: How many people are affected by hypophosphatasia ?

Output: Severe forms of hypophosphatasia affect an estimated 1 in 100,000 newborns. Milder cases, such as those that appear in childhood or adulthood, probably occur more frequently.  Hypophosphatasia has been reported worldwide in people of various ethnic backgrounds. This condition appears to be most common in white populations. It is particularly frequent in a Mennonite population in Manitoba, Canada, where about 1 in 2,500 infants is born with severe features of the condition. </s>


Input: What are the genetic changes related to hypophosphatasia ?

Output: Mutations in the ALPL gene cause hypophosphatasia.  The ALPL gene provides instructions for making an enzyme called alkaline phosphatase. This enzyme plays an essential role in mineralization of the skeleton and teeth. Mutations in the ALPL gene lead to the production of an abnormal version of alkaline phosphatase that cannot participate effectively in the mineralization process. A shortage of alkaline phosphatase allows several other substances, which are normally processed by the enzyme, to build up abnormally in the body. Researchers believe that a buildup of one of these compounds, inorganic pyrophosphate (PPi), underlies the defective mineralization of bones and teeth in people with hypophosphatasia.  ALPL mutations that almost completely eliminate the activity of alkaline phosphatase usually result in the more severe forms of hypophosphatasia. Other mutations, which reduce but do not eliminate the activity of the enzyme, are often responsible for milder forms of the condition. </s>


Input: Is hypophosphatasia inherited ?

Output: The severe forms of hypophosphatasia that appear early in life are inherited in an autosomal recessive pattern. Autosomal recessive inheritance means that two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene but do not show signs and symptoms of the disorder.  Milder forms of hypophosphatasia can have either an autosomal recessive or an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder. </s>


Input: What are the treatments for hypophosphatasia ?

Output: These resources address the diagnosis or management of hypophosphatasia:  - Gene Review: Gene Review: Hypophosphatasia  - Genetic Testing Registry: Adult hypophosphatasia  - Genetic Testing Registry: Childhood hypophosphatasia  - Genetic Testing Registry: Hypophosphatasia  - Genetic Testing Registry: Infantile hypophosphatasia  - MedlinePlus Encyclopedia: Osteomalacia   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) supravalvular aortic stenosis ?

Output: Supravalvular aortic stenosis (SVAS) is a heart defect that develops before birth. This defect is a narrowing (stenosis) of the large blood vessel that carries blood from the heart to the rest of the body (the aorta). The condition is described as supravalvular because the section of the aorta that is narrowed is located just above the valve that connects the aorta with the heart (the aortic valve). Some people with SVAS also have defects in other blood vessels, most commonly stenosis of the artery from the heart to the lungs (the pulmonary artery). An abnormal heart sound during a heartbeat (heart murmur) can often be heard during a chest exam. If SVAS is not treated, the aortic narrowing can lead to shortness of breath, chest pain, and ultimately heart failure.  The severity of SVAS varies considerably, even among family members. Some affected individuals die in infancy, while others never experience symptoms of the disorder. </s>


Input: How many people are affected by supravalvular aortic stenosis ?

Output: SVAS occurs in 1 in 20,000 newborns worldwide. </s>


Input: What are the genetic changes related to supravalvular aortic stenosis ?

Output: Mutations in the ELN gene cause SVAS. The ELN gene provides instructions for making a protein called tropoelastin. Multiple copies of the tropoelastin protein attach to one another and are processed to form a mature protein called elastin. Elastin is the major component of elastic fibers, which are slender bundles of proteins that provide strength and flexibility to connective tissue (tissue that supports the body's joints and organs). Elastic fibers are found in the intricate lattice that forms in the spaces between cells (the extracellular matrix), where they give structural support to organs and tissues such as the heart, skin, lungs, ligaments, and blood vessels. Elastic fibers make up approximately 50 percent of the aorta, the rest being primarily muscle cells called vascular smooth muscle cells that line the aorta. Together, elastic fibers and vascular smooth muscle cells provide flexibility and resilience to the aorta.  Most of the ELN gene mutations that cause SVAS lead to a decrease in the production of tropoelastin. A shortage of tropoelastin reduces the amount of mature elastin protein that is processed and available for forming elastic fibers. As a result, elastic fibers that make up the aorta are thinner than normal. To compensate, the smooth muscle cells that line the aorta increase in number, making the aorta thicker and narrower than usual. A thickened aorta is less flexible and resilient to the stress of constant blood flow and pumping of the heart. Over time, the wall of the aorta can become damaged. Aortic narrowing causes the heart to work harder to pump blood through the aorta, resulting in the signs and symptoms of SVAS. </s>


Input: Is supravalvular aortic stenosis 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. However, some people who inherit the altered gene never develop features of SVAS. (This situation is known as reduced penetrance.)  In some cases, a person inherits the mutation from one parent who has the mutation. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family. </s>


Input: What are the treatments for supravalvular aortic stenosis ?

Output: These resources address the diagnosis or management of supravalvular aortic stenosis:  - Children's Hospital of Philadelphia  - Genetic Testing Registry: Supravalvar aortic stenosis  - Monroe Carell Jr. Children's Hospital at Vanderbilt   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) epidermolytic hyperkeratosis ?

Output: Epidermolytic hyperkeratosis is a skin disorder that is present at birth. Affected babies may have very red skin (erythroderma) and severe blisters. Because newborns with this disorder are missing the protection provided by normal skin, they are at risk of becoming dehydrated and developing infections in the skin or throughout the body (sepsis).  As affected individuals get older, blistering is less frequent, erythroderma becomes less evident, and the skin becomes thick (hyperkeratotic), especially over joints, on areas of skin that come into contact with each other, or on the scalp or neck. This thickened skin is usually darker than normal. Bacteria can grow in the thick skin, often causing a distinct odor.  Epidermolytic hyperkeratosis can be categorized into two types. People with PS-type epidermolytic hyperkeratosis have thick skin on the palms of their hands and soles of their feet (palmoplantar or palm/sole hyperkeratosis) in addition to other areas of the body. People with the other type, NPS-type, do not have extensive palmoplantar hyperkeratosis but do have hyperkeratosis on other areas of the body.  Epidermolytic hyperkeratosis is part of a group of conditions called ichthyoses, which refers to the scaly skin seen in individuals with related disorders. However, in epidermolytic hyperkeratosis, the skin is thick but not scaly as in some of the other conditions in the group. </s>


Input: How many people are affected by epidermolytic hyperkeratosis ?

