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

Output: Jacobsen syndrome is caused by a deletion of genetic material at the end of the long (q) arm of chromosome 11. The size of the deletion varies among affected individuals, with most affected people missing 5 million to 16 million DNA building blocks (also written as 5 Mb to 16 Mb). In almost all affected people, the deletion includes the tip of chromosome 11. Larger deletions tend to cause more severe signs and symptoms than smaller deletions.  The features of Jacobsen syndrome are likely related to the loss of multiple genes on chromosome 11. Depending on its size, the deleted region can contain from about 170 to more than 340 genes. Many of these genes have not been well characterized. However, genes in this region appear to be critical for the normal development of many parts of the body, including the brain, facial features, and heart. Only a few genes have been studied as possible contributors to the specific features of Jacobsen syndrome; researchers are working to determine which additional genes may be associated with this condition. </s>


Input: Is Jacobsen syndrome inherited ?

Output: Most cases of Jacobsen syndrome are not inherited. They result from a chromosomal deletion that occurs as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family, although they can pass the chromosome deletion to their children.  Between 5 and 10 percent of people with Jacobsen syndrome inherit the chromosome abnormality from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which a segment from chromosome 11 has traded places with a segment from another chromosome. In a balanced translocation, no genetic material is gained or lost. Balanced translocations usually do not cause any health problems; however, they can become unbalanced as they are passed to the next generation.  Children who inherit an unbalanced translocation can have a chromosomal rearrangement with some missing genetic material and some extra genetic material. Individuals with Jacobsen syndrome who inherit an unbalanced translocation are missing genetic material from the end of the long arm of chromosome 11 and have extra genetic material from another chromosome. These chromosomal changes result in the health problems characteristic of this disorder. </s>


Input: What are the treatments for Jacobsen syndrome ?

Output: These resources address the diagnosis or management of Jacobsen syndrome:  - 11q Research & Resource Group: Concerns and Recommendations  - Genetic Testing Registry: 11q partial monosomy syndrome  - Unique: Chromosome 11q Deletion Disorder: Jacobsen 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) Mainzer-Saldino syndrome ?

Output: Mainzer-Saldino syndrome is a disorder characterized by kidney disease, eye problems, and skeletal abnormalities.  People with Mainzer-Saldino syndrome have chronic kidney disease that begins in childhood and gets worse over time. The rate at which the kidney disease worsens is variable, but the condition eventually leads to kidney failure in most affected individuals.  Degeneration of the light-sensitive tissue at the back of the eye (the retina) almost always occurs in this disorder, but the age at which this feature develops varies. Some affected individuals are blind or have severe vision impairment beginning in infancy, with the pattern of vision loss resembling a condition called Leber congenital amaurosis. In other people with Mainzer-Saldino syndrome, the retinal degeneration begins in childhood, but some vision is retained into early adulthood. The vision loss in these affected individuals resembles a category of retinal disorders called rod-cone dystrophies. The most common rod-cone dystrophy is called retinitis pigmentosa, and the vision problems in Mainzer-Saldino syndrome are sometimes referred to as such. However, the abnormal deposits of pigment in the retina from which retinitis pigmentosa gets its name are often not found in Mainzer-Saldino syndrome. As a result, some researchers use terms such as "atypical retinitis pigmentosa without pigment" to describe the retinal degeneration that occurs in Mainzer-Saldino syndrome.  The skeletal abnormality most characteristic of Mainzer-Saldino syndrome consists of cone-shaped ends of the bones (epiphyses) in the fingers (phalanges) that can be seen on x-ray images after the first year of life. Affected individuals may also have abnormalities of the thigh bones that occur in the epiphyses and adjacent areas where bone growth occurs (the metaphyses). Occasionally, other skeletal abnormalities occur, including short stature and premature fusion of certain skull bones (craniosynostosis) that affects the shape of the head and face. Affected individuals may also have a small rib cage, which sometimes causes breathing problems in infancy, but the breathing problems are usually mild.  A small number of individuals with this disorder have additional problems affecting other organs. These can include liver disease resulting in a buildup of scar tissue in the liver (hepatic fibrosis); cerebellar ataxia, which is difficulty with coordination and balance arising from problems with a part of the brain called the cerebellum; and mild intellectual disability. </s>


Input: How many people are affected by Mainzer-Saldino syndrome ?

Output: Mainzer-Saldino syndrome is a rare disorder; its prevalence is unknown. At least 20 cases have been reported. </s>


Input: What are the genetic changes related to Mainzer-Saldino syndrome ?

Output: Mainzer-Saldino syndrome is usually caused by mutations in the IFT140 gene. This gene provides instructions for making a protein that is involved in the formation and maintenance of cilia, which are microscopic, finger-like projections that stick out from the surface of cells and participate in signaling pathways that transmit information within and between cells. Cilia are important for the structure and function of many types of cells, including cells in the kidneys, liver, and brain. Light-sensing cells (photoreceptors) in the retina also contain cilia, which are essential for normal vision. Cilia also play a role in the development of the bones, although the mechanism is not well understood.  The movement of substances within cilia and similar structures called flagella is known as intraflagellar transport (IFT). This process is essential for the assembly and maintenance of these cell structures. During intraflagellar transport, cells use molecules called IFT particles to carry materials to and from the tips of cilia. IFT particles are made of proteins produced from related genes that belong to the IFT gene family. Each IFT particle is made up of two groups of IFT proteins: complex A, which includes at least six proteins, and complex B, which includes at least 15 proteins. The protein produced from the IFT140 gene forms part of IFT complex A (IFT-A).  Mutations in the IFT140 gene that cause Mainzer-Saldino syndrome may change the shape of the IFT140 protein or affect its interactions with other IFT proteins, likely impairing the assembly of IFT-A and the development or maintenance of cilia. As a result, fewer cilia may be present or functional, affecting many organs and tissues in the body and resulting in the signs and symptoms of Mainzer-Saldino syndrome. Disorders such as Mainzer-Saldino syndrome that are caused by problems with cilia and involve bone abnormalities are called skeletal ciliopathies.  While IFT140 gene mutations are believed to account for most cases of Mainzer-Saldino syndrome, mutations in additional genes that have not been identified may also cause this disorder. </s>


Input: Is Mainzer-Saldino 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 Mainzer-Saldino syndrome ?

Output: These resources address the diagnosis or management of Mainzer-Saldino syndrome:  - MedlinePlus Encyclopedia: Electroretinography  - National Institutes of Diabetes and Digestive and Kidney Diseases: Treatment Methods for Kidney Failure in Children   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) Angelman syndrome ?

Output: Angelman syndrome is a complex genetic disorder that primarily affects the nervous system. Characteristic features of this condition include delayed development, intellectual disability, severe speech impairment, and problems with movement and balance (ataxia). Most affected children also have recurrent seizures (epilepsy) and a small head size (microcephaly). Delayed development becomes noticeable by the age of 6 to 12 months, and other common signs and symptoms usually appear in early childhood.  Children with Angelman syndrome typically have a happy, excitable demeanor with frequent smiling, laughter, and hand-flapping movements. Hyperactivity, a short attention span, and a fascination with water are common. Most affected children also have difficulty sleeping and need less sleep than usual.  With age, people with Angelman syndrome become less excitable, and the sleeping problems tend to improve. However, affected individuals continue to have intellectual disability, severe speech impairment, and seizures throughout their lives. Adults with Angelman syndrome have distinctive facial features that may be described as "coarse." Other common features include unusually fair skin with light-colored hair and an abnormal side-to-side curvature of the spine (scoliosis). The life expectancy of people with this condition appears to be nearly normal. </s>


Input: How many people are affected by Angelman syndrome ?

Output: Angelman syndrome affects an estimated 1 in 12,000 to 20,000 people. </s>


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

Output: Many of the characteristic features of Angelman syndrome result from the loss of function of a gene called UBE3A. People normally inherit one copy of the UBE3A gene from each parent. Both copies of this gene are turned on (active) in many of the body's tissues. In certain areas of the brain, however, only the copy inherited from a person's mother (the maternal copy) is active. This parent-specific gene activation is caused by a phenomenon called genomic imprinting. If the maternal copy of the UBE3A gene is lost because of a chromosomal change or a gene mutation, a person will have no active copies of the gene in some parts of the brain.  Several different genetic mechanisms can inactivate or delete the maternal copy of the UBE3A gene. Most cases of Angelman syndrome (about 70 percent) occur when a segment of the maternal chromosome 15 containing this gene is deleted. In other cases (about 11 percent), Angelman syndrome is caused by a mutation in the maternal copy of the UBE3A gene.  In a small percentage of cases, Angelman syndrome results when a person inherits two copies of chromosome 15 from his or her father (paternal copies) instead of one copy from each parent. This phenomenon is called paternal uniparental disomy. Rarely, Angelman syndrome can also be caused by a chromosomal rearrangement called a translocation, or by a mutation or other defect in the region of DNA that controls activation of the UBE3A gene. These genetic changes can abnormally turn off (inactivate) UBE3A or other genes on the maternal copy of chromosome 15.  The causes of Angelman syndrome are unknown in 10 to 15 percent of affected individuals. Changes involving other genes or chromosomes may be responsible for the disorder in these cases.  In some people who have Angelman syndrome, the loss of a gene called OCA2 is associated with light-colored hair and fair skin. The OCA2 gene is located on the segment of chromosome 15 that is often deleted in people with this disorder. However, loss of the OCA2 gene does not cause the other signs and symptoms of Angelman syndrome. The protein produced from this gene helps determine the coloring (pigmentation) of the skin, hair, and eyes. </s>


Input: Is Angelman syndrome inherited ?

