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nord_457_1 | Symptoms of Fetal Hydantoin Syndrome | The specific symptoms and physical features associated with fetal hydantoin syndrome can vary greatly from one infant to another. Symptoms may not be noticeable at birth (congenital), but will become apparent as an affected child grows older.Although researchers have been able to establish a clear syndrome with characteristic or “core” symptoms, much about the disorder is not fully understood. Several factors including the small number of identified cases, the lack of large clinical studies, and the possibility of genes or other factors influencing the disorder prevent physicians from developing an accurate picture of associated symptoms and prognosis. Therefore, it is important to note that affected individuals may not have all of the symptoms discussed below. Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis.Affected infants may be small at birth due to growth deficiency during development (prenatal growth deficiency). Growth deficiency may be mild to moderate in severity and can continue during the newborn period (postnatal growth deficiency).Distinctive facial features may be present including a flat, broad bridge of the nose; a short nose; eyes that are farther apart from each other than usual (hypertelorism); crossed eyes (strabismus); eyelids that droop (ptosis); a large, wide mouth; malformed ears; mild webbing of the neck (pterygium colli); and microcephaly. Affected infants often have a gap or cleft of missing tissue of the upper lip (cleft lip) and/or a gap or cleft of missing tissue on the roof of the mouth (cleft palate).Affected infants may also exhibit stiff, tapered fingers, underdeveloped fingers and toes, toes that resembled fingers (digitalized toes), and malformed, underdeveloped fingernails and toenails. An increased number of fingerprint arches have also been noted. Some infants may have increased hair on the body and face.Some infants and children may experience delays in reaching developmental milestones such as learning to sit up or crawl (developmental delays). As affected children grow older, the developmental delays improve, but studies suggest that children may remain slightly behind unexposed siblings. The neurological effects of phenytoin exposure in utero have not been clearly established by studies, which have demonstrated conflicting results. Borderline to mild intellectual disability has been reported in some cases, and some studies have suggested that children exposed to phenytoin in the womb have a greater risk of developing learning disabilities, particularly in verbal skills. Reports in the medical literature disagree as to the likelihood of infants with fetal hydantoin syndrome experiencing developmental delays or intellectual disability. The exact risk of these findings in these children is not fully understood. More research is necessary to determine the specific long-term risks in neurological development of infants and children exposed to phenytoin in utero.Additional symptoms occurring with varying frequencies have been reported in the medical literature including congenital heart defects, cardiac rhythm disturbances, behavioral abnormalities such as attention deficit hyperactivity disorder, ocular defects including nearsightedness (myopia), joint laxity, kidney abnormalities, and inguinal and umbilical hernia. Inguinal hernia is when a portion of the intestines pushes through the muscular layers of the abdominal wall. An umbilical hernia is when the intestines or fatty tissue pushes through the area near the bellybutton.Case reports in the medical literature have suggested that infants with fetal hydantoin syndrome may be at an increased risk for the occurrence of certain benign or malignant tumors such as neuroblastoma, Wilm’s tumor, or ectodermal tumors, but such an increased risk is not proven. | Symptoms of Fetal Hydantoin Syndrome. The specific symptoms and physical features associated with fetal hydantoin syndrome can vary greatly from one infant to another. Symptoms may not be noticeable at birth (congenital), but will become apparent as an affected child grows older.Although researchers have been able to establish a clear syndrome with characteristic or “core” symptoms, much about the disorder is not fully understood. Several factors including the small number of identified cases, the lack of large clinical studies, and the possibility of genes or other factors influencing the disorder prevent physicians from developing an accurate picture of associated symptoms and prognosis. Therefore, it is important to note that affected individuals may not have all of the symptoms discussed below. Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis.Affected infants may be small at birth due to growth deficiency during development (prenatal growth deficiency). Growth deficiency may be mild to moderate in severity and can continue during the newborn period (postnatal growth deficiency).Distinctive facial features may be present including a flat, broad bridge of the nose; a short nose; eyes that are farther apart from each other than usual (hypertelorism); crossed eyes (strabismus); eyelids that droop (ptosis); a large, wide mouth; malformed ears; mild webbing of the neck (pterygium colli); and microcephaly. Affected infants often have a gap or cleft of missing tissue of the upper lip (cleft lip) and/or a gap or cleft of missing tissue on the roof of the mouth (cleft palate).Affected infants may also exhibit stiff, tapered fingers, underdeveloped fingers and toes, toes that resembled fingers (digitalized toes), and malformed, underdeveloped fingernails and toenails. An increased number of fingerprint arches have also been noted. Some infants may have increased hair on the body and face.Some infants and children may experience delays in reaching developmental milestones such as learning to sit up or crawl (developmental delays). As affected children grow older, the developmental delays improve, but studies suggest that children may remain slightly behind unexposed siblings. The neurological effects of phenytoin exposure in utero have not been clearly established by studies, which have demonstrated conflicting results. Borderline to mild intellectual disability has been reported in some cases, and some studies have suggested that children exposed to phenytoin in the womb have a greater risk of developing learning disabilities, particularly in verbal skills. Reports in the medical literature disagree as to the likelihood of infants with fetal hydantoin syndrome experiencing developmental delays or intellectual disability. The exact risk of these findings in these children is not fully understood. More research is necessary to determine the specific long-term risks in neurological development of infants and children exposed to phenytoin in utero.Additional symptoms occurring with varying frequencies have been reported in the medical literature including congenital heart defects, cardiac rhythm disturbances, behavioral abnormalities such as attention deficit hyperactivity disorder, ocular defects including nearsightedness (myopia), joint laxity, kidney abnormalities, and inguinal and umbilical hernia. Inguinal hernia is when a portion of the intestines pushes through the muscular layers of the abdominal wall. An umbilical hernia is when the intestines or fatty tissue pushes through the area near the bellybutton.Case reports in the medical literature have suggested that infants with fetal hydantoin syndrome may be at an increased risk for the occurrence of certain benign or malignant tumors such as neuroblastoma, Wilm’s tumor, or ectodermal tumors, but such an increased risk is not proven. | 457 | Fetal Hydantoin Syndrome |
nord_457_2 | Causes of Fetal Hydantoin Syndrome | Maternal use of anti-seizure medications such as phenytoin, which is often used to treat epileptic seizures, can result in multiple effects on the developing embryo and fetus, including fetal hydantoin syndrome. The specific amount of phenytoin ingestion required to cause the disorder has not been determined. Phenytoin is often given with other anti-seizure drugs and other (adjunct) medications that may influence development of the disorder. Fetal hydantoin syndrome may be caused by a combination of specific genetic and environmental factors.It is not known whether the adverse effects of phenytoin during fetal development are due to the drug itself or if they are caused by one of phenytoin’s by-products (metabolites). In addition, the potential role of other factors remains unclear, such as genetic influences that affect phenytoin metabolism or additional environmental factors (e.g. smoking). There have been reports in the medical literature that women with mutations in the methylenetetrahydrofolate reductase (MTHFR) gene are at an increased risk of having an infant with fetal hydantoin syndrome. Researchers believe that the protein product of this gene plays a role in the proper breakdown (metabolism) of phenytoin or one of its metabolites.Another theory speculates that intermediate metabolites of phenytoin are responsible for its teratogenesis. These intermediate metabolites are free radicals that bind to DNA, proteins and lipids adversely affecting neurodevelopment. Genetic differences in formation of these free radicals, drug clearance, and repair mechanisms may explain different susceptibility across individuals.Determining the precise, underlying reasons why fetal hydantoin syndrome develops, requires further research to discover the specific genetic and environmental factors that play a role in the development of the disorder. | Causes of Fetal Hydantoin Syndrome. Maternal use of anti-seizure medications such as phenytoin, which is often used to treat epileptic seizures, can result in multiple effects on the developing embryo and fetus, including fetal hydantoin syndrome. The specific amount of phenytoin ingestion required to cause the disorder has not been determined. Phenytoin is often given with other anti-seizure drugs and other (adjunct) medications that may influence development of the disorder. Fetal hydantoin syndrome may be caused by a combination of specific genetic and environmental factors.It is not known whether the adverse effects of phenytoin during fetal development are due to the drug itself or if they are caused by one of phenytoin’s by-products (metabolites). In addition, the potential role of other factors remains unclear, such as genetic influences that affect phenytoin metabolism or additional environmental factors (e.g. smoking). There have been reports in the medical literature that women with mutations in the methylenetetrahydrofolate reductase (MTHFR) gene are at an increased risk of having an infant with fetal hydantoin syndrome. Researchers believe that the protein product of this gene plays a role in the proper breakdown (metabolism) of phenytoin or one of its metabolites.Another theory speculates that intermediate metabolites of phenytoin are responsible for its teratogenesis. These intermediate metabolites are free radicals that bind to DNA, proteins and lipids adversely affecting neurodevelopment. Genetic differences in formation of these free radicals, drug clearance, and repair mechanisms may explain different susceptibility across individuals.Determining the precise, underlying reasons why fetal hydantoin syndrome develops, requires further research to discover the specific genetic and environmental factors that play a role in the development of the disorder. | 457 | Fetal Hydantoin Syndrome |
nord_457_3 | Affects of Fetal Hydantoin Syndrome | Fetal hydantoin syndrome affects males and females in equal numbers. The exact incidence and prevalence of the disorder is unknown. Studies have suggested that approximately 5%-10% of infants exposed to phenytoin during pregnancy will develop fetal hydantoin syndrome. | Affects of Fetal Hydantoin Syndrome. Fetal hydantoin syndrome affects males and females in equal numbers. The exact incidence and prevalence of the disorder is unknown. Studies have suggested that approximately 5%-10% of infants exposed to phenytoin during pregnancy will develop fetal hydantoin syndrome. | 457 | Fetal Hydantoin Syndrome |
nord_457_4 | Related disorders of Fetal Hydantoin Syndrome | Symptoms of the following disorders can be similar to those of fetal hydantoin syndrome. Comparisons may be useful for a differential diagnosis.Other anti-seizure medications can cause a characteristic pattern of mental and physical birth defects similar to those seen in infants exposed to phenytoin during pregnancy. Such drugs include valproate, carbamazepine, primidone, and phenobarbital. NORD has a separate report called fetal valproate syndrome that discusses infants whose mothers took valproate during pregnancy. Infants with fetal valproate syndrome are at a greater risk of developing neurological abnormalities than are infants whose mothers took other types of anti-seizure medications. (For more information on this disorder, choose “fetal valproate syndrome” as your search term in the Rare Disease Database.)Coffin-Siris syndrome (CSS) is a rare genetic disorder that may be evident at birth (congenital). The disorder may be characterized by abnormalities of the head and facial (craniofacial) area, resulting in a coarse facial appearance. Craniofacial malformations may include an abnormally small head (microcephaly); a wide nose with a low nasal bridge; a wide mouth with thick, prominent lips; thick eyebrows and eyelashes (hypertrichosis); and sparse scalp hair. In addition, affected infants and children typically have short fifth fingers (“pinkies”) and toes with underdeveloped (hypoplastic) or absent nails; other malformations of the fingers and toes; and eye abnormalities. Feeding difficulties and frequent respiratory infections during infancy, diminished muscle tone (hypotonia), abnormal looseness (laxity) of the joints, delayed bone age, developmental delays, hearing loss, and intellectual disability may also be present. The specific symptoms and severity can vary among affected individuals. Treatment is directed towards the symptoms that are present in an individual with CSS. Mutations in five different genes, ARID1A, ARID1B, SMARCA4, SMARCB1, and SMARCE1, have been found to cause CSS. Researchers believe the disease can be transmitted genetically as an autosomal dominant trait but most cases appear to be the result of a new mutation. (For more information on this disorder, choose “Coffin Siris” as your search term in the Rare Disease Database.)Fetal alcohol syndrome (FAS) is a characteristic pattern of mental and physical birth defects that results due to maternal use of alcohol during pregnancy. The range and severity of associated abnormalities may vary greatly from one infant to another. However, characteristic features may include growth delays before and after birth (prenatal and postnatal growth retardation); malformations of the skull and facial (craniofacial) region; brain abnormalities; and/or additional physical findings. FAS may also be associated with varying degrees of intellectual disability, learning abnormalities, and/or behavioral problems that, in some cases, may occur in the absence of obvious physical abnormalities. (For more information on this disorder, choose “fetal alcohol syndrome” as your search term in the Rare Disease Database.) | Related disorders of Fetal Hydantoin Syndrome. Symptoms of the following disorders can be similar to those of fetal hydantoin syndrome. Comparisons may be useful for a differential diagnosis.Other anti-seizure medications can cause a characteristic pattern of mental and physical birth defects similar to those seen in infants exposed to phenytoin during pregnancy. Such drugs include valproate, carbamazepine, primidone, and phenobarbital. NORD has a separate report called fetal valproate syndrome that discusses infants whose mothers took valproate during pregnancy. Infants with fetal valproate syndrome are at a greater risk of developing neurological abnormalities than are infants whose mothers took other types of anti-seizure medications. (For more information on this disorder, choose “fetal valproate syndrome” as your search term in the Rare Disease Database.)Coffin-Siris syndrome (CSS) is a rare genetic disorder that may be evident at birth (congenital). The disorder may be characterized by abnormalities of the head and facial (craniofacial) area, resulting in a coarse facial appearance. Craniofacial malformations may include an abnormally small head (microcephaly); a wide nose with a low nasal bridge; a wide mouth with thick, prominent lips; thick eyebrows and eyelashes (hypertrichosis); and sparse scalp hair. In addition, affected infants and children typically have short fifth fingers (“pinkies”) and toes with underdeveloped (hypoplastic) or absent nails; other malformations of the fingers and toes; and eye abnormalities. Feeding difficulties and frequent respiratory infections during infancy, diminished muscle tone (hypotonia), abnormal looseness (laxity) of the joints, delayed bone age, developmental delays, hearing loss, and intellectual disability may also be present. The specific symptoms and severity can vary among affected individuals. Treatment is directed towards the symptoms that are present in an individual with CSS. Mutations in five different genes, ARID1A, ARID1B, SMARCA4, SMARCB1, and SMARCE1, have been found to cause CSS. Researchers believe the disease can be transmitted genetically as an autosomal dominant trait but most cases appear to be the result of a new mutation. (For more information on this disorder, choose “Coffin Siris” as your search term in the Rare Disease Database.)Fetal alcohol syndrome (FAS) is a characteristic pattern of mental and physical birth defects that results due to maternal use of alcohol during pregnancy. The range and severity of associated abnormalities may vary greatly from one infant to another. However, characteristic features may include growth delays before and after birth (prenatal and postnatal growth retardation); malformations of the skull and facial (craniofacial) region; brain abnormalities; and/or additional physical findings. FAS may also be associated with varying degrees of intellectual disability, learning abnormalities, and/or behavioral problems that, in some cases, may occur in the absence of obvious physical abnormalities. (For more information on this disorder, choose “fetal alcohol syndrome” as your search term in the Rare Disease Database.) | 457 | Fetal Hydantoin Syndrome |
nord_457_5 | Diagnosis of Fetal Hydantoin Syndrome | There is no diagnostic testing that can identify fetal hydantoin syndrome. A diagnosis is made clinically based upon identification of characteristic symptoms in an affected infant in conjunction with a history of phenytoin exposure during gestation. It is important to note that the majority of infants born to women who take phenytoin during pregnancy will not develop fetal hydantoin syndrome. | Diagnosis of Fetal Hydantoin Syndrome. There is no diagnostic testing that can identify fetal hydantoin syndrome. A diagnosis is made clinically based upon identification of characteristic symptoms in an affected infant in conjunction with a history of phenytoin exposure during gestation. It is important to note that the majority of infants born to women who take phenytoin during pregnancy will not develop fetal hydantoin syndrome. | 457 | Fetal Hydantoin Syndrome |
nord_457_6 | Therapies of Fetal Hydantoin Syndrome | Prevention
It is recommended that women be treated with a single anticonvulsant prior to conception and throughout pregnancy, since it appears that children exposed to multiple anticonvulsants may be at a greater risk for significant birth defects.Also, it is recommended that women taking phenytoin take folic acid supplements, both before conception and during pregnancy as a preventive measure against malformations.
Counseling is recommended for women to discuss the risks that seizures prevent for both the developing fetus and the expectant mother as well as the risks to the developing fetus involved with taking anti-seizure medications during pregnancy.Treatment
The treatment of fetal hydantoin syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, oral surgeons, plastic surgeons, neurologists, psychologists, and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment.Infants with fetal hydantoin syndrome can benefit from early developmental intervention to ensure that affected children reach their potential. Affected children may benefit from occupational, physical and speech therapy. Various methods of rehabilitative and behavioral therapy may be beneficial. Additional medical, social and/or vocational services may be necessary. Psychosocial support for the entire family is essential as well.When cleft lip and/or palate are present, the coordinated efforts of a team of specialists may be used to plan an affected child’s treatment and rehabilitation. Cleft lip may be surgically corrected. Generally surgeons repair the lip when the child is still an infant. A second surgery is sometimes necessary for cosmetic purposes when the child is older. Cleft palate may be repaired by surgery or covered by an artificial device (prosthesis) that closes or blocks the opening. Surgical repair can be carried out in stages or in a single operation, according to the nature and severity of the defect. The first palate surgery is usually scheduled during the toddler period. | Therapies of Fetal Hydantoin Syndrome. Prevention
It is recommended that women be treated with a single anticonvulsant prior to conception and throughout pregnancy, since it appears that children exposed to multiple anticonvulsants may be at a greater risk for significant birth defects.Also, it is recommended that women taking phenytoin take folic acid supplements, both before conception and during pregnancy as a preventive measure against malformations.
Counseling is recommended for women to discuss the risks that seizures prevent for both the developing fetus and the expectant mother as well as the risks to the developing fetus involved with taking anti-seizure medications during pregnancy.Treatment
The treatment of fetal hydantoin syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, oral surgeons, plastic surgeons, neurologists, psychologists, and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment.Infants with fetal hydantoin syndrome can benefit from early developmental intervention to ensure that affected children reach their potential. Affected children may benefit from occupational, physical and speech therapy. Various methods of rehabilitative and behavioral therapy may be beneficial. Additional medical, social and/or vocational services may be necessary. Psychosocial support for the entire family is essential as well.When cleft lip and/or palate are present, the coordinated efforts of a team of specialists may be used to plan an affected child’s treatment and rehabilitation. Cleft lip may be surgically corrected. Generally surgeons repair the lip when the child is still an infant. A second surgery is sometimes necessary for cosmetic purposes when the child is older. Cleft palate may be repaired by surgery or covered by an artificial device (prosthesis) that closes or blocks the opening. Surgical repair can be carried out in stages or in a single operation, according to the nature and severity of the defect. The first palate surgery is usually scheduled during the toddler period. | 457 | Fetal Hydantoin Syndrome |
nord_458_0 | Overview of Fetal Retinoid Syndrome | Fetal retinoid syndrome is a pattern of mental and physical birth defects (congenital malformations) that can result from a mother taking retinoids during pregnancy. The absolute risk of congenital malformations following oral isotretinoin therapy is currently unclear. Overall malformation rates in liveborn infants from prospectively reported pregnancies range from 5% to 20%.Retinoids are the synthetic (man-made) forms of vitamin A used to treat various skin (dermatological) conditions. The most well-known retinoid is isotretinoin (commonly referred to by one of its former brand names, Accutane or Roaccutane, a drug used to treat severe cystic acne. Isotretinoin and its commercially available brands, although effective in the treatment of acne, can cause developmental abnormalities in the fetus (teratogenic effects) and therefore should not be used during pregnancy due to the risk of birth defects. The range and severity of associated abnormalities are variable and dependent on timing of exposure in pregnancy. However, characteristic features may include malformations of the skull and facial (craniofacial) region; central nervous system (CNS) abnormalities; heart abnormalities; and/or additional physical findings. Additional anomalies may include renal, thymus gland abnormality and parathyroid gland abnormalities. | Overview of Fetal Retinoid Syndrome. Fetal retinoid syndrome is a pattern of mental and physical birth defects (congenital malformations) that can result from a mother taking retinoids during pregnancy. The absolute risk of congenital malformations following oral isotretinoin therapy is currently unclear. Overall malformation rates in liveborn infants from prospectively reported pregnancies range from 5% to 20%.Retinoids are the synthetic (man-made) forms of vitamin A used to treat various skin (dermatological) conditions. The most well-known retinoid is isotretinoin (commonly referred to by one of its former brand names, Accutane or Roaccutane, a drug used to treat severe cystic acne. Isotretinoin and its commercially available brands, although effective in the treatment of acne, can cause developmental abnormalities in the fetus (teratogenic effects) and therefore should not be used during pregnancy due to the risk of birth defects. The range and severity of associated abnormalities are variable and dependent on timing of exposure in pregnancy. However, characteristic features may include malformations of the skull and facial (craniofacial) region; central nervous system (CNS) abnormalities; heart abnormalities; and/or additional physical findings. Additional anomalies may include renal, thymus gland abnormality and parathyroid gland abnormalities. | 458 | Fetal Retinoid Syndrome |
nord_458_1 | Symptoms of Fetal Retinoid Syndrome | Characteristic features of infants with fetal retinoid syndrome include abnormalities of the craniofacial region, CNS and cardiovascular system. The specific symptoms and physical findings can vary from one infant to another. Affected infants may not have all the symptoms listed below.Craniofacial differences
Some affected infants may have small heads (microcephaly) and small, low-set ears (microtia) with narrowing (stenosis) of the ear canals or are born missing ears. Abnormalities of the middle and inner ears may also be present including hearing loss. Additional craniofacial findings include widely spaced eyes (hypertelorism), incomplete closure of the roof of the mouth (cleft palate), an abnormal groove in the upper lip (cleft lip) and/or underdevelopment of the middle area of the face (midface hypoplasia). Some affected infants may experience paralysis (palsy) of certain facial nerves.Cardiovascular abnormalities
Potential cardiovascular abnormalities following retinoid exposure include structural (anatomical) malformations of the heart such as transposition of the great vessels; hypoplastic left heart syndrome; ventricular septal defects (VSDs) and tetralogy of Fallot.Hypoplastic left heart syndrome is characterized by underdevelopment of the left ventricle, the aortic and/or mitral valves and the ascending aorta.VSDs are abnormal openings that may occur in any portion of the ventricular septum, the fibrous partition that divides the heart’s two lower pumping chambers (ventricles). The size and location of the defect will determine the severity of symptoms. Small VSDs may close without treatment or become less significant as affected infants mature and grow. If a moderately-sized defect is present, the heart may be unable to pump blood effectively, resulting in an abnormally rapid rate of breathing (tachypnea), wheezing, an unusually fast heartbeat (tachycardia) and/or failure to grow and gain weight at the expected rate (failure to thrive). In some children, without appropriate treatment, large VSDs may cause life-threatening complications during infancy.Tetralogy of Fallot is a rare form of cyanotic heart disease. Cyanosis is the abnormal bluish discoloration of the skin and mucous membranes (lips and tongue) that occurs due to low levels of circulating oxygen in the blood. Tetralogy of Fallot consists of a combination of four different heart defects: a ventricular septal defect; obstructed outflow of blood from the right ventricle to the lungs due to an abnormal narrowing of the opening between the pulmonary artery and the right ventricle of the heart (pulmonary stenosis); a displaced aorta that causes blood to flow into the aorta from both the right and left ventricles and abnormal enlargement of the right ventricle.CNS abnormalities
Some infants with fetal retinoid syndrome may develop CNS abnormalities including hydrocephalus, a condition in which accumulation of excessive cerebrospinal fluid (CSF) in the skull causes pressure on the tissues of the brain, resulting in a variety of symptoms. In some children, the forebrain (prosencephalon) may fail to develop resulting in holoprosencephaly.Infants with fetal retinoid syndrome may have neurodevelopmental delays, for example, they may have learning disabilities and have delays in reaching developmental milestones such as sitting or crawling. Affected infants may also develop a condition known as microcephaly, where the head circumference is smaller than would be expected for their age and gender due to developmental issues. This can also result in developmental and intellectual disabilities. Additional complications that may arise due to microcephaly include balance and coordination problems as well as seizures.Additional abnormalities
Infants with fetal retinoid syndrome may experience abnormalities of thymus function. The thymus gland is located below the thyroid gland in the neck in front of the chest and is the primary gland of the lymphatic system. The thymus gland makes white blood cells needed to protect the body from infection.Other reported abnormalities include webbing of the fingers (syndactyly), skeletal malformations affecting the legs and spine, and/or low muscle tone (hypotonia). Some infants may also develop eye problems such as microphthalmia, a condition where one or both eyeballs are very small, leading to possible vision loss. Some infants are born with their eyes missing (anophthalmia). | Symptoms of Fetal Retinoid Syndrome. Characteristic features of infants with fetal retinoid syndrome include abnormalities of the craniofacial region, CNS and cardiovascular system. The specific symptoms and physical findings can vary from one infant to another. Affected infants may not have all the symptoms listed below.Craniofacial differences
Some affected infants may have small heads (microcephaly) and small, low-set ears (microtia) with narrowing (stenosis) of the ear canals or are born missing ears. Abnormalities of the middle and inner ears may also be present including hearing loss. Additional craniofacial findings include widely spaced eyes (hypertelorism), incomplete closure of the roof of the mouth (cleft palate), an abnormal groove in the upper lip (cleft lip) and/or underdevelopment of the middle area of the face (midface hypoplasia). Some affected infants may experience paralysis (palsy) of certain facial nerves.Cardiovascular abnormalities
Potential cardiovascular abnormalities following retinoid exposure include structural (anatomical) malformations of the heart such as transposition of the great vessels; hypoplastic left heart syndrome; ventricular septal defects (VSDs) and tetralogy of Fallot.Hypoplastic left heart syndrome is characterized by underdevelopment of the left ventricle, the aortic and/or mitral valves and the ascending aorta.VSDs are abnormal openings that may occur in any portion of the ventricular septum, the fibrous partition that divides the heart’s two lower pumping chambers (ventricles). The size and location of the defect will determine the severity of symptoms. Small VSDs may close without treatment or become less significant as affected infants mature and grow. If a moderately-sized defect is present, the heart may be unable to pump blood effectively, resulting in an abnormally rapid rate of breathing (tachypnea), wheezing, an unusually fast heartbeat (tachycardia) and/or failure to grow and gain weight at the expected rate (failure to thrive). In some children, without appropriate treatment, large VSDs may cause life-threatening complications during infancy.Tetralogy of Fallot is a rare form of cyanotic heart disease. Cyanosis is the abnormal bluish discoloration of the skin and mucous membranes (lips and tongue) that occurs due to low levels of circulating oxygen in the blood. Tetralogy of Fallot consists of a combination of four different heart defects: a ventricular septal defect; obstructed outflow of blood from the right ventricle to the lungs due to an abnormal narrowing of the opening between the pulmonary artery and the right ventricle of the heart (pulmonary stenosis); a displaced aorta that causes blood to flow into the aorta from both the right and left ventricles and abnormal enlargement of the right ventricle.CNS abnormalities
Some infants with fetal retinoid syndrome may develop CNS abnormalities including hydrocephalus, a condition in which accumulation of excessive cerebrospinal fluid (CSF) in the skull causes pressure on the tissues of the brain, resulting in a variety of symptoms. In some children, the forebrain (prosencephalon) may fail to develop resulting in holoprosencephaly.Infants with fetal retinoid syndrome may have neurodevelopmental delays, for example, they may have learning disabilities and have delays in reaching developmental milestones such as sitting or crawling. Affected infants may also develop a condition known as microcephaly, where the head circumference is smaller than would be expected for their age and gender due to developmental issues. This can also result in developmental and intellectual disabilities. Additional complications that may arise due to microcephaly include balance and coordination problems as well as seizures.Additional abnormalities
Infants with fetal retinoid syndrome may experience abnormalities of thymus function. The thymus gland is located below the thyroid gland in the neck in front of the chest and is the primary gland of the lymphatic system. The thymus gland makes white blood cells needed to protect the body from infection.Other reported abnormalities include webbing of the fingers (syndactyly), skeletal malformations affecting the legs and spine, and/or low muscle tone (hypotonia). Some infants may also develop eye problems such as microphthalmia, a condition where one or both eyeballs are very small, leading to possible vision loss. Some infants are born with their eyes missing (anophthalmia). | 458 | Fetal Retinoid Syndrome |
nord_458_2 | Causes of Fetal Retinoid Syndrome | Maternal use of synthetic vitamin A (retinoids) such as isotretinoin (Accutane) during pregnancy can result in multiple effects on the developing embryo and fetus including miscarriage, premature delivery and a variety of birth defects. Commercially available isotretinoin brand products include, Absorica, Amnesteem, Claravis, Myorisan and Zenatane; as well as various types of generics available globally.There is debate in the medical literature as to the specific risks for individual pregnancies following retinoid exposure. However, it is known that there is an increased risk of birth defects in women who become pregnant while taking retinoids such as isotretinoin. It is estimated that a 35% risk of fetal retinoid syndrome exists in infants of women who take isotretinoin beyond the 15th day following conception. Some researchers believe that birth defects do not occur in women who discontinue isotretinoin one month before conception. It is also unknown what specific dosage of retinoids may result in birth defects. More research is needed to determine the specific risks and long-term effects when women are inadvertently exposed to retinoids during pregnancy. | Causes of Fetal Retinoid Syndrome. Maternal use of synthetic vitamin A (retinoids) such as isotretinoin (Accutane) during pregnancy can result in multiple effects on the developing embryo and fetus including miscarriage, premature delivery and a variety of birth defects. Commercially available isotretinoin brand products include, Absorica, Amnesteem, Claravis, Myorisan and Zenatane; as well as various types of generics available globally.There is debate in the medical literature as to the specific risks for individual pregnancies following retinoid exposure. However, it is known that there is an increased risk of birth defects in women who become pregnant while taking retinoids such as isotretinoin. It is estimated that a 35% risk of fetal retinoid syndrome exists in infants of women who take isotretinoin beyond the 15th day following conception. Some researchers believe that birth defects do not occur in women who discontinue isotretinoin one month before conception. It is also unknown what specific dosage of retinoids may result in birth defects. More research is needed to determine the specific risks and long-term effects when women are inadvertently exposed to retinoids during pregnancy. | 458 | Fetal Retinoid Syndrome |
nord_458_3 | Affects of Fetal Retinoid Syndrome | Fetal retinoid syndrome affects males and females in equal numbers. The exact incidence of fetal retinoid syndrome is unknown and because many children with fetal retinoid syndrome often go unrecognized. The disorder is under-diagnosed, making it difficult to determine the true frequency of the disorder in the general population. | Affects of Fetal Retinoid Syndrome. Fetal retinoid syndrome affects males and females in equal numbers. The exact incidence of fetal retinoid syndrome is unknown and because many children with fetal retinoid syndrome often go unrecognized. The disorder is under-diagnosed, making it difficult to determine the true frequency of the disorder in the general population. | 458 | Fetal Retinoid Syndrome |
nord_458_4 | Related disorders of Fetal Retinoid Syndrome | Related disorders of Fetal Retinoid Syndrome. | 458 | Fetal Retinoid Syndrome |
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nord_458_5 | Diagnosis of Fetal Retinoid Syndrome | Confirmed diagnosis of fetal retinoid syndrome is made following clinical examination of an affected infant in conjunction with a history of retinoid exposure during pregnancy.
Prenatal diagnosis may be possible by ultrasound where fetal abnormalities such as central nervous system and heart abnormalities may be detected. | Diagnosis of Fetal Retinoid Syndrome. Confirmed diagnosis of fetal retinoid syndrome is made following clinical examination of an affected infant in conjunction with a history of retinoid exposure during pregnancy.
