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What are the genetic changes related to microphthalmia with linear skin defects syndrome ?
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Mutations in the HCCS gene or a deletion of genetic material that includes the HCCS gene cause microphthalmia with linear skin defects syndrome. The HCCS gene carries instructions for producing an enzyme called holocytochrome c-type synthase. This enzyme is active in many tissues of the body and is found in the mitochondria, the energy-producing centers within cells. Within the mitochondria, the holocytochrome c-type synthase enzyme helps produce a molecule called cytochrome c. Cytochrome c is involved in a process called oxidative phosphorylation, by which mitochondria generate adenosine triphosphate (ATP), the cell's main energy source. It also plays a role in the self-destruction of cells (apoptosis). HCCS gene mutations result in a holocytochrome c-type synthase enzyme that cannot perform its function. A deletion of genetic material that includes the HCCS gene prevents the production of the enzyme. A lack of functional holocytochrome c-type synthase enzyme can damage cells by impairing their ability to generate energy. In addition, without the holocytochrome c-type synthase enzyme, the damaged cells may not be able to undergo apoptosis. These cells may instead die in a process called necrosis that causes inflammation and damages neighboring cells. During early development this spreading cell damage may lead to the eye abnormalities and other signs and symptoms of microphthalmia with linear skin defects syndrome.
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Is microphthalmia with linear skin defects syndrome inherited ?
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This condition is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. Some cells produce a normal amount of the holocytochrome c-type synthase enzyme and other cells produce none. The resulting overall reduction in the amount of this enzyme leads to the signs and symptoms of microphthalmia with linear skin defects syndrome. In males (who have only one X chromosome), mutations result in a total loss of the holocytochrome c-type synthase enzyme. A lack of this enzyme appears to be lethal very early in development, so almost no males are born with microphthalmia with linear skin defects syndrome. A few affected individuals with male appearance but who have two X chromosomes have been identified. Most cases of microphthalmia with linear skin defects syndrome occur in people with no history of the disorder in their family. These cases usually result from the deletion of a segment of the X chromosome during the formation of reproductive cells (eggs and sperm) or in early fetal development. They may also result from a new mutation in the HCCS gene.
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What are the treatments for microphthalmia with linear skin defects syndrome ?
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These resources address the diagnosis or management of microphthalmia with linear skin defects syndrome: - Gene Review: Gene Review: Microphthalmia with Linear Skin Defects Syndrome - Genetic Testing Registry: Microphthalmia, syndromic, 7 These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) color vision deficiency ?
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Color vision deficiency (sometimes called color blindness) represents a group of conditions that affect the perception of color. Red-green color vision defects are the most common form of color vision deficiency. Affected individuals have trouble distinguishing between some shades of red, yellow, and green. Blue-yellow color vision defects (also called tritan defects), which are rarer, cause problems with differentiating shades of blue and green and cause difficulty distinguishing dark blue from black. These two forms of color vision deficiency disrupt color perception but do not affect the sharpness of vision (visual acuity). A less common and more severe form of color vision deficiency called blue cone monochromacy causes very poor visual acuity and severely reduced color vision. Affected individuals have additional vision problems, which can include increased sensitivity to light (photophobia), involuntary back-and-forth eye movements (nystagmus), and nearsightedness (myopia). Blue cone monochromacy is sometimes considered to be a form of achromatopsia, a disorder characterized by a partial or total lack of color vision with other vision problems.
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How many people are affected by color vision deficiency ?
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Red-green color vision defects are the most common form of color vision deficiency. This condition affects males much more often than females. Among populations with Northern European ancestry, it occurs in about 1 in 12 males and 1 in 200 females. Red-green color vision defects have a lower incidence in almost all other populations studied. Blue-yellow color vision defects affect males and females equally. This condition occurs in fewer than 1 in 10,000 people worldwide. Blue cone monochromacy is rarer than the other forms of color vision deficiency, affecting about 1 in 100,000 people worldwide. Like red-green color vision defects, blue cone monochromacy affects males much more often than females.
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What are the genetic changes related to color vision deficiency ?
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Mutations in the OPN1LW, OPN1MW, and OPN1SW genes cause the forms of color vision deficiency described above. The proteins produced from these genes play essential roles in color vision. They are found in the retina, which is the light-sensitive tissue at the back of the eye. The retina contains two types of light receptor cells, called rods and cones, that transmit visual signals from the eye to the brain. Rods provide vision in low light. Cones provide vision in bright light, including color vision. There are three types of cones, each containing a specific pigment (a photopigment called an opsin) that is most sensitive to particular wavelengths of light. The brain combines input from all three types of cones to produce normal color vision. The OPN1LW, OPN1MW, and OPN1SW genes provide instructions for making the three opsin pigments in cones. The opsin made from the OPN1LW gene is more sensitive to light in the yellow/orange part of the visible spectrum (long-wavelength light), and cones with this pigment are called long-wavelength-sensitive or L cones. The opsin made from the OPN1MW gene is more sensitive to light in the middle of the visible spectrum (yellow/green light), and cones with this pigment are called middle-wavelength-sensitive or M cones. The opsin made from the OPN1SW gene is more sensitive to light in the blue/violet part of the visible spectrum (short-wavelength light), and cones with this pigment are called short-wavelength-sensitive or S cones. Genetic changes involving the OPN1LW or OPN1MW gene cause red-green color vision defects. These changes lead to an absence of L or M cones or to the production of abnormal opsin pigments in these cones that affect red-green color vision. Blue-yellow color vision defects result from mutations in the OPN1SW gene. These mutations lead to the premature destruction of S cones or the production of defective S cones. Impaired S cone function alters perception of the color blue, making it difficult or impossible to detect differences between shades of blue and green and causing problems with distinguishing dark blue from black. Blue cone monochromacy occurs when genetic changes affecting the OPN1LW and OPN1MW genes prevent both L and M cones from functioning normally. In people with this condition, only S cones are functional, which leads to reduced visual acuity and poor color vision. The loss of L and M cone function also underlies the other vision problems in people with blue cone monochromacy. Some problems with color vision are not caused by gene mutations. These nonhereditary conditions are described as acquired color vision deficiencies. They can be caused by other eye disorders, such as diseases involving the retina, the nerve that carries visual information from the eye to the brain (the optic nerve), or areas of the brain involved in processing visual information. Acquired color vision deficiencies can also be side effects of certain drugs, such as chloroquine (which is used to treat malaria), or result from exposure to particular chemicals, such as organic solvents.
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Is color vision deficiency inherited ?
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Red-green color vision defects and blue cone monochromacy are inherited in an X-linked recessive pattern. The OPN1LW and OPN1MW genes are located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one genetic change in each cell is sufficient to cause the condition. Males are affected by X-linked recessive disorders much more frequently than females because in females (who have two X chromosomes), a genetic change would have to occur on both copies of the chromosome to cause the disorder. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. Blue-yellow color vision defects are inherited in an autosomal dominant pattern, which means one copy of the altered OPN1SW gene in each cell is sufficient to cause the condition. In many cases, an affected person inherits the condition from an affected parent.
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What are the treatments for color vision deficiency ?
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These resources address the diagnosis or management of color vision deficiency: - Gene Review: Gene Review: Red-Green Color Vision Defects - Genetic Testing Registry: Colorblindness, partial, deutan series - Genetic Testing Registry: Cone monochromatism - Genetic Testing Registry: Protan defect - Genetic Testing Registry: Red-green color vision defects - Genetic Testing Registry: Tritanopia - MedlinePlus Encyclopedia: Color Vision Test - MedlinePlus Encyclopedia: Colorblind 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
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What is (are) Dandy-Walker malformation ?
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Dandy-Walker malformation affects brain development, primarily development of the cerebellum, which is the part of the brain that coordinates movement. In individuals with this condition, various parts of the cerebellum develop abnormally, resulting in malformations that can be observed with medical imaging. The central part of the cerebellum (the vermis) is absent or very small and may be abnormally positioned. The right and left sides of the cerebellum may be small as well. In affected individuals, a fluid-filled cavity between the brainstem and the cerebellum (the fourth ventricle) and the part of the skull that contains the cerebellum and the brainstem (the posterior fossa) are abnormally large. These abnormalities often result in problems with movement, coordination, intellect, mood, and other neurological functions. In the majority of individuals with Dandy-Walker malformation, signs and symptoms caused by abnormal brain development are present at birth or develop within the first year of life. Some children have a buildup of fluid in the brain (hydrocephalus) that may cause increased head size (macrocephaly). Up to half of affected individuals have intellectual disability that ranges from mild to severe, and those with normal intelligence may have learning disabilities. Children with Dandy-Walker malformation often have delayed development, particularly a delay in motor skills such as crawling, walking, and coordinating movements. People with Dandy-Walker malformation may experience muscle stiffness and partial paralysis of the lower limbs (spastic paraplegia), and they may also have seizures. While rare, hearing and vision problems can be features of this condition. Less commonly, other brain abnormalities have been reported in people with Dandy-Walker malformation. These abnormalities include an underdeveloped or absent tissue connecting the left and right halves of the brain (agenesis of the corpus callosum), a sac-like protrusion of the brain through an opening at the back of the skull (occipital encephalocele), or a failure of some nerve cells (neurons) to migrate to their proper location in the brain during development. These additional brain malformations are associated with more severe signs and symptoms. Dandy-Walker malformation typically affects only the brain, but problems in other systems can include heart defects, malformations of the urogenital tract, extra fingers or toes (polydactyly) or fused fingers or toes (syndactyly), or abnormal facial features. In 10 to 20 percent of people with Dandy-Walker malformation, signs and symptoms of the condition do not appear until late childhood or into adulthood. These individuals typically have a different range of features than those affected in infancy, including headaches, an unsteady walking gait, paralysis of facial muscles (facial palsy), increased muscle tone, muscle spasms, and mental and behavioral changes. Rarely, people with Dandy-Walker malformation have no health problems related to the condition. Problems related to hydrocephalus or complications of its treatment are the most common cause of death in people with Dandy-Walker malformation.