Output: Most cases of Angelman syndrome are not inherited, particularly those caused by a deletion in the maternal chromosome 15 or by paternal uniparental disomy. These genetic changes occur as random events during the formation of reproductive cells (eggs and sperm) or in early embryonic development. Affected people typically have no history of the disorder in their family.  Rarely, a genetic change responsible for Angelman syndrome can be inherited. For example, it is possible for a mutation in the UBE3A gene or in the nearby region of DNA that controls gene activation to be passed from one generation to the next. </s>


Input: What are the treatments for Angelman syndrome ?

Output: These resources address the diagnosis or management of Angelman syndrome:  - Gene Review: Gene Review: Angelman Syndrome  - Genetic Testing Registry: Angelman syndrome  - MedlinePlus Encyclopedia: Speech Disorders   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) mucopolysaccharidosis type I ?

Output: Mucopolysaccharidosis type I (MPS I) is a condition that affects many parts of the body. This disorder was once divided into three separate syndromes: Hurler syndrome (MPS I-H), Hurler-Scheie syndrome (MPS I-H/S), and Scheie syndrome (MPS I-S), listed from most to least severe. Because there is so much overlap between each of these three syndromes, MPS I is currently divided into the severe and attenuated types.  Children with MPS I often have no signs or symptoms of the condition at birth, although some have a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). People with severe MPS I generally begin to show other signs and symptoms of the disorder within the first year of life, while those with the attenuated form have milder features that develop later in childhood.  Individuals with MPS I may have a large head (macrocephaly), a buildup of fluid in the brain (hydrocephalus), heart valve abnormalities, distinctive-looking facial features that are described as "coarse," an enlarged liver and spleen (hepatosplenomegaly), and a large tongue (macroglossia). Vocal cords can also enlarge, resulting in a deep, hoarse voice. The airway may become narrow in some people with MPS I, causing frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea).  People with MPS I often develop clouding of the clear covering of the eye (cornea), which can cause significant vision loss. Affected individuals may also have hearing loss and recurrent ear infections.  Some individuals with MPS I have short stature and joint deformities (contractures) that affect mobility. Most people with the severe form of the disorder also have dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Carpal tunnel syndrome develops in many children with this disorder and is characterized by numbness, tingling, and weakness in the hand and fingers. Narrowing of the spinal canal (spinal stenosis) in the neck can compress and damage the spinal cord.  While both forms of MPS I can affect many different organs and tissues, people with severe MPS I experience a decline in intellectual function and a more rapid disease progression. Developmental delay is usually present by age 1, and severely affected individuals eventually lose basic functional skills (developmentally regress). Children with this form of the disorder usually have a shortened lifespan, sometimes living only into late childhood. Individuals with attenuated MPS I typically live into adulthood and may or may not have a shortened lifespan. Some people with the attenuated type have learning disabilities, while others have no intellectual impairments. Heart disease and airway obstruction are major causes of death in people with both types of MPS I. </s>


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

Output: Severe MPS I occurs in approximately 1 in 100,000 newborns. Attenuated MPS I is less common and occurs in about 1 in 500,000 newborns. </s>


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

Output: Mutations in the IDUA gene cause MPS I. The IDUA gene provides instructions for producing an enzyme that is involved in the breakdown of large sugar molecules called glycosaminoglycans (GAGs). GAGs were originally called mucopolysaccharides, which is where this condition gets its name. Mutations in the IDUA gene reduce or completely eliminate the function of the IDUA enzyme. The lack of IDUA enzyme activity leads to the accumulation of GAGs within cells, specifically inside the lysosomes. Lysosomes are compartments in the cell that digest and recycle different types of molecules. Conditions that cause molecules to build up inside the lysosomes, including MPS I, are called lysosomal storage disorders. The accumulation of GAGs increases the size of the lysosomes, which is why many tissues and organs are enlarged in this disorder. Researchers believe that the GAGs may also interfere with the functions of other proteins inside the lysosomes and disrupt the movement of molecules inside the cell. </s>


Input: Is mucopolysaccharidosis type I inherited ?

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


Input: What are the treatments for mucopolysaccharidosis type I ?

Output: These resources address the diagnosis or management of mucopolysaccharidosis type I:  - Baby's First Test  - Gene Review: Gene Review: Mucopolysaccharidosis Type I  - Genetic Testing Registry: Mucopolysaccharidosis type I  - MedlinePlus Encyclopedia: Hurler Syndrome  - MedlinePlus Encyclopedia: Mucopolysaccharides  - MedlinePlus Encyclopedia: Scheie Syndrome  - National MPS Society: Treatments   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) autosomal dominant nocturnal frontal lobe epilepsy ?

Output: Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is an uncommon form of epilepsy that runs in families. This disorder causes seizures that usually occur at night (nocturnally) while an affected person is sleeping. Some people with ADNFLE also have seizures during the day.  The seizures characteristic of ADNFLE tend to occur in clusters, with each one lasting from a few seconds to a few minutes. Some people have mild seizures that simply cause them to wake up from sleep. Others have more severe episodes that can include sudden, repetitive movements such as flinging or throwing motions of the arms and bicycling movements of the legs. The person may get out of bed and wander around, which can be mistaken for sleepwalking. The person may also cry out or make moaning, gasping, or grunting sounds. These episodes are sometimes misdiagnosed as nightmares, night terrors, or panic attacks.  In some types of epilepsy, including ADNFLE, a pattern of neurological symptoms called an aura often precedes a seizure. The most common symptoms associated with an aura in people with ADNFLE are tingling, shivering, a sense of fear, dizziness (vertigo), and a feeling of falling or being pushed. Some affected people have also reported a feeling of breathlessness, overly fast breathing (hyperventilation), or choking. It is unclear what brings on seizures in people with ADNFLE. Episodes may be triggered by stress or fatigue, but in most cases the seizures do not have any recognized triggers.  The seizures associated with ADNFLE can begin anytime from infancy to mid-adulthood, but most begin in childhood. The episodes tend to become milder and less frequent with age. In most affected people, the seizures can be effectively controlled with medication.  Most people with ADNFLE are intellectually normal, and there are no problems with their brain function between seizures. However, some people with ADNFLE have experienced psychiatric disorders (such as schizophrenia), behavioral problems, or intellectual disability. It is unclear whether these additional features are directly related to epilepsy in these individuals. </s>


Input: How many people are affected by autosomal dominant nocturnal frontal lobe epilepsy ?

Output: ADNFLE appears to be an uncommon form of epilepsy; its prevalence is unknown. This condition has been reported in more than 100 families worldwide. </s>


Input: What are the genetic changes related to autosomal dominant nocturnal frontal lobe epilepsy ?

Output: Mutations in the CHRNA2, CHRNA4, and CHRNB2 genes can cause ADNFLE. These genes provide instructions for making different parts (subunits) of a larger molecule called a neuronal nicotinic acetylcholine receptor (nAChR). This receptor plays an important role in chemical signaling between nerve cells (neurons) in the brain.  Communication between neurons depends on chemicals called neurotransmitters, which are released from one neuron and taken up by neighboring neurons. Researchers believe that mutations in the CHRNA2, CHRNA4, and CHRNB2 genes affect the normal release and uptake of certain neurotransmitters in the brain. The resulting changes in signaling between neurons likely trigger the abnormal brain activity associated with seizures.  The seizures associated with ADNFLE begin in areas of the brain called the frontal lobes. These regions of the brain are involved in many critical functions, including reasoning, planning, judgment, and problem-solving. It is unclear why mutations in the CHRNA2, CHRNA4, and CHRNB2 genes cause seizures in the frontal lobes rather than elsewhere in the brain. Researchers are also working to determine why these seizures occur most often during sleep.  The genetic cause of ADNFLE has been identified in only a small percentage of affected families. In some cases, a gene other than those that make up the nAChR are involved. In the remaining families, the cause of the condition is unknown. Researchers are searching for other genetic changes, including mutations in other subunits of nAChR, that may underlie the condition. </s>


Input: Is autosomal dominant nocturnal frontal lobe epilepsy 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 raise the risk of developing epilepsy. About 70 percent of people who inherit a mutation in the CHRNA2, CHRNA4, or CHRNB2 gene will develop seizures. In most cases, an affected person has one affected parent and other relatives with the condition. Other cases are described as sporadic, which means an affected person has no family history of the disorder. </s>


Input: What are the treatments for autosomal dominant nocturnal frontal lobe epilepsy ?

Output: These resources address the diagnosis or management of ADNFLE:  - Gene Review: Gene Review: Autosomal Dominant Nocturnal Frontal Lobe Epilepsy  - Genetic Testing Registry: Epilepsy, nocturnal frontal lobe, type 1  - Genetic Testing Registry: Epilepsy, nocturnal frontal lobe, type 2  - Genetic Testing Registry: Epilepsy, nocturnal frontal lobe, type 3  - Genetic Testing Registry: Epilepsy, nocturnal frontal lobe, type 4  - MedlinePlus Encyclopedia: Epilepsy   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) ocular albinism ?