Prenatal diagnosis may be possible by ultrasound where fetal abnormalities such as central nervous system and heart abnormalities may be detected. | 458 | Fetal Retinoid Syndrome |
nord_458_6 | Therapies of Fetal Retinoid Syndrome | Prevention
Due to the severity of the birth defects that an infant may develop following retinoid exposure, use of oral retinoids is strictly prohibited during pregnancy. Women should be counselled carefully regarding the risks of isotretinoin treatment and should be screened and monitored for pregnancy while on the medication. Throughout the course of isotretinoin therapy, two forms of contraception are recommended, and pregnancy should be avoided until the isotretinoin therapy has been discontinued.Continual use of birth control (contraception) is needed for safety precautions during isotretinoin therapy in women of childbearing age. Evidence from medical literature states that contraception use should be started one month before isotretinoin therapy and continued for three months after therapy has been stopped.Treatment
The treatment of fetal retinoid syndrome is directed toward the specific problems affecting each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, cardiologists, specialists who assess and treat hearing problems (audiologists), eye specialists and additional health care professionals may need to plan an affected child’s treatment systematically and comprehensively. Other treatment is symptomatic and supportive. | Therapies of Fetal Retinoid Syndrome. Prevention
Due to the severity of the birth defects that an infant may develop following retinoid exposure, use of oral retinoids is strictly prohibited during pregnancy. Women should be counselled carefully regarding the risks of isotretinoin treatment and should be screened and monitored for pregnancy while on the medication. Throughout the course of isotretinoin therapy, two forms of contraception are recommended, and pregnancy should be avoided until the isotretinoin therapy has been discontinued.Continual use of birth control (contraception) is needed for safety precautions during isotretinoin therapy in women of childbearing age. Evidence from medical literature states that contraception use should be started one month before isotretinoin therapy and continued for three months after therapy has been stopped.Treatment
The treatment of fetal retinoid syndrome is directed toward the specific problems affecting each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, cardiologists, specialists who assess and treat hearing problems (audiologists), eye specialists and additional health care professionals may need to plan an affected child’s treatment systematically and comprehensively. Other treatment is symptomatic and supportive. | 458 | Fetal Retinoid Syndrome |
nord_459_0 | Overview of Fetal Valproate Syndrome | SummaryFetal valproate syndrome (FVS) is a rare condition that is caused by exposure of the unborn baby to valproic acid or sodium valproate (VPA) during the first three months of pregnancy (the first trimester). VPA is a medication used to treat certain types of seizures (epilepsy), bipolar disorder and migraines. Although many babies exposed to VPA are born healthy, a small percentage of pregnant women who take this medication can have a baby born with FVS. The exact prevalence of this condition remains to be established. Symptoms of this condition may include neural tube defects such as spina bifida, distinctive facial features, congenital heart defects and other musculoskeletal abnormalities.IntroductionAnti-seizure medications, also known as antiepileptic or anticonvulsant medications are among the most common teratogens prescribed to women of childbearing age. Prenatal exposure to VPA causes teratogenic effects in the fetus, specifically FVS. A teratogen is a drug that interferes with the development of a fetus. Studies have indicated that FVS is associated with greater risk of neurological and cognitive abnormalities than other anti-seizure medications. | Overview of Fetal Valproate Syndrome. SummaryFetal valproate syndrome (FVS) is a rare condition that is caused by exposure of the unborn baby to valproic acid or sodium valproate (VPA) during the first three months of pregnancy (the first trimester). VPA is a medication used to treat certain types of seizures (epilepsy), bipolar disorder and migraines. Although many babies exposed to VPA are born healthy, a small percentage of pregnant women who take this medication can have a baby born with FVS. The exact prevalence of this condition remains to be established. Symptoms of this condition may include neural tube defects such as spina bifida, distinctive facial features, congenital heart defects and other musculoskeletal abnormalities.IntroductionAnti-seizure medications, also known as antiepileptic or anticonvulsant medications are among the most common teratogens prescribed to women of childbearing age. Prenatal exposure to VPA causes teratogenic effects in the fetus, specifically FVS. A teratogen is a drug that interferes with the development of a fetus. Studies have indicated that FVS is associated with greater risk of neurological and cognitive abnormalities than other anti-seizure medications. | 459 | Fetal Valproate Syndrome |
nord_459_1 | Symptoms of Fetal Valproate Syndrome | The use of VPA as a single drug (monotherapy) in the first trimester of pregnancy was associated with significantly increased risks of major and minor malformations, including a 20-fold increase in neural tube defects (NTDs) such as spina bifida, cleft lip and palate, cardiovascular abnormalities, genitourinary defects, developmental delay, endocrine disorders, limb defects, and autism as compared with no-use of antiepileptic drugs (AEDs) or with use of other AEDs.Spina bifida is a birth defect where there is the incomplete closure of bony spine. It occurs when the tube of tissue that lies along the center of the early embryo (neural tube) does not completely fuse during fetal growth. Part of the contents of the spinal canal may protrude through this opening (bifida cystica). Depending on the severity of the opening, a variety of neurological and physical symptoms may occur. (For more information on this disorder choose “spina bifida” as your search term in the Rare Disease Database.)Distinctive facial features are characteristic of FVS. Infants with FVS may have a vertical fold of skin on either side of the nose that forms a groove under the eye (epicanthal folds); a small, upturned nose with a flat bridge; a small mouth (microstomia); a long, thin, upper lip; a downturned mouth; and/or minor abnormalities of the ears.Other abnormalities that may be found in a few affected individuals include: underdeveloped nails of the fingers and toes; dislocation of the hip; long, thin fingers and toes (arachnodactyly); overlapping fingers and toes; separation of the rectus muscle of the abdominal wall (diastasis recti); absence of the first rib; a condition in which the urinary opening is on the underside of the penis (hypospadias); abnormalities of the heart; softening of the windpipe (tracheomalacia); and/or a club foot.Children with FVS have a higher chance of developmental problems such as decreased cognitive function, attention deficit disorder, learning difficulties and often the communication problems of autism spectrum disorder.Growth deficiency and an unusually small head (microcephaly) may also occur when VPA is taken alone or in combination with other antiepileptic drugs during pregnancy. | Symptoms of Fetal Valproate Syndrome. The use of VPA as a single drug (monotherapy) in the first trimester of pregnancy was associated with significantly increased risks of major and minor malformations, including a 20-fold increase in neural tube defects (NTDs) such as spina bifida, cleft lip and palate, cardiovascular abnormalities, genitourinary defects, developmental delay, endocrine disorders, limb defects, and autism as compared with no-use of antiepileptic drugs (AEDs) or with use of other AEDs.Spina bifida is a birth defect where there is the incomplete closure of bony spine. It occurs when the tube of tissue that lies along the center of the early embryo (neural tube) does not completely fuse during fetal growth. Part of the contents of the spinal canal may protrude through this opening (bifida cystica). Depending on the severity of the opening, a variety of neurological and physical symptoms may occur. (For more information on this disorder choose “spina bifida” as your search term in the Rare Disease Database.)Distinctive facial features are characteristic of FVS. Infants with FVS may have a vertical fold of skin on either side of the nose that forms a groove under the eye (epicanthal folds); a small, upturned nose with a flat bridge; a small mouth (microstomia); a long, thin, upper lip; a downturned mouth; and/or minor abnormalities of the ears.Other abnormalities that may be found in a few affected individuals include: underdeveloped nails of the fingers and toes; dislocation of the hip; long, thin fingers and toes (arachnodactyly); overlapping fingers and toes; separation of the rectus muscle of the abdominal wall (diastasis recti); absence of the first rib; a condition in which the urinary opening is on the underside of the penis (hypospadias); abnormalities of the heart; softening of the windpipe (tracheomalacia); and/or a club foot.Children with FVS have a higher chance of developmental problems such as decreased cognitive function, attention deficit disorder, learning difficulties and often the communication problems of autism spectrum disorder.Growth deficiency and an unusually small head (microcephaly) may also occur when VPA is taken alone or in combination with other antiepileptic drugs during pregnancy. | 459 | Fetal Valproate Syndrome |
nord_459_2 | Causes of Fetal Valproate Syndrome | FVS is a rare condition that may occur when a baby is exposed to VPA (brand names include Depakene, depakine, convulex, depakote, encorate, valpakine, etc) during the first trimester. It is believed that VPA crosses the placenta and interferes with normal development causing developmental abnormalities in the fetus (teratogenesis).If a woman with epilepsy wishes to have children, the recommended treatment is to avoid VPA and use a single drug or a newer antiepileptic medication. Although it has been advised to avoid VPA during pregnancy to prevent FVS, there are circumstances when the use of VPA is necessary. Studies have shown that there is a dose-effect relationship between prenatal exposure to VPA and fetal abnormalities. A dose-effect relationship is when there is a link between the effect of the drug and the dose of the drug. The dose-effect relationship between fetal abnormalities and prenatal exposure to VPA is that higher doses of VPA have been associated with a greater risk compared to lower doses of VPA in developing fetal abnormalities. Multiple reports have shown a higher risk of fetal abnormality where the maternal VPA doses during pregnancy were above 1000 mg/day or blood concentrations were above 70 μg/ml. The most common abnormalities are cardiac and NTDs. However, the typical facial dysmorphic features and minor skeletal abnormalities that may occur within the both low and high doses in VPA use. There are several variables that have to be taken into account which include not only the specific antiepileptic drug used but also the dose of the drug used. VPA in combination with other antiepileptic drugs may also increase the risk of developing fetal abnormalities. | Causes of Fetal Valproate Syndrome. FVS is a rare condition that may occur when a baby is exposed to VPA (brand names include Depakene, depakine, convulex, depakote, encorate, valpakine, etc) during the first trimester. It is believed that VPA crosses the placenta and interferes with normal development causing developmental abnormalities in the fetus (teratogenesis).If a woman with epilepsy wishes to have children, the recommended treatment is to avoid VPA and use a single drug or a newer antiepileptic medication. Although it has been advised to avoid VPA during pregnancy to prevent FVS, there are circumstances when the use of VPA is necessary. Studies have shown that there is a dose-effect relationship between prenatal exposure to VPA and fetal abnormalities. A dose-effect relationship is when there is a link between the effect of the drug and the dose of the drug. The dose-effect relationship between fetal abnormalities and prenatal exposure to VPA is that higher doses of VPA have been associated with a greater risk compared to lower doses of VPA in developing fetal abnormalities. Multiple reports have shown a higher risk of fetal abnormality where the maternal VPA doses during pregnancy were above 1000 mg/day or blood concentrations were above 70 μg/ml. The most common abnormalities are cardiac and NTDs. However, the typical facial dysmorphic features and minor skeletal abnormalities that may occur within the both low and high doses in VPA use. There are several variables that have to be taken into account which include not only the specific antiepileptic drug used but also the dose of the drug used. VPA in combination with other antiepileptic drugs may also increase the risk of developing fetal abnormalities. | 459 | Fetal Valproate Syndrome |
nord_459_3 | Affects of Fetal Valproate Syndrome | FVS affects males and females in equal numbers. There is a 20-fold increase in neural tube defects, cleft lip and palate, cardiovascular abnormalities, genitourinary defects, developmental delay, endocrine disorders, limb defects, and autism, when VPA is used during the 1st trimester of pregnancy compared to no use of antiepileptic drugs. | Affects of Fetal Valproate Syndrome. FVS affects males and females in equal numbers. There is a 20-fold increase in neural tube defects, cleft lip and palate, cardiovascular abnormalities, genitourinary defects, developmental delay, endocrine disorders, limb defects, and autism, when VPA is used during the 1st trimester of pregnancy compared to no use of antiepileptic drugs. | 459 | Fetal Valproate Syndrome |
nord_459_4 | Related disorders of Fetal Valproate Syndrome | Fetal abnormalities caused by other antiepileptic drugs may be similar to those of FVS. The determining factor is the identification of the drugs the mother was taking during the first three months of pregnancy.
Symptoms of the following disorders can be similar to those of FVS. Comparisons of these disorders may be useful for a differential diagnosis:Fetal hydantoin syndrome is a characteristic pattern of mental and physical birth defects that results from maternal use of the antiepileptic drug phenytoin (Dilantin) during pregnancy. (For more information on this disorder choose “Fetal hydantoin syndrome as your search term in the Rare Disease Database.)Fetal alcohol syndrome is a characteristic pattern of mental and physical birth defects that results due to maternal use of alcohol during pregnancy. (For more information on this disorder, choose “fetal alcohol syndrome” as your search term in the Rare Disease Database.) | Related disorders of Fetal Valproate Syndrome. Fetal abnormalities caused by other antiepileptic drugs may be similar to those of FVS. The determining factor is the identification of the drugs the mother was taking during the first three months of pregnancy.
Symptoms of the following disorders can be similar to those of FVS. Comparisons of these disorders may be useful for a differential diagnosis:Fetal hydantoin syndrome is a characteristic pattern of mental and physical birth defects that results from maternal use of the antiepileptic drug phenytoin (Dilantin) during pregnancy. (For more information on this disorder choose “Fetal hydantoin syndrome as your search term in the Rare Disease Database.)Fetal alcohol syndrome is a characteristic pattern of mental and physical birth defects that results due to maternal use of alcohol during pregnancy. (For more information on this disorder, choose “fetal alcohol syndrome” as your search term in the Rare Disease Database.) | 459 | Fetal Valproate Syndrome |
nord_459_5 | Diagnosis of Fetal Valproate Syndrome | There is no diagnostic testing that can identify FVS. A diagnosis is made clinically based upon identification of characteristic symptoms in an affected infant in conjunction with a history of VPA exposure during pregnancy.Because FVS is considered a diagnosis of exclusion (diagnosis made by a process of elimination), other medical conditions that have similar symptoms must be ruled out prior to making this diagnosis.Prenatal diagnosis may be possible by ultrasound where fetal abnormalities such as neural tube defects and organ abnormalities may be detected. | Diagnosis of Fetal Valproate Syndrome. There is no diagnostic testing that can identify FVS. A diagnosis is made clinically based upon identification of characteristic symptoms in an affected infant in conjunction with a history of VPA exposure during pregnancy.Because FVS is considered a diagnosis of exclusion (diagnosis made by a process of elimination), other medical conditions that have similar symptoms must be ruled out prior to making this diagnosis.Prenatal diagnosis may be possible by ultrasound where fetal abnormalities such as neural tube defects and organ abnormalities may be detected. | 459 | Fetal Valproate Syndrome |
nord_459_6 | Therapies of Fetal Valproate Syndrome | Prevention
If possible, VPA should be avoided during pregnancy. If the use of antiepileptic medications during pregnancy cannot be avoided, they should be administered as a single drug. The lowest possible dose of the antiepileptic medication should be used as well as constant monitoring of the amount of the drug (serum concentration) should be performed.Also, it is recommended that women taking valproate take folic acid supplements, both before conception and during pregnancy to reduce the risk of malformations.However, most women with epilepsy have healthy children. While some infants exposed to an anticonvulsant drug in utero have abnormalities, others do not. Genetic differences in the fetal response to medications probably play a role. The risk of recurrence of FVS in a subsequent pregnancy exposed to VPA would therefore appear to be high, possibly due to inherent problems with the metabolism of VPA in the mothers concerned. Regular counseling is recommended for women with epilepsy to discuss the risks that seizures present for both the developing fetus and the expectant mother.Treatment
The treatment of FVS is directed toward the specific symptoms that are apparent in the child. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, oral surgeons, plastic surgeons, neurologists, psychologists, and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment.Infants with FVS can benefit from early developmental intervention to ensure that affected children reach their potential. Affected children may benefit from occupational, physical and speech therapy. Various methods of rehabilitative and behavioral therapy may be beneficial. Additional medical, social and/or vocational services may be necessary. Psychosocial support for the entire family is essential as well.Some children with mild spina bifida may not require treatment, but surgery may be considered for children with moderate to severe spina bifida. Surgery may help prevent the worsening of the condition in some children, but cannot restore the lost muscle function. In those extreme cases where the sac (meningocele) breaks or appears about to break, immediate surgery becomes essential. Individuals with severe spina bifida may develop contractures (shortening of the muscles) and abnormalities of posture. This is due to the paralysis of muscles in the legs. A child with spina bifida should have the necessary therapy (orthopedic and physical) beginning at an early age to prevent contractures. (For more information on this disorder choose “spina bifida” as your search term in the Rare Disease Database).Surgery may be necessary to correct heart defects as well as other physical abnormalities that may be present. | Therapies of Fetal Valproate Syndrome. Prevention
If possible, VPA should be avoided during pregnancy. If the use of antiepileptic medications during pregnancy cannot be avoided, they should be administered as a single drug. The lowest possible dose of the antiepileptic medication should be used as well as constant monitoring of the amount of the drug (serum concentration) should be performed.Also, it is recommended that women taking valproate take folic acid supplements, both before conception and during pregnancy to reduce the risk of malformations.However, most women with epilepsy have healthy children. While some infants exposed to an anticonvulsant drug in utero have abnormalities, others do not. Genetic differences in the fetal response to medications probably play a role. The risk of recurrence of FVS in a subsequent pregnancy exposed to VPA would therefore appear to be high, possibly due to inherent problems with the metabolism of VPA in the mothers concerned. Regular counseling is recommended for women with epilepsy to discuss the risks that seizures present for both the developing fetus and the expectant mother.Treatment
The treatment of FVS is directed toward the specific symptoms that are apparent in the child. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, oral surgeons, plastic surgeons, neurologists, psychologists, and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment.Infants with FVS can benefit from early developmental intervention to ensure that affected children reach their potential. Affected children may benefit from occupational, physical and speech therapy. Various methods of rehabilitative and behavioral therapy may be beneficial. Additional medical, social and/or vocational services may be necessary. Psychosocial support for the entire family is essential as well.Some children with mild spina bifida may not require treatment, but surgery may be considered for children with moderate to severe spina bifida. Surgery may help prevent the worsening of the condition in some children, but cannot restore the lost muscle function. In those extreme cases where the sac (meningocele) breaks or appears about to break, immediate surgery becomes essential. Individuals with severe spina bifida may develop contractures (shortening of the muscles) and abnormalities of posture. This is due to the paralysis of muscles in the legs. A child with spina bifida should have the necessary therapy (orthopedic and physical) beginning at an early age to prevent contractures. (For more information on this disorder choose “spina bifida” as your search term in the Rare Disease Database).Surgery may be necessary to correct heart defects as well as other physical abnormalities that may be present. | 459 | Fetal Valproate Syndrome |
nord_460_0 | Overview of FG Syndrome Type 1 | FG syndrome type 1 (FGS1) is an X-linked genetic disorder that is characterized by poor muscle tone (hypotonia), intellectual disability, constipation and or anal anomalies and complete or partial absence of the part of the brain that connects the two hemispheres of the brain (corpus callosum). Other features of the disorder are small and simple ears, tall and prominent forehead, wide and flat thumbs and great toes and down slanting eyes. FGS1 is an X-linked genetic disorder typically caused by a change (variant or mutation) in the MED12 gene. The spectrum of disorders caused by variants in this gene is still being defined. Some individuals previously diagnosed with FGS1 do not have a MED12 gene variant and, therefore, probably have a different reason for intellectual disability. | Overview of FG Syndrome Type 1. FG syndrome type 1 (FGS1) is an X-linked genetic disorder that is characterized by poor muscle tone (hypotonia), intellectual disability, constipation and or anal anomalies and complete or partial absence of the part of the brain that connects the two hemispheres of the brain (corpus callosum). Other features of the disorder are small and simple ears, tall and prominent forehead, wide and flat thumbs and great toes and down slanting eyes. FGS1 is an X-linked genetic disorder typically caused by a change (variant or mutation) in the MED12 gene. The spectrum of disorders caused by variants in this gene is still being defined. Some individuals previously diagnosed with FGS1 do not have a MED12 gene variant and, therefore, probably have a different reason for intellectual disability. | 460 | FG Syndrome Type 1 |
nord_460_1 | Symptoms of FG Syndrome Type 1 | FG syndrome type 1 (FGS1) is an X-linked genetic disorder that is characterized by poor muscle tone (hypotonia), intellectual disability, constipation and or anal anomalies and complete or partial absence of the part of the brain that connects the two hemispheres of the brain (corpus callosum). Other features of the disorder are small and simple ears, tall and prominent forehead, wide and flat thumbs and great toes and down slanting eyes. Additional features may include a large head (macrocephaly), widely spaced eyes (ocular hypertelorism) and upswept frontal hair. Seizures and congenital heart defects have also been reported.Individuals with FGS1 often have characteristic behaviors that can include hyperactivity, friendliness and attention seeking. | Symptoms of FG Syndrome Type 1. FG syndrome type 1 (FGS1) is an X-linked genetic disorder that is characterized by poor muscle tone (hypotonia), intellectual disability, constipation and or anal anomalies and complete or partial absence of the part of the brain that connects the two hemispheres of the brain (corpus callosum). Other features of the disorder are small and simple ears, tall and prominent forehead, wide and flat thumbs and great toes and down slanting eyes. Additional features may include a large head (macrocephaly), widely spaced eyes (ocular hypertelorism) and upswept frontal hair. Seizures and congenital heart defects have also been reported.Individuals with FGS1 often have characteristic behaviors that can include hyperactivity, friendliness and attention seeking. | 460 | FG Syndrome Type 1 |
nord_460_2 | Causes of FG Syndrome Type 1 | FGS1 is typically caused by a variant in the MED12 gene on the X chromosome located at Xq13.1. The MED12 gene is responsible for production of the MED12 (TRAP230) protein that is involved in the regulation of transcription.FGS1 is an X-linked genetic disorder. X-linked genetic disorders are conditions caused by an abnormal gene on the X chromosome and occur mostly in males. Females that have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes, and one is inactivated so that the genes on that chromosome are nonfunctioning. It is usually the X chromosome with the abnormal gene that is inactivated. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a disease gene, he will develop the disease. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.Males with X-linked disorders pass the disease gene to all of their daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. | Causes of FG Syndrome Type 1. FGS1 is typically caused by a variant in the MED12 gene on the X chromosome located at Xq13.1. The MED12 gene is responsible for production of the MED12 (TRAP230) protein that is involved in the regulation of transcription.FGS1 is an X-linked genetic disorder. X-linked genetic disorders are conditions caused by an abnormal gene on the X chromosome and occur mostly in males. Females that have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes, and one is inactivated so that the genes on that chromosome are nonfunctioning. It is usually the X chromosome with the abnormal gene that is inactivated. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a disease gene, he will develop the disease. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.Males with X-linked disorders pass the disease gene to all of their daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. | 460 | FG Syndrome Type 1 |
nord_460_3 | Affects of FG Syndrome Type 1 | The prevalence of FGS1 is unknown. The spectrum of disorders caused by variants in this gene is still being defined. Some individuals previously diagnosed with FGS1 do not have a MED12 gene variant and, therefore, probably have a different reason for intellectual disability. | Affects of FG Syndrome Type 1. The prevalence of FGS1 is unknown. The spectrum of disorders caused by variants in this gene is still being defined. Some individuals previously diagnosed with FGS1 do not have a MED12 gene variant and, therefore, probably have a different reason for intellectual disability. | 460 | FG Syndrome Type 1 |
nord_460_4 | Related disorders of FG Syndrome Type 1 | Symptoms of the following disorders can be similar to those of FGS1 syndrome. Comparisons may be useful for a differential diagnosis:Lujan syndrome is an X-linked genetic disorder in the spectrum of disorders caused by variants in the MED12 gene. This condition is characterized by intellectual disability, hypotonia, large head, tall and thin body, long and thin face and high and narrow palate. Additional features that may be present include small jaw, long hands with hyperextensible digits, abnormalities of the corpus callosum and nasal speech.X-linked Ohdo syndrome (XLOS) is also caused by variants in the MED12 gene. Typical clinical features in XLOS include intellectual disability, blepharophimosis, ptosis, epicanthal folds, broad nasal bridge, small mouth, small jaw, triangular face and coarse facial features. Common behavior traits include hyperactivity, aggression, hand-flapping, and friendly personality. Additional features include hypotonia, joint hypermobility and hearing loss.Several families have recently been described with non-syndromic intellectual disability due to MED12 gene variants distinct from those described in individuals with FGS1, Lujan syndrome and XLOS. The range of clinical features associated with MED12 variants is expected to continue to evolve as more individuals are reported. | Related disorders of FG Syndrome Type 1. Symptoms of the following disorders can be similar to those of FGS1 syndrome. Comparisons may be useful for a differential diagnosis:Lujan syndrome is an X-linked genetic disorder in the spectrum of disorders caused by variants in the MED12 gene. This condition is characterized by intellectual disability, hypotonia, large head, tall and thin body, long and thin face and high and narrow palate. Additional features that may be present include small jaw, long hands with hyperextensible digits, abnormalities of the corpus callosum and nasal speech.X-linked Ohdo syndrome (XLOS) is also caused by variants in the MED12 gene. Typical clinical features in XLOS include intellectual disability, blepharophimosis, ptosis, epicanthal folds, broad nasal bridge, small mouth, small jaw, triangular face and coarse facial features. Common behavior traits include hyperactivity, aggression, hand-flapping, and friendly personality. Additional features include hypotonia, joint hypermobility and hearing loss.Several families have recently been described with non-syndromic intellectual disability due to MED12 gene variants distinct from those described in individuals with FGS1, Lujan syndrome and XLOS. The range of clinical features associated with MED12 variants is expected to continue to evolve as more individuals are reported. | 460 | FG Syndrome Type 1 |
nord_460_5 | Diagnosis of FG Syndrome Type 1 | FGS1 syndrome is suspected based on the presence of physical characteristics. Molecular genetic testing for the MED12 gene is available and is the only way to confirm the diagnosis. | Diagnosis of FG Syndrome Type 1. FGS1 syndrome is suspected based on the presence of physical characteristics. Molecular genetic testing for the MED12 gene is available and is the only way to confirm the diagnosis. | 460 | FG Syndrome Type 1 |
nord_460_6 | Therapies of FG Syndrome Type 1 | Treatment
The symptoms of FGS1 syndrome are treated individually. This usually involves care by a team of healthcare providers including a pediatrician, neurologist, cardiologist, surgeon, gastroenterologist and psychologist. Early intervention with physical, occupational and speech therapy should be initiated as soon as possible.Genetic counseling is recommended for affected individuals and their family members. | Therapies of FG Syndrome Type 1. Treatment
The symptoms of FGS1 syndrome are treated individually. This usually involves care by a team of healthcare providers including a pediatrician, neurologist, cardiologist, surgeon, gastroenterologist and psychologist. Early intervention with physical, occupational and speech therapy should be initiated as soon as possible.Genetic counseling is recommended for affected individuals and their family members. | 460 | FG Syndrome Type 1 |
nord_461_0 | Overview of Fibrillary Glomerulonephritis | SummaryFibrillary glomerulonephritis (GN) is an uncommon kidney disease of the glomerulus, the site where waste is filtered from the body. Unusual fibril proteins plug the glomerulus, causing it to become inflamed. It mostly affects middle-aged adults between 41 and 80 years and can cause blood and protein in the urine (hematuria and proteinuria, respectively), which makes the urine look red or foamy. Other symptoms include decreased kidney function (renal insufficiency), swelling in the legs or feet and high blood pressure (hypertension). It is diagnosed with a kidney biopsy. While the exact cause is unknown, it is often found in patients with a history of other diseases including cancer, autoimmune diseases, hepatitis C, hypertension and diabetes. Treatment is typically aimed at the associated diseases since no treatments have been shown to be effective yet for fibrillary glomerulonephritis. 40-50% of patients with fibrillary glomerulonephritis will progress to end stage renal disease within two to six years, depending on the severity. These patients will eventually require a kidney transplant and dialysis. The disease may return even after a kidney transplant, but it is usually less severe.IntroductionFibrillary glomerulonephritis and immunotactoid glomerulopathy, a similar but rarer condition, are two forms of nonamyloid fibrillary glomerular deposition diseases. Similar to amyloidosis, fibrils deposit in the wall of the glomerulus (in the basement membrane), but these fibrils are made from immunoglobulins rather than amyloid proteins. Under normal conditions, the glomerulus filters the blood to form urine and keeps the fibrils (which are important for cell structure). The word “fibrillary” refers to these protein fibers and “glomerulonephritis” refers to inflammation (“-itis”) of the kidney filters (“glomerulonephr-“). The buildup of these fibril proteins can activate the immune system and lead to inflammation and kidney damage. Scientists do not fully understand why these fibrils begin depositing in the glomerulus, but most suspect that certain underlying diseases play a role. Over time, the damaged glomeruli spill proteins into the urine and eventually lose their ability to filter blood altogether. | Overview of Fibrillary Glomerulonephritis . SummaryFibrillary glomerulonephritis (GN) is an uncommon kidney disease of the glomerulus, the site where waste is filtered from the body. Unusual fibril proteins plug the glomerulus, causing it to become inflamed. It mostly affects middle-aged adults between 41 and 80 years and can cause blood and protein in the urine (hematuria and proteinuria, respectively), which makes the urine look red or foamy. Other symptoms include decreased kidney function (renal insufficiency), swelling in the legs or feet and high blood pressure (hypertension). It is diagnosed with a kidney biopsy. While the exact cause is unknown, it is often found in patients with a history of other diseases including cancer, autoimmune diseases, hepatitis C, hypertension and diabetes. Treatment is typically aimed at the associated diseases since no treatments have been shown to be effective yet for fibrillary glomerulonephritis. 40-50% of patients with fibrillary glomerulonephritis will progress to end stage renal disease within two to six years, depending on the severity. These patients will eventually require a kidney transplant and dialysis. The disease may return even after a kidney transplant, but it is usually less severe.IntroductionFibrillary glomerulonephritis and immunotactoid glomerulopathy, a similar but rarer condition, are two forms of nonamyloid fibrillary glomerular deposition diseases. Similar to amyloidosis, fibrils deposit in the wall of the glomerulus (in the basement membrane), but these fibrils are made from immunoglobulins rather than amyloid proteins. Under normal conditions, the glomerulus filters the blood to form urine and keeps the fibrils (which are important for cell structure). The word “fibrillary” refers to these protein fibers and “glomerulonephritis” refers to inflammation (“-itis”) of the kidney filters (“glomerulonephr-“). The buildup of these fibril proteins can activate the immune system and lead to inflammation and kidney damage. Scientists do not fully understand why these fibrils begin depositing in the glomerulus, but most suspect that certain underlying diseases play a role. Over time, the damaged glomeruli spill proteins into the urine and eventually lose their ability to filter blood altogether. | 461 | Fibrillary Glomerulonephritis |
nord_461_1 | Symptoms of Fibrillary Glomerulonephritis | The most common symptoms of fibrillary glomerulonephritis include: | Symptoms of Fibrillary Glomerulonephritis . The most common symptoms of fibrillary glomerulonephritis include: | 461 | Fibrillary Glomerulonephritis |
nord_461_2 | Causes of Fibrillary Glomerulonephritis | The causes of fibrillary glomerulonephritis are currently unknown and are being researched. Antibodies (immunoglobulins) build up in the glomerulus, often in patients with an underlying disease such as cancer (particularly leukemia, lymphoma and multiple myeloma), a monoclonal gammopathy or an autoimmune disease (Crohn’s disease, Graves’ disease, immune thrombocytopenia, etc.). | Causes of Fibrillary Glomerulonephritis . The causes of fibrillary glomerulonephritis are currently unknown and are being researched. Antibodies (immunoglobulins) build up in the glomerulus, often in patients with an underlying disease such as cancer (particularly leukemia, lymphoma and multiple myeloma), a monoclonal gammopathy or an autoimmune disease (Crohn’s disease, Graves’ disease, immune thrombocytopenia, etc.). | 461 | Fibrillary Glomerulonephritis |
nord_461_3 | Affects of Fibrillary Glomerulonephritis | Patients with a history of cancer (particularly leukemia or multiple myeloma), a monoclonal gammopathy or an autoimmune disease (particularly Crohn’s disease, lupus, Graves’ disease, or immune thrombocytopenia [ITP]) are at risk for fibrillary glomerulonephritis. | Affects of Fibrillary Glomerulonephritis . Patients with a history of cancer (particularly leukemia or multiple myeloma), a monoclonal gammopathy or an autoimmune disease (particularly Crohn’s disease, lupus, Graves’ disease, or immune thrombocytopenia [ITP]) are at risk for fibrillary glomerulonephritis. | 461 | Fibrillary Glomerulonephritis |
nord_461_4 | Related disorders of Fibrillary Glomerulonephritis | Immunotactoid glomerulopathy – a similar disease in which antibodies (immunoglobulins) and microtubules affect the glomerulus rather than fibrils.Fibronectin glomerulopathy – a similar disease in which a protein called fibronectin-1 affects the glomerulus rather than fibrils.Collagenofibrotic glomerulopathy – a similar disease in which collagen affects the glomerulus rather than fibrils. | Related disorders of Fibrillary Glomerulonephritis . Immunotactoid glomerulopathy – a similar disease in which antibodies (immunoglobulins) and microtubules affect the glomerulus rather than fibrils.Fibronectin glomerulopathy – a similar disease in which a protein called fibronectin-1 affects the glomerulus rather than fibrils.Collagenofibrotic glomerulopathy – a similar disease in which collagen affects the glomerulus rather than fibrils. | 461 | Fibrillary Glomerulonephritis |
nord_461_5 | Diagnosis of Fibrillary Glomerulonephritis | A diagnosis is made from a kidney biopsy to look at the fibrils under an electron microscope and immunofluorescence microscope. Routine lab tests may detect the blood and protein in the urine, but a biopsy is the only way to determine which proteins are affecting the glomerulus.Clinical Testing and Work-upAbnormal results from routine blood and urine tests are the first line of evidence for kidney damage. Kidney function tests can then detect the severity of kidney damage. After a kidney biopsy confirms the diagnosis of fibrillary glomerulonephritis, a physician will likely order more blood tests and imaging. These tests are important to find any underlying cancer, hepatitis or autoimmune disease which may be associated with the glomerulonephritis. In some patients, finding and treating the underlying condition can decrease the severity of the kidney disease. In the case when an underlying condition is not found, treatment focuses on controlling the hypertension, protein in the urine and progression of the kidney disease. | Diagnosis of Fibrillary Glomerulonephritis . A diagnosis is made from a kidney biopsy to look at the fibrils under an electron microscope and immunofluorescence microscope. Routine lab tests may detect the blood and protein in the urine, but a biopsy is the only way to determine which proteins are affecting the glomerulus.Clinical Testing and Work-upAbnormal results from routine blood and urine tests are the first line of evidence for kidney damage. Kidney function tests can then detect the severity of kidney damage. After a kidney biopsy confirms the diagnosis of fibrillary glomerulonephritis, a physician will likely order more blood tests and imaging. These tests are important to find any underlying cancer, hepatitis or autoimmune disease which may be associated with the glomerulonephritis. In some patients, finding and treating the underlying condition can decrease the severity of the kidney disease. In the case when an underlying condition is not found, treatment focuses on controlling the hypertension, protein in the urine and progression of the kidney disease. | 461 | Fibrillary Glomerulonephritis |
nord_461_6 | Therapies of Fibrillary Glomerulonephritis | TreatmentThere is currently no approved therapy to treat fibrillary glomerulonephritis with unknown cause. Many therapies have been tried with little success including steroids, plasmapheresis, cyclophosphamide and cyclosporine. Clinicians will likely focus instead on controlling the symptoms such as hypertension, proteinuria and kidney insufficiency. If an underlying condition is present (see Affected Populations), clinicians will instead focus on treating the underlying condition, which may improve symptoms of fibrillary glomerulonephritis.Patients who progress to end-stage renal disease will likely need a kidney transplant and/or dialysis, although fibrillary glomerulonephritis can recur after a kidney transplant. | Therapies of Fibrillary Glomerulonephritis . TreatmentThere is currently no approved therapy to treat fibrillary glomerulonephritis with unknown cause. Many therapies have been tried with little success including steroids, plasmapheresis, cyclophosphamide and cyclosporine. Clinicians will likely focus instead on controlling the symptoms such as hypertension, proteinuria and kidney insufficiency. If an underlying condition is present (see Affected Populations), clinicians will instead focus on treating the underlying condition, which may improve symptoms of fibrillary glomerulonephritis.Patients who progress to end-stage renal disease will likely need a kidney transplant and/or dialysis, although fibrillary glomerulonephritis can recur after a kidney transplant. | 461 | Fibrillary Glomerulonephritis |