Output: Epidermolytic hyperkeratosis affects approximately 1 in 200,000 to 300,000 people worldwide. </s>


Input: What are the genetic changes related to epidermolytic hyperkeratosis ?

Output: Mutations in the KRT1 or KRT10 genes are responsible for epidermolytic hyperkeratosis. These genes provide instructions for making proteins called keratin 1 and keratin 10, which are found in cells called keratinocytes in the outer layer of the skin (the epidermis). The tough, fibrous keratin proteins attach to each other and form fibers called intermediate filaments, which form networks and provide strength and resiliency to the epidermis.  Mutations in the KRT1 or KRT10 genes lead to changes in the keratin proteins, preventing them from forming strong, stable intermediate filament networks within cells. Without a strong network, keratinocytes become fragile and are easily damaged, which can lead to blistering in response to friction or mild trauma. It is unclear how these mutations cause the overgrowth of epidermal cells that results in hyperkeratotic skin.  KRT1 gene mutations are associated with PS-type epidermal hyperkeratosis, and KRT10 gene mutations are usually associated with NPS-type. The keratin 1 protein is present in the keratinocytes of the skin on the palms of the hands and the soles of the feet as well as other parts of the body, so mutations in the KRT1 gene lead to skin problems in these areas. The keratin 10 protein is not found in the skin of the palms and soles, so these areas are unaffected by mutations in the KRT10 gene. </s>


Input: Is epidermolytic hyperkeratosis inherited ?

Output: Epidermolytic hyperkeratosis can have different inheritance patterns. About half of the cases of this condition result from new mutations in the KRT1 or KRT10 gene and occur in people with no history of the disorder in their family.  When epidermolytic hyperkeratosis is inherited, it is usually in an autosomal dominant pattern, which means one copy of the altered KRT1 or KRT10 gene in each cell is sufficient to cause the disorder.  Very rarely, epidermolytic hyperkeratosis caused by mutations in the KRT10 gene can be 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 epidermolytic hyperkeratosis ?

Output: These resources address the diagnosis or management of epidermolytic hyperkeratosis:  - Genetic Testing Registry: Bullous ichthyosiform erythroderma  - The Swedish Information Centre for Rare Diseases: Ichthyosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) progressive familial heart block ?

Output: Progressive familial heart block is a genetic condition that alters the normal beating of the heart. A normal heartbeat is controlled by electrical signals that move through the heart in a highly coordinated way. These signals begin in a specialized cluster of cells called the sinoatrial node (the heart's natural pacemaker) located in the heart's upper chambers (the atria). From there, a group of cells called the atrioventricular node carries the electrical signals to another cluster of cells called the bundle of His. This bundle separates into multiple thin spindles called bundle branches, which carry electrical signals into the heart's lower chambers (the ventricles). Electrical impulses move from the sinoatrial node down to the bundle branches, stimulating a normal heartbeat in which the ventricles contract slightly later than the atria.  Heart block occurs when the electrical signaling is obstructed anywhere from the atria to the ventricles. In people with progressive familial heart block, the condition worsens over time: early in the disorder, the electrical signals are partially blocked, but the block eventually becomes complete, preventing any signals from passing through the heart. Partial heart block causes a slow or irregular heartbeat (bradycardia or arrhythmia, respectively), and can lead to the buildup of scar tissue (fibrosis) in the cells that carry electrical impulses. Fibrosis contributes to the development of complete heart block, resulting in uncoordinated electrical signaling between the atria and the ventricles and inefficient pumping of blood in the heart. Complete heart block can cause a sensation of fluttering or pounding in the chest (palpitations), shortness of breath, fainting (syncope), or sudden cardiac arrest and death.  Progressive familial heart block can be divided into type I and type II, with type I being further divided into types IA and IB. These types differ in where in the heart signaling is interrupted and the genetic cause. In types IA and IB, the heart block originates in the bundle branch, and in type II, the heart block originates in the atrioventricular node. The different types of progressive familial heart block have similar signs and symptoms.  Most cases of heart block are not genetic and are not considered progressive familial heart block. The most common cause of heart block is fibrosis of the heart, which occurs as a normal process of aging. Other causes of heart block can include the use of certain medications or an infection of the heart tissue. </s>


Input: How many people are affected by progressive familial heart block ?

Output: The prevalence of progressive familial heart block is unknown. In the United States, about 1 in 5,000 individuals have complete heart block from any cause; worldwide, about 1 in 2,500 individuals have complete heart block. </s>


Input: What are the genetic changes related to progressive familial heart block ?

Output: Mutations in the SCN5A and TRPM4 genes cause most cases of progressive familial heart block types IA and IB, respectively. The proteins produced from these genes are channels that allow positively charged atoms (cations) into and out of cells. Both channels are abundant in heart (cardiac) cells and play key roles in these cells' ability to generate and transmit electrical signals. These channels play a major role in signaling the start of each heartbeat, coordinating the contractions of the atria and ventricles, and maintaining a normal heart rhythm.  The SCN5A and TRPM4 gene mutations that cause progressive familial heart block alter the normal function of the channels. As a result of these channel alterations, cardiac cells have difficulty producing and transmitting the electrical signals that are necessary to coordinate normal heartbeats, leading to heart block. Death of these impaired cardiac cells over time can lead to fibrosis, worsening the heart block.  Mutations in other genes, some of which are unknown, account for the remaining cases of progressive familial heart block. </s>


Input: Is progressive familial heart block inherited ?

Output: Progressive familial heart block types I and II are inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. Some people with TRPM4 gene mutations never develop the condition, a situation known as reduced penetrance.  In most cases, an affected person has one parent with progressive familial heart block. </s>


Input: What are the treatments for progressive familial heart block ?

Output: These resources address the diagnosis or management of progressive familial heart block:  - American Heart Association: Common Tests for Arrhythmia  - Genetic Testing Registry: Progressive familial heart block type 1A  - Genetic Testing Registry: Progressive familial heart block type 1B  - Genetic Testing Registry: Progressive familial heart block type 2  - MedlinePlus Health Topic: Pacemakers and Implantable Defibrillators  - National Heart, Lung, and Blood Institute: How Does a Pacemaker Work?  - National Heart, Lung, and Blood Institute: How is Sudden Cardiac Arrest Diagnosed?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) fucosidosis ?