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How many people are affected by Dandy-Walker malformation ?
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Dandy-Walker malformation is estimated to affect 1 in 10,000 to 30,000 newborns.
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What are the genetic changes related to Dandy-Walker malformation ?
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Researchers have found mutations in a few genes that are thought to cause Dandy-Walker malformation, but these mutations account for only a small number of cases. Dandy-Walker malformation has also been associated with many chromosomal abnormalities. This condition can be a feature of some conditions in which there is an extra copy of one chromosome in each cell (trisomy). Dandy-Walker malformation most often occurs in people with trisomy 18 (an extra copy of chromosome 18), but can also occur in people with trisomy 13, trisomy 21, or trisomy 9. This condition can also be associated with missing (deletions) or copied (duplications) pieces of certain chromosomes. Dandy-Walker malformation can also be a feature of genetic syndromes that are caused by mutations in specific genes. However, the brain malformations associated with Dandy-Walker malformation often occur as an isolated feature (not associated with other health problems), and in these cases the cause is frequently unknown. Research suggests that Dandy-Walker malformation could be caused by environmental factors that affect early development before birth. For example, exposure of the fetus to substances that cause birth defects (teratogens) may be involved in the development of this condition. In addition, a mother with diabetes is more likely than a healthy mother to have a child with Dandy-Walker malformation.
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Is Dandy-Walker malformation inherited ?
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Most cases of Dandy-Walker malformation are sporadic, which means they occur in people with no history of the disorder in their family. A small percentage of cases seem to run in families; however, Dandy-Walker malformation does not have a clear pattern of inheritance. Multiple genetic and environmental factors likely play a part in determining the risk of developing this disorder. First-degree relatives (such as siblings and children) of people with Dandy-Walker malformation have an increased risk of developing the condition compared with people in the general population. When Dandy-Walker malformation is a feature of a genetic condition, it is inherited in the pattern of that condition.
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What are the treatments for Dandy-Walker malformation ?
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These resources address the diagnosis or management of Dandy-Walker malformation: - Genetic Testing Registry: Dandy-Walker syndrome - National Hydrocephalus Foundation: Treatment of Hydrocephalus 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
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What is (are) factor XIII deficiency ?
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Factor XIII deficiency is a rare bleeding disorder. Researchers have identified an inherited form and a less severe form that is acquired during a person's lifetime. Signs and symptoms of inherited factor XIII deficiency begin soon after birth, usually with abnormal bleeding from the umbilical cord stump. If the condition is not treated, affected individuals may have episodes of excessive and prolonged bleeding that can be life-threatening. Abnormal bleeding can occur after surgery or minor trauma. The condition can also cause spontaneous bleeding into the joints or muscles, leading to pain and disability. Women with inherited factor XIII deficiency tend to have heavy or prolonged menstrual bleeding (menorrhagia) and may experience recurrent pregnancy losses (miscarriages). Other signs and symptoms of inherited factor XIII deficiency include nosebleeds, bleeding of the gums, easy bruising, problems with wound healing, and abnormal scar formation. Inherited factor XIII deficiency also increases the risk of spontaneous bleeding inside the skull (intracranial hemorrhage), which is the leading cause of death in people with this condition. Acquired factor XIII deficiency becomes apparent later in life. People with the acquired form are less likely to have severe or life-threatening episodes of abnormal bleeding than those with the inherited form.
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How many people are affected by factor XIII deficiency ?
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Inherited factor XIII deficiency affects 1 to 3 per million people worldwide. Researchers suspect that mild factor XIII deficiency, including the acquired form of the disorder, is underdiagnosed because many affected people never have a major episode of abnormal bleeding that would lead to a diagnosis.
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What are the genetic changes related to factor XIII deficiency ?
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Inherited factor XIII deficiency results from mutations in the F13A1 gene or, less commonly, the F13B gene. These genes provide instructions for making the two parts (subunits) of a protein called factor XIII. This protein plays a critical role in the coagulation cascade, which is a series of chemical reactions that forms blood clots in response to injury. After an injury, clots seal off blood vessels to stop bleeding and trigger blood vessel repair. Factor XIII acts at the end of the cascade to strengthen and stabilize newly formed clots, preventing further blood loss. Mutations in the F13A1 or F13B gene significantly reduce the amount of functional factor XIII available to participate in blood clotting. In most people with the inherited form of the condition, factor XIII levels in the bloodstream are less than 5 percent of normal. A loss of this protein's activity weakens blood clots, preventing the clots from stopping blood loss effectively. The acquired form of factor XIII deficiency results when the production of factor XIII is reduced or when the body uses factor XIII faster than cells can replace it. Acquired factor XIII deficiency is generally mild because levels of factor XIII in the bloodstream are 20 to 70 percent of normal; levels above 10 percent of normal are usually adequate to prevent spontaneous bleeding episodes. Acquired factor XIII deficiency can be caused by disorders including an inflammatory disease of the liver called hepatitis, scarring of the liver (cirrhosis), inflammatory bowel disease, overwhelming bacterial infections (sepsis), and several types of cancer. Acquired factor XIII deficiency can also be caused by abnormal activation of the immune system, which produces specialized proteins called autoantibodies that attack and disable the factor XIII protein. The production of autoantibodies against factor XIII is sometimes associated with immune system diseases such as systemic lupus erythematosus and rheumatoid arthritis. In other cases, the trigger for autoantibody production is unknown.
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Is factor XIII deficiency inherited ?
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Inherited factor XIII deficiency is considered to have an autosomal recessive pattern of inheritance, which means that it results when both copies of either the F13A1 gene or the F13B gene in each cell have mutations. Some people, including parents of individuals with factor XIII deficiency, carry a single mutated copy of the F13A1 or F13B gene in each cell. These mutation carriers have a reduced amount of factor XIII in their bloodstream (20 to 60 percent of normal), and they may experience abnormal bleeding after surgery, dental work, or major trauma. However, most people who carry one mutated copy of the F13A1 or F13B gene do not have abnormal bleeding episodes under normal circumstances, and so they never come to medical attention. The acquired form of factor XIII deficiency is not inherited and does not run in families.
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What are the treatments for factor XIII deficiency ?
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These resources address the diagnosis or management of factor XIII deficiency: - Genetic Testing Registry: Factor xiii, a subunit, deficiency of - Genetic Testing Registry: Factor xiii, b subunit, deficiency of 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
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What is (are) FOXG1 syndrome ?
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FOXG1 syndrome is a condition characterized by impaired development and structural brain abnormalities. Affected infants are small at birth, and their heads grow more slowly than normal, leading to an unusually small head size (microcephaly) by early childhood. The condition is associated with a particular pattern of brain malformations that includes a thin or underdeveloped connection between the right and left halves of the brain (a structure called the corpus callosum), reduced folds and grooves (gyri) on the surface of the brain, and a smaller than usual amount of brain tissue known as white matter. FOXG1 syndrome affects most aspects of development, and children with the condition typically have severe intellectual disability. Abnormal or involuntary movements, such as jerking movements of the arms and legs and repeated hand motions, are common, and most affected children do not learn to sit or walk without assistance. Babies and young children with FOXG1 syndrome often have feeding problems, sleep disturbances, seizures, irritability, and excessive crying. The condition is also characterized by limited communication and social interaction, including poor eye contact and a near absence of speech and language skills. Because of these social impairments, FOXG1 syndrome is classified as an autism spectrum disorder. FOXG1 syndrome was previously described as a congenital variant of Rett syndrome, which is a similar disorder of brain development. Both disorders are characterized by impaired development, intellectual disability, and problems with communication and language. However, Rett syndrome is diagnosed almost exclusively in females, while FOXG1 syndrome affects both males and females. Rett syndrome also involves a period of apparently normal early development that does not occur in FOXG1 syndrome. Because of these differences, physicians and researchers now usually consider FOXG1 syndrome to be distinct from Rett syndrome.
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How many people are affected by FOXG1 syndrome ?
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FOXG1 syndrome appears to be rare. At least 30 affected individuals have been described in the medical literature.
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What are the genetic changes related to FOXG1 syndrome ?
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As its name suggests, FOXG1 syndrome is caused by changes involving the FOXG1 gene. This gene provides instructions for making a protein called forkhead box G1. This protein plays an important role in brain development before birth, particularly in a region of the embryonic brain known as the telencephalon. The telencephalon ultimately develops into several critical structures, including the the largest part of the brain (the cerebrum), which controls most voluntary activity, language, sensory perception, learning, and memory. In some cases, FOXG1 syndrome is caused by mutations within the FOXG1 gene itself. In others, the condition results from a deletion of genetic material from a region of the long (q) arm of chromosome 14 that includes the FOXG1 gene. All of these genetic changes prevent the production of forkhead box G1 or impair the protein's function. A shortage of functional forkhead box G1 disrupts normal brain development starting before birth, which appears to underlie the structural brain abnormalities and severe developmental problems characteristic of FOXG1 syndrome.