Output: Ocular albinism is a genetic condition that primarily affects the eyes. This condition reduces the coloring (pigmentation) of the iris, which is the colored part of the eye, and the retina, which is the light-sensitive tissue at the back of the eye. Pigmentation in the eye is essential for normal vision.  Ocular albinism is characterized by severely impaired sharpness of vision (visual acuity) and problems with combining vision from both eyes to perceive depth (stereoscopic vision). Although the vision loss is permanent, it does not worsen over time. Other eye abnormalities associated with this condition include rapid, involuntary eye movements (nystagmus); eyes that do not look in the same direction (strabismus); and increased sensitivity to light (photophobia). Many affected individuals also have abnormalities involving the optic nerves, which carry visual information from the eye to the brain.  Unlike some other forms of albinism, ocular albinism does not significantly affect the color of the skin and hair. People with this condition may have a somewhat lighter complexion than other members of their family, but these differences are usually minor.  The most common form of ocular albinism is known as the Nettleship-Falls type or type 1. Other forms of ocular albinism are much rarer and may be associated with additional signs and symptoms, such as hearing loss. </s>


Input: How many people are affected by ocular albinism ?

Output: The most common form of this disorder, ocular albinism type 1, affects at least 1 in 60,000 males. The classic signs and symptoms of this condition are much less common in females. </s>


Input: What are the genetic changes related to ocular albinism ?

Output: Ocular albinism type 1 results from mutations in the GPR143 gene. This gene provides instructions for making a protein that plays a role in pigmentation of the eyes and skin. It helps control the growth of melanosomes, which are cellular structures that produce and store a pigment called melanin. Melanin is the substance that gives skin, hair, and eyes their color. In the retina, this pigment also plays a role in normal vision.  Most mutations in the GPR143 gene alter the size or shape of the GPR143 protein. Many of these genetic changes prevent the protein from reaching melanosomes to control their growth. In other cases, the protein reaches melanosomes normally but mutations disrupt the protein's function. As a result of these changes, melanosomes in skin cells and the retina can grow abnormally large. Researchers are uncertain how these giant melanosomes are related to vision loss and other eye abnormalities in people with ocular albinism.  Rare cases of ocular albinism are not caused by mutations in the GPR143 gene. In these cases, the genetic cause of the condition is often unknown. </s>


Input: Is ocular albinism inherited ?

Output: Ocular albinism type 1 is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the GPR143 gene in each cell is sufficient to cause the characteristic features of ocular albinism. Because females have two copies of the X chromosome, women with only one copy of a GPR143 mutation in each cell usually do not experience vision loss or other significant eye abnormalities. They may have mild changes in retinal pigmentation that can be detected during an eye examination. </s>


Input: What are the treatments for ocular albinism ?

Output: These resources address the diagnosis or management of ocular albinism:  - Gene Review: Gene Review: Ocular Albinism, X-Linked  - Genetic Testing Registry: Albinism ocular late onset sensorineural deafness  - Genetic Testing Registry: Albinism, ocular, with sensorineural deafness  - Genetic Testing Registry: Ocular albinism, type I  - MedlinePlus Encyclopedia: Albinism   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) hereditary leiomyomatosis and renal cell cancer ?

Output: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a disorder in which affected individuals tend to develop benign tumors containing smooth muscle tissue (leiomyomas) in the skin and, in females, the uterus. This condition also increases the risk of kidney cancer.  In this disorder, growths on the skin (cutaneous leiomyomas) typically develop in the third decade of life. Most of these growths arise from the tiny muscles around the hair follicles that cause "goosebumps". They appear as bumps or nodules on the trunk, arms, legs, and occasionally on the face. Cutaneous leiomyomas may be the same color as the surrounding skin, or they may be darker. Some affected individuals have no cutaneous leiomyomas or only a few, but the growths tend to increase in size and number over time. Cutaneous leiomyomas are often more sensitive than the surrounding skin to cold or light touch, and may be painful.  Most women with HLRCC also develop uterine leiomyomas (fibroids). While uterine fibroids are very common in the general population, women with HLRCC tend to have numerous large fibroids that appear earlier than in the general population.  Approximately 10 percent to 16 percent of people with HLRCC develop a type of kidney cancer called renal cell cancer. The signs and symptoms of renal cell cancer may include lower back pain, blood in the urine, or a mass in the kidney that can be felt upon physical examination. Some people with renal cell cancer have no symptoms until the disease is advanced. The average age at which people with HLRCC are diagnosed with kidney cancer is in their forties.  This disorder, especially if it appears in individuals or families without renal cell cancer, is also sometimes called multiple cutaneous leiomyomatosis (MCL) or multiple cutaneous and uterine leiomyomatosis (MCUL). </s>


Input: How many people are affected by hereditary leiomyomatosis and renal cell cancer ?

Output: HLRCC has been reported in approximately 100 families worldwide. Its prevalence is unknown. </s>


Input: What are the genetic changes related to hereditary leiomyomatosis and renal cell cancer ?

Output: Mutations in the FH gene cause hereditary leiomyomatosis and renal cell cancer. The FH gene provides instructions for making an enzyme called fumarase (also known as fumarate hydratase). This enzyme participates in an important series of reactions known as the citric acid cycle or Krebs cycle, which allows cells to use oxygen and generate energy. Specifically, fumarase helps convert a molecule called fumarate to a molecule called malate.  People with HLRCC are born with one mutated copy of the FH gene in each cell. The second copy of the FH gene in certain cells may also acquire mutations as a result of environmental factors such as ultraviolet radiation from the sun or a mistake that occurs as DNA copies itself during cell division.  FH gene mutations may interfere with the enzyme's role in the citric acid cycle, resulting in a buildup of fumarate. Researchers believe that the excess fumarate may interfere with the regulation of oxygen levels in the cell. Chronic oxygen deficiency (hypoxia) in cells with two mutated copies of the FH gene may encourage tumor formation and result in the tendency to develop leiomyomas and renal cell cancer. </s>


Input: Is hereditary leiomyomatosis and renal cell cancer inherited ?

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


Input: What are the treatments for hereditary leiomyomatosis and renal cell cancer ?

Output: These resources address the diagnosis or management of HLRCC:  - Gene Review: Gene Review: Hereditary Leiomyomatosis and Renal Cell Cancer  - Genetic Testing Registry: Hereditary leiomyomatosis and renal cell cancer  - MedlinePlus Encyclopedia: Renal Cell Carcinoma   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) gray platelet syndrome ?

Output: Gray platelet syndrome is a bleeding disorder associated with abnormal platelets, which are blood cell fragments involved in blood clotting. People with this condition tend to bruise easily and have an increased risk of nosebleeds (epistaxis). They may also experience abnormally heavy or extended bleeding following surgery, dental work, or minor trauma. Women with gray platelet syndrome often have irregular, heavy periods (menometrorrhagia). These bleeding problems are usually mild to moderate, but they have been life-threatening in a few affected individuals.  A condition called myelofibrosis, which is a buildup of scar tissue (fibrosis) in the bone marrow, is another common feature of gray platelet syndrome. Bone marrow is the spongy tissue in the center of long bones that produces most of the blood cells the body needs, including platelets. The scarring associated with myelofibrosis damages bone marrow, preventing it from making enough blood cells. Other organs, particularly the spleen, start producing more blood cells to compensate; this process often leads to an enlarged spleen (splenomegaly). </s>


Input: How many people are affected by gray platelet syndrome ?

Output: Gray platelet syndrome appears to be a rare disorder. About 60 cases have been reported worldwide. </s>


Input: What are the genetic changes related to gray platelet syndrome ?

Output: Gray platelet syndrome can be caused by mutations in the NBEAL2 gene. Little is known about the protein produced from this gene. It appears to play a role in the formation of alpha-granules, which are sacs inside platelets that contain growth factors and other proteins that are important for blood clotting and wound healing. In response to an injury that causes bleeding, the proteins stored in alpha-granules help platelets stick to one another to form a plug that seals off damaged blood vessels and prevents further blood loss.  Mutations in the NBEAL2 gene disrupt the normal production of alpha-granules. Without alpha-granules, platelets are unusually large and fewer in number than usual (macrothrombocytopenia). The abnormal platelets also appear gray when viewed under a microscope, which gives this condition its name. A lack of alpha-granules impairs the normal activity of platelets during blood clotting, increasing the risk of abnormal bleeding. Myelofibrosis is thought to occur because the growth factors and other proteins that are normally packaged into alpha-granules leak out into the bone marrow. The proteins lead to fibrosis that affects the bone marrow's ability to make new blood cells.  Some people with gray platelet syndrome do not have an identified mutation in the NBEAL2 gene. In these individuals, the cause of the condition is unknown. </s>


Input: Is gray platelet syndrome inherited ?

Output: When gray platelet syndrome is caused by NBEAL2 gene mutations, it has an autosomal recessive pattern of inheritance, 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 altered gene in each cell.  Gray platelet syndrome can also be inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. An affected person often inherits the condition from one affected parent. Researchers are working to determine which gene or genes are associated with the autosomal dominant form of gray platelet syndrome. </s>


Input: What are the treatments for gray platelet syndrome ?