Output: Fucosidosis is a condition that affects many areas of the body, especially the brain. Affected individuals have intellectual disability that worsens with age, and many develop dementia later in life. People with this condition often have delayed development of motor skills such as walking; the skills they do acquire deteriorate over time. Additional signs and symptoms of fucosidosis include impaired growth; abnormal bone development (dysostosis multiplex); seizures; abnormal muscle stiffness (spasticity); clusters of enlarged blood vessels forming small, dark red spots on the skin (angiokeratomas); distinctive facial features that are often described as "coarse"; recurrent respiratory infections; and abnormally large abdominal organs (visceromegaly).  In severe cases, symptoms typically appear in infancy, and affected individuals usually live into late childhood. In milder cases, symptoms begin at age 1 or 2, and affected individuals tend to survive into mid-adulthood.  In the past, researchers described two types of this condition based on symptoms and age of onset, but current opinion is that the two types are actually a single disorder with signs and symptoms that range in severity. </s>


Input: How many people are affected by fucosidosis ?

Output: Fucosidosis is a rare condition; approximately 100 cases have been reported worldwide. This condition appears to be most prevalent in Italy, Cuba, and the southwestern United States. </s>


Input: What are the genetic changes related to fucosidosis ?

Output: Mutations in the FUCA1 gene cause fucosidosis. The FUCA1 gene provides instructions for making an enzyme called alpha-L-fucosidase. This enzyme plays a role in the breakdown of complexes of sugar molecules (oligosaccharides) attached to certain proteins (glycoproteins) and fats (glycolipids). Alpha-L-fucosidase is responsible for cutting (cleaving) off a sugar molecule called fucose toward the end of the breakdown process.  FUCA1 gene mutations severely reduce or eliminate the activity of the alpha-L-fucosidase enzyme. A lack of enzyme activity results in an incomplete breakdown of glycolipids and glycoproteins. These partially broken down compounds gradually accumulate within various cells and tissues throughout the body and cause cells to malfunction. Brain cells are particularly sensitive to the buildup of glycolipids and glycoproteins, which can result in cell death. Loss of brain cells is thought to cause the neurological symptoms of fucosidosis. Accumulation of glycolipids and glycoproteins also occurs in other organs such as the liver, spleen, skin, heart, pancreas, and kidneys, contributing to the additional symptoms of fucosidosis. </s>


Input: Is fucosidosis 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 fucosidosis ?

Output: These resources address the diagnosis or management of fucosidosis:  - Genetic Testing Registry: Fucosidosis   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) Alzheimer disease ?

Output: Alzheimer disease is a degenerative disease of the brain that causes dementia, which is a gradual loss of memory, judgment, and ability to function. This disorder usually appears in people older than age 65, but less common forms of the disease appear earlier in adulthood.  Memory loss is the most common sign of Alzheimer disease. Forgetfulness may be subtle at first, but the loss of memory worsens over time until it interferes with most aspects of daily living. Even in familiar settings, a person with Alzheimer disease may get lost or become confused. Routine tasks such as preparing meals, doing laundry, and performing other household chores can be challenging. Additionally, it may become difficult to recognize people and name objects. Affected people increasingly require help with dressing, eating, and personal care.  As the disorder progresses, some people with Alzheimer disease experience personality and behavioral changes and have trouble interacting in a socially appropriate manner. Other common symptoms include agitation, restlessness, withdrawal, and loss of language skills. People with this disease usually require total care during the advanced stages of the disease. Affected individuals usually survive 8 to 10 years after the appearance of symptoms, but the course of the disease can range from 1 to 25 years. Death usually results from pneumonia, malnutrition, or general body wasting (inanition).  Alzheimer disease can be classified as early-onset or late-onset. The signs and symptoms of the early-onset form appear before age 65, while the late-onset form appears after age 65. The early-onset form is much less common than the late-onset form, accounting for less than 5 percent of all cases of Alzheimer disease. </s>


Input: How many people are affected by Alzheimer disease ?

Output: Alzheimer disease currently affects an estimated 2.4 million to 4.5 million Americans. Because the risk of developing Alzheimer disease increases with age and more people are living longer, the number of people with this disease is expected to increase significantly in coming decades. </s>


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

Output: Most cases of early-onset Alzheimer disease are caused by gene mutations that can be passed from parent to child. Researchers have found that this form of the disorder can result from mutations in one of three genes: APP, PSEN1, or PSEN2. When any of these genes is altered, large amounts of a toxic protein fragment called amyloid beta peptide are produced in the brain. This peptide can build up in the brain to form clumps called amyloid plaques, which are characteristic of Alzheimer disease. A buildup of toxic amyloid beta peptide and amyloid plaques may lead to the death of nerve cells and the progressive signs and symptoms of this disorder.  Some evidence indicates that people with Down syndrome have an increased risk of developing Alzheimer disease. Down syndrome, a condition characterized by intellectual disability and other health problems, occurs when a person is born with an extra copy of chromosome 21 in each cell. As a result, people with Down syndrome have three copies of many genes in each cell, including the APP gene, instead of the usual two copies. Although the connection between Down syndrome and Alzheimer disease is unclear, the production of excess amyloid beta peptide in cells may account for the increased risk. People with Down syndrome account for less than 1 percent of all cases of Alzheimer disease.  The causes of late-onset Alzheimer disease are less clear. The late-onset form does not clearly run in families, although clusters of cases have been reported in some families. This disorder is probably related to variations in one or more genes in combination with lifestyle and environmental factors. A gene called APOE has been studied extensively as a risk factor for the disease. In particular, a variant of this gene called the e4 allele seems to increase an individual's risk for developing late-onset Alzheimer disease. Researchers are investigating many additional genes that may play a role in Alzheimer disease risk. </s>


Input: Is Alzheimer disease inherited ?