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Is FOXG1 syndrome inherited ?
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FOXG1 syndrome is considered an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. All reported cases have resulted from new mutations or deletions involving the FOXG1 gene and have occurred in people with no history of the disorder in their family. Because the condition is so severe, no one with FOXG1 syndrome has been known to have children.
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What are the treatments for FOXG1 syndrome ?
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These resources address the diagnosis or management of FOXG1 syndrome: - Genetic Testing Registry: Rett syndrome, congenital variant 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
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What is (are) acute promyelocytic leukemia ?
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Acute promyelocytic leukemia is a form of acute myeloid leukemia, a cancer of the blood-forming tissue (bone marrow). In normal bone marrow, hematopoietic stem cells produce red blood cells (erythrocytes) that carry oxygen, white blood cells (leukocytes) that protect the body from infection, and platelets (thrombocytes) that are involved in blood clotting. In acute promyelocytic leukemia, immature white blood cells called promyelocytes accumulate in the bone marrow. The overgrowth of promyelocytes leads to a shortage of normal white and red blood cells and platelets in the body, which causes many of the signs and symptoms of the condition. People with acute promyelocytic leukemia are especially susceptible to developing bruises, small red dots under the skin (petechiae), nosebleeds, bleeding from the gums, blood in the urine (hematuria), or excessive menstrual bleeding. The abnormal bleeding and bruising occur in part because of the low number of platelets in the blood (thrombocytopenia) and also because the cancerous cells release substances that cause excessive bleeding. The low number of red blood cells (anemia) can cause people with acute promyelocytic leukemia to have pale skin (pallor) or excessive tiredness (fatigue). In addition, affected individuals may heal slowly from injuries or have frequent infections due to the loss of normal white blood cells that fight infection. Furthermore, the leukemic cells can spread to the bones and joints, which may cause pain in those areas. Other general signs and symptoms may occur as well, such as fever, loss of appetite, and weight loss. Acute promyelocytic leukemia is most often diagnosed around age 40, although it can be diagnosed at any age.
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How many people are affected by acute promyelocytic leukemia ?
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Acute promyelocytic leukemia accounts for about 10 percent of acute myeloid leukemia cases. Acute promyelocytic leukemia occurs in approximately 1 in 250,000 people in the United States.
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What are the genetic changes related to acute promyelocytic leukemia ?
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The mutation that causes acute promyelocytic leukemia involves two genes, the PML gene on chromosome 15 and the RARA gene on chromosome 17. A rearrangement of genetic material (translocation) between chromosomes 15 and 17, written as t(15;17), fuses part of the PML gene with part of the RARA gene. The protein produced from this fused gene is known as PML-RAR. This mutation is acquired during a person's lifetime and is present only in certain cells. This type of genetic change, called a somatic mutation, is not inherited. The PML-RAR protein functions differently than the protein products of the normal PML and RARA genes. The protein produced from the RARA gene, RAR, is involved in the regulation of gene transcription, which is the first step in protein production. Specifically, this protein helps control the transcription of certain genes important in the maturation (differentiation) of white blood cells beyond the promyelocyte stage. The protein produced from the PML gene acts as a tumor suppressor, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way. The PML-RAR protein interferes with the normal function of both the PML and the RAR proteins. As a result, blood cells are stuck at the promyelocyte stage, and they proliferate abnormally. Excess promyelocytes accumulate in the bone marrow and normal white blood cells cannot form, leading to acute promyelocytic leukemia. The PML-RARA gene fusion accounts for up to 98 percent of cases of acute promyelocytic leukemia. Translocations involving the RARA gene and other genes have been identified in a few cases of acute promyelocytic leukemia.
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Is acute promyelocytic leukemia inherited ?
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Acute promyelocytic leukemia is not inherited but arises from a translocation in the body's cells that occurs after conception.
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What are the treatments for acute promyelocytic leukemia ?
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These resources address the diagnosis or management of acute promyelocytic leukemia: - American Cancer Society: Diagnosis of Acute Myeloid Leukemia - American Cancer Society: Treatment of Acute Promyelocytic (M3) Leukemia - Genetic Testing Registry: Acute promyelocytic leukemia - MedlinePlus Encyclopedia: Acute Myeloid Leukemia - National Cancer Institute: Adult Acute Myeloid Leukemia Treatment - National Cancer Institute: Leukemia - National Heart Lung and Blood Institute: Bone Marrow Tests These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) C3 glomerulopathy ?
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C3 glomerulopathy is a group of related conditions that cause the kidneys to malfunction. The major features of C3 glomerulopathy include high levels of protein in the urine (proteinuria), blood in the urine (hematuria), reduced amounts of urine, low levels of protein in the blood, and swelling in many areas of the body. Affected individuals may have particularly low levels of a protein called complement component 3 (or C3) in the blood. The kidney problems associated with C3 glomerulopathy tend to worsen over time. About half of affected individuals develop end-stage renal disease (ESRD) within 10 years after their diagnosis. ESRD is a life-threatening condition that prevents the kidneys from filtering fluids and waste products from the body effectively. Researchers have identified two major forms of C3 glomerulopathy: dense deposit disease and C3 glomerulonephritis. Although the two disorders cause similar kidney problems, the features of dense deposit disease tend to appear earlier than those of C3 glomerulonephritis, usually in adolescence. However, the signs and symptoms of either disease may not begin until adulthood. One of the two forms of C3 glomerulopathy, dense deposit disease, can also be associated with other conditions unrelated to kidney function. For example, people with dense deposit disease may have acquired partial lipodystrophy, a condition characterized by a lack of fatty (adipose) tissue under the skin in the upper part of the body. Additionally, some people with dense deposit disease develop a buildup of yellowish deposits called drusen in the light-sensitive tissue at the back of the eye (the retina). These deposits usually appear in childhood or adolescence and can cause vision problems later in life.
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How many people are affected by C3 glomerulopathy ?
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C3 glomerulopathy is very rare, affecting 1 to 2 per million people worldwide. It is equally common in men and women.
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What are the genetic changes related to C3 glomerulopathy ?
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C3 glomerulopathy is associated with changes in many genes. Most of these genes provide instructions for making proteins that help regulate a part of the body's immune response known as the complement system. This system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. The complement system must be carefully regulated so it targets only unwanted materials and does not damage the body's healthy cells. A specific mutation in one of the complement system-related genes, CFHR5, has been found to cause C3 glomerulopathy in people from the Mediterranean island of Cyprus. Mutation in the C3 and CFH genes, as well as other complement system-related genes, have been found to cause the condition in other populations. The known mutations account for only a small percentage of all cases of C3 glomerulopathy. In most cases, the cause of the condition is unknown. Several normal variants (polymorphisms) in complement system-related genes are associated with an increased likelihood of developing C3 glomerulopathy. In some cases, the increased risk is related to a group of specific variants in several genes, a combination known as a C3 glomerulopathy at-risk haplotype. While these polymorphisms increase the risk of C3 glomerulopathy, many people who inherit these genetic changes will never develop the condition. The genetic changes related to C3 glomerulopathy "turn up," or increase the activation of, the complement system. The overactive system damages structures called glomeruli in the kidneys. These structures are clusters of tiny blood vessels that help filter waste products from the blood. Damage to glomeruli prevents the kidneys from filtering waste products normally and can lead to ESRD. Studies suggest that uncontrolled activation of the complement system also causes the other health problems that can occur with dense deposit disease, including acquired partial lipodystrophy and a buildup of drusen in the retina. Researchers are working to determine how these associated health problems are related to overactivity of the complement system. Studies suggest that C3 glomerulopathy can also result from the presence of specialized proteins called autoantibodies. Autoantibodies cause the condition by altering the activity of proteins involved in regulating the complement system.
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Is C3 glomerulopathy inherited ?
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Most cases of C3 glomerulopathy are sporadic, which means they occur in people with no history of the disorder in their family. Only a few reported families have had more than one family member with C3 glomerulopathy. However, many affected people have had close relatives with autoimmune diseases, which occur when the immune system malfunctions and attacks the body's tissues and organs. The connection between C3 glomerulopathy and autoimmune diseases is not fully understood.
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What are the treatments for C3 glomerulopathy ?
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These resources address the diagnosis or management of C3 glomerulopathy: - Gene Review: Gene Review: Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II - Genetic Testing Registry: C3 Glomerulonephritis - Genetic Testing Registry: CFHR5 deficiency - Genetic Testing Registry: CFHR5-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II - Genetic Testing Registry: Factor H deficiency - Genetic Testing Registry: Mesangiocapillary glomerulonephritis, type II - National Institute of Diabetes and Digestive and Kidney Diseases: Kidney Failure: Choosing a Treatment That's Right for You 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
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What is (are) 2-hydroxyglutaric aciduria ?