Output: These resources address the diagnosis or management of gray platelet syndrome:  - Genetic Testing Registry: Gray platelet syndrome  - National Heart Lung and Blood Institute: How is Thrombocytopenia Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) Rothmund-Thomson syndrome ?

Output: Rothmund-Thomson syndrome is a rare condition that affects many parts of the body, especially the skin. People with this condition typically develop redness on the cheeks between ages 3 months and 6 months. Over time the rash spreads to the arms and legs, causing patchy changes in skin coloring, areas of thinning skin (atrophy), and small clusters of blood vessels just under the skin (telangiectases). These skin problems persist for life and are collectively known as poikiloderma.  Rothmund-Thomson syndrome is also characterized by sparse hair, eyebrows, and eyelashes; slow growth and small stature; abnormalities of the teeth and nails; and gastrointestinal problems in infancy, such as chronic diarrhea and vomiting. Some affected children develop a clouding of the lens of the eye (cataract), which affects vision. Many people with this disorder have skeletal abnormalities including absent or malformed bones, fused bones, and low bone mineral density (osteopenia or osteoporosis). Some of these abnormalities affect the development of bones in the forearms and the thumbs, and are known as radial ray malformations.  People with Rothmund-Thomson syndrome have an increased risk of developing cancer, particularly a form of bone cancer called osteosarcoma. These bone tumors most often develop during childhood or adolescence. Several types of skin cancer, including basal cell carcinoma and squamous cell carcinoma, are also more common in people with this disorder.  The varied signs and symptoms of Rothmund-Thomson syndrome overlap with features of other disorders, namely Baller-Gerold syndrome and RAPADILINO syndrome. These syndromes are also characterized by radial ray defects, skeletal abnormalities, and slow growth. All of these conditions can be caused by mutations in the same gene. Based on these similarities, researchers are investigating whether Rothmund-Thomson syndrome, Baller-Gerold syndrome, and RAPADILINO syndrome are separate disorders or part of a single syndrome with overlapping signs and symptoms. </s>


Input: How many people are affected by Rothmund-Thomson syndrome ?

Output: Rothmund-Thomson syndrome is a rare disorder; its incidence is unknown. About 300 people with this condition have been reported worldwide in scientific studies. </s>


Input: What are the genetic changes related to Rothmund-Thomson syndrome ?

Output: Mutations in the RECQL4 gene cause about two-thirds of all cases of Rothmund-Thomson syndrome. This gene provides instructions for making one member of a protein family called RecQ helicases. Helicases are enzymes that bind to DNA and temporarily unwind the two spiral strands (double helix) of the DNA molecule. This unwinding is necessary for copying (replicating) DNA in preparation for cell division, and for repairing damaged DNA. The RECQL4 protein helps stabilize genetic information in the body's cells and plays a role in replicating and repairing DNA.  RECQL4 mutations lead to the production of an abnormally short, nonfunctional version of the RECQL4 protein or prevent cells from making any of this protein. A shortage of the RECQL4 protein may prevent normal DNA replication and repair, causing widespread damage to a person's genetic information over time. It is unclear how a loss of this protein's activity leads to the specific features of Rothmund-Thomson syndrome.  In about one-third of individuals with Rothmund-Thomson syndrome, no mutation in the RECQL4 gene has been found. The cause of the condition in these individuals is unknown; however, researchers suspect that these cases may result from mutations in a gene related to the RECQL4 gene.  In some cases, chromosomal abnormalities have been identified in people with Rothmund-Thomson syndrome. These abnormalities include extra or missing genetic material, usually from chromosome 7 or chromosome 8, in some of an affected person's cells. Researchers believe that these chromosomal changes arise because of the overall instability of an affected person's genetic information; they do not cause the disorder. </s>


Input: Is Rothmund-Thomson 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 Rothmund-Thomson syndrome ?

Output: These resources address the diagnosis or management of Rothmund-Thomson syndrome:  - Gene Review: Gene Review: Rothmund-Thomson Syndrome  - Genetic Testing Registry: Rothmund-Thomson syndrome  - MedlinePlus Encyclopedia: Cataract  - MedlinePlus Encyclopedia: Osteosarcoma   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) familial exudative vitreoretinopathy ?

Output: Familial exudative vitreoretinopathy is a hereditary disorder that can cause progressive vision loss. This condition affects the retina, the specialized light-sensitive tissue that lines the back of the eye. The disorder prevents blood vessels from forming at the edges of the retina, which reduces the blood supply to this tissue.  The signs and symptoms of familial exudative vitreoretinopathy vary widely, even within the same family. In many affected individuals, the retinal abnormalities never cause any vision problems. In others, a reduction in the retina's blood supply causes the retina to fold, tear, or separate from the back of the eye (retinal detachment). This retinal damage can lead to vision loss and blindness. Other eye abnormalities are also possible, including eyes that do not look in the same direction (strabismus) and a visible whiteness (leukocoria) in the normally black pupil.  Some people with familial exudative vitreoretinopathy also have reduced bone mineral density, which weakens bones and increases the risk of fractures. </s>


Input: How many people are affected by familial exudative vitreoretinopathy ?

Output: The prevalence of familial exudative vitreoretinopathy is unknown. It appears to be rare, although affected people with normal vision may never come to medical attention. </s>


Input: What are the genetic changes related to familial exudative vitreoretinopathy ?

Output: Mutations in the FZD4, LRP5, and NDP genes can cause familial exudative vitreoretinopathy. These genes provide instructions for making proteins that participate in a chemical signaling pathway that affects the way cells and tissues develop. In particular, the proteins produced from the FZD4, LRP5, and NDP genes appear to play critical roles in the specialization of retinal cells and the establishment of a blood supply to the retina and the inner ear. The LRP5 protein also helps regulate bone formation.  Mutations in the FZD4, LRP5, or NDP gene disrupt chemical signaling during early development, which interferes with the formation of blood vessels at the edges of the retina. The resulting abnormal blood supply to this tissue leads to retinal damage and vision loss in some people with familial exudative vitreoretinopathy.  The eye abnormalities associated with familial exudative vitreoretinopathy tend to be similar no matter which gene is altered. However, affected individuals with LRP5 gene mutations often have reduced bone mineral density in addition to vision loss. Mutations in the other genes responsible for familial exudative vitreoretinopathy do not appear to affect bone density.  In some cases, the cause of familial exudative vitreoretinopathy is unknown. Researchers believe that mutations in several as-yet-unidentified genes are responsible for the disorder in these cases. </s>


Input: Is familial exudative vitreoretinopathy inherited ?

Output: Familial exudative vitreoretinopathy has different inheritance patterns depending on the gene involved. Most commonly, the condition results from mutations in the FZD4 or LRP5 gene and has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. Most people with autosomal dominant familial exudative vitreoretinopathy inherit the altered gene from a parent, although the parent may not have any signs and symptoms associated with this disorder.  Familial exudative vitreoretinopathy caused by LRP5 gene mutations can also have an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with autosomal recessive familial exudative vitreoretinopathy each carry one copy of the mutated gene, but they do not have the disorder.  When familial exudative vitreoretinopathy is caused by mutations in the NDP gene, it has an X-linked recessive pattern of inheritance. The NDP gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. </s>


Input: What are the treatments for familial exudative vitreoretinopathy ?

Output: These resources address the diagnosis or management of familial exudative vitreoretinopathy:  - Gene Review: Gene Review: Familial Exudative Vitreoretinopathy, Autosomal Dominant  - Gene Review: Gene Review: NDP-Related Retinopathies  - Genetic Testing Registry: Exudative vitreoretinopathy 1  - Genetic Testing Registry: Exudative vitreoretinopathy 3  - Genetic Testing Registry: Exudative vitreoretinopathy 4  - Genetic Testing Registry: Familial exudative vitreoretinopathy, X-linked   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) spondyloperipheral dysplasia ?

Output: Spondyloperipheral dysplasia is a disorder that impairs bone growth. This condition is characterized by flattened bones of the spine (platyspondyly) and unusually short fingers and toes (brachydactyly), with the exception of the first (big) toes. Other skeletal abnormalities associated with spondyloperipheral dysplasia include short stature, shortened long bones of the arms and legs, exaggerated curvature of the lower back (lordosis), and an inward- and upward-turning foot (clubfoot). Additionally, some affected individuals have nearsightedness (myopia), hearing loss, and intellectual disability. </s>


Input: How many people are affected by spondyloperipheral dysplasia ?

Output: This condition is rare; only a few affected individuals have been reported worldwide. </s>


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

Output: Spondyloperipheral dysplasia is one of a spectrum of skeletal disorders caused by mutations in the COL2A1 gene. This gene provides instructions for making a protein that forms type II collagen. This type of collagen is found mostly in the clear gel that fills the eyeball (the vitreous) and in cartilage. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Type II collagen is essential for the normal development of bones and other connective tissues that form the body's supportive framework.  Mutations in the COL2A1 gene interfere with the assembly of type II collagen molecules, reducing the amount of this type of collagen in the body. Instead of forming collagen molecules, the abnormal COL2A1 protein builds up in cartilage cells (chondrocytes). These changes disrupt the normal development of bones and other connective tissues, leading to the signs and symptoms of spondyloperipheral dysplasia. </s>


Input: Is spondyloperipheral dysplasia inherited ?