Output: The early-onset form of Alzheimer disease is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the altered gene from one affected parent.  The inheritance pattern of late-onset Alzheimer disease is uncertain. People who inherit one copy of the APOE e4 allele have an increased chance of developing the disease; those who inherit two copies of the allele are at even greater risk. It is important to note that people with the APOE e4 allele inherit an increased risk of developing Alzheimer disease, not the disease itself. Not all people with Alzheimer disease have the e4 allele, and not all people who have the e4 allele will develop the disease. </s>


Input: What are the treatments for Alzheimer disease ?

Output: These resources address the diagnosis or management of Alzheimer disease:  - Alzheimer's Disease Research Center, Washington University School of Medicine  - Gene Review: Gene Review: Alzheimer Disease Overview  - Gene Review: Gene Review: Early-Onset Familial Alzheimer Disease  - Genetic Testing Registry: Alzheimer disease 2  - Genetic Testing Registry: Alzheimer disease, type 3  - Genetic Testing Registry: Alzheimer disease, type 4  - Genetic Testing Registry: Alzheimer's disease  - MedlinePlus Encyclopedia: Alzheimer's Disease  - Michigan Alzheimer's Disease Research Center  - University of California Davis Alzheimer's Disease Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) centronuclear myopathy ?

Output: Centronuclear myopathy is a condition characterized by muscle weakness (myopathy) and wasting (atrophy) in the skeletal muscles, which are the muscles used for movement. The severity of centronuclear myopathy varies among affected individuals, even among members of the same family.  People with centronuclear myopathy begin experiencing muscle weakness at any time from birth to early adulthood. The muscle weakness slowly worsens over time and can lead to delayed development of motor skills, such as crawling or walking; muscle pain during exercise; and difficulty walking. Some affected individuals may need wheelchair assistance as the muscles atrophy and weakness becomes more severe. In rare instances, the muscle weakness improves over time.  Some people with centronuclear myopathy experience mild to severe breathing problems related to the weakness of muscles needed for breathing. People with centronuclear myopathy may have droopy eyelids (ptosis) and weakness in other facial muscles, including the muscles that control eye movement. People with this condition may also have foot abnormalities, a high arch in the roof of the mouth (high-arched palate), and abnormal side-to-side curvature of the spine (scoliosis). Rarely, individuals with centronuclear myopathy have a weakened heart muscle (cardiomyopathy), disturbances in nerve function (neuropathy), or intellectual disability.  A key feature of centronuclear myopathy is the displacement of the nucleus in muscle cells, which can be viewed under a microscope. Normally the nucleus is found at the edges of the rod-shaped muscle cells, but in people with centronuclear myopathy the nucleus is located in the center of these cells. How the change in location of the nucleus affects muscle cell function is unknown. </s>


Input: How many people are affected by centronuclear myopathy ?

Output: Centronuclear myopathy is a rare condition; its exact prevalence is unknown. </s>


Input: What are the genetic changes related to centronuclear myopathy ?

Output: Centronuclear myopathy is most often caused by mutations in the DNM2, BIN1, or TTN gene. The proteins produced from the DNM2 and BIN1 genes are involved in endocytosis, a process that brings substances into the cell. The protein produced from the BIN1 gene plays an additional role in the formation of tube-like structures called transverse tubules (or T tubules), which are found within the membrane of muscle fibers. These tubules help transmit the electrical impulses necessary for normal muscle tensing (contraction) and relaxation. The protein produced from the DNM2 gene also regulates the actin cytoskeleton, which makes up the muscle fiber's structural framework. DNM2 and BIN1 gene mutations lead to abnormal muscle fibers that cannot contract and relax normally, resulting in muscle weakness.  The TTN gene provides instructions for making a protein called titin that is an essential component of muscle fiber structures called sarcomeres. Sarcomeres are the basic units of muscle contraction; they are made of proteins that generate the mechanical force needed for muscles to contract. TTN gene mutations decrease or alter titin's activity in muscle fibers. It is unclear how these mutations lead to centronuclear myopathy, but it is likely that the altered protein cannot interact with other proteins in the sarcomere, leading to dysfunction of the sarcomere. Abnormal sarcomeres prevent muscle fibers from contracting and relaxing normally, resulting in muscle weakness.  Some people with centronuclear myopathy do not have identified mutations in the DNM2, BIN1, or TTN genes. Mutations in other genes associated with this condition are found in a small percentage of cases. Some males with signs and symptoms of severe centronuclear myopathy may have a condition called X-linked myotubular myopathy, which is similar to centronuclear myopathy, and is often considered a subtype of the condition, but has a different genetic cause. In some people with centronuclear myopathy, the cause of the disorder is unknown. Researchers are looking for additional genes that are associated with centronuclear myopathy. </s>


Input: Is centronuclear myopathy inherited ?

Output: When centronuclear myopathy is caused by mutations in the DNM2 gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered DNM2 gene in each cell is sufficient to cause the disorder. Rarely, BIN1 gene mutations that are inherited in an autosomal dominant pattern can cause centronuclear myopathy.  Centronuclear myopathy caused by TTN gene mutations and most cases caused by BIN1 gene mutations are 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.  Other cases of centronuclear myopathy that are not caused by these genes are typically inherited in an autosomal recessive manner, although some follow an autosomal dominant pattern. </s>


Input: What are the treatments for centronuclear myopathy ?

Output: These resources address the diagnosis or management of centronuclear myopathy:  - Genetic Testing Registry: Autosomal recessive centronuclear myopathy  - Genetic Testing Registry: Myopathy, centronuclear  - Genetic Testing Registry: Myopathy, centronuclear, 1  - Genetic Testing Registry: Myopathy, centronuclear, 4  - Genetic Testing Registry: Myopathy, centronuclear, 5   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) glutathione synthetase deficiency ?

Output: Glutathione synthetase deficiency is a disorder that prevents the production of an important molecule called glutathione. Glutathione helps prevent damage to cells by neutralizing harmful molecules generated during energy production. Glutathione also plays a role in processing medications and cancer-causing compounds (carcinogens), and building DNA, proteins, and other important cellular components.  Glutathione synthetase deficiency can be classified into three types: mild, moderate, and severe. Mild glutathione synthetase deficiency usually results in the destruction of red blood cells (hemolytic anemia). In addition, affected individuals may release large amounts of a compound called 5-oxoproline in their urine (5-oxoprolinuria). This compound builds up when glutathione is not processed correctly in cells.  Individuals with moderate glutathione synthetase deficiency may experience symptoms beginning shortly after birth including hemolytic anemia, 5-oxoprolinuria, and elevated acidity in the blood and tissues (metabolic acidosis).  In addition to the features present in moderate glutathione synthetase deficiency, individuals affected by the severe form of this disorder may experience neurological symptoms. These problems may include seizures; a generalized slowing down of physical reactions, movements, and speech (psychomotor retardation); intellectual disability; and a loss of coordination (ataxia). Some people with severe glutathione synthetase deficiency also develop recurrent bacterial infections. </s>


Input: How many people are affected by glutathione synthetase deficiency ?