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2-hydroxyglutaric aciduria is a condition that causes progressive damage to the brain. The major types of this disorder are called D-2-hydroxyglutaric aciduria (D-2-HGA), L-2-hydroxyglutaric aciduria (L-2-HGA), and combined D,L-2-hydroxyglutaric aciduria (D,L-2-HGA). The main features of D-2-HGA are delayed development, seizures, weak muscle tone (hypotonia), and abnormalities in the largest part of the brain (the cerebrum), which controls many important functions such as muscle movement, speech, vision, thinking, emotion, and memory. Researchers have described two subtypes of D-2-HGA, type I and type II. The two subtypes are distinguished by their genetic cause and pattern of inheritance, although they also have some differences in signs and symptoms. Type II tends to begin earlier and often causes more severe health problems than type I. Type II may also be associated with a weakened and enlarged heart (cardiomyopathy), a feature that is typically not found with type I. L-2-HGA particularly affects a region of the brain called the cerebellum, which is involved in coordinating movements. As a result, many affected individuals have problems with balance and muscle coordination (ataxia). Additional features of L-2-HGA can include delayed development, seizures, speech difficulties, and an unusually large head (macrocephaly). Typically, signs and symptoms of this disorder begin during infancy or early childhood. The disorder worsens over time, usually leading to severe disability by early adulthood. Combined D,L-2-HGA causes severe brain abnormalities that become apparent in early infancy. Affected infants have severe seizures, weak muscle tone (hypotonia), and breathing and feeding problems. They usually survive only into infancy or early childhood.
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How many people are affected by 2-hydroxyglutaric aciduria ?
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2-hydroxyglutaric aciduria is a rare disorder. D-2-HGA and L-2-HGA have each been reported to affect fewer than 150 individuals worldwide. Combined D,L-2-HGA appears to be even rarer, with only about a dozen reported cases.
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What are the genetic changes related to 2-hydroxyglutaric aciduria ?
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The different types of 2-hydroxyglutaric aciduria result from mutations in several genes. D-2-HGA type I is caused by mutations in the D2HGDH gene; type II is caused by mutations in the IDH2 gene. L-2-HGA results from mutations in the L2HGDH gene. Combined D,L-2-HGA is caused by mutations in the SLC25A1 gene. The D2HGDH and L2HGDH genes provide instructions for making enzymes that are found in mitochondria, which are the energy-producing centers within cells. The enzymes break down compounds called D-2-hydroxyglutarate and L-2-hydroxyglutarate, respectively, as part of a series of reactions that produce energy for cell activities. Mutations in either of these genes lead to a shortage of functional enzyme, which allows D-2-hydroxyglutarate or L-2-hydroxyglutarate to build up in cells. At high levels, these compounds can damage cells and lead to cell death. Brain cells appear to be the most vulnerable to the toxic effects of these compounds, which may explain why the signs and symptoms of D-2-HGA type I and L-2-HGA primarily involve the brain. The IDH2 gene provides instructions for making an enzyme in mitochondria that normally produces a different compound. When the enzyme is altered by mutations, it takes on a new, abnormal function: production of the potentially toxic compound D-2-hydroxyglutarate. The resulting excess of this compound damages brain cells, leading to the signs and symptoms of D-2-HGA type II. It is unclear why an accumulation of D-2-hydroxyglutarate may be associated with cardiomyopathy in some people with this form of the condition. The SLC25A1 gene provides instructions for making a protein that transports certain molecules, such as citrate, in and out of mitochondria. Mutations in the SLC25A1 gene reduce the protein's function, which prevents it from carrying out this transport. Through processes that are not fully understood, a loss of this transport allows both D-2-hydroxyglutarate and L-2-hydroxyglutarate to build up, which damages brain cells. Researchers suspect that an imbalance of other molecules, particularly citrate, also contributes to the severe signs and symptoms of combined D,L-2-HGA.
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Is 2-hydroxyglutaric aciduria inherited ?
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D-2-HGA type I, L-2-HGA, and combined D,L-2-HGA all have 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 mutated gene, but they typically do not show signs and symptoms of the condition. D-2-HGA type II is considered an autosomal dominant disorder because one copy of the altered gene in each cell is sufficient to cause the condition. The disorder typically results from a new mutation in the IDH2 gene and occurs in people with no history of the condition in their family.
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What are the treatments for 2-hydroxyglutaric aciduria ?
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These resources address the diagnosis or management of 2-hydroxyglutaric aciduria: - Genetic Testing Registry: Combined d-2- and l-2-hydroxyglutaric aciduria - Genetic Testing Registry: D-2-hydroxyglutaric aciduria 1 - Genetic Testing Registry: D-2-hydroxyglutaric aciduria 2 - Genetic Testing Registry: L-2-hydroxyglutaric aciduria 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
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What is (are) congenital central hypoventilation syndrome ?
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Congenital central hypoventilation syndrome (CCHS) is a disorder that affects breathing. People with this disorder take shallow breaths (hypoventilate), especially during sleep, resulting in a shortage of oxygen and a buildup of carbon dioxide in the blood. Ordinarily, the part of the nervous system that controls involuntary body processes (autonomic nervous system) would react to such an imbalance by stimulating the individual to breathe more deeply or wake up. This reaction is impaired in people with CCHS, and they must be supported with a machine to help them breathe (mechanical ventilation) or a device that stimulates a normal breathing pattern (diaphragm pacemaker). Some affected individuals need this support 24 hours a day, while others need it only at night. Symptoms of CCHS usually become apparent shortly after birth. Affected infants hypoventilate upon falling asleep and exhibit a bluish appearance of the skin or lips (cyanosis). Cyanosis is caused by lack of oxygen in the blood. In some milder cases, CCHS may be diagnosed later in life. In addition to the breathing problem, people with this disorder may have difficulty regulating their heart rate and blood pressure, for example in response to exercise or changes in body position. They may have abnormalities in the nerves that control the digestive tract (Hirschsprung disease), resulting in severe constipation, intestinal blockage, and enlargement of the colon. They are also at increased risk of developing certain tumors of the nervous system called neuroblastomas, ganglioneuromas, and ganglioneuroblastomas. Some affected individuals develop learning difficulties or other neurological problems, which may be worsened by oxygen deprivation if treatment to support their breathing is not completely effective. Individuals with CCHS usually have eye abnormalities, including a decreased response of the pupils to light. They also have decreased perception of pain, low body temperature, and occasional episodes of profuse sweating. People with CCHS, especially children, may have a characteristic appearance with a short, wide, somewhat flattened face often described as "box-shaped." Life expectancy and the extent of any cognitive disabilities depend on the severity of the disorder, timing of the diagnosis, and the success of treatment.
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How many people are affected by congenital central hypoventilation syndrome ?
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CCHS is a relatively rare disorder. Approximately 1,000 individuals with this condition have been identified. Researchers believe that some cases of sudden infant death syndrome (SIDS) or sudden unexplained death in children may be caused by undiagnosed CCHS.
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What are the genetic changes related to congenital central hypoventilation syndrome ?
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Mutations in the PHOX2B gene cause CCHS. The PHOX2B gene provides instructions for making a protein that acts early in development to help promote the formation of nerve cells (neurons) and regulate the process by which the neurons mature to carry out specific functions (differentiation). The protein is active in the neural crest, which is a group of cells in the early embryo that give rise to many tissues and organs. Neural crest cells migrate to form parts of the autonomic nervous system, many tissues in the face and skull, and other tissue and cell types. Mutations are believed to interfere with the PHOX2B protein's role in promoting neuron formation and differentiation, especially in the autonomic nervous system, resulting in the problems regulating breathing and other body functions that occur in CCHS.
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Is congenital central hypoventilation syndrome inherited ?
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This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. More than 90 percent of cases of CCHS result from new mutations in the PHOX2B gene. These cases occur in people with no history of the disorder in their family. Occasionally an affected person inherits the mutation from one affected parent. The number of such cases has been increasing as better treatment has allowed more affected individuals to live into adulthood. About 5 to 10 percent of affected individuals inherit the mutation from a seemingly unaffected parent with somatic mosaicism. Somatic mosaicism means that some of the body's cells have a PHOX2B gene mutation, and others do not. A parent with mosaicism for a PHOX2B gene mutation may not show any signs or symptoms of CCHS.
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What are the treatments for congenital central hypoventilation syndrome ?
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These resources address the diagnosis or management of CCHS: - Gene Review: Gene Review: Congenital Central Hypoventilation Syndrome - Genetic Testing Registry: Congenital central hypoventilation - MedlinePlus Encyclopedia: Hirschsprung's Disease These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) 22q11.2 duplication ?
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22q11.2 duplication is a condition caused by an extra copy of a small piece of chromosome 22. The duplication occurs near the middle of the chromosome at a location designated q11.2. The features of this condition vary widely, even among members of the same family. Affected individuals may have developmental delay, intellectual disability, slow growth leading to short stature, and weak muscle tone (hypotonia). Many people with the duplication have no apparent physical or intellectual disabilities.
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How many people are affected by 22q11.2 duplication ?
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The prevalence of the 22q11.2 duplication in the general population is difficult to determine. Because many individuals with this duplication have no associated symptoms, their duplication may never be detected. Most people tested for the 22q11.2 duplication have come to medical attention as a result of developmental delay or other problems affecting themselves or a family member. In one study, about 1 in 700 people tested for these reasons had the 22q11.2 duplication. Overall, more than 60 individuals with the duplication have been identified.
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What are the genetic changes related to 22q11.2 duplication ?