nord_462_0 | Overview of Fibrodysplasia Ossificans Progressiva | Fibrodysplasia ossificans progressiva (FOP) is a very rare genetic connective tissue disorder characterized by the abnormal development of bone in areas of the body where bone is not normally present (heterotopic ossification), such as the ligaments, tendons, and skeletal muscles. Specifically, this disorder causes the body's skeletal muscles and soft connective tissues to undergo a metamorphosis, essentially a transformation into bone, progressively locking joints in place and making movement difficult or impossible. Patients with FOP have malformed big toes that are present at birth (congenital). Other skeletal malformations may occur. The abnormal episodic development of bone at multiple soft tissue sites frequently leads to stiffness in affected areas, limited movement, and eventual ankylosis (fusion) of affected joints (neck, back, shoulders, elbows, hips knees, wrists, ankles, jaw – often in that order).Episodic flare-ups (inflammatory soft tissue swellings) of FOP usually begin during early childhood and progress throughout life. Most cases of FOP occur as the result of a sporadic new mutation and the genetic mutation that results in this disorder has been identified. FOP is caused by the mutation of a gene (ACVR1) in the bone morphogenetic protein (BMP) pathway, which is important during the formation of the skeleton in the embryo and the repair of the skeleton following birth. | Overview of Fibrodysplasia Ossificans Progressiva. Fibrodysplasia ossificans progressiva (FOP) is a very rare genetic connective tissue disorder characterized by the abnormal development of bone in areas of the body where bone is not normally present (heterotopic ossification), such as the ligaments, tendons, and skeletal muscles. Specifically, this disorder causes the body's skeletal muscles and soft connective tissues to undergo a metamorphosis, essentially a transformation into bone, progressively locking joints in place and making movement difficult or impossible. Patients with FOP have malformed big toes that are present at birth (congenital). Other skeletal malformations may occur. The abnormal episodic development of bone at multiple soft tissue sites frequently leads to stiffness in affected areas, limited movement, and eventual ankylosis (fusion) of affected joints (neck, back, shoulders, elbows, hips knees, wrists, ankles, jaw – often in that order).Episodic flare-ups (inflammatory soft tissue swellings) of FOP usually begin during early childhood and progress throughout life. Most cases of FOP occur as the result of a sporadic new mutation and the genetic mutation that results in this disorder has been identified. FOP is caused by the mutation of a gene (ACVR1) in the bone morphogenetic protein (BMP) pathway, which is important during the formation of the skeleton in the embryo and the repair of the skeleton following birth. | 462 | Fibrodysplasia Ossificans Progressiva |
nord_462_1 | Symptoms of Fibrodysplasia Ossificans Progressiva | All individuals with classic FOP have malformations of the great toes and, in approximately 50% of patients, the thumbs. These changes in the skeleton are present at birth (congenital) and are the first clinical signs of this disorder. The most common skeletal malformation associated with FOP is a shortened great toe with a malformed distal first metatarsal and a missing or abnormal first phalanx and/or interphalangeal joint. Other malformations of the toes and fingers may include inward turning of the great toe toward the other toes (hallux valgus), abnormally short fingers and toes (microdactyly), and/or permanent fixation of the fifth finger in a bent position (clinodactyly). Other congenital signs of FOP include proximal medial tibial osteochondromas, malformation of the upper part of the spinal column (cervical vertebrae), and an abnormally short broad neck of the bone in the thigh that extends from the knee to the pelvis (femur).Progressive bone formation in connective tissues (heterotopic ossification) usually occurs during early childhood, and progresses throughout life. The abnormal development of bone may occur spontaneously but often occurs following an episode of soft tissue injury or a viral illness. The first sign of heterotopic ossification is the appearance of firm tender swellings on certain parts of the body, especially the back, neck, and/or shoulders. These soft tissue swellings mature through a cartilage-to-bone (endochondral) pathway to form mature heterotopic bone. The ectopic bone growth usually involves tendons, ligaments, skeletal muscle tissue, and connective tissues such as fascia and aponeuroses. In many cases, pain and stiffness occurs in these areas. On some occasions, a low-grade fever may herald the development of these swellings. Although the swellings eventually regress, they usually harden into mature bone as they decrease in size.In the affected areas, bone slowly replaces connective tissue. The neck, back, chest, arms, and legs are usually the first areas affected. The disease eventually affects the hips, ankles, wrists, elbows, shoulders, and/or jaw as well as the abdominal wall. In some affected individuals, the progression of bone development may be rapid; in others, the process may be gradual. Even among identical twins, the disease progression may vary greatly, reflecting different environment impacts such as traumatic episodes.Chronic swelling in various parts of the body is a common physical characteristic of individuals with FOP. Swelling may occur coordinately with the abnormal bone formation that characterizes FOP, or it may occur when recently-formed bone presses on lymphatic vessels, obstructing the flow of tissue fluid. In addition, swelling may also be caused by a lack of pumping action within the hardened (ossified) muscle and can cause blood and tissue fluids to pool in a limb (e.g., arms and/or legs).Abnormal development of bone eventually leads to stiffness and limited movement of affected joints. If the jaw is involved, affected individuals may have trouble eating and/or speaking. In addition, abnormal development of bone may lead to progressive deformity of the spine including side-to-side (scoliosis) and, in some cases, front-to-back curvature of the spine (kyphosis). As is the case for skeletal bone, the bone that develops in abnormal areas may fracture and then undergo fracture repair. As the disease progresses, individuals with FOP experience increasingly limited mobility that causes problems with balance, difficulty walking and/or sitting, and/or severely restricted movement.FOP may eventually result in complete immobilization. Affected individuals may experience progressive pain and stiffness in affected areas, complete fusion of the spine, and/or pain in affected areas of the body caused by abnormal bony growths that compress the nerves in these areas (entrapment neuropathies). As mobility begins to deteriorate, affected individuals may exhibit an increased susceptibility to respiratory infection or right sided congestive heart failure. Hearing impairment is seen in approximately 50% of affected individuals. In some cases of more severe forms of variant FOP, individuals may exhibit hair loss or mild cognitive delay. | Symptoms of Fibrodysplasia Ossificans Progressiva. All individuals with classic FOP have malformations of the great toes and, in approximately 50% of patients, the thumbs. These changes in the skeleton are present at birth (congenital) and are the first clinical signs of this disorder. The most common skeletal malformation associated with FOP is a shortened great toe with a malformed distal first metatarsal and a missing or abnormal first phalanx and/or interphalangeal joint. Other malformations of the toes and fingers may include inward turning of the great toe toward the other toes (hallux valgus), abnormally short fingers and toes (microdactyly), and/or permanent fixation of the fifth finger in a bent position (clinodactyly). Other congenital signs of FOP include proximal medial tibial osteochondromas, malformation of the upper part of the spinal column (cervical vertebrae), and an abnormally short broad neck of the bone in the thigh that extends from the knee to the pelvis (femur).Progressive bone formation in connective tissues (heterotopic ossification) usually occurs during early childhood, and progresses throughout life. The abnormal development of bone may occur spontaneously but often occurs following an episode of soft tissue injury or a viral illness. The first sign of heterotopic ossification is the appearance of firm tender swellings on certain parts of the body, especially the back, neck, and/or shoulders. These soft tissue swellings mature through a cartilage-to-bone (endochondral) pathway to form mature heterotopic bone. The ectopic bone growth usually involves tendons, ligaments, skeletal muscle tissue, and connective tissues such as fascia and aponeuroses. In many cases, pain and stiffness occurs in these areas. On some occasions, a low-grade fever may herald the development of these swellings. Although the swellings eventually regress, they usually harden into mature bone as they decrease in size.In the affected areas, bone slowly replaces connective tissue. The neck, back, chest, arms, and legs are usually the first areas affected. The disease eventually affects the hips, ankles, wrists, elbows, shoulders, and/or jaw as well as the abdominal wall. In some affected individuals, the progression of bone development may be rapid; in others, the process may be gradual. Even among identical twins, the disease progression may vary greatly, reflecting different environment impacts such as traumatic episodes.Chronic swelling in various parts of the body is a common physical characteristic of individuals with FOP. Swelling may occur coordinately with the abnormal bone formation that characterizes FOP, or it may occur when recently-formed bone presses on lymphatic vessels, obstructing the flow of tissue fluid. In addition, swelling may also be caused by a lack of pumping action within the hardened (ossified) muscle and can cause blood and tissue fluids to pool in a limb (e.g., arms and/or legs).Abnormal development of bone eventually leads to stiffness and limited movement of affected joints. If the jaw is involved, affected individuals may have trouble eating and/or speaking. In addition, abnormal development of bone may lead to progressive deformity of the spine including side-to-side (scoliosis) and, in some cases, front-to-back curvature of the spine (kyphosis). As is the case for skeletal bone, the bone that develops in abnormal areas may fracture and then undergo fracture repair. As the disease progresses, individuals with FOP experience increasingly limited mobility that causes problems with balance, difficulty walking and/or sitting, and/or severely restricted movement.FOP may eventually result in complete immobilization. Affected individuals may experience progressive pain and stiffness in affected areas, complete fusion of the spine, and/or pain in affected areas of the body caused by abnormal bony growths that compress the nerves in these areas (entrapment neuropathies). As mobility begins to deteriorate, affected individuals may exhibit an increased susceptibility to respiratory infection or right sided congestive heart failure. Hearing impairment is seen in approximately 50% of affected individuals. In some cases of more severe forms of variant FOP, individuals may exhibit hair loss or mild cognitive delay. | 462 | Fibrodysplasia Ossificans Progressiva |
nord_462_2 | Causes of Fibrodysplasia Ossificans Progressiva | Most cases of FOP occur sporadically, with a single affected individual within a family. When a familial pattern has been identified, FOP is inherited as an autosomal dominant trait with complete penetrance.In April 2006, an international team of researchers led by Eileen M. Shore, PhD and Frederick Kaplan MD of the University of Pennsylvania, published results of research identifying the genetic mutation that causes FOP. The team found that FOP is caused by a mutation of a gene on chromosome 2 (2q23-24) for a receptor in the BMP signaling pathway called ACVR1.Bone morphogenetic proteins are regulatory proteins important in embryonic skeletal formation and in post-natal repair of the skeleton. The gene identified as the FOP gene encodes a BMP receptor called Activin Receptor Type IA, or ACVR1, one of four known BMP Type I receptors. BMP receptors, located at the cell surface, help determine the fate of the stem cells in which they are expressed by transmitting signals into the cell. The classic clinical FOP presentation is caused by the specific substitution of a particular amino acid (arginine, at position 206) in the ACVR1 protein for another amino acid (histidine). This amino acid substitution induces activation of signaling by the ACVR1 receptor. In 2012, an ACVR1 (Arg206His; R206H) knock-in mouse was reported with a similar phenotype as human FOP. Extremely rare and illustrative phenotypic and genotypic variants of FOP have been reported, but in all patients to date, heterozygous activating mutations are present in the ACVR1 gene.Chromosomes, present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22, and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome, and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further subdivided into multiple numbered regions (bands), which reflect the location of the thousands of genes that are reside within each chromosome. For example, chromosome 2q23-24 refers to a location from bands 23 and 24 on the long arm of chromosome 2.Genes are encoded within the chromosomal DNAs that are inherited from the father and the mother. Cells have two copies of each gene (except for some genes encoded by the X and Y chromosomes); one gene copy is inherited from the father and one from the mother. Phenotypic variation (including genetic diseases) is determined by differences in the DNA sequences of the genes that specify a particular trait.Dominant genetic disorders are caused by abnormal DNA sequence changes in one of the two copies of a given gene. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from an affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females. | Causes of Fibrodysplasia Ossificans Progressiva. Most cases of FOP occur sporadically, with a single affected individual within a family. When a familial pattern has been identified, FOP is inherited as an autosomal dominant trait with complete penetrance.In April 2006, an international team of researchers led by Eileen M. Shore, PhD and Frederick Kaplan MD of the University of Pennsylvania, published results of research identifying the genetic mutation that causes FOP. The team found that FOP is caused by a mutation of a gene on chromosome 2 (2q23-24) for a receptor in the BMP signaling pathway called ACVR1.Bone morphogenetic proteins are regulatory proteins important in embryonic skeletal formation and in post-natal repair of the skeleton. The gene identified as the FOP gene encodes a BMP receptor called Activin Receptor Type IA, or ACVR1, one of four known BMP Type I receptors. BMP receptors, located at the cell surface, help determine the fate of the stem cells in which they are expressed by transmitting signals into the cell. The classic clinical FOP presentation is caused by the specific substitution of a particular amino acid (arginine, at position 206) in the ACVR1 protein for another amino acid (histidine). This amino acid substitution induces activation of signaling by the ACVR1 receptor. In 2012, an ACVR1 (Arg206His; R206H) knock-in mouse was reported with a similar phenotype as human FOP. Extremely rare and illustrative phenotypic and genotypic variants of FOP have been reported, but in all patients to date, heterozygous activating mutations are present in the ACVR1 gene.Chromosomes, present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22, and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome, and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further subdivided into multiple numbered regions (bands), which reflect the location of the thousands of genes that are reside within each chromosome. For example, chromosome 2q23-24 refers to a location from bands 23 and 24 on the long arm of chromosome 2.Genes are encoded within the chromosomal DNAs that are inherited from the father and the mother. Cells have two copies of each gene (except for some genes encoded by the X and Y chromosomes); one gene copy is inherited from the father and one from the mother. Phenotypic variation (including genetic diseases) is determined by differences in the DNA sequences of the genes that specify a particular trait.Dominant genetic disorders are caused by abnormal DNA sequence changes in one of the two copies of a given gene. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from an affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females. | 462 | Fibrodysplasia Ossificans Progressiva |
nord_462_3 | Affects of Fibrodysplasia Ossificans Progressiva | FOP is a very rare inherited connective tissue disorder that was first identified in the 18th century. Of an estimated 4000 affected individuals worldwide, there are approximately 900 known patients. This disorder affects males and females equally, and people from all ethnicities.Malformations of the toes and fingers are often present at birth (congenital); abnormal development of extra-skeletal bone usually begins during early childhood. In some rare cases, onset of abnormal bone growth may not occur until late adolescence or early adulthood. Affected individuals may have periods of time where they are free of new episodes of bone growths. However, new episodes of bone growth may begin at any time for no apparent reason (spontaneously). | Affects of Fibrodysplasia Ossificans Progressiva. FOP is a very rare inherited connective tissue disorder that was first identified in the 18th century. Of an estimated 4000 affected individuals worldwide, there are approximately 900 known patients. This disorder affects males and females equally, and people from all ethnicities.Malformations of the toes and fingers are often present at birth (congenital); abnormal development of extra-skeletal bone usually begins during early childhood. In some rare cases, onset of abnormal bone growth may not occur until late adolescence or early adulthood. Affected individuals may have periods of time where they are free of new episodes of bone growths. However, new episodes of bone growth may begin at any time for no apparent reason (spontaneously). | 462 | Fibrodysplasia Ossificans Progressiva |
nord_462_4 | Related disorders of Fibrodysplasia Ossificans Progressiva | Symptoms of the following disorders may be similar to those of fibrodysplasia ossificans progressiva. Comparisons may be useful for differential diagnosis:Aggressive juvenile fibromatosis is a condition in which cells called fibroblasts increase in number in tendon, ligament and other connective tissues. This overgrowth of cells may invade adjacent tissues, causing pain and disability. The resulting lesions may resemble the tissue swelling associated with FOP. However, individuals with aggressive juvenile fibromatosis do not have the toe malformation that is associated with FOP nor do they develop heterotopic ossification.Progressive osseous heteroplasia (POH) is an extremely rare inherited disorder characterized by the abnormal development of bone in areas of the body where bone is not normally present (heterotopic ossification). Unlike FOP, the initial bone growth may develop on the surface of the skin (osseous plaques). These areas may become progressively widespread and come together (coalesce) to form even larger areas of hardened and thickened skin (dermal ossification). Progressive osseous heteroplasia spreads to deeper levels of the skin and to various muscle, fatty, and connective tissues of the body. As the disorder continues to progress, the abnormal development of bone may lead to stiffening and limited movement of affected joints. In severe cases, affected joints may become permanently fixed (ankylosed). In addition, arms and legs may become malformed and not grow to full length. The genetic basis of progressive osseous heteroplasia is a heterozygous inactivating mutation in the gene encoding the paternally-inherited allele of the alpha subunit of the stimulatory G-protein of adenylyl cyclase (GNAS). GNAS mutations have been identified in approximately 70% of affected individuals. POH is a distinct developmental disorder and belongs to a spectrum of clinical conditions that have the common feature of ossification of the skin (osteoma cutis). Although skeletal malformations have been noted, individuals with progressive osseous heteroplasia do not have the toe malformation that is characteristic of FOP. (For more information on this disorder, choose “Progressive Osseous Heteroplasia” as your search term in the Rare Disease Database.) | Related disorders of Fibrodysplasia Ossificans Progressiva. Symptoms of the following disorders may be similar to those of fibrodysplasia ossificans progressiva. Comparisons may be useful for differential diagnosis:Aggressive juvenile fibromatosis is a condition in which cells called fibroblasts increase in number in tendon, ligament and other connective tissues. This overgrowth of cells may invade adjacent tissues, causing pain and disability. The resulting lesions may resemble the tissue swelling associated with FOP. However, individuals with aggressive juvenile fibromatosis do not have the toe malformation that is associated with FOP nor do they develop heterotopic ossification.Progressive osseous heteroplasia (POH) is an extremely rare inherited disorder characterized by the abnormal development of bone in areas of the body where bone is not normally present (heterotopic ossification). Unlike FOP, the initial bone growth may develop on the surface of the skin (osseous plaques). These areas may become progressively widespread and come together (coalesce) to form even larger areas of hardened and thickened skin (dermal ossification). Progressive osseous heteroplasia spreads to deeper levels of the skin and to various muscle, fatty, and connective tissues of the body. As the disorder continues to progress, the abnormal development of bone may lead to stiffening and limited movement of affected joints. In severe cases, affected joints may become permanently fixed (ankylosed). In addition, arms and legs may become malformed and not grow to full length. The genetic basis of progressive osseous heteroplasia is a heterozygous inactivating mutation in the gene encoding the paternally-inherited allele of the alpha subunit of the stimulatory G-protein of adenylyl cyclase (GNAS). GNAS mutations have been identified in approximately 70% of affected individuals. POH is a distinct developmental disorder and belongs to a spectrum of clinical conditions that have the common feature of ossification of the skin (osteoma cutis). Although skeletal malformations have been noted, individuals with progressive osseous heteroplasia do not have the toe malformation that is characteristic of FOP. (For more information on this disorder, choose “Progressive Osseous Heteroplasia” as your search term in the Rare Disease Database.) | 462 | Fibrodysplasia Ossificans Progressiva |
nord_462_5 | Diagnosis of Fibrodysplasia Ossificans Progressiva | Misdiagnosis of FOP is common but can be avoided simply by examining the individual’s toes for the characteristic feature, short great toes. The diagnosis may be confirmed by a thorough clinical evaluation, characteristic physical findings, and sequencing of the ACVR1 gene. | Diagnosis of Fibrodysplasia Ossificans Progressiva. Misdiagnosis of FOP is common but can be avoided simply by examining the individual’s toes for the characteristic feature, short great toes. The diagnosis may be confirmed by a thorough clinical evaluation, characteristic physical findings, and sequencing of the ACVR1 gene. | 462 | Fibrodysplasia Ossificans Progressiva |
nord_462_6 | Therapies of Fibrodysplasia Ossificans Progressiva | TreatmentBiopsies should be avoided when FOP is suspected because these tests may result in rapid bone formation in those areas where tissue is removed. Intramuscular injections (e.g., immunizations) must be avoided. Injections of local anesthetics and and stretching of the jaw for dental therapy should be avoided. People with FOP should avoid any situations, such as falls, that may cause blunt trauma, since trauma may cause abnormal bone development. Various viral illnesses including influenza and influenza-like illnesses may provoke flare-ups of the condition.In 2023, palovarotene (Sohonos) was approved by the U.S. Food and Drug Administration (FDA) as the first treatment for FOP to reduce extra-skeletal bone formation in adults and children aged 8 years and older for females, and 10 years and older for males. Preventative (prophylactic) antibiotic therapy may be appropriate to prevent infection in affected individuals with an increased susceptibility to respiratory infections due to progressive mobility impairment.Certain types of drugs have been used to relieve pain and swelling associated with FOP during acute flare-ups (most notably corticosteroids) and non-steroidal anti-inflammatory medication between flare-ups.Affected individuals may benefit from occupational therapy. Special shoes, braces, and other devices that assist in walking and weight-bearing have been used to help people with FOP. An occupational therapist can help obtain special devices or tools to assist in daily activities.A team approach for infants diagnosed with FOP is also recommended and may include special social, educational and medical services.Genetic counseling is recommended for individuals with FOP and their families. Other treatment is symptomatic and supportive. | Therapies of Fibrodysplasia Ossificans Progressiva. TreatmentBiopsies should be avoided when FOP is suspected because these tests may result in rapid bone formation in those areas where tissue is removed. Intramuscular injections (e.g., immunizations) must be avoided. Injections of local anesthetics and and stretching of the jaw for dental therapy should be avoided. People with FOP should avoid any situations, such as falls, that may cause blunt trauma, since trauma may cause abnormal bone development. Various viral illnesses including influenza and influenza-like illnesses may provoke flare-ups of the condition.In 2023, palovarotene (Sohonos) was approved by the U.S. Food and Drug Administration (FDA) as the first treatment for FOP to reduce extra-skeletal bone formation in adults and children aged 8 years and older for females, and 10 years and older for males. Preventative (prophylactic) antibiotic therapy may be appropriate to prevent infection in affected individuals with an increased susceptibility to respiratory infections due to progressive mobility impairment.Certain types of drugs have been used to relieve pain and swelling associated with FOP during acute flare-ups (most notably corticosteroids) and non-steroidal anti-inflammatory medication between flare-ups.Affected individuals may benefit from occupational therapy. Special shoes, braces, and other devices that assist in walking and weight-bearing have been used to help people with FOP. An occupational therapist can help obtain special devices or tools to assist in daily activities.A team approach for infants diagnosed with FOP is also recommended and may include special social, educational and medical services.Genetic counseling is recommended for individuals with FOP and their families. Other treatment is symptomatic and supportive. | 462 | Fibrodysplasia Ossificans Progressiva |
nord_463_0 | Overview of Fibrolamellar Carcinoma | Fibrolamellar carcinoma is a rare form of cancer that affects the liver. Unlike most cancers of the liver, it occurs with greater frequency in adolescents and young adults who are otherwise healthy. There are often no symptoms or signs of the disorder for a long time. Symptoms that can develop include abdominal pain, unintended weight loss, and a general feeling of poor health (malaise). Treatment is usually through surgical removal (resection) of the tumor. When surgery is not possible or is unsuccessful, then other therapies may be considered. Recurrence following successful surgical removal of a tumor can occur, meaning that sometimes the tumor can come back after it was removed. The exact, underlying cause of this disorder is unknown.The term fibrolamellar comes from the fibrous bands of tissue that occur in a unique “lamellar” pattern when tissue from a tumor is viewed under a microscope. Fibrolamellar carcinoma was first reported in the medical literature in 1956 and described as a different type of liver cancer from the more common kind of liver cancer, hepatocellular carcinoma (HCC). Most people with HCC have an underlying liver disease called cirrhosis, which is scarring of the liver that can occur as a result of long term liver damage due to hepatitis or alcohol use. Most people with fibrolamellar carcinoma do not have an underlying liver disease and do not have cirrhosis. Many physicians now consider fibrolamellar carcinoma a separate form of cancer distinct from HCC. | Overview of Fibrolamellar Carcinoma. Fibrolamellar carcinoma is a rare form of cancer that affects the liver. Unlike most cancers of the liver, it occurs with greater frequency in adolescents and young adults who are otherwise healthy. There are often no symptoms or signs of the disorder for a long time. Symptoms that can develop include abdominal pain, unintended weight loss, and a general feeling of poor health (malaise). Treatment is usually through surgical removal (resection) of the tumor. When surgery is not possible or is unsuccessful, then other therapies may be considered. Recurrence following successful surgical removal of a tumor can occur, meaning that sometimes the tumor can come back after it was removed. The exact, underlying cause of this disorder is unknown.The term fibrolamellar comes from the fibrous bands of tissue that occur in a unique “lamellar” pattern when tissue from a tumor is viewed under a microscope. Fibrolamellar carcinoma was first reported in the medical literature in 1956 and described as a different type of liver cancer from the more common kind of liver cancer, hepatocellular carcinoma (HCC). Most people with HCC have an underlying liver disease called cirrhosis, which is scarring of the liver that can occur as a result of long term liver damage due to hepatitis or alcohol use. Most people with fibrolamellar carcinoma do not have an underlying liver disease and do not have cirrhosis. Many physicians now consider fibrolamellar carcinoma a separate form of cancer distinct from HCC. | 463 | Fibrolamellar Carcinoma |
nord_463_1 | Symptoms of Fibrolamellar Carcinoma | The signs and symptoms usually arise with advanced disease. For many years, affected individuals may not have any noticeable signs or symptoms (asymptomatic) because they are otherwise healthy. Initial symptoms are nonspecific, which means they can be seen in a variety of different medical conditions. Every person is unique and how this disorder affects one person can be different from how it affects another person. Fibrolamellar carcinoma may not cause problems for many, many years or it can be aggressive, quickly spreading locally or spreading to other parts of the body (metastasizing). When symptoms do develop, they can include abdominal pain or discomfort, unintended weight loss, and a general feeling of poor health (malaise). Abdominal pain is the most common symptom, although it can vary in both duration and intensity. Additional symptoms can include shoulder or back pain, fever, nausea or vomiting, loss of appetite, night sweats, the accumulation of fluid in the abdominal cavity causing swelling of the abdomen (ascites), enlargement or swelling (distention) of the abdomen, a feeling of fullness in the stomach, and enlargement of the liver (hepatomegaly). Sometimes, there is a mass in the liver that can be felt by touch (palpable). Yellowing of the skin and whites of the eyes (jaundice) can also occur and is usually caused by blockage (obstruction) of the biliary tract, which includes the liver, gallbladder, and biliary ducts. These organs and structures help to regulate and release bile, which is made by the liver to help with digestion. A rare finding that has been reported is gynecomastia, a condition characterized by an increase in breast tissues in males. Other uncommon findings are low blood sugar levels (hypoglycemia) because the tumor uses up glucose in the body, or changes in mental status such as confusion due to the buildup of ammonia in the body. | Symptoms of Fibrolamellar Carcinoma. The signs and symptoms usually arise with advanced disease. For many years, affected individuals may not have any noticeable signs or symptoms (asymptomatic) because they are otherwise healthy. Initial symptoms are nonspecific, which means they can be seen in a variety of different medical conditions. Every person is unique and how this disorder affects one person can be different from how it affects another person. Fibrolamellar carcinoma may not cause problems for many, many years or it can be aggressive, quickly spreading locally or spreading to other parts of the body (metastasizing). When symptoms do develop, they can include abdominal pain or discomfort, unintended weight loss, and a general feeling of poor health (malaise). Abdominal pain is the most common symptom, although it can vary in both duration and intensity. Additional symptoms can include shoulder or back pain, fever, nausea or vomiting, loss of appetite, night sweats, the accumulation of fluid in the abdominal cavity causing swelling of the abdomen (ascites), enlargement or swelling (distention) of the abdomen, a feeling of fullness in the stomach, and enlargement of the liver (hepatomegaly). Sometimes, there is a mass in the liver that can be felt by touch (palpable). Yellowing of the skin and whites of the eyes (jaundice) can also occur and is usually caused by blockage (obstruction) of the biliary tract, which includes the liver, gallbladder, and biliary ducts. These organs and structures help to regulate and release bile, which is made by the liver to help with digestion. A rare finding that has been reported is gynecomastia, a condition characterized by an increase in breast tissues in males. Other uncommon findings are low blood sugar levels (hypoglycemia) because the tumor uses up glucose in the body, or changes in mental status such as confusion due to the buildup of ammonia in the body. | 463 | Fibrolamellar Carcinoma |
nord_463_2 | Causes of Fibrolamellar Carcinoma | As with many forms of cancer, the exact, underlying cause of fibrolamellar carcinoma is unknown. Researchers speculate that multiple factors including genetic and environmental ones play a role in the disorder’s development. Current research suggests that abnormalities of DNA (deoxyribonucleic acid), which is the carrier of the body’s genetic code, are the underlying basis that causes cells to become malignant.Researchers have determined that many people with fibrolamellar carcinoma have the same underlying genetic abnormality called a DNAJB1-PRKACA fusion gene. This genetic abnormality is highly specific to fibrolamellar carcinoma, meaning it is not found in normal liver tissue or elsewhere in other organs. Genes normally produce (encode) proteins that have several functions within the body. The abnormality found in fibrolamellar carcinoma is caused when there is a loss of genetic material (deletion) on chromosome 19, which leads to the abnormal combination of two genes, the DNAJB1 and the PRKACA genes (see figure below). The fusion of these two areas on the DNA creates a new gene called a “chimeric” gene, which in turn produces an abnormal protein product. Similar to the fusion of the two genes, the fusion protein is an abnormal combination of the two normal proteins (see figure below). Researchers believe that the abnormal protein created by this chimeric gene may contribute to or influence the development of fibrolamellar carcinoma, or be the main factor driving tumor formation and growth. The exact reason why the loss of genetic material and fusion of these two genes happens is not fully understood. The exact way that the fusion protein causes the cells to grow excessively as a cancer is also not fully understood.Figure: FLC fusion gene and proteinOther types of liver cancer are usually associated with underlying disease (e.g. hepatitis) or damage (e.g. scarring [cirrhosis]) to the liver. Generally, individuals with fibrolamellar carcinoma do not have any identified or proven risk factors other than the presence of the DNAJB1-PRKACA chimeric gene. Researchers are studying the disorder to try and determine where there are specific environmental risk factors, or any additional genetic risk factors. | Causes of Fibrolamellar Carcinoma. As with many forms of cancer, the exact, underlying cause of fibrolamellar carcinoma is unknown. Researchers speculate that multiple factors including genetic and environmental ones play a role in the disorder’s development. Current research suggests that abnormalities of DNA (deoxyribonucleic acid), which is the carrier of the body’s genetic code, are the underlying basis that causes cells to become malignant.Researchers have determined that many people with fibrolamellar carcinoma have the same underlying genetic abnormality called a DNAJB1-PRKACA fusion gene. This genetic abnormality is highly specific to fibrolamellar carcinoma, meaning it is not found in normal liver tissue or elsewhere in other organs. Genes normally produce (encode) proteins that have several functions within the body. The abnormality found in fibrolamellar carcinoma is caused when there is a loss of genetic material (deletion) on chromosome 19, which leads to the abnormal combination of two genes, the DNAJB1 and the PRKACA genes (see figure below). The fusion of these two areas on the DNA creates a new gene called a “chimeric” gene, which in turn produces an abnormal protein product. Similar to the fusion of the two genes, the fusion protein is an abnormal combination of the two normal proteins (see figure below). Researchers believe that the abnormal protein created by this chimeric gene may contribute to or influence the development of fibrolamellar carcinoma, or be the main factor driving tumor formation and growth. The exact reason why the loss of genetic material and fusion of these two genes happens is not fully understood. The exact way that the fusion protein causes the cells to grow excessively as a cancer is also not fully understood.Figure: FLC fusion gene and proteinOther types of liver cancer are usually associated with underlying disease (e.g. hepatitis) or damage (e.g. scarring [cirrhosis]) to the liver. Generally, individuals with fibrolamellar carcinoma do not have any identified or proven risk factors other than the presence of the DNAJB1-PRKACA chimeric gene. Researchers are studying the disorder to try and determine where there are specific environmental risk factors, or any additional genetic risk factors. | 463 | Fibrolamellar Carcinoma |
nord_463_3 | Affects of Fibrolamellar Carcinoma | Fibrolamellar carcinoma is an ultra rare form of cancer. It affects both men and women and affects approximately 1 in 5,000,000 people in the general population. Fibrolamellar carcinoma occurs with greater frequency among young adults with a median age of diagnosis of 25. It is found all over the world and the rate of occurrence can vary geographically. The disorder accounts for about 1% of all people with primary liver cancer in the United States, but accounts for about 5.8 percent of all people with primary liver cancer in Mexico. | Affects of Fibrolamellar Carcinoma. Fibrolamellar carcinoma is an ultra rare form of cancer. It affects both men and women and affects approximately 1 in 5,000,000 people in the general population. Fibrolamellar carcinoma occurs with greater frequency among young adults with a median age of diagnosis of 25. It is found all over the world and the rate of occurrence can vary geographically. The disorder accounts for about 1% of all people with primary liver cancer in the United States, but accounts for about 5.8 percent of all people with primary liver cancer in Mexico. | 463 | Fibrolamellar Carcinoma |
nord_463_4 | Related disorders of Fibrolamellar Carcinoma | Symptoms of the following disorders can be similar to those of fibrolamellar carcinoma. Comparisons may be useful for a differential diagnosis.Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver. Most people have an underlying liver disease such as infection with hepatitis B or C virus, damage from long term alcohol use, or non-alcoholic fatty liver disease. Most people have cirrhosis, which is scarring of the liver that can occur as a result of damage from chronic liver diseases. If HCC is found early, there may be curative treatments offered. However, HCC often does not cause any symptoms, especially early in the disease course. If HCC is diagnosed at a late stage, patients may not be able to receive curative treatments, and care is then geared toward helping people have a better quality of life. Although HCC does not necessarily cause symptoms, many individuals will have symptoms caused by the underlying liver disease. The exact cause of HCC is not fully understood. (For more information on this disorder, choose “hepatocellular carcinoma” as your search term in the Rare Disease Database.)There are several types of benign masses or noncancerous tumors that can occur in the liver including focal nodular hyperplasia (FNH), adenoma, cyst, and hemangioma. A form of cancer which arise from the biliary tree that resides in and near the liver is called cholangiocarcinoma. Cancer that originates in another area of the body such as the colon or pancreas can also spread (metastasize) to the liver. Sometimes, even infections called abscesses that occur from bacteria or parasites can appear like a mass. All of these conditions need to be differentiated from fibrolamellar carcinoma. | Related disorders of Fibrolamellar Carcinoma. Symptoms of the following disorders can be similar to those of fibrolamellar carcinoma. Comparisons may be useful for a differential diagnosis.Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver. Most people have an underlying liver disease such as infection with hepatitis B or C virus, damage from long term alcohol use, or non-alcoholic fatty liver disease. Most people have cirrhosis, which is scarring of the liver that can occur as a result of damage from chronic liver diseases. If HCC is found early, there may be curative treatments offered. However, HCC often does not cause any symptoms, especially early in the disease course. If HCC is diagnosed at a late stage, patients may not be able to receive curative treatments, and care is then geared toward helping people have a better quality of life. Although HCC does not necessarily cause symptoms, many individuals will have symptoms caused by the underlying liver disease. The exact cause of HCC is not fully understood. (For more information on this disorder, choose “hepatocellular carcinoma” as your search term in the Rare Disease Database.)There are several types of benign masses or noncancerous tumors that can occur in the liver including focal nodular hyperplasia (FNH), adenoma, cyst, and hemangioma. A form of cancer which arise from the biliary tree that resides in and near the liver is called cholangiocarcinoma. Cancer that originates in another area of the body such as the colon or pancreas can also spread (metastasize) to the liver. Sometimes, even infections called abscesses that occur from bacteria or parasites can appear like a mass. All of these conditions need to be differentiated from fibrolamellar carcinoma. | 463 | Fibrolamellar Carcinoma |