Output: This condition is probably 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 spondyloperipheral dysplasia ?

Output: These resources address the diagnosis or management of spondyloperipheral dysplasia:  - Genetic Testing Registry: Spondyloperipheral dysplasia  - MedlinePlus Encyclopedia: Nearsightedness   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) platyspondylic lethal skeletal dysplasia, Torrance type ?

Output: Platyspondylic lethal skeletal dysplasia, Torrance type is a severe disorder of bone growth. People with this condition have very short arms and legs, underdeveloped pelvic bones, and unusually short fingers and toes (brachydactyly). This disorder is also characterized by flattened spinal bones (platyspondyly) and an exaggerated curvature of the lower back (lordosis). Infants with this condition are born with a small chest with short ribs that can restrict the growth and expansion of the lungs.  As a result of these serious health problems, some affected fetuses do not survive to term. Infants born with platyspondylic lethal skeletal dysplasia, Torrance type usually die at birth or shortly thereafter from respiratory failure. A few affected people with milder signs and symptoms have lived into adulthood. </s>


Input: How many people are affected by platyspondylic lethal skeletal dysplasia, Torrance type ?

Output: This condition is very rare; only a few affected individuals have been reported worldwide. </s>


Input: What are the genetic changes related to platyspondylic lethal skeletal dysplasia, Torrance type ?

Output: Platyspondylic lethal skeletal dysplasia, Torrance type is one of a spectrum of skeletal disorders caused by mutations in the COL2A1 gene. This gene provides instructions for making a protein that forms type II collagen. This type of collagen is found mostly in the clear gel that fills the eyeball (the vitreous) and in cartilage. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Type II collagen is essential for the normal development of bones and other connective tissues that form the body's supportive framework.  All of the COL2A1 mutations that have been found to cause platyspondylic lethal skeletal dysplasia, Torrance type occur in a region of the protein called the C-propeptide domain. These mutations interfere with the assembly of type II collagen molecules, reducing the amount of this type of collagen in the body. Instead of forming collagen molecules, the abnormal COL2A1 protein builds up in cartilage cells (chondrocytes). These changes disrupt the normal development of bones and other connective tissues, leading to the skeletal abnormalities characteristic of platyspondylic lethal skeletal dysplasia, Torrance type. </s>


Input: Is platyspondylic lethal skeletal dysplasia, Torrance type 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 platyspondylic lethal skeletal dysplasia, Torrance type ?

Output: These resources address the diagnosis or management of platyspondylic lethal skeletal dysplasia, Torrance type:  - Genetic Testing Registry: Platyspondylic lethal skeletal dysplasia Torrance type  - MedlinePlus Encyclopedia: Lordosis   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) Allan-Herndon-Dudley syndrome ?

Output: Allan-Herndon-Dudley syndrome is a rare disorder of brain development that causes moderate to severe intellectual disability and problems with movement. This condition, which occurs exclusively in males, disrupts development from before birth. Although affected males have impaired speech and a limited ability to communicate, they seem to enjoy interaction with other people.  Most children with Allan-Herndon-Dudley syndrome have weak muscle tone (hypotonia) and underdevelopment of many muscles (muscle hypoplasia). As they get older, they usually develop joint deformities called contractures, which restrict the movement of certain joints. Abnormal muscle stiffness (spasticity), muscle weakness, and involuntary movements of the arms and legs also limit mobility. As a result, many people with Allan-Herndon-Dudley syndrome are unable to walk independently and become wheelchair-bound by adulthood. </s>


Input: How many people are affected by Allan-Herndon-Dudley syndrome ?

Output: Allan-Herndon-Dudley syndrome appears to be a rare disorder. About 25 families with individuals affected by this condition have been reported worldwide. </s>


Input: What are the genetic changes related to Allan-Herndon-Dudley syndrome ?

Output: Mutations in the SLC16A2 gene cause Allan-Herndon-Dudley syndrome. The SLC16A2 gene, also known as MCT8, provides instructions for making a protein that plays a critical role in the development of the nervous system. This protein transports a particular hormone into nerve cells in the developing brain. This hormone, called triiodothyronine or T3, is produced by a butterfly-shaped gland in the lower neck called the thyroid. T3 appears to be critical for the normal formation and growth of nerve cells, as well as the development of junctions between nerve cells (synapses) where cell-to-cell communication occurs. T3 and other forms of thyroid hormone also help regulate the development of other organs and control the rate of chemical reactions in the body (metabolism).  Gene mutations alter the structure and function of the SLC16A2 protein. As a result, this protein is unable to transport T3 into nerve cells effectively. A lack of this critical hormone in certain parts of the brain disrupts normal brain development, resulting in intellectual disability and problems with movement. Because T3 is not taken up by nerve cells, excess amounts of this hormone continue to circulate in the bloodstream. Increased T3 levels in the blood may be toxic to some organs and contribute to the signs and symptoms of Allan-Herndon-Dudley syndrome. </s>


Input: Is Allan-Herndon-Dudley syndrome inherited ?

Output: This condition is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In X-linked recessive inheritance, a female with one altered copy of the gene in each cell is called a carrier. She can pass on the mutated gene, but usually does not experience signs and symptoms of the disorder. Carriers of SLC16A2 mutations have normal intelligence and do not experience problems with movement. Some carriers have been diagnosed with thyroid disease, a condition which is relatively common in the general population. It is unclear whether thyroid disease is related to SLC16A2 gene mutations in these cases. </s>


Input: What are the treatments for Allan-Herndon-Dudley syndrome ?

Output: These resources address the diagnosis or management of Allan-Herndon-Dudley syndrome:  - Gene Review: Gene Review: MCT8-Specific Thyroid Hormone Cell-Membrane Transporter Deficiency  - Genetic Testing Registry: Allan-Herndon-Dudley syndrome  - MedlinePlus Encyclopedia: Intellectual Disability  - MedlinePlus Encyclopedia: T3 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) triosephosphate isomerase deficiency ?

Output: Triosephosphate isomerase deficiency is a disorder characterized by a shortage of red blood cells (anemia), movement problems, increased susceptibility to infection, and muscle weakness that can affect breathing and heart function.  The anemia in this condition begins in infancy. Since the anemia results from the premature breakdown of red blood cells (hemolysis), it is known as hemolytic anemia. A shortage of red blood cells to carry oxygen throughout the body leads to extreme tiredness (fatigue), pale skin (pallor), and shortness of breath. When the red cells are broken down, iron and a molecule called bilirubin are released; individuals with triosephosphate isomerase deficiency have an excess of these substances circulating in the blood. Excess bilirubin in the blood causes jaundice, which is a yellowing of the skin and the whites of the eyes.  Movement problems typically become apparent by age 2 in people with triosephosphate isomerase deficiency. The movement problems are caused by impairment of motor neurons, which are specialized nerve cells in the brain and spinal cord that control muscle movement. This impairment leads to muscle weakness and wasting (atrophy) and causes the movement problems typical of triosephosphate isomerase deficiency, including involuntary muscle tensing (dystonia), tremors, and weak muscle tone (hypotonia). Affected individuals may also develop seizures.  Weakness of other muscles, such as the heart (a condition known as cardiomyopathy) and the muscle that separates the abdomen from the chest cavity (the diaphragm) can also occur in triosephosphate isomerase deficiency. Diaphragm weakness can cause breathing problems and ultimately leads to respiratory failure.  Individuals with triosephosphate isomerase deficiency are at increased risk of developing infections because they have poorly functioning white blood cells. These immune system cells normally recognize and attack foreign invaders, such as viruses and bacteria, to prevent infection. The most common infections in people with triosephosphate isomerase deficiency are bacterial infections of the respiratory tract.  People with triosephosphate isomerase deficiency often do not survive past childhood due to respiratory failure. In a few rare cases, affected individuals without severe nerve damage or muscle weakness have lived into adulthood. </s>


Input: How many people are affected by triosephosphate isomerase deficiency ?

Output: Triosephosphate isomerase deficiency is likely a rare condition; approximately 40 cases have been reported in the scientific literature. </s>


Input: What are the genetic changes related to triosephosphate isomerase deficiency ?

Output: Mutations in the TPI1 gene cause triosephosphate isomerase deficiency. This gene provides instructions for making an enzyme called triosephosphate isomerase 1. This enzyme is involved in a critical energy-producing process known as glycolysis. During glycolysis, the simple sugar glucose is broken down to produce energy for cells.  TPI1 gene mutations lead to the production of unstable enzymes or enzymes with decreased activity. As a result, glycolysis is impaired and cells have a decreased supply of energy. Red blood cells depend solely on the breakdown of glucose for energy, and without functional glycolysis, red blood cells die earlier than normal. Cells with high energy demands, such as nerve cells in the brain, white blood cells, and heart (cardiac) muscle cells are also susceptible to cell death due to reduced energy caused by impaired glycolysis. Nerve cells in the part of the brain involved in coordinating movements (the cerebellum) are particularly affected in people with triosephosphate isomerase deficiency.  Death of red and white blood cells, nerve cells in the brain, and cardiac muscle cells leads to the signs and symptoms of triosephosphate isomerase deficiency. </s>


Input: Is triosephosphate isomerase 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 triosephosphate isomerase deficiency ?