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People with 22q11.2 duplication have an extra copy of some genetic material at position q11.2 on chromosome 22. In most cases, this extra genetic material consists of a sequence of about 3 million DNA building blocks (base pairs), also written as 3 megabases (Mb). The 3 Mb duplicated region contains 30 to 40 genes. For many of these genes, little is known about their function. A small percentage of affected individuals have a shorter duplication in the same region. Researchers are working to determine which duplicated genes may contribute to the developmental delay and other problems that sometimes affect people with this condition.
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Is 22q11.2 duplication inherited ?
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The inheritance of 22q11.2 duplication is considered autosomal dominant because the duplication affects one of the two copies of chromosome 22 in each cell. About 70 percent of affected individuals inherit the duplication from a parent. In other cases, the duplication is not inherited and instead occurs as a random event during the formation of reproductive cells (eggs and sperm) or in early fetal development. These affected people typically have no history of the disorder in their family, although they can pass the duplication to their children.
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What are the treatments for 22q11.2 duplication ?
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These resources address the diagnosis or management of 22q11.2 duplication: - Gene Review: Gene Review: 22q11.2 Duplication - Genetic Testing Registry: 22q11.2 duplication 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
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What is (are) Legius syndrome ?
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Legius syndrome is a condition characterized by changes in skin coloring (pigmentation). Almost all affected individuals have multiple caf-au-lait spots, which are flat patches on the skin that are darker than the surrounding area. Another pigmentation change, freckles in the armpits and groin, may occur in some affected individuals. Other signs and symptoms of Legius syndrome may include an abnormally large head (macrocephaly) and unusual facial characteristics. Although most people with Legius syndrome have normal intelligence, some affected individuals have been diagnosed with learning disabilities, attention deficit disorder (ADD), or attention deficit hyperactivity disorder (ADHD). Many of the signs and symptoms of Legius syndrome also occur in a similar disorder called neurofibromatosis type 1. It can be difficult to tell the two disorders apart in early childhood. However, the features of the two disorders differ later in life.
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How many people are affected by Legius syndrome ?
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The prevalence of Legius syndrome is unknown. Many individuals with this disorder are likely misdiagnosed because the signs and symptoms of Legius syndrome are similar to those of neurofibromatosis type 1.
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What are the genetic changes related to Legius syndrome ?
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Mutations in the SPRED1 gene cause Legius syndrome. The SPRED1 gene provides instructions for making the Spred-1 protein. This protein controls (regulates) an important cell signaling pathway that is involved in the growth and division of cells (proliferation), the process by which cells mature to carry out specific functions (differentiation), cell movement, and the self-destruction of cells (apoptosis). Mutations in the SPRED1 gene lead to a nonfunctional protein that can no longer regulate the pathway, resulting in overactive signaling. It is unclear how mutations in the SPRED1 gene cause the signs and symptoms of Legius syndrome.
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Is Legius syndrome inherited ?
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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.
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What are the treatments for Legius syndrome ?
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These resources address the diagnosis or management of Legius syndrome: - Children's Tumor Foundation: NF1 or Legius Syndrome--An Emerging Challenge of Clinical Diagnosis - Gene Review: Gene Review: Legius Syndrome - Genetic Testing Registry: Legius 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
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What is (are) dihydrolipoamide dehydrogenase deficiency ?
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Dihydrolipoamide dehydrogenase deficiency is a severe condition that can affect several body systems. Signs and symptoms of this condition usually appear shortly after birth, and they can vary widely among affected individuals. A common feature of dihydrolipoamide dehydrogenase deficiency is a potentially life-threatening buildup of lactic acid in tissues (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. Neurological problems are also common in this condition; the first symptoms in affected infants are often decreased muscle tone (hypotonia) and extreme tiredness (lethargy). As the problems worsen, affected infants can have difficulty feeding, decreased alertness, and seizures. Liver problems can also occur in dihydrolipoamide dehydrogenase deficiency, ranging from an enlarged liver (hepatomegaly) to life-threatening liver failure. In some affected people, liver disease, which can begin anytime from infancy to adulthood, is the primary symptom. The liver problems are usually associated with recurrent vomiting and abdominal pain. Rarely, people with dihydrolipoamide dehydrogenase deficiency experience weakness of the muscles used for movement (skeletal muscles), particularly during exercise; droopy eyelids; or a weakened heart muscle (cardiomyopathy). Other features of this condition include excess ammonia in the blood (hyperammonemia), a buildup of molecules called ketones in the body (ketoacidosis), or low blood sugar levels (hypoglycemia). Typically, the signs and symptoms of dihydrolipoamide dehydrogenase deficiency occur in episodes that may be triggered by fever, injury, or other stresses on the body. Affected individuals are usually symptom-free between episodes. Many infants with this condition do not survive the first few years of life because of the severity of these episodes. Affected individuals who survive past early childhood often have delayed growth and neurological problems, including intellectual disability, muscle stiffness (spasticity), difficulty coordinating movements (ataxia), and seizures.
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How many people are affected by dihydrolipoamide dehydrogenase deficiency ?
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Dihydrolipoamide dehydrogenase deficiency occurs in an estimated 1 in 35,000 to 48,000 individuals of Ashkenazi Jewish descent. This population typically has liver disease as the primary symptom. In other populations, the prevalence of dihydrolipoamide dehydrogenase deficiency is unknown, but the condition is likely rare.
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What are the genetic changes related to dihydrolipoamide dehydrogenase deficiency ?
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Mutations in the DLD gene cause dihydrolipoamide dehydrogenase deficiency. This gene provides instructions for making an enzyme called dihydrolipoamide dehydrogenase (DLD). DLD is one component of three different groups of enzymes that work together (enzyme complexes): branched-chain alpha-keto acid dehydrogenase (BCKD), pyruvate dehydrogenase (PDH), and alpha ()-ketoglutarate dehydrogenase (KGDH). The BCKD enzyme complex is involved in the breakdown of three protein building blocks (amino acids) commonly found in protein-rich foods: leucine, isoleucine, and valine. Breakdown of these amino acids produces molecules that can be used for energy. The PDH and KGDH enzyme complexes are involved in other reactions in the pathways that convert the energy from food into a form that cells can use. Mutations in the DLD gene impair the function of the DLD enzyme, which prevents the three enzyme complexes from functioning properly. As a result, molecules that are normally broken down and their byproducts build up in the body, damaging tissues and leading to lactic acidosis and other chemical imbalances. In addition, the production of cellular energy is diminished. The brain is especially affected by the buildup of molecules and the lack of cellular energy, resulting in the neurological problems associated with dihydrolipoamide dehydrogenase deficiency. Liver problems are likely also related to decreased energy production in cells. The degree of impairment of each complex contributes to the variability in the features of this condition.
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Is dihydrolipoamide dehydrogenase deficiency inherited ?
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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.
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What are the treatments for dihydrolipoamide dehydrogenase deficiency ?
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These resources address the diagnosis or management of dihydrolipoamide dehydrogenase deficiency: - Gene Review: Gene Review: Dihydrolipoamide Dehydrogenase Deficiency - Genetic Testing Registry: Maple syrup urine disease, type 3 These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) atypical hemolytic-uremic syndrome ?
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Atypical hemolytic-uremic syndrome is a disease that primarily affects kidney function. This condition, which can occur at any age, causes abnormal blood clots (thrombi) to form in small blood vessels in the kidneys. These clots can cause serious medical problems if they restrict or block blood flow. Atypical hemolytic-uremic syndrome is characterized by three major features related to abnormal clotting: hemolytic anemia, thrombocytopenia, and kidney failure. Hemolytic anemia occurs when red blood cells break down (undergo hemolysis) prematurely. In atypical hemolytic-uremic syndrome, red blood cells can break apart as they squeeze past clots within small blood vessels. Anemia results if these cells are destroyed faster than the body can replace them. This condition can lead to unusually pale skin (pallor), yellowing of the eyes and skin (jaundice), fatigue, shortness of breath, and a rapid heart rate. Thrombocytopenia is a reduced level of circulating platelets, which are cell fragments that normally assist with blood clotting. In people with atypical hemolytic-uremic syndrome, fewer platelets are available in the bloodstream because a large number of platelets are used to make abnormal clots. Thrombocytopenia can cause easy bruising and abnormal bleeding. As a result of clot formation in small blood vessels, people with atypical hemolytic-uremic syndrome experience kidney damage and acute kidney failure that lead to end-stage renal disease (ESRD) in about half of all cases. These life-threatening complications prevent the kidneys from filtering fluids and waste products from the body effectively. Atypical hemolytic-uremic syndrome should be distinguished from a more common condition called typical hemolytic-uremic syndrome. The two disorders have different causes and different signs and symptoms. Unlike the atypical form, the typical form is caused by infection with certain strains of Escherichia coli bacteria that produce toxic substances called Shiga-like toxins. The typical form is characterized by severe diarrhea and most often affects children younger than 10. The typical form is less likely than the atypical form to involve recurrent attacks of kidney damage that lead to ESRD.
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How many people are affected by atypical hemolytic-uremic syndrome ?
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The incidence of atypical hemolytic-uremic syndrome is estimated to be 1 in 500,000 people per year in the United States. The atypical form is probably about 10 times less common than the typical form.
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What are the genetic changes related to atypical hemolytic-uremic syndrome ?