Output: Glutathione synthetase deficiency is very rare. This disorder has been described in more than 70 people worldwide. </s>


Input: What are the genetic changes related to glutathione synthetase deficiency ?

Output: Mutations in the GSS gene cause glutathione synthetase deficiency. The GSS gene provides instructions for making an enzyme called glutathione synthetase. This enzyme is involved in a process called the gamma-glutamyl cycle, which takes place in most of the body's cells. This cycle is necessary for producing a molecule called glutathione. Glutathione protects cells from damage caused by unstable oxygen-containing molecules, which are byproducts of energy production. Glutathione is called an antioxidant because of its role in protecting cells from the damaging effects of these unstable molecules. Mutations in the GSS gene prevent cells from making adequate levels of glutathione, leading to the signs and symptoms of glutathione synthetase deficiency. </s>


Input: Is glutathione synthetase deficiency inherited ?

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


Input: What are the treatments for glutathione synthetase deficiency ?

Output: These resources address the diagnosis or management of glutathione synthetase deficiency:  - Baby's First Test  - Genetic Testing Registry: Glutathione synthetase deficiency of erythrocytes, hemolytic anemia due to  - Genetic Testing Registry: Gluthathione synthetase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) Koolen-de Vries syndrome ?

Output: Koolen-de Vries syndrome is a disorder characterized by developmental delay and mild to moderate intellectual disability. People with this disorder typically have a disposition that is described as cheerful, sociable, and cooperative. They usually have weak muscle tone (hypotonia) in childhood. About half have recurrent seizures (epilepsy).  Affected individuals often have distinctive facial features including a high, broad forehead; droopy eyelids (ptosis); a narrowing of the eye openings (blepharophimosis); outer corners of the eyes that point upward (upward-slanting palpebral fissures); skin folds covering the inner corner of the eyes (epicanthal folds); a bulbous nose; and prominent ears. Males with Koolen-de Vries syndrome often have undescended testes (cryptorchidism). Defects in the walls between the chambers of the heart (septal defects) or other cardiac abnormalities, kidney problems, and skeletal anomalies such as foot deformities occur in some affected individuals. </s>


Input: How many people are affected by Koolen-de Vries syndrome ?

Output: The prevalence of Koolen-de Vries syndrome is estimated to be 1 in 16,000. However, the underlying genetic cause is often not identified in people with intellectual disability, so this condition is likely underdiagnosed. </s>


Input: What are the genetic changes related to Koolen-de Vries syndrome ?

Output: Koolen-de Vries syndrome is caused by genetic changes that eliminate the function of one copy of the KANSL1 gene in each cell. Most affected individuals are missing a small amount of genetic material, including the KANSL1 gene, from one copy of chromosome 17. This type of genetic abnormality is called a microdeletion. A small number of individuals with Koolen-de Vries syndrome do not have a chromosome 17 microdeletion but instead have a mutation within the KANSL1 gene that causes one copy of the gene to be nonfunctional.  The microdeletion that causes Koolen-de Vries syndrome occurs on the long (q) arm of chromosome 17 at a location designated q21.31. While the exact size of the deletion varies among affected individuals, most are missing a sequence of about 500,000 DNA building blocks (base pairs) containing several genes. However, because individuals with KANSL1 gene mutations have the same signs and symptoms as those with the microdeletion, researchers have concluded that the loss of this gene accounts for the features of this disorder.  The KANSL1 gene provides instructions for making a protein that helps regulate gene activity (expression) by modifying chromatin. Chromatin is the complex of DNA and protein that packages DNA into chromosomes. The protein produced from the KANSL1 gene is found in most organs and tissues of the body before birth and throughout life. By its involvement in controlling the activity of other genes, this protein plays an important role in the development and function of many parts of the body. Loss of one copy of this gene impairs normal development and function, but the relationship of KANSL1 gene loss to the specific signs and symptoms of Koolen-de Vries syndrome is unclear. </s>


Input: Is Koolen-de Vries syndrome inherited ?

Output: Koolen-de Vries syndrome is considered an autosomal dominant condition because a deletion or mutation affecting one copy of the KANSL1 gene in each cell is sufficient to cause the disorder. In most cases, the disorder is not inherited. The genetic change occurs most often as a random event during the formation of reproductive cells (eggs and sperm) or in early fetal development. Affected people typically have no history of the disorder in their family. While it is possible for them to pass the condition on to their children, no individuals with Koolen-de Vries syndrome have been known to reproduce.  Most people with Koolen-de Vries syndrome caused by a deletion have had at least one parent with a common variant of the 17q21.31 region of chromosome 17 called the H2 lineage. This variant is found in 20 percent of people of European and Middle Eastern descent, although it is rare in other populations. In the H2 lineage, a 900 kb segment of DNA, which includes the region deleted in most cases of Koolen-de Vries syndrome, has undergone an inversion. An inversion involves two breaks in a chromosome; the resulting piece of DNA is reversed and reinserted into the chromosome.  People with the H2 lineage have no health problems related to the inversion. However, genetic material can be lost or duplicated when the inversion is passed to the next generation. Other, unknown factors are thought to play a role in this process. So while the inversion is very common, only an extremely small percentage of parents with the inversion have a child affected by Koolen-de Vries syndrome. </s>


Input: What are the treatments for Koolen-de Vries syndrome ?

Output: These resources address the diagnosis or management of Koolen-de Vries syndrome:  - Gene Review: Gene Review: KANSL1-Related Intellectual Disability Syndrome  - Genetic Testing Registry: Koolen-de Vries 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) Williams syndrome ?