Output: These resources address the diagnosis or management of triosephosphate isomerase deficiency:  - Genetic Testing Registry: Triosephosphate isomerase deficiency  - MedlinePlus Encyclopedia: Hemolytic Anemia  - National Heart, Lung, and Blood Institute: How is Hemolytic Anemia Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) Clouston syndrome ?

Output: Clouston syndrome is a form of ectodermal dysplasia, a group of about 150 conditions characterized by abnormal development of some or all of the ectodermal structures, which include the skin, hair, nails, teeth, and sweat glands. Specifically, Clouston syndrome is characterized by abnormalities of the hair, nails, and skin, with the teeth and sweat glands being unaffected.  In infants with Clouston syndrome, scalp hair is sparse, patchy, and lighter in color than the hair of other family members; it is also fragile and easily broken. By puberty, the hair problems may worsen until all the hair on the scalp is lost (total alopecia). The eyelashes, eyebrows, underarm (axillary) hair, and pubic hair are also sparse or absent.  Abnormal growth of fingernails and toenails (nail dystrophy) is also characteristic of Clouston syndrome. The nails may appear white in the first years of life. They grow slowly and gradually become thick and misshapen. In some people with Clouston syndrome, nail dystrophy is the most noticeable feature of the disorder.  Many people with Clouston syndrome have thick skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis); areas of the skin, especially over the joints, that are darker in color than the surrounding skin (hyperpigmentation); and widened and rounded tips of the fingers (clubbing). </s>


Input: How many people are affected by Clouston syndrome ?

Output: The prevalence of Clouston syndrome is unknown. Cases have been reported in many populations; the disorder is especially common among people of French-Canadian descent. </s>


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

Output: Clouston syndrome is caused by mutations in the GJB6 gene. This gene provides instructions for making a protein called gap junction beta 6, more commonly known as connexin 30. Connexin 30 is a member of the connexin protein family. Connexin proteins form channels called gap junctions, which permit the transport of nutrients, charged atoms (ions), and signaling molecules between neighboring cells. The size of the gap junction and the types of particles that move through it are determined by the particular connexin proteins that make up the channel. Gap junctions made with connexin 30 transport potassium ions and certain small molecules.  Connexin 30 is found in several different tissues throughout the body, including the skin (especially on the palms of the hands and soles of the feet), hair follicles, and nail beds, and plays a role in the growth and development of these tissues.  GJB6 gene mutations that cause Clouston syndrome change single protein building blocks (amino acids) in the connexin 30 protein. Although the effects of these mutations are not fully understood, they lead to abnormalities in the growth, division, and maturation of cells in the hair follicles, nails, and skin. </s>


Input: Is Clouston syndrome inherited ?

Output: This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family. </s>


Input: What are the treatments for Clouston syndrome ?

Output: These resources address the diagnosis or management of Clouston syndrome:  - Gene Review: Gene Review: Hidrotic Ectodermal Dysplasia 2  - Genetic Testing Registry: Hidrotic ectodermal dysplasia 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) familial hypertrophic cardiomyopathy ?

Output: Familial hypertrophic cardiomyopathy is a heart condition characterized by thickening (hypertrophy) of the heart (cardiac) muscle. Thickening usually occurs in the interventricular septum, which is the muscular wall that separates the lower left chamber of the heart (the left ventricle) from the lower right chamber (the right ventricle). In some people, thickening of the interventricular septum impedes the flow of oxygen-rich blood from the heart, which may lead to an abnormal heart sound during a heartbeat (heart murmur) and other signs and symptoms of the condition. Other affected individuals do not have physical obstruction of blood flow, but the pumping of blood is less efficient, which can also lead to symptoms of the condition. Cardiac hypertrophy often begins in adolescence or young adulthood, although it can develop at any time throughout life.  The symptoms of familial hypertrophic cardiomyopathy are variable, even within the same family. Many affected individuals have no symptoms. Other people with familial hypertrophic cardiomyopathy may experience chest pain; shortness of breath, especially with physical exertion; a sensation of fluttering or pounding in the chest (palpitations); lightheadedness; dizziness; and fainting.  While most people with familial hypertrophic cardiomyopathy are symptom-free or have only mild symptoms, this condition can have serious consequences. It can cause abnormal heart rhythms (arrhythmias) that may be life threatening. People with familial hypertrophic cardiomyopathy have an increased risk of sudden death, even if they have no other symptoms of the condition. A small number of affected individuals develop potentially fatal heart failure, which may require heart transplantation. </s>


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

Output: Familial hypertrophic cardiomyopathy affects an estimated 1 in 500 people worldwide. It is the most common genetic heart disease in the United States. </s>


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

Output: Mutations in one of several genes can cause familial hypertrophic cardiomyopathy; the most commonly involved genes are MYH7, MYBPC3, TNNT2, and TNNI3. Other genes, including some that have not been identified, may also be involved in this condition.  The proteins produced from the genes associated with familial hypertrophic cardiomyopathy play important roles in contraction of the heart muscle by forming muscle cell structures called sarcomeres. Sarcomeres, which are the basic units of muscle contraction, are made up of thick and thin protein filaments. The overlapping thick and thin filaments attach to each other and release, which allows the filaments to move relative to one another so that muscles can contract. In the heart, regular contractions of cardiac muscle pump blood to the rest of the body.  The protein produced from the MYH7 gene, called cardiac beta ()-myosin heavy chain, is the major component of the thick filament in sarcomeres. The protein produced from the MYBPC3 gene, cardiac myosin binding protein C, associates with the thick filament, providing structural support and helping to regulate muscle contractions.  The TNNT2 and TNNI3 genes provide instructions for making cardiac troponin T and cardiac troponin I, respectively, which are two of the three proteins that make up the troponin protein complex found in cardiac muscle cells. The troponin complex associates with the thin filament of sarcomeres. It controls muscle contraction and relaxation by regulating the interaction of the thick and thin filaments.  It is unknown how mutations in sarcomere-related genes lead to hypertrophy of the heart muscle and problems with heart rhythm. The mutations may result in an altered sarcomere protein or reduce the amount of the protein. An abnormality in or shortage of any one of these proteins may impair the function of the sarcomere, disrupting normal cardiac muscle contraction. Research shows that, in affected individuals, contraction and relaxation of the heart muscle is abnormal, even before hypertrophy develops. However, it is not clear how these contraction problems are related to hypertrophy or the symptoms of familial hypertrophic cardiomyopathy. </s>


Input: Is familial hypertrophic cardiomyopathy 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. Rarely, both copies of the gene are altered, leading to more severe signs and symptoms.  In most cases, an affected person has one parent with the condition. </s>


Input: What are the treatments for familial hypertrophic cardiomyopathy ?

Output: These resources address the diagnosis or management of familial hypertrophic cardiomyopathy:  - Cleveland Clinic  - Gene Review: Gene Review: Hypertrophic Cardiomyopathy Overview  - Genetic Testing Registry: Familial hypertrophic cardiomyopathy 1  - Genetic Testing Registry: Familial hypertrophic cardiomyopathy 2  - Genetic Testing Registry: Familial hypertrophic cardiomyopathy 4  - Genetic Testing Registry: Familial hypertrophic cardiomyopathy 7  - MedlinePlus Encyclopedia: Hypertrophic Cardiomyopathy  - Stanford University Hospitals and Clinics  - The Sarcomeric Human Cardiomyopathies Registry (ShaRe)   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) keratitis-ichthyosis-deafness syndrome ?

Output: Keratitis-ichthyosis-deafness (KID) syndrome is characterized by eye problems, skin abnormalities, and hearing loss.  People with KID syndrome usually have keratitis, which is inflammation of the front surface of the eye (the cornea). The keratitis may cause pain, increased sensitivity to light (photophobia), abnormal blood vessel growth over the cornea (neovascularization), and scarring. Over time, affected individuals experience a loss of sharp vision (reduced visual acuity); in severe cases the keratitis can lead to blindness.  Most people with KID syndrome have thick, hard skin on the palms of the hands and soles of the feet (palmoplantar keratoderma). Affected individuals also have thick, reddened patches of skin (erythrokeratoderma) that are dry and scaly (ichthyosis). These dry patches can occur anywhere on the body, although they most commonly affect the neck, groin, and armpits. Breaks in the skin often occur and may lead to infections. In severe cases these infections can be life-threatening, especially in infancy. Approximately 12 percent of people with KID syndrome develop a type of skin cancer called squamous cell carcinoma, which may also affect mucous membranes such as the lining of the mouth.  Partial hair loss is a common feature of KID syndrome, and often affects the eyebrows and eyelashes. Affected individuals may also have small, abnormally formed nails.  Hearing loss in this condition is usually profound, but occasionally is less severe. </s>


Input: How many people are affected by keratitis-ichthyosis-deafness syndrome ?

Output: KID syndrome is a rare disorder. Its prevalence is unknown. Approximately 100 cases have been reported. </s>


Input: What are the genetic changes related to keratitis-ichthyosis-deafness syndrome ?