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Atypical hemolytic-uremic syndrome often results from a combination of environmental and genetic factors. Mutations in at least seven genes appear to increase the risk of developing the disorder. Mutations in a gene called CFH are most common; they have been found in about 30 percent of all cases of atypical hemolytic-uremic syndrome. Mutations in the other genes have each been identified in a smaller percentage of cases. The genes associated with atypical hemolytic-uremic syndrome provide instructions for making proteins involved in a part of the body's immune response known as the complement system. This system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. The complement system must be carefully regulated so it targets only unwanted materials and does not attack the body's healthy cells. The regulatory proteins associated with atypical hemolytic-uremic syndrome protect healthy cells by preventing activation of the complement system when it is not needed. Mutations in the genes associated with atypical hemolytic-uremic syndrome lead to uncontrolled activation of the complement system. The overactive system attacks cells that line blood vessels in the kidneys, causing inflammation and the formation of abnormal clots. These abnormalities lead to kidney damage and, in many cases, kidney failure and ESRD. Although gene mutations increase the risk of atypical hemolytic-uremic syndrome, studies suggest that they are often not sufficient to cause the disease. In people with certain genetic changes, the signs and symptoms of the disorder may be triggered by factors including certain medications (such as anticancer drugs), chronic diseases, viral or bacterial infections, cancers, organ transplantation, or pregnancy. Some people with atypical hemolytic-uremic syndrome do not have any known genetic changes or environmental triggers for the disease. In these cases, the disorder is described as idiopathic.
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Is atypical hemolytic-uremic syndrome inherited ?
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Most cases of atypical hemolytic-uremic syndrome are sporadic, which means that they occur in people with no apparent history of the disorder in their family. Less than 20 percent of all cases have been reported to run in families. When the disorder is familial, it can have an autosomal dominant or an autosomal recessive pattern of inheritance. Autosomal dominant inheritance means one copy of an altered gene in each cell is sufficient to increase the risk of the disorder. In some cases, an affected person inherits the mutation from one affected parent. However, most people with the autosomal dominant form of atypical hemolytic-uremic syndrome have no history of the disorder in their family. Because not everyone who inherits a gene mutation will develop the signs and symptoms of the disease, an affected individual may have unaffected relatives who carry a copy of the mutation. Autosomal recessive inheritance means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
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What are the treatments for atypical hemolytic-uremic syndrome ?
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These resources address the diagnosis or management of atypical hemolytic-uremic syndrome: - Gene Review: Gene Review: Atypical Hemolytic-Uremic Syndrome - Genetic Testing Registry: Atypical hemolytic uremic syndrome - Genetic Testing Registry: Atypical hemolytic-uremic syndrome 1 - Genetic Testing Registry: Atypical hemolytic-uremic syndrome 2 - Genetic Testing Registry: Atypical hemolytic-uremic syndrome 3 - Genetic Testing Registry: Atypical hemolytic-uremic syndrome 4 - Genetic Testing Registry: Atypical hemolytic-uremic syndrome 5 - Genetic Testing Registry: Atypical hemolytic-uremic syndrome 6 - MedlinePlus Encyclopedia: Hemolytic Anemia - MedlinePlus Encyclopedia: Hemolytic-Uremic Syndrome - MedlinePlus Encyclopedia: Thrombocytopenia - National Institute of Diabetes and Digestive and Kidney Diseases: Kidney Failure: Choosing a Treatment That's Right for You 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
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What is (are) familial idiopathic basal ganglia calcification ?
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Familial idiopathic basal ganglia calcification (FIBGC, formerly known as Fahr disease) is a condition characterized by abnormal deposits of calcium (calcification) in the brain. These calcium deposits typically occur in the basal ganglia, which are structures deep within the brain that help start and control movement; however, other brain regions can also be affected. The signs and symptoms of FIBGC include movement disorders and psychiatric or behavioral difficulties. These problems begin in adulthood, usually in a person's thirties. The movement difficulties experienced by people with FIBGC include involuntary tensing of various muscles (dystonia), problems coordinating movements (ataxia), and uncontrollable movements of the limbs (choreoathetosis). Affected individuals often have seizures as well. The psychiatric and behavioral problems include difficulty concentrating, memory loss, changes in personality, a distorted view of reality (psychosis), and decline in intellectual function (dementia). An estimated 20 to 30 percent of people with FIBGC have one of these psychiatric disorders. The severity of this condition varies among affected individuals; some people have no symptoms related to the brain calcification, whereas other people have significant movement and psychiatric problems.
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How many people are affected by familial idiopathic basal ganglia calcification ?
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FIBGC is thought to be a rare disorder; about 60 affected families have been described in the medical literature. However, because brain imaging tests are needed to recognize the calcium deposits, this condition is believed to be underdiagnosed.
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What are the genetic changes related to familial idiopathic basal ganglia calcification ?
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Mutations in the SLC20A2 gene cause nearly half of all cases of FIBGC. A small percentage of cases are caused by mutations in the PDGFRB gene. Other cases of FIBGC appear to be associated with changes in chromosomes 2, 7, 9, and 14, although specific genes have yet to be identified. These findings suggest that multiple genes are involved in this condition. The SLC20A2 gene provides instructions for making a protein called sodium-dependent phosphate transporter 2 (PiT-2). This protein plays a major role in regulating phosphate levels within the body (phosphate homeostasis) by transporting phosphate across cell membranes. The SLC20A2 gene mutations that cause FIBGC lead to the production of a PiT-2 protein that cannot effectively transport phosphate into cells. As a result, phosphate levels in the bloodstream rise. In the brain, the excess phosphate combines with calcium and forms deposits. The PDGFRB gene provides instructions for making a protein that plays a role in turning on (activating) signaling pathways that control many cell processes. It is unclear how PDGFRB gene mutations cause FIBGC. Mutations may alter signaling within cells that line blood vessels in the brain, causing them to take in excess calcium, and leading to calcification of the lining of these blood vessels. Alternatively, changes in the PDGFRB protein could alter phosphate transport signaling pathways, causing an increase in phosphate levels and the formation of calcium deposits. Researchers suggest that calcium deposits lead to the characteristic features of FIBGC by interrupting signaling pathways in various parts of the brain. Calcium deposits may disrupt the pathways that connect the basal ganglia to other areas of the brain, particularly the frontal lobes. These areas at the front of the brain are involved in reasoning, planning, judgment, and problem-solving. The regions of the brain that regulate social behavior, mood, and motivation may also be affected. Research has shown that people with significant calcification tend to have more signs and symptoms of FIBGC than people with little or no calcification. However, this association does not apply to all people with FIBGC.
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Is familial idiopathic basal ganglia calcification inherited ?
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FIBGC is inherited in an autosomal dominant pattern. Autosomal dominant inheritance means one copy of an altered SLC20A2 or PDGFRB gene in each cell is sufficient to cause the disorder. This condition appears to follow an autosomal dominant pattern of inheritance when the genetic cause is not known. In most cases, an affected person has one parent with the condition.
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What are the treatments for familial idiopathic basal ganglia calcification ?
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These resources address the diagnosis or management of FIBGC: - Dystonia Medical Research Foundation: Treatments - Gene Review: Gene Review: Primary Familial Brain Calcification - Genetic Testing Registry: Basal ganglia calcification, idiopathic, 2 - Genetic Testing Registry: Basal ganglia calcification, idiopathic, 4 - Genetic Testing Registry: Idiopathic basal ganglia calcification 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
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What is (are) Miyoshi myopathy ?
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Miyoshi myopathy is a muscle disorder that primarily affects muscles away from the center of the body (distal muscles), such as those in the legs. During early to mid-adulthood, affected individuals typically begin to experience muscle weakness and wasting (atrophy) in one or both calves. If only one leg is affected, the calves appear different in size (asymmetrical). Calf weakness can make it difficult to stand on tiptoe. As Miyoshi myopathy slowly progresses, the muscle weakness and atrophy spread up the leg to the muscles in the thigh and buttock. Eventually, affected individuals may have difficulty climbing stairs or walking for an extended period of time. Some people with Miyoshi myopathy may eventually need wheelchair assistance. Rarely, the upper arm or shoulder muscles are mildly affected in Miyoshi myopathy. In a few cases, abnormal heart rhythms (arrhythmias) have developed. Individuals with Miyoshi myopathy have highly elevated levels of an enzyme called creatine kinase (CK) in their blood, which often indicates muscle disease.
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How many people are affected by Miyoshi myopathy ?
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The exact prevalence of Miyoshi myopathy is unknown. In Japan, where the condition was first described, it is estimated to affect 1 in 440,000 individuals.
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What are the genetic changes related to Miyoshi myopathy ?
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Miyoshi myopathy is caused by mutations in the DYSF or ANO5 gene. When this condition is caused by ANO5 gene mutations it is sometimes referred to as distal anoctaminopathy. The DYSF and ANO5 genes provide instructions for making proteins primarily found in muscles that are used for movement (skeletal muscles). The protein produced from the DYSF gene, called dysferlin, is found in the thin membrane called the sarcolemma that surrounds muscle fibers. Dysferlin is thought to aid in repairing the sarcolemma when it becomes damaged or torn due to muscle strain. The ANO5 gene provides instructions for making a protein called anoctamin-5. This protein is located within the membrane of a cell structure called the endoplasmic reticulum, which is involved in protein production, processing, and transport. Anoctamin-5 is thought to act as a channel, allowing charged chlorine atoms (chloride ions) to flow in and out of the endoplasmic reticulum. The regulation of chloride flow within muscle cells plays a role in controlling muscle tensing (contraction) and relaxation. DYSF or ANO5 gene mutations often result in a decrease or elimination of the corresponding protein. A lack of dysferlin leads to a reduced ability to repair damage done to the sarcolemma of muscle fibers. As a result, damage accumulates and leads to atrophy of the muscle fiber. It is unclear why this damage leads to the specific pattern of weakness and atrophy that is characteristic of Miyoshi myopathy. The effects of the loss of anoctamin-5 are also unclear. While chloride is necessary for normal muscle function, it is unknown how a lack of this chloride channel causes the signs and symptoms of Miyoshi myopathy.