nord_463_5 | Diagnosis of Fibrolamellar Carcinoma | A diagnosis of fibrolamellar carcinoma is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation, and a variety of specialized tests. A diagnosis of fibrolamellar carcinoma can be difficult because symptoms may be nonspecific and can be caused by many different types of disorders. Because the disorder occurs in young adults, a diagnosis of cancer is usually not suspected initially until many other more common conditions are ruled out. Clinical Testing and Workup
Doctors may recommend advanced imaging techniques such as computed tomography (CT) scan, magnetic resonance imaging (MRI), or ultrasound to try and confirm a diagnosis. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of specific organs and bodily tissues. During an ultrasound, reflected sound waves are used to create an image of internal organs or structures such as the liver. A doctor may need to perform a biopsy to confirm a diagnosis. During a biopsy, a doctor will use CT or ultrasound imaging to obtain a sample area in the liver with a needle in order to examine the tissue under the microscope. Rarely, a small part of tumor has to be surgically removed to obtain the sample to study. A biopsy may be necessary to distinguish fibrolamellar carcinoma from benign tumors such as FNH or other cancers such as HCC. The tissue sample then oftentimes undergoes immunostaining to aid in a diagnosis. During immunostaining, antibodies are applied to a sample of the tumor from a biopsy or from surgical removal. The antibodies are used to test for certain proteins (markers), for example CK7 and CD68, which are highly expressed in individuals with fibrolamellar carcinoma. Detection of these markers does not confirm a diagnosis of fibrolamellar carcinoma but is another finding indicative of the disorder. Some physicians have advocated a test known as fluorescent in situ hybridization (FISH). During a FISH exam, probes marked by a specific color of fluorescent dye are attached to a specific gene allowing researchers to better view that specific region of the chromosome. This allows physician to detect the DNAJB1-PRKACA chimeric gene on chromosome 19. There is no known blood test that can make a diagnosis of fibrolamellar carcinoma. In other forms of liver cancer such as hepatocellular carcinoma, there are elevated levels of alpha fetoprotein in the blood. Physicians may run a blood test to see whether this protein is present. This helps to distinguish fibrolamellar carcinoma from hepatocellular carcinoma. | Diagnosis of Fibrolamellar Carcinoma. A diagnosis of fibrolamellar carcinoma is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation, and a variety of specialized tests. A diagnosis of fibrolamellar carcinoma can be difficult because symptoms may be nonspecific and can be caused by many different types of disorders. Because the disorder occurs in young adults, a diagnosis of cancer is usually not suspected initially until many other more common conditions are ruled out. Clinical Testing and Workup
Doctors may recommend advanced imaging techniques such as computed tomography (CT) scan, magnetic resonance imaging (MRI), or ultrasound to try and confirm a diagnosis. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of specific organs and bodily tissues. During an ultrasound, reflected sound waves are used to create an image of internal organs or structures such as the liver. A doctor may need to perform a biopsy to confirm a diagnosis. During a biopsy, a doctor will use CT or ultrasound imaging to obtain a sample area in the liver with a needle in order to examine the tissue under the microscope. Rarely, a small part of tumor has to be surgically removed to obtain the sample to study. A biopsy may be necessary to distinguish fibrolamellar carcinoma from benign tumors such as FNH or other cancers such as HCC. The tissue sample then oftentimes undergoes immunostaining to aid in a diagnosis. During immunostaining, antibodies are applied to a sample of the tumor from a biopsy or from surgical removal. The antibodies are used to test for certain proteins (markers), for example CK7 and CD68, which are highly expressed in individuals with fibrolamellar carcinoma. Detection of these markers does not confirm a diagnosis of fibrolamellar carcinoma but is another finding indicative of the disorder. Some physicians have advocated a test known as fluorescent in situ hybridization (FISH). During a FISH exam, probes marked by a specific color of fluorescent dye are attached to a specific gene allowing researchers to better view that specific region of the chromosome. This allows physician to detect the DNAJB1-PRKACA chimeric gene on chromosome 19. There is no known blood test that can make a diagnosis of fibrolamellar carcinoma. In other forms of liver cancer such as hepatocellular carcinoma, there are elevated levels of alpha fetoprotein in the blood. Physicians may run a blood test to see whether this protein is present. This helps to distinguish fibrolamellar carcinoma from hepatocellular carcinoma. | 463 | Fibrolamellar Carcinoma |
nord_463_6 | Therapies of Fibrolamellar Carcinoma | Treatment
The treatment of fibrolamellar carcinoma is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists: physicians with expertise in the diagnosis and treatment of liver disorders (hepatologists), physicians who specialize in the diagnosis and treatment of cancer (medical oncologists), physicians who use radiation to treat cancer (radiation oncologists), physicians who use imaging to perform various interventions (interventional radiologists), surgeons who perform an operation to remove the cancer, and other healthcare professionals. Psychosocial support for the entire family is essential as well. Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as disease stage; presence of cancer in lymph nodes or other areas of the body; tumor size and exact location within the liver; the presence or absence of certain symptoms; an individual’s age and general health; and/or other elements. All of these factors are taken into consideration when deciding if surgery can be performed. Similarly, decisions concerning the use of particular drug regimens and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the patient based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.The main treatment option for fibrolamellar carcinoma is surgical removal (resection) of the tumor. Generally, liver resection has proven the most effective method in treating individuals with fibrolamellar carcinoma. The surrounding lymph nodes are also removed because of the risk of the cancer spreading. When the entire tumor can be removed surgically (complete resection) the prognosis is generally considered to be much improved. Fibrolamellar carcinoma can come back (recur) in individuals who have been successfully treated by surgery. Recurrence is usually treated with additional surgery. There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. Instead, various treatments including chemotherapy have been reported in the medical literature as part of smaller studies. Additional treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with fibrolamellar carcinoma. | Therapies of Fibrolamellar Carcinoma. Treatment
The treatment of fibrolamellar carcinoma is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists: physicians with expertise in the diagnosis and treatment of liver disorders (hepatologists), physicians who specialize in the diagnosis and treatment of cancer (medical oncologists), physicians who use radiation to treat cancer (radiation oncologists), physicians who use imaging to perform various interventions (interventional radiologists), surgeons who perform an operation to remove the cancer, and other healthcare professionals. Psychosocial support for the entire family is essential as well. Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as disease stage; presence of cancer in lymph nodes or other areas of the body; tumor size and exact location within the liver; the presence or absence of certain symptoms; an individual’s age and general health; and/or other elements. All of these factors are taken into consideration when deciding if surgery can be performed. Similarly, decisions concerning the use of particular drug regimens and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the patient based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.The main treatment option for fibrolamellar carcinoma is surgical removal (resection) of the tumor. Generally, liver resection has proven the most effective method in treating individuals with fibrolamellar carcinoma. The surrounding lymph nodes are also removed because of the risk of the cancer spreading. When the entire tumor can be removed surgically (complete resection) the prognosis is generally considered to be much improved. Fibrolamellar carcinoma can come back (recur) in individuals who have been successfully treated by surgery. Recurrence is usually treated with additional surgery. There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. Instead, various treatments including chemotherapy have been reported in the medical literature as part of smaller studies. Additional treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with fibrolamellar carcinoma. | 463 | Fibrolamellar Carcinoma |
nord_464_0 | Overview of Fibromuscular Dysplasia | Fibromuscular dysplasia, commonly called FMD, is a disease that causes one or more arteries in the body to have abnormal cell development in the artery wall. As a result, areas of narrowing (stenosis), aneurysms, or tears (dissection) may occur. If narrowing or a tear causes a decrease in blood flow through the artery, symptoms may result. FMD is most commonly found in the arteries that supply the kidneys with blood (renal arteries) and the arteries called the carotid and vertebral arteries which are found in the neck and supply the brain with blood. Less commonly, FMD affects the arteries in the abdomen (supplying the liver, spleen and intestines) and extremities (legs and arms). In more than one-half of people with this disease, there will be evidence of FMD in more than one artery.Recently, studies have shown that some women who were healthy and who have a sudden tearing of a coronary artery (called sudden coronary artery dissection or “SCAD”) probably have undiagnosed FMD. SCAD was previously thought to be a separate condition to FMD, but now we are starting to understand that many people have FMD as the main reason for their coronary tear. | Overview of Fibromuscular Dysplasia. Fibromuscular dysplasia, commonly called FMD, is a disease that causes one or more arteries in the body to have abnormal cell development in the artery wall. As a result, areas of narrowing (stenosis), aneurysms, or tears (dissection) may occur. If narrowing or a tear causes a decrease in blood flow through the artery, symptoms may result. FMD is most commonly found in the arteries that supply the kidneys with blood (renal arteries) and the arteries called the carotid and vertebral arteries which are found in the neck and supply the brain with blood. Less commonly, FMD affects the arteries in the abdomen (supplying the liver, spleen and intestines) and extremities (legs and arms). In more than one-half of people with this disease, there will be evidence of FMD in more than one artery.Recently, studies have shown that some women who were healthy and who have a sudden tearing of a coronary artery (called sudden coronary artery dissection or “SCAD”) probably have undiagnosed FMD. SCAD was previously thought to be a separate condition to FMD, but now we are starting to understand that many people have FMD as the main reason for their coronary tear. | 464 | Fibromuscular Dysplasia |
nord_464_1 | Symptoms of Fibromuscular Dysplasia | Some people with this disease do not have symptoms or findings on a physical examination. The signs and/or symptoms that a person with FMD may experience depend on the arteries affected and whether there is narrowing, tears, or aneurysms within them. Any pain or clinical sign related to FMD typically comes from the organ that is supplied by that artery. For example, FMD in the kidney arteries may cause high blood pressure. FMD in the carotid arteries may cause headaches or a swooshing sound in the ears (called pulsatile tinnitus). Some patients with FMD may have no symptoms at all but are diagnosed with this disease when a physician hears a noise over one of the arteries due to disturbed or turbulent blood flow within the vessel. This noise is known as a bruit.A person with severe carotid FMD causing severe narrowing or a tear in a carotid or vertebral artery may have neurologic symptoms involving the facial nerves (drooping of the eye lid, unequal size of the pupils, for example), stroke or transient ischemic attack. People with carotid FMD have a higher risk for aneurysms of the arteries in the brain (intracranial aneurysms). Bleeding in the brain (intracranial hemorrhage) may occur if an aneurysm ruptures, and it is important to identify and treat brain aneurysms early to prevent this.FMD involving the arteries that supply the intestines, liver and spleen with blood (mesenteric arteries) can result in abdominal pain after eating and unintended weight loss. FMD in the arms and legs can cause limb discomfort with exercise or can lead to unequal blood pressures in the arms. | Symptoms of Fibromuscular Dysplasia. Some people with this disease do not have symptoms or findings on a physical examination. The signs and/or symptoms that a person with FMD may experience depend on the arteries affected and whether there is narrowing, tears, or aneurysms within them. Any pain or clinical sign related to FMD typically comes from the organ that is supplied by that artery. For example, FMD in the kidney arteries may cause high blood pressure. FMD in the carotid arteries may cause headaches or a swooshing sound in the ears (called pulsatile tinnitus). Some patients with FMD may have no symptoms at all but are diagnosed with this disease when a physician hears a noise over one of the arteries due to disturbed or turbulent blood flow within the vessel. This noise is known as a bruit.A person with severe carotid FMD causing severe narrowing or a tear in a carotid or vertebral artery may have neurologic symptoms involving the facial nerves (drooping of the eye lid, unequal size of the pupils, for example), stroke or transient ischemic attack. People with carotid FMD have a higher risk for aneurysms of the arteries in the brain (intracranial aneurysms). Bleeding in the brain (intracranial hemorrhage) may occur if an aneurysm ruptures, and it is important to identify and treat brain aneurysms early to prevent this.FMD involving the arteries that supply the intestines, liver and spleen with blood (mesenteric arteries) can result in abdominal pain after eating and unintended weight loss. FMD in the arms and legs can cause limb discomfort with exercise or can lead to unequal blood pressures in the arms. | 464 | Fibromuscular Dysplasia |
nord_464_2 | Causes of Fibromuscular Dysplasia | The cause of FMD is not yet known, but several theories have been suggested. A number of case reports in the literature have identified the disease in multiple members of the same family including twins. As a result, it is felt that there may be a genetic cause. However, a relative may have different artery involvement, different disease severity, or not develop FMD at all. In fact, most individuals with FMD do not have a family member who also has the disease. Among some individuals with FMD, there is a family history of other vascular problems, such as blood vessel aneurysms.FMD is far more commonly seen in women than in men, resulting in the theory that hormones may play an important role in disease development. However, in small population studies, one’s reproductive history (number of pregnancies and when they occurred) as well as use of birth control pills did not correlate with the development of FMD.Other possible causes of FMD include abnormal development of the arteries that supply the vessel wall with blood, resulting in inadequate oxygen supply; the anatomic position or movement of the artery within the body; certain medications, and tobacco use. It is possible that many factors contribute to the development of FMD. This area requires further research. | Causes of Fibromuscular Dysplasia. The cause of FMD is not yet known, but several theories have been suggested. A number of case reports in the literature have identified the disease in multiple members of the same family including twins. As a result, it is felt that there may be a genetic cause. However, a relative may have different artery involvement, different disease severity, or not develop FMD at all. In fact, most individuals with FMD do not have a family member who also has the disease. Among some individuals with FMD, there is a family history of other vascular problems, such as blood vessel aneurysms.FMD is far more commonly seen in women than in men, resulting in the theory that hormones may play an important role in disease development. However, in small population studies, one’s reproductive history (number of pregnancies and when they occurred) as well as use of birth control pills did not correlate with the development of FMD.Other possible causes of FMD include abnormal development of the arteries that supply the vessel wall with blood, resulting in inadequate oxygen supply; the anatomic position or movement of the artery within the body; certain medications, and tobacco use. It is possible that many factors contribute to the development of FMD. This area requires further research. | 464 | Fibromuscular Dysplasia |
nord_464_3 | Affects of Fibromuscular Dysplasia | FMD affects women far more commonly than men, although men and children can be affected with this disease. In children with FMD, the disease seems to more commonly present with significant narrowing rather than tears of arteries and also seems to involve the arteries to the kidneys and intestines more commonly than the carotid vessels. In the pediatric population, FMD affects both boys and girls. | Affects of Fibromuscular Dysplasia. FMD affects women far more commonly than men, although men and children can be affected with this disease. In children with FMD, the disease seems to more commonly present with significant narrowing rather than tears of arteries and also seems to involve the arteries to the kidneys and intestines more commonly than the carotid vessels. In the pediatric population, FMD affects both boys and girls. | 464 | Fibromuscular Dysplasia |
nord_464_4 | Related disorders of Fibromuscular Dysplasia | The vascular subtype of Ehlers-Danlos syndrome (type IV) has been associated with the most common type of fibromuscular dysplasia, known as multifocal FMD. This syndrome should be suspected in patients with multiple aneurysms and/or tears (dissections) in arteries in addition to the typical angiographic findings of fibromuscular dysplasia. There have been isolated reports of fibromuscular dysplasia associated with other disorders, including Alport syndrome, pheochromocytoma, Marfan syndrome, and moyamoya disease. (For more information on these disorders, search for the term in the Rare Disease Database.) | Related disorders of Fibromuscular Dysplasia. The vascular subtype of Ehlers-Danlos syndrome (type IV) has been associated with the most common type of fibromuscular dysplasia, known as multifocal FMD. This syndrome should be suspected in patients with multiple aneurysms and/or tears (dissections) in arteries in addition to the typical angiographic findings of fibromuscular dysplasia. There have been isolated reports of fibromuscular dysplasia associated with other disorders, including Alport syndrome, pheochromocytoma, Marfan syndrome, and moyamoya disease. (For more information on these disorders, search for the term in the Rare Disease Database.) | 464 | Fibromuscular Dysplasia |
nord_464_5 | Diagnosis of Fibromuscular Dysplasia | In order to diagnosis FMD, a test must be done to image the blood vessels. There are many options for imaging the arteries, including specialized blood vessel ultrasound known as duplex ultrasound; a CAT scan of the arteries which is obtained after a dye is given through the veins, or a special type of MRI. In many cases, the diagnosis of FMD requires that a procedure known as an arteriogram be performed. Arteriography is a procedure that is performed by a radiologist, vascular surgeon, cardiologist, or vascular medicine specialist with appropriate training. It involves inserting a wire into or near the affected artery and injecting contrast material, a dye that can be detected by an X-ray machine. An X-ray of the affected area is then taken and examined. The individual is usually awake during an arteriogram procedure although medications may be given to keep her or him comfortable. This outpatient procedure usually lasts from one to two hours with a recovery period of up to six hours (this varies widely). | Diagnosis of Fibromuscular Dysplasia. In order to diagnosis FMD, a test must be done to image the blood vessels. There are many options for imaging the arteries, including specialized blood vessel ultrasound known as duplex ultrasound; a CAT scan of the arteries which is obtained after a dye is given through the veins, or a special type of MRI. In many cases, the diagnosis of FMD requires that a procedure known as an arteriogram be performed. Arteriography is a procedure that is performed by a radiologist, vascular surgeon, cardiologist, or vascular medicine specialist with appropriate training. It involves inserting a wire into or near the affected artery and injecting contrast material, a dye that can be detected by an X-ray machine. An X-ray of the affected area is then taken and examined. The individual is usually awake during an arteriogram procedure although medications may be given to keep her or him comfortable. This outpatient procedure usually lasts from one to two hours with a recovery period of up to six hours (this varies widely). | 464 | Fibromuscular Dysplasia |
nord_464_6 | Therapies of Fibromuscular Dysplasia | Treatment
There is no cure for FMD. Treatments are focused on managing symptoms and complications of FMD, including high blood pressure and headaches. Antiplatelet medications, such as aspirin, may be prescribed along with medications to treat high blood pressure (anti hypertensives). Many patients with FMD suffer from headaches, and a number of medications are available to help control and prevent headaches. All patients with FMD who use tobacco should be encouraged to quit.In some cases of FMD, an attempt should be made to improve the flow of blood through a severely narrowed vessel. The kind of treatment used for narrowing due to FMD depends largely upon which arteries are affected and the presence and severity of the symptoms. In most cases, such procedures are done using balloon angioplasty, a procedure known as percutaneous transluminal angioplasty (PTA). PTA is often performed at the same time as an arteriogram.If an angioplasty is performed, a catheter is extended into the affected artery and a small balloon is inflated in the artery. A metal stent is typically not required to keep the vessel open, but may be needed in some cases, such as for treatment of a tear (dissection) of a blood vessel. If angioplasty is performed, the procedure and recovery period may be longer than an arteriogram done for diagnosis only. Occasionally, traditional open surgery is performed to treat severe narrowing due to FMD, particularly those that cannot be treated with angioplasty.Patients with FMD who are found to have a significant aneurysm within the brain or renal arteries may need to undergo surgery even without symptoms. In such cases, it is recommended that the aneurysm be treated to prevent rupture which can be potentially life threatening. The type of treatment for an arterial aneurysm depends on its location and size. Treatment options for aneurysms include traditional open surgery or a less invasive angiogram-based procedure which treats the aneurysm using special vascular coils and/or stents.The appropriate treatment will vary with each individual and severity, location, and extent of disease. The treatment plan should be discussed in depth with a specialist who is very knowledgeable about FMD and its natural history. | Therapies of Fibromuscular Dysplasia. Treatment
There is no cure for FMD. Treatments are focused on managing symptoms and complications of FMD, including high blood pressure and headaches. Antiplatelet medications, such as aspirin, may be prescribed along with medications to treat high blood pressure (anti hypertensives). Many patients with FMD suffer from headaches, and a number of medications are available to help control and prevent headaches. All patients with FMD who use tobacco should be encouraged to quit.In some cases of FMD, an attempt should be made to improve the flow of blood through a severely narrowed vessel. The kind of treatment used for narrowing due to FMD depends largely upon which arteries are affected and the presence and severity of the symptoms. In most cases, such procedures are done using balloon angioplasty, a procedure known as percutaneous transluminal angioplasty (PTA). PTA is often performed at the same time as an arteriogram.If an angioplasty is performed, a catheter is extended into the affected artery and a small balloon is inflated in the artery. A metal stent is typically not required to keep the vessel open, but may be needed in some cases, such as for treatment of a tear (dissection) of a blood vessel. If angioplasty is performed, the procedure and recovery period may be longer than an arteriogram done for diagnosis only. Occasionally, traditional open surgery is performed to treat severe narrowing due to FMD, particularly those that cannot be treated with angioplasty.Patients with FMD who are found to have a significant aneurysm within the brain or renal arteries may need to undergo surgery even without symptoms. In such cases, it is recommended that the aneurysm be treated to prevent rupture which can be potentially life threatening. The type of treatment for an arterial aneurysm depends on its location and size. Treatment options for aneurysms include traditional open surgery or a less invasive angiogram-based procedure which treats the aneurysm using special vascular coils and/or stents.The appropriate treatment will vary with each individual and severity, location, and extent of disease. The treatment plan should be discussed in depth with a specialist who is very knowledgeable about FMD and its natural history. | 464 | Fibromuscular Dysplasia |
nord_465_0 | Overview of Fibrosing Mediastinitis | Fibrosing mediastinitis (FM) is a rare disease characterized by dense invasive fibrotic infiltration of the mediastinum (middle portion of the chest, situated between the lungs) and/or hilar regions (areas between the upper and lower lobes of each lung) of the chest causing narrowing or occlusion of important chest structures, including pulmonary arteries, pulmonary veins, the superior vena cava, airways/bronchi, or the esophagus. Because of the vital nature of these structures, this slowly progressive disease is associated with significant morbidity and can be fatal if it affects both lungs.There are two recognized subtypes of FM: 1) post-Histoplasma fibrosing mediastinitis (PHFM) and 2) idiopathic FM. The former is thought to represent an aberrantly prolonged and robust immune reaction to a remote infection with the soil-based fungus Histoplasma capsulatum, perhaps related to ongoing reaction to residual fungal antigens found within lymph nodes regions of the central chest. The latter is even rarer and is associated with IgG4-related disease, ANCA vasculitis, and rare histiocytic disorders.Both subtypes of FM are rare. Symptoms typically do not develop until the disease has progressed to the point of causing severe compromise of blood flow within an affected vessel or air flow within an affected central airway. The build-up of scar tissue usually occurs very slowly (1 mm/year), though more rapid growth has been observed occasionally. Symptoms may appear suddenly, even though the process has progressed slowly for years, once a critical limitation of blood/air flow occurs. The growth of mediastinal scar tissue itself causes no symptoms.Histoplasmosis is caused by the most common endemic parasitic fungus in the United States, Histoplasma capsulatum. It resides in soil and thrives when specific conditions with respect to acidity, temperature, nitrogen content, and humidity are present, resulting in large geographic areas of endemicity, most notably along the Mississippi and Ohio River valleys. It also occasionally causes disease in Central and South America. Histoplasma species are also found in Europe, Asia, Africa, and Australia, though histoplasmosis is less prevalent in these regions. It also flourishes in soil fertilized by bird droppings and is found in bat guano; chicken houses and caves or bridge underpasses contaminated with guano are notorious sources of H. capsulatum infection. In urban settings, most exposure is probably related to soil disruption leading to fungal spores becoming airborne. The inhaled fungus typically causes a limited, asymptomatic infection. A minority will experience nonspecific upper respiratory or flu-like symptoms, with progressive pneumonia requiring antifungal treatment being uncommon. Disseminated / systemic infection is rare and most often observed in those who are severely immunocompromised. In endemic areas in the United States, nearly all persons are exposed/infected in childhood.It is not known why some individuals develop an excessively exuberant immune response to the organism, leading to the excessive scarring and obstruction of vessels or airways that characterizes FM. Fungal yeast forms have been observed to persist within mediastinal lymph nodes; these specimens almost never grow in culture, indicating they most likely represent long-dead fungus, but the continued presence of fungal antigens within or around these fungal forms may stimulate an ongoing immune response in some individuals. Calcification of formerly infected lymph nodes is typical but may require years to develop. Calcifications are also frequently observed within the abnormal mediastinal tissue of PHFM. | Overview of Fibrosing Mediastinitis. Fibrosing mediastinitis (FM) is a rare disease characterized by dense invasive fibrotic infiltration of the mediastinum (middle portion of the chest, situated between the lungs) and/or hilar regions (areas between the upper and lower lobes of each lung) of the chest causing narrowing or occlusion of important chest structures, including pulmonary arteries, pulmonary veins, the superior vena cava, airways/bronchi, or the esophagus. Because of the vital nature of these structures, this slowly progressive disease is associated with significant morbidity and can be fatal if it affects both lungs.There are two recognized subtypes of FM: 1) post-Histoplasma fibrosing mediastinitis (PHFM) and 2) idiopathic FM. The former is thought to represent an aberrantly prolonged and robust immune reaction to a remote infection with the soil-based fungus Histoplasma capsulatum, perhaps related to ongoing reaction to residual fungal antigens found within lymph nodes regions of the central chest. The latter is even rarer and is associated with IgG4-related disease, ANCA vasculitis, and rare histiocytic disorders.Both subtypes of FM are rare. Symptoms typically do not develop until the disease has progressed to the point of causing severe compromise of blood flow within an affected vessel or air flow within an affected central airway. The build-up of scar tissue usually occurs very slowly (1 mm/year), though more rapid growth has been observed occasionally. Symptoms may appear suddenly, even though the process has progressed slowly for years, once a critical limitation of blood/air flow occurs. The growth of mediastinal scar tissue itself causes no symptoms.Histoplasmosis is caused by the most common endemic parasitic fungus in the United States, Histoplasma capsulatum. It resides in soil and thrives when specific conditions with respect to acidity, temperature, nitrogen content, and humidity are present, resulting in large geographic areas of endemicity, most notably along the Mississippi and Ohio River valleys. It also occasionally causes disease in Central and South America. Histoplasma species are also found in Europe, Asia, Africa, and Australia, though histoplasmosis is less prevalent in these regions. It also flourishes in soil fertilized by bird droppings and is found in bat guano; chicken houses and caves or bridge underpasses contaminated with guano are notorious sources of H. capsulatum infection. In urban settings, most exposure is probably related to soil disruption leading to fungal spores becoming airborne. The inhaled fungus typically causes a limited, asymptomatic infection. A minority will experience nonspecific upper respiratory or flu-like symptoms, with progressive pneumonia requiring antifungal treatment being uncommon. Disseminated / systemic infection is rare and most often observed in those who are severely immunocompromised. In endemic areas in the United States, nearly all persons are exposed/infected in childhood.It is not known why some individuals develop an excessively exuberant immune response to the organism, leading to the excessive scarring and obstruction of vessels or airways that characterizes FM. Fungal yeast forms have been observed to persist within mediastinal lymph nodes; these specimens almost never grow in culture, indicating they most likely represent long-dead fungus, but the continued presence of fungal antigens within or around these fungal forms may stimulate an ongoing immune response in some individuals. Calcification of formerly infected lymph nodes is typical but may require years to develop. Calcifications are also frequently observed within the abnormal mediastinal tissue of PHFM. | 465 | Fibrosing Mediastinitis |
nord_465_1 | Symptoms of Fibrosing Mediastinitis | Typically, people with PHFM were originally exposed/infected with H. capsulatum as children but the symptoms begin in most patients in the third or fourth decade of life. No evidence suggests an association with specific ancestry or gender. Patients may present with shortness of breath (dyspnea), fatigue or loss of stamina, cough with blood (hemoptysis) or without, chronic chest (pleuritic) pain, recurrent pulmonary infections or pneumonias, difficulty swallowing (dysphagia), or swelling of the arms and face. These symptoms most commonly occur because there is an occlusion or critical narrowing of one of the main vessels in the chest, such as the superior vena cava (the vein which returns blood from the head, neck, and arms the heart), pulmonary arteries, and/or pulmonary veins. Superior vena cava (SVC) syndrome, characterized by face and arm swelling due to obstruction of the vena cava, is a common symptom. Some patients do not develop this syndrome despite having obstruction of the SVC because collateral alternative veins (sometimes visible on the anterior chest) enlarge sufficiently to bypass the SVC as it becomes slowly obstructed and successfully return blood to the heart. Cough and shortness of breath are the most common symptoms when obstruction of a central airway occurs. Pulmonary venous obstruction usually presents with shortness of breath, coughing blood, or sometimes collection of fluid in the space between the lung and the chest wall (pleural effusion). Symptoms can be present for years before diagnosis.Patients with idiopathic FM may present symptoms of fever, chills, sweats, shortness of breath, cough, or chest pain. They may also have fibrosis or inflammation elsewhere in the body which may cause symptoms at those other sites. | Symptoms of Fibrosing Mediastinitis. Typically, people with PHFM were originally exposed/infected with H. capsulatum as children but the symptoms begin in most patients in the third or fourth decade of life. No evidence suggests an association with specific ancestry or gender. Patients may present with shortness of breath (dyspnea), fatigue or loss of stamina, cough with blood (hemoptysis) or without, chronic chest (pleuritic) pain, recurrent pulmonary infections or pneumonias, difficulty swallowing (dysphagia), or swelling of the arms and face. These symptoms most commonly occur because there is an occlusion or critical narrowing of one of the main vessels in the chest, such as the superior vena cava (the vein which returns blood from the head, neck, and arms the heart), pulmonary arteries, and/or pulmonary veins. Superior vena cava (SVC) syndrome, characterized by face and arm swelling due to obstruction of the vena cava, is a common symptom. Some patients do not develop this syndrome despite having obstruction of the SVC because collateral alternative veins (sometimes visible on the anterior chest) enlarge sufficiently to bypass the SVC as it becomes slowly obstructed and successfully return blood to the heart. Cough and shortness of breath are the most common symptoms when obstruction of a central airway occurs. Pulmonary venous obstruction usually presents with shortness of breath, coughing blood, or sometimes collection of fluid in the space between the lung and the chest wall (pleural effusion). Symptoms can be present for years before diagnosis.Patients with idiopathic FM may present symptoms of fever, chills, sweats, shortness of breath, cough, or chest pain. They may also have fibrosis or inflammation elsewhere in the body which may cause symptoms at those other sites. | 465 | Fibrosing Mediastinitis |
nord_465_2 | Causes of Fibrosing Mediastinitis | In the majority of patients, FM is triggered by the body’s abnormal excessive immune reaction to prior exposure to Histoplasma capsulatum, a fungus found in soil in endemic areas, most notably along the Mississippi and Ohio River valleys in the United States. The fungus resides in the soil, becomes airborne when the soil is disturbed, and is subsequently inhaled. Histoplasma is also associated with bird and bat droppings, the former of which do not appear to become infected by the fungus but may carry the fungus on their feathers, while the GI tracts of the latter may become colonized with the fungus. Idiopathic FM is not related to histoplasmosis. It has been reported in the setting of autoimmune disease, Behcet disease, ANCA-associated vasculitides including granulomatosis with polyangitis, IgG4-related disease, rheumatic fever, prior radiation therapy, severe viral infections of coxsackie B, or trauma. It can occur in association with other idiopathic fibroinflammatory disorders at sites outside the chest, including retroperitoneal fibrosis, sclerosing cholangitis, Riedel thyroiditis, pseudotumor of the orbit, and others (many of which are now recognized as other manifestations of systemic IgG4-related disease). | Causes of Fibrosing Mediastinitis. In the majority of patients, FM is triggered by the body’s abnormal excessive immune reaction to prior exposure to Histoplasma capsulatum, a fungus found in soil in endemic areas, most notably along the Mississippi and Ohio River valleys in the United States. The fungus resides in the soil, becomes airborne when the soil is disturbed, and is subsequently inhaled. Histoplasma is also associated with bird and bat droppings, the former of which do not appear to become infected by the fungus but may carry the fungus on their feathers, while the GI tracts of the latter may become colonized with the fungus. Idiopathic FM is not related to histoplasmosis. It has been reported in the setting of autoimmune disease, Behcet disease, ANCA-associated vasculitides including granulomatosis with polyangitis, IgG4-related disease, rheumatic fever, prior radiation therapy, severe viral infections of coxsackie B, or trauma. It can occur in association with other idiopathic fibroinflammatory disorders at sites outside the chest, including retroperitoneal fibrosis, sclerosing cholangitis, Riedel thyroiditis, pseudotumor of the orbit, and others (many of which are now recognized as other manifestations of systemic IgG4-related disease). | 465 | Fibrosing Mediastinitis |
nord_465_3 | Affects of Fibrosing Mediastinitis | Of the entire population who are exposed to Histoplasma, only a tiny fraction (far fewer than 1%) develop the excessive response to the fungal infection that is the basis of PHFM. Of the many millions of people with repeated exposures to Histoplasma while living in endemic areas, the vast majority never develop symptomatic histoplasmosis, and far fewer go on to develop PHFM. It is estimated that there are only a few hundred cases of PHFM in the United States. At Vanderbilt University Medical Center, a referral center for this condition in an endemic area, approximately 10 new cases have been evaluated annually over the last few decades. PHFM is seen only in individuals who lived in an endemic region sometime during their life. Idiopathic FM is believed to be even rarer, with an estimated several dozen cases known in the United States. | Affects of Fibrosing Mediastinitis. Of the entire population who are exposed to Histoplasma, only a tiny fraction (far fewer than 1%) develop the excessive response to the fungal infection that is the basis of PHFM. Of the many millions of people with repeated exposures to Histoplasma while living in endemic areas, the vast majority never develop symptomatic histoplasmosis, and far fewer go on to develop PHFM. It is estimated that there are only a few hundred cases of PHFM in the United States. At Vanderbilt University Medical Center, a referral center for this condition in an endemic area, approximately 10 new cases have been evaluated annually over the last few decades. PHFM is seen only in individuals who lived in an endemic region sometime during their life. Idiopathic FM is believed to be even rarer, with an estimated several dozen cases known in the United States. | 465 | Fibrosing Mediastinitis |