Output: Williams syndrome is a developmental disorder that affects many parts of the body. This condition is characterized by mild to moderate intellectual disability or learning problems, unique personality characteristics, distinctive facial features, and heart and blood vessel (cardiovascular) problems.  People with Williams syndrome typically have difficulty with visual-spatial tasks such as drawing and assembling puzzles, but they tend to do well on tasks that involve spoken language, music, and learning by repetition (rote memorization). Affected individuals have outgoing, engaging personalities and tend to take an extreme interest in other people. Attention deficit disorder (ADD), problems with anxiety, and phobias are common among people with this disorder.  Young children with Williams syndrome have distinctive facial features including a broad forehead, a short nose with a broad tip, full cheeks, and a wide mouth with full lips. Many affected people have dental problems such as teeth that are small, widely spaced, crooked, or missing. In older children and adults, the face appears longer and more gaunt.  A form of cardiovascular disease called supravalvular aortic stenosis (SVAS) occurs frequently in people with Williams syndrome. Supravalvular aortic stenosis is a narrowing of the large blood vessel that carries blood from the heart to the rest of the body (the aorta). If this condition is not treated, the aortic narrowing can lead to shortness of breath, chest pain, and heart failure. Other problems with the heart and blood vessels, including high blood pressure (hypertension), have also been reported in people with Williams syndrome.  Additional signs and symptoms of Williams syndrome include abnormalities of connective tissue (tissue that supports the body's joints and organs) such as joint problems and soft, loose skin. Affected people may also have increased calcium levels in the blood (hypercalcemia) in infancy, developmental delays, problems with coordination, and short stature. Medical problems involving the eyes and vision, the digestive tract, and the urinary system are also possible. </s>


Input: How many people are affected by Williams syndrome ?

Output: Williams syndrome affects an estimated 1 in 7,500 to 10,000 people. </s>


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

Output: Williams syndrome is caused by the deletion of genetic material from a specific region of chromosome 7. The deleted region includes 26 to 28 genes, and researchers believe that a loss of several of these genes probably contributes to the characteristic features of this disorder.  CLIP2, ELN, GTF2I, GTF2IRD1, and LIMK1 are among the genes that are typically deleted in people with Williams syndrome. Researchers have found that loss of the ELN gene is associated with the connective tissue abnormalities and cardiovascular disease (specifically supravalvular aortic stenosis) found in many people with this disease. Studies suggest that deletion of CLIP2, GTF2I, GTF2IRD1, LIMK1, and perhaps other genes may help explain the characteristic difficulties with visual-spatial tasks, unique behavioral characteristics, and other cognitive difficulties seen in people with Williams syndrome. Loss of the GTF2IRD1 gene may also contribute to the distinctive facial features often associated with this condition.  Researchers believe that the presence or absence of the NCF1 gene on chromosome 7 is related to the risk of developing hypertension in people with Williams syndrome. When the NCF1 gene is included in the part of the chromosome that is deleted, affected individuals are less likely to develop hypertension. Therefore, the loss of this gene appears to be a protective factor. People with Williams syndrome whose NCF1 gene is not deleted have a higher risk of developing hypertension.  The relationship between other genes in the deleted region of chromosome 7 and the signs and symptoms of Williams syndrome is under investigation or unknown. </s>


Input: Is Williams syndrome inherited ?

Output: Most cases of Williams syndrome are not inherited but occur as random events during the formation of reproductive cells (eggs or sperm) in a parent of an affected individual. These cases occur in people with no history of the disorder in their family.  Williams syndrome is considered an autosomal dominant condition because one copy of the altered chromosome 7 in each cell is sufficient to cause the disorder. In a small percentage of cases, people with Williams syndrome inherit the chromosomal deletion from a parent with the condition. </s>


Input: What are the treatments for Williams syndrome ?

Output: These resources address the diagnosis or management of Williams syndrome:  - Gene Review: Gene Review: Williams Syndrome  - Genetic Testing Registry: Williams syndrome  - MedlinePlus Encyclopedia: Williams 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) juvenile primary osteoporosis ?

Output: Juvenile primary osteoporosis is a skeletal disorder characterized by thinning of the bones (osteoporosis) that begins in childhood. Osteoporosis is caused by a shortage of calcium and other minerals in bones (decreased bone mineral density), which makes the bones brittle and prone to fracture. Affected individuals often have multiple fractures in the long bones of the arms and legs, especially in the regions where new bone forms (metaphyses). They also have fractures in the bones that form the spine (vertebrae), which can cause collapse of the affected vertebrae (compressed vertebrae). Multiple fractures can cause bone pain and lead to movement problems. </s>


Input: How many people are affected by juvenile primary osteoporosis ?

Output: The prevalence of juvenile primary osteoporosis is unknown. Nearly 1 in 10 adults over age 50 have osteoporosis, but the condition is uncommon in children. Osteoporosis can occur at a young age as a feature of other conditions but rarely occurs without other signs and symptoms (primary osteoporosis). </s>


Input: What are the genetic changes related to juvenile primary osteoporosis ?

Output: Mutations in the LRP5 gene can cause juvenile primary osteoporosis. This gene provides instructions for making a protein that participates in a chemical signaling pathway that affects the way cells and tissues develop. In particular, the LRP5 protein is involved in the regulation of bone mineral density.  LRP5 gene mutations that cause juvenile primary osteoporosis result in an LRP5 protein that cannot transmit signals along the pathway. The resulting reduction in signaling impairs proper bone development, causing decreased bone mineral density and osteoporosis at a young age.  Many people with childhood-onset osteoporosis do not have a mutation in the LRP5 gene. (When its cause is unknown, the condition is often called idiopathic juvenile osteoporosis). It is likely that mutations in other genes that have not been identified are involved in this condition. </s>


Input: Is juvenile primary osteoporosis inherited ?

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


Input: What are the treatments for juvenile primary osteoporosis ?

Output: These resources address the diagnosis or management of juvenile primary osteoporosis:  - Lucile Packard Children's Hospital at Stanford: Juvenile Osteoporosis  - MedlinePlus Encyclopedia: Bone Mineral Density Test  - Merck Manual Home Health Edition: Osteoporosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) acatalasemia ?

