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genetic changes | What are the genetic changes related to ovarian cancer ? | Cancers occur when a buildup of mutations in critical genesthose that control cell growth and division or repair damaged DNAallow cells to grow and divide uncontrollably to form a tumor. Most cases of ovarian cancer are sporadic; in these cases the associated genetic changes are acquired during a person's lifetime and are present only in certain cells in the ovary. These changes, which are called somatic mutations, are not inherited. Somatic mutations in the TP53 gene occur in almost half of all ovarian cancers. The protein produced from this gene is described as a tumor suppressor because it helps keep cells from growing and dividing too fast or in an uncontrolled way. Most of these mutations change single protein building blocks (amino acids) in the p53 protein, which reduces or eliminates the protein's tumor suppressor function. Because the altered protein is less able to regulate cell growth and division, a cancerous tumor may develop. Somatic mutations in many other genes have also been found in ovarian cancer cells. In hereditary ovarian cancer, the associated genetic changes are passed down within a family. These changes, classified as germline mutations, are present in all the body's cells. In people with germline mutations, other inherited and somatic gene changes, together with environmental and lifestyle factors, also influence whether a woman will develop ovarian cancer. Germline mutations are involved in more than one-fifth of ovarian cancer cases. Between 65 and 85 percent of these mutations are in the BRCA1 or BRCA2 gene. These gene mutations are described as "high penetrance" because they are associated with a high risk of developing ovarian cancer, breast cancer, and several other types of cancer in women. Compared to a 1.6 percent lifetime risk of developing ovarian cancer for women in the total population, the lifetime risk in women with a BRCA1 gene mutation is 40 to 60 percent, and the lifetime risk in women with a BRCA2 gene mutation is 20 to 35 percent. Men with mutations in these genes also have an increased risk of developing several forms of cancer. The proteins produced from the BRCA1 and BRCA2 genes are tumor suppressors that are involved in fixing damaged DNA, which helps to maintain the stability of a cell's genetic information. Mutations in these genes impair DNA repair, allowing potentially damaging mutations to persist in DNA. As these defects accumulate, they can trigger cells to grow and divide without control or order to form a tumor. A significantly increased risk of ovarian cancer is also a feature of certain rare genetic syndromes, including a disorder called Lynch syndrome. Lynch syndrome is most often associated with mutations in the MLH1 or MSH2 gene and accounts for between 10 and 15 percent of hereditary ovarian cancers. Other rare genetic syndromes may also be associated with an increased risk of ovarian cancer. The proteins produced from the genes associated with these syndromes act as tumor suppressors. Mutations in any of these genes can allow cells to grow and divide unchecked, leading to the development of a cancerous tumor. Like BRCA1 and BRCA2, these genes are considered "high penetrance" because mutations greatly increase a person's chance of developing cancer. In addition to ovarian cancer, mutations in these genes increase the risk of several other types of cancer in both men and women. Germline mutations in dozens of other genes have been studied as possible risk factors for ovarian cancer. These genes are described as "low penetrance" or "moderate penetrance" because changes in each of these genes appear to make only a small or moderate contribution to overall ovarian cancer risk. Some of these genes provide instructions for making proteins that interact with the proteins produced from the BRCA1 or BRCA2 genes. Others act through different pathways. Researchers suspect that the combined influence of variations in these genes may significantly impact a person's risk of developing ovarian cancer. In many families, the genetic changes associated with hereditary ovarian cancer are unknown. Identifying additional genetic risk factors for ovarian cancer is an active area of medical research. In addition to genetic changes, researchers have identified many personal and environmental factors that contribute to a woman's risk of developing ovarian cancer. These factors include age, ethnic background, and hormonal and reproductive factors. A history of ovarian cancer in closely related family members is also an important risk factor, particularly if the cancer occurred in early adulthood. |
inheritance | Is ovarian cancer inherited ? | Most cases of ovarian cancer are not caused by inherited genetic factors. These cancers are associated with somatic mutations that are acquired during a person's lifetime, and they do not cluster in families. A predisposition to cancer caused by a germline mutation is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase a person's chance of developing cancer. Although ovarian cancer occurs only in women, the mutated gene can be inherited from either the mother or the father. It is important to note that people inherit an increased likelihood of developing cancer, not the disease itself. Not all people who inherit mutations in these genes will ultimately develop cancer. In many cases of ovarian cancer that clusters in families, the genetic basis for the disease and the mechanism of inheritance are unclear. |
treatment | What are the treatments for ovarian cancer ? | These resources address the diagnosis or management of ovarian cancer: - Dana-Farber Cancer Institute - Familial Ovarian Cancer Registry - Fred Hutchinson Cancer Research Center - Gene Review: Gene Review: BRCA1 and BRCA2 Hereditary Breast/Ovarian Cancer - Genetic Testing Registry: Hereditary breast and ovarian cancer syndrome - Genetic Testing Registry: Ovarian cancer - Genomics Education Programme (UK): Hereditary Breast and Ovarian Cancer - M.D. Anderson Cancer Center - MedlinePlus Encyclopedia: BRCA1 and BRCA2 Gene Testing - MedlinePlus Encyclopedia: CA-125 Blood Test - Memorial Sloan-Kettering Cancer 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 |
information | What is (are) multiple lentigines syndrome ? | Multiple lentigines syndrome (formerly called LEOPARD syndrome) is a condition that affects many areas of the body. The characteristic features associated with the condition include brown skin spots called lentigines that are similar to freckles, abnormalities in the electrical signals that control the heartbeat, widely spaced eyes (ocular hypertelorism), a narrowing of the artery from the heart to the lungs (pulmonary stenosis), abnormalities of the genitalia, short stature, and hearing loss. These features vary, however, even among affected individuals in the same family. Not all individuals affected with multiple lentigines syndrome have all the characteristic features of this condition. The lentigines seen in multiple lentigines syndrome typically first appear in mid-childhood, mostly on the face, neck, and upper body. Affected individuals may have thousands of brown skin spots by the time they reach puberty. Unlike freckles, the appearance of lentigines has nothing to do with sun exposure. In addition to lentigines, people with this condition may have lighter brown skin spots called caf-au-lait spots. Caf-au-lait spots tend to develop before the lentigines, appearing within the first year of life in most affected people. Abnormal electrical signaling in the heart can be a sign of other heart problems. Of the people with multiple lentigines syndrome who have heart problems, about 80 percent have hypertrophic cardiomyopathy, which is a thickening of the heart muscle that forces the heart to work harder to pump blood. The hypertrophic cardiomyopathy in affected individuals most often affects the lower left chamber of the heart (the left ventricle). Up to 20 percent of people with multiple lentigines syndrome who have heart problems have pulmonary stenosis. People with multiple lentigines syndrome can have a distinctive facial appearance. In addition to ocular hypertelorism, affected individuals may have droopy eyelids (ptosis), thick lips, and low-set ears. Abnormalities of the genitalia occur most often in males with multiple lentigines syndrome. The most common abnormality in affected males is undescended testes (cryptorchidism). Other males may have a urethra that opens on the underside of the penis (hypospadias). Males with multiple lentigines syndrome may have a reduced ability to have biological children (decreased fertility). Females with multiple lentigines syndrome may have poorly developed ovaries and delayed puberty. At birth, people with multiple lentigines syndrome are typically of normal weight and height, but in some, growth slows over time. This slow growth results in short stature in 50 to 75 percent of people with multiple lentigines syndrome. Approximately 20 percent of individuals with multiple lentigines syndrome develop hearing loss. This hearing loss is caused by abnormalities in the inner ear (sensorineural deafness) and can be present from birth or develop later in life. Other signs and symptoms of multiple lentigines syndrome include learning disorders, mild developmental delay, a sunken or protruding chest, and extra folds of skin on the back of the neck. Many of the signs and symptoms of multiple lentigines syndrome also occur in a similar disorder called Noonan syndrome. It can be difficult to tell the two disorders apart in early childhood. However, the features of the two disorders differ later in life. |
frequency | How many people are affected by multiple lentigines syndrome ? | Multiple lentigines syndrome is thought to be a rare condition; approximately 200 cases have been reported worldwide. |
genetic changes | What are the genetic changes related to multiple lentigines syndrome ? | Mutations in the PTPN11, RAF1, or BRAF genes cause multiple lentigines syndrome. Approximately 90 percent of individuals with multiple lentigines syndrome have mutations in the PTPN11 gene. RAF1 and BRAF gene mutations are responsible for a total of about 10 percent of cases. A small proportion of people with multiple lentigines syndrome do not have an identified mutation in any of these three genes. In these individuals, the cause of the condition is unknown. The PTPN11, RAF1, and BRAF genes all provide instructions for making proteins that are involved in important signaling pathways needed for the proper formation of several types of tissue during development. These proteins also play roles in the regulation of cell division, cell movement (migration), and cell differentiation (the process by which cells mature to carry out specific functions). Mutations in the PTPN11, RAF1, or BRAF genes lead to the production of a protein that functions abnormally. This abnormal functioning impairs the protein's ability to respond to cell signals. A disruption in the regulation of systems that control cell growth and division leads to the characteristic features of multiple lentigines syndrome. |
inheritance | Is multiple lentigines syndrome inherited ? | 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. |
treatment | What are the treatments for multiple lentigines syndrome ? | These resources address the diagnosis or management of multiple lentigines syndrome: - Cincinnati Children's Hospital: Cardiomyopathies - Gene Review: Gene Review: Noonan Syndrome with Multiple Lentigines - Genetic Testing Registry: LEOPARD syndrome 1 - Genetic Testing Registry: LEOPARD syndrome 2 - Genetic Testing Registry: LEOPARD syndrome 3 - Genetic Testing Registry: Noonan syndrome with multiple lentigines - MedlinePlus Encyclopedia: Hypertrophic Cardiomyopathy 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 |