nord_465_4 | Related disorders of Fibrosing Mediastinitis | Symptoms of the following disorders can be similar to, or caused by, FM. Others may have a similar radiographic appearance as FM leading to misdiagnosis. Understanding of each condition may be critical for correct diagnosis.Superior vena cava syndrome occurs as a result of occlusion of the superior vena cava vessel, which may also happen from other causes, such as central intravenous catheters or other mass lesions involving the upper mediastinum, including tumors and cancers. Mediastinal granuloma (MG) is a different late complication of histoplasmosis, but may be confused with FM. Patients with MG develop bulky enlarged intrathoracic / mediastinal lymph nodes in response to Histoplasma infection, likely also related to an inappropriately robust immune response. These lymph nodes eventually become surrounded by a thin fibrous capsule and their interiors ultimately turn into semiliquid debris of remnant lymph nodes (differing from FM, which are uniformly dense fibrotic tissue depositions within the mediastinum). These enlarged, encapsulated mediastinal (or hilar) masses occasionally cause extrinsic compression of the same structures affected by FM (SVC, airways, pulmonary vasculature), but crucially there is no invasion of any of these structures with scar tissue which is the hallmark of FM. MG can usually be distinguished from FM by careful review of computed tomography (CT) scans of the chest by experts with experience with both diseases. MG may also affect children as young as two years of age, whereas FM is uncommon in patients under 20 years of age. MG is occasionally also caused by mycobacteria such as the bacterium responsible for tuberculosis (TB), so testing for TB should be performed in patients with MGs who have risk factors for TB or who have not lived in areas in which Histoplasma is endemic. Symptoms of MG may include fatigue, dyspnea, chest pain, pain while swallowing, or difficulty swallowing. In the past it was thought that MG would eventually progress to FM, but the best evidence now supports that they are separate conditions. Surgical resection is the most effective therapy for symptomatic MG, whereas surgery in FM is high risk and rarely of therapeutic value, making accurate distinction between MG and FM of utmost importance.Sarcoidosis, an uncommon inflammatory disease characterized by the inappropriate production of granulomatous inflammation, frequently affects the lungs and intrathoracic lymph nodes. Granulomatous inflammation is part of an appropriate immune response to fungal or mycobacterial infections. When this occurs as an autoinflammatory reaction in the absence of current or recent infection with an inciting pathogen, sarcoidosis is diagnosed. Sarcoidosis can cause bulky lymph node enlargement in the mediastinum or hilar areas of the chest which may develop internal calcifications over time. These enlarged nodes are sometimes large enough to push on and compress adjacent structures like blood vessels or airways. Such extrinsic compression of nearby structures tends to differ in CT scan appearance from the invasive fibrotic narrowing which occurs in fibrosing mediastinitis, which helps distinguish these two diseases. Additionally, in sarcoidosis severe enough to cause compromise of critical intrathoracic structures, there tends to be a known diagnosis of sarcoidosis from manifestations earlier in the course of this chronic disease, or inflammatory involvement of the lung or other organs characteristic of sarcoidosis. Finally, patients with fibrosing mediastinitis often have elevated antibody titers to Histoplasma antigens, indicating an ongoing immune response. This would not be expected in sarcoidosis. Finally, acute or subacute adenitis during an active histoplasmosis infection can mimic FM. Adenitis refers to active inflammation/infection within a lymph node. While histoplasmosis is usually a self-limited illness, a minority of infected individuals will develop a progressive pneumonia and/or progressive enlargement of intrathoracic lymph nodes where there is ongoing infection with living Histoplasma fungal organisms, prompting a robust inflammatory response. Sometimes these lymph nodes become large enough to compress nearby structures and cause symptoms like chest pain. Similarly to mediastinal granuloma and sarcoidosis, an enlarged lymph node due to active Histoplasma adenitis can cause extrinsic compression of nearby structures, but not infiltrative obliteration of these structures as is seen in FM. Histoplasma adenitis should also lack internal calcifications which are often seen in PHFM and MG. Finally, patients with Histoplasma adenitis sometimes have detectable Histoplasma antigens (proteins shed by living Histoplasma organisms) in urine or blood, indicative of ongoing active infection. These antigens should not be present in FM or MG, as the inciting infection has long been eradicated in these post-Histoplasma conditions. | Related disorders of Fibrosing Mediastinitis. Symptoms of the following disorders can be similar to, or caused by, FM. Others may have a similar radiographic appearance as FM leading to misdiagnosis. Understanding of each condition may be critical for correct diagnosis.Superior vena cava syndrome occurs as a result of occlusion of the superior vena cava vessel, which may also happen from other causes, such as central intravenous catheters or other mass lesions involving the upper mediastinum, including tumors and cancers. Mediastinal granuloma (MG) is a different late complication of histoplasmosis, but may be confused with FM. Patients with MG develop bulky enlarged intrathoracic / mediastinal lymph nodes in response to Histoplasma infection, likely also related to an inappropriately robust immune response. These lymph nodes eventually become surrounded by a thin fibrous capsule and their interiors ultimately turn into semiliquid debris of remnant lymph nodes (differing from FM, which are uniformly dense fibrotic tissue depositions within the mediastinum). These enlarged, encapsulated mediastinal (or hilar) masses occasionally cause extrinsic compression of the same structures affected by FM (SVC, airways, pulmonary vasculature), but crucially there is no invasion of any of these structures with scar tissue which is the hallmark of FM. MG can usually be distinguished from FM by careful review of computed tomography (CT) scans of the chest by experts with experience with both diseases. MG may also affect children as young as two years of age, whereas FM is uncommon in patients under 20 years of age. MG is occasionally also caused by mycobacteria such as the bacterium responsible for tuberculosis (TB), so testing for TB should be performed in patients with MGs who have risk factors for TB or who have not lived in areas in which Histoplasma is endemic. Symptoms of MG may include fatigue, dyspnea, chest pain, pain while swallowing, or difficulty swallowing. In the past it was thought that MG would eventually progress to FM, but the best evidence now supports that they are separate conditions. Surgical resection is the most effective therapy for symptomatic MG, whereas surgery in FM is high risk and rarely of therapeutic value, making accurate distinction between MG and FM of utmost importance.Sarcoidosis, an uncommon inflammatory disease characterized by the inappropriate production of granulomatous inflammation, frequently affects the lungs and intrathoracic lymph nodes. Granulomatous inflammation is part of an appropriate immune response to fungal or mycobacterial infections. When this occurs as an autoinflammatory reaction in the absence of current or recent infection with an inciting pathogen, sarcoidosis is diagnosed. Sarcoidosis can cause bulky lymph node enlargement in the mediastinum or hilar areas of the chest which may develop internal calcifications over time. These enlarged nodes are sometimes large enough to push on and compress adjacent structures like blood vessels or airways. Such extrinsic compression of nearby structures tends to differ in CT scan appearance from the invasive fibrotic narrowing which occurs in fibrosing mediastinitis, which helps distinguish these two diseases. Additionally, in sarcoidosis severe enough to cause compromise of critical intrathoracic structures, there tends to be a known diagnosis of sarcoidosis from manifestations earlier in the course of this chronic disease, or inflammatory involvement of the lung or other organs characteristic of sarcoidosis. Finally, patients with fibrosing mediastinitis often have elevated antibody titers to Histoplasma antigens, indicating an ongoing immune response. This would not be expected in sarcoidosis. Finally, acute or subacute adenitis during an active histoplasmosis infection can mimic FM. Adenitis refers to active inflammation/infection within a lymph node. While histoplasmosis is usually a self-limited illness, a minority of infected individuals will develop a progressive pneumonia and/or progressive enlargement of intrathoracic lymph nodes where there is ongoing infection with living Histoplasma fungal organisms, prompting a robust inflammatory response. Sometimes these lymph nodes become large enough to compress nearby structures and cause symptoms like chest pain. Similarly to mediastinal granuloma and sarcoidosis, an enlarged lymph node due to active Histoplasma adenitis can cause extrinsic compression of nearby structures, but not infiltrative obliteration of these structures as is seen in FM. Histoplasma adenitis should also lack internal calcifications which are often seen in PHFM and MG. Finally, patients with Histoplasma adenitis sometimes have detectable Histoplasma antigens (proteins shed by living Histoplasma organisms) in urine or blood, indicative of ongoing active infection. These antigens should not be present in FM or MG, as the inciting infection has long been eradicated in these post-Histoplasma conditions. | 465 | Fibrosing Mediastinitis |
nord_465_5 | Diagnosis of Fibrosing Mediastinitis | Diagnosing either form of FM is best accomplished by chest CT, a scan that shows the abnormal tissue in the mediastinum. The characteristic appearance of a mediastinal abnormality on chest CT scan in a person who has lived in a region with endemic histoplasmosis can definitively diagnose PHFM in many cases, especially when assessed by a pulmonologist or radiologist with expertise in this disease.A chest CT scan enhanced with intravenous contrast is often necessary to highlight any vascular narrowing which may be present. Non-enhanced chest CT scans are also useful for definitively identifying calcifications within the abnormal mediastinal tissue, which are characteristic of PHFM. A perfusion nuclear medicine scan might also be performed to quantify the degree of reduction in blood flow to parts of the lung by vascular narrowing. Magnetic resonance angiography (MRA) of the heart or cardiac MRI (cMRI) can be helpful in special circumstances, especially to better evaluate the pulmonary veins where they enter the left atrium, which are commonly affected by FM.The chest CT scan might also demonstrate one or more nodules within lung tissue, which may also have internal calcifications. These lung nodules often represent the initial focus of inhaled Histoplasma infection within the lungs. Calcifications within the spleen (an immune organ which also helps respond to Histoplasma infection) or, less commonly, the liver, are often also seen. There may be signs of infarction of the lung in patients with complete obstruction of blood flow into or out of a region of the lung, including thickening of septal membranes within the lung or scattered opacities. In situations where definitive diagnosis is not possible based on the CT scan alone, which most commonly occurs when characteristic internal calcifications within the mediastinal abnormality are absent, Histoplasma serologies are often helpful. This test detects antibodies responding to Histoplasma, and is positive in most but not all cases of PHFM. Ideally, an assay which detects Histoplasma antibodies by both complement fixation and immunodiffusion should be used. Histoplasma antigen testing, which detects proteins shed by living Histoplasma organisms, is invariably negative in FM. Lack of calcifications within a lesion otherwise meeting radiographic criteria for FM often also prompts serological evaluation for conditions known to be associated with idiopathic FM, including IgG4-related disease and granulomatosis with polyangiitis.Occasionally, biopsy of abnormal mediastinal tissue is required to exclude malignancy such as a lymphoma, especially if the CT scan shows that the abnormal tissue lacks internal calcifications characteristic of a post-Histoplasma syndrome. This can be accomplished via bronchoscopy using linear endobronchial ultrasound guidance to obtain transbronchial needle aspiration samples of the lesion, via CT-guided transthoracic needle biopsy, or surgical biopsy via thoracotomy or mediastinoscopy. Of note, bronchoscopic biopsy should be approached with caution if the lesion is most likely a mediastinal granuloma based on radiographic appearance, as transbronchial sampling of these lesions via the non-sterile airways can contaminate them with bacteria and lead to an infection requiring surgical intervention. Given this, and the fact that the primary alternative diagnosis in many such cases is lymphoma, which tends to require a large surgical biopsy specimen for definitive characterization, surgical biopsy is often preferred to distinguish between mediastinal granuloma and lymphoma. Intra-operative recognition of an encapsulated mediastinal granuloma also permits marsupialization of the lesion via resection of the free wall of the MG capsule during the same procedure, which is the therapeutic operation of choice for this condition.Diagnosis may be delayed for years because symptoms are not specific or characteristic findings are not recognized on scans. Erroneous initial diagnoses include asthma, pneumonia, chronic obstructive lung disease, pulmonary embolism with lung infarction, and, in cases involving compromise of the pulmonary veins, mitral stenosis with congestive heart failure. The current widespread use of CT of the chest has greatly improved detection and diagnosis of FM. | Diagnosis of Fibrosing Mediastinitis. Diagnosing either form of FM is best accomplished by chest CT, a scan that shows the abnormal tissue in the mediastinum. The characteristic appearance of a mediastinal abnormality on chest CT scan in a person who has lived in a region with endemic histoplasmosis can definitively diagnose PHFM in many cases, especially when assessed by a pulmonologist or radiologist with expertise in this disease.A chest CT scan enhanced with intravenous contrast is often necessary to highlight any vascular narrowing which may be present. Non-enhanced chest CT scans are also useful for definitively identifying calcifications within the abnormal mediastinal tissue, which are characteristic of PHFM. A perfusion nuclear medicine scan might also be performed to quantify the degree of reduction in blood flow to parts of the lung by vascular narrowing. Magnetic resonance angiography (MRA) of the heart or cardiac MRI (cMRI) can be helpful in special circumstances, especially to better evaluate the pulmonary veins where they enter the left atrium, which are commonly affected by FM.The chest CT scan might also demonstrate one or more nodules within lung tissue, which may also have internal calcifications. These lung nodules often represent the initial focus of inhaled Histoplasma infection within the lungs. Calcifications within the spleen (an immune organ which also helps respond to Histoplasma infection) or, less commonly, the liver, are often also seen. There may be signs of infarction of the lung in patients with complete obstruction of blood flow into or out of a region of the lung, including thickening of septal membranes within the lung or scattered opacities. In situations where definitive diagnosis is not possible based on the CT scan alone, which most commonly occurs when characteristic internal calcifications within the mediastinal abnormality are absent, Histoplasma serologies are often helpful. This test detects antibodies responding to Histoplasma, and is positive in most but not all cases of PHFM. Ideally, an assay which detects Histoplasma antibodies by both complement fixation and immunodiffusion should be used. Histoplasma antigen testing, which detects proteins shed by living Histoplasma organisms, is invariably negative in FM. Lack of calcifications within a lesion otherwise meeting radiographic criteria for FM often also prompts serological evaluation for conditions known to be associated with idiopathic FM, including IgG4-related disease and granulomatosis with polyangiitis.Occasionally, biopsy of abnormal mediastinal tissue is required to exclude malignancy such as a lymphoma, especially if the CT scan shows that the abnormal tissue lacks internal calcifications characteristic of a post-Histoplasma syndrome. This can be accomplished via bronchoscopy using linear endobronchial ultrasound guidance to obtain transbronchial needle aspiration samples of the lesion, via CT-guided transthoracic needle biopsy, or surgical biopsy via thoracotomy or mediastinoscopy. Of note, bronchoscopic biopsy should be approached with caution if the lesion is most likely a mediastinal granuloma based on radiographic appearance, as transbronchial sampling of these lesions via the non-sterile airways can contaminate them with bacteria and lead to an infection requiring surgical intervention. Given this, and the fact that the primary alternative diagnosis in many such cases is lymphoma, which tends to require a large surgical biopsy specimen for definitive characterization, surgical biopsy is often preferred to distinguish between mediastinal granuloma and lymphoma. Intra-operative recognition of an encapsulated mediastinal granuloma also permits marsupialization of the lesion via resection of the free wall of the MG capsule during the same procedure, which is the therapeutic operation of choice for this condition.Diagnosis may be delayed for years because symptoms are not specific or characteristic findings are not recognized on scans. Erroneous initial diagnoses include asthma, pneumonia, chronic obstructive lung disease, pulmonary embolism with lung infarction, and, in cases involving compromise of the pulmonary veins, mitral stenosis with congestive heart failure. The current widespread use of CT of the chest has greatly improved detection and diagnosis of FM. | 465 | Fibrosing Mediastinitis |
nord_465_6 | Therapies of Fibrosing Mediastinitis | TreatmentThere is no standard therapy for either form of FM. The natural history of idiopathic FM is not known, but there are reports of individual patients who improve after treatment with drugs directed at the underlying etiology. There are also some cases of spontaneous improvement in idiopathic FM, which has not been seen in PHFM. Reports of individual patients with idiopathic FM due to various underlying diseases describe use of the following drugs: prednisone, tamoxifen, non-steroid anti-inflammatory medication such as indomethacin, and immunosuppressants such as azathioprine or cyclosporin. Data is not available about the effectiveness of these treatments, and most reports are individual cases, so it is not possible to be sure whether a favorable response was actually caused by the treatment. There are no known effective medical therapies for PHFM. Antifungal therapies and corticosteroids have not demonstrated benefit. A single small study involving three patients with FM exhibiting metabolic overactivity within the abnormal fibrotic tissue (as evidenced by intense uptake of fluorodeoxyglucose on positron emission tomography scan) demonstrated decrease in the metabolic activity and some decrease in the size of the mediastinal abnormalities after treatment with rituximab. This work has not been duplicated in a larger study or studied in a clinical trial, so it remains unclear if rituximab represents an effective treatment. Medical treatments can help address some of the symptoms and complications caused by fibrosing mediastinitis. When fluid retention occurs related to vascular obstructions, patients are treated with diuretic therapy. Antibiotics can be used to treat complications such as pneumonia. Regular exercise is beneficial for heart and muscle function, and is encouraged for all patients as tolerated.Given the lack of effective medical therapies for PHFM, a mechanical approach has been used to address narrowings caused by FM. When vessels carrying blood to or from the lungs are blocked, pulmonary arterial and/or pulmonary venous catheterization with stenting of the affected vessel(s) to prop them open can be done to restore more normal blood flow. Stenting can also be used to address narrowing of the superior vena cava if it is causing symptoms of SVC syndrome (including arm or neck swelling, headaches). These vascular stenting procedures are typically performed by interventional radiologists or interventional cardiologists. When airways are narrowed by scar tissue, airway stents can be placed via bronchoscopy to hold these airways open. This is generally used as a last resort, as these stents may also promote airway inflammation by foreign body reaction / friction with airway mucosa, which sometimes leads to worsened inflammatory airway narrowing. If the scar tissue of FM is localized, surgical resection has been used rarely, but is high risk and appropriate for very few patients. This is not a preferred method of treatment and should only be used in the most extreme cases due to a high level of morbidity and mortality associated with surgery in this condition. Surgical intervention should only be considered at specialized centers with extensive experience in managing FM. Finally, patients with FM can cough up blood (hemoptysis). This may happen via several mechanisms, including an increase in blood pressure in the pulmonary circulation due to pulmonary venous obstruction or narrowing (“pseudo-mitral stenosis”), or the creation of more fragile arterial collateral vessels to bypass obstructed pulmonary arteries which can rupture in the airways. The latter, which generally results in a larger degree of bleeding and is occasionally life-threatening, can be addressed via angiography to identify the aberrant vessel(s) which can then be selectively embolized. The former is generally self-limited but recurrent episodes can be a significant nuisance and lead to repeated hospitalizations. Inhaled tranexamic acid can be used to shorten these episodes. PrognosisThe prognosis of FM depends on the subtype (post-Histoplasma vs. idiopathic) and the extent of involvement of mediastinal structures. Idiopathic FM has not been well studied related to its extreme rarity, but existing data suggests it is rarely life threatening. PHFM affects one lung in approximately 80% of affected individuals and both lungs in the remaining 20%. Progressive unilateral disease often leads to the loss of function of that lung, sometimes referred to as “autoamputation.” With a remaining healthy lung, life expectancy tends to be normal. Chest pain from vascular narrowing, intermittent coughing up of blood, fluid collecting outside of the affected lung (pleural effusion) and intermittent pneumonias may continue to affect some with unilateral disease. The early mortality rate when fibrosing mediastinitis affects both lungs is substantial. Recognition of bilateral disease should lead to careful consideration of vascular stenting when vascular narrowing(s) are present. This is associated with symptomatic improvement in most patients and may improve survival in those with both lungs affected. Vascular stenting may also be considered in unilateral disease associated with refractory chest discomfort or pleural effusion. | Therapies of Fibrosing Mediastinitis. TreatmentThere is no standard therapy for either form of FM. The natural history of idiopathic FM is not known, but there are reports of individual patients who improve after treatment with drugs directed at the underlying etiology. There are also some cases of spontaneous improvement in idiopathic FM, which has not been seen in PHFM. Reports of individual patients with idiopathic FM due to various underlying diseases describe use of the following drugs: prednisone, tamoxifen, non-steroid anti-inflammatory medication such as indomethacin, and immunosuppressants such as azathioprine or cyclosporin. Data is not available about the effectiveness of these treatments, and most reports are individual cases, so it is not possible to be sure whether a favorable response was actually caused by the treatment. There are no known effective medical therapies for PHFM. Antifungal therapies and corticosteroids have not demonstrated benefit. A single small study involving three patients with FM exhibiting metabolic overactivity within the abnormal fibrotic tissue (as evidenced by intense uptake of fluorodeoxyglucose on positron emission tomography scan) demonstrated decrease in the metabolic activity and some decrease in the size of the mediastinal abnormalities after treatment with rituximab. This work has not been duplicated in a larger study or studied in a clinical trial, so it remains unclear if rituximab represents an effective treatment. Medical treatments can help address some of the symptoms and complications caused by fibrosing mediastinitis. When fluid retention occurs related to vascular obstructions, patients are treated with diuretic therapy. Antibiotics can be used to treat complications such as pneumonia. Regular exercise is beneficial for heart and muscle function, and is encouraged for all patients as tolerated.Given the lack of effective medical therapies for PHFM, a mechanical approach has been used to address narrowings caused by FM. When vessels carrying blood to or from the lungs are blocked, pulmonary arterial and/or pulmonary venous catheterization with stenting of the affected vessel(s) to prop them open can be done to restore more normal blood flow. Stenting can also be used to address narrowing of the superior vena cava if it is causing symptoms of SVC syndrome (including arm or neck swelling, headaches). These vascular stenting procedures are typically performed by interventional radiologists or interventional cardiologists. When airways are narrowed by scar tissue, airway stents can be placed via bronchoscopy to hold these airways open. This is generally used as a last resort, as these stents may also promote airway inflammation by foreign body reaction / friction with airway mucosa, which sometimes leads to worsened inflammatory airway narrowing. If the scar tissue of FM is localized, surgical resection has been used rarely, but is high risk and appropriate for very few patients. This is not a preferred method of treatment and should only be used in the most extreme cases due to a high level of morbidity and mortality associated with surgery in this condition. Surgical intervention should only be considered at specialized centers with extensive experience in managing FM. Finally, patients with FM can cough up blood (hemoptysis). This may happen via several mechanisms, including an increase in blood pressure in the pulmonary circulation due to pulmonary venous obstruction or narrowing (“pseudo-mitral stenosis”), or the creation of more fragile arterial collateral vessels to bypass obstructed pulmonary arteries which can rupture in the airways. The latter, which generally results in a larger degree of bleeding and is occasionally life-threatening, can be addressed via angiography to identify the aberrant vessel(s) which can then be selectively embolized. The former is generally self-limited but recurrent episodes can be a significant nuisance and lead to repeated hospitalizations. Inhaled tranexamic acid can be used to shorten these episodes. PrognosisThe prognosis of FM depends on the subtype (post-Histoplasma vs. idiopathic) and the extent of involvement of mediastinal structures. Idiopathic FM has not been well studied related to its extreme rarity, but existing data suggests it is rarely life threatening. PHFM affects one lung in approximately 80% of affected individuals and both lungs in the remaining 20%. Progressive unilateral disease often leads to the loss of function of that lung, sometimes referred to as “autoamputation.” With a remaining healthy lung, life expectancy tends to be normal. Chest pain from vascular narrowing, intermittent coughing up of blood, fluid collecting outside of the affected lung (pleural effusion) and intermittent pneumonias may continue to affect some with unilateral disease. The early mortality rate when fibrosing mediastinitis affects both lungs is substantial. Recognition of bilateral disease should lead to careful consideration of vascular stenting when vascular narrowing(s) are present. This is associated with symptomatic improvement in most patients and may improve survival in those with both lungs affected. Vascular stenting may also be considered in unilateral disease associated with refractory chest discomfort or pleural effusion. | 465 | Fibrosing Mediastinitis |
nord_466_0 | Overview of Fibrous Dysplasia | SummaryFibrous dysplasia (FD) is a rare bone disorder. Bone affected by this disorder is replaced by abnormal scar-like (fibrous) connective tissue. This abnormal fibrous tissue weakens the bone, making it abnormally fragile and prone to fracture. Pain may occur in the affected areas. As children grow, affected bone may become misshapen (dysplastic). FD may only affect one solitary bone (monostotic disease) or the disorder can be widespread, affecting multiple bones throughout the body (polyostotic disease). The severity of the disorder can vary greatly from one person to another. Any part of the skeleton can be affected, but the long bones of the legs, the bones of the face and skull (craniofacial area), and the ribs are most often affected. FD is usually diagnosed in children or young adults, but mild cases may go undiagnosed until adulthood. In some cases, FD may not require treatment; in other cases, certain medications and surgical procedures may be recommended.IntroductionFD was first described in the medical literature in 1938 by Dr. Lichtenstein and in 1942 by Drs. Lichtenstein and Jaffe. Fibrous dysplasia can occur as part of a larger disorder such as McCune-Albright syndrome (fibrous dysplasia-café au lait spots-endocrine dysfunction) or Mazabraud syndrome (fibrous dysplasia-myxomas). The term Jaffe-Lichtenstein syndrome is sometimes used synonymously with monostotic FD or to denote cases of polyostotic FD with café au lait spots, but no endocrine dysfunction. These disorders most likely represent a spectrum of disease associated with activating mutations of the GNAS1 gene. | Overview of Fibrous Dysplasia. SummaryFibrous dysplasia (FD) is a rare bone disorder. Bone affected by this disorder is replaced by abnormal scar-like (fibrous) connective tissue. This abnormal fibrous tissue weakens the bone, making it abnormally fragile and prone to fracture. Pain may occur in the affected areas. As children grow, affected bone may become misshapen (dysplastic). FD may only affect one solitary bone (monostotic disease) or the disorder can be widespread, affecting multiple bones throughout the body (polyostotic disease). The severity of the disorder can vary greatly from one person to another. Any part of the skeleton can be affected, but the long bones of the legs, the bones of the face and skull (craniofacial area), and the ribs are most often affected. FD is usually diagnosed in children or young adults, but mild cases may go undiagnosed until adulthood. In some cases, FD may not require treatment; in other cases, certain medications and surgical procedures may be recommended.IntroductionFD was first described in the medical literature in 1938 by Dr. Lichtenstein and in 1942 by Drs. Lichtenstein and Jaffe. Fibrous dysplasia can occur as part of a larger disorder such as McCune-Albright syndrome (fibrous dysplasia-café au lait spots-endocrine dysfunction) or Mazabraud syndrome (fibrous dysplasia-myxomas). The term Jaffe-Lichtenstein syndrome is sometimes used synonymously with monostotic FD or to denote cases of polyostotic FD with café au lait spots, but no endocrine dysfunction. These disorders most likely represent a spectrum of disease associated with activating mutations of the GNAS1 gene. | 466 | Fibrous Dysplasia |
nord_466_1 | Symptoms of Fibrous Dysplasia | The severity and specific symptoms of FD can vary greatly from one person to another. Most affected individuals only have one bone involved and often there are no associated symptoms (asymptomatic). Many times, FD is discovered incidentally when x-rays are performed for another reason. Conversely, some affected individuals can have multiple bones affected and develop severe and potentially disabling or disfiguring symptoms. In most affected individuals, onset of symptoms is usually in childhood; it is unusual for the onset of the disorder to occur after 10.FD is a benign (noncancerous) disorder and does not spread. The bone or bones that are affected by the disorder are usually established early in life and it is very rare for new areas to become affected. The areas affected may be described as lesions. FD lesions may progressively grow and expand until an affected bone finishes growing. These lesions can eventually cause affected bones to become abnormally weakened, misshapen, and prone to facture. Bone pain can also occur and may be severe in some patients.Specific symptoms associated with FD depend upon the specific bones involved. Any part of the skeleton can potentially be affected, but the long bones of the arms and legs, the bones of the face and skull (craniofacial area), and the ribs are most often affected. Monostotic FD often presents as a painless swelling on the ribs. FD affecting the spine can cause abnormal curvature of the spine (scoliosis). When the long bones of the legs are affected, this can lead to frequent fractures due to weight bearing when walking or standing. Additionally, the long bones can eventually become bowed. In children, their legs may not be of equal length (limb length discrepancy). Eventually, this can affect a person’s ability to walk, causing an abnormal gait (e.g. walking with a limp).FD of the craniofacial region can cause a variety of symptoms depending on the type and specific location of the lesions(s). Such symptoms can include pain, nasal congestion, misaligned or displaced teeth, uneven jaws, and facial asymmetry, in which one side of the face does not match the other side. FD in the craniofacial region can alter the facial features resulting in an abnormally prominent forehead (frontal bossing), bulging eyes (proptosis), and difference in the vertical positions of the eyes so that the eyes are uneven (vertical dystopia). The degree of facial abnormality can vary greatly from one person to another. The shape of the skull may be altered in certain cases.FD can potentially cause a variety of neurological symptoms as areas of abnormal tissue development can compress nearby nerves. Specific symptoms are related to the specific nerves involved. For example, vision loss and hearing impairment can occur because of compression of optic and auditory nerves in the skull. However, vision loss and hearing impairment only occur in rare instances.The abnormal structure of affected bone can lead to degenerative arthritis in adjacent joints.Women with FD may be at risk of increased pain during pregnancy because of the estrogen receptors found in FD.Although the term tumor may be used to describe FD lesions, these growths are benign (non-cancerous). Only in extremely rare cases do FD lesions become cancerous (malignant transformation). These malignant tumors developed in individuals who had been radiated for bone pain; a treatment option that has been abandoned. | Symptoms of Fibrous Dysplasia. The severity and specific symptoms of FD can vary greatly from one person to another. Most affected individuals only have one bone involved and often there are no associated symptoms (asymptomatic). Many times, FD is discovered incidentally when x-rays are performed for another reason. Conversely, some affected individuals can have multiple bones affected and develop severe and potentially disabling or disfiguring symptoms. In most affected individuals, onset of symptoms is usually in childhood; it is unusual for the onset of the disorder to occur after 10.FD is a benign (noncancerous) disorder and does not spread. The bone or bones that are affected by the disorder are usually established early in life and it is very rare for new areas to become affected. The areas affected may be described as lesions. FD lesions may progressively grow and expand until an affected bone finishes growing. These lesions can eventually cause affected bones to become abnormally weakened, misshapen, and prone to facture. Bone pain can also occur and may be severe in some patients.Specific symptoms associated with FD depend upon the specific bones involved. Any part of the skeleton can potentially be affected, but the long bones of the arms and legs, the bones of the face and skull (craniofacial area), and the ribs are most often affected. Monostotic FD often presents as a painless swelling on the ribs. FD affecting the spine can cause abnormal curvature of the spine (scoliosis). When the long bones of the legs are affected, this can lead to frequent fractures due to weight bearing when walking or standing. Additionally, the long bones can eventually become bowed. In children, their legs may not be of equal length (limb length discrepancy). Eventually, this can affect a person’s ability to walk, causing an abnormal gait (e.g. walking with a limp).FD of the craniofacial region can cause a variety of symptoms depending on the type and specific location of the lesions(s). Such symptoms can include pain, nasal congestion, misaligned or displaced teeth, uneven jaws, and facial asymmetry, in which one side of the face does not match the other side. FD in the craniofacial region can alter the facial features resulting in an abnormally prominent forehead (frontal bossing), bulging eyes (proptosis), and difference in the vertical positions of the eyes so that the eyes are uneven (vertical dystopia). The degree of facial abnormality can vary greatly from one person to another. The shape of the skull may be altered in certain cases.FD can potentially cause a variety of neurological symptoms as areas of abnormal tissue development can compress nearby nerves. Specific symptoms are related to the specific nerves involved. For example, vision loss and hearing impairment can occur because of compression of optic and auditory nerves in the skull. However, vision loss and hearing impairment only occur in rare instances.The abnormal structure of affected bone can lead to degenerative arthritis in adjacent joints.Women with FD may be at risk of increased pain during pregnancy because of the estrogen receptors found in FD.Although the term tumor may be used to describe FD lesions, these growths are benign (non-cancerous). Only in extremely rare cases do FD lesions become cancerous (malignant transformation). These malignant tumors developed in individuals who had been radiated for bone pain; a treatment option that has been abandoned. | 466 | Fibrous Dysplasia |
nord_466_2 | Causes of Fibrous Dysplasia | The underlying cause of FD is not fully understood. Researchers believe that the disorder is caused by a change (mutation) in a gene called GNAS1. This gene mutation occurs after fertilization of the embryo (somatic mutation) and is therefore not inherited, nor will affected individuals pass the mutation on to their children. Affected individuals have some cells with a normal copy of this gene and some cells with the abnormal gene (mosaic pattern). The variability of symptoms of FD is due, in part, to the ratio of healthy cells to abnormal cells. Researchers do not know why these somatic mutations occur; they appear to develop randomly for unknown reasons (sporadically).The GNAS1 gene creates (encodes) a protein known as a G-protein. In FD, a gain-of-function mutation in the GNAS1 gene results in the overproduction of this G-protein. In turn, this results in the overproduction of a molecule known as cyclic adenosine monophosphate (cAMP), which is involved in the change (differentiation) of osteoblasts in bone. Osteoblasts are bone-forming cells that form new bone. The human skeleton is living tissue that is constantly changing (remodeling). It is believed that FD involves increased bone turnover. Bone turnover is a normal process in which bone gradually breaks down (bone resorption) and then reforms. Bone turnover involves osteoblasts and cells that control bone resorption (osteoclasts). The interaction between osteoclasts and osteoblasts determines how bone reforms. The interaction is a complex process that involves many factors. Improper differentiation of osteoblasts due to mutation of the GNAS1 gene is believed to contribute to the development of FD. The activity of the osteoclasts in removing bone probably allows skeletal progenitor cells including immature osteoblasts and fibrous tissue to have more space to grow and multiply.When other cells such as endocrine or skin cells are involved in addition to osteoblasts, McCune-Albright syndrome develops. | Causes of Fibrous Dysplasia. The underlying cause of FD is not fully understood. Researchers believe that the disorder is caused by a change (mutation) in a gene called GNAS1. This gene mutation occurs after fertilization of the embryo (somatic mutation) and is therefore not inherited, nor will affected individuals pass the mutation on to their children. Affected individuals have some cells with a normal copy of this gene and some cells with the abnormal gene (mosaic pattern). The variability of symptoms of FD is due, in part, to the ratio of healthy cells to abnormal cells. Researchers do not know why these somatic mutations occur; they appear to develop randomly for unknown reasons (sporadically).The GNAS1 gene creates (encodes) a protein known as a G-protein. In FD, a gain-of-function mutation in the GNAS1 gene results in the overproduction of this G-protein. In turn, this results in the overproduction of a molecule known as cyclic adenosine monophosphate (cAMP), which is involved in the change (differentiation) of osteoblasts in bone. Osteoblasts are bone-forming cells that form new bone. The human skeleton is living tissue that is constantly changing (remodeling). It is believed that FD involves increased bone turnover. Bone turnover is a normal process in which bone gradually breaks down (bone resorption) and then reforms. Bone turnover involves osteoblasts and cells that control bone resorption (osteoclasts). The interaction between osteoclasts and osteoblasts determines how bone reforms. The interaction is a complex process that involves many factors. Improper differentiation of osteoblasts due to mutation of the GNAS1 gene is believed to contribute to the development of FD. The activity of the osteoclasts in removing bone probably allows skeletal progenitor cells including immature osteoblasts and fibrous tissue to have more space to grow and multiply.When other cells such as endocrine or skin cells are involved in addition to osteoblasts, McCune-Albright syndrome develops. | 466 | Fibrous Dysplasia |
nord_466_3 | Affects of Fibrous Dysplasia | Fibrous dysplasia affects males and females in equal numbers. The disorder is diagnosed earlier in children and young children. The exact incidence and prevalence of the disorder is unknown. Mild cases may go undiagnosed, making it difficult to determine the true frequency of FD in the general population. The monostotic form is more common than the polyostotic form; according to some reports by a ratio of 4:1. | Affects of Fibrous Dysplasia. Fibrous dysplasia affects males and females in equal numbers. The disorder is diagnosed earlier in children and young children. The exact incidence and prevalence of the disorder is unknown. Mild cases may go undiagnosed, making it difficult to determine the true frequency of FD in the general population. The monostotic form is more common than the polyostotic form; according to some reports by a ratio of 4:1. | 466 | Fibrous Dysplasia |
nord_466_4 | Related disorders of Fibrous Dysplasia | Symptoms of the following disorders can be similar to those of fibrous dysplasia. Comparisons may be useful for a differential diagnosis.