Output: KID syndrome is caused by mutations in the GJB2 gene. This gene provides instructions for making a protein called gap junction beta 2, more commonly known as connexin 26. Connexin 26 is a member of the connexin protein family. Connexin proteins form channels called gap junctions that permit the transport of nutrients, charged atoms (ions), and signaling molecules between neighboring cells that are in contact with each other. Gap junctions made with connexin 26 transport potassium ions and certain small molecules.  Connexin 26 is found in cells throughout the body, including the inner ear and the skin. In the inner ear, channels made from connexin 26 are found in a snail-shaped structure called the cochlea. These channels may help to maintain the proper level of potassium ions required for the conversion of sound waves to electrical nerve impulses. This conversion is essential for normal hearing. In addition, connexin 26 may be involved in the maturation of certain cells in the cochlea. Connexin 26 also plays a role in the growth and maturation of the outermost layer of skin (the epidermis).  The GJB2 gene mutations that cause KID syndrome change single protein building blocks (amino acids) in connexin 26. The mutations are thought to result in channels that constantly leak ions, which impairs the health of the cells and increases cell death. Death of cells in the skin and the inner ear may underlie the ichthyosis and deafness that occur in KID syndrome. It is unclear how GJB2 gene mutations affect the eye.  Because at least one of the GJB2 gene mutations identified in people with KID syndrome also occurs in hystrix-like ichthyosis with deafness (HID), a disorder with similar features but without keratitis, many researchers categorize KID syndrome and HID as a single disorder, which they call KID/HID. It is not known why some people with this mutation have eye problems while others do not. </s>


Input: Is keratitis-ichthyosis-deafness syndrome inherited ?

Output: KID syndrome is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. However, most cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  A few families have had a condition resembling KID syndrome with an autosomal recessive pattern of inheritance. In autosomal recessive inheritance, both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Affected individuals in these families have liver disease, which is not a feature of the autosomal dominant form. The autosomal recessive condition is sometimes called Desmons syndrome. It is unknown whether it is also caused by GJB2 gene mutations. </s>


Input: What are the treatments for keratitis-ichthyosis-deafness syndrome ?

Output: These resources address the diagnosis or management of keratitis-ichthyosis-deafness syndrome:  - Genetic Testing Registry: Autosomal recessive keratitis-ichthyosis-deafness syndrome  - Genetic Testing Registry: Keratitis-ichthyosis-deafness syndrome, autosomal dominant   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) 7q11.23 duplication syndrome ?

Output: 7q11.23 duplication syndrome is a condition that can cause a variety of neurological and behavioral problems as well as other abnormalities.  People with 7q11.23 duplication syndrome typically have delayed development of speech and delayed motor skills such as crawling and walking. Speech problems and abnormalities in the way affected individuals walk and stand may persist throughout life. Affected individuals may also have weak muscle tone (hypotonia) and abnormal movements, such as involuntary movements of one side of the body that mirror intentional movements of the other side.  Behavioral problems associated with this condition include anxiety disorders (such as social phobias and selective mutism, which is an inability to speak in certain circumstances), attention deficit hyperactivity disorder (ADHD), physical aggression, excessively defiant behavior (oppositional disorder), and autistic behaviors that affect communication and social interaction. While the majority of people with 7q11.23 duplication syndrome have low-average to average intelligence, intellectual development varies widely in this condition, from intellectual disability to, rarely, above-average intelligence. About one-fifth of people with 7q11.23 duplication syndrome experience seizures.  About half of individuals with 7q11.23 duplication syndrome have enlargement (dilatation) of the blood vessel that carries blood from the heart to the rest of the body (the aorta); this enlargement can get worse over time. Aortic dilatation can lead to life-threatening complications if the wall of the aorta separates into layers (aortic dissection) or breaks open (ruptures).  The characteristic appearance of people with 7q11.23 duplication syndrome can include a large head (macrocephaly) that is flattened in the back (brachycephaly), a broad forehead, straight eyebrows, and deep-set eyes with long eyelashes. The nose may be broad at the tip with the area separating the nostrils attaching lower than usual on the face (low insertion of the columella), resulting in a shortened area between the nose and the upper lip (philtrum). A high arch in the roof of the mouth (high-arched palate) and ear abnormalities may also occur in affected individuals. </s>


Input: How many people are affected by 7q11.23 duplication syndrome ?

Output: The prevalence of this disorder is estimated to be 1 in 7,500 to 20,000 people. </s>


Input: What are the genetic changes related to 7q11.23 duplication syndrome ?

Output: 7q11.23 duplication syndrome results from an extra copy of a region on the long (q) arm of chromosome 7 in each cell. This region is called the Williams-Beuren syndrome critical region (WBSCR) because its deletion causes a different disorder called Williams syndrome, also known as Williams-Beuren syndrome. The region, which is 1.5 to 1.8 million DNA base pairs (Mb) in length, includes 26 to 28 genes.  Extra copies of several of the genes in the duplicated region, including the ELN and GTF2I genes, likely contribute to the characteristic features of 7q11.23 duplication syndrome. Researchers suggest that an extra copy of the ELN gene in each cell may be related to the increased risk for aortic dilatation in 7q11.23 duplication syndrome. Studies suggest that an extra copy of the GTF2I gene may be associated with some of the behavioral features of the disorder. However, the specific causes of these features are unclear.  Researchers are studying additional genes in the duplicated region, but none have been definitely linked to any of the specific signs or symptoms of 7q11.23 duplication syndrome. </s>


Input: Is 7q11.23 duplication syndrome inherited ?

Output: 7q11.23 duplication syndrome is considered to be an autosomal dominant condition, which means one copy of chromosome 7 with the duplication in each cell is sufficient to cause the disorder. Most cases result from a duplication that occurs during the formation of reproductive cells (eggs and sperm) or in early fetal development. These cases occur in people with no history of the disorder in their family. Less commonly, an affected person inherits the chromosome with a duplicated segment from a parent. </s>


Input: What are the treatments for 7q11.23 duplication syndrome ?

Output: These resources address the diagnosis or management of 7q11.23 duplication syndrome:  - Cardiff University (United Kingdom): Copy Number Variant Research  - Gene Review: Gene Review: 7q11.23 Duplication Syndrome  - Genetic Testing Registry: Williams-Beuren region duplication syndrome  - University of Antwerp (Belgium): 7q11.23 Research Project  - University of Louisville: 7q11.23 Duplication Syndrome Research  - University of Toronto: 7q11.23 Duplication Syndrome Research   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) 22q13.3 deletion syndrome ?

Output: 22q13.3 deletion syndrome, which is also commonly known as Phelan-McDermid syndrome, is a disorder caused by the loss of a small piece of chromosome 22. The deletion occurs near the end of the chromosome at a location designated q13.3.  The features of 22q13.3 deletion syndrome vary widely and involve many parts of the body. Characteristic signs and symptoms include developmental delay, moderate to profound intellectual disability, decreased muscle tone (hypotonia), and absent or delayed speech. Some people with this condition have autism or autistic-like behavior that affects communication and social interaction, such as poor eye contact, sensitivity to touch, and aggressive behaviors. They may also chew on non-food items such as clothing. Less frequently, people with this condition have seizures.  Individuals with 22q13.3 deletion syndrome tend to have a decreased sensitivity to pain. Many also have a reduced ability to sweat, which can lead to a greater risk of overheating and dehydration. Some people with this condition have episodes of frequent vomiting and nausea (cyclic vomiting) and backflow of stomach acids into the esophagus (gastroesophageal reflux).  People with 22q13.3 deletion syndrome typically have distinctive facial features, including a long, narrow head; prominent ears; a pointed chin; droopy eyelids (ptosis); and deep-set eyes. Other physical features seen with this condition include large and fleshy hands and/or feet, a fusion of the second and third toes (syndactyly), and small or abnormal toenails. Some affected individuals have rapid (accelerated) growth. </s>


Input: How many people are affected by 22q13.3 deletion syndrome ?

Output: At least 500 cases of 22q13.3 deletion syndrome are known. </s>


Input: What are the genetic changes related to 22q13.3 deletion syndrome ?

Output: 22q13.3 deletion syndrome is caused by a deletion near the end of the long (q) arm of chromosome 22. The signs and symptoms of 22q13.3 deletion syndrome are probably related to the loss of multiple genes in this region. The size of the deletion varies among affected individuals.  A ring chromosome 22 can also cause 22q13.3 deletion syndrome. A ring chromosome is a circular structure that occurs when a chromosome breaks in two places, the tips of the chromosome are lost, and the broken ends fuse together. People with ring chromosome 22 have one copy of this abnormal chromosome in some or all of their cells. Researchers believe that several critical genes near the end of the long (q) arm of chromosome 22 are lost when the ring chromosome 22 forms. If one of the chromosome break points is at position 22q13.3, people with ring chromosome 22 have similar signs and symptoms as those with a simple deletion.  Researchers are working to identify all of the genes that contribute to the features of 22q13.3 deletion syndrome. They have determined that the loss of a particular gene on chromosome 22, SHANK3, is likely to be responsible for many of the syndrome's characteristic signs (such as developmental delay, intellectual disability, and impaired speech). Additional genes in the deleted region probably contribute to the varied features of 22q13.3 deletion syndrome. </s>


Input: Is 22q13.3 deletion syndrome inherited ?