information | What is (are) congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency ? | Congenital adrenal hyperplasia (CAH) due to 11-beta-hydroxylase deficiency is one of a group of disorders (collectively called congenital adrenal hyperplasia) that affect the adrenal glands. The adrenal glands are located on top of the kidneys and produce a variety of hormones that regulate many essential functions in the body. In people with CAH due to 11-beta-hydroxylase deficiency, the adrenal glands produce excess androgens, which are male sex hormones. There are two types of CAH due to 11-beta-hydroxylase deficiency, the classic form and the non-classic form. The classic form is the more severe of the two types. Females with the classic form of CAH due to 11-beta-hydroxylase deficiency have external genitalia that do not look clearly male or female (ambiguous genitalia). However, the internal reproductive organs develop normally. Males and females with the classic form of this condition have early development of their secondary sexual characteristics such as growth of facial and pubic hair, deepening of the voice, appearance of acne, and onset of a growth spurt. The early growth spurt can prevent growth later in adolescence and lead to short stature in adulthood. In addition, approximately two-thirds of individuals with the classic form of CAH due to 11-beta-hydroxylase deficiency have high blood pressure (hypertension). Hypertension typically develops within the first year of life. Females with the non-classic form of CAH due to 11-beta-hydroxylase deficiency have normal female genitalia. As affected females get older, they may develop excessive body hair growth (hirsutism) and irregular menstruation. Males with the non-classic form of this condition do not typically have any signs or symptoms except for short stature. Hypertension is not a feature of the non-classic form of CAH due to 11-beta-hydroxylase deficiency. |
frequency | How many people are affected by congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency ? | CAH due to 11-beta-hydroxylase deficiency accounts for 5 to 8 percent of all cases of congenital adrenal hyperplasia. It is estimated that CAH due to 11-beta-hydroxylase deficiency occurs in 1 in 100,000 to 200,000 newborns. This condition is more common in Moroccan Jews living in Israel, occurring in approximately 1 in 5,000 to 7,000 newborns. The classic form of CAH due to 11-beta-hydroxylase deficiency appears to be much more common than the non-classic form. |
genetic changes | What are the genetic changes related to congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency ? | Mutations in the CYP11B1 gene cause CAH due to 11-beta-hydroxylase deficiency. The CYP11B1 gene provides instructions for making an enzyme called 11-beta-hydroxylase. This enzyme is found in the adrenal glands, where it helps produce hormones called cortisol and corticosterone. Cortisol has numerous functions, such as maintaining blood sugar levels, protecting the body from stress, and suppressing inflammation. Corticosterone gets converted to the hormone aldosterone, which helps control blood pressure by maintaining proper salt and fluid levels in the body. CAH due to 11-beta-hydroxylase deficiency is caused by a shortage (deficiency) of the 11-beta-hydroxylase enzyme. When 11-beta-hydroxylase is lacking, precursors that are used to form cortisol and corticosterone build up in the adrenal glands and are converted to androgens. The excess production of androgens leads to abnormalities of sexual development, particularly in females with CAH due to 11-beta-hydroxylase deficiency. A buildup in the precursors used to form corticosterone increases salt retention, leading to hypertension in individuals with the classic form of CAH due to 11-beta-hydroxylase deficiency. The amount of functional 11-beta-hydroxylase enzyme that an individual produces typically determines the extent of abnormal sexual development. Individuals with the classic form of the condition usually have CYP11B1 gene mutations that result in the production of an enzyme with low levels of function or no function at all. Individuals with the non-classic form of the condition typically have CYP11B1 gene mutations that lead to the production of an enzyme with moderately reduced function. The severity of the signs and symptoms of sexual development do not appear to be related to the severity of the hypertension. |
inheritance | Is congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency inherited ? | 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. |
treatment | What are the treatments for congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency ? | These resources address the diagnosis or management of congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: - Genetic Testing Registry: Deficiency of steroid 11-beta-monooxygenase - MedlinePlus Encyclopedia: Congenital Adrenal Hyperplasia 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 |
information | What is (are) adult polyglucosan body disease ? | Adult polyglucosan body disease is a condition that affects the nervous system. People with this condition have problems walking due to reduced sensation in their legs (peripheral neuropathy) and progressive muscle weakness and stiffness (spasticity). Damage to the nerves that control bladder function, a condition called neurogenic bladder, causes affected individuals to have progressive difficulty controlling the flow of urine. About half of people with adult polyglucosan body disease experience a decline in intellectual function (dementia). People with adult polyglucosan body disease typically first experience signs and symptoms related to the condition between ages 30 and 60. |
frequency | How many people are affected by adult polyglucosan body disease ? | Adult polyglucosan body disease is a rare condition; although its exact prevalence is unknown, at least 50 affected individuals have been described in the medical literature. |
genetic changes | What are the genetic changes related to adult polyglucosan body disease ? | Mutations in the GBE1 gene cause adult polyglucosan body disease. The GBE1 gene provides instructions for making the glycogen branching enzyme. This enzyme is involved in the production of a complex sugar called glycogen, which is a major source of stored energy in the body. Most GBE1 gene mutations result in a shortage (deficiency) of the glycogen branching enzyme, which leads to the production of abnormal glycogen molecules. These abnormal glycogen molecules, called polyglucosan bodies, accumulate within cells and cause damage. Nerve cells (neurons) appear to be particularly vulnerable to the accumulation of polyglucosan bodies in people with this disorder, leading to impaired neuronal function. Some mutations in the GBE1 gene that cause adult polyglucosan body disease do not result in a shortage of glycogen branching enzyme. In people with these mutations, the activity of this enzyme is normal. How mutations cause the disease in these individuals is unclear. Other people with adult polyglucosan body disease do not have identified mutations in the GBE1 gene. In these individuals, the cause of the disease is unknown. |
inheritance | Is adult polyglucosan body disease inherited ? | 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. |
treatment | What are the treatments for adult polyglucosan body disease ? | These resources address the diagnosis or management of adult polyglucosan body disease: - Gene Review: Gene Review: Adult Polyglucosan Body Disease - Genetic Testing Registry: Polyglucosan body disease, adult - MedlinePlus Encyclopedia: Neurogenic Bladder - MedlinePlus Encyclopedia: Spasticity 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 |
information | What is (are) cerebral cavernous malformation ? | Cerebral cavernous malformations are collections of small blood vessels (capillaries) in the brain that are enlarged and irregular in structure. These capillaries have abnormally thin walls, and they lack other support tissues, such as elastic fibers, which normally make them stretchy. As a result, the blood vessels are prone to leakage, which can cause the health problems related to this condition. Cavernous malformations can occur anywhere in the body, but usually produce serious signs and symptoms only when they occur in the brain and spinal cord (which are described as cerebral). Approximately 25 percent of individuals with cerebral cavernous malformations never experience any related health problems. Other people with this condition may experience serious signs and symptoms such as headaches, seizures, paralysis, hearing or vision loss, and bleeding in the brain (cerebral hemorrhage). Severe brain hemorrhages can result in death. The location and number of cerebral cavernous malformations determine the severity of this disorder. These malformations can change in size and number over time. There are two forms of the condition: familial and sporadic. The familial form is passed from parent to child, and affected individuals typically have multiple cerebral cavernous malformations. The sporadic form occurs in people with no family history of the disorder. These individuals typically have only one malformation. |
frequency | How many people are affected by cerebral cavernous malformation ? | Cerebral cavernous malformations affect about 0.5 percent of the population worldwide. |
genetic changes | What are the genetic changes related to cerebral cavernous malformation ? | Mutations in at least three genes, KRIT1 (also known as CCM1), CCM2, and PDCD10 (also known as CCM3), cause familial cerebral cavernous malformations. The precise functions of these genes are not fully understood. Studies show that the proteins produced from these genes are found in the junctions connecting neighboring blood vessel cells. The proteins interact with each other as part of a complex that strengthens the interactions between cells and limits leakage from the blood vessels. Mutations in any of the three genes impair the function of the protein complex, resulting in weakened cell-to-cell junctions and increased leakage from vessels as seen in cerebral cavernous malformations. Mutations in these three genes account for 85 to 95 percent of all cases of familial cerebral cavernous malformations. The remaining 5 to 15 percent of cases may be due to mutations in unidentified genes or to other unknown causes. Mutations in the KRIT1, CCM2, and PDCD10 genes are not involved in sporadic cerebral cavernous malformations. The cause of this form of the condition is unknown. |
inheritance | Is cerebral cavernous malformation inherited ? | This condition has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In the familial form, an affected person inherits the mutation from one affected parent. Most people with cerebral cavernous malformations have the sporadic form of the disorder. These cases occur in people with no history of the disorder in their family. |
treatment | What are the treatments for cerebral cavernous malformation ? | These resources address the diagnosis or management of cerebral cavernous malformation: - Angioma Alliance: Imaging and Diagnostics - Gene Review: Gene Review: Familial Cerebral Cavernous Malformation - Genetic Testing Registry: Cerebral cavernous malformation - Genetic Testing Registry: Cerebral cavernous malformations 1 - Genetic Testing Registry: Cerebral cavernous malformations 2 - Genetic Testing Registry: Cerebral cavernous malformations 3 - MedlinePlus Encyclopedia: Cerebral angiography 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 |