A variety of benign and malignant bone tumors or disorders associated with such tumors can cause symptoms similar to those seen in FD. Such tumors include ossifying fibromas, osteofibrous dysplasia, osteosarcomas, adamantinomas, eosinophilic granulomas, chondrosarcoma, Ollier disease, multiple exostoses, and neurofibromatosis. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)McCune-Albright syndrome (MAS) is an extremely rare disorder characterized by polyostotic fibrous dysplasia that occurs with at least two additional findings – patches of abnormal skin pigmentation (i.e., areas of light-brown skin [cafe-au-lait spots] with jagged borders); abnormalities in the glands that regulate the body’s rate of growth, its sexual development, and certain other metabolic functions (multiple endocrine dysfunction). Depending on the number and location of the skeletal abnormalities, mobility may be impaired, as well as vision and/or hearing and the individual may experience substantial pain. Malfunctioning endocrine glands can result in the development of secondary sexual characteristics at an age younger than normal (precocious puberty). MAS is caused by a genetic change (mutation) in the GNAS gene that occurs randomly, for no apparent reason (sporadic). In individuals with the disorder, this sporadic genetic mutation is present in only some of the body’s cells (mosaic pattern). The symptoms and physical characteristics associated with the disorder vary greatly from person to person, depending upon the specific body cells and tissues that are affected by the genetic mutation. This mutation occurs after fertilization (postzygotic somatic mutation). It is not inherited from the parents. The range of severity of the disorder is very broad: some children are diagnosed in early infancy with obvious anomalies of bone and increased hormone production by one or more of the endocrine glands; others show no evidence of bone, skin or endocrine malfunction in childhood and may enter puberty at an appropriate age. (For more information on this disorder, choose “McCune-Albright syndrome” as your search term in the Rare Disease Database.)Mazabraud syndrome is an extremely rare disorder characterized by the association of FD with multiple myxomas, which are benign tumors consisting of connective tissue. Myxomas usually involve large muscle groups. In some cases, affected individuals may only have a solitary myxoma. Most cases of Mazabraud syndrome are associated with polyostotic FD, but monostotic FD has been reported as well. FD lesions usually affect the long bones of the leg. Females are affected more often than males in the cases report so far in the medical literature (which number fewer than 100). The growths associated with Mazabraud syndrome are benign, but malignant transformation has been reported in rare cases. Myxomas have neven been found to be cancerous, but FD bone lesions can sometimes transform; the relationship between myxoomas and FD is not fully understood.Cherubism is a rare disorder characterized by displacement of normal bone tissue with areas of fibrous growth (fibrous dysplasia) within the upper and/or lower jaw bones (maxilla and/or mandible) on both sides of the face (bilateral). This causes abnormal expansion of the jaw bones, unusual chubbiness and swelling of the face, and, in severe cases, “upturning” of the eyes. In some cases, fibrous dysplasia may also occur in other bones of the body, particularly the ribs. Some affected individuals may also exhibit other abnormalities such as multiple, patchy areas of dark pigmentation (cafe-au-lait spots) and/or several warty birthmarks (nevi) on the skin. Symptoms usually become apparent in the third or fourth year of life. Cherubism is thought to be inherited in an autosomal dominant pattern with variable expressivity and penetrance. Whereas 100% of affected males with a defective gene for cherubism will exhibit the characteristics typically associated with the disorder (high penetrance), only 50 to 75% of females with the disease gene demonstrate symptoms of the disease (reduced penetrance). Mutations in the SH3BP2 gene are associated with approximately 80% of individuals with cherubism.Paget’s disease of bone is a chronic, slowly progressive skeletal condition of abnormally rapid bone destruction (osteolytic) and reformation (osteoblastic). The new bone may occur in one or more regions of the body and is structurally abnormal, dense and fragile. This abnormal development may cause bone pain, arthritis, deformities and fractures. The bones most frequently affected are in the spine, skull, pelvis and lower legs. The exact cause of Paget’s disease is controversial, although studies implicate gene abnormalities and chronic viral infections. The disorder is usually not diagnosed until after 50 years of age. (For more information on this disorder, choose “Paget’s” as your search term in the Rare Disease Database.) | Related disorders of Fibrous Dysplasia. Symptoms of the following disorders can be similar to those of fibrous dysplasia. Comparisons may be useful for a differential diagnosis.
A variety of benign and malignant bone tumors or disorders associated with such tumors can cause symptoms similar to those seen in FD. Such tumors include ossifying fibromas, osteofibrous dysplasia, osteosarcomas, adamantinomas, eosinophilic granulomas, chondrosarcoma, Ollier disease, multiple exostoses, and neurofibromatosis. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)McCune-Albright syndrome (MAS) is an extremely rare disorder characterized by polyostotic fibrous dysplasia that occurs with at least two additional findings – patches of abnormal skin pigmentation (i.e., areas of light-brown skin [cafe-au-lait spots] with jagged borders); abnormalities in the glands that regulate the body’s rate of growth, its sexual development, and certain other metabolic functions (multiple endocrine dysfunction). Depending on the number and location of the skeletal abnormalities, mobility may be impaired, as well as vision and/or hearing and the individual may experience substantial pain. Malfunctioning endocrine glands can result in the development of secondary sexual characteristics at an age younger than normal (precocious puberty). MAS is caused by a genetic change (mutation) in the GNAS gene that occurs randomly, for no apparent reason (sporadic). In individuals with the disorder, this sporadic genetic mutation is present in only some of the body’s cells (mosaic pattern). The symptoms and physical characteristics associated with the disorder vary greatly from person to person, depending upon the specific body cells and tissues that are affected by the genetic mutation. This mutation occurs after fertilization (postzygotic somatic mutation). It is not inherited from the parents. The range of severity of the disorder is very broad: some children are diagnosed in early infancy with obvious anomalies of bone and increased hormone production by one or more of the endocrine glands; others show no evidence of bone, skin or endocrine malfunction in childhood and may enter puberty at an appropriate age. (For more information on this disorder, choose “McCune-Albright syndrome” as your search term in the Rare Disease Database.)Mazabraud syndrome is an extremely rare disorder characterized by the association of FD with multiple myxomas, which are benign tumors consisting of connective tissue. Myxomas usually involve large muscle groups. In some cases, affected individuals may only have a solitary myxoma. Most cases of Mazabraud syndrome are associated with polyostotic FD, but monostotic FD has been reported as well. FD lesions usually affect the long bones of the leg. Females are affected more often than males in the cases report so far in the medical literature (which number fewer than 100). The growths associated with Mazabraud syndrome are benign, but malignant transformation has been reported in rare cases. Myxomas have neven been found to be cancerous, but FD bone lesions can sometimes transform; the relationship between myxoomas and FD is not fully understood.Cherubism is a rare disorder characterized by displacement of normal bone tissue with areas of fibrous growth (fibrous dysplasia) within the upper and/or lower jaw bones (maxilla and/or mandible) on both sides of the face (bilateral). This causes abnormal expansion of the jaw bones, unusual chubbiness and swelling of the face, and, in severe cases, “upturning” of the eyes. In some cases, fibrous dysplasia may also occur in other bones of the body, particularly the ribs. Some affected individuals may also exhibit other abnormalities such as multiple, patchy areas of dark pigmentation (cafe-au-lait spots) and/or several warty birthmarks (nevi) on the skin. Symptoms usually become apparent in the third or fourth year of life. Cherubism is thought to be inherited in an autosomal dominant pattern with variable expressivity and penetrance. Whereas 100% of affected males with a defective gene for cherubism will exhibit the characteristics typically associated with the disorder (high penetrance), only 50 to 75% of females with the disease gene demonstrate symptoms of the disease (reduced penetrance). Mutations in the SH3BP2 gene are associated with approximately 80% of individuals with cherubism.Paget’s disease of bone is a chronic, slowly progressive skeletal condition of abnormally rapid bone destruction (osteolytic) and reformation (osteoblastic). The new bone may occur in one or more regions of the body and is structurally abnormal, dense and fragile. This abnormal development may cause bone pain, arthritis, deformities and fractures. The bones most frequently affected are in the spine, skull, pelvis and lower legs. The exact cause of Paget’s disease is controversial, although studies implicate gene abnormalities and chronic viral infections. The disorder is usually not diagnosed until after 50 years of age. (For more information on this disorder, choose “Paget’s” as your search term in the Rare Disease Database.) | 466 | Fibrous Dysplasia |
nord_466_5 | Diagnosis of Fibrous Dysplasia | A diagnosis of fibrous dysplasia is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. Individuals with mild forms of monostotic FD may be diagnosed incidentally when receiving an x-ray for another reason.Clinical Testing and Workup
Specialized imaging techniques may be used to evaluate bone. Such imaging techniques include computerized tomography (CT) scanning and magnetic resonance imaging (MRI). During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues. The abnormal tissue in FD resembles ground glass when seen on x-ray. These tests may be used to determine how extensively bones are affected.A bone scan, also known as bone scintigraphy, is used to determine the extent of bone disease and may be used when a solitary FD lesion is found to confirm a diagnosis of monostotic FD or to discover whether additional affected areas are present (polyostotic FD). During this test, a harmless radioactive dye is injected into an arm vein. A special camera that can track the dye as it travels through bone is used to create a picture of the skeleton and determine all affected areas.Bone biopsy is the surgical removal and microscopic examination of a small sample of affected tissue. A bone biopsy can reveal characteristic changes to bone that occur in individuals with FD and may be necessary to distinguish a FD lesion from other types of growths or tumors if it is unclear after an x-ray.A highly sensitive, specific form of polymerase chain reaction (PCR) has been used to detect somatic mutations of the GNAS1 gene that characterize FD. PCR is a laboratory test that has been described as a form of “photocopying.” It enables researchers to enlarge and repeatedly copy sequences of DNA. As a result, they are able to closely analyze DNA and more easily identify genes and genetic changes (mutations). In FD, a specific form of PCR testing can detect activating mutations of GNAS1 in peripheral blood cells. | Diagnosis of Fibrous Dysplasia. A diagnosis of fibrous dysplasia is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. Individuals with mild forms of monostotic FD may be diagnosed incidentally when receiving an x-ray for another reason.Clinical Testing and Workup
Specialized imaging techniques may be used to evaluate bone. Such imaging techniques include computerized tomography (CT) scanning and magnetic resonance imaging (MRI). During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues. The abnormal tissue in FD resembles ground glass when seen on x-ray. These tests may be used to determine how extensively bones are affected.A bone scan, also known as bone scintigraphy, is used to determine the extent of bone disease and may be used when a solitary FD lesion is found to confirm a diagnosis of monostotic FD or to discover whether additional affected areas are present (polyostotic FD). During this test, a harmless radioactive dye is injected into an arm vein. A special camera that can track the dye as it travels through bone is used to create a picture of the skeleton and determine all affected areas.Bone biopsy is the surgical removal and microscopic examination of a small sample of affected tissue. A bone biopsy can reveal characteristic changes to bone that occur in individuals with FD and may be necessary to distinguish a FD lesion from other types of growths or tumors if it is unclear after an x-ray.A highly sensitive, specific form of polymerase chain reaction (PCR) has been used to detect somatic mutations of the GNAS1 gene that characterize FD. PCR is a laboratory test that has been described as a form of “photocopying.” It enables researchers to enlarge and repeatedly copy sequences of DNA. As a result, they are able to closely analyze DNA and more easily identify genes and genetic changes (mutations). In FD, a specific form of PCR testing can detect activating mutations of GNAS1 in peripheral blood cells. | 466 | Fibrous Dysplasia |
nord_466_6 | Therapies of Fibrous Dysplasia | Treatment
The treatment of FD is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, general internists, orthopedic surgeons, endocrinologists, and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment. Psychosocial support for the entire family is essential as well.Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as disease progression; size of the lesion(s); the presence or absence of certain symptoms; an individual’s age and general health; and/or other elements. Decisions concerning the use of particular drug regimens, surgical treatments and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the patient based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors. Being seen by a physician(s) with familiarity in treating individuals with FD is recommended.In many cases, FD lesions do not cause any symptoms (asymptomatic). In such cases, observation and patient education may be all that is needed. Follow up x-rays every six months are recommended to determine whether the lesion has progressed.Individuals with FD have been treated with drugs known as bisphosphonates such as pamidronate or alendronate. These drugs reduce bone turnover by inhibiting bone resorption. Calcium and vitamin D may be given along with the drug. Some affected individuals respond favorably to such therapy with the main benefit being decreased bone pain. Other affected individuals do not respond to therapy with bisphosphonates or relapse after an initial period of improvement. Relapse of bone pain is more common in individuals with polyostotic FD. The most potent bisphosphonate intravenous zoledronic acid may be used in such cases and is the most effective in improving bone pain.Surgery is often used to treat individuals with FD, although most physicians recommend a conservative strategy. Surgery should be undertaken only for lesions that causing difficulty in some way. Surgery may be undertaken to correct disfigurement or deformity, to correct limb length discrepancy, to eradicate symptomatic lesions (e.g. those causing pain and/or compressing a nerve), to treat specific complications such as scoliosis, or to prevent fracture. Standard surgical procedures are effective in most adults with monostotic FD. | Therapies of Fibrous Dysplasia. Treatment
The treatment of FD is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, general internists, orthopedic surgeons, endocrinologists, and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment. Psychosocial support for the entire family is essential as well.Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as disease progression; size of the lesion(s); the presence or absence of certain symptoms; an individual’s age and general health; and/or other elements. Decisions concerning the use of particular drug regimens, surgical treatments and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the patient based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors. Being seen by a physician(s) with familiarity in treating individuals with FD is recommended.In many cases, FD lesions do not cause any symptoms (asymptomatic). In such cases, observation and patient education may be all that is needed. Follow up x-rays every six months are recommended to determine whether the lesion has progressed.Individuals with FD have been treated with drugs known as bisphosphonates such as pamidronate or alendronate. These drugs reduce bone turnover by inhibiting bone resorption. Calcium and vitamin D may be given along with the drug. Some affected individuals respond favorably to such therapy with the main benefit being decreased bone pain. Other affected individuals do not respond to therapy with bisphosphonates or relapse after an initial period of improvement. Relapse of bone pain is more common in individuals with polyostotic FD. The most potent bisphosphonate intravenous zoledronic acid may be used in such cases and is the most effective in improving bone pain.Surgery is often used to treat individuals with FD, although most physicians recommend a conservative strategy. Surgery should be undertaken only for lesions that causing difficulty in some way. Surgery may be undertaken to correct disfigurement or deformity, to correct limb length discrepancy, to eradicate symptomatic lesions (e.g. those causing pain and/or compressing a nerve), to treat specific complications such as scoliosis, or to prevent fracture. Standard surgical procedures are effective in most adults with monostotic FD. | 466 | Fibrous Dysplasia |
nord_467_0 | Overview of Fiebre mediterránea familiar | La fiebre mediterránea familiar (FMF) es una enfermedad inflamatoria hereditaria caracterizada por episodios recurrentes (ataques) de fiebre e inflamación aguda de las membranas que recubren el abdomen, las articulaciones y los pulmones. Algunas personas afectadas pueden desarrollar erupciones en la piel (eritema (piel enrojecida) que parece erisipela, un tipo de infección en la piel en que hay ulceras, dolor, calor, enrojecimiento e hinchazón) que afectan la parte inferior de las piernas.Con menos frecuencia, puede ocurrir inflamación de la membrana que recubre el corazón (pericardio) o el cerebro y la médula espinal (meninges). Algunas personas pueden desarrollar una afección grave conocida como amiloidosis, en la que ciertas proteínas llamadas amiloides se acumulan en varios tejidos del cuerpo.En la FMF, el amiloide se acumula en los riñones (amiloidosis renal), donde puede afectar la función renal y provocar complicaciones muy graves, como insuficiencia renal.Los síntomas específicos y la gravedad de la FMF son muy variables. Algunas personas desarrollan amiloidosis, pero ninguno de los otros síntomas asociados con la FMF. Estos casos a veces se denominan FMF tipo 2.La FMF es causada por cambios (mutaciones o variantes patogénicas) en el gen MEFV y generalmente se heredan de forma autosómica recesiva, pero se han descrito algunos casos con herencia dominante.La FMF se clasifica como un síndrome autoinflamatorio. Los síndromes autoinflamatorios son un grupo de trastornos caracterizados por episodios recurrentes de inflamación debido a una anomalía del sistema inmunológico innato. Los síndromes autoinflamatoiros no son lo mismo que los síndromes autoinmunes, en los que el sistema inmunológico adaptativo funciona mal y ataca por error al tejido sano. La FMF es el síndrome autoinflamatorio más común. También se considera un tipo de fiebre periódica hereditaria.La FMF tiene una alta prevalencia en el sureste mediterráneo, en algunas zonas de Italia, Grecia y España. | Overview of Fiebre mediterránea familiar. La fiebre mediterránea familiar (FMF) es una enfermedad inflamatoria hereditaria caracterizada por episodios recurrentes (ataques) de fiebre e inflamación aguda de las membranas que recubren el abdomen, las articulaciones y los pulmones. Algunas personas afectadas pueden desarrollar erupciones en la piel (eritema (piel enrojecida) que parece erisipela, un tipo de infección en la piel en que hay ulceras, dolor, calor, enrojecimiento e hinchazón) que afectan la parte inferior de las piernas.Con menos frecuencia, puede ocurrir inflamación de la membrana que recubre el corazón (pericardio) o el cerebro y la médula espinal (meninges). Algunas personas pueden desarrollar una afección grave conocida como amiloidosis, en la que ciertas proteínas llamadas amiloides se acumulan en varios tejidos del cuerpo.En la FMF, el amiloide se acumula en los riñones (amiloidosis renal), donde puede afectar la función renal y provocar complicaciones muy graves, como insuficiencia renal.Los síntomas específicos y la gravedad de la FMF son muy variables. Algunas personas desarrollan amiloidosis, pero ninguno de los otros síntomas asociados con la FMF. Estos casos a veces se denominan FMF tipo 2.La FMF es causada por cambios (mutaciones o variantes patogénicas) en el gen MEFV y generalmente se heredan de forma autosómica recesiva, pero se han descrito algunos casos con herencia dominante.La FMF se clasifica como un síndrome autoinflamatorio. Los síndromes autoinflamatorios son un grupo de trastornos caracterizados por episodios recurrentes de inflamación debido a una anomalía del sistema inmunológico innato. Los síndromes autoinflamatoiros no son lo mismo que los síndromes autoinmunes, en los que el sistema inmunológico adaptativo funciona mal y ataca por error al tejido sano. La FMF es el síndrome autoinflamatorio más común. También se considera un tipo de fiebre periódica hereditaria.La FMF tiene una alta prevalencia en el sureste mediterráneo, en algunas zonas de Italia, Grecia y España. | 467 | Fiebre mediterránea familiar |
nord_467_1 | Symptoms of Fiebre mediterránea familiar | Los síntomas y la gravedad de la FMF pueden variar mucho de una persona a otra, incluso entre miembros de una misma familia.La forma clásica de FMF se caracteriza por: | Symptoms of Fiebre mediterránea familiar. Los síntomas y la gravedad de la FMF pueden variar mucho de una persona a otra, incluso entre miembros de una misma familia.La forma clásica de FMF se caracteriza por: | 467 | Fiebre mediterránea familiar |
nord_467_2 | Causes of Fiebre mediterránea familiar | La FMF es causada por cambios (mutaciones o variantes patogénicas) del gen MEFV.Se han identificado más de 400 mutaciones diferentes del gen MEFV, aunque sólo cuatro son claramente patogénicas.El gen MEFV contiene instrucciones para crear (codificar) una proteína conocida como pirina. Las mutaciones del gen MEFV resultan en niveles deficientes de pirina funcional. La pirina es fundamental para el funcionamiento adecuado del sistema inmunológico innato al regular o inhibir la respuesta inflamatoria del cuerpo. Una variante patogénica del gen MEFV provoca una liberación excesiva de interleucina-1B. La interleucina-1B es una citoquina proinflamatoria (una proteína especializada secretada por ciertas células del sistema inmunológico que estimula o inhibe la función de otras células del sistema inmunológico).Las variantes del gen MEFV están registrados en un sitio web específico https://infevers.umai-montpellier.fr/web/HerenciaLa enfermedad se hereda con un patrón autosómico recesivo. Las enfermedades hereditarias están determinadas por la combinación de genes de un rasgo particular que se encuentran en los cromosomas recibidos del padre y de la madre.Los trastornos genéticos recesivos ocurren cuando una persona hereda un gen mutado que no funciona de cada padre. Si una persona recibe un gen funcional y un gen no funcional para la enfermedad, la persona será portadora de la enfermedad, pero generalmente no mostrará síntomas. El riesgo de que dos padres portadores transmitan el gen no funcional y, por lo tanto, tengan un hijo afectado es del 25% con cada embarazo. El riesgo de tener un hijo portador, al igual que los padres, es del 50% con cada embarazo. La probabilidad de que un niño reciba genes funcionales de ambos padres es del 25%. El riesgo es el mismo para hombres y mujeres.Aunque la FMF es un trastorno autosómico recesivo, algunas personas que heredan sólo una variante patogénica (heterocigotos) pueden tener síntomas de enfermedad inflamatoria muy similares a los de la FMF. Estas personas también tienen mayor riesgo que la población general de desarrollar otras enfermedades inflamatorias como la enfermedad de Bechet y la enfermedad de Crohn. La gravedad de la enfermedad en estos casos suele ser similar a la de las personas que heredan dos genes de la enfermedad (homocigotos) o a los de las personas que tienen dos variantes patogénicas diferentes (heterocigotos compuestos) y estas personas generalmente requieren tratamiento.No se comprende completamente la razón por la que algunas personas con un solo gen mutado desarrollan síntomas. Se necesita más investigación para determinar por qué ocurre esto y si hay síntomas específicos en estos casos. | Causes of Fiebre mediterránea familiar. La FMF es causada por cambios (mutaciones o variantes patogénicas) del gen MEFV.Se han identificado más de 400 mutaciones diferentes del gen MEFV, aunque sólo cuatro son claramente patogénicas.El gen MEFV contiene instrucciones para crear (codificar) una proteína conocida como pirina. Las mutaciones del gen MEFV resultan en niveles deficientes de pirina funcional. La pirina es fundamental para el funcionamiento adecuado del sistema inmunológico innato al regular o inhibir la respuesta inflamatoria del cuerpo. Una variante patogénica del gen MEFV provoca una liberación excesiva de interleucina-1B. La interleucina-1B es una citoquina proinflamatoria (una proteína especializada secretada por ciertas células del sistema inmunológico que estimula o inhibe la función de otras células del sistema inmunológico).Las variantes del gen MEFV están registrados en un sitio web específico https://infevers.umai-montpellier.fr/web/HerenciaLa enfermedad se hereda con un patrón autosómico recesivo. Las enfermedades hereditarias están determinadas por la combinación de genes de un rasgo particular que se encuentran en los cromosomas recibidos del padre y de la madre.Los trastornos genéticos recesivos ocurren cuando una persona hereda un gen mutado que no funciona de cada padre. Si una persona recibe un gen funcional y un gen no funcional para la enfermedad, la persona será portadora de la enfermedad, pero generalmente no mostrará síntomas. El riesgo de que dos padres portadores transmitan el gen no funcional y, por lo tanto, tengan un hijo afectado es del 25% con cada embarazo. El riesgo de tener un hijo portador, al igual que los padres, es del 50% con cada embarazo. La probabilidad de que un niño reciba genes funcionales de ambos padres es del 25%. El riesgo es el mismo para hombres y mujeres.Aunque la FMF es un trastorno autosómico recesivo, algunas personas que heredan sólo una variante patogénica (heterocigotos) pueden tener síntomas de enfermedad inflamatoria muy similares a los de la FMF. Estas personas también tienen mayor riesgo que la población general de desarrollar otras enfermedades inflamatorias como la enfermedad de Bechet y la enfermedad de Crohn. La gravedad de la enfermedad en estos casos suele ser similar a la de las personas que heredan dos genes de la enfermedad (homocigotos) o a los de las personas que tienen dos variantes patogénicas diferentes (heterocigotos compuestos) y estas personas generalmente requieren tratamiento.No se comprende completamente la razón por la que algunas personas con un solo gen mutado desarrollan síntomas. Se necesita más investigación para determinar por qué ocurre esto y si hay síntomas específicos en estos casos. | 467 | Fiebre mediterránea familiar |
nord_467_3 | Affects of Fiebre mediterránea familiar | La frecuencia de la FMF en cualquier lugar depende del origen étnico de la población. La FMF puede afectar a personas de cualquier grupo étnico, pero las tasas son mucho más altas en ciertas poblaciones mediterráneas, incluidas personas de ascendencia armenia, turca, árabe y judía del norte de África. En estas poblaciones, la prevalencia se estima en 1 en 200.En Estados Unidos, la FMF se encuentra con frecuencia en judíos asquenazíes e inmigrantes de Oriente Medio y Armenia.La FMF afecta a hombres y mujeres en igual número, aunque algunos estudios sugieren que los hombres son afectados más que las mujeres. | Affects of Fiebre mediterránea familiar. La frecuencia de la FMF en cualquier lugar depende del origen étnico de la población. La FMF puede afectar a personas de cualquier grupo étnico, pero las tasas son mucho más altas en ciertas poblaciones mediterráneas, incluidas personas de ascendencia armenia, turca, árabe y judía del norte de África. En estas poblaciones, la prevalencia se estima en 1 en 200.En Estados Unidos, la FMF se encuentra con frecuencia en judíos asquenazíes e inmigrantes de Oriente Medio y Armenia.La FMF afecta a hombres y mujeres en igual número, aunque algunos estudios sugieren que los hombres son afectados más que las mujeres. | 467 | Fiebre mediterránea familiar |
nord_467_4 | Related disorders of Fiebre mediterránea familiar | Los síntomas de los siguientes trastornos pueden ser similares a los de la FMF. Las comparaciones pueden ser útiles para un diagnóstico diferencial.Los síndromes autoinflamatorios son un grupo de trastornos raros caracterizados por episodios recurrentes de inflamación debido a una anomalía del sistema inmunológico innato. Los síntomas de estos síndromes a menudo incluyen fiebre periódica, erupción cutánea, dolor abdominal, dolor en las articulaciones, dolor en los huesos y otros hallazgos característicos asociados con la inflamación crónica. Estos trastornos incluyen los síndromes periódicos asociados a la criopirina (síndrome autoinflamatorio familiar por resfriado, síndrome de Muckle-Wells y NOMID/CINCA), deficiencia de mevalonato quinasa (MKD) y síndrome periódico asociado al receptor de TNF (TRAPS).La fiebre periódica, estomatitis aftosa, faringitis y adenitis (PFAPA) es un trastorno poco común caracterizado por episodios recurrentes de fiebre. La fiebre suele aparecer junto con aftas bucales (estomatitis aftosa), dolor de garganta enrojecido (faringitis) e inflamación de las glándulas del cuello (adenitis cervical). Los episodios comienzan repentina y generalmente duran entre 3 y 7 días. El tiempo entre episodios puede variar, pero suele ser de 3 a 8 semanas. Entre episodios, los niños afectados no se ven afectados y crecen normalmente. La PFAPA generalmente ocurre durante la niñez y eventualmente desaparece durante la adolescencia o la edad adulta. Se desconoce la causa exacta de la PFAPA. | Related disorders of Fiebre mediterránea familiar. Los síntomas de los siguientes trastornos pueden ser similares a los de la FMF. Las comparaciones pueden ser útiles para un diagnóstico diferencial.Los síndromes autoinflamatorios son un grupo de trastornos raros caracterizados por episodios recurrentes de inflamación debido a una anomalía del sistema inmunológico innato. Los síntomas de estos síndromes a menudo incluyen fiebre periódica, erupción cutánea, dolor abdominal, dolor en las articulaciones, dolor en los huesos y otros hallazgos característicos asociados con la inflamación crónica. Estos trastornos incluyen los síndromes periódicos asociados a la criopirina (síndrome autoinflamatorio familiar por resfriado, síndrome de Muckle-Wells y NOMID/CINCA), deficiencia de mevalonato quinasa (MKD) y síndrome periódico asociado al receptor de TNF (TRAPS).La fiebre periódica, estomatitis aftosa, faringitis y adenitis (PFAPA) es un trastorno poco común caracterizado por episodios recurrentes de fiebre. La fiebre suele aparecer junto con aftas bucales (estomatitis aftosa), dolor de garganta enrojecido (faringitis) e inflamación de las glándulas del cuello (adenitis cervical). Los episodios comienzan repentina y generalmente duran entre 3 y 7 días. El tiempo entre episodios puede variar, pero suele ser de 3 a 8 semanas. Entre episodios, los niños afectados no se ven afectados y crecen normalmente. La PFAPA generalmente ocurre durante la niñez y eventualmente desaparece durante la adolescencia o la edad adulta. Se desconoce la causa exacta de la PFAPA. | 467 | Fiebre mediterránea familiar |
nord_467_5 | Diagnosis of Fiebre mediterránea familiar | El diagnóstico de FMF se basa en la identificación de los síntomas característicos, una historia detallada del paciente, una evaluación clínica exhaustiva y una variedad de pruebas especializadas. Estas pruebas pueden ayudar a obtener un diagnóstico de FMF o evaluar el alcance del trastorno. El diagnóstico oportuno de la FMF es importante para evitar diagnósticos erróneos y cirugías innecesarias (ya que a muchos niños se les diagnostica erróneamente apendicitis).Pruebas clínicas y análisisDurante un episodio, se puede realizar un análisis de sangre conocido como velocidad de sedimentación globular. La tasa de sedimentación mide cuánto tiempo tardan los glóbulos rojos (eritrocitos) en asentarse en un tubo de ensayo durante un período determinado. Muchas personas con FMF tienen una tasa de sedimentación elevada, lo que es un indicio de inflamación. Los análisis de sangre también pueden revelar niveles elevados de glóbulos blancos, que son indicativos de una respuesta del sistema inmunológico, proteína C reactiva elevada, que se eleva durante períodos de inflamación y/o niveles elevados de fibrinógeno (una sustancia que ayuda a detener el sangrado). Sin embargo, estas pruebas sólo son efectivas durante un episodio de FMF y vuelven a la normalidad o casi a la normalidad cuando termina el episodio.Los análisis de orina pueden revelar una pérdida excesiva de una proteína llamada albúmina, que puede ser indicativa de enfermedad renal.El diagnóstico de FMF puede confirmarse mediante pruebas genéticas moleculares, que pueden identificar las mutaciones en el gen MEFV.Las pruebas genéticas moleculares están disponibles a través de laboratorios de diagnóstico comerciales y académicos. | Diagnosis of Fiebre mediterránea familiar. El diagnóstico de FMF se basa en la identificación de los síntomas característicos, una historia detallada del paciente, una evaluación clínica exhaustiva y una variedad de pruebas especializadas. Estas pruebas pueden ayudar a obtener un diagnóstico de FMF o evaluar el alcance del trastorno. El diagnóstico oportuno de la FMF es importante para evitar diagnósticos erróneos y cirugías innecesarias (ya que a muchos niños se les diagnostica erróneamente apendicitis).Pruebas clínicas y análisisDurante un episodio, se puede realizar un análisis de sangre conocido como velocidad de sedimentación globular. La tasa de sedimentación mide cuánto tiempo tardan los glóbulos rojos (eritrocitos) en asentarse en un tubo de ensayo durante un período determinado. Muchas personas con FMF tienen una tasa de sedimentación elevada, lo que es un indicio de inflamación. Los análisis de sangre también pueden revelar niveles elevados de glóbulos blancos, que son indicativos de una respuesta del sistema inmunológico, proteína C reactiva elevada, que se eleva durante períodos de inflamación y/o niveles elevados de fibrinógeno (una sustancia que ayuda a detener el sangrado). Sin embargo, estas pruebas sólo son efectivas durante un episodio de FMF y vuelven a la normalidad o casi a la normalidad cuando termina el episodio.Los análisis de orina pueden revelar una pérdida excesiva de una proteína llamada albúmina, que puede ser indicativa de enfermedad renal.El diagnóstico de FMF puede confirmarse mediante pruebas genéticas moleculares, que pueden identificar las mutaciones en el gen MEFV.Las pruebas genéticas moleculares están disponibles a través de laboratorios de diagnóstico comerciales y académicos. | 467 | Fiebre mediterránea familiar |