Output: Most cases of 22q13.3 deletion syndrome are not inherited. The deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family, though they can pass the chromosome deletion to their children.  When 22q13.3 deletion syndrome is inherited, its inheritance pattern is considered autosomal dominant because a deletion in one copy of chromosome 22 in each cell is sufficient to cause the condition. About 15 to 20 percent of people with 22q13.3 deletion syndrome inherit a chromosome abnormality from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which a segment from one chromosome has traded places with a segment from another chromosome, but no genetic material is gained or lost. Balanced translocations usually do not cause any health problems; however, they can become unbalanced as they are passed to the next generation. Children who inherit an unbalanced translocation can have a chromosomal rearrangement with extra or missing genetic material. Individuals with 22q13.3 deletion syndrome who inherit an unbalanced translocation are missing genetic material from the long arm of chromosome 22, which results in the health problems characteristic of this disorder. </s>


Input: What are the treatments for 22q13.3 deletion syndrome ?

Output: These resources address the diagnosis or management of 22q13.3 deletion syndrome:  - Gene Review: Gene Review: Phelan-McDermid Syndrome  - Genetic Testing Registry: 22q13.3 deletion syndrome  - MedlinePlus Encyclopedia: Sweating--absent   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) ALG6-congenital disorder of glycosylation ?

Output: ALG6-congenital disorder of glycosylation (ALG6-CDG, also known as congenital disorder of glycosylation type Ic) is an inherited condition that affects many parts of the body. The signs and symptoms of ALG6-CDG vary widely among people with the condition.  Individuals with ALG6-CDG typically develop signs and symptoms of the condition during infancy. They may have difficulty gaining weight and growing at the expected rate (failure to thrive). Affected infants often have weak muscle tone (hypotonia) and developmental delay.  People with ALG6-CDG may have seizures, problems with coordination and balance (ataxia), or stroke-like episodes that involve an extreme lack of energy (lethargy) and temporary paralysis. They may also develop blood clotting disorders. Some individuals with ALG6-CDG have eye abnormalities including eyes that do not look in the same direction (strabismus) and an eye disorder called retinitis pigmentosa, which causes vision loss. Females with ALG6-CDG have hypergonadotropic hypogonadism, which affects the production of hormones that direct sexual development. As a result, most females with ALG6-CDG do not go through puberty. </s>


Input: How many people are affected by ALG6-congenital disorder of glycosylation ?

Output: The prevalence of ALG6-CDG is unknown, but it is thought to be the second most common type of congenital disorder of glycosylation. More than 30 cases of ALG6-CDG have been described in the scientific literature. </s>


Input: What are the genetic changes related to ALG6-congenital disorder of glycosylation ?

Output: ALG6-CDG is caused by mutations in the ALG6 gene. This gene provides instructions for making an enzyme that is involved in a process called glycosylation. Glycosylation is the process by which sugar molecules (monosaccharides) and complex chains of sugar molecules (oligosaccharides) are added to proteins and fats. Glycosylation modifies proteins and fats so they can perform a wider variety of functions. The enzyme produced from the ALG6 gene transfers a simple sugar called glucose to the growing oligosaccharide. Once the correct number of sugar molecules are linked together, the oligosaccharide is attached to a protein or fat.  ALG6 gene mutations lead to the production of an abnormal enzyme with reduced or no activity. Without a properly functioning enzyme, glycosylation cannot proceed normally, and oligosaccharides are incomplete. As a result, glycosylation is reduced or absent. The wide variety of signs and symptoms in ALG6-CDG are likely due to impaired glycosylation of proteins and fats that are needed for normal function in many organs and tissues, including the brain, eyes, liver, and hormone-producing (endocrine) system. </s>


Input: Is ALG6-congenital disorder of glycosylation inherited ?

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


Input: What are the treatments for ALG6-congenital disorder of glycosylation ?

Output: These resources address the diagnosis or management of ALG6-CDG:  - Gene Review: Gene Review: Congenital Disorders of N-Linked Glycosylation Pathway Overview   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) sialuria ?

Output: Sialuria is a rare disorder that has variable effects on development. Affected infants are often born with a yellow tint to the skin and the whites of the eyes (neonatal jaundice), an enlarged liver and spleen (hepatosplenomegaly), and unusually small red blood cells (microcytic anemia). They may develop a somewhat flat face and distinctive-looking facial features that are described as "coarse." Temporarily delayed development and weak muscle tone (hypotonia) have also been reported.  Young children with sialuria tend to have frequent upper respiratory infections and episodes of dehydration and stomach upset (gastroenteritis). Older children may have seizures and learning difficulties. In some affected children, intellectual development is nearly normal.  The features of sialuria vary widely among affected people. Many of the problems associated with this disorder appear to improve with age, although little is known about the long-term effects of the disease. It is likely that some adults with sialuria never come to medical attention because they have very mild signs and symptoms or no health problems related to the condition. </s>


Input: How many people are affected by sialuria ?

Output: Fewer than 10 people worldwide have been diagnosed with sialuria. There are probably more people with the disorder who have not been diagnosed, as sialuria can be difficult to detect because of its variable features. </s>


Input: What are the genetic changes related to sialuria ?

Output: Mutations in the GNE gene cause sialuria. The GNE gene provides instructions for making an enzyme found in cells and tissues throughout the body. This enzyme is involved in a chemical pathway that produces sialic acid, which is a simple sugar that attaches to the ends of more complex molecules on the surface of cells. By modifying these molecules, sialic acid influences a wide variety of cellular functions including cell movement (migration), attachment of cells to one another (adhesion), signaling between cells, and inflammation.  The enzyme produced from the GNE gene is carefully controlled to ensure that cells produce an appropriate amount of sialic acid. A feedback system shuts off the enzyme when no more sialic acid is needed. The mutations responsible for sialuria disrupt this feedback mechanism, resulting in an overproduction of sialic acid. This simple sugar builds up within cells and is excreted in urine. Researchers are working to determine how an accumulation of sialic acid in the body interferes with normal development in people with sialuria. </s>


Input: Is sialuria inherited ?

Output: This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most reported cases have occurred in people with no known history of the disorder in their family and may result from new mutations in the gene. </s>


Input: What are the treatments for sialuria ?

Output: These resources address the diagnosis or management of sialuria:  - Gene Review: Gene Review: Sialuria  - Genetic Testing Registry: Sialuria  - MedlinePlus Encyclopedia: Hepatosplenomegaly (image)  - MedlinePlus Encyclopedia: Newborn Jaundice   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) Schindler disease ?

Output: Schindler disease is an inherited disorder that primarily causes neurological problems.  There are three types of Schindler disease. Schindler disease type I, also called the infantile type, is the most severe form. Babies with Schindler disease type I appear healthy at birth, but by the age of 8 to 15 months they stop developing new skills and begin losing skills they had already acquired (developmental regression). As the disorder progresses, affected individuals develop blindness and seizures, and eventually they lose awareness of their surroundings and become unresponsive. People with this form of the disorder usually do not survive past early childhood.  Schindler disease type II, also called Kanzaki disease, is a milder form of the disorder that usually appears in adulthood. Affected individuals may develop mild cognitive impairment and hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss). They may experience weakness and loss of sensation due to problems with the nerves connecting the brain and spinal cord to muscles and sensory cells (peripheral nervous system). Clusters of enlarged blood vessels that form small, dark red spots on the skin (angiokeratomas) are characteristic of this form of the disorder.  Schindler disease type III is intermediate in severity between types I and II. Affected individuals may exhibit signs and symptoms beginning in infancy, including developmental delay, seizures, a weakened and enlarged heart (cardiomyopathy), and an enlarged liver (hepatomegaly). In other cases, people with this form of the disorder exhibit behavioral problems beginning in early childhood, with some features of autism spectrum disorders. Autism spectrum disorders are characterized by impaired communication and socialization skills. </s>


Input: How many people are affected by Schindler disease ?

Output: Schindler disease is very rare. Only a few individuals with each type of the disorder have been identified. </s>


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

Output: Mutations in the NAGA gene cause Schindler disease. The NAGA gene provides instructions for making the enzyme alpha-N-acetylgalactosaminidase. This enzyme works in the lysosomes, which are compartments within cells that digest and recycle materials. Within lysosomes, the enzyme helps break down complexes called glycoproteins and glycolipids, which consist of sugar molecules attached to certain proteins and fats. Specifically, alpha-N-acetylgalactosaminidase helps remove a molecule called alpha-N-acetylgalactosamine from sugars in these complexes.  Mutations in the NAGA gene interfere with the ability of the alpha-N-acetylgalactosaminidase enzyme to perform its role in breaking down glycoproteins and glycolipids. These substances accumulate in the lysosomes and cause cells to malfunction and eventually die. Cell damage in the nervous system and other tissues and organs of the body leads to the signs and symptoms of Schindler disease. </s>


Input: Is Schindler disease inherited ?

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


Input: What are the treatments for Schindler disease ?

Output: These resources address the diagnosis or management of Schindler disease:  - Genetic Testing Registry: Kanzaki disease  - Genetic Testing Registry: Schindler disease, type 1   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>