information | What is (are) succinate-CoA ligase deficiency ? | Succinate-CoA ligase deficiency is an inherited disorder that affects the early development of the brain and other body systems. One of the earliest signs of the disorder is very weak muscle tone (severe hypotonia), which appears in the first few months of life. Severe hypotonia delays the development of motor skills such as holding up the head and rolling over. Many affected children also have muscle weakness and reduced muscle mass, which prevents them from standing and walking independently. Additional features of succinate-CoA ligase deficiency can include progressive abnormal curvature of the spine (scoliosis or kyphosis), uncontrolled movements (dystonia), severe hearing loss, and seizures beginning in childhood. In most affected children, a substance called methylmalonic acid builds up abnormally in the body and is excreted in urine (methylmalonic aciduria). Most children with succinate-CoA ligase deficiency also experience a failure to thrive, which means that they gain weight and grow more slowly than expected. Succinate-CoA ligase deficiency causes breathing difficulties that often lead to recurrent infections of the respiratory tract. These infections can be life-threatening, and most people with succinate-CoA ligase deficiency live only into childhood or adolescence. A few individuals with succinate-CoA ligase deficiency have had an even more severe form of the disorder known as fatal infantile lactic acidosis. Affected infants develop a toxic buildup of lactic acid in the body (lactic acidosis) in the first day of life, which leads to muscle weakness and breathing difficulties. Children with fatal infantile lactic acidosis usually live only a few days after birth. |
frequency | How many people are affected by succinate-CoA ligase deficiency ? | Although the exact prevalence of succinate-CoA ligase deficiency is unknown, it appears to be very rare. This condition occurs more frequently among people from the Faroe Islands in the North Atlantic Ocean. |
genetic changes | What are the genetic changes related to succinate-CoA ligase deficiency ? | Succinate-CoA ligase deficiency results from mutations in the SUCLA2 or SUCLG1 gene. SUCLG1 gene mutations can cause fatal infantile lactic acidosis, while mutations in either gene can cause the somewhat less severe form of the condition. The SUCLA2 and SUCLG1 genes each provide instructions for making one part (subunit) of an enzyme called succinate-CoA ligase. This enzyme plays a critical role in mitochondria, which are structures within cells that convert the energy from food into a form that cells can use. Mitochondria each contain a small amount of DNA, known as mitochondrial DNA or mtDNA, which is essential for the normal function of these structures. Succinate-CoA ligase is involved in producing and maintaining the building blocks of mitochondrial DNA. Mutations in either the SUCLA2 or SUCLG1 gene disrupt the normal function of succinate-CoA ligase. A shortage (deficiency) of this enzyme leads to problems with the production and maintenance of mitochondrial DNA. A reduction in the amount of mitochondrial DNA (known as mitochondrial DNA depletion) impairs mitochondrial function in many of the body's cells and tissues. These problems lead to hypotonia, muscle weakness, and the other characteristic features of succinate-CoA ligase deficiency. |
inheritance | Is succinate-CoA ligase deficiency inherited ? | 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. |
treatment | What are the treatments for succinate-CoA ligase deficiency ? | These resources address the diagnosis or management of succinate-CoA ligase deficiency: - Gene Review: Gene Review: SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form, with Mild Methylmalonic Aciduria - Genetic Testing Registry: Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria) - Genetic Testing Registry: Mitochondrial DNA depletion syndrome 9 (encephalomyopathic with methylmalonic aciduria) - MedlinePlus Encyclopedia: Hypotonia - MedlinePlus Encyclopedia: Lactic Acidosis 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 |
information | What is (are) Cowden syndrome ? | Cowden syndrome is a disorder characterized by multiple noncancerous, tumor-like growths called hamartomas and an increased risk of developing certain cancers. Almost everyone with Cowden syndrome develops hamartomas. These growths are most commonly found on the skin and mucous membranes (such as the lining of the mouth and nose), but they can also occur in the intestine and other parts of the body. The growth of hamartomas on the skin and mucous membranes typically becomes apparent by a person's late twenties. Cowden syndrome is associated with an increased risk of developing several types of cancer, particularly cancers of the breast, a gland in the lower neck called the thyroid, and the lining of the uterus (the endometrium). Other cancers that have been identified in people with Cowden syndrome include colorectal cancer, kidney cancer, and a form of skin cancer called melanoma. Compared with the general population, people with Cowden syndrome develop these cancers at younger ages, often beginning in their thirties or forties. Other diseases of the breast, thyroid, and endometrium are also common in Cowden syndrome. Additional signs and symptoms can include an enlarged head (macrocephaly) and a rare, noncancerous brain tumor called Lhermitte-Duclos disease. A small percentage of affected individuals have delayed development or intellectual disability. The features of Cowden syndrome overlap with those of another disorder called Bannayan-Riley-Ruvalcaba syndrome. People with Bannayan-Riley-Ruvalcaba syndrome also develop hamartomas and other noncancerous tumors. Both conditions can be caused by mutations in the PTEN gene. Some people with Cowden syndrome have had relatives diagnosed with Bannayan-Riley-Ruvalcaba syndrome, and other individuals have had the characteristic features of both conditions. Based on these similarities, researchers have proposed that Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome represent a spectrum of overlapping features known as PTEN hamartoma tumor syndrome instead of two distinct conditions. Some people have some of the characteristic features of Cowden syndrome, particularly the cancers associated with this condition, but do not meet the strict criteria for a diagnosis of Cowden syndrome. These individuals are often described as having Cowden-like syndrome. |
frequency | How many people are affected by Cowden syndrome ? | Although the exact prevalence of Cowden syndrome is unknown, researchers estimate that it affects about 1 in 200,000 people. |
genetic changes | What are the genetic changes related to Cowden syndrome ? | Changes involving at least four genes, PTEN, SDHB, SDHD, and KLLN, have been identified in people with Cowden syndrome or Cowden-like syndrome. Most cases of Cowden syndrome and a small percentage of cases of Cowden-like syndrome result from mutations in the PTEN gene. The protein produced from the PTEN gene is a tumor suppressor, which means that it normally prevents cells from growing and dividing (proliferating) too rapidly or in an uncontrolled way. Mutations in the PTEN gene prevent the protein from regulating cell proliferation effectively, leading to uncontrolled cell division and the formation of hamartomas and cancerous tumors. The PTEN gene likely has other important functions within cells; however, it is unclear how mutations in this gene cause the other features of Cowden syndrome, such as macrocephaly and intellectual disability. Other cases of Cowden syndrome and Cowden-like syndrome result from changes involving the KLLN gene. This gene provides instructions for making a protein called killin. Like the protein produced from the PTEN gene, killin probably acts as a tumor suppressor. The genetic change that causes Cowden syndrome and Cowden-like syndrome is known as promoter hypermethylation. The promoter is a region of DNA near the gene that controls gene activity (expression). Hypermethylation occurs when too many small molecules called methyl groups are attached to the promoter region. The extra methyl groups reduce the expression of the KLLN gene, which means that less killin is produced. A reduced amount of killin may allow abnormal cells to survive and proliferate inappropriately, which can lead to the formation of tumors. A small percentage of people with Cowden syndrome or Cowden-like syndrome have variations in the SDHB or SDHD gene. These genes provide instructions for making parts of an enzyme called succinate dehydrogenase (SDH), which is important for energy production in the cell. This enzyme also plays a role in signaling pathways that regulate cell survival and proliferation. Variations in the SDHB or SDHD gene alter the function of the SDH enzyme. Studies suggest that the defective enzyme may allow cells to grow and divide unchecked, leading to the formation of hamartomas and cancerous tumors. However, researchers are uncertain whether the identified SDHB and SDHD gene variants are directly associated with Cowden syndrome and Cowden-like syndrome. Some of the variants described above have also been identified in people without the features of these conditions. When Cowden syndrome and Cowden-like syndrome are not related to changes in the PTEN, SDHB, SDHD, or KLLN genes, the cause of the conditions is unknown. |
inheritance | Is Cowden syndrome inherited ? | Cowden syndrome and Cowden-like syndrome are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the condition and increase the risk of developing cancer. In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family. |
treatment | What are the treatments for Cowden syndrome ? | These resources address the diagnosis or management of Cowden syndrome: - Gene Review: Gene Review: PTEN Hamartoma Tumor Syndrome (PHTS) - Genetic Testing Registry: Cowden syndrome - Genetic Testing Registry: Cowden syndrome 1 - Genetic Testing Registry: Cowden syndrome 2 - National Cancer Institute: Genetic Testing for Hereditary Cancer Syndromes - University of Iowa: Are Tests for Cowden Syndrome Available? - University of Iowa: How is Cowden Syndrome Diagnosed? - University of Iowa: What Should I Be Doing About This Condition? 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 |
information | What is (are) familial glucocorticoid deficiency ? | Familial glucocorticoid deficiency is a condition that occurs when the adrenal glands, which are hormone-producing glands located on top of each kidney, do not produce certain hormones called glucocorticoids. These hormones, which include cortisol and corticosterone, aid in immune system function, play a role in maintaining normal blood sugar levels, help trigger nerve cell signaling in the brain, and serve many other purposes in the body. A shortage of adrenal hormones (adrenal insufficiency) causes the signs and symptoms of familial glucocorticoid deficiency. These signs and symptoms often begin in infancy or early childhood. Most affected children first develop low blood sugar (hypoglycemia). These hypoglycemic children can fail to grow and gain weight at the expected rate (failure to thrive). If left untreated, hypoglycemia can lead to seizures, learning difficulties, and other neurological problems. Hypoglycemia that is left untreated for prolonged periods can lead to neurological damage and death. Other features of familial glucocorticoid deficiency can include recurrent infections and skin coloring darker than that of other family members (hyperpigmentation). There are multiple types of familial glucocorticoid deficiency, which are distinguished by their genetic cause. |
frequency | How many people are affected by familial glucocorticoid deficiency ? | The prevalence of familial glucocorticoid deficiency is unknown. |