nord_467_6 | Therapies of Fiebre mediterránea familiar | No existe cura para la FMF, pero existen tratamientos efectivos. Los tratamientos específicos están dirigidos a los síntomas específicos aparentes en cada persona afectada.Muchas personas son tratadas con el medicamento principal llamado colchicina, un compuesto complejo que reduce la inflamación. Más del 90% de las personas afectadas que toman el medicamento muestran una marcada mejoría en la duración y frecuencia de los episodios. La colchicina también es eficaz para prevenir la acumulación de amiloide en los riñones. Sin embargo, la colchicina requiere un cumplimiento diario estricto y no se usa para tratar un episodio que ya ha comenzado. Por lo tanto, aumentar la dosis durante un episodio no es beneficioso. En 2009, la Administración de Alimentos y Medicamentos de EE. UU. (FDA) aprobó el producto de colchicina oral Colcrys para tratar la FMF.La colchicina puede prevenir el desarrollo de amiloidosis renal, incluso si no es eficaz en el tratamiento de los ataques de FMF. La amiloidosis renal en etapa temprana es reversible. Algunas personas con FMF y amiloidosis eventualmente desarrollan enfermedad renal terminal (ESRD) y finalmente requieren un trasplante de riñón. Inicialmente, una persona afectada puede someterse a diálisis. La diálisis es un procedimiento en el que se utiliza una máquina para realizar algunas de las funciones del riñón: filtrar los productos de desecho del torrente sanguíneo, ayudar a controlar la presión arterial y ayudar a mantener niveles adecuados de sustancias químicas esenciales como el potasio.La ESRD no es reversible, por lo que las personas eventualmente necesitarán un trasplante de riñón. La tasa de progresión de la disfunción renal a ESRD puede variar mucho de un individuo a otro. Con la colchicina, ha disminuido el número de personas con FMF que requieren un trasplante de riñón. La mayoría de las personas con FMF que finalmente requirieron un trasplante de riñón no pudieron tomar colchicina o no tomaron la dosis diaria requerida.Se pueden usar medicamentos antiinflamatorios no esteroides (AINE) y analgésicos (analgésicos) para tratar a las personas durante un episodio febril o inflamatorio. Los AINE también se utilizan para tratar dolores articulares y musculares que no responden a la colchicina.En 2016, la FDA aprobó el anticuerpo monocloncal Ilaris (canakinumab) que bloquea la actividad de la interleucina-1 para tratar la FMF.Se recomienda el asesoramiento genético a las personas afectadas y sus familias.Algunas personas que no han respondido al tratamiento con colchicina han sido tratadas con anakinra (Kineret). Anakinra es un antagonista del receptor de interkeucina-1 (IL1); bloquea la actividad de la interleucina-1. Es necesaria más investigación para determinar la seguridad y eficacia a largo plazo de anakinra para personas con FMF.El fármaco rilonacept (Arcalyst) bloquea la actividad de la interleucina-1 y está aprobado por la FDA para el tratamiento de trastornos autoinflamatorios como el síndrome autoinflamatorio por resfriado. Se está estudiando como una terapia potencial para personas con FMF. Es necesaria más investigación para determinar la seguridad y eficacia a largo plazo de este medicamento en el tratamiento de personas con FMF.Otros medicamentos que se han utilizado en personas que no responden a la colchicina incluyen talidomida, etanercept, interferón alfa y sulfasalazina. Es necesaria más investigación para determinar la seguridad y eficacia a largo plazo de estos posibles tratamientos para la FMF.Curso de la enfermedadLa FMF suele ocurrir durante la infancia. Los ataques inflamatorios duran de 1 a 3 días. El curso de la enfermedad es mejor si las personas afectadas son tratadas temprano.Aunque los episodios de FMF pueden ocurrir espontáneamente sin motivo identificable, en algunos casos se han identificado ciertos desencadenantes. Estos desencadenantes incluyen infección, traumatismo, ejercicio vigoroso y estrés. En las mujeres, el inicio de su período (menstruación) puede desencadenar un episodio. | Therapies of Fiebre mediterránea familiar. No existe cura para la FMF, pero existen tratamientos efectivos. Los tratamientos específicos están dirigidos a los síntomas específicos aparentes en cada persona afectada.Muchas personas son tratadas con el medicamento principal llamado colchicina, un compuesto complejo que reduce la inflamación. Más del 90% de las personas afectadas que toman el medicamento muestran una marcada mejoría en la duración y frecuencia de los episodios. La colchicina también es eficaz para prevenir la acumulación de amiloide en los riñones. Sin embargo, la colchicina requiere un cumplimiento diario estricto y no se usa para tratar un episodio que ya ha comenzado. Por lo tanto, aumentar la dosis durante un episodio no es beneficioso. En 2009, la Administración de Alimentos y Medicamentos de EE. UU. (FDA) aprobó el producto de colchicina oral Colcrys para tratar la FMF.La colchicina puede prevenir el desarrollo de amiloidosis renal, incluso si no es eficaz en el tratamiento de los ataques de FMF. La amiloidosis renal en etapa temprana es reversible. Algunas personas con FMF y amiloidosis eventualmente desarrollan enfermedad renal terminal (ESRD) y finalmente requieren un trasplante de riñón. Inicialmente, una persona afectada puede someterse a diálisis. La diálisis es un procedimiento en el que se utiliza una máquina para realizar algunas de las funciones del riñón: filtrar los productos de desecho del torrente sanguíneo, ayudar a controlar la presión arterial y ayudar a mantener niveles adecuados de sustancias químicas esenciales como el potasio.La ESRD no es reversible, por lo que las personas eventualmente necesitarán un trasplante de riñón. La tasa de progresión de la disfunción renal a ESRD puede variar mucho de un individuo a otro. Con la colchicina, ha disminuido el número de personas con FMF que requieren un trasplante de riñón. La mayoría de las personas con FMF que finalmente requirieron un trasplante de riñón no pudieron tomar colchicina o no tomaron la dosis diaria requerida.Se pueden usar medicamentos antiinflamatorios no esteroides (AINE) y analgésicos (analgésicos) para tratar a las personas durante un episodio febril o inflamatorio. Los AINE también se utilizan para tratar dolores articulares y musculares que no responden a la colchicina.En 2016, la FDA aprobó el anticuerpo monocloncal Ilaris (canakinumab) que bloquea la actividad de la interleucina-1 para tratar la FMF.Se recomienda el asesoramiento genético a las personas afectadas y sus familias.Algunas personas que no han respondido al tratamiento con colchicina han sido tratadas con anakinra (Kineret). Anakinra es un antagonista del receptor de interkeucina-1 (IL1); bloquea la actividad de la interleucina-1. Es necesaria más investigación para determinar la seguridad y eficacia a largo plazo de anakinra para personas con FMF.El fármaco rilonacept (Arcalyst) bloquea la actividad de la interleucina-1 y está aprobado por la FDA para el tratamiento de trastornos autoinflamatorios como el síndrome autoinflamatorio por resfriado. Se está estudiando como una terapia potencial para personas con FMF. Es necesaria más investigación para determinar la seguridad y eficacia a largo plazo de este medicamento en el tratamiento de personas con FMF.Otros medicamentos que se han utilizado en personas que no responden a la colchicina incluyen talidomida, etanercept, interferón alfa y sulfasalazina. Es necesaria más investigación para determinar la seguridad y eficacia a largo plazo de estos posibles tratamientos para la FMF.Curso de la enfermedadLa FMF suele ocurrir durante la infancia. Los ataques inflamatorios duran de 1 a 3 días. El curso de la enfermedad es mejor si las personas afectadas son tratadas temprano.Aunque los episodios de FMF pueden ocurrir espontáneamente sin motivo identificable, en algunos casos se han identificado ciertos desencadenantes. Estos desencadenantes incluyen infección, traumatismo, ejercicio vigoroso y estrés. En las mujeres, el inicio de su período (menstruación) puede desencadenar un episodio. | 467 | Fiebre mediterránea familiar |
nord_468_0 | Overview of Filariasis | Filariasis is an infectious tropical disease caused by any one of several thread-like parasitic round worms. The two species of worms most often associated with this disease are Wuchereria bancrofti and Brugia malayi. The larval form of the parasite transmits the disease to humans by the bite of a mosquito. In the early stages of the infection, the patient characteristically complains of fever, chills, headaches and skin lesions. Any one of several antiparasitic agents may be effective in eliminating the worm. However, if the disease is left untreated, obstruction of the lymph flow will cause particular areas of the body especially the legs and external genitals, to swell profoundly. Symptoms are primarily a response to adult worms that cause inflammation. Chronic inflammation may progress to hardening of the lymphatic vessels (fibrosis) and obstruction of the lymph flow. | Overview of Filariasis. Filariasis is an infectious tropical disease caused by any one of several thread-like parasitic round worms. The two species of worms most often associated with this disease are Wuchereria bancrofti and Brugia malayi. The larval form of the parasite transmits the disease to humans by the bite of a mosquito. In the early stages of the infection, the patient characteristically complains of fever, chills, headaches and skin lesions. Any one of several antiparasitic agents may be effective in eliminating the worm. However, if the disease is left untreated, obstruction of the lymph flow will cause particular areas of the body especially the legs and external genitals, to swell profoundly. Symptoms are primarily a response to adult worms that cause inflammation. Chronic inflammation may progress to hardening of the lymphatic vessels (fibrosis) and obstruction of the lymph flow. | 468 | Filariasis |
nord_468_1 | Symptoms of Filariasis | Some people with filariasis have no symptoms. Other affected individuals may have episodes of acute inflammation of lymphatic vessels (lymphangitis) along with high temperatures, shaking chills, body aches, and swollen lymph nodes. Excessive amounts of fluid may accumulate (edema) in the affected areas (i.e., arms and/or legs), but the accumulation typically resolves after the other symptoms are gone. Attacks may also be accompanied by acute inflammation of the genitalia leading, in males, to inflammation, pain and swelling of the testes (orchitis), sperm track (funiculitis), and/or sperm ducts (epididymitis). The scrotum may become abnormally swollen and painful.Bancroftian filariasis affects both the legs and the genitals. The Malayan variety affects the legs below the knees.Some people with filariasis have abnormally high levels of certain white blood cells (eosinophilia) during acute episodes of symptoms. When the inflammation resolves, these levels return to normal.Filariasis may cause chronic lymph node swelling (lymphadenopathy) even in the absence of other symptoms. Longstanding obstruction of the lymphatic vessels may lead to several other conditions. These include accumulation of fluid in the scrotum (hydrocele), the presence of lymphatic fluid in the urine (chyluria), and/or abnormally enlarged lymphatic vessels (varices). Other symptoms may include progressive edema (elephantiasis) of the female external genitalia (vulva), breasts, and/or arms and legs. Chronic edema may result in skin that is abnormally thick and has a “warty” appearance. | Symptoms of Filariasis. Some people with filariasis have no symptoms. Other affected individuals may have episodes of acute inflammation of lymphatic vessels (lymphangitis) along with high temperatures, shaking chills, body aches, and swollen lymph nodes. Excessive amounts of fluid may accumulate (edema) in the affected areas (i.e., arms and/or legs), but the accumulation typically resolves after the other symptoms are gone. Attacks may also be accompanied by acute inflammation of the genitalia leading, in males, to inflammation, pain and swelling of the testes (orchitis), sperm track (funiculitis), and/or sperm ducts (epididymitis). The scrotum may become abnormally swollen and painful.Bancroftian filariasis affects both the legs and the genitals. The Malayan variety affects the legs below the knees.Some people with filariasis have abnormally high levels of certain white blood cells (eosinophilia) during acute episodes of symptoms. When the inflammation resolves, these levels return to normal.Filariasis may cause chronic lymph node swelling (lymphadenopathy) even in the absence of other symptoms. Longstanding obstruction of the lymphatic vessels may lead to several other conditions. These include accumulation of fluid in the scrotum (hydrocele), the presence of lymphatic fluid in the urine (chyluria), and/or abnormally enlarged lymphatic vessels (varices). Other symptoms may include progressive edema (elephantiasis) of the female external genitalia (vulva), breasts, and/or arms and legs. Chronic edema may result in skin that is abnormally thick and has a “warty” appearance. | 468 | Filariasis |
nord_468_2 | Causes of Filariasis | Filariasis is a rare infectious tropical disorder caused by the round worm parasites (nematode) Wuchereria bancrofti or Brugia malayi. Symptoms result primarily from inflammatory reactions to the adult worms. Some people may also develop hypersensitivity reactions to the small larval parasites (microfilariae). | Causes of Filariasis. Filariasis is a rare infectious tropical disorder caused by the round worm parasites (nematode) Wuchereria bancrofti or Brugia malayi. Symptoms result primarily from inflammatory reactions to the adult worms. Some people may also develop hypersensitivity reactions to the small larval parasites (microfilariae). | 468 | Filariasis |
nord_468_3 | Affects of Filariasis | Filariasis is common disease in tropical regions of the world. The organism W. bancrofti is present throughout Africa, Asia, China, and South America. B. malayi is found in southern and southeast Asia. Filariasis is extremely rare in North America and occurs only when these organisms are imported from tropical regions. The infection is transmitted by several different types of tropical mosquitos which transfer the larval stage of the organism (microfilariae) from one host to another. Lymphatic filariasis affects about 120 million people worldwide. Short-term travelers to areas where it is endemic are at low risk for this infection. People who visit endemic areas for extended periods of time, and especially those who are in areas or situations in which they are intensely exposed to infected mosquitoes, can become infected. Most infections seen in the U.S. are in immigrants from endemic countries, according to the Centers for Disease Control and Prevention (CDC). | Affects of Filariasis. Filariasis is common disease in tropical regions of the world. The organism W. bancrofti is present throughout Africa, Asia, China, and South America. B. malayi is found in southern and southeast Asia. Filariasis is extremely rare in North America and occurs only when these organisms are imported from tropical regions. The infection is transmitted by several different types of tropical mosquitos which transfer the larval stage of the organism (microfilariae) from one host to another. Lymphatic filariasis affects about 120 million people worldwide. Short-term travelers to areas where it is endemic are at low risk for this infection. People who visit endemic areas for extended periods of time, and especially those who are in areas or situations in which they are intensely exposed to infected mosquitoes, can become infected. Most infections seen in the U.S. are in immigrants from endemic countries, according to the Centers for Disease Control and Prevention (CDC). | 468 | Filariasis |
nord_468_4 | Related disorders of Filariasis | Symptoms of the following disorders can be similar to those of Filariasis. Comparisons may be useful for a differential diagnosis:Acanthocheilonemiasis is a tropical infectious disease caused by a multicellular parasite (filarial worm [nematode]), called Acanthocheilonema perstans. This parasite is found most commonly in Africa. Initially people with Acanthocheilonemiasis may have no symptoms. Symptoms may include itchy skin (pruritis), abdominal pain, chest pain, muscle pain (myalgias), and/or areas of swelling under the skin. Other symptoms may include an abnormally enlarged liver and spleen (hepatosplenomegaly), and inflammation in the affected organs. (For more information on this disorder, choose “Acanthocheilo” as your search term in the Rare Disease Database.)Filarial Disease, or the general term “filariasis,” may also refer to a group of parasitic diseases caused by various species of filarial worms (nematodes). These include mumu, loiasis (Calabar swellings), dirofilariasis (human infection by dog heartworm), and onchocerciasis (river blindness). All these except dirofilariasis can be acquired only in the tropics, where they are common, but are extremely rare in temperate climates such as North America. Taken together, filarial diseases of all types affect approximately 100 million people worldwide. | Related disorders of Filariasis. Symptoms of the following disorders can be similar to those of Filariasis. Comparisons may be useful for a differential diagnosis:Acanthocheilonemiasis is a tropical infectious disease caused by a multicellular parasite (filarial worm [nematode]), called Acanthocheilonema perstans. This parasite is found most commonly in Africa. Initially people with Acanthocheilonemiasis may have no symptoms. Symptoms may include itchy skin (pruritis), abdominal pain, chest pain, muscle pain (myalgias), and/or areas of swelling under the skin. Other symptoms may include an abnormally enlarged liver and spleen (hepatosplenomegaly), and inflammation in the affected organs. (For more information on this disorder, choose “Acanthocheilo” as your search term in the Rare Disease Database.)Filarial Disease, or the general term “filariasis,” may also refer to a group of parasitic diseases caused by various species of filarial worms (nematodes). These include mumu, loiasis (Calabar swellings), dirofilariasis (human infection by dog heartworm), and onchocerciasis (river blindness). All these except dirofilariasis can be acquired only in the tropics, where they are common, but are extremely rare in temperate climates such as North America. Taken together, filarial diseases of all types affect approximately 100 million people worldwide. | 468 | Filariasis |
nord_468_5 | Diagnosis of Filariasis | The diagnosis of filariasis requires examination of a blood smear for the presence of the larval round worm W. bancrofti or B. malayi. Since the number of parasites (parasitemia) in the blood is higher during the night, blood samples are best obtained at night. When parasites are not found in the blood, the adult worms may occasionally be found in a lymph node sample from an infected individual.A somewhat easier diagnostic test was recently developed that may be used at any time during the day. It is based on detecting the presence of antibodies generated in reaction to the foreign bodies, the parasites themselves. | Diagnosis of Filariasis. The diagnosis of filariasis requires examination of a blood smear for the presence of the larval round worm W. bancrofti or B. malayi. Since the number of parasites (parasitemia) in the blood is higher during the night, blood samples are best obtained at night. When parasites are not found in the blood, the adult worms may occasionally be found in a lymph node sample from an infected individual.A somewhat easier diagnostic test was recently developed that may be used at any time during the day. It is based on detecting the presence of antibodies generated in reaction to the foreign bodies, the parasites themselves. | 468 | Filariasis |
nord_468_6 | Therapies of Filariasis | TreatmentProgressively increasing doses of any one of the major anti-parasiticide drugs is the treatment for the disorder. Among these drugs are: ivermectin, albendazole, and diethylcarbamazine. These drugs work to get rid of the larval worm, to inhiobit reproduction of the adult worm, or to kill the adult worm. Notwithstanding that these drugs are effective they do, the use of each is subject to substantial side effects (adverse reactions). These side effects may be alleviated by using antihistamines and/or anti-inflammatory drugs.The elimination of adult worms must be undertaken with care because high concentration of dead worms in the lymph or blood can provoke dangerous allergic reactions and abscesses.Surgery may be used to treat some people with filariasis who develop an abnormal accumulation of fluid in the scrotum (hydrocele). Surgery may also be performed to remove the remains of adult worms and calcifications developing around them. Treatment of elephantiasis of the legs usually consists of elevation and support from elastic stockings.In the tropical areas of the world, mosquito control is an important part of prevention of filariasis. Filariasis is usually a self-limited disease unless reinfection occurs. Therefore some cases, especially those brought into temperate regions of the world (i.e., North America), may be left untreated because there is no danger of spreading the disease. | Therapies of Filariasis. TreatmentProgressively increasing doses of any one of the major anti-parasiticide drugs is the treatment for the disorder. Among these drugs are: ivermectin, albendazole, and diethylcarbamazine. These drugs work to get rid of the larval worm, to inhiobit reproduction of the adult worm, or to kill the adult worm. Notwithstanding that these drugs are effective they do, the use of each is subject to substantial side effects (adverse reactions). These side effects may be alleviated by using antihistamines and/or anti-inflammatory drugs.The elimination of adult worms must be undertaken with care because high concentration of dead worms in the lymph or blood can provoke dangerous allergic reactions and abscesses.Surgery may be used to treat some people with filariasis who develop an abnormal accumulation of fluid in the scrotum (hydrocele). Surgery may also be performed to remove the remains of adult worms and calcifications developing around them. Treatment of elephantiasis of the legs usually consists of elevation and support from elastic stockings.In the tropical areas of the world, mosquito control is an important part of prevention of filariasis. Filariasis is usually a self-limited disease unless reinfection occurs. Therefore some cases, especially those brought into temperate regions of the world (i.e., North America), may be left untreated because there is no danger of spreading the disease. | 468 | Filariasis |
nord_469_0 | Overview of Filippi Syndrome | Filippi syndrome is an extremely rare genetic disorder that may be apparent at birth (congenital). The disorder is characterized by an unusual facial appearance, abnormalities of the fingers and toes, and mild to severe mental retardation. Primary physical findings include growth delays, webbing or fusion (syndactyly) of certain fingers and toes, inward deviation or bending (clinodactyly) of the fifth fingers (“pinkies”) and microcephaly, condition that indicates that the head circumference is smaller than would be expected for an infant's age and sex. Filippi syndrome is transmitted as an autosomal recessive trait. | Overview of Filippi Syndrome. Filippi syndrome is an extremely rare genetic disorder that may be apparent at birth (congenital). The disorder is characterized by an unusual facial appearance, abnormalities of the fingers and toes, and mild to severe mental retardation. Primary physical findings include growth delays, webbing or fusion (syndactyly) of certain fingers and toes, inward deviation or bending (clinodactyly) of the fifth fingers (“pinkies”) and microcephaly, condition that indicates that the head circumference is smaller than would be expected for an infant's age and sex. Filippi syndrome is transmitted as an autosomal recessive trait. | 469 | Filippi Syndrome |
nord_469_1 | Symptoms of Filippi Syndrome | Filippi syndrome is characterized by growth delays before and after birth (prenatal and postnatal growth retardation), a low birth weight, and short stature. Affected individuals also have characteristic abnormalities of the head and facial (craniofacial) area, resulting in a distinctive facial appearance. Affected infants may often exhibit microcephaly, condition that indicates that the head circumference is smaller than would be expected for an infant's age and sexIndividuals with Filippi syndrome also have malformations of the fingers and toes (digits). These may include webbing or fusion (syndactyly) of certain digits, such as the third and fourth fingers and/or the second, third, and fourth toes. Partial or complete webbing of these particular digits is sometimes referred to as “syndactyly type I.” The severity of the syndactyly may be variable, ranging from webbing of skin and other soft tissues to fusion of bone within the affected digits. Filippi syndrome may also be characterized by additional digital abnormalities. In some cases, there may be inward deviation (clinodactyly) of the fifth fingers (pinkies). In addition, the fingers and toes may appear unusually short (brachydactyly), particularly due to abnormalities of bones within the body of the hands and feet (metacarpals and metatarsals).Individuals with Filippi syndrome have distinctive facial features including a high forehead, a broad bridge of the nose, thin nostrils, an abnormally thin upper lip and widely spaced eyes (hypertelorism). Filippi syndrome is also characterized by mild to severe mental retardation and some affected individuals may have defective language and speech development, potentially resulting in an inability to speak.Some individuals with the disorder may have additional physical abnormalities including delayed bone age, incomplete closure of the roof of the mouth (cleft palate) and a dislocated elbow. In some affected males, the testes may fail to descend into the scrotum (cryptorchidism). In one report, skin and teeth abnormalities were also noted. | Symptoms of Filippi Syndrome. Filippi syndrome is characterized by growth delays before and after birth (prenatal and postnatal growth retardation), a low birth weight, and short stature. Affected individuals also have characteristic abnormalities of the head and facial (craniofacial) area, resulting in a distinctive facial appearance. Affected infants may often exhibit microcephaly, condition that indicates that the head circumference is smaller than would be expected for an infant's age and sexIndividuals with Filippi syndrome also have malformations of the fingers and toes (digits). These may include webbing or fusion (syndactyly) of certain digits, such as the third and fourth fingers and/or the second, third, and fourth toes. Partial or complete webbing of these particular digits is sometimes referred to as “syndactyly type I.” The severity of the syndactyly may be variable, ranging from webbing of skin and other soft tissues to fusion of bone within the affected digits. Filippi syndrome may also be characterized by additional digital abnormalities. In some cases, there may be inward deviation (clinodactyly) of the fifth fingers (pinkies). In addition, the fingers and toes may appear unusually short (brachydactyly), particularly due to abnormalities of bones within the body of the hands and feet (metacarpals and metatarsals).Individuals with Filippi syndrome have distinctive facial features including a high forehead, a broad bridge of the nose, thin nostrils, an abnormally thin upper lip and widely spaced eyes (hypertelorism). Filippi syndrome is also characterized by mild to severe mental retardation and some affected individuals may have defective language and speech development, potentially resulting in an inability to speak.Some individuals with the disorder may have additional physical abnormalities including delayed bone age, incomplete closure of the roof of the mouth (cleft palate) and a dislocated elbow. In some affected males, the testes may fail to descend into the scrotum (cryptorchidism). In one report, skin and teeth abnormalities were also noted. | 469 | Filippi Syndrome |
nord_469_2 | Causes of Filippi Syndrome | Filippi syndrome is transmitted as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. Some cases of Filippi syndrome have had parents who were related by blood (consanguineous). All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder. | Causes of Filippi Syndrome. Filippi syndrome is transmitted as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. Some cases of Filippi syndrome have had parents who were related by blood (consanguineous). All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder. | 469 | Filippi Syndrome |
nord_469_3 | Affects of Filippi Syndrome | Filippi syndrome is a rare genetic disorder that appears to affect males and females equally. Since the disorder was originally described in 1985 (G. Filippi), approximately 18 cases have been reported in the medical literature, including affected siblings within certain families (kindreds) as well as isolated cases.Filippi syndrome is sometimes classified as one of the “craniodigital syndromes,” several disorders loosely grouped together because of similar abnormalities affecting the head and fingers and toes. | Affects of Filippi Syndrome. Filippi syndrome is a rare genetic disorder that appears to affect males and females equally. Since the disorder was originally described in 1985 (G. Filippi), approximately 18 cases have been reported in the medical literature, including affected siblings within certain families (kindreds) as well as isolated cases.Filippi syndrome is sometimes classified as one of the “craniodigital syndromes,” several disorders loosely grouped together because of similar abnormalities affecting the head and fingers and toes. | 469 | Filippi Syndrome |
nord_469_4 | Related disorders of Filippi Syndrome | Symptoms of the following disorders may be similar to those of Filippi syndrome. Comparisons may be useful for a differential diagnosis:KBG syndrome is a rare genetic disorder characterized by mild to moderate mental retardation and speech defects, abnormalities of the head and facial (craniofacial) area, short stature, and additional skeletal malformations. Characteristic facial features include a relatively round face and short head (brachycephaly); broad eyebrows that grow together across the base of the nose (synophrys); a high nasal bridge; “bow-shaped” lips; and prominent ears. In addition, certain teeth may be abnormally large (macrodontia) whereas others may be absent (oligodontia). Skeletal abnormalities may include delayed bone age; abnormal shortness of certain bones of the fingers; webbing or fusion (syndactyly) of the second and third toes; or malformations of bones within the spinal column (vertebrae). KBG syndrome is inherited as an autosomal dominant trait. (For further information, choose “KBG” as your search term in the Rare Disease Database.)Scott craniodigital syndrome is a rare genetic disorder characterized by mental retardation, distinctive abnormalities of the craniofacial area, and malformations of the fingers and toes (digits). Craniofacial features typically include a relatively short head (brachycephaly); a small, narrow nose; widely spaced eyes (ocular hypertelorism); and an abnormally small lower jaw (mandible). Affected infants and children may also have webbing or fusion of certain fingers and toes; abnormal skin ridge patterns (dermatoglyphic patterns) on the palms; and/or a foot deformity in which there is inward deviation of the heel (talipes varus). Additional characteristic features may include unusually thick scalp hair with an extended hairline; long, dark eyelashes; abnormally thick eyebrows; and generalized excessive hair growth (hirsutism). Scott craniodigital syndrome is thought to be inherited as an X-linked recessive trait. (For further information, choose “Scott craniodigital” as your search term in the Rare Disease Database.)Blepharonasofacial syndrome is a rare genetic disorder characterized by distinctive facial abnormalities and mental retardation. Physical features typically include an abnormally increased horizontal distance between the inner angles (i.e., canthi) of the eyelids (telecanthus); downwardly slanting eyelid folds (palpebral fissures); an unusually “bulky” nose with a low nasal bridge; and a “trapezoidal” shaped upper lip with a pouting lower lip. In addition, facial expressions may seem fixed or mask-like. Affected individuals may also have poor coordination; abnormal looseness (laxity) of the joints; mild webbing or fusion (syndactyly) of soft tissues of the fingers; and a condition in which there is abnormal muscle stiffness (rigidity) with irregular, involuntary twisting or distorted posturing of affected muscles (torsion dystonia). Blepharonasofacial syndrome is inherited as an autosomal dominant trait.There are additional congenital disorders that may be characterized by craniofacial abnormalities, webbing or fusion of certain fingers and toes, mental retardation, and/or other symptoms and findings similar to those potentially associated with Filippi syndrome. (For more information on these disorders, choose the exact disease name in question as your search term in the Rare Disease Database.) | Related disorders of Filippi Syndrome. Symptoms of the following disorders may be similar to those of Filippi syndrome. Comparisons may be useful for a differential diagnosis:KBG syndrome is a rare genetic disorder characterized by mild to moderate mental retardation and speech defects, abnormalities of the head and facial (craniofacial) area, short stature, and additional skeletal malformations. Characteristic facial features include a relatively round face and short head (brachycephaly); broad eyebrows that grow together across the base of the nose (synophrys); a high nasal bridge; “bow-shaped” lips; and prominent ears. In addition, certain teeth may be abnormally large (macrodontia) whereas others may be absent (oligodontia). Skeletal abnormalities may include delayed bone age; abnormal shortness of certain bones of the fingers; webbing or fusion (syndactyly) of the second and third toes; or malformations of bones within the spinal column (vertebrae). KBG syndrome is inherited as an autosomal dominant trait. (For further information, choose “KBG” as your search term in the Rare Disease Database.)Scott craniodigital syndrome is a rare genetic disorder characterized by mental retardation, distinctive abnormalities of the craniofacial area, and malformations of the fingers and toes (digits). Craniofacial features typically include a relatively short head (brachycephaly); a small, narrow nose; widely spaced eyes (ocular hypertelorism); and an abnormally small lower jaw (mandible). Affected infants and children may also have webbing or fusion of certain fingers and toes; abnormal skin ridge patterns (dermatoglyphic patterns) on the palms; and/or a foot deformity in which there is inward deviation of the heel (talipes varus). Additional characteristic features may include unusually thick scalp hair with an extended hairline; long, dark eyelashes; abnormally thick eyebrows; and generalized excessive hair growth (hirsutism). Scott craniodigital syndrome is thought to be inherited as an X-linked recessive trait. (For further information, choose “Scott craniodigital” as your search term in the Rare Disease Database.)Blepharonasofacial syndrome is a rare genetic disorder characterized by distinctive facial abnormalities and mental retardation. Physical features typically include an abnormally increased horizontal distance between the inner angles (i.e., canthi) of the eyelids (telecanthus); downwardly slanting eyelid folds (palpebral fissures); an unusually “bulky” nose with a low nasal bridge; and a “trapezoidal” shaped upper lip with a pouting lower lip. In addition, facial expressions may seem fixed or mask-like. Affected individuals may also have poor coordination; abnormal looseness (laxity) of the joints; mild webbing or fusion (syndactyly) of soft tissues of the fingers; and a condition in which there is abnormal muscle stiffness (rigidity) with irregular, involuntary twisting or distorted posturing of affected muscles (torsion dystonia). Blepharonasofacial syndrome is inherited as an autosomal dominant trait.There are additional congenital disorders that may be characterized by craniofacial abnormalities, webbing or fusion of certain fingers and toes, mental retardation, and/or other symptoms and findings similar to those potentially associated with Filippi syndrome. (For more information on these disorders, choose the exact disease name in question as your search term in the Rare Disease Database.) | 469 | Filippi Syndrome |