Output: Acatalasemia is a condition characterized by very low levels of an enzyme called catalase. Many people with acatalasemia never have any health problems related to the condition and are diagnosed because they have affected family members.  Some of the first reported individuals with acatalasemia developed open sores (ulcers) inside the mouth that led to the death of soft tissue (gangrene). When mouth ulcers and gangrene occur with acatalasemia, the condition is known as Takahara disease. These complications are rarely seen in more recent cases of acatalasemia, probably because of improvements in oral hygiene.  Studies suggest that people with acatalasemia have an increased risk of developing type 2 diabetes mellitus, which is the most common form of diabetes. A higher percentage of people with acatalasemia have type 2 diabetes mellitus than in the general population, and the disease tends to develop at an earlier age (in a person's thirties or forties, on average). Researchers speculate that acatalasemia could also be a risk factor for other common, complex diseases; however, only a small number of cases have been studied. </s>


Input: How many people are affected by acatalasemia ?

Output: More than 100 cases of acatalasemia have been reported in the medical literature. Researchers estimate that the condition occurs in about 1 in 12,500 people in Japan, 1 in 20,000 people in Hungary, and 1 in 25,000 people in Switzerland. The prevalence of acatalasemia in other populations is unknown. </s>


Input: What are the genetic changes related to acatalasemia ?

Output: Mutations in the CAT gene can cause acatalasemia. This gene provides instructions for making the enzyme catalase, which breaks down hydrogen peroxide molecules into oxygen and water. Hydrogen peroxide is produced through chemical reactions within cells. At low levels, it is involved in several chemical signaling pathways, but at high levels it is toxic to cells. If hydrogen peroxide is not broken down by catalase, additional reactions convert it into compounds called reactive oxygen species that can damage DNA, proteins, and cell membranes.  Mutations in the CAT gene greatly reduce the activity of catalase. A shortage of this enzyme can allow hydrogen peroxide to build up to toxic levels in certain cells. For example, hydrogen peroxide produced by bacteria in the mouth may accumulate in and damage soft tissues, leading to mouth ulcers and gangrene. A buildup of hydrogen peroxide may also damage beta cells of the pancreas, which release a hormone called insulin that helps control blood sugar. Malfunctioning beta cells are thought to underlie the increased risk of type 2 diabetes mellitus in people with acatalasemia. It is unclear why some people have no health problems associated with a loss of catalase activity.  Many people with reduced catalase activity do not have an identified mutation in the CAT gene; in these cases, the cause of the condition is unknown. Researchers believe that other genetic and environmental factors can also influence the activity of catalase. </s>


Input: Is acatalasemia inherited ?

Output: Acatalasemia has an autosomal recessive pattern of inheritance, which means both copies of the CAT gene in each cell have mutations. When both copies of the gene are altered, the activity of catalase is reduced to less than 10 percent of normal.  When only one of the two copies of the CAT gene has a mutation, the activity of catalase is reduced by approximately half. This reduction in catalase activity is often called hypocatalasemia. Like acatalasemia, hypocatalasemia usually does not cause any health problems. </s>


Input: What are the treatments for acatalasemia ?

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


Input: What is (are) Kuskokwim syndrome ?

Output: Kuskokwim syndrome is characterized by joint deformities called contractures that restrict the movement of affected joints. This condition has been found only in a population of native Alaskans known as Yup'ik Eskimos, who live in and around a region of southwest Alaska known as the Kuskokwim River Delta.  In Kuskokwim syndrome, contractures most commonly affect the knees, ankles, and elbows, although other joints, particularly of the lower body, can be affected. The contractures are usually present at birth and worsen during childhood. They tend to stabilize after childhood, and they remain throughout life.  Some individuals with this condition have other bone abnormalities, most commonly affecting the spine, pelvis, and feet. Affected individuals can develop an inward curve of the lower back (lordosis), a spine that curves to the side (scoliosis), wedge-shaped spinal bones, or an abnormality of the collarbones (clavicles) described as clubbing. Affected individuals are typically shorter than their peers and they may have an abnormally large head (macrocephaly). </s>


Input: How many people are affected by Kuskokwim syndrome ?

Output: Kuskokwim syndrome is extremely rare. It affects a small number of people from the Yup'ik Eskimo population in southwest Alaska. </s>


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

Output: Kuskokwim syndrome is caused by mutations in the FKBP10 gene, which provides instructions for making the FKBP10 protein (formerly known as FKBP65). This protein is important for the correct processing of complex molecules called collagens, which provide structure and strength to connective tissues that support the body's bones, joints, and organs. Collagen molecules are cross-linked to one another to form long, thin fibrils, which are found in the spaces around cells (the extracellular matrix). The formation of cross-links results in very strong collagen fibrils. The FKBP10 protein attaches to collagens and plays a role in their cross-linking.  A mutation in the FKBP10 gene alters the FKBP10 protein, making it unstable and easily broken down. As a result, people with Kuskokwim syndrome have only about 5 percent of the normal amount of FKBP10 protein. This reduction in protein levels impairs collagen cross-linking and leads to a disorganized network of collagen molecules. It is unclear how these changes in the collagen matrix are involved in the development of joint contractures and other abnormalities in people with Kuskokwim syndrome. </s>


Input: Is Kuskokwim 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 Kuskokwim syndrome ?

Output: These resources address the diagnosis or management of Kuskokwim syndrome:  - Genetic Testing Registry: Kuskokwim disease  - Mount Sinai Hospital: Contractures Information   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) ankylosing spondylitis ?

Output: Ankylosing spondylitis is a form of ongoing joint inflammation (chronic inflammatory arthritis) that primarily affects the spine. This condition is characterized by back pain and stiffness that typically appear in adolescence or early adulthood. Over time, back movement gradually becomes limited as the bones of the spine (vertebrae) fuse together. This progressive bony fusion is called ankylosis.  The earliest symptoms of ankylosing spondylitis result from inflammation of the joints between the pelvic bones (the ilia) and the base of the spine (the sacrum). These joints are called sacroiliac joints, and inflammation of these joints is known as sacroiliitis. The inflammation gradually spreads to the joints between the vertebrae, causing a condition called spondylitis. Ankylosing spondylitis can involve other joints as well, including the shoulders, hips, and, less often, the knees. As the disease progresses, it can affect the joints between the spine and ribs, restricting movement of the chest and making it difficult to breathe deeply. People with advanced disease are also more prone to fractures of the vertebrae.  Ankylosing spondylitis affects the eyes in up to 40 percent of cases, leading to episodes of eye inflammation called acute iritis. Acute iritis causes eye pain and increased sensitivity to light (photophobia). Rarely, ankylosing spondylitis can also cause serious complications involving the heart, lungs, and nervous system. </s>


Input: How many people are affected by ankylosing spondylitis ?