genetic changes | What are the genetic changes related to familial glucocorticoid deficiency ? | Mutations in the MC2R, MRAP, and NNT genes account for the majority of cases of familial glucocorticoid deficiency; mutations in other genes, some known and some unidentified, can also cause this condition. The MC2R gene provides instructions for making a protein called adrenocorticotropic hormone (ACTH) receptor, which is found primarily in the adrenal glands. The protein produced from the MRAP gene transports the ACTH receptor from the interior of the cell to the cell membrane. When the ACTH receptor is embedded within the cell membrane, it is turned on (activated) by the MRAP protein. Activated ACTH receptor can then attach (bind) to ACTH, and this binding triggers the adrenal glands to produce glucocorticoids. MC2R gene mutations lead to the production of a receptor that cannot be transported to the cell membrane or, if it does get to the cell membrane, cannot bind to ACTH. MRAP gene mutations impair the transport of the ACTH receptor to the cell membrane. Without the binding of the ACTH receptor to its hormone, there is no signal to trigger the adrenal glands to produce glucocorticoids. The NNT gene provides instructions for making an enzyme called nicotinamide nucleotide transhydrogenase. This enzyme is found embedded in the inner membrane of structures called mitochondria, which are the energy-producing centers of cells. This enzyme helps produce a substance called NADPH, which is involved in removing potentially toxic molecules called reactive oxygen species that can damage DNA, proteins, and cell membranes. NNT gene mutations impair the enzyme's ability to produce NADPH, leading to an increase in reactive oxygen species in adrenal gland tissues. Over time, these toxic molecules can impair the function of adrenal gland cells and lead to their death (apoptosis), diminishing the production of glucocorticoids. |
inheritance | Is familial glucocorticoid deficiency inherited ? | 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. |
treatment | What are the treatments for familial glucocorticoid deficiency ? | These resources address the diagnosis or management of familial glucocorticoid deficiency: - Genetic Testing Registry: ACTH resistance - Genetic Testing Registry: Glucocorticoid deficiency 2 - Genetic Testing Registry: Glucocorticoid deficiency 3 - Genetic Testing Registry: Glucocorticoid deficiency 4 - Genetic Testing Registry: Natural killer cell deficiency, familial isolated 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 |
information | What is (are) caudal regression syndrome ? | Caudal regression syndrome is a disorder that impairs the development of the lower (caudal) half of the body. Affected areas can include the lower back and limbs, the genitourinary tract, and the gastrointestinal tract. In this disorder, the bones of the lower spine (vertebrae) are frequently misshapen or missing, and the corresponding sections of the spinal cord are also irregular or missing. Affected individuals may have incomplete closure of the vertebrae around the spinal cord, a fluid-filled sac on the back covered by skin that may or may not contain part of the spinal cord, or tufts of hair at the base of the spine. People with caudal regression syndrome can also have an abnormal side-to-side curvature of the spine (scoliosis). The spinal abnormalities may affect the size and shape of the chest, leading to breathing problems in some individuals. Individuals with caudal regression syndrome may have small hip bones with a limited range of motion. The buttocks tend to be flat and dimpled. The bones of the legs are typically underdeveloped, most frequently the upper leg bones (femurs). In some individuals, the legs are bent with the knees pointing out to the side and the feet tucked underneath the hips (sometimes called a frog leg-like position). Affected individuals may be born with inward- and upward-turning feet (clubfeet), or the feet may be outward- and upward-turning (calcaneovalgus). Some people experience decreased sensation in their lower limbs. Abnormalities in the genitourinary tract in caudal regression syndrome are extremely varied. Often the kidneys are malformed; defects include a missing kidney (unilateral renal agenesis), kidneys that are fused together (horseshoe kidney), or duplication of the tubes that carry urine from each kidney to the bladder (ureteral duplication). These kidney abnormalities can lead to frequent urinary tract infections and progressive kidney failure. Additionally, affected individuals may have protrusion of the bladder through an opening in the abdominal wall (bladder exstrophy). Damage to the nerves that control bladder function, a condition called neurogenic bladder, causes affected individuals to have progressive difficulty controlling the flow of urine. Genital abnormalities in males can include the urethra opening on the underside of the penis (hypospadia) or undescended testes (cryptorchidism). Females may have an abnormal connection between the rectum and vagina (rectovaginal fistula). In severe cases, both males and females have a lack of development of the genitalia (genital agenesis). People with caudal regression syndrome may have abnormal twisting (malrotation) of the large intestine, an obstruction of the anal opening (imperforate anus), soft out-pouchings in the lower abdomen (inguinal hernias), or other malformations of the gastrointestinal tract. Affected individuals are often constipated and may experience loss of control of bladder and bowel function. |
frequency | How many people are affected by caudal regression syndrome ? | Caudal regression syndrome is estimated to occur in 1 to 2.5 per 100,000 newborns. This condition is much more common in infants born to mothers with diabetes when it affects an estimated 1 in 350 newborns. |
genetic changes | What are the genetic changes related to caudal regression syndrome ? | Caudal regression syndrome is a complex condition that may have different causes in different people. The condition is likely caused by the interaction of multiple genetic and environmental factors. One risk factor for the development of caudal regression syndrome is the presence of diabetes in the mother. It is thought that increased blood sugar levels and other metabolic problems related to diabetes may have a harmful effect on a developing fetus, increasing the likelihood of developing caudal regression syndrome. The risks to the fetus are further increased if the mother's diabetes is poorly managed. Caudal regression syndrome also occurs in infants of non-diabetic mothers, so researchers are trying to identify other factors that contribute to the development of this complex disorder. Some researchers believe that a disruption of fetal development around day 28 of pregnancy causes caudal regression syndrome. The developmental problem is thought to affect the middle layer of embryonic tissue known as the mesoderm. Disruption of normal mesoderm development impairs normal formation of parts of the skeleton, gastrointestinal system, and genitourinary system. Other researchers think that caudal regression syndrome results from the presence of an abnormal artery in the abdomen, which diverts blood flow away from the lower areas of the developing fetus. Decreased blood flow to these areas is thought to interfere with their development and result in the signs and symptoms of caudal regression syndrome. Some scientists believe that the abnormal development of the mesoderm causes the reduction of blood flow, while other scientists believe that the reduction in blood flow causes the abnormal mesoderm development. Many scientists think that the cause of caudal regression syndrome is a combination of abnormal mesoderm development and decreased blood flow to the caudal areas of the fetus. |
inheritance | Is caudal regression syndrome inherited ? | Caudal regression syndrome occurs sporadically, which means it occurs in people with no history of the condition in their family. Multiple genetic and environmental factors likely play a part in determining the risk of developing this condition. |
treatment | What are the treatments for caudal regression syndrome ? | These resources address the diagnosis or management of caudal regression syndrome: - MedlinePlus Encyclopedia: Bladder Exstrophy Repair - MedlinePlus Encyclopedia: Clubfoot - MedlinePlus Encyclopedia: Inguinal Hernia Repair - MedlinePlus Encyclopedia: Neurogenic Bladder 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 |
information | What is (are) Mowat-Wilson syndrome ? | Mowat-Wilson syndrome is a genetic condition that affects many parts of the body. Major signs of this disorder frequently include distinctive facial features, intellectual disability, delayed development, an intestinal disorder called Hirschsprung disease, and other birth defects. Children with Mowat-Wilson syndrome have a square-shaped face with deep-set, widely spaced eyes. They also have a broad nasal bridge with a rounded nasal tip; a prominent and pointed chin; large, flaring eyebrows; and uplifted earlobes with a dimple in the middle. These facial features become more distinctive with age, and adults with Mowat-Wilson syndrome have an elongated face with heavy eyebrows and a pronounced chin and jaw. Affected people tend to have a smiling, open-mouthed expression, and they typically have friendly and happy personalities. Mowat-Wilson syndrome is often associated with an unusually small head (microcephaly), structural brain abnormalities, and intellectual disability ranging from moderate to severe. Speech is absent or severely impaired, and affected people may learn to speak only a few words. Many people with this condition can understand others' speech, however, and some use sign language to communicate. If speech develops, it is delayed until mid-childhood or later. Children with Mowat-Wilson syndrome also have delayed development of motor skills such as sitting, standing, and walking. More than half of people with Mowat-Wilson syndrome are born with an intestinal disorder called Hirschsprung disease that causes severe constipation, intestinal blockage, and enlargement of the colon. Chronic constipation also occurs frequently in people with Mowat-Wilson syndrome who have not been diagnosed with Hirschsprung disease. Other features of Mowat-Wilson syndrome include short stature, seizures, heart defects, and abnormalities of the urinary tract and genitalia. Less commonly, this condition also affects the eyes, teeth, hands, and skin coloring (pigmentation). Although many different medical issues have been associated with Mowat-Wilson syndrome, not every individual with this condition has all of these features. |
frequency | How many people are affected by Mowat-Wilson syndrome ? | The prevalence of Mowat-Wilson syndrome is unknown. More than 200 people with this condition have been reported in the medical literature. |
genetic changes | What are the genetic changes related to Mowat-Wilson syndrome ? | Mutations in the ZEB2 gene cause Mowat-Wilson syndrome. The ZEB2 gene provides instructions for making a protein that plays a critical role in the formation of many organs and tissues before birth. This protein is a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of particular genes. Researchers believe that the ZEB2 protein is involved in the development of tissues that give rise to the nervous system, digestive tract, facial features, heart, and other organs. Mowat-Wilson syndrome almost always results from a loss of one working copy of the ZEB2 gene in each cell. In some cases, the entire gene is deleted. In other cases, mutations within the gene lead to the production of an abnormally short, nonfunctional version of the ZEB2 protein. A shortage of this protein disrupts the normal development of many organs and tissues, which causes the varied signs and symptoms of Mowat-Wilson syndrome. |
inheritance | Is Mowat-Wilson syndrome inherited ? | 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. |
treatment | What are the treatments for Mowat-Wilson syndrome ? | These resources address the diagnosis or management of Mowat-Wilson syndrome: - Gene Review: Gene Review: Mowat-Wilson Syndrome - Genetic Testing Registry: Mowat-Wilson syndrome - 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 |