nord_469_5 | Diagnosis of Filippi Syndrome | The diagnosis of Filippi syndrome may be made at birth or during early infancy based upon a thorough clinical evaluation and characteristic physical findings. Specialized testing, such as certain advanced imaging techniques, may also be conducted to detect or characterize particular findings that may be associated with the disorder. | Diagnosis of Filippi Syndrome. The diagnosis of Filippi syndrome may be made at birth or during early infancy based upon a thorough clinical evaluation and characteristic physical findings. Specialized testing, such as certain advanced imaging techniques, may also be conducted to detect or characterize particular findings that may be associated with the disorder. | 469 | Filippi Syndrome |
nord_469_6 | Therapies of Filippi Syndrome | TreatmentThe treatment of Filippi syndrome is directed toward the specific symptoms that are apparent in each individual. Such treatment may require the coordinated efforts of a team of medical professionals who may need to systematically and comprehensively plan an affected child's treatment. These professionals may include pediatricians; physicians who specialize in disorders of the skeleton, joints, muscles, and related tissues (orthopedists); and/or other health care professionals.In some affected individuals, treatment may include surgical repair of certain skeletal or other abnormalities potentially associated with the disorder. The surgical procedures performed will depend upon the severity of the anatomical abnormalities, their associated symptoms, and other factors.Early intervention may be important in ensuring that affected children reach their potential. Special services that may be beneficial include special education, physical therapy, speech therapy, or other medical, social, and/or vocational services. Genetic counseling will also be of benefit for individuals with Filippi syndrome and their families. Other treatment is symptomatic and supportive.These disorders include Chitayat syndrome, Zerres syndrome, Kelly syndrome, Woods syndrome and Pfeiffer-Kapferer syndrome | Therapies of Filippi Syndrome. TreatmentThe treatment of Filippi syndrome is directed toward the specific symptoms that are apparent in each individual. Such treatment may require the coordinated efforts of a team of medical professionals who may need to systematically and comprehensively plan an affected child's treatment. These professionals may include pediatricians; physicians who specialize in disorders of the skeleton, joints, muscles, and related tissues (orthopedists); and/or other health care professionals.In some affected individuals, treatment may include surgical repair of certain skeletal or other abnormalities potentially associated with the disorder. The surgical procedures performed will depend upon the severity of the anatomical abnormalities, their associated symptoms, and other factors.Early intervention may be important in ensuring that affected children reach their potential. Special services that may be beneficial include special education, physical therapy, speech therapy, or other medical, social, and/or vocational services. Genetic counseling will also be of benefit for individuals with Filippi syndrome and their families. Other treatment is symptomatic and supportive.These disorders include Chitayat syndrome, Zerres syndrome, Kelly syndrome, Woods syndrome and Pfeiffer-Kapferer syndrome | 469 | Filippi Syndrome |
nord_470_0 | Overview of Fitz Hugh Curtis Syndrome | Fitz-Hugh-Curtis syndrome is a rare disorder that occurs almost exclusively in women. It is characterized by inflammation of the membrane lining the stomach (peritoneum) and the tissues surrounding the liver (perihepatitis). The muscle that separates the stomach and the chest (diaphragm), which plays an essential role in breathing, may also be affected. Common symptoms include severe pain in the upper right area (quadrant) of the abdomen, fever, chills, headaches, and a general feeling of poor health (malaise). Fitz-Hugh-Curtis syndrome is a complication of pelvic inflammatory disease (PID), a general term for infection of the upper genital tract in women. Infection is most often caused by Neisseria gonorrhoeae and Chlamydia trachomatis. | Overview of Fitz Hugh Curtis Syndrome. Fitz-Hugh-Curtis syndrome is a rare disorder that occurs almost exclusively in women. It is characterized by inflammation of the membrane lining the stomach (peritoneum) and the tissues surrounding the liver (perihepatitis). The muscle that separates the stomach and the chest (diaphragm), which plays an essential role in breathing, may also be affected. Common symptoms include severe pain in the upper right area (quadrant) of the abdomen, fever, chills, headaches, and a general feeling of poor health (malaise). Fitz-Hugh-Curtis syndrome is a complication of pelvic inflammatory disease (PID), a general term for infection of the upper genital tract in women. Infection is most often caused by Neisseria gonorrhoeae and Chlamydia trachomatis. | 470 | Fitz Hugh Curtis Syndrome |
nord_470_1 | Symptoms of Fitz Hugh Curtis Syndrome | Fitz-Hugh-Curtis syndrome is characterized by the onset of sudden, severe pain in the upper right area of the abdomen. Pain may spread to additional areas including the right shoulder and the inside of the right arm. Movement often increases pain. The upper right area may be extremely tender. Additional symptoms may occur in some cases including fever, chills, night sweats, vomiting and nausea. Some affected individuals may develop headaches, hiccupping, and a general feeling of poor health (malaise). Some affected individuals may have symptoms associated with pelvic inflammatory disease including fever, vaginal discharge, and lower abdominal pain. Lower abdominal pain may precede, follow, or occur simultaneously with upper abdominal pain. | Symptoms of Fitz Hugh Curtis Syndrome. Fitz-Hugh-Curtis syndrome is characterized by the onset of sudden, severe pain in the upper right area of the abdomen. Pain may spread to additional areas including the right shoulder and the inside of the right arm. Movement often increases pain. The upper right area may be extremely tender. Additional symptoms may occur in some cases including fever, chills, night sweats, vomiting and nausea. Some affected individuals may develop headaches, hiccupping, and a general feeling of poor health (malaise). Some affected individuals may have symptoms associated with pelvic inflammatory disease including fever, vaginal discharge, and lower abdominal pain. Lower abdominal pain may precede, follow, or occur simultaneously with upper abdominal pain. | 470 | Fitz Hugh Curtis Syndrome |
nord_470_2 | Causes of Fitz Hugh Curtis Syndrome | Most cases of Fitz-Hugh-Curtis syndrome are caused by infection with the bacterium Chlamydia trachomatis, which causes Chlamydia or the organism Neisseria gonorrhoeae, which causes gonorrhea. Chlamydia and gonorrhea are common sexually transmitted diseases (STDs). Researchers believe that more cases of Fitz-Hugh-Curtis syndrome are caused by infection with Chlamydia trachomatis than with Neisseria gonorrhoeae. The exact process by which such infections cause Fitz-Hugh-Curtis syndrome (pathogenesis) is not completely understood. Some researchers believe that it occurs because of infection of the liver and surrounding tissue, which may result from bacteria traveling from the pelvis directly to the liver or via the bloodstream or lymphatic system. Some researchers have speculated that Fitz-Hugh-Curtis syndrome may occur because of an improper immune system response (autoimmunity) to infection with Neisseria gonorrhoeae or Chlamydia trachomatis. Autoimmune disorders are caused when the body's natural defenses (antibodies, lymphocytes, etc), against invading organisms suddenly begin to attack perfectly healthy tissue. Several studies have demonstrated that individuals with Fitz-Hugh-Curtis syndrome have high levels of antibodies against Chlamydia trachomatis. More research is necessary to determine what role autoimmunity plays in the development of Fitz-Hugh-Curtis syndrome. Fitz-Hugh-Curtis syndrome is characterized by the developed of string-like, fibrous scar tissue (adhesions) between the liver and the abdominal wall or the diaphragm. | Causes of Fitz Hugh Curtis Syndrome. Most cases of Fitz-Hugh-Curtis syndrome are caused by infection with the bacterium Chlamydia trachomatis, which causes Chlamydia or the organism Neisseria gonorrhoeae, which causes gonorrhea. Chlamydia and gonorrhea are common sexually transmitted diseases (STDs). Researchers believe that more cases of Fitz-Hugh-Curtis syndrome are caused by infection with Chlamydia trachomatis than with Neisseria gonorrhoeae. The exact process by which such infections cause Fitz-Hugh-Curtis syndrome (pathogenesis) is not completely understood. Some researchers believe that it occurs because of infection of the liver and surrounding tissue, which may result from bacteria traveling from the pelvis directly to the liver or via the bloodstream or lymphatic system. Some researchers have speculated that Fitz-Hugh-Curtis syndrome may occur because of an improper immune system response (autoimmunity) to infection with Neisseria gonorrhoeae or Chlamydia trachomatis. Autoimmune disorders are caused when the body's natural defenses (antibodies, lymphocytes, etc), against invading organisms suddenly begin to attack perfectly healthy tissue. Several studies have demonstrated that individuals with Fitz-Hugh-Curtis syndrome have high levels of antibodies against Chlamydia trachomatis. More research is necessary to determine what role autoimmunity plays in the development of Fitz-Hugh-Curtis syndrome. Fitz-Hugh-Curtis syndrome is characterized by the developed of string-like, fibrous scar tissue (adhesions) between the liver and the abdominal wall or the diaphragm. | 470 | Fitz Hugh Curtis Syndrome |
nord_470_3 | Affects of Fitz Hugh Curtis Syndrome | The vast majority of cases occur in women of reproductive age who have pelvic inflammatory disease (PID). Approximately 4-14 percent of women with PID develop Fitz-Hugh-Curtis syndrome. It occurs with greater frequency in adolescents with PID because they are more susceptible to infection. The actual incidence of Fitz-Hugh-Curtis syndrome in the general population is unknown. In extremely rare cases, it has occurred in men. Fitz-Hugh-Curtis syndrome was first described in the medical literature in 1920. | Affects of Fitz Hugh Curtis Syndrome. The vast majority of cases occur in women of reproductive age who have pelvic inflammatory disease (PID). Approximately 4-14 percent of women with PID develop Fitz-Hugh-Curtis syndrome. It occurs with greater frequency in adolescents with PID because they are more susceptible to infection. The actual incidence of Fitz-Hugh-Curtis syndrome in the general population is unknown. In extremely rare cases, it has occurred in men. Fitz-Hugh-Curtis syndrome was first described in the medical literature in 1920. | 470 | Fitz Hugh Curtis Syndrome |
nord_470_4 | Related disorders of Fitz Hugh Curtis Syndrome | Symptoms of the following disorders can be similar to those of Fitz-Hugh-Curtis syndrome. Comparisons may be useful for a differential diagnosis.Viral hepatitis is inflammation of the liver caused by infection with a virus. There are five types of viral hepatitis named A, B, C, D, and E. Hepatitis types A, B and C are the most common. Some individuals may not develop apparent symptoms (asymptomatic). Symptoms that can occur include nausea, vomiting, headaches, muscle aches, pain in the abdomen, and yellowing of the whites of the eyes and the mucous membranes (jaundice). (For more information on this disorder, choose “hepatiti” as your search term in the Rare Disease Database.)(For more information on this disorder, choose “cholecystiti” as your search term in the Rare Disease Database.)A variety of additional conditions may resemble Fitz-Hugh-Curtis syndrome including cholelithiasis, pyelonephritis, pancreatitis, herpes zoster, appendicitis, nephrolithiasis, peptic ulcer disease, and bacterial, fungal or viral pneumonia. (For more information on these conditions, choose the specific name as your search term in the Rare Disease DatabaseCholecystitis is inflammation of the gallbladder, the pear-shaped muscular sac that lies below the liver. The gallbladder's main function is to store and concentrate bile and to expel the bile through the bile duct during the digestion of fats. (Bile is a greenish-brown liquid produced by the liver that breaks down fats present in the small intestine during digestion.) Cholecystitis may come on suddenly (acute) or may persist over a period of time (chronic). Acute cholecystitis is usually caused by obstruction of the outlet of the gallbladder, which is often due to the development of a stone formed in the biliary tract (gallstone or biliary calculus). Repeated mild episodes of acute cholecystitis may result in chronic cholecystitis, which may be characterized by thickening and shrinking of the gallbladder walls and a resulting inability to store bile. Cholecystitis may cause a variety of symptoms including severe pain in the right side of the abdomen (right upper quadrant) and/or back, nausea, vomiting, indigestion, fever, and persistent yellowing of the skin, mucous membranes, and whites of the eyes (jaundice). In some cases, there may be additional symptoms. | Related disorders of Fitz Hugh Curtis Syndrome. Symptoms of the following disorders can be similar to those of Fitz-Hugh-Curtis syndrome. Comparisons may be useful for a differential diagnosis.Viral hepatitis is inflammation of the liver caused by infection with a virus. There are five types of viral hepatitis named A, B, C, D, and E. Hepatitis types A, B and C are the most common. Some individuals may not develop apparent symptoms (asymptomatic). Symptoms that can occur include nausea, vomiting, headaches, muscle aches, pain in the abdomen, and yellowing of the whites of the eyes and the mucous membranes (jaundice). (For more information on this disorder, choose “hepatiti” as your search term in the Rare Disease Database.)(For more information on this disorder, choose “cholecystiti” as your search term in the Rare Disease Database.)A variety of additional conditions may resemble Fitz-Hugh-Curtis syndrome including cholelithiasis, pyelonephritis, pancreatitis, herpes zoster, appendicitis, nephrolithiasis, peptic ulcer disease, and bacterial, fungal or viral pneumonia. (For more information on these conditions, choose the specific name as your search term in the Rare Disease DatabaseCholecystitis is inflammation of the gallbladder, the pear-shaped muscular sac that lies below the liver. The gallbladder's main function is to store and concentrate bile and to expel the bile through the bile duct during the digestion of fats. (Bile is a greenish-brown liquid produced by the liver that breaks down fats present in the small intestine during digestion.) Cholecystitis may come on suddenly (acute) or may persist over a period of time (chronic). Acute cholecystitis is usually caused by obstruction of the outlet of the gallbladder, which is often due to the development of a stone formed in the biliary tract (gallstone or biliary calculus). Repeated mild episodes of acute cholecystitis may result in chronic cholecystitis, which may be characterized by thickening and shrinking of the gallbladder walls and a resulting inability to store bile. Cholecystitis may cause a variety of symptoms including severe pain in the right side of the abdomen (right upper quadrant) and/or back, nausea, vomiting, indigestion, fever, and persistent yellowing of the skin, mucous membranes, and whites of the eyes (jaundice). In some cases, there may be additional symptoms. | 470 | Fitz Hugh Curtis Syndrome |
nord_470_5 | Diagnosis of Fitz Hugh Curtis Syndrome | A diagnosis of Fitz-Hugh-Curtis syndrome is made through the exclusion of other causes of upper right abdominal pain. A diagnosis may be confirmed with a variety of specialized tests including x-ray examination, diagnostic laparoscopy, and certain laboratory exams. X-ray examination may include ultrasound, chest or stomach radiographs, and computed tomography (CT) scanning. X-rays are used to rule out other possible conditions or reveal characteristic inflammation of the perihepatic region. During a laparoscopy, a small, thing tube is inserted in the abdominal cavity through a small incision in the stomach. A laparoscopic exam allows a physician to view the liver and surrounding tissue. Laboratory exams can identify infection with Chlamydia trachomatis or Neisseria gonorrhoeae. | Diagnosis of Fitz Hugh Curtis Syndrome. A diagnosis of Fitz-Hugh-Curtis syndrome is made through the exclusion of other causes of upper right abdominal pain. A diagnosis may be confirmed with a variety of specialized tests including x-ray examination, diagnostic laparoscopy, and certain laboratory exams. X-ray examination may include ultrasound, chest or stomach radiographs, and computed tomography (CT) scanning. X-rays are used to rule out other possible conditions or reveal characteristic inflammation of the perihepatic region. During a laparoscopy, a small, thing tube is inserted in the abdominal cavity through a small incision in the stomach. A laparoscopic exam allows a physician to view the liver and surrounding tissue. Laboratory exams can identify infection with Chlamydia trachomatis or Neisseria gonorrhoeae. | 470 | Fitz Hugh Curtis Syndrome |
nord_470_6 | Therapies of Fitz Hugh Curtis Syndrome | TreatmentThe treatment of Fitz-Hugh-Curtis syndrome is directed toward the specific symptoms that are apparent in each individual. Antibiotic therapy is the mainstay treatment for individuals with Fitz-Hugh-Curtis syndrome. Different regimens of tetracycline, doxycycline, ofloxacin, metronidazole, and additional antibiotics may be prescribed to fight the underlying infection. Pain medications (analgesics) such as acetaminophen and codeine may be used in some cases. The Centers for Disease Control and Prevention (CDC) has released guidelines on the treatment of pelvic inflammatory disease.In some cases, antibiotic therapy may not provide relief of symptoms and a surgical procedure known as a laparotomy may be performed. During a laparotomy, a small, thin instrument is inserted in the abdominal cavity through a small incision made in the abdomen. Physicians can then destroy any fibrous scar tissue (adhesions) found in the perihepatic region. | Therapies of Fitz Hugh Curtis Syndrome. TreatmentThe treatment of Fitz-Hugh-Curtis syndrome is directed toward the specific symptoms that are apparent in each individual. Antibiotic therapy is the mainstay treatment for individuals with Fitz-Hugh-Curtis syndrome. Different regimens of tetracycline, doxycycline, ofloxacin, metronidazole, and additional antibiotics may be prescribed to fight the underlying infection. Pain medications (analgesics) such as acetaminophen and codeine may be used in some cases. The Centers for Disease Control and Prevention (CDC) has released guidelines on the treatment of pelvic inflammatory disease.In some cases, antibiotic therapy may not provide relief of symptoms and a surgical procedure known as a laparotomy may be performed. During a laparotomy, a small, thin instrument is inserted in the abdominal cavity through a small incision made in the abdomen. Physicians can then destroy any fibrous scar tissue (adhesions) found in the perihepatic region. | 470 | Fitz Hugh Curtis Syndrome |
nord_471_0 | Overview of Floating Harbor Syndrome | Floating-Harbor syndrome (FHS) is an extremely rare genetic disorder characterized by a distinctive facial appearance, various skeletal malformations, delayed bone age, and expressive and receptive language delays. Children may be below average height for their age (short stature). Additional symptoms including mild to moderate intellectual disability have also been reported. The specific symptoms and severity FHS can vary greatly from one person to another. FHS is caused by mutations in the SRCAP gene. This mutation is inherited in an autosomal dominant manner, although most cases of FHS occur randomly (sporadically) as the result of a new (de novo) mutation. Treatment is symptomatic and supportive.Floating-Harbor syndrome was named after the two hospitals where, during the 1970s, the first cases were identified and reported in the medical literature; namely, the Boston Floating Hospital and Harbor General Hospital in California. | Overview of Floating Harbor Syndrome. Floating-Harbor syndrome (FHS) is an extremely rare genetic disorder characterized by a distinctive facial appearance, various skeletal malformations, delayed bone age, and expressive and receptive language delays. Children may be below average height for their age (short stature). Additional symptoms including mild to moderate intellectual disability have also been reported. The specific symptoms and severity FHS can vary greatly from one person to another. FHS is caused by mutations in the SRCAP gene. This mutation is inherited in an autosomal dominant manner, although most cases of FHS occur randomly (sporadically) as the result of a new (de novo) mutation. Treatment is symptomatic and supportive.Floating-Harbor syndrome was named after the two hospitals where, during the 1970s, the first cases were identified and reported in the medical literature; namely, the Boston Floating Hospital and Harbor General Hospital in California. | 471 | Floating Harbor Syndrome |
nord_471_1 | Symptoms of Floating Harbor Syndrome | Although researchers have been able to establish a clear syndrome with characteristic or “core” symptoms, much about the disorder is not fully understood. Several factors including the small number of identified cases, the lack of large clinical studies, and the possibility of other genes influencing the disorder prevent physicians from developing a complete picture of associated symptoms and prognosis. Therefore, it is important to note that affected individuals may not have all of the symptoms discussed below. Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis.In some cases, delayed growth may occur before birth (prenatal growth retardation) resulting in low birth weight. Typically, growth deficiencies become apparent during the first year of life. Affected children may be below average height for their age (short stature), usually below the 5th percentile. The head size is typically in the average range. In addition to growth deficiencies, children with FHS have a delay in bone aging in the first decade of life, which means that the rate of growth and calcification of the bones is slower than normal.Infants and children with FHS have distinctive facial features including a triangularly-shaped face; low-set ears; deep-set eyes with abnormally long eyelashes; thin lips; a broad, linear mouth; a prominent, triangular-shaped nose that is narrow at the root and broadens at the base; the bottom of the sheet of cartilage and bone (nasal septum) that separates the right and left nostrils (columella) may be low-hanging; the nostrils are large; and the groove that runs from the nose to the upper lip (philtrum) is short. These facial characteristics are the most distinctive features of FHS. Although they may change as an affected individual ages, the key features remain constant. Speech and language deficits are common in children with FHS. Expressive language deficits are most common and often most severely affected. Expressive language is the ability of a person to ‘output’ language or how people express themselves such as through speech or writing. It also encompasses the use of gestures and facial expressions. Some affected children also have receptive language deficits, in which they are unable to understand words and gestures. Affected individuals may have difficulty speaking (dysarthria) and exhibit a distinct, high-pitched nasally voice. In some cases, speech may be absent. Children may be described as having verbal dyspraxia, which refers to the difficulty or inability to coordinate the precise movements required to produce clear speech despite the absence of damage to the nerves or muscles. The severity of expressive and receptive language abnormalities can vary widely. Intellectual disability that is typically mild to moderate in degree has been reported. Learning disabilities are common as well. Affected individuals exhibit various skeletal malformations including short fingers and toes (brachydactyly); broad fingertips that give the appearance of clubbing; short, broad thumbs; and prominent joints. The pinkies may be fixed or ‘locked’ in a bent position (clinodactyly). Some individuals may have abnormalities of the collarbones (clavicles) including underdevelopment (hypoplasia) of the collarbone or the development of a ‘false joint’ (pseudoarthrosis). A false joint is a bony structure that usually develops at the site of a poorly united fracture that allows abnormal movement of the affected bones. Children with FHS may exhibit behavioral abnormalities including hyperactivity, impulsivity, short attention span, aggression, anxiousness, and obsessive behaviors such as repeated skin picking. Behavioral issues often improve in adulthood. Additional symptoms have been reported in individuals with FHS including short bones in the hands (metacarpals); the presence of 11 pairs of ribs instead of 12; malformed (dysplastic) hips; abnormal curvature of the spine (kyphoscoliosis); seizures; backflow or leakage of the contents of the stomach into the esophagus (gastroesophageal reflux); farsightedness (hyperopia); crossed eyes (strabismus); recurrent middle ear infections (otitis media); and conductive hearing loss. Conductive hearing loss occurs when there is impaired transmission of sound from the outer or middle ear to the inner ear. Dental anomalies may also occur including extra (supernumerary) teeth, delayed loss of primary (“baby”) teeth, abnormally small teeth (microdontia), and malocclusion, a condition in which the upper teeth are improperly positioned in relation to the lower teeth.In some cases, affected individuals may exhibit kidney abnormalities such as cysts on the kidneys or swelling (distention) of the kidneys due to the abnormal accumulation of urine (hydronephrosis). Hydronephrosis develops because of blockage within the urinary tract that prevents urine from being evacuated through the bladder. In some cases, there may be absence of the kidneys (agenesis). In some cases, the onset of puberty may occur earlier than normal. Males may have undescended testicles (cryptorchidism) and hypospadias, a condition in which the tube that is connected to the bladder and discharges urine from the body (urethra) opens on the underside of the penis instead of the tip. Other conditions that have been reported in individuals with FHS include Celiac disease, congenital heart defects, mild underactivity of the thyroid (hypothyroidism), and, in adulthood, high blood pressure (hypertension). | Symptoms of Floating Harbor Syndrome. Although researchers have been able to establish a clear syndrome with characteristic or “core” symptoms, much about the disorder is not fully understood. Several factors including the small number of identified cases, the lack of large clinical studies, and the possibility of other genes influencing the disorder prevent physicians from developing a complete picture of associated symptoms and prognosis. Therefore, it is important to note that affected individuals may not have all of the symptoms discussed below. Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis.In some cases, delayed growth may occur before birth (prenatal growth retardation) resulting in low birth weight. Typically, growth deficiencies become apparent during the first year of life. Affected children may be below average height for their age (short stature), usually below the 5th percentile. The head size is typically in the average range. In addition to growth deficiencies, children with FHS have a delay in bone aging in the first decade of life, which means that the rate of growth and calcification of the bones is slower than normal.Infants and children with FHS have distinctive facial features including a triangularly-shaped face; low-set ears; deep-set eyes with abnormally long eyelashes; thin lips; a broad, linear mouth; a prominent, triangular-shaped nose that is narrow at the root and broadens at the base; the bottom of the sheet of cartilage and bone (nasal septum) that separates the right and left nostrils (columella) may be low-hanging; the nostrils are large; and the groove that runs from the nose to the upper lip (philtrum) is short. These facial characteristics are the most distinctive features of FHS. Although they may change as an affected individual ages, the key features remain constant. Speech and language deficits are common in children with FHS. Expressive language deficits are most common and often most severely affected. Expressive language is the ability of a person to ‘output’ language or how people express themselves such as through speech or writing. It also encompasses the use of gestures and facial expressions. Some affected children also have receptive language deficits, in which they are unable to understand words and gestures. Affected individuals may have difficulty speaking (dysarthria) and exhibit a distinct, high-pitched nasally voice. In some cases, speech may be absent. Children may be described as having verbal dyspraxia, which refers to the difficulty or inability to coordinate the precise movements required to produce clear speech despite the absence of damage to the nerves or muscles. The severity of expressive and receptive language abnormalities can vary widely. Intellectual disability that is typically mild to moderate in degree has been reported. Learning disabilities are common as well. Affected individuals exhibit various skeletal malformations including short fingers and toes (brachydactyly); broad fingertips that give the appearance of clubbing; short, broad thumbs; and prominent joints. The pinkies may be fixed or ‘locked’ in a bent position (clinodactyly). Some individuals may have abnormalities of the collarbones (clavicles) including underdevelopment (hypoplasia) of the collarbone or the development of a ‘false joint’ (pseudoarthrosis). A false joint is a bony structure that usually develops at the site of a poorly united fracture that allows abnormal movement of the affected bones. Children with FHS may exhibit behavioral abnormalities including hyperactivity, impulsivity, short attention span, aggression, anxiousness, and obsessive behaviors such as repeated skin picking. Behavioral issues often improve in adulthood. Additional symptoms have been reported in individuals with FHS including short bones in the hands (metacarpals); the presence of 11 pairs of ribs instead of 12; malformed (dysplastic) hips; abnormal curvature of the spine (kyphoscoliosis); seizures; backflow or leakage of the contents of the stomach into the esophagus (gastroesophageal reflux); farsightedness (hyperopia); crossed eyes (strabismus); recurrent middle ear infections (otitis media); and conductive hearing loss. Conductive hearing loss occurs when there is impaired transmission of sound from the outer or middle ear to the inner ear. Dental anomalies may also occur including extra (supernumerary) teeth, delayed loss of primary (“baby”) teeth, abnormally small teeth (microdontia), and malocclusion, a condition in which the upper teeth are improperly positioned in relation to the lower teeth.In some cases, affected individuals may exhibit kidney abnormalities such as cysts on the kidneys or swelling (distention) of the kidneys due to the abnormal accumulation of urine (hydronephrosis). Hydronephrosis develops because of blockage within the urinary tract that prevents urine from being evacuated through the bladder. In some cases, there may be absence of the kidneys (agenesis). In some cases, the onset of puberty may occur earlier than normal. Males may have undescended testicles (cryptorchidism) and hypospadias, a condition in which the tube that is connected to the bladder and discharges urine from the body (urethra) opens on the underside of the penis instead of the tip. Other conditions that have been reported in individuals with FHS include Celiac disease, congenital heart defects, mild underactivity of the thyroid (hypothyroidism), and, in adulthood, high blood pressure (hypertension). | 471 | Floating Harbor Syndrome |
nord_471_2 | Causes of Floating Harbor Syndrome | Floating-Harbor syndrome is caused by a mutation in the SRCAP gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body.Investigators have determined that the SRCAP gene is located on the short arm (p) of chromosome 16 (16p11). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. In FHS, mutations in the SRCAP gene often occur as a new (sporadic or de novo) mutation, which means that in nearly all cases the gene mutation has occurred at the time of the formation of the egg or sperm for that child only, and no other family member will be affected. There are no silent carriers of FHS (i.e. if one carries a mutation in SRCAP, he/she will show signs of FHS).Although most cases are due to sporadic mutations, dominant inheritance (where a trait is transmitted from either an affected mother or father to a child) has been documented in a few families. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.The SRCAP gene creates (encodes) a protein that has several functions in the body. This protein is a cofactor (i.e. a substance required for a protein’s biological activity) for the CREB-binding protein (CREBBP). Mutations in the gene that produces CREB-binding protein cause Rubinstein-Taybi syndrome, a rare disorder with many overlapping symptoms to FHS. | Causes of Floating Harbor Syndrome. Floating-Harbor syndrome is caused by a mutation in the SRCAP gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body.Investigators have determined that the SRCAP gene is located on the short arm (p) of chromosome 16 (16p11). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. In FHS, mutations in the SRCAP gene often occur as a new (sporadic or de novo) mutation, which means that in nearly all cases the gene mutation has occurred at the time of the formation of the egg or sperm for that child only, and no other family member will be affected. There are no silent carriers of FHS (i.e. if one carries a mutation in SRCAP, he/she will show signs of FHS).Although most cases are due to sporadic mutations, dominant inheritance (where a trait is transmitted from either an affected mother or father to a child) has been documented in a few families. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.The SRCAP gene creates (encodes) a protein that has several functions in the body. This protein is a cofactor (i.e. a substance required for a protein’s biological activity) for the CREB-binding protein (CREBBP). Mutations in the gene that produces CREB-binding protein cause Rubinstein-Taybi syndrome, a rare disorder with many overlapping symptoms to FHS. | 471 | Floating Harbor Syndrome |
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