Output: Ankylosing spondylitis is part of a group of related diseases known as spondyloarthropathies. In the United States, spondyloarthropathies affect 3.5 to 13 per 1,000 people. </s>


Input: What are the genetic changes related to ankylosing spondylitis ?

Output: Ankylosing spondylitis is likely caused by a combination of genetic and environmental factors, most of which have not been identified. However, researchers have found variations in several genes that influence the risk of developing this disorder.  The HLA-B gene provides instructions for making a protein that plays an important role in the immune system. The HLA-B gene is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). The HLA-B gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. A variation of the HLA-B gene called HLA-B27 increases the risk of developing ankylosing spondylitis. Although many people with ankylosing spondylitis have the HLA-B27 variation, most people with this version of the HLA-B gene never develop the disorder. It is not known how HLA-B27 increases the risk of developing ankylosing spondylitis.  Variations in several additional genes, including ERAP1, IL1A, and IL23R, have also been associated with ankylosing spondylitis. Although these genes play critical roles in the immune system, it is unclear how variations in these genes affect a person's risk of developing ankylosing spondylitis. Changes in genes that have not yet been identified are also believed to affect the chances of developing ankylosing spondylitis and influence the progression of the disorder. Some of these genes likely play a role in the immune system, while others may have different functions. Researchers are working to identify these genes and clarify their role in ankylosing spondylitis. </s>


Input: Is ankylosing spondylitis inherited ?

Output: Although ankylosing spondylitis can occur in more than one person in a family, it is not a purely genetic disease. Multiple genetic and environmental factors likely play a part in determining the risk of developing this disorder. As a result, inheriting a genetic variation linked with ankylosing spondylitis does not mean that a person will develop the condition, even in families in which more than one family member has the disorder. For example, about 80 percent of children who inherit HLA-B27 from a parent with ankylosing spondylitis do not develop the disorder. </s>


Input: What are the treatments for ankylosing spondylitis ?

Output: These resources address the diagnosis or management of ankylosing spondylitis:  - Genetic Testing Registry: Ankylosing spondylitis  - MedlinePlus Encyclopedia: Ankylosing Spondylitis  - MedlinePlus Encyclopedia: HLA-B27 Antigen   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) renal tubular acidosis with deafness ?

Output: Renal tubular acidosis with deafness is a disorder characterized by kidney (renal) problems and hearing loss. The kidneys normally filter fluid and waste products from the body and remove them in urine; however, in people with this disorder, the kidneys do not remove enough acidic compounds from the body. Instead, the acids are absorbed back into the bloodstream, and the blood becomes too acidic. This chemical imbalance, called metabolic acidosis, can result in a range of signs and symptoms that vary in severity. Metabolic acidosis often causes nausea, vomiting, and dehydration; affected infants tend to have problems feeding and gaining weight (failure to thrive). Most children and adults with renal tubular acidosis with deafness have short stature, and many develop kidney stones.  The metabolic acidosis that occurs in renal tubular acidosis with deafness may also lead to softening and weakening of the bones, called rickets in children and osteomalacia in adults. This bone disorder is characterized by bone pain, bowed legs, and difficulty walking. Rarely, people with renal tubular acidosis with deafness have episodes of hypokalemic paralysis, a condition that causes extreme muscle weakness associated with low levels of potassium in the blood (hypokalemia).  In people with renal tubular acidosis with deafness, hearing loss caused by changes in the inner ear (sensorineural hearing loss) usually begins between childhood and young adulthood, and gradually gets worse. An inner ear abnormality affecting both ears occurs in most people with this disorder. This feature, which is called enlarged vestibular aqueduct, can be seen with medical imaging. The vestibular aqueduct is a bony canal that runs from the inner ear into the temporal bone of the skull and toward the brain. The relationship between enlarged vestibular aqueduct and hearing loss is unclear. In renal tubular acidosis with deafness, enlarged vestibular aqueduct typically occurs in individuals whose hearing loss begins in childhood. </s>


Input: How many people are affected by renal tubular acidosis with deafness ?

Output: Renal tubular acidosis with deafness is a rare disorder; its prevalence is unknown. </s>


Input: What are the genetic changes related to renal tubular acidosis with deafness ?

Output: Renal tubular acidosis with deafness is caused by mutations in the ATP6V1B1 or ATP6V0A4 gene. These genes provide instructions for making proteins that are parts (subunits) of a large protein complex known as vacuolar H+-ATPase (V-ATPase). V-ATPases are a group of similar complexes that act as pumps to move positively charged hydrogen atoms (protons) across membranes. Because acids are substances that can "donate" protons to other molecules, this movement of protons helps regulate the relative acidity (pH) of cells and their surrounding environment. Tight control of pH is necessary for most biological reactions to proceed properly.  The V-ATPase that includes subunits produced from the ATP6V1B1 and ATP6V0A4 genes is found in the inner ear and in nephrons, which are the functional structures within the kidneys. Each nephron consists of two parts: a renal corpuscle (also known as a glomerulus) that filters the blood, and a renal tubule that reabsorbs substances that are needed and eliminates unneeded substances in urine. The V-ATPase is involved in regulating the amount of acid that is removed from the blood into the urine, and also in maintaining the proper pH of the fluid in the inner ear (endolymph).  Mutations in the ATP6V1B1 or ATP6V0A4 gene impair the function of the V-ATPase complex and reduce the body's capability to control the pH of the blood and the fluid in the inner ear, resulting in the signs and symptoms of renal tubular acidosis with deafness. </s>


Input: Is renal tubular acidosis with deafness 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 renal tubular acidosis with deafness ?

Output: These resources address the diagnosis or management of renal tubular acidosis with deafness:  - Genetic Testing Registry: Renal tubular acidosis with progressive nerve deafness  - MedlinePlus Encyclopedia: Audiometry  - MedlinePlus Encyclopedia: Kidney Function Tests   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>