information | What is (are) intranuclear rod myopathy ? | Intranuclear rod myopathy is a disorder that primarily affects skeletal muscles, which are muscles that the body uses for movement. People with intranuclear rod myopathy have severe muscle weakness (myopathy) and poor muscle tone (hypotonia) throughout the body. Signs and symptoms of this condition are apparent in infancy and include feeding and swallowing difficulties, a weak cry, and difficulty with controlling head movements. Affected babies are sometimes described as "floppy" and may be unable to move on their own. The severe muscle weakness that occurs in intranuclear rod myopathy also affects the muscles used for breathing. Individuals with this disorder may take shallow breaths (hypoventilate), especially during sleep, resulting in a shortage of oxygen and a buildup of carbon dioxide in the blood. Frequent respiratory infections and life-threatening breathing difficulties can occur. Because of the respiratory problems, most affected individuals do not survive past infancy. Those who do survive have delayed development of motor skills such as sitting, crawling, standing, and walking. The name intranuclear rod myopathy comes from characteristic abnormal rod-shaped structures that can be seen in the nucleus of muscle cells when muscle tissue is viewed under a microscope. |
frequency | How many people are affected by intranuclear rod myopathy ? | Intranuclear rod myopathy is a rare disorder that has been identified in only a small number of individuals. Its exact prevalence is unknown. |
genetic changes | What are the genetic changes related to intranuclear rod myopathy ? | Intranuclear rod myopathy is caused by a mutation in the ACTA1 gene. This gene provides instructions for making a protein called skeletal alpha ()-actin, which is part of the actin protein family. Actin proteins are important for cell movement and the tensing of muscle fibers (muscle contraction). Thin filaments made up of actin molecules and thick filaments made up of another protein called myosin are the primary components of muscle fibers and are important for muscle contraction. Attachment (binding) and release of the overlapping thick and thin filaments allows them to move relative to each other so that the muscles can contract. ACTA1 gene mutations that cause intranuclear rod myopathy result in the accumulation of rods of skeletal -actin in the nucleus of muscle cells. Normally, most actin is found in the fluid surrounding the nucleus (the cytoplasm), with small amounts in the nucleus itself. Researchers suggest that the ACTA1 gene mutations that cause intranuclear rod myopathy may interfere with the normal transport of actin between the nucleus and the cytoplasm, resulting in the accumulation of actin in the nucleus and the formation of intranuclear rods. Abnormal accumulation of actin in the nucleus of muscle cells and a corresponding reduction of available actin in muscle fibers may impair muscle contraction and lead to the muscle weakness seen in intranuclear rod myopathy. In some people with intranuclear rod myopathy, no ACTA1 gene mutations have been identified. The cause of the disorder in these individuals is unknown. |
inheritance | Is intranuclear rod myopathy inherited ? | Intranuclear rod myopathy is an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases are not inherited; they result from new mutations in the gene and occur in people with no history of the disorder in their family. |
treatment | What are the treatments for intranuclear rod myopathy ? | These resources address the diagnosis or management of intranuclear rod myopathy: - Genetic Testing Registry: Nemaline myopathy 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 |
information | What is (are) craniofacial microsomia ? | Craniofacial microsomia is a term used to describe a spectrum of abnormalities that primarily affect the development of the skull (cranium) and face before birth. Microsomia means abnormal smallness of body structures. Most people with craniofacial microsomia have differences in the size and shape of facial structures between the right and left sides of the face (facial asymmetry). In about two-thirds of cases, both sides of the face have abnormalities, which usually differ from one side to the other. Other individuals with craniofacial microsomia are affected on only one side of the face. The facial characteristics in craniofacial microsomia typically include underdevelopment of one side of the upper or lower jaw (maxillary or mandibular hypoplasia), which can cause dental problems and difficulties with feeding and speech. In cases of severe mandibular hypoplasia, breathing may also be affected. People with craniofacial microsomia usually have ear abnormalities affecting one or both ears, typically to different degrees. They may have growths of skin (skin tags) in front of the ear (preauricular tags), an underdeveloped or absent external ear (microtia or anotia), or a closed or absent ear canal; these abnormalities may lead to hearing loss. Eye problems are less common in craniofacial microsomia, but some affected individuals have an unusually small eyeball (microphthalmia) or other eye abnormalities that result in vision loss. Abnormalities in other parts of the body, such as malformed bones of the spine (vertebrae), abnormally shaped kidneys, and heart defects, may also occur in people with craniofacial microsomia. Many other terms have been used for craniofacial microsomia. These other names generally refer to forms of craniofacial microsomia with specific combinations of signs and symptoms, although sometimes they are used interchangeably. Hemifacial microsomia often refers to craniofacial microsomia with maxillary or mandibular hypoplasia. People with hemifacial microsomia and noncancerous (benign) growths in the eye called epibulbar dermoids may be said to have Goldenhar syndrome or oculoauricular dysplasia. |
frequency | How many people are affected by craniofacial microsomia ? | Craniofacial microsomia has been estimated to occur in between 1 in 5,600 and 1 in 26,550 newborns. However, this range may be an underestimate because not all medical professionals agree on the criteria for diagnosis of this condition, and because mild cases may never come to medical attention. For reasons that are unclear, the disorder occurs about 50 percent more often in males than in females. |
genetic changes | What are the genetic changes related to craniofacial microsomia ? | It is unclear what genes are involved in craniofacial microsomia. This condition results from problems in the development of structures in the embryo called the first and second pharyngeal arches (also called branchial or visceral arches). Tissue layers in the six pairs of pharyngeal arches give rise to the muscles, arteries, nerves, and cartilage of the face and neck. Specifically, the first and second pharyngeal arches develop into the lower jaw, the nerves and muscles used for chewing and facial expression, the external ear, and the bones of the middle ear. Interference with the normal development of these structures can result in the abnormalities characteristic of craniofacial microsomia. There are several factors that can disrupt the normal development of the first and second pharyngeal arches and lead to craniofacial microsomia. Some individuals with this condition have chromosomal abnormalities such as deletions or duplications of genetic material; these individuals often have additional developmental problems or malformations. Occasionally, craniofacial microsomia occurs in multiple members of a family in a pattern that suggests inheritance of a causative gene mutation, but the gene or genes involved are unknown. In other families, individuals seem to inherit a predisposition to the disorder. The risk of craniofacial microsomia can also be increased by environmental factors, such as certain drugs taken by the mother during pregnancy. In most affected individuals, the cause of the disorder is unknown. It is not well understood why certain disruptions to development affect the first and second pharyngeal arches in particular. Researchers suggest that these structures may develop together in such a way that they respond as a unit to these disruptions. |
inheritance | Is craniofacial microsomia inherited ? | Craniofacial microsomia most often occurs in a single individual in a family and is not inherited. If the condition is caused by a chromosomal abnormality, it may be inherited from one affected parent or it may result from a new abnormality in the chromosome and occur in people with no history of the disorder in their family. In 1 to 2 percent of cases, craniofacial microsomia is inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. In rare cases, the condition is inherited in an autosomal recessive pattern, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. The gene or genes involved in craniofacial microsomia are unknown. In some affected families, people seem to inherit an increased risk of developing craniofacial microsomia, not the condition itself. In these cases, some combination of genetic changes and environmental factors may be involved. |
treatment | What are the treatments for craniofacial microsomia ? | These resources address the diagnosis or management of craniofacial microsomia: - Children's Hospital and Medical Center of the University of Nebraska - Gene Review: Gene Review: Craniofacial Microsomia Overview - Genetic Testing Registry: Goldenhar syndrome - Seattle Children's Hospital - Virginia Commonwealth University 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 |
information | What is (are) aromatase deficiency ? | Aromatase deficiency is a condition characterized by reduced levels of the female sex hormone estrogen and increased levels of the male sex hormone testosterone. Females with aromatase deficiency have a typical female chromosome pattern (46,XX) but are born with external genitalia that do not appear clearly female or male (ambiguous genitalia). These individuals typically have normal internal reproductive organs, but develop ovarian cysts early in childhood, which impair the release of egg cells from the ovaries (ovulation). In adolescence, most affected females do not develop secondary sexual characteristics, such as breast growth and menstrual periods. They tend to develop acne and excessive body hair growth (hirsutism). Men with this condition have a typical male chromosome pattern (46,XY) and are born with male external genitalia. Some men with this condition have decreased sex drive, abnormal sperm production, or testes that are small or undescended (cryptorchidism). There are other features associated with aromatase deficiency that can affect both males and females. Affected individuals are abnormally tall because of excessive growth of long bones in the arms and legs. The abnormal bone growth results in slowed mineralization of bones (delayed bone age) and thinning of the bones (osteoporosis), which can lead to bone fractures with little trauma. Males and females with aromatase deficiency can have abnormally high blood sugar (hyperglycemia) because the body does not respond correctly to the hormone insulin. In addition, they can have excessive weight gain and a fatty liver. Women who are pregnant with fetuses that have aromatase deficiency often experience mild symptoms of the disorder even though they themselves do not have the disorder. These women may develop hirsutism, acne, an enlarged clitoris (clitoromegaly), and a deep voice. These features can appear as early as 12 weeks of pregnancy and go away soon after delivery. |
frequency | How many people are affected by aromatase deficiency ? | The prevalence of aromatase deficiency is unknown; approximately 20 cases have been described in the medical literature. |