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Is Miyoshi myopathy inherited ?
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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.
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What are the treatments for Miyoshi myopathy ?
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These resources address the diagnosis or management of Miyoshi myopathy: - Gene Review: Gene Review: ANO5-Related Muscle Diseases - Gene Review: Gene Review: Dysferlinopathy - Genetic Testing Registry: Miyoshi muscular dystrophy 1 - Genetic Testing Registry: Miyoshi muscular dystrophy 3 These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) white sponge nevus ?
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White sponge nevus is a condition characterized by the formation of white patches of tissue called nevi (singular: nevus) that appear as thickened, velvety, sponge-like tissue. The nevi are most commonly found on the moist lining of the mouth (oral mucosa), especially on the inside of the cheeks (buccal mucosa). Affected individuals usually develop multiple nevi. Rarely, white sponge nevi also occur on the mucosae (singular: mucosa) of the nose, esophagus, genitals, or anus. The nevi are caused by a noncancerous (benign) overgrowth of cells. White sponge nevus can be present from birth but usually first appears during early childhood. The size and location of the nevi can change over time. In the oral mucosa, both sides of the mouth are usually affected. The nevi are generally painless, but the folds of extra tissue can promote bacterial growth, which can lead to infection that may cause discomfort. The altered texture and appearance of the affected tissue, especially the oral mucosa, can be bothersome for some affected individuals.
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How many people are affected by white sponge nevus ?
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The exact prevalence of white sponge nevus is unknown, but it is estimated to affect less than 1 in 200,000 individuals worldwide.
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What are the genetic changes related to white sponge nevus ?
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Mutations in the KRT4 or KRT13 gene cause white sponge nevus. These genes provide instructions for making proteins called keratins. Keratins are a group of tough, fibrous proteins that form the structural framework of epithelial cells, which are cells that line the surfaces and cavities of the body and make up the different mucosae. The keratin 4 protein (produced from the KRT4 gene) and the keratin 13 protein (produced from the KRT13 gene) partner together to form molecules known as intermediate filaments. These filaments assemble into networks that provide strength and resilience to the different mucosae. Networks of intermediate filaments protect the mucosae from being damaged by friction or other everyday physical stresses. Mutations in the KRT4 or KRT13 gene disrupt the structure of the keratin protein. As a result, keratin 4 and keratin 13 are mismatched and do not fit together properly, leading to the formation of irregular intermediate filaments that are easily damaged with little friction or trauma. Fragile intermediate filaments in the oral mucosa might be damaged when eating or brushing one's teeth. Damage to intermediate filaments leads to inflammation and promotes the abnormal growth and division (proliferation) of epithelial cells, causing the mucosae to thicken and resulting in white sponge nevus.
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Is white sponge nevus inherited ?
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This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell can be sufficient to cause the disorder. However, some people who have a mutation that causes white sponge nevus do not develop these abnormal growths; this phenomenon is called reduced penetrance.
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What are the treatments for white sponge nevus ?
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These resources address the diagnosis or management of white sponge nevus: - Genetic Testing Registry: White sponge nevus of cannon 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
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What is (are) familial hemophagocytic lymphohistiocytosis ?
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Familial hemophagocytic lymphohistiocytosis is a disorder in which the immune system produces too many activated immune cells (lymphocytes) called T cells, natural killer cells, B cells, and macrophages (histiocytes). Excessive amounts of immune system proteins called cytokines are also produced. This overactivation of the immune system causes fever and damages the liver and spleen, resulting in enlargement of these organs. Familial hemophagocytic lymphohistiocytosis also destroys blood-producing cells in the bone marrow, a process called hemophagocytosis. As a result, affected individuals have low numbers of red blood cells (anemia) and a reduction in the number of blood cells involved in clotting (platelets). A reduction in platelets may cause easy bruising and abnormal bleeding. The brain may also be affected in familial hemophagocytic lymphohistiocytosis. As a result, affected individuals may experience irritability, delayed closure of the bones of the skull in infants, neck stiffness, abnormal muscle tone, impaired muscle coordination, paralysis, blindness, seizures, and coma. In addition to neurological problems, familial hemophagocytic lymphohistiocytosis can cause abnormalities of the heart, kidneys, and other organs and tissues. Affected individuals also have an increased risk of developing cancers of blood-forming cells (leukemia and lymphoma). Signs and symptoms of familial hemophagocytic lymphohistiocytosis usually become apparent during infancy, although occasionally they appear later in life. They usually occur when the immune system launches an exaggerated response to an infection, but may also occur in the absence of infection. Without treatment, most people with familial hemophagocytic lymphohistiocytosis survive only a few months.
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How many people are affected by familial hemophagocytic lymphohistiocytosis ?
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Familial hemophagocytic lymphohistiocytosis occurs in approximately 1 in 50,000 individuals worldwide.
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What are the genetic changes related to familial hemophagocytic lymphohistiocytosis ?
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Familial hemophagocytic lymphohistiocytosis may be caused by mutations in any of several genes. These genes provide instructions for making proteins that help destroy or deactivate lymphocytes that are no longer needed. By controlling the number of activated lymphocytes, these genes help regulate immune system function. Approximately 40 to 60 percent of cases of familial hemophagocytic lymphohistiocytosis are caused by mutations in the PRF1 or UNC13D genes. Smaller numbers of cases are caused by mutations in other known genes. In some affected individuals, the genetic cause of the disorder is unknown. The gene mutations that cause familial hemophagocytic lymphohistiocytosis impair the body's ability to regulate the immune system. These changes result in the exaggerated immune response characteristic of this condition.
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Is familial hemophagocytic lymphohistiocytosis inherited ?
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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.
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What are the treatments for familial hemophagocytic lymphohistiocytosis ?
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These resources address the diagnosis or management of familial hemophagocytic lymphohistiocytosis: - Gene Review: Gene Review: Hemophagocytic Lymphohistiocytosis, Familial - Genetic Testing Registry: Familial hemophagocytic lymphohistiocytosis - Genetic Testing Registry: Hemophagocytic lymphohistiocytosis, familial, 2 - Genetic Testing Registry: Hemophagocytic lymphohistiocytosis, familial, 3 - Genetic Testing Registry: Hemophagocytic lymphohistiocytosis, familial, 4 - Genetic Testing Registry: Hemophagocytic lymphohistiocytosis, familial, 5 - The Merck Manual for Healthcare Professionals - University of Minnesota: Pediatric Blood & Marrow Transplantation Center These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) spinocerebellar ataxia type 6 ?
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Spinocerebellar ataxia type 6 (SCA6) is a condition characterized by progressive problems with movement. People with this condition initially experience problems with coordination and balance (ataxia). Other early signs and symptoms of SCA6 include speech difficulties, involuntary eye movements (nystagmus), and double vision. Over time, individuals with SCA6 may develop loss of coordination in their arms, tremors, and uncontrolled muscle tensing (dystonia). Signs and symptoms of SCA6 typically begin in a person's forties or fifties but can appear anytime from childhood to late adulthood. Most people with this disorder require wheelchair assistance by the time they are in their sixties.
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How many people are affected by spinocerebellar ataxia type 6 ?
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The worldwide prevalence of SCA6 is estimated to be less than 1 in 100,000 individuals.
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What are the genetic changes related to spinocerebellar ataxia type 6 ?
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Mutations in the CACNA1A gene cause SCA6. The CACNA1A gene provides instructions for making a protein that forms a part of some calcium channels. These channels transport positively charged calcium atoms (calcium ions) across cell membranes. The movement of these ions is critical for normal signaling between nerve cells (neurons) in the brain and other parts of the nervous system. The CACNA1A gene provides instructions for making one part (the alpha-1 subunit) of a calcium channel called CaV2.1. CaV2.1 channels play an essential role in communication between neurons in the brain. The CACNA1A gene mutations that cause SCA6 involve a DNA segment known as a CAG trinucleotide repeat. This segment is made up of a series of three DNA building blocks (cytosine, adenine, and guanine) that appear multiple times in a row. Normally, the CAG segment is repeated 4 to 18 times within the gene. In people with SCA6, the CAG segment is repeated 20 to 33 times. People with 20 repeats tend to experience signs and symptoms of SCA6 beginning in late adulthood, while people with a larger number of repeats usually have signs and symptoms from mid-adulthood. An increase in the length of the CAG segment leads to the production of an abnormally long version of the alpha-1 subunit. This version of the subunit alters the location and function of the CaV2.1 channels. Normally the alpha-1 subunit is located within the cell membrane; the abnormal subunit is found in the cell membrane as well as in the fluid inside cells (cytoplasm), where it clusters together and forms clumps (aggregates). The effect these aggregates have on cell functioning is unknown. The lack of normal calcium channels in the cell membrane impairs cell communication between neurons in the brain. Diminished cell communication leads to cell death. Cells within the cerebellum, which is the part of the brain that coordinates movement, are particularly sensitive to the accumulation of these aggregates. Over time, a loss of cells in the cerebellum causes the movement problems characteristic of SCA6.