genetic changes | What are the genetic changes related to aromatase deficiency ? | Mutations in the CYP19A1 gene cause aromatase deficiency. The CYP19A1 gene provides instructions for making an enzyme called aromatase. This enzyme converts a class of hormones called androgens, which are involved in male sexual development, to different forms of estrogen. In females, estrogen guides female sexual development before birth and during puberty. In both males and females, estrogen plays a role in regulating bone growth and blood sugar levels. During fetal development, aromatase converts androgens to estrogens in the placenta, which is the link between the mother's blood supply and the fetus. This conversion in the placenta prevents androgens from directing sexual development in female fetuses. After birth, the conversion of androgens to estrogens takes place in multiple tissues. CYP19A1 gene mutations that cause aromatase deficiency decrease or eliminate aromatase activity. A shortage of functional aromatase results in an inability to convert androgens to estrogens before birth and throughout life. As a result, there is a decrease in estrogen production and an increase in the levels of androgens, including testosterone. In affected individuals, these abnormal hormone levels lead to impaired female sexual development, unusual bone growth, insulin resistance, and other signs and symptoms of aromatase deficiency. In women who are pregnant with an affected fetus, excess androgens in the placenta pass into the woman's bloodstream, which may cause her to have temporary signs and symptoms of aromatase deficiency. |
inheritance | Is aromatase deficiency inherited ? | 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. |
treatment | What are the treatments for aromatase deficiency ? | These resources address the diagnosis or management of aromatase deficiency: - Genetic Testing Registry: Aromatase deficiency - MedlinePlus Encyclopedia: Ovarian Overproduction of Androgens 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 |
information | What is (are) cri-du-chat syndrome ? | Cri-du-chat (cat's cry) syndrome, also known as 5p- (5p minus) syndrome, is a chromosomal condition that results when a piece of chromosome 5 is missing. Infants with this condition often have a high-pitched cry that sounds like that of a cat. The disorder is characterized by intellectual disability and delayed development, small head size (microcephaly), low birth weight, and weak muscle tone (hypotonia) in infancy. Affected individuals also have distinctive facial features, including widely set eyes (hypertelorism), low-set ears, a small jaw, and a rounded face. Some children with cri-du-chat syndrome are born with a heart defect. |
frequency | How many people are affected by cri-du-chat syndrome ? | Cri-du-chat syndrome occurs in an estimated 1 in 20,000 to 50,000 newborns. This condition is found in people of all ethnic backgrounds. |
genetic changes | What are the genetic changes related to cri-du-chat syndrome ? | Cri-du-chat syndrome is caused by a deletion of the end of the short (p) arm of chromosome 5. This chromosomal change is written as 5p-. The size of the deletion varies among affected individuals; studies suggest that larger deletions tend to result in more severe intellectual disability and developmental delay than smaller deletions. The signs and symptoms of cri-du-chat syndrome are probably related to the loss of multiple genes on the short arm of chromosome 5. Researchers believe that the loss of a specific gene, CTNND2, is associated with severe intellectual disability in some people with this condition. They are working to determine how the loss of other genes in this region contributes to the characteristic features of cri-du-chat syndrome. |
inheritance | Is cri-du-chat syndrome inherited ? | Most cases of cri-du-chat syndrome are not inherited. The deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family. About 10 percent of people with cri-du-chat syndrome inherit the chromosome abnormality from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which no genetic material is gained or lost. Balanced translocations usually do not cause any health problems; however, they can become unbalanced as they are passed to the next generation. Children who inherit an unbalanced translocation can have a chromosomal rearrangement with extra or missing genetic material. Individuals with cri-du-chat syndrome who inherit an unbalanced translocation are missing genetic material from the short arm of chromosome 5, which results in the intellectual disability and health problems characteristic of this disorder. |
treatment | What are the treatments for cri-du-chat syndrome ? | These resources address the diagnosis or management of cri-du-chat syndrome: - Cri du Chat Syndrome Support Group (UK): Diagnosis - Cri du Chat Syndrome Support Group (UK): Therapies - Genetic Testing Registry: 5p partial monosomy syndrome - MedlinePlus Encyclopedia: Cri du Chat 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 |
information | What is (are) Schwartz-Jampel syndrome ? | Schwartz-Jampel syndrome is a rare condition characterized by permanent muscle stiffness (myotonia) and bone abnormalities known as chondrodysplasia. The signs and symptoms of this condition become apparent sometime after birth, usually in early childhood. Either muscle stiffness or chondrodysplasia can appear first. The muscle and bone abnormalities worsen in childhood, although most affected individuals have a normal lifespan. The specific features of Schwartz-Jampel syndrome vary widely. Myotonia involves continuous tensing (contraction) of muscles used for movement (skeletal muscles) throughout the body. This sustained muscle contraction causes stiffness that interferes with eating, sitting, walking, and other movements. Sustained contraction of muscles in the face leads to a fixed, "mask-like" facial expression with narrow eye openings (blepharophimosis) and pursed lips. This facial appearance is very specific to Schwartz-Jampel syndrome. Affected individuals may also be nearsighted and experience abnormal blinking or spasms of the eyelids (blepharospasm). Chondrodysplasia affects the development of the skeleton, particularly the long bones in the arms and legs and the bones of the hips. These bones are shortened and unusually wide at the ends, so affected individuals have short stature. The long bones may also be abnormally curved (bowed). Other bone abnormalities associated with Schwartz-Jampel syndrome include a protruding chest (pectus carinatum), abnormal curvature of the spine, flattened bones of the spine (platyspondyly), and joint abnormalities called contractures that further restrict movement. Researchers originally described two types of Schwartz-Jampel syndrome. Type 1 has the signs and symptoms described above, while type 2 has more severe bone abnormalities and other health problems and is usually life-threatening in early infancy. Researchers have since discovered that the condition they thought was Schwartz-Jampel syndrome type 2 is actually part of another disorder, Stve-Wiedemann syndrome, which is caused by mutations in a different gene. They have recommended that the designation Schwartz-Jampel syndrome type 2 no longer be used. |
frequency | How many people are affected by Schwartz-Jampel syndrome ? | Schwartz-Jampel syndrome appears to be a rare condition. About 150 cases have been reported in the medical literature. |
genetic changes | What are the genetic changes related to Schwartz-Jampel syndrome ? | Schwartz-Jampel syndrome is caused by mutations in the HSPG2 gene. This gene provides instructions for making a protein known as perlecan. This protein is found in the extracellular matrix, which is the intricate lattice of proteins and other molecules that forms in the spaces between cells. Specifically, it is found in part of the extracellular matrix called the basement membrane, which is a thin, sheet-like structure that separates and supports cells in many tissues. Perlecan is also found in cartilage, a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Perlecan has multiple functions, including cell signaling and the normal maintenance of basement membranes and cartilage. The protein also plays a critical role at the neuromuscular junction, which is the area between the ends of nerve cells and muscle cells where signals are relayed to trigger muscle contraction. The mutations that cause Schwartz-Jampel syndrome reduce the amount of perlecan that is produced or lead to a version of perlecan that is only partially functional. A reduction in the amount or function of this protein disrupts the normal development of cartilage and bone tissue, which underlies chondrodysplasia in affected individuals. A reduced amount of functional perlecan at the neuromuscular junction likely alters the balance of other molecules that signal when muscles should contract and when they should relax. As a result, muscle contraction is triggered continuously, leading to myotonia. |
inheritance | Is Schwartz-Jampel syndrome inherited ? | 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. |
treatment | What are the treatments for Schwartz-Jampel syndrome ? | These resources address the diagnosis or management of Schwartz-Jampel syndrome: - Genetic Testing Registry: Schwartz Jampel syndrome type 1 - National Institute of Neurological Disorders and Stroke: Myotonia Information Page 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 |
information | What is (are) Meckel syndrome ? | Meckel syndrome is a disorder with severe signs and symptoms that affect many parts of the body. The most common features are enlarged kidneys with numerous fluid-filled cysts; an occipital encephalocele, which is a sac-like protrusion of the brain through an opening at the back of the skull; and the presence of extra fingers and toes (polydactyly). Most affected individuals also have a buildup of scar tissue (fibrosis) in the liver. Other signs and symptoms of Meckel syndrome vary widely among affected individuals. Numerous abnormalities of the brain and spinal cord (central nervous system) have been reported in people with Meckel syndrome, including a group of birth defects known as neural tube defects. These defects occur when a structure called the neural tube, a layer of cells that ultimately develops into the brain and spinal cord, fails to close completely during the first few weeks of embryonic development. Meckel syndrome can also cause problems with development of the eyes and other facial features, heart, bones, urinary system, and genitalia. Because of their serious health problems, most individuals with Meckel syndrome die before or shortly after birth. Most often, affected infants die of respiratory problems or kidney failure. |
frequency | How many people are affected by Meckel syndrome ? | Meckel syndrome affects 1 in 13,250 to 1 in 140,000 people worldwide. It is more common in certain populations; for example, the condition affects about 1 in 9,000 people of Finnish ancestry and about 1 in 3,000 people of Belgian ancestry. |
genetic changes | What are the genetic changes related to Meckel syndrome ? | Meckel syndrome can be caused by mutations in one of at least eight genes. The proteins produced from these genes are known or suspected to play roles in cell structures called cilia. Cilia are microscopic, finger-like projections that stick out from the surface of cells and are involved in signaling pathways that transmit information between cells. Cilia are important for the structure and function of many types of cells, including brain cells and certain cells in the kidneys and liver. Mutations in the genes associated with Meckel syndrome lead to problems with the structure and function of cilia. Defects in these cell structures probably disrupt important chemical signaling pathways during early development. Although researchers believe that defective cilia are responsible for most of the features of this disorder, it remains unclear how they lead to specific developmental abnormalities of the brain, kidneys, and other parts of the body. Mutations in the eight genes known to be associated with Meckel syndrome account for about 75 percent of all cases of the condition. In the remaining cases, the genetic cause is unknown. Mutations in several other genes have been identified in people with features similar to those of Meckel syndrome, although it is unclear whether these individuals actually have Meckel syndrome or a related disorder (often described as a "Meckel-like phenotype"). |
inheritance | Is Meckel syndrome inherited ? | 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. |
treatment | What are the treatments for Meckel syndrome ? | These resources address the diagnosis or management of Meckel syndrome: - Genetic Testing Registry: Meckel syndrome type 1 - Genetic Testing Registry: Meckel syndrome type 2 - Genetic Testing Registry: Meckel syndrome type 3 - Genetic Testing Registry: Meckel syndrome type 4 - Genetic Testing Registry: Meckel syndrome type 5 - Genetic Testing Registry: Meckel syndrome type 6 - Genetic Testing Registry: Meckel syndrome type 7 - Genetic Testing Registry: Meckel syndrome type 8 - Genetic Testing Registry: Meckel syndrome, type 10 - Genetic Testing Registry: Meckel syndrome, type 9 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 |
information | What is (are) celiac disease ? | Celiac disease is a condition in which the immune system is abnormally sensitive to gluten, a protein found in wheat, rye, and barley. Celiac disease is an autoimmune disorder; autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. Without a strict, lifelong gluten-free diet, inflammation resulting from immune system overactivity may cause a wide variety of signs and symptoms involving many parts of the body. Celiac disease can develop at any age after an individual starts eating foods containing gluten. The classic symptoms of the condition result from inflammation affecting the gastrointestinal tract. This inflammation damages the villi, which are small, finger-like projections that line the small intestine and provide a greatly increased surface area to absorb nutrients. In celiac disease, the villi become shortened and eventually flatten out. Intestinal damage causes diarrhea and poor absorption of nutrients, which may lead to weight loss. Abdominal pain, swelling (distention), and food intolerances are common in celiac disease. Inflammation associated with celiac disease may lead to an increased risk of developing certain gastrointestinal cancers such as cancers of the small intestine or esophagus. Inflammation and poor nutrient absorption may lead to problems affecting many other organs and systems of the body in affected individuals. These health problems may include iron deficiency that results in a low number of red blood cells (anemia), vitamin deficiencies, low bone mineral density (osteoporosis), itchy skin rashes (dermatitis herpetiformis), defects in the enamel of the teeth, chronic fatigue, joint pain, poor growth, delayed puberty, infertility, or repeated miscarriages. Neurological problems have also been associated with celiac disease; these include migraine headaches, depression, attention deficit hyperactivity disorder (ADHD), and recurrent seizures (epilepsy). Many people with celiac disease have one or more of these varied health problems but do not have gastrointestinal symptoms. This form of the condition is called nonclassic celiac disease. Researchers now believe that nonclassic celiac disease is actually more common than the classic form. Celiac disease often goes undiagnosed because many of its signs and symptoms are nonspecific, which means they may occur in many disorders. Most people who have one or more of these nonspecific health problems do not have celiac disease. On average, a diagnosis of celiac disease is not made until 6 to 10 years after symptoms begin. Some people have silent celiac disease, in which they have no symptoms of the disorder. However, people with silent celiac disease do have immune proteins in their blood (antibodies) that are common in celiac disease. They also have inflammatory damage to their small intestine that can be detected with a biopsy. In a small number of cases, celiac disease does not improve with a gluten-free diet and progresses to a condition called refractory sprue. Refractory sprue is characterized by chronic inflammation of the gastrointestinal tract, poor absorption of nutrients, and an increased risk of developing a type of cancer of the immune cells called T-cell lymphoma. |
frequency | How many people are affected by celiac disease ? | Celiac disease is a common disorder. Its prevalence has been estimated at about 1 in 100 people worldwide. |
genetic changes | What are the genetic changes related to celiac disease ? | The risk of developing celiac disease is increased by certain variants of the HLA-DQA1 and HLA-DQB1 genes. These genes provide instructions for making proteins that play a critical role in the immune system. The HLA-DQA1 and HLA-DQB1 genes belong to a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders such as viruses and bacteria. The proteins produced from the HLA-DQA1 and HLA-DQB1 genes attach (bind) to each other to form a functional protein complex called an antigen-binding DQ heterodimer. This complex, which is present on the surface of certain immune system cells, attaches to protein fragments (peptides) outside the cell. If the immune system recognizes the peptides as foreign (such as viral or bacterial peptides), it triggers a response to attack the invading viruses or bacteria. Celiac disease is associated with an inappropriate immune response to a segment of the gluten protein called gliadin. This inappropriate activation of the immune system causes inflammation that damages the body's organs and tissues and leads to the signs and symptoms of celiac disease. Almost all people with celiac disease have specific variants of the HLA-DQA1 and HLA-DQB1 genes, which seem to increase the risk of an inappropriate immune response to gliadin. However, these variants are also found in 30 percent of the general population, and only 3 percent of individuals with the gene variants develop celiac disease. It appears likely that other contributors, such as environmental factors and changes in other genes, also influence the development of this complex disorder. |
inheritance | Is celiac disease inherited ? | Celiac disease tends to cluster in families. Parents, siblings, or children (first-degree relatives) of people with celiac disease have between a 4 and 15 percent chance of developing the disorder. However, the inheritance pattern is unknown. |
treatment | What are the treatments for celiac disease ? | These resources address the diagnosis or management of celiac disease: - Beth Israel Deaconess: Celiac Center - Columbia University Celiac Disease Center - Gene Review: Gene Review: Celiac Disease - Genetic Testing Registry: Celiac disease - Massachusetts General Hospital Center for Celiac Research and Treatment - MedlinePlus Encyclopedia: Celiac Disease Nutritional Considerations - North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition: Gluten-Free Diet Guide - University of Chicago Celiac Disease Center These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care |
information | What is (are) Lesch-Nyhan syndrome ? | Lesch-Nyhan syndrome is a condition that occurs almost exclusively in males. It is characterized by neurological and behavioral abnormalities and the overproduction of uric acid. Uric acid is a waste product of normal chemical processes and is found in blood and urine. Excess uric acid can be released from the blood and build up under the skin and cause gouty arthritis (arthritis caused by an accumulation of uric acid in the joints). Uric acid accumulation can also cause kidney and bladder stones. The nervous system and behavioral disturbances experienced by people with Lesch-Nyhan syndrome include abnormal involuntary muscle movements, such as tensing of various muscles (dystonia), jerking movements (chorea), and flailing of the limbs (ballismus). People with Lesch-Nyhan syndrome usually cannot walk, require assistance sitting, and generally use a wheelchair. Self-injury (including biting and head banging) is the most common and distinctive behavioral problem in individuals with Lesch-Nyhan syndrome. |
frequency | How many people are affected by Lesch-Nyhan syndrome ? | The prevalence of Lesch-Nyhan syndrome is approximately 1 in 380,000 individuals. This condition occurs with a similar frequency in all populations. |
genetic changes | What are the genetic changes related to Lesch-Nyhan syndrome ? | Mutations in the HPRT1 gene cause Lesch-Nyhan syndrome. The HPRT1 gene provides instructions for making an enzyme called hypoxanthine phosphoribosyltransferase 1. This enzyme is responsible for recycling purines, a type of building block of DNA and its chemical cousin RNA. Recycling purines ensures that cells have a plentiful supply of building blocks for the production of DNA and RNA. HPRT1 gene mutations that cause Lesch-Nyhan syndrome result in a severe shortage (deficiency) or complete absence of hypoxanthine phosphoribosyltransferase 1. When this enzyme is lacking, purines are broken down but not recycled, producing abnormally high levels of uric acid. For unknown reasons, a deficiency of hypoxanthine phosphoribosyltransferase 1 is associated with low levels of a chemical messenger in the brain called dopamine. Dopamine transmits messages that help the brain control physical movement and emotional behavior, and its shortage may play a role in the movement problems and other features of this disorder. However, it is unclear how a shortage of hypoxanthine phosphoribosyltransferase 1 causes the neurological and behavioral problems characteristic of Lesch-Nyhan syndrome. Some people with HPRT1 gene mutations produce some functional enzyme. These individuals are said to have Lesch-Nyhan variant. The signs and symptoms of Lesch-Nyhan variant are often milder than those of Lesch-Nyhan syndrome and do not include self-injury. |
inheritance | Is Lesch-Nyhan syndrome inherited ? | This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. |
treatment | What are the treatments for Lesch-Nyhan syndrome ? | These resources address the diagnosis or management of Lesch-Nyhan syndrome: - Gene Review: Gene Review: Lesch-Nyhan Syndrome - Genetic Testing Registry: Lesch-Nyhan syndrome - MedlinePlus Encyclopedia: Lesch-Nyhan Syndrome - MedlinePlus Encyclopedia: Uric Acid Crystals 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 |
information | What is (are) dopa-responsive dystonia ? | Dopa-responsive dystonia is a disorder that involves involuntary muscle contractions, tremors, and other uncontrolled movements (dystonia). The features of this condition range from mild to severe. This form of dystonia is called dopa-responsive dystonia because the signs and symptoms typically improve with sustained use of a medication known as L-Dopa. Signs and symptoms of dopa-responsive dystonia usually appear during childhood, most commonly around age 6. The first signs of the condition are typically the development of inward- and upward-turning feet (clubfeet) and dystonia in the lower limbs. The dystonia spreads to the upper limbs over time; beginning in adolescence, the whole body is typically involved. Affected individuals may have unusual limb positioning and a lack of coordination when walking or running. Some people with this condition have sleep problems or episodes of depression more frequently than would normally be expected. Over time, affected individuals often develop a group of movement abnormalities called parkinsonism. These abnormalities include unusually slow movement (bradykinesia), muscle rigidity, tremors, and an inability to hold the body upright and balanced (postural instability). The movement difficulties associated with dopa-responsive dystonia usually worsen with age but stabilize around age 30. A characteristic feature of dopa-responsive dystonia is worsening of movement problems later in the day and an improvement of symptoms in the morning, after sleep (diurnal fluctuation). Rarely, the movement problems associated with dopa-responsive dystonia do not appear until adulthood. In these adult-onset cases, parkinsonism usually develops before dystonia, and movement problems are slow to worsen and do not show diurnal fluctuations. |