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Is spinocerebellar ataxia type 6 inherited ?
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This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition. As the altered CACNA1A gene is passed down from one generation to the next, the length of the CAG trinucleotide repeat often slightly increases. A larger number of repeats is usually associated with an earlier onset of signs and symptoms. This phenomenon is called anticipation.
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What are the treatments for spinocerebellar ataxia type 6 ?
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These resources address the diagnosis or management of SCA6: - Gene Review: Gene Review: Spinocerebellar Ataxia Type 6 - Genetic Testing Registry: Spinocerebellar ataxia 6 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
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What is (are) auriculo-condylar syndrome ?
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Auriculo-condylar syndrome is a condition that affects facial development, particularly development of the ears and lower jaw (mandible). Most people with auriculo-condylar syndrome have malformed outer ears ("auriculo-" refers to the ears). A hallmark of this condition is an ear abnormality called a "question-mark ear," in which the ears have a distinctive question-mark shape caused by a split that separates the upper part of the ear from the earlobe. Other ear abnormalities that can occur in auriculo-condylar syndrome include cupped ears, ears with fewer folds and grooves than usual (described as "simple"), narrow ear canals, small skin tags in front of or behind the ears, and ears that are rotated backward. Some affected individuals also have hearing loss. Abnormalities of the mandible are another characteristic feature of auriculo-condylar syndrome. These abnormalities often include an unusually small chin (micrognathia) and malfunction of the temporomandibular joint (TMJ), which connects the lower jaw to the skull. Problems with the TMJ affect how the upper and lower jaws fit together and can make it difficult to open and close the mouth. The term "condylar" in the name of the condition refers to the mandibular condyle, which is the upper portion of the mandible that forms part of the TMJ. Other features of auriculo-condylar syndrome can include prominent cheeks, an unusually small mouth (microstomia), differences in the size and shape of facial structures between the right and left sides of the face (facial asymmetry), and an opening in the roof of the mouth (cleft palate). These features vary, even among affected members of the same family.
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How many people are affected by auriculo-condylar syndrome ?
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Auriculo-condylar syndrome appears to be a rare disorder. More than two dozen affected individuals have been described in the medical literature.
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What are the genetic changes related to auriculo-condylar syndrome ?
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Auriculo-condylar syndrome can be caused by mutations in either the GNAI3 or PLCB4 gene. These genes provide instructions for making proteins that are involved in chemical signaling within cells. They help transmit information from outside the cell to inside the cell, which instructs the cell to grow, divide, or take on specialized functions. Studies suggest that the proteins produced from the GNAI3 and PLCB4 genes contribute to the development of the first and second pharyngeal arches, which are structures in the embryo that ultimately develop into the jawbones, facial muscles, middle ear bones, ear canals, outer ears, and related tissues. Mutations in these genes alter the formation of the lower jaw: instead of developing normally, the lower jaw becomes shaped more like the smaller upper jaw (maxilla). This abnormal shape leads to micrognathia and problems with TMJ function. Researchers are working to determine how mutations in these genes lead to the other developmental abnormalities associated with auriculo-condylar syndrome. In some people with the characteristic features of auriculo-condylar syndrome, a mutation in the GNAI3 or PLCB4 gene has not been found. The cause of the condition is unknown in these individuals.
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Is auriculo-condylar syndrome inherited ?
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This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is typically sufficient to cause the disorder. In some 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. Some people who have one altered copy of the GNAI3 or PLCB4 gene have no features related to auriculo-condylar syndrome. (This situation is known as reduced penetrance.) It is unclear why some people with a mutated gene develop the condition and other people with a mutated gene do not.
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What are the treatments for auriculo-condylar syndrome ?
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These resources address the diagnosis or management of auriculo-condylar syndrome: - Genetic Testing Registry: Auriculocondylar syndrome 1 - Genetic Testing Registry: Auriculocondylar syndrome 2 - MedlinePlus Encyclopedia: Cleft Lip and Palate - MedlinePlus Encyclopedia: Pinna Abnormalities and Low-Set Ears 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
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What is (are) ankyloblepharon-ectodermal defects-cleft lip/palate syndrome ?
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Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a form of ectodermal dysplasia, a group of about 150 conditions characterized by abnormal development of ectodermal tissues including the skin, hair, nails, teeth, and sweat glands. Among the most common features of AEC syndrome are missing patches of skin (erosions). In affected infants, skin erosions most commonly occur on the scalp. They tend to recur throughout childhood and into adulthood, frequently affecting the scalp, neck, hands, and feet. The skin erosions range from mild to severe and can lead to infection, scarring, and hair loss. Other ectodermal abnormalities in AEC syndrome include changes in skin coloring; brittle, sparse, or missing hair; misshapen or absent fingernails and toenails; and malformed or missing teeth. Affected individuals also report increased sensitivity to heat and a reduced ability to sweat. Many infants with AEC syndrome are born with an eyelid condition known as ankyloblepharon filiforme adnatum, in which strands of tissue partially or completely fuse the upper and lower eyelids. Most people with AEC syndrome are also born with an opening in the roof of the mouth (a cleft palate), a split in the lip (a cleft lip), or both. Cleft lip or cleft palate can make it difficult for affected infants to suck, so these infants often have trouble feeding and do not grow and gain weight at the expected rate (failure to thrive). Additional features of AEC syndrome can include limb abnormalities, most commonly fused fingers and toes (syndactyly). Less often, affected individuals have permanently bent fingers and toes (camptodactyly) or a deep split in the hands or feet with missing fingers or toes and fusion of the remaining digits (ectrodactyly). Hearing loss is common, occurring in more than 90 percent of children with AEC syndrome. Some affected individuals have distinctive facial features, such as small jaws that cannot open fully and a narrow space between the upper lip and nose (philtrum). Other signs and symptoms can include the opening of the urethra on the underside of the penis (hypospadias) in affected males, digestive problems, absent tear duct openings in the eyes, and chronic sinus or ear infections. A condition known as Rapp-Hodgkin syndrome has signs and symptoms that overlap considerably with those of AEC syndrome. These two syndromes were classified as separate disorders until it was discovered that they both result from mutations in the same part of the same gene. Most researchers now consider Rapp-Hodgkin syndrome and AEC syndrome to be part of the same disease spectrum.
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How many people are affected by ankyloblepharon-ectodermal defects-cleft lip/palate syndrome ?
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AEC syndrome is a rare condition; its prevalence is unknown. All forms of ectodermal dysplasia together occur in about 1 in 100,000 newborns in the United States.
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What are the genetic changes related to ankyloblepharon-ectodermal defects-cleft lip/palate syndrome ?
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AEC syndrome is caused by mutations in the TP63 gene. This gene provides instructions for making a protein known as p63, which plays an essential role in early development. The p63 protein is a transcription factor, which means that it attaches (binds) to DNA and controls the activity of particular genes. The p63 protein turns many different genes on and off during development. It appears to be especially critical for the development of ectodermal structures, such as the skin, hair, teeth, and nails. Studies suggest that it also plays important roles in the development of the limbs, facial features, urinary system, and other organs and tissues. The TP63 gene mutations responsible for AEC syndrome interfere with the ability of p63 to turn target genes on and off at the right times. It is unclear how these changes lead to abnormal ectodermal development and the specific features of AEC syndrome.
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Is ankyloblepharon-ectodermal defects-cleft lip/palate syndrome inherited ?
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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.
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What are the treatments for ankyloblepharon-ectodermal defects-cleft lip/palate syndrome ?
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These resources address the diagnosis or management of AEC syndrome: - Gene Review: Gene Review: TP63-Related Disorders - Genetic Testing Registry: Hay-Wells syndrome of ectodermal dysplasia - Genetic Testing Registry: Rapp-Hodgkin 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
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What is (are) homocystinuria ?
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Homocystinuria is an inherited disorder in which the body is unable to process certain building blocks of proteins (amino acids) properly. There are multiple forms of homocystinuria, which are distinguished by their signs and symptoms and genetic cause. The most common form of homocystinuria is characterized by nearsightedness (myopia), dislocation of the lens at the front of the eye, an increased risk of abnormal blood clotting, and brittle bones that are prone to fracture (osteoporosis) or other skeletal abnormalities. Some affected individuals also have developmental delay and learning problems. Less common forms of homocystinuria can cause intellectual disability, failure to grow and gain weight at the expected rate (failure to thrive), seizures, problems with movement, and a blood disorder called megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number of red blood cells (anemia), and the remaining red blood cells are larger than normal (megaloblastic). The signs and symptoms of homocystinuria typically develop within the first year of life, although some mildly affected people may not develop features until later in childhood or adulthood.
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How many people are affected by homocystinuria ?
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The most common form of homocystinuria affects at least 1 in 200,000 to 335,000 people worldwide. The disorder appears to be more common in some countries, such as Ireland (1 in 65,000), Germany (1 in 17,800), Norway (1 in 6,400), and Qatar (1 in 1,800). The rarer forms of homocystinuria each have a small number of cases reported in the scientific literature.
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