frequency | How many people are affected by dopa-responsive dystonia ? | Dopa-responsive dystonia is estimated to affect 1 per million people worldwide. However, the disorder is likely underdiagnosed because the condition may not be identified in people with mild symptoms, or it may be misdiagnosed in people who have symptoms similar to other movement disorders. |
genetic changes | What are the genetic changes related to dopa-responsive dystonia ? | Mutations in the GCH1 gene are the most common cause of dopa-responsive dystonia. Less often, mutations in the TH or SPR gene cause this condition. The GCH1 gene provides instructions for making an enzyme called GTP cyclohydrolase. This enzyme is involved in the first of three steps in the production of a molecule called tetrahydrobiopterin (BH4). The SPR gene, which provides instructions for making the sepiapterin reductase enzyme, is involved in the last step of tetrahydrobiopterin production. Tetrahydrobiopterin helps process several protein building blocks (amino acids), and is involved in the production of chemicals called neurotransmitters, which transmit signals between nerve cells in the brain. Specifically, tetrahydrobiopterin is involved in the production of two neurotransmitters called dopamine and serotonin. Among their many functions, dopamine transmits signals within the brain to produce smooth physical movements, and serotonin regulates mood, emotion, sleep, and appetite. The protein produced from the TH gene is also involved in dopamine production. The TH gene provides instructions for making the enzyme tyrosine hydroxylase, which helps convert the amino acid tyrosine to dopamine. Mutations in the GCH1 or SPR gene impair the production of tetrahydrobiopterin, which leads to a decrease in the amount of available dopamine. TH gene mutations result in the production of a tyrosine hydroxylase enzyme with reduced function, which leads to a decrease in dopamine production. A reduction in the amount of dopamine interferes with the brain's ability to produce smooth physical movements, resulting in the dystonia, tremor, and other movement problems associated with dopa-responsive dystonia. Sleep and mood disorders also occur in some individuals with GCH1 or SPR gene mutations; these disorders likely result from a disruption in the production of serotonin. Problems with sleep and episodes of depression are not seen in people with dopa-responsive dystonia caused by TH gene mutations, which is sometimes referred to as Segawa syndrome. Some people with dopa-responsive dystonia do not have an identified mutation in the GCH1, TH, or SPR gene. The cause of the condition in these individuals is unknown. |
inheritance | Is dopa-responsive dystonia inherited ? | When dopa-responsive dystonia is caused by mutations in the GCH1 gene, it 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 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 inherit the altered GCH1 gene never develop features of dopa-responsive dystonia. (This situation is known as reduced penetrance.) It is unclear why some people with a mutated gene develop the disease and other people with a mutated gene do not. For unknown reasons, dopa-responsive dystonia caused by mutations in the GCH1 gene affects females two to four times more often than males. When TH gene mutations are responsible for causing dopa-responsive dystonia, it 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. When dopa-responsive dystonia is caused by mutations in the SPR gene, it can have either an autosomal recessive or, less commonly, an autosomal dominant pattern of inheritance. |
treatment | What are the treatments for dopa-responsive dystonia ? | These resources address the diagnosis or management of dopa-responsive dystonia: - Dartmouth-Hitchcock Children's Hospital at Dartmouth - Gene Review: Gene Review: Dystonia Overview - Gene Review: Gene Review: GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia - Genetic Testing Registry: Dystonia 5, Dopa-responsive type - Genetic Testing Registry: Segawa syndrome, autosomal recessive - Genetic Testing Registry: Sepiapterin reductase deficiency These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care |
information | What is (are) cutis laxa ? | Cutis laxa is a disorder of connective tissue, which is the tissue that forms the body's supportive framework. Connective tissue provides structure and strength to the muscles, joints, organs, and skin. The term "cutis laxa" is Latin for loose or lax skin, and this condition is characterized by skin that is sagging and not stretchy (inelastic). The skin often hangs in loose folds, causing the face and other parts of the body to have a droopy appearance. Extremely wrinkled skin may be particularly noticeable on the neck and in the armpits and groin. Cutis laxa can also affect connective tissue in other parts of the body, including the heart, blood vessels, joints, intestines, and lungs. The disorder can cause heart problems and abnormal narrowing, bulging, or tearing of critical arteries. Affected individuals may have soft out-pouchings in the lower abdomen (inguinal hernia) or around the belly button (umbilical hernia). Pouches called diverticula can also develop in the walls of certain organs, such as the bladder and intestines. During childhood, some people with cutis laxa develop a lung disease called emphysema, which can make it difficult to breathe. Depending on which organs and tissues are affected, the signs and symptoms of cutis laxa can range from mild to life-threatening. Researchers have described several different forms of cutis laxa. The forms are often distinguished by their pattern of inheritance: autosomal dominant, autosomal recessive, or X-linked. In general, the autosomal recessive forms of cutis laxa tend to be more severe than the autosomal dominant form. In addition to the features described above, some people with autosomal recessive cutis laxa have delayed development, intellectual disability, seizures, and problems with movement that can worsen over time. The X-linked form of cutis laxa is often called occipital horn syndrome. This form of the disorder is considered a mild type of Menkes syndrome, which is a condition that affects copper levels in the body. In addition to sagging and inelastic skin, occipital horn syndrome is characterized by wedge-shaped calcium deposits in a bone at the base of the skull (the occipital bone), coarse hair, and loose joints. |
frequency | How many people are affected by cutis laxa ? | Cutis laxa is a rare disorder. About 200 affected families worldwide have been reported. |
genetic changes | What are the genetic changes related to cutis laxa ? | Cutis laxa can be caused by mutations in the ATP6V0A2, ATP7A, EFEMP2, ELN, or FBLN5 gene. Most of these genes are involved in the formation and function of elastic fibers, which are slender bundles of proteins that provide strength and flexibility to connective tissue throughout the body. Elastic fibers allow the skin to stretch, the lungs to expand and contract, and arteries to handle blood flowing through them at high pressure. The major component of elastic fibers, a protein called elastin, is produced from the ELN gene. Other proteins that appear to have critical roles in the assembly of elastic fibers are produced from the EFEMP2, FBLN5, and ATP6V0A2 genes. Mutations in any of these genes disrupt the formation, assembly, or function of elastic fibers. A shortage of these fibers weakens connective tissue in the skin, arteries, lungs, and other organs. These defects in connective tissue underlie the major features of cutis laxa. Occipital horn syndrome is caused by mutations in the ATP7A gene. This gene provides instructions for making a protein that is important for regulating copper levels in the body. Mutations in the ATP7A gene result in poor distribution of copper to the body's cells. A reduced supply of copper can decrease the activity of numerous copper-containing enzymes that are necessary for the structure and function of bone, skin, hair, blood vessels, and the nervous system. The signs and symptoms of occipital horn syndrome are caused by the reduced activity of these copper-containing enzymes. Mutations in the genes described above account for only a small percentage of all cases of cutis laxa. Researchers suspect that mutations in other genes, which have not been identified, can also be responsible for the condition. Rare cases of cutis laxa are acquired, which means they are probably not caused by inherited gene mutations. Acquired cutis laxa appears later in life and is related to the destruction of normal elastic fibers. The causes of acquired cutis laxa are unclear, although it may occur as a side effect of treatment with medications that remove copper from the body (copper chelating drugs). |
inheritance | Is cutis laxa inherited ? | Cutis laxa can have an autosomal dominant, autosomal recessive, or X-linked recessive pattern of inheritance. When cutis laxa is caused by ELN mutations, it has an autosomal dominant inheritance pattern. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. Rarely, cases of cutis laxa resulting from FBLN5 mutations can also have an autosomal dominant pattern of inheritance. Researchers have described at least two forms of autosomal recessive cutis laxa. Type I results from mutations in the EFEMP2 or FBLN5 gene, while type II is caused by mutations in the ATP6V02 gene. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Occipital horn syndrome has an X-linked recessive pattern of inheritance. It results from mutations in the ATP7A gene, which is located on the X chromosome. The X chromosome is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. |
treatment | What are the treatments for cutis laxa ? | These resources address the diagnosis or management of cutis laxa: - Gene Review: Gene Review: ATP6V0A2-Related Cutis Laxa - Gene Review: Gene Review: ATP7A-Related Copper Transport Disorders - Gene Review: Gene Review: EFEMP2-Related Cutis Laxa - Gene Review: Gene Review: FBLN5-Related Cutis Laxa - Genetic Testing Registry: Autosomal recessive cutis laxa type IA - Genetic Testing Registry: Cutis laxa with osteodystrophy - Genetic Testing Registry: Cutis laxa, X-linked - Genetic Testing Registry: Cutis laxa, autosomal dominant - MedlinePlus Encyclopedia: Colon Diverticula (image) - MedlinePlus Encyclopedia: Emphysema (image) - MedlinePlus Encyclopedia: Hernia 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 |
information | What is (are) Bjrnstad syndrome ? | Bjrnstad syndrome is a rare disorder characterized by abnormal hair and hearing problems. Affected individuals have a condition known as pili torti, which means "twisted hair," so named because the strands appear twisted when viewed under a microscope. The hair is brittle and breaks easily, leading to short hair that grows slowly. In Bjrnstad syndrome, pili torti usually affects only the hair on the head; eyebrows, eyelashes, and hair on other parts of the body are normal. The proportion of hairs affected and the severity of brittleness and breakage can vary. This hair abnormality commonly begins before the age of 2. It may become milder with age, particularly after puberty. People with Bjrnstad syndrome also have hearing problems that become evident in early childhood. The hearing loss, which is caused by changes in the inner ear (sensorineural deafness), can range from mild to severe. Mildly affected individuals may be unable to hear sounds at certain frequencies, while severely affected individuals may not be able to hear at all. |
frequency | How many people are affected by Bjrnstad syndrome ? | Bjrnstad syndrome is a rare condition, although its prevalence is unknown. It has been found in populations worldwide